ISBN: 978-1-84076-139-9

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Preface

One of the pleasures of respiratory medicine is also its greatest challenge - it has

so many diseases within its subspecialty area, as well as encompassing many of the

problems seen in acute medical practice, that it requires an extensive knowledge

of medicine. Judging from the previous editions of this book, learning through the

question and answer format has proven popular and attractive. We have completely

rewritten this text and included many new cases to discuss. Those which remain

have all been reviewed and updated as necessary. All the authors have an extensive

international experience of general internal as well as respiratory medicine, and

virtually every case is an actual clinical problem or presentation that they have

encountered over the last few years.

The book is, in the same way as respiratory medicine, predominantly based on

radiological presentations. There is a huge variety of radiological questions, and

the reasons for any particular answer are carefully explained. The same applies to

the physiological questions, an area absurdly neglected in much of today’s teaching

and training modules. In order to maintain the reader’s interest, there is no

particular sequence to the question list, and the reader can dip in and out, select a

topic from the index, or just work through the book. All the main topic areas are

covered: radiology, physiology, infection, malignancy, interstitial lung disease,

diseases of the pleura, immunology and immunosuppression, respiratory

complications of systemic diseases, hereditary conditions, sleep-disordered

breathing, asthma, chronic obstructive pulmonary disease, respiratory failure, and

problems around the intensive care unit. If you answer all the 200 or so questions

and understand their meaning, this book, intended for trainees as well as general

physicians, will, we hope, have enhanced your knowledge of respiratory medicine.

And if you have enjoyed this style of education as much as we have enjoyed putting

the book together, we will have succeeded in our task.

Stephen G Spiro

Richard K Albert

Jeremy Brown

Neal Navani

Classification of cases

All references are to question and

answer numbers

Thoracic oncology

Sleep medicine

6, 19, 22, 31, 34, 39, 41, 55, 66, 86, 96,

16, 63, 85, 111, 115, 159, 164, 171, 179

97, 99, 104, 107, 117, 128, 132, 133,

136, 139, 147, 149, 152, 153, 154, 157,

Respiratory physiology

169, 176, 177, 178, 189, 191, 199

23, 27, 43, 59, 68, 69, 77, 91, 93, 98,

101, 108, 114, 119, 141, 146, 148, 158,

Lung infections

160, 161, 181, 192

7, 13, 14, 17, 18, 33, 36, 42, 44, 48, 54,

56, 62, 64, 71, 72, 73, 76, 79, 89, 95,

Pulmonary vascular disease

100, 102, 103, 105, 110, 113, 116, 120,

12, 49, 52, 60, 84, 183

127, 130, 131, 134, 156, 185, 186, 188,

194, 203, 204

Respiratory complications of systemic

diseases

Airways disease

38, 73, 75, 81, 90, 155, 162, 163, 182

1, 2, 5, 11, 28, 45, 47, 78, 106, 112,

121, 126, 129, 137, 144, 145, 150, 167,

Chest wall disease

173, 174, 193, 200

21, 51, 87, 122, 146

Interstitial lung disease

Miscellaneous

4, 8, 15, 25, 30, 40, 53, 57, 67, 80, 92,

9, 10, 32, 35, 40, 50, 61, 65, 88, 118,

94, 109, 124, 125, 135, 140, 142, 143,

123, 138, 166, 172, 175, 187, 195, 196,

151, 165, 168, 170, 180, 184, 190, 197

198, 201

Pleural disease

3, 20, 24, 26, 29, 37, 45, 46, 58, 70, 74,

82, 83, 202

Abbreviations

ACE

angiotensin-converting enzyme

HIV

human immunodeficiency

ADH

antidiuretic hormone

virus

AIDS

acquired immune deficiency

HPOA

hypertrophic pulmonary

syndrome

osteoarthropathy

ANCA

antineutrophil cytoplasmic

HRCT

high-resolution computed

antibody

tomography

ARDS

acute respiratory distress

INR

International Normalized

syndrome

Ratio

BAL

bronchoalveolar lavage

K_CO

carbon monoxide transfer

BCG

Bacille Calmette-Guérin

coefficient

BiPAP

bi-level positive airway

LAM

lymphangioleiomyomatosis

pressure

LEMS

Lambert-Eaton myasthenic

BMI

body mass index

syndrome

bronchiolitis obliterans

LIP

lymphocytic interstitial

BTS

British Thoracic Society

pneumonitis

CAP

community-acquired

MDI

metered dose inhaler

pneumonia

MRC

Medical Research Council

CFTR

cystic fibrosis transmembrane

MRI

magnetic resonance imaging

regulator

OSA

obstructive sleep apnoea

CMV

cytomegalovirus

PaCO₂

arterial partial pressure of

CNS

central nervous system

carbon dioxide

COPD

chronic obstructive

PaO₂

arterial partial pressure of

pulmonary disease

oxygen

CPAP

continuous positive airway

PAS

periodic acid-Schiff

pressure

PAVM

pulmonary arteriovenous

CRP

C-reactive protein

malformation

CSF

cerebrospinal fluid

PCR

polymerase chain reaction

computed tomography

PEFR

peak expiratory flow rate

DL_CO

diffusing capacity of the lung

PET

positron emission

to carbon monoxide

tomography

DPI

dry powder inhaler

PiO₂

inspired partial pressure of

EAA

extrinsic allergic alveolitis

oxygen

EBUS

endobronchial ultrasound

respiratory exchange ratio

ECG

electrocardiograph

(quotient)

ELISA

enzyme-linked

residual volume

immunosorbent assay

SaO₂

arterial oxygen saturation

ESR

erythrocyte sedimentation

tuberculosis

rate

TLC

total lung capacity

FEV₁

forced expiratory volume in 1s

VATS

video-assisted thoracoscopic

FiO₂

fraction of inspired oxygen

surgery

FRC

functional residual capacity

vital capacity

FVC

forced vital capacity

VO₂max

maximal oxygen uptake

GINA

Global Initative for Asthma

V/Q

ventilation/perfusion

GOLD

Global Initiative for Chronic

Obstructive Lung Disease

1, 2: Answers

1b REDUCE

INCREASE

TREATMENT STEPS

Step 1

Step 2

Step 3

Step 4

Step 5

asthma education

environmental control

as needed rapid-

acting ß

as needed rapid-acting ß

2-agonist

SELECT ONE

ADD ONE OR MORE

ADD ONE OR BOTH

low-dose ICS*

low-dose ICS plus

medium- or high-dose

oral

long-acting ß₂-agonist

ICS plus long-acting

glucocorticosteroid

ß₂-agonist

(lowest dose)

leukotriene modifier**

medium- or high-dose ICS

leukotriene modifier

anti-IgE treatment

low-dose ICS plus

sustained-release

leukotriene modifier

theophylline

low-dose ICS plus

sustained-release

theophylline

* inhaled glucocorticosteroids

** receptor antagonist or synthesis inhibitors

1 i. This is the daily PEFR measurement. Measurements are lowest in the early

morning and highest in the afternoon as all individuals show at least a 10% diurnal

rhythm for peak flow. In asthma, this is exaggerated, and a more than 20% diurnal

variability is consistent with a diagnosis of asthma.

ii. Patients with asthma should be managed according to a stepwise regime (e.g. GINA;

1b). They should be started at the most appropriate step for their symptoms and

moved up when their asthma is uncontrolled and down when it is well controlled.

2 i. The flow-volume loop demonstrates a reduction in the maximum inspiratory and

expiratory flows, which both plateau over a large proportion of the FVC manoeuvre

and a low FVC <3 l. The reduction in flow is more marked during inspiration, and this

is typical of narrowing of the extrathoracic trachea.

ii. The initial diagnosis of asthma should be avoided on the basis of the physical signs,

which, in addition to stridor, are most marked in inspiration but often audible during

expiration. A simple test to detect upper airway obstruction is the ratio of FEV₁ to peak

flow, i.e. FEV₁ (ml)/PEFR (l/min). This is usually less than 10, but in upper airway

obstruction the peak flow is affected most, e.g. 2000 ml ÷ 150 l/min = 13.

The data would also be compatible with a high tracheal or laryngeal area of

narrowing/collapse, as after a tracheostomy.

Another cause of this presentation is a high tracheal tumour, which, because of its

slow onset, may mimic asthma. However, the wheeze will be fixed and the symptoms

constant, unlike in asthma.

iii. A mixture of oxygen (21%) and helium (79%) as helium is less dense than nitrogen,

allowing a greater flow of gas.

3, 4: Answers

3 i. The chest X-ray demonstrates

extensive pleural plaques. These are

Asbestos-related pulmonary

evident both above the hemi-

manifestations

diaphragms and also along the ribs

• Pleural plaques

throughout the thorax.

• Benign pleural effusion

ii. This is a benign condition and

• Diffuse pleural thickening

rarely causes symptoms. The plaques

• Rounded atelectasis (Blesovsky sign)

occur after a latent period of

• Asbestosis (pulmonary fibrosis)

approximately 20-40 years following

• Mesothelioma

asbestos exposure and almost

• Non-small-cell lung cancer

exclusively involve the parietal pleura.

Plaques may grow over time, but as

they are not considered premalignant

no further action is required.

iii. Asbestos may affect the lung in several ways (Box).

4 i. The HRCT axial cut demonstrates reticular opacities, traction bronchiectasis,

and honeycombing in a subpleural and basal distribution. Honeycombing is

recognized by the presence of one or more rows of clustered cysts (<5 mm in

diameter) and implies a poor prognosis. The features are characteristic of idiopathic

pulmonary fibrosis. HRCT is a very reliable method of making the diagnosis, and

lung biopsy (which would demonstrate usual interstitial pneumonitis) is not

required in most cases.

ii. The examination features would include digital clubbing (25-50% of cases) and

fine end-inspiratory ‘Velcro-like’ crackles at the bases. The pansystolic murmur of

tricuspid regurgitation, a raised jugular venous pressure, and peripheral oedema

may herald the development of pulmonary hypertension.

iii. No cause for idiopathic pulmonary fibrosis has been discovered. It may,

however, be associated with connective tissue diseases (e.g. rheumatoid arthritis,

scleroderma and mixed connective tissue diseases) and in this context has a better

prognosis. The condition is linked to an increased incidence of lung cancer and is

a cause of respiratory failure and secondary pulmonary hypertension. The 5-year

survival is worse than for many extrathoracic cancers, at 20-40%.

iv. The treatment options are limited. A combination of N-acetylcysteine,

prednisolone, and azathioprine is recommended to reduce the rate of decline of

lung function, although it does not improve mortality. Lung transplant is rarely

performed for patients with idiopathic pulmonary fibrosis, since most patients

present over the age of 60 (the cut-off for transplantation in the UK).

5, 6: Answers

National Institute for

GOLD criteria

Health and Clinical

COPD

(2008)

Excellence criteria (2004)

severity

FEV₁ % predicted

Mild

>80%

50-80%

Moderate

50-80%

30-49%

Severe

30-49%

<30%

Very severe <30% or <50%

with chronic

respiratory failure

5 i. The posteroanterior chest X-ray shows hyperinflated lung fields, flattening of

the diaphragms, a general reduction in lung density, and a peripheral pruning of

vascular markings consistent with COPD.

ii. The severity of COPD is most usefully assessed by spirometry. The GOLD

(Global Initiative for Chronic Obstructive Lung Disease) guidelines define COPD

from when the post-bronchodilator FEV₁/FVC ratio is <0.7 (Table).

Other factors that predict the prognosis and exacerbation rate include transfer

factor for carbon monoxide, breathlessness (according to the MRC scale), exercise

capacity, BMI, PaO₂, and cor pulmonale.

6 i. The chest X-ray (6a) shows a large right hilar mass and no obvious primary

tumour. The primary tumour may be resectable, but only if there is no mediastinal

disease present. A CT of the thorax and upper abdomen should be performed (6b).

Such a CT scan in fact has shown the primary tumour behind the hilar mass, sitting

in the apical segment of the right lower lobe. It is cavitating, suggesting a squamous

cell lesion. The CT scan confirms the hilar nodal enlargement and also shows

enlarged subcarinal nodes, making the patient almost certainly inoperable. In

otherwise operable cases of non-small-cell lung cancer, liver metastases are seen on

CT in 5% and adrenal deposits in 7% of patients.

ii. CT scanning gives a 30-40% false-positive and also a false-negative rate, and is

therefore much less reliable than a PET scan, which has a specificity of 85-90% for

identifying tumour.

iii. The maximum size of ‘normal’ nodes on a CT scan is 10 mm in the node’s short

axis, although this will be falsely negative in up to 40% of cases, particularly with

adenocarcinomas.

7, 8: Questions

7 The photomicrograph (7) shows a

Gram stain of sputum expectorated by a

19-year-old male with symptoms of

fever, rigors, and a productive cough of

2 days’ duration. He has experienced

four episodes of radiographically docu-

mented pneumonia and numerous

episodes of acute otitis media and

sinusitis in the past.

i. What does the Gram stain show?

ii. What is the most likely diagnosis?

iii.

What additional diagnostic

considerations are raised by this clinical

presentation?

8 This 50-year-old male presented with

gradually progressive dyspnoea over the

course of 6 months. His mother had

become unwell at that time, and he had started visiting her daily to look after her.

Her chest X-ray (8a) is shown.

i. Describe the appearances seen on the HRCT (8b) of the lungs.

ii. What important history would you obtain?

iii. What is the likely diagnosis?

iv. How would you treat this condition?

v. What is the differential diagnosis of bilateral upper lobe shadowing?

7, 8: Answers

7 i. The sputum Gram stain shows numerous polymorphonuclear leukocytes,

strands of mucus, and many Gram-positive, lancet-shaped diplococci. Refractile

capsules are evident on many of the bacteria.

ii. The young patient has an acute pneumococcal pneumonia and has suffered

numerous recurrent respiratory infections.

iii. Most patients with recurrent respiratory infections have no identifiable host

defect. However, recurrent pneumonias in the same lobe or segment should suggest

an anatomical abnormality. When multiple sites have been involved, disorders of

mucociliary clearance such as cystic fibrosis or the ciliary dyskinesia syndrome

(Kartagener’s syndrome) are an important consideration.

Recurrent infections with encapsulated organisms such as the pneumococcus are

consistent with a defect in opsonization (e.g. complement, IgG or IgG subtype

deficiencies). Deficiencies of complement components are rare and are best

managed by immunization and by the early treatment of infectious complications.

Immunoglobulin deficiencies can also be primary (inherited) or acquired due to

acquired B-cell disorders, medications, or intercurrent illnesses. IgA is heavily

concentrated in mucosal secretions, where it inhibits bacterial adherence. Although

selective IgA deficiency is common, it rarely results in serious respiratory infection

unless other deficiencies coexist. IgG deficiency (either generalized or restricted to

subclasses IgG1 and IgG3) predisposes to more frequent and more severe

respiratory infections. Intravenous immunoglobulin replacement may be helpful.

8 i. The HRCT (8b) shows diffuse ground-glass shadowing with some areas of

centrilobular nodularity. The chest X-ray (8a) shows a mainly upper lobe nodular

infiltrate.

ii. Ask about exposure to any pets or unusual dusts or chemicals. In this case, the

patient had had a cockatoo that he had been feeding since his mother had become

unwell. Budgerigars and pigeons are common causes of this, as are the classical

irritants encountered in farmer’s lung, bark-stripper’s lung, etc.

iii. EAA or hypersensitivity pneumonitis may be caused by exposure to a variety of

dusts and antigens, and may be confirmed by avian precipitins in the serum and

removal of the source, i.e. the bird. A careful occupational history is essential.

iv. Patients must be instructed to avoid the allergen or precipitant. Oral

prednisolone may be used during the initial few weeks until the patient feels better,

although there is no definite evidence on optimal dose and duration.

v. The differential diagnosis includes sarcoidosis, pneumoconiosis, ankylosing

spondylosis, and TB.

9, 10: Answers

9 i. A pulse oximeter is a spectrophotometer that measures the absorption of light

at two wavelengths, one in the infrared range at a wavelength of 940 nm (absorbed

by oxyhaemoglobin) and the other at a wavelength of 660 nm (absorbed by reduced

haemoglobin).The absorption at these two wavelengths is compared, and the

percentages of oxygenated and reduced haemoglobin are calculated. The pulse

oximeter compares absorption measured during systole and diastole and uses the

difference to reflect only the absorption of arterial blood, thereby limiting errors

induced by absorbance in venous blood and other tissues.

ii. The accuracy of most oximeters decreases below 75% saturation. Above this

level, the accuracy is approximately 4%.

iii. Standard pulse oximeters are unable to distinguish dyshaemoglobins, most

notably carboxyhaemoglobin and methaemoglobin, from oxyhaemoglobin. In

smoke inhalation, pulse oximetry reflects absorption by both oxyhaemoglobin and

carboxyhaemoglobin, and thus may overestimate the true oxygenation status. Any

factor that affects assessment of the arterial pulse (e.g. motion, low-perfusion states)

may distort the reading. Specific light sources, such as fluorescent or infrared lamps,

can cause erroneous signals if the oximeter probe is not shielded. Dark skin

pigmentation and darker coloured nail polishes can also interfere with light

transmission, thereby lowering oximeter readings.

10 i. There is gross widening of the mediastinum on the plain chest radiograph

(10a), even allowing for the anteroposterior nature of the examination. The severity

of the injury and the mediastinal widening make traumatic aortic transection a

definite possibility.

ii. The aortogram

(10b) shows a bulge in the region of the distal aortic

arch/proximal descending aorta. This is clearly shown on digital subtraction

angiography (10c) to be due to disruption of the aortic wall.

iii. This lesion is characteristically seen at the aortic isthmus, i.e. the junction

between the aortic arch and the descending aorta. This injury is believed to occur

because the arch can move forward with deceleration whereas the descending aorta

is relatively fixed. Immediate exsanguination will occur in many cases. Those

individuals who reach hospital can undergo repair of the ruptured segment, usually

with the insertion of a short length of prosthetic graft. Spinal cord ischaemia can

occur either before or during surgery, with consequent lower limb paralysis.

11, 12: Questions

11 i. What has been done to this patient

whose chest X-ray (11) is shown here,

and why?

ii.

How would the patient have

presented?

iii. What are the potential risks of the

treatment?

12 This 72-year-old female presented

with a

3-month history of malaise,

sweats, weight loss, cough, and occa-

sional haemoptysis. She developed a

pneumonia that was treated with

antibiotics but responded poorly, and

she remained unwell with a low-grade

fever. She was mildly anaemic with an

ESR of 120 mm in 1 hr and a CRP value

of 92 mg/l.

i. What does the radiograph (12) show,

and what is the differential diagnosis?

ii. How would you make the correct

diagnosis?

iii. How would you treat the patient?

11, 12: Answers

11 i. The image shows an endotracheal stent. Stents are deployed for the

management of extrinsic compression of an airway.

ii. The most likely cause of tracheal compression is a retrosternal goitre, and the

patient would have presented with stridor. However, this should be managed

surgically and not with a stent. Malignant masses or lymph nodes are the most

common cause of more distal main airway compression and may need stenting.

Although airway stents are an effective initial treatment, definitive management of

the underlying lesion should be first choice, for example using surgery (although

this is unlikely as the disease is usually advanced by the time major airway occlusion

occurs). Radiotherapy and chemotherapy can be effective, especially in small-cell

lung cancers. However, in tracheal cancers and squamous cell lung cancers, where

the disease often relapses locally after chemotherapy and radiotherapy, stents can

dramatically relieve symptoms.

iii. Airway stents also may become a nidus of infection and may become blocked

due to secretions, resulting in a sudden deterioration in respiratory status.

12 i. The chest radiograph shows multiple lesions of variable size throughout both

lung fields, most of which have cavitated. The differential diagnosis includes

staphylococcal pneumonia, lymphoma, TB, cavitating squamous cell carcinoma,

and a vasculitis - most likely Wegener’s granulomatosis.

ii. This female had Wegener’s granulomatosis. The diagnosis was made by

identifying cytoplasmic ANCA in high titre in the peripheral blood. This is positive

in more than 90% of cases and negative in classic polyarteritis nodosa and other

vasculitides. The titres of cytoplasmic ANCA parallel disease activity and return to

normal when the disease is in remission. They can predict reactivation if a rise is

detected in patients in remission.

iii. Untreated disease is fatal, with a median survival of 5 months. The treatment of

Wegener’s granulomatosis, whether confined to the lung or more extensive with

renal involvement, is with prednisolone and cyclophosphamide. In general,

prednisolone is given at 1 mg/kg for 4 weeks and then slowly tailed down to a

maintenance of 10 mg/day. Cyclophosphamide is commenced at 100-150 mg

orally, and is then reduced by 25 mg every 2-3 months to 50 mg/day. Treatment is

continued for 1 year after remission has been achieved.

Approximately 75% of patients achieve a complete remission, and a further 15%

a partial remission. Serial cytoplasmic ANCA titres should be performed to predict

relapse, which can occur in up to 50% of cases. The prognosis is better for

Wegener’s granulomatosis that is confined to the lung.

13, 14: Questions

13a

13b

13 This previously well 36-year-old East African female has had increasing

shortness of breath for 3 weeks associated with a dry cough and some retrosternal

chest pain on deep breathing. On examination, she is pyrexial at 37.7°C and

cyanosed, with a respiratory rate of 40 breaths/min. Auscultation of the chest

reveals some fine bilateral crepitations, and blood and sputum cultures are both

negative. Her chest X-ray (13a) and CT scan (13b) are shown.

i. What is the likely diagnosis?

ii. How can the diagnosis be confirmed, and what is a likely underlying condition?

iii. What is the recommended treatment?

14 Shown here (14) is a swollen right

ankle and diffuse macular rash in a

young female with cystic fibrosis.

i. What is the diagnosis?

ii. What is the medical treatment and

prognosis?

13, 14: Answers

13 i. The combination of an insidious but progressive illness with cough, marked

hypoxaemia, and a chest radiograph showing bilateral perihilar infiltrates with

peripheral sparing (13a) (confirmed as mainly upper lobe symmetrical ground-glass

infiltrates with peripheral sparing on CT scan (13b)) are highly suggestive of

Pneumocystis jirovecii pneumonia (formerly Pneumocystis carinii pneumonia or

PCP). In addition, the patient belongs to a high-risk population (sub-Saharan

African).

ii. P. jirovecii pneumonia is the classical opportunistic pneumonia affecting HIV-

positive patients, especially once their lymphocyte CD4-positive count has fallen to

less than 200 cells/μl. Presentation is usually a slow onset of dyspnoea associated

with an unproductive cough, sometimes associated with a distinctive retrosternal

pain on inspiration or coughing. The pyrexia is relatively mild, and chest signs are

often limited. Patients characteristically have a fall in oxygen saturations on exercise

and a marked reduction in their carbon monoxide transfer factor.

Diagnosis requires obtaining a BAL or induced sputum sample for cytology, in

which the characteristic cysts can be identified by cytology using Grocott’s

methenamine silver staining (which stains the cysts black), or immunofluorescence

with specific antibodies. A classical presentation in someone known to be HIV

positive can be treated empirically, reserving invasive investigations for if the patient

fails to respond. Pneumocystis jirovecii pneumonia also occurs in patients with

other T-cell defects such as those who have had organ or bone marrow

transplantation, or individuals on long-term immuosuppression.

iii. Treatment is with high-dose co-trimoxazole (120 mg/kg in divided doses daily

for 3 days, and then 90 mg/kg). If the PaO₂ is <9.3 kPa (70 mmHg) or the alveolar

oxygen gradient is >4.7 kPa (33 mmHg), adjuvant corticosteroids have been shown

to improve outcome (e.g. 40 mg prednisolone twice a day for 5 days, followed by

40 mg for 5 days and then 20 mg for 11 days). For patients who are intolerant of

Septrin (co-trimoxazole), second-line therapy is usually primaquine 15 mg once

daily and clindamycin 600 mg four times a day.

14 i. The illustration shows a diffuse vasculitis involving the skin and synovium.

Vasculitis of the skin may also be nodular or purpuric (without thrombocytopenia).

It is associated with severe pulmonary disease and chronic Pseudomonas aeruginosa

infection. It has been attributed to an overspill into the systemic circulation of

immune complexes resulting from the hyperimmune stimulation associated with

chronic pulmonary disease.

ii. Medical treatment consists of short-term, high-dose oral steroids. This will

usually produce complete resolution. Immunosuppressive agents have been used,

but experience with them is limited.

15, 16: Questions

15 A 40-year-old male presented with a

15a

3-week history of cough, malaise, and

fevers that had not responded to a

variety of broad-spectrum antibiotics.

His blood tests showed an ESR of 115

mm/hr, a CRP of 194 mg/l and a white

cell

count of

15.3x10⁹/l

(22%

eosinophils at

3.5x10⁹/l). Microbio-

logical tests, including sputum and

blood cultures, serology for parasitic

infections, and analysis of sputum and

faeces for parasites, were all negative.

His chest X-ray is shown here (15a).

i. The chest X-ray has a characteristic

appearance suggestive of which disease?

ii. How can the diagnosis be confirmed?

iii. What is the treatment and prognosis?

SpO

SpO₂

100

bpm

140

Pulse

120

100

1:00am

3:00am

5:00am

150

16 i. What is this test (16), and what does it show?

ii. How useful is this type of study in sleep-disordered breathing?

15, 16: Answers

15 i. The chest X-ray shows patchy

15b

dense consolidation affecting the lung

peripheries, with sparing of the medial

aspects of the lung. These appearances

were confirmed by the CT scan of the

thorax (15b). This is highly suggestive

of an eosinophilic pneumonia, an

idiopathic disorder characterized by

eosinophilic infiltration of the lung

parenchyma. Acute (develops over days)

and chronic (develops over weeks or months) forms occur, but the characteristic

peripheral shadowing is most associated with the chronic form.

ii. The blood eosinophil count is not always raised, especially early in the disease,

but BAL fluid will contain a high proportion of eosinophils (usually >25%, but

90% is not uncommon with pulmonary eosinophilia), and this confirms the

diagnosis. Blood IgE levels are usually elevated. Other lung diseases associated with

blood eosinophilia are Löffler’s syndrome (transient pulmonary infiltrates often

associated with parasitic infections such as Ascaris or Strongyloides), or drugs such

as aspirin

[aminosalicylic acid] and sulphonamides

[sulfonamides]), allergic

bronchopulmonary aspergillosis, Churg-Strauss syndrome, and idiopathic

hypereosinophilic syndrome. Asthma is also frequently associated with a mild

eosinophilia.

iii. Eosinophilic pneumonias usually respond rapidly to oral corticosteroids, with

a complete resolution of symptoms and radiological abnormalities within 1 month

on tapering courses of oral prednisolone starting at between 30 and 60 mg/day.

16 i. The test is an overnight recording of SaO₂ and heart rate.

ii. The equipment will calculate the number of oxygen dips of >4% and give an

hourly dip rate, which will identify sleep apnoea. This is an effective and simple

screen test for OSA and can easily be carried out by the patient at home. It does not

record snoring or actual sleep. It is useful for central apnoea and also for assessing

the requirement for domiciliary oxygen in hypoxaemic patients, such as those with

severe COPD. If the results are not clear cut, a more sophisticated sleep study is

required.

17, 18: Questions

17 This is the chest X-ray (17) of a 16-

year-old male who presented with a 3-

week history of a dry cough and fevers.

i. What does the chest X-ray show?

ii. What is the likely diagnosis?

iii. What contact tracing procedures

should be instigated?

This

65-year-old female has

rheumatoid arthritis, and her physician

wishes to commence immuno-

suppression. There is, however, a

concern over reactivating a latent TB

infection. A tuberculin skin test is

positive, and a gamma-interferon test is

negative.

i. Describe the chest X-ray (18).

ii. How would you interpret the other

results?

iii.

Does the patient require

antituberculous therapy?

17, 18: Answers

17 i. Unilateral enlarged paratracheal lymph nodes.

ii. Primary pulmonary TB. The initial infection with Mycobacterium tuberculosis

in children with no prior history of exposure to the disease leads to a small primary

focus of infection, usually in the middle to lower zones on the chest X-ray when

visible, and associated with enlarged mediastinal nodes on the affected side. The

mycobacteria disseminate into the blood from the enlarged nodes and can therefore

be seeded throughout the body, but they have a predilection for areas of relatively

high oxygen tension such as the apices of the lungs, the CNS, and the metaphyses

of the long bones.

Primary disease causes symptoms in only a minority of patients (less than 10%),

usually resolves spontaneously (often leaving a tuberculoma), and is associated with

conversion to a positive tuberculin skin test after 6 weeks. However, primary disease

can be complicated by progressive local disease within the lungs, bronchial

obstruction by enlarged nodes (especially the middle lobe, leading to bronchiectasis),

bronchogenic TB due to the rupture of a caseating node into the bronchial tree,

pleural or pericardial effusions, miliary TB, and tuberculous meningitis.

iii. Contact tracing is initiated to identify (a) cases who have caught TB from the

index case, (b) the potential source of infection for the index case, and (c) other

patients who may have been infected by this source. Recommendations vary

between countries but usually suggest the screening of all subjects who live with the

index case and other close contacts such as school classmates.

Screening requires a clinical history, chest X-ray, and tuberculin skin testing (at

least in children or those who have not been given the BCG vaccine). The new

gamma-interferon blood tests for TB identify whether the patient has circulating

lymphocytes that recognize an antigen specific for M. tuberculosis, and may provide

a more specific and sensitive test for identifying infected patients than tuberculin

skin testing.

18 i. The chest X-ray shows calcified lymph nodes and volume loss on the left, with

marked, very thick calcified pleura indicating previous TB infection.

ii. The positive tuberculin skin test is in keeping with previous TB infection but

may also occur following BCG vaccination and in patients with latent or active TB.

The gamma-interferon test is specific for TB infection and is not usually positive in

patients who have had a BCG. The test is raised in patients with latent TB infection.

iii. Taking the above answers into account, this patient has evidence of previous

TB infection but no latent TB, and she will not require TB prophylaxis prior to

immunosuppression.

19, 20: Answers

Nodule size

(mm)*

Low-risk patient^†

High-risk patient^‡

No follow-up needed^§

Follow-up CT at 12 mo; if

unchanged, no further follow-up^||

>4-6

Follow-up CT at 12 mo;

Initial follow-up CT at 6-12 mo

if unchanged, no further

then at 18-24 mo if no change^||

follow-up^||

>6-8

Initial follow-up CT at

Initial follow-up CT at 3-6 mo

6-12 mo then at 18-24 mo

then at 9-12 and 24 mo if no

if no change

change

Follow-up CT at around 3,

Same as for low-risk patient

9, and 24 mo, dynamic

contrast-enhanced CT,

PET, and/or biopsy

* Average of length and width. ^† Minimal or absent history of smoking and of other known

risk factors. ^‡ History of smoking or of other known risk factors. ^§ The risk of malignancy in

this category (<1%) is substantially less than that in a baseline CT scan of an asymptomatic

smoker. ^|| Non-solid (ground-glass) or partly solid nodules may require longer follow-up to

exclude indolent adenocarcinoma.

19 i. The CT scan demonstrates a 7 mm nodule in the left lower lobe with

background changes of emphysema.

ii. The causes of this nodule include malignancy (primary or secondary) or benign

causes such as past or current infection. In order to distinguish malignant from

benign nodules, the Fleischner Society have published guidelines (Table) on the

management of solitary pulmonary nodules, taking into account the relatively slow

doubling time of lung cancer.

20 Massive pleural fibroma, with spontaneous hypoglycaemia. The huge size of the

tumour in an otherwise healthy patient suggests that it is benign in nature. The

diagnosis is easily confirmed by percutaneous needle biopsy. Large mesenchymal

tumours may produce insulin-like growth factors. It is probable that these peptides

both stimulate the growth of the tumour itself, which may attain great size, and lead

to spontaneous hypoglycaemia. Insulin-like growth factors are normally produced

under the control of growth hormone, and their abnormal production leads to its

suppression by a negative feedback mechanism. Plasma insulin and C-peptide levels

are also low. Despite their large size, the tumours can be removed quite easily

surgically as they usually arise from the parietal pleura on a finger-like stalk. Resection

leads to complete resolution of the biochemical abnormalities.

21, 22: Questions

21a

21b

21 This is the chest radiograph (21a)

and CT scan (21b) of the thorax of a 78-

year-old male who has presented with a

minor haemoptysis. He was treated for

TB in the 1950s.

i. What is the cause of the most striking finding?

ii. What was this a treatment for, and what other operative therapies are there for

this disease?

22 This male presents having had right

anterior chest pain for 1 month.

i. What is the abnormality on the chest

X-ray (22)?

ii. Which cell type of lung cancer is most

commonly associated with this

complication, and what test is best for

recognizing this?

iii. How would you treat the symptoms?

21, 22: Answers

21 i. The CT scan shows that the patient has previously been treated with plombage

- the insertion of inert balls made of Leucite extrapleurally inside the chest. These

collapse the underlying lung.

ii. Plombage was a surgical therapy for TB used before antibiotic therapy was

available. Other surgical treatments included crushing of the phrenic nerve (which

leaves a small supraclavicular scar and a raised hemidiaphragm on the treated side)

and thoracoplasty, in which the ribs over the upper lobe were removed. All these

treatments collapsed the underlying lung and controlled TB by making the affected

lobe underventilated and therefore hypoxic (as Mycobacterium tuberculosis

requires aerobic conditions to grow). Antituberculous chemotherapy now means

these operations are generally obsolete, although thoracoplasty may very rarely be

used to control highly drug-resistant TB.

Nowadays, the main relevance of these surgical treatments are the long-term

complications. Thoracoplasty causes a restrictive lung function impairment which

can lead to type 2 respiratory failure that responds well to chronic nocturnal non-

invasive ventilation, and plombage can become infected or cause pressure effects on

local structures.

22 i. The chest X-ray shows a mass destroying the right third rib and an associated

soft tissue mass. There is a large tumour mass in the left upper lobe. The patient had

presented with chest pain, and a non-small-cell lung cancer was diagnosed at

bronchoscopy. Small-cell lung cancers most commonly develop bony metastases in

up to 40% of patients, but they can occur in any cell type. The bony lesion is usually

lytic, i.e. destructive, but tissue masses of tumour can grow out from the bony

lesion, as in this case. The vertebral bodies are another common site for this.

ii. Bone lesions are usually identified at staging, although the great majority present

with symptoms of pain, bone tenderness, and an elevated serum alkaline

phosphatase, or serum calcium if extensive. The PET scan has surpassed isotope

bone scanning and CT scanning as the most useful test to identify these lesions.

iii. If the lesion is solitary and painful, a single fraction of radiotherapy is effective

in 70-80% of cases. This can be repeated as necessary. Analgesia should follow the

pain ladder, starting with paracetamol and a non-steroidal anti-inflammatory

medication. This can be increased to opiates, initially short acting to assess dose

requirement, and then to slow-release preparations with short-acting top-ups as

necessary. It is important to administer antinausea medication as necessary and to

add aperients to prevent predictable constipation.

23, 24: Questions

23 Patient A has a large left pleural effusion and a single breath gas transfer factor

(DL_CO) of 55% of normal, along with a transfer coefficient (K_CO) that is 90% of

normal. Patient B with bullous emphysema has a DL_CO of 55%.

i. What is the K_CO? How is it measured?

ii. Why does the K_CO in Patient A correct to near normal?

iii. What is the K_CO likely to be in Patient B (i.e. high, normal, or low), and why?

24 This is the chest radiograph (24) of a

30-year-old male who is aysmptomatic

apart from mild dyspnoea on exertion.

i. What does the chest radiograph show?

ii. What are the possible causes?

iii. What should the lung function tests

show?

iv. What is the management?

Lung function results

FEV₁

2.7 (65% expected)

FVC

3.8 (61% expected)

23, 24: Answers

23 i. The K_CO is the single breath gas transfer factor (DL_CO) corrected by the

alveolar volume. The alveolar volume is measured by an inert gas technique -

usually using helium - which is inspired together with the carbon monoxide. As the

helium is inert, it will not escape from the lungs, and the dilutional decrease

measured on expiration will give the alveolar volume, that is, the volume of lung

that saw the helium and therefore the carbon monoxide. In other word, it is the

amount of volume that was available in the circumstances of this test for gas

exchange. The DL_CO divided by the alveolar volume gives the transfer coefficient,

which is the quality of gas exchange in those areas of the lungs that were available

to the two gases.

ii. The K_CO in Patient A corrects to near normal as the alveolar volume is essentially

that of the non-affected lung, i.e. the right lung, which will exchange gas normally.

iii. Here, the K_CO is likely to be low. In a patient with emphysema, the DL_CO will

be low because of poor ventilation and perfusion balance due to parenchymal

damage. The lung volumes, however, will be normal or larger than normal, and

the alveolar volume will be normal or high. Correcting a low DL_CO by a normal or

high alveolar volume will give a low K_CO. This low (often very low) K_CO is

characteristic of emphysema.

24 i. The chest radiograph shows marked pleural thickening affecting the right

hemithorax.

ii. The likely causes of unilateral pleural thickening are previous empyema, TB, or

haemothorax on the affected side. In addition, pleural tumours, in particular

mesothelioma, can cause pleural thickening, which would be progressive and

usually associated with pain and pleural effusions. Benign asbestos-related pleural

disease is usually bilateral. Rarer causes include radiotherapy or drug reactions (e.g.

practolol, methysergide, dantrolene, methotrexate, and drugs associated with a

lupus-like syndrome such as procainamide, isoniazid, and hydralazine).

iii. The lung function tests should show a restrictive defect with reduced lung

volumes and a normal transfer factor. In this patient, the FEV₁ was 2.7 (65% of

predicted) and the FVC 3.1 (61% of predicted), giving a ratio of 87%.

iv. Benign pleural thickening requires no further investigation, and there is no

specific treatment except for surgical removal of the pleura. However, surgery is

difficult due to the dense adhesions of pleura to the lung, and it is reserved for when

the physiological effects of the pleural thickening are severe. Over several months,

initially quite marked pleural thickening after empyema or haemothorax can often

undergo a significant degree of resolution without intervention. Progressive pleural

thickening needs to be biopsied (either CT-guided or VATS) to exclude the presence

of tumour.

25, 26: Questions

25 A 72-year-old female presented with

25a

a several week history of increasing

shortness of breath and dry cough. She

had recently been admitted for

management of cardiac failure and atrial

fibrillation but was not now in cardiac

failure. On examination, she was

apyrexial and had fine inspiratory

crepitations in both lung fields. Blood

and sputum cultures were negative, and

blood tests including white cell count

were unremarkable except for a CRP of

34 mg/l.

i. Describe the radiological appearances (25a).

ii. What is the differential diagnosis, and what specific questions in the history are

important?

iii. How can the most likely diagnosis for this radiological appearance be

confirmed?

26 Shown here is the chest X-ray (26) of

a patient who presented with neck

swelling that started after a severe

coughing fit.

i. What does this chest X-ray show?

ii. What is the likely underlying cause?

iii. How should the patient be managed?

25, 26: Answers

25 i. The chest X-ray (25a) shows bilateral

25b

peripheral airspace shadowing suggestive

of consolidation. The CT scan

(25b)

shows patchy

dense

peripheral

consolidation.

ii. Pneumonia should always be con-

sidered as a cause of consolidation, but the

long history, lack of systemic symptoms,

and normal temperature count against an

infective cause in this case. The CT scan

appearances are characteristic of an

organizing pneumonia, a complication of amiodarone treatment. It can also occur

in response to infection, radiotherapy, and chemotherapy, or with no obvious cause

(cryptogenic organizing pneumonia). The history should specifically ask about

treatment with amiodarone as well as any treatment for cancer. About 5% of

patients on amiodarone develop respiratory complications, the incidence being

higher in patients receiving more than 400 mg/day. Amiodarone can cause an

interstitial pneumonitis, organizing pneumonia (as in this case), or rarely non-

cardiogenic pulmonary oedema. Other causes of non-infective consolidation include

alveolar cell carcinoma, lymphoma, pulmonary eosinophilia, and vasculitis.

iii. The radiological appearance combined with a history of amiodarone use is usually

adequate to make the diagnosis. CT scans may demonstrate that the patches of

consolidation and the liver are of relatively high density due to the accumulation of

iodine. Lung function tests will show a restrictive defect with a low transfer factor.

BAL may recover ‘foamy’ macrophages containing phospholipids due to the inhibition

of phospholipase by amiodarone. Although transbronchial biopsy will only

occasionally obtain diagnostic material, a VATS biopsy of organizing pneumonia will

show the characteristic budding of fibroproliferative material into the airways. The

treatment is to stop amiodarone and start oral corticosteroids (30-60 mg/day, weaning

off over several months), which are usually very effective for organizing pneumonia.

26 i. The X-ray shows marked subcutaneous emphysema that is delineating the

tissue planes of the soft tissues of the neck and thorax.

ii. A small pneumothorax or pneumomediastinum due to the rupture of alveoli as

a consequence of the coughing fit. This is more likely to happen in patients with

asthma or COPD.

iii. A CT scan of the thorax may be necessary to identify the pneumothorax or

pneumomediastinum. Most cases settle spontaneously without the need for an

intercostal drain to control the pneumothorax, or surgical intervention.

27-29: Questions

27 This 66-year-old male has breathlessness on minimal exertion and is hypoxic at

rest. Examination of his chest reveals dry inspiratory crackles. Explain the lung

function test abnormalities: FEV₁ 50% normal; FVC 55% normal, FEV₁/FVC ratio

95%; TLC 60% normal; FRC 60% normal; RV 80% normal; DL_CO 40% normal;

K_CO 80% normal.

Pre-bronchodilator

Post-bronchodilator

FEV₁ (l)

2.1

2.5

FEV₁ %

predicted

FVC (l)

3.3

3.5

FEV₁/ FVC %

28 This spirometry (Table) is from a 25-year-old male who complains of a cough

at night.

i. What is the diagnosis?

ii. What constitutes a significant bronchodilator response?

iii. What other investigations might be useful?

29 A 75-year-old male presents with this

chest X-ray (29).

i. What are the most likely causes, and

how would you make the diagnosis?

ii. If cytology is negative, what next?

iii. If this proves malignant, what

treatment would you suggest?

27-29: Answers

27 The spirometry shows a restrictive defect together with uniformly and greatly

reduced lung volumes. This is very suggestive of intrapulmonary disease. In

addition, the DL_CO is drastically reduced, at 40% of normal. When it is corrected

for the lung volume that ‘saw’ the carbon monoxide for measuring diffusion, the

gas transfer partially corrects to 80% of normal. This still, however, means there

is intrapulmonary disease, but the lung units that took in the carbon monoxide and

helium were 80% efficient. If the low DL_CO were due to extrathoracic disease, it

would not have been so low, and it would have corrected to normal as the reduced

lung volume exposed to the measurement gases would have been exchanging

normally in the lung that took in the carbon monoxide/helium mixture.

28 i. The diagnosis is asthma.

ii. A bronchodilator response is significant if the FEV₁ rises by 15% and 200 ml.

iii. Other investigations that are useful in the diagnosis of asthma include peak flow

monitoring morning and evening for a period of 2-3 weeks, sputum or blood

eosinophil count, intradermal skin prick testing, bronchial challenges

(in a

specialized laboratory), exhaled nitric oxide, and bronchoscopy (to exclude airway

obstruction and for bronchial biopsies that may show Charcot-Leyden crystals). In

a young person, a 6-min exercise test of free-range running can induce a post-

exercise drop in PEFR of >20%, which is diagnostic.

29 i. A large effusion in an elderly male is likely to be malignant, from either an

adenocarcinoma or a mesothelioma. In a female, breast cancer can cause this

appearance. The other important cause is TB. Rarer causes include chylothorax,

post-traumatic haemothorax, and post-pneumonia empyema, but the patient would

then be ill.

ii. The initial step would be aspiration for cytology and bacteriology. In malignancy,

cytology is positive in 50-60% of cases. Repeating the procedure hardly improves

the yield. If negative, a CT scan may show a pleural tumour, and a guided core

biopsy can be carried out.

iii. Treatment of a large malignant effusion should be by a pleurodesis, ideally by

VATS and talc pleurodesis. If a diagnosis has not been made prior to VATS, any

suspicious area can be biopsied under direct vision. If malignancy is probable, talc

can then be instilled.

30, 31: Questions

30 A 30-year-old HIV-positive female

30a

presented with a 3-month history of dry

cough and dyspnoea on exercise. She

had no systemic symptoms. On

examination, she looked well and was

apyrexial. The only abnormal signs were

fine crepitations in the lung bases. Her

blood tests were normal, with a CD4-

positive cell count within the normal

range. Sputum and/or BAL cultures

were consistently negative for myco-

bacteria, bacteria, respiratory viruses,

and Pneumocystis. The BAL differential

cell count showed 65% lymphocytes. These are the presentation chest radiograph

findings (30a).

i. Describe the abnormalities of the chest radiograph.

ii. Name six non-infective respiratory complications of HIV infection.

iii. Which are the most likely for this patient?

31 A 60-year-old Caucasian male has a

2-month history of fevers, night sweats,

and weight loss.

i. Describe what can be seen in the

photograph (31).

ii. What is the differential diagnosis?

30, 31: Answers

30 i. The chest radiograph shows an asymmetrical nodular consolidation mainly

affecting the left lower lobe. CT demonstrated ground-glass shadowing, some small

nodules, and thickened interlobular septae.

ii.

• Malignant: Kaposi’s sarcoma, lung cancer, pulmonary lymphoma.

• Inflammatory: non-specific interstitial pneumonitis, LIP, organizing

pneumonia.

• Other: COPD, bronchiectasis, pulmonary hypertension.

iii. The nodular lung shadowing, and high proportion of lymphocytes in the BAL

fluid suggest that the patient has LIP. LIP is characterized by a lymphocytic

infiltration of the alveoli and septa, and causes cough and dyspnoea with systemic

symptoms in some patients. The diagnosis requires a lung biopsy to exclude other

diseases associated with lymphocytic BAL fluid, mainly pulmonary lymphoma,

which can have a similar presentation. Treatment is with prednisolone and

sometimes chlorambucil, and can be effective. Long-term complications of LIP

include lung fibrosis and bronchiectasis.

31 i. The picture shows enlarged cervical

Differential diagnosis of anterior

lymphadenopathy in the anterior triangle

cervical lymphadenopathy

(anterior to the sternomastoid).

ii. The Table

lists

the

differential

Infectious

diagnoses.

• TB

• Viral, e.g. HIV, Epstein-Barr virus,

CMV

• Toxoplasmosis

• Cat scratch disease (Bartonella

henselae)

• Histoplasmosis,

coccidioidomycosis

• Non-tuberculous mycobacteria

Malignancy

• Lymphoma

• Secondaries, e.g. lung, stomach

Reactive

• Secondary to mouth, throat, and

local skin infections

Drug reactions, e.g. phenytoin

Sarcoidosis

Langerhans cell histiocytosis

Storage diseases, e.g. Gaucher’s

disease

32, 33: Questions

32a

32b

32 A 72-year-old male presented to his

GP with a history of hoarseness. Other

than moderate hypertension, he had no other past history of note. A radiograph

(32a) and CT (32b) were done.

i. What abnormality is present, and what is the likely aetiology?

ii. What classification system can be applied to this abnormality?

iii. Why is the patient hoarse?

iv. How would this condition be managed, and what risks should be discussed with

the patient?

33 This is the chest X-ray (33) of a 64-

year-old male who has a long history of

recurrent chest infections, chronic ear

infections, and sinusitis.

i. What does the X ray show, and what

is the likely diagnosis?

ii. How is it inherited, and what is the

major defect?

ii. How can the diagnosis be confirmed?

iv. What other complications should be

discussed with the patient?

32, 33: Answers

32 i. This patient has a large aneurysm of the aortic arch. The most likely aetiology

is hypertension, but serological testing for syphilis would be appropriate. If it had

been located at the junction of the arch and descending aorta, a post-traumatic

origin would have been a possibility.

ii. Aortic aneurysms may be classified in several ways. A ‘true’ aneurysm is

contained within all the layers of the aortic wall, although these may be greatly

thinned and it is common for the aneurysm to be lined with old and new thrombus.

Depending on the appearance of the aneurysm, it may be described as ‘saccular’,

as in this case, or ‘fusiform’ if the dilatation is more cylindrical. If the aneurysm is

formed from a localized hole in the aortic wall connecting with a cavity lined only

by thrombus, it is described as a ‘false’ aneurysm. An aortic dissection is often

labelled as a ‘dissecting aneurysm’. This condition is characterized by the entry of

blood into the layers of the aortic wall through a split in the intima with prograde

and/or retrograde extension of this process along a variable length of the aorta.

iii. The left recurrent laryngeal nerve has been stretched by the aneurysm.

iv. Hypertension should be controlled and the aneurysm size monitored. If it is

static, a conservative approach may be appropriate in someone of moderate general

health or advanced age in view of the operative risk. Expansion would dictate

surgical excision, probably with replacement of the aortic arch under hypothermic

circulatory arrest. The patient should be warned of the magnitude of operative risk

(>10% mortality) and specifically advised of the additional risk of perioperative

cerebral damage.

33 i. Dextrocardia with some basal bronchial wall thickening. The diagnosis is

Kartagener’s syndrome - primary ciliary dyskinesia causing recurrent respiratory

tract infections, sinusitis, and bronchiectasis, as well as dextrocardia.

ii. Primary ciliary dyskinesia is an autosomal recessive disorder with incomplete

penetrance, and occurs in 1 in 15,000-30,000 people in developed countries.

Structural defects in ciliary proteins, including the dynein arms, cause the cilia to

be immotile. This results in a failure of mucociliary function, mucous collection, and

recurrent infections in the lungs and sinuses, with secondary bronchiectasis.

iii. The diagnosis is made by the saccharin test: a small tablet of saccharin is placed

in the anterior nares, and the time before the patient experiences a sweet taste is

recorded - longer than 40 min suggests ciliary dysfunction. The defect can be

confirmed by specialized tests of ciliary movement in nasal mucosal biopsies and/or

by electron microscopy of cilial structure. Bronchiectasis can be shown by HRCT.

iv. Many patients suffer from mucous retention in the ear, and most male patients

are also infertile and need to be warned about this.

34, 35: Questions

34a

34 i. Describe the bronchoscopic appearances seen here (34a).

ii. What sign would you expect the patient to demonstrate?

iii. Describe the findings of a flow-volume loop from a patient with this condition,

and indicate which other conditions may cause a similar flow-volume loop.

35 The mediastinum is divided into three compartments for the classification of

mass lesions. The anterior compartment lies between the sternum and the anterior

surface of the pericardium and the great vessels. The middle compartment contains

the intrathoracic organs and extends to the vertebral column. The posterior

compartment comprises the paravertebral spaces. List the more common mass

lesions found in each compartment.

34, 35: Answers

34b

TLC

34 i. The image shows a tumour causing obstruction of the trachea. The trachea can

be recognized by the presence of cartilaginous rings anteriorly.

ii. The patient is likely to have inspiratory stridor, which can occur with any cause

of extrathoracic airway obstruction. Typical flow-volume loops are shown in 34b.

Fixed lesions are characterized by a lack of changes in calibre during inhalation or

exhalation, and produce a constant degree of airflow limitation during the entire

respiratory cycle. A fixed lesion may be extrathoracic or intrathoracic, and results

in a flattening of both the inspiratory and the expiratory portions of the

flow-volume loop (A). Its causes include post-intubation strictures, goitres, and

tracheal tumours.

iii. Variable lesions are characterized by changes in airway lesion calibre during

breathing. A variable extrathoracic obstructing lesion results in the limitation of

inspiratory flow, seen as a flattening in the inspiratory limb of the flow-volume

loop (B). During expiration, the air is forced out of the lungs through a narrowed

(but potentially expandable) extrathoracic airway. Therefore, the maximal

expiratory flow-volume curve may be normal. Causes of variable extrathoracic

lesions include glottic strictures, tumours, and vocal cord paralysis.

• Anterior: thymoma, thymic carcinoma, thymic cyst, lymphoma, benign or

malignant teratoma, seminoma, parathyroid adenoma, retrosternal thyroid

goitre, lipoma, leiomyoma, cystic hygroma.

• Middle: lymphoma, benign mediastinal lymphadenopathy, granulomatous

diseases (TB, sarcoid), metastatic lymphadenopathy, foregut cysts, oesophageal

disorders (achalasia, diverticulae, tumours), aneurysms.

• Posterior: peripheral nerve tumours (schwannoma, neurofibroma,

ganglioneuroma), paraspinal abscess, thoracic duct cysts, extramedullary

haematopoiesis.

36, 37: Answers

36 i. Cavitation within the left upper lobe, with an air-fluid level present in an area

of dense consolidation. The history of fevers and foul-smelling sputum suggests

that this is a cavitating pneumonia.

ii. Community-acquired cavitating pneumonias are associated with:

• Anaerobes (associated with aspiration).

• Gram-negative coliforms, including Klebsiella pneumoniae (which classically

causes an expanding pneumonia in the upper lobe, especially in patients such

as alcoholics who have a degree of immunosuppression).

• Staphylococcus aureus (usually multiple small cavitations, often occurring after

influenza infection).

• 5% of pneumonias due to Streptococcus pneumoniae.

On the right patient background or in the right geographical area, other pathogens

that cause cavitating lung infections include Mycobacterium tuberculosis, non-

tuberculous mycobacteria, actinomycosis, Nocardia, Aspergillus, and other moulds,

Burkholderia pseudomallei (melioidosis), endemic fungi (e.g. histoplasmosis,

coccidioidomycosis), and flukes (paragonimiasis). In addition, septic emboli from

infected indwelling lines or right-sided endocarditis will cause multiple cavitating

lesions that are often peripheral and associated with effusions.

iii. Microscopy of sputum (including staining for acid-fast bacilli) and cultures of

the blood and sputum. Consider a CT scan of the thorax and bronchoscopy to

define the cavities in greater detail and to exclude a proximal bronchial lesion

causing obstruction to the bronchus supplying the affected lobe.

37 Hydropneumothorax. The presence of a large quantity of both air and fluid in

the pleural cavity in a patient with these symptoms is strongly suggestive of rupture

of the oesophagus. The fluid was turbid but not purulent. The underlying cause

was ulceration of the oesophagus by tuberculous mediastinal lymph nodes.

Rupture of the oesophagus can occur in previously fit individuals, for example

after violent vomiting or impaction of a food bolus or foreign body, and is a medical

emergency. It may initially cause retrosternal or pleural pain. It may be missed at

oesophagoscopy if the tear is small, and is best diagnosed by a barium swallow.

Immediate repair by a thoracic surgeon is the treatment of choice.

Rupture can occur as the result of an oesophageal tumour causing necrosis of

the wall. This may also occur with a tracheal tumour or metastatic subcarinal

nodes. Ensleevement of the lesion with an oesophageal tube can give good

palliation.

Other possible causes of hydropneumothorax include the rupture of a large lung

abscess, empyema, and the rupture of a tuberculous cavity into the pleural space.

Simple aspiration would be inadequate, and drainage with a large-bore intercostal

tube is mandatory, together with appropriate intravenous antibiotic therapy.

38, 39: Answers

38 i. The histology shows dense calcium deposits in the lung parenchyma.

ii. Metastatic calcification. In addition to the pulmonary manifestations, it can also

affect the heart, stomach, kidney, and lung.

iii. Up to 60-80% of patients on chronic haemodialysis have evidence of metastatic

pulmonary calcification on autopsy, most commonly those with secondary

hyperparathyroidism and patients with an elevated calcium phosphate product.

Less commonly associated diagnoses include primary hyperparathyroidism,

multiple myeloma, Paget’s disease, hypervitaminosis D, and malignancies.

39 i. This is superior vena caval obstruction, and in an adult (as depicted), lung

cancer, small-cell type in particular, is the most likely cause. It is seen in up to 10%

of new cases of small-cell tumour. In a younger patient, a lymphoma will be the

probable diagnosis. It can present with headaches, especially on bending forward.

There will be oedema of the upper limbs and face, especially periorbitally. The

oedema can cause a gruff voice and throat pain. The patient may notice the

collateral venous pathways in the chest and upper abdomen.

ii. Ultrasound of the neck may identify supraclavicular or scalene nodal enlargement

that can be aspirated for cytology under ultrasound. CT scanning will usually show

extensive mediastinal nodal masses that are easily accessed by CT-guided biopsy.

Failing this, bronchoscopy and biopsy, or EBUS-guided transbronchial biopsy is

usually possible and safe.

iii. If the condition is due to small-cell carcinoma, chemotherapy is as effective as

radiotherapy, which is the treatment of choice in non-small-cell lung cancer,

followed by chemotherapy if the patient is fit enough. Excellent symptomatic relief

can be rapidly achieved by a superior vena cava stent provided vascular studies

show the superior vena cava to be just compressed and not completely occluded by

tumour.

iv. Other presentations of mediastinal involvement include:

• Recurrent laryngeal nerve entrapment in the subaortic fossa.

• Dysphagia due to subcarinal lymph nodes pushing posteriorly into the mid-

oesophagus.

• Breathlessness and a high hemidiaphragm due to phrenic nerve entrapment.

• Breathlessness due to atrial fibrillation and/or pericardial involvement, and

effusion from invasion by a left lower lobe tumour.

• Horner’s syndrome owing to sympathetic chain involvement in the upper

mediastinum.

• Chylothorax due to rupture of the lymphatic duct by tumour (more common

with lymphoma).

40, 41: Answers

40 i. The CT scan shows bilateral tethered pneumothoraces (a drain is also visible

posteriorly on the left side). In addition, the lung parenchyma contains multiple

thin-walled cysts of varying sizes.

ii. In a young female with a history of pneumothoraces, the CT finding of thin-

walled cysts is highly suggestive of lymphangioleimoymatosis (LAM). LAM is

restricted to females mainly of child-bearing age, and is characterized by atypical

smooth muscle proliferation in the lung

(and occasionally mediastinum,

retroperitoneal lymphatics, or uterus) causing lung cysts, recurrent

pneumothoraces, or chylous effusions. Progression is variable, but respiratory

failure occurs in some patients.

In the differential diagnosis, histiocytosis X should be considered but is very

unusual in non-smokers and the cysts are usually much more variable in size and

shape than in LAM. Bullae and emphysema need to be considered, but the cysts of

LAM are too small and central to be bullae and they also have a well-circumscribed

wall, unlike emphysematous change. Other diseases associated with cysts include

LIP and EAA, but the cysts in these conditions are associated with other parenchyal

abnormalities.

iii. LAM can be isolated or associated with about 1% of cases of the autosomally

dominant inherited disorder tuberous sclerosis. The clinical features of tuberous

sclerosis (subungual fibromas, facial angiolipomas, retinal astrocytomas, renal

angiomyolipomas) need to be looked for, and renal imaging may be necessary to

identify the renal tumours. The patient’s lung function should be measured and

usually shows an obstructive defect with impaired gas transfer and gas trapping.

The diagnosis is confirmed by lung biopsy, which can be obtained at the same time

as surgical treatment of the pneumothoraces is undertaken. Treatment is difficult

but mainly involves hormonal manipulation, e.g. intramuscular medroxy-

progesterone injections.

41 i. This cytology sample shows large, irregularly shaped cells with prominent

nucleoli and coarsely clumped chromatin, indicative of non-small-cell carcinoma.

Intercellular bridges, seen as fine parallel lines between cells, correspond to

desmosomes and are characteristic of squamous cell carcinoma. The histological

feature of keratin pearl formation is not usually visible on cytology specimens.

Despite this, experienced cytologists can reliably distinguish squamous cell

carcinoma from other types of non-small-cell lung cancer on cytology alone.

ii. The sensitivity of bronchial brushings is primarily determined by whether the

lesion that is brushed is visible to the bronchoscopist. Larger, more proximal lesions

have a higher yield on bronchial brushing.

42, 43: Questions

42 A previously well 30-year-old female

presented to hospital with a 2-week

history of dry cough and fevers that had

not responded to a 5-day course of

amoxicillin. On examination, her

temperature was

38°C, she had a

respiratory rate of 20 breaths/min, and

fine

crepitations

were audible

throughout both lung fields. Her oxygen

saturation was 92% breathing air. 42 is

her chest radiograph on admission. Her

HIV test was negative.

i. What does the chest radiograph show?

ii. What are the most likely organisms

for this presentation?

iii. How would you manage this patient?

43 A colleague asks for assistance in

interpreting the lung volumes measured

in the patient whose radiograph is

shown here (43). The TLC measured by

helium dilution was

83% of that

predicted, and the RV was 95% of that

predicted.

i. How can you explain the normal TLC

and RV?

ii. What test would you recommend?

42, 43: Answers

42 i. The chest radiograph shows a fine reticulonodular shadowing throughout

both lung fields.

ii. The combination of a relatively insidious presentation of an infective respiratory

infection with diffuse shadowing would suggest a CAP caused by one of the ‘atypical’

organisms, especially as there has been no response to amoxicillin. These include

Mycoplasma pneumoniae and Chlamydophila pneumoniae, which together cause

around 25% of all cases of CAP (and a higher proportion of the milder cases treated

outside hospital), and the rarer organisms Legionella pneumophila, Chlamydophila

psittaci, and Coxiella burnetii (the cause of Q fever), which are often grouped with

these organisms. Rather than ‘atypical’, a better term for these bacteria is perhaps

‘fastidious’ as they are difficult to culture. Although Mycoplasma and Chlamydophila

classically present in this manner, they often also cause a lobar pneumonia that is

indistinguishable from Streptococcus pneumoniae CAP. Legionella pneumophila is

one of the three organisms that are the common causes of severe CAP, the other

organisms being Strep. pneumoniae and Staphylococcus aureus.

iii. The patient should have blood and sputum cultures, and should be given oxygen

and antibiotics. The important therapeutic point is that atypical/fastidious

organisms do not respond to beta-lactam antibiotics but are sensitive to macrolides.

As a consequence, most guidelines suggest a combination of beta-lactams and a

macrolide as first-line therapy for patients with CAP admitted to hospital.

Identification of an atypical infection requires paired serology samples 2 weeks

apart, although a single high level of IgM to Mycoplasma is enough to confirm M.

pneumoniae infection. In addition Legionella antigen can be detected in the urine

if L. pneumophila serotype 1 is the cause (70% of Legionella cases).

43 i. The TLC and RV appear falsely low because the radiograph suggests larger

than normal lung volumes with flat diaphragms. This is a common problem when

the helium dilution technique or any other inert gas technique is used to measure

lung volumes in the presence of severe airflow obstruction or bullous lung disease.

This is because the test does not allow sufficient rebreathing or washout time for the

inert gas to enter the poorly ventilated areas of the lung. There is thus often a gross

underestimation of the true lung volume. Gas dilution techniques are, however, quite

accurate when used in normal subjects or patients without airflow obstruction.

ii. Repeating the measurement of lung volumes using a body plethysmograph will

provide much more accurate estimates in patients with airway problems and

emphysema. The method has the advantage that it measures the total volume of gas

in the lung, including any that is trapped behind closed airways not communicating

easily with the mouth. Plethysmography is, therefore, the technique of choice in

patients with airflow obstruction.

44-46: Questions

Results of CSF analysis

Appearance

Fibrinous

Predominant cell

Lymphocytes

Cell count/mm³

550

CSF glucose (serum value)

2.1 mmol/l (7.5 mmol/l)

CSF protein

3.1 g/l

Organisms

No organisms seen

44 A 65-year-old has experienced fevers and a change of personality over the last

3 weeks. The results of the CSF analysis are shown in the Table.

i. What is the likely diagnosis?

ii. How could the diagnosis be confirmed?

46 i. What is the probable diagnosis of

this scan (46)?

ii. What is the cause?

iii. What is the possible treatment?

45 A 23-year-old male has a history of

asthma and has presented to the

Accident & Emergency department

following a sudden onset of severe

breathlessness.

i. What does the chest X-ray (45) show?

ii. What should be the management?

44-46: Answers

44 i. The results show a lymphocytic meningitis with a low CSF glucose and a very

high protein level. This is consistent with tuberculous meningitis.

ii. Organisms are rarely seen on specific staining of CSF for acid-fast bacilli. Culture

for Mycobacterium tuberculosis is also often negative, and the diagnostic yield may

be improved by requesting PCR for M. tuberculosis. Other causes of a lymphocytic

CSF include listeriosis, cryptococcosis, and sarcoid. HIV testing is recommended for

all patients with TB.

45 i. The chest X-ray shows a right-sided pneumothorax, a complication of asthma.

ii. Treatment should be with high-flow oxygen and an intercostal chest drain. High-

flow oxygen as well as an intercostal tube is recommended as pure oxygen may

help to flush away the inert nitrogen, which constitutes 80% of room air, from the

pleural space.

46 i. Malignant mesothelioma. The scan shows generalized pleural thickening of an

irregular nature around the left lung and involves the mediastinum. The tumour

will also grow into the lung fissures. The differential diagnosis includes

adenocarcinoma, but these usually cause irregular growth and pleural masses

without the uniformity of mesothelioma.

ii. Around 70% of patients will have a history of exposure to asbestos. Typical

occupation groups include plumbers, shipyard workers, boilermen, and sometimes

demolition workers. Partners can occasionally be exposed from workers returning

home in affected clothing. Crocidolite, which is an amphibole (straight) fibre and

can easily penetrate through the tissues, is responsible for 90% of cases. About

1,800 cases a year are seen in the UK, with an expected peak incidence in 2020.

iii. Treatment remains controversial. Surgical resection is a very occasional option

in early disease but requires an extensive operation in terms of an extrapleural

pneumonectomy. There is little evidence that this is superior to other treatments or

to simply best supportive care, with a median survival of 19 months. Radiotherapy

is useful for treating diagnostic aspiration or VATS sites to prevent tumour growing

through the chest wall. Although chemotherapy is widely used, it may produce a

partial response in only 20% of cases. A recent trial of pemetrexed (Alimta) with

cisplatin recorded a doubling of response rate compared with cisplatin alone (41%

versus

17%) and better median survival times

(12.1 versus

9.3 months).

Chemotherapy should only be considered in good performance status patients.

47, 48: Questions

47 A 20-year-old patient is complaining

PEFR

of severe breathlessness after each time

l/min

he roller-blades. The result of exercise

600

testing revealed is shown in 47.

500

i. What does the exercise test show?

400

ii. What is the diagnosis?

300

iii. How would you manage this

200

condition?

100

iv. What is the pathogenesis of this

condition?

-10

10 15 20 25 Time (min)

v. What drugs are allowed by the

Pre-exercise Post-exercise

Olympic committee before competition?

48 This chest radiograph (48) is of a 51-

year-old male from south-east Asia with

dyspnoea and leg swelling. He was

jaundiced and had jugular venous

distension and ascites on physical

examination.

i. What are the radiographic findings?

ii. What infection could account for

both the clinical and the radiographic

abnormalities?

iii.

How can this diagnosis be

established?

iv. How is it treated?

47, 48: Answers

47 i. A 40% fall in peak flow reading after exercise compared with the pre-exercise

value.

ii. Exercise-induced asthma. This diagnosis requires a minimum change of 25% in

PEFR from the pre-exercise value to the lowest measurement - usually found 10-20

min post-exercise. During exercise, a rise in PEFR is commonly seen.

iii. Advise the patient to inhale a beta-agonist 15 min before exercise and to warm

up adequately.

iv. Exercise results in isocapnic hyperventilation and an inhalation of cold air, which

results in water loss from the airway lining, causing airway cooling and

hypertonicity. These result in vasoconstriction, mast-cell activation, and stimulation

of the neural reflexes that cause rebound vasodilatation, oedema, and bronchial

hyperreactivity. Mucosal thickening and smooth muscle contraction will then occur,

leading to bronchoconstriction of the airways. Current research shows that

leukotrienes may also play an important role in exercise-induced asthma.

v. Beta-agonists and sodium cromoglicate (cromolyn).

48 i. The chest radiograph shows enlargement of the pulmonary arteries, suggesting

pulmonary hypertension.

ii. The combination of pulmonary hypertension and hepatic failure should suggest

the diagnosis of schistosomiasis when the patient originates from an area in which

this infection occurs. Schistosomiaisis is caused by one of the blood flukes

Schistosoma mansoni, S. japonica or S. haematobia, which are endemic to tropical

areas with an appropriate intermediate host population of freshwater snails.

Free-swimming cercariae penetrate human skin and then become schistosomulae

that migrate through the lungs to mature in specific mesenteric venous plexuses.

Pulmonary manifestations including cough and wheezing, and infiltrates can

accompany the systemic symptoms of ‘Katayama fever’ during the migration of

schistosomulae through the lungs in acute schistosomiasis.

Eggs produced by the mature flukes are carried downstream from the mesentery

and lodge in the liver. A massive and inappropriate granulomatous inflammatory

response to the schistosomal eggs then results in tissue injury and fibrosis. The liver

eventually becomes cirrhotic, and portosystemic collateral channels permit embolic

eggs to reach the lungs, where a similar inflammatory response ensues. The end

result is pulmonary hypertension and cor pulmonale.

iii. The diagnosis of schistosomiasis is based on identification of the eggs in the

stools or urine of patients with a compatible clinical presentation and a history of

travel or residence in an endemic area (parts of South America, the Caribbean,

Africa, and the Middle and Far East).

iv. Treatment with praziquantel is effective in preventing further egg production

but may not improve the lesions.

49, 50: Questions

Test

Result

Reference range

FiO₂

0.5

7.54

7.35-7.45

PaCO₂

3.7 kPa

4.6-6.0 kPa

(28 mmHg)

(35-46 mmHg)

PaO₂

9.1 kPa

12-16 kPa

(69 mmHg)

(91-122 mmHg)

HCO₃

18 mmol/l

22-30 mmol/l

49 These arterial blood gas tensions (Table) are from a 25-year-old male with

nocturnal confusion 24 hr after the pinning of a fractured femur sustained in a

motor vehicle accident. No abnormality was detected on physical examination or

chest radiography. What is the likely diagnosis and management?

50a

50b

50 Shown here (50a) is a photomicrograph of normal human alveolar macrophages

obtained by BAL and incubated in vitro. 50b shows the same cell preparation after

it has been incubated with gamma-interferon.

i. What are the primary functions of alveolar macrophages?

ii. What are the roles of the secretory products of alveolar macrophages?

49, 50: Answers

49 Fat embolism syndrome. Acute lung injury arises due to a deposition of fat

globules displaced from the marrow of the fractured bone into the pulmonary

arteries, with a subsequent release of free fatty acids. The syndrome begins with

tachypnoea very soon after the trauma or orthopaedic surgery. Chest radiographs

may initially be normal but may progress to show a pattern of ARDS, at which

time chest examination will reveal widespread fine crackles.

Treatment is with oxygen and is supportive, as for any other form of acute lung

injury. Corticosteroids are of no benefit, except possibly if given early. Other

features of the syndrome include CNS effects ranging from mild disorientation to

seizures and coma, usually 12-36 hr after injury. Petechiae may be present,

particularly in the conjunctivae and over the upper extremities and axillae. Both of

these features are the result of microvascular injury.

50 i. Alveolar macrophages are the resident phagocytic cells in the lung. They serve

as scavengers of inhaled particulate material and senescent cells, and are the

sentinels against invasion of the lung by infectious agents.

ii. Non-specific scavenger receptors permit the alveolar macrophage to bind and

ingest inert substances without initiating an inflammatory response. In contrast,

the ingestion of infectious pathogens typically stimulates a brisk response that

results in macrophage activation and inflammatory cell recruitment. These events

are regulated by networks of secretory products, primarily cytokines. Gamma-

interferon, produced by lymphocytes, is a potent macrophage-activating factor. The

alveolar macrophage can also be activated by autocrine cytokines, including tumour

necrosis factor, interleukin-1, and granulocyte-macrophage colony-stimulating

factor.

These mediators promote morphological changes such as the spreading and

clumping seen in 50b. Metabolic changes include stimulation of the oxidative burst

pathway, an upregulation of inflammatory cytokine production, and an increased

expression of cell surface receptors mediating adhesion, phagocytosis, and antigen

presentation.

Other macrophage-derived cytokines, such as interleukin-1 and transforming

growth factor, provide an autocrine negative feedback mechanism by

downregulating many of these macrophage functions. Macrophage-derived

chemotactic factors, including leukotriene B4 and the interleukin-8 chemokine

family, recruit neutrophils to the site of infection, while other products attract

monocytes and lymphocytes. Additional interactions between macrophage-derived

cytokines and epithelial cells, endothelial cells, fibroblasts, and lymphocyte

subpopulations further alter the inflammatory response.

51, 52: Questions

51 The patient whose X-ray (51) is

shown here had polio 30 years ago and

was clinically stable until recently when

he developed fatigue, joint pains, muscle

weakness, swallowing difficulties, and

dyspnoea.

i. What disorder does this patient have,

and what are the underlying factors

responsible

for

his

breathing

abnormality?

ii. How is sleep affected in this disorder?

iii. How is this disorder managed?

52a

52b

52 A 34-year-old female presented with

shortness of breath and chest discomfort

that had lasted for 5 days. Six months earlier, she had been intubated for a period of

12 days, had had slow resolution of her culture-negative pneumonia, suffered an upper

extremity venous thrombosis in conjunction with a central line, was thrombocytopenic

and given a diagnosis of idiopathic thrombocytopenic purpura, and was discharged on

prednisone and warfarin, both of which were discontinued 2 weeks prior to her

current presentation. She had suffered three miscarriages.

BAL returned pink fluid with a red blood cell count of 6400 cells/cm³ and 165 white

blood cells (68% mononuclear, 12% polymorphonuclear, 1% eosinophils). The

anticardiolipin IgG was 69 IU and IgM was 22 IU (>20 IU being considered

moderately positive). 52a shows her chest X-ray, and 52b a VATS biopsy.

i. What does the pathology show?

ii. What is the diagnosis?

51, 52: Answers

51 i. This patient has post-polio syndrome, which usually occurs two to three

decades after the acute infection and recovery. These patients usually have

kyphoscoliosis, which causes restriction and can blunt the hypercapnic drive

because of mechanical impairment. In addition, they may also have decreased

respiratory drive as a result of damage to their medullary neurones and may also

have respiratory muscle weakness. Patients who did not have respiratory

involvement with the initial infection are unlikely to develop such weakness or

kyphoscoliosis.

ii. In the early stages, respiration during sleep is more likely to be affected. Initially,

short central apnoeas occur, and as the condition progresses these become longer

and more frequent. Sleep abnormalities include decreased sleep efficiency and

increased arousal frequency. Eventually, awake respiration can be affected.

iii. Patients with predominantly central sleep apnoea should be managed with

BiPAP during sleep, which is delivered via a nasal mask. A 20 cmH₂O inspiratory

pressure support can be achieved with this, with expiratory support of 5 cmH₂O

delivering a defined number of breaths. This must be timed support, per minute

rather than triggered by the patient’s breathing. Some patients who have more

severe disease that includes irregularities in awake breathing will require ventilatory

support during both sleep and wakefulness. Early ventilation systems included the

negative-pressure tank apparatus. Nasal positive-pressure ventilation is now more

commonly used.

52 i. Alveolar hemorrhage and small-vessel thrombotic occlusion.

ii. Catastrophic antiphospholipid antibody syndrome. Pulmonary damage in this

syndrome involves both chronic venous macro- and micro-thromboembolism, but

non-thromboembolic lung injury caused by capillaritis with pulmonary

haemorrhage is increasingly seen. The diagnosis of catastrophic antiphospholipid

antibody syndrome requires:

1.Evidence of involvement of three or more organs, systems, or tissues.

2.Development of manifestations simultaneously or in less than 1 week.

3.Confirmation by histopathology of small-vessel occlusion in at least one organ

or tissue.

4.Laboratory confirmation of the presence of antiphospholipid antibodies.

The diagnosis is considered definite if all four criteria are met and is probable with:

• All four criteria with only two organs, systems, or tissues.

• All four criteria without confirmation 6 weeks apart due to death.

• Criteria 1, 2, and 4.

• Criteria 1, 3, and 4 with a third event in more than a week but less than 1

month despite anticoagulation.

53, 54: Questions

53a

53b

53 A 58-year-old female with a history of asthma presents with a 3-month history

of dry cough, lower extremity oedema, fatigue, and shortness of breath that has

worsened markedly over the last 2 weeks accompanied by a 9 kg (20 lb) weight

gain. On physical examination, she has bibasilar crackles, her jugular venous

pressure is elevated, and she has bilateral lower extremity oedema. Her chest X-ray

is shown in 53a.

She has a white blood cell count of 7000 cells/cm³, 25% of which are eosinophils.

BAL has demonstrated a white blood cell count of 133 cells/cm³ with 4%

neutrophils, 20% lymphocytes, 17% eosinophils, and 55% macrophages. Her

transbronchial lung biopsy is shown in 53b.

i. What does the lung biopsy show?

ii. What is the diagnosis?

iii. What is the treatment?

54 This 32-year-old male presented with

a 3-month history of a dry cough with

fevers and night sweats.

i. Describe the chest X-ray (54).

ii. What is the differential diagnosis?

iii. How might the diagnosis be made?

53, 54: Answers

53 i. The lung biopsy shows diffuse inflammation with an infiltration of

eosinophils.

ii. Chronic eosinophilic pneumonia. This results from an idiopathic accumulation

of eosinophils in the lungs with inflammation and tissue destruction resulting from

the release of eosinophilic granules. Patients generally present in the third or fourth

decade, and the condition is more common in females. Symptoms may be present

for months prior to diagnosis (a mean of 7.7 months in one study). Fifty per cent

of patients have an associated history of asthma.

Establishing the diagnosis involves excluding other causes of pulmonary

eosinophilia such as Churg-Strauss syndrome, drug- or toxin-induced pulmonary

eosinophilia (non-steroidal anti-inflammatory agents, nitrofurantoin, ampicillin,

aluminum silicate and particulate metal exposure, crack and heroine inhalation),

helminthic infections, and tropical pulmonary eosinophilia. The chest X-ray

classically shows the ‘photographic negative shadow of pulmonary oedema’, but

this finding is only present in 25-50% of patients.

iii. Chronic eosinophilic pneumonia is extremely corticosteroid responsive such that

symptoms rapidly decrease with prednisone doses of 40-60 mg/day, and after 2-4

weeks radiographic findings decrease by 50% or resolve completely. Unfortunately,

chronic eosinophilic pneumonia can recur if corticosteroids are tapered too rapidly.

Accordingly, treatment should be continued for at least 2-3 months, and the doses

should then be tapered. In one study, 75% of patients required therapy for more

than 1 year, with the average duration of treatment being 19 months. Some patients

require lifelong treatment.

54 i. The chest X-ray shows lymphadenopathy in the right paratracheal and left

hilar regions.

ii. The differential diagnosis lies between sarcoid, TB, and lymphoma.

iii. The history does not help to differentiate between these conditions so a tissue

diagnosis is mandatory. Once lymphadenopathy of the cervical (which commonly

co-exists with mediastinal nodes) and other peripheral nodes has been excluded by

physical examination and ultrasound examination of the neck, bronchoscopy may

be a reasonable first step as it has a high yield for the diagnosis of sarcoid and TB.

Furthermore, transbronchial biopsies should also be taken of lung parenchyma,

which can demonstrate non-caseating granulomas in up to 70% of patients with

sarcoid and 50% of those with TB. Transbronchial needle aspiration of the

mediastinal lymph nodes can also be performed during bronchoscopy, and the

technique has more recently become aided by ultrasound guidance (EBUS) for

higher yields. If bronchoscopic samples are negative, mediastinoscopy is necessary

for a definitive diagnosis.

55, 56: Questions

55 This male patient feels well but

has a squamous cell carcinoma in

his right upper lobe.

i. What does this test (55) show?

ii.

Should it be routine in

asymptomatic subjects with lung

cancer?

iii.

What is the differential

diagnosis of the abnormality?

56 This is the chest X-ray (56) of a 54-

year-old Bengali male who had

haemoptysis when arriving at Heathrow

airport to visit his family. On closer

questioning, he gave a 3-month history

of weight loss, malaise with night

sweats, and a cough.

i. What is the likely diagnosis?

ii. How would you prove the diagnosis?

iii. In what circumstances would you

need to take steps to assess the other

passengers on the plane?

55, 56: Answers

55 i. This isotope bone scan shows a single area of increased uptake in the anterior

part of the right second rib, which, if malignant, would render the tumour

inoperable.

ii. Routine bone scans in asymptomatic individuals are positive in 4-6% of cases.

In half of these the cause will not be cancer, i.e. it will be a false-positive result.

Any such lesion would therefore need to be confirmed by biopsy. This scan is

therefore not recommended for routine staging.

iii. The differential diagnosis should also include Paget’s disease, recent bone

trauma, parathyroidism, and active arthritis.

A PET scan is more specific for identifying bony lesions due to malignancy, and when

employed in potentially operable individuals, it makes bone scanning redundant.

However, the bone scan remains useful in those with bone pains and lung cancer.

56 i. Active pulmonary TB.

ii. Sputum samples for microscopy for Mycobacterium tuberculosis using acid-fast

or auramine staining. The presence of acid-fast bacilli (smear positive) is highly

suggestive of TB, but can occur with disease resulting from environmental

mycobacteria or some rare filamentous bacterial infection (e.g. Nocardia). Infection

is confirmed by a positive culture, but even with modern fast-culture techniques,

this can take up to 6 weeks.

A positive culture also allows the identification of drug sensitivities, a vital

consideration if resistance is suspected (e.g. in patients with poor compliance with

previous treatment for TB, those who have received suboptimal treatment for other

reasons, and those who have acquired the disease in countries with a high incidence

of drug resistance, such as the Baltic States).

If the sputum is smear negative (no acid-fast bacilli present), the diagnosis may

have to be clinical. Inflammatory markers such as CRP and ESR are usually high,

but a positive tuberculin skin test or gamma-interferon test is to be expected in

patients from countries with a high incidence of TB such as the Indian subcontinent,

owing to frequent past exposure to M. tuberculosis; this is therefore of limited help

in confirming the diagnosis. In many smear-negative patients, bronchoscopy to

obtain bronchial washings from the affected area will be smear positive and can

confirm the diagnosis.

iii. If the patient is smear positive, this indicates that there is a high bacillary load

in the sputum (>10³ bacteria/ml) and that close contacts are at risk of contracting

the disease. Screening is usually limited to the immediate family and housemates.

If, however, a smear-positive patient has recently flown on a flight of 8 hr or more

duration, the passengers are advised to seek medical advice (World Health

Organization, Tuberculosis and Air Travel: Guidelines for Prevention and Control,

2nd edition, 2006).

57, 58: Questions

57 This chest radiograph (57) is of a 26-

year-old male who had repeated synco-

pal episodes and required permanent

pacemaker insertion for complete heart

block. He had also experienced several

months of lethargy and intermittent dull

retrosternal chest pain.

i. What diagnostic possibility does the

radiography suggest?

ii.

What investigations could be

undertaken?

iii. What is the cause of the pain?

iv. When are corticosteroids indicated?

58 This chest radiograph (58) is of a

patient with cystic fibrosis.

i. What does it show?

ii. Why is a spontaneous pneumothorax

different in cystic fibrosis?

iii. What is the optimum medical

management?

iv. What is the optimum surgical

management?

57, 58: Answers

57 i. This patient has stage III sarcoidosis with cardiac involvement. Cardiac disease

in this condition may cause a range of ventricular and supraventricular arrhythmias

and conduction defects. Cardiomyopathy may rarely develop.

ii. ECG and Holter monitoring to document arrhythmias; two-dimensional

echocardiography may show ventricular septal thinning, localized regional wall

abnormalities, or a generalized cardiomyopathy. Thallium scintigraphy may show

regions of abnormal perfusion. Endocardial biopsy may yield positive histology in

less than 40% of cases. Cardiac MRI is useful for identifying potential cardiac

sarcoidosis.

iii. Chest pain is common in sarcoidosis (at least 25%) and may be pleuritic or dull

and retrosternal. It may be severe and sometimes mimic a myocardial infarct.

Cardiac sarcoidosis is a difficult diagnosis to establish without a myocardial biopsy.

Even then, a clear association between an arrhythmia and sarcoidosis is difficult

unless the sarcoidosis is clearly active in other sites.

iv. Arrhythmias and cardiomyopathy should be treated in the usual way.

Corticosteroids would be indicated if standard treatment were ineffective or if the

sarcoidosis were active at other sites. Monitoring of the response of cardiac sarcoid

to corticosteroids is difficult.

58 i. A large right tension pneumothorax. The incidence of pneumothorax increases

with disease severity and may be associated with a poor prognosis. It occurs due to

the rupture of subpleural blebs through the visceral pleura, usually in the upper

lobes. The incidence of pneumothorax is higher in patients with widespread pre-

existing lung disease.

ii. A pneumothorax in cystic fibrosis is different from that occurring in other

patients owing to its association with large amounts of purulent secretions. This can

make physiotherapy difficult and lung re-expansion very slow. In addition, patients

with cystic fibrosis who get pneumothoraces usually have severe disease and can

become extremely sick with a pneumothorax.

iii. Patients with pneumothoraces need prompt medical treatment. At the time of

the pneumothorax, they should be commenced on intravenous antibiotics. If large,

the pneumothorax should be drained immediately. If the patient is breathless, a

small pneumothorax requires intercostal drainage under radiological control. An

intubated pneumothorax makes physiotherapy easier. A small pneumothorax in an

asymptomatic patient may be aspirated or observed for 2-3 days.

iv. If a pneumothorax fails to resolve with maximal medical management within a

week, prompt surgical intervention should be considered. With the advent of organ

transplantation, extensive pleurodesis or pleurectomy is not appropriate. The best

surgical option is video-assisted stapling of the apical subpleural bleb under direct

vision.

59, 60: Questions

Result

Normal range

PEFR (l/min)

450

383-518

FEV₁ (l)

2.75

2.34-3.16

FVC (l)

4.05

3.45-4.66

FEV₁/FVC (%)

58-79

DL_CO (haemoglobin corrected)

7.88

6.70-9.06

Alveolar volume (l)

1.47

1.25-1.69

K_CO (haemoglobin corrected)

5.36

2.63-3.55

K_CO = transfer coefficient in DL_CO/alveolar volume.

59 A 30-year-old male was admitted with

fever, cough with haemoptysis, and

dyspnoea. A few red blood cells but no

microorganisms were noted on a sputum

Gram stain.

i. What does the lung function test (Table)

show?

ii. What does this chest radiograph (59)

show?

iii. What is the cause?

iv. Name three important conditions

associated with this and the laboratory

investigations that would differentiate them.

60 This is a radiological imaging test (60)

of a 40-year-old male presenting with

dyspnoea on exertion that had evolved

over a week and was not associated with

fevers, cough or any respiratory signs. His

ECG showed a sinus tachycardia, right

bundle branch block, and inverted T

waves in leads V1-V3.

i. What is this investigation, and what

does it show?

ii. How should the patient be managed?

iii. How else may this patient’s condition

present?

59, 60: Answers

59 i. A high K_CO, i.e. increased diffusion capacity across the alveolar-capillary

membrane. Additional carbon monoxide uptake occurs in the lungs because of the

presence of alveolar haemorrhage.

ii. A bilateral alveolar filling pattern.

iii. Pulmonary haemorrhage.

iv. Three important associated conditions and the laboratory investigations that

differentiate them are:

• Goodpasture’s disease: antiglomerular basement membrane antibody.

• Wegener’s granulomatosis: cytoplasmic ANCA.

• Systemic vasculitis: antinuclear antibody, anti-double-stranded DNA antibody.

60 i. This is a CT pulmonary angiogram, and it confirms the clinical suspicion of

pulmonary embolus. There are filling defects in both pulmonary arteries due to the

presence of a clot. CT pulmonary angiograms have transformed the diagnosis of

pulmonary emboli by providing a rapid test that is readily available for emergencies

and can be used in patients with other significant lung pathology, whereas clinicians

previously had to rely on V/Q scans, which are not readily interpretable in the

presence of other lung disease such as COPD.

ii. As well as fluid resuscitation and oxygen, the patient needs to be anticoagulated

with treatment-dose heparin or low molecular weight heparin for several days and

then to take warfarin to prevent recurrence. How long warfarin should be taken

depends on the clinical situation: if the patient has a well-documented predisposing

factor for a pulmonary embolus, such as a recent operation or long-haul flight, the

warfarin can probably be discontinued after 3 months. However, if there is no risk

factor, warfarin is conventionally suggested for a longer period, usually 6 months.

If this is a second episode, a procoagulant screen will be necessary, and

consideration will be given to lifelong treatment with warfarin. Whether

investigations for occult malignancy should be performed is controversial as the

detection rate is less than 5%.

iii. Pulmonary emboli can present, like this case, as a cause of acute dyspnoea and

may be associated with haemoptysis and pleuritic chest pain. On examination, there

are often few signs, but there may be a pleural rub or small effusion. Massive

pulmonary emboli can present with cardiogenic shock, signs of right heart strain,

and sometimes cardiac arrest. Multiple small pulmonary emboli can cause

pulmonary hypertension and present with an insidious onset of dyspnoea; there

may also be signs of pulmonary hypertension on examination.

61, 62: Questions

61 A 65-year-old ex-smoker with a past history of TB as a child and of laryngeal

carcinoma necessitating a laryngectomy at age 61 presented having coughed up

approximately 150 ml of fresh blood. He had been previously well except for a

history of minor haemoptysis over several months.

i. What are the common causes of a major life-threatening haemoptysis, and what

are the most likely potential causes in this patient?

ii. What is the immediate management of this patient?

iii. How can further major haemoptysis be prevented?

62 This histology (62) was obtained from a mediastinal lymph node of an HIV-

positive male. What stain has been used, and what does it show?

61, 62: Answers

61 i. The common causes of major

haemoptysis (>200 ml blood over 24 hr) are

bronchiectasis, lung cancer, and mycetomas.

Rarer causes include TB, invasive aspergillosis,

PAVM, a pulmonary artery aneurysm, a

vascular-bronchial fistula, and vasculitis.

Other common causes of haemoptysis, e.g.

pneumonia, pulmonary embolism, and left

ventricular failure, generally cause only minor

haemoptysis.

In this patient, the history of laryngeal

carcinoma means that he is at high risk of

developing a lung carcinoma, and the previous TB could have caused focal

bronchiectasis or lung cavities that have subsequently been colonized by Aspergillus

to form a mycetoma. The chest radiograph (61) demonstrates bilateral apical scarring

and fibrosis with loss of volume in the upper lobes and a cavity in the left upper lobe,

but no obvious lung malignancy. The cavity does not contain an obvious mycetoma.

ii. The immediate management includes obtaining a full blood count, clotting, and

cross-match. It is rare for a patient to lose enough blood to require transfusion, but if

this is the case, the patient is at high risk and active measures will be necessary to try

to stop the bleeding (see below). A chest X-ray may identify the likely source, but CT

scanning is often necessary to identify patches of bronchiectasis or confirm potential

cancers or mycetomas identified on the chest X-ray. Bronchoscopy is helpful in

identifying the side from which the bleeding is originating and can give helpful

diagnostic information if bronchial washings are positive for Aspergillus or the

cytology identifies fungal elements or malignant cells. Patients are often given

antibiotics in case bacterial infection has helped to cause the bleeding (although there

is little evidence that they are beneficial), and the pro-thrombotic agent tranexamic acid

can be used.

iii. Life-threatening haemoptysis or continuing major haemoptysis needs intervention

with either surgery to remove the affected lobe, or arterial embolization. Embolization

is often the only option due to the patient’s poor lung function or underlying condition,

and also because there are often extensive scarring and pleural changes that make

surgery technically challenging. Antifungal agents (eg itraconazole 200 mg twice a

day) may help in patients with major haemoptysis caused by mycetomas.

62 A Ziehl-Neelsen stain has been used, with which acid-fast bacilli appear red.

This should be distinguished from the more rapid auramine fluorescence stain with

which acid-fast bacilli fluoresce on a dark background. Neither stain is specific for

Mycobacterium tuberculosis and may identify other non-tuberculous mycobacteria,

including the Mycobacterium avium complex.

63, 64: Answers

63 i. CPAP acts as a pneumatic splint. It increases the intraluminal pressure within

the upper airway and thus counteracts the transmural forces that favour airway

closure. The typical site of obstruction in patients with OSA is between the

nasopharynx and the larynx. This region is narrowed during sleep due to a

reduction in muscle tone, and individuals with OSA have on average a smaller

diameter pharyngeal lumen.

ii. Poorly fitting masks result in air leakage. This not only reduces the applied

airway pressure, but also can cause conjunctivitis if the air leak is directed towards

the eye. A poorly fitting mask can also bruise or cause ulceration of the bridge of

the nose. These problems can be avoided by selecting and properly fitting the

appropriate mask type and size. Most patients initially experience nasal congestion,

but this complaint frequently diminishes with continued use. Intranasal

vasoconstrictors, anticholinergic agents, and steroids have been used in this setting.

Humidification of air within the CPAP system can also help if these measures are

ineffective.

iii. Compliance rates vary from 45% to 80% and studies show the average hours

used is fewer than 5 per night. There are no consistent clinical predictors of

compliance, although one study suggested that patients who complain of side-

effects were those found to be less compliant. Follow-up and support by physicians,

as well as personalizing the type of CPAP device and mask, may be important in

improving patient compliance.

64 i. This lateral chest radiograph (64) shows homogeneous consolidation within

the middle lobe. The horizontal fissure is bowed upwards, suggesting some swelling

of the lobe.

ii. Streptococcus pneumoniae is the most common cause of CAP and is the most

typical cause of lobar pneumonia. However, it is often unappreciated that most

other common bacterial causes of pneumonia can also cause lobar consolidation,

including Legionella, and Staphylococcus aureus, and as many as 50% of

Mycoplasma pneumoniae pneumonias are lobar.

iii. Klebsiella pneumoniae is also a cause of a swollen lobe on the chest radiograph

but as in this example, which is due to Mycoplasma pneumoniae, any bacterial

pathogen can potentially do this.

65, 66: Answers

65 i. A ‘rolling’ hiatus hernia. In this condition, the herniated stomach protrudes

into the chest through the hiatus beside the lower oesophagus. The

oesophagogastric junction is usually normally located.

ii. These patients may be remarkably symptom-free, and the condition may be

spotted as an incidental finding. Moderate dysphagia and fullness with meals are,

however, common and may worsen as a meal progresses due to distension of the

intrathoracic stomach. Acid reflux is not a feature because the oesophagogastric

junction is usually competent and because the intrathoracic stomach further

prevents reflux by pressing on the lower oesophagus.

iii. Surgical management is usually advised. This is the only effective way to manage

dysphagia due to this condition, and if the hernia is not reduced there is a risk of

ulceration and perforation or even strangulation of the herniated stomach.

Reduction of the hernia may be accomplished via a low left lateral thoracotomy

or a laparotomy. Advantages of a thoracic approach include better access to the

oesophagogastric junction and hernial sac. An abdominal approach may be helpful

in the event that concurrent abdominal surgery is required but offers poorer access

to divide the adhesions, which are frequently present in the hernial sac.

66 i. This is likely to be a small-cell cancer because the disease appears very bulky.

This most aggressive cell type classically presents with advanced spread within the

chest to the hilar and mediastinal lymph nodes, the primary tumour often being

indistinguishable from the nodal disease. Pleural effusion is present in 20% of

presentations.

ii. This type of cancer is staged as limited disease, which is confined to the

hemithorax and ipsilateral supraclavicular fossa, or extensive disease, which is

present when disease is also found outside the hemithorax. The recommended

staging tests include routine blood tests, chest X-ray and CT scanning of the thorax

to include the liver and adrenal glands. Bone and brain scans are made only if

symptoms indicate.

iii. Treatment is by cytotoxic chemotherapy. Cisplatin and etoposide form the drug

combination of choice for four or six courses. Around 50% of patients will obtain

a complete response and another 30% a partial response. Those with a complete

response and a good partial response should receive mediastinal radiotherapy,

which confers a 5% better 2-year survival, and also prophylactic whole-brain

radiotherapy. There is no agreed effective second-line therapy, although reasonable

results have been reported with oral topotecan.

iv. The overall 2-year survival for small-cell carcinoma is 7%. For those with a

good prognosis (high performance status and normal biochemistry), the 2-year

survival is 15-20%. Of those alive at 2 years, 25% will relapse with small-cell

disease, and another 20% will develop non-small-cell lung cancers within 5 years.

67, 68: Questions

67 A 45-year-old female, originally from Jamaica, has a 3-year history of a dry

cough and gradual exertional breathlessness. Her HRCT is shown here (67).

i. Describe the HRCT appearances.

ii. How may the diagnosis be confirmed?

iii. When is treatment indicated?

Flow (1/s)

Expiration

Inspiration

Change in lung volume (l)

68 This 45-year-old, non-smoking male produced the flow-volume curve in 68.

i. Is it of normal or abnormal shape?

ii. What is point A? How is it usually measured?

iii. Why does the expiratory curve decrease progressively in flow as the RV is

approached?

iv. Why is the inspiratory curve semicircular in shape and dissimilar to the

expiratory curve?

67, 68: Answers

67 i. The HRCT axial cut demonstrates lung parenchymal nodules in a

bronchovascular distribution, characteristic of sarcoidosis.

ii. The diagnosis may be confirmed pathologically by the demonstration of non-

caseating granulomas and a negative culture for TB. This may be achieved by

transbronchial or open lung biopsy, the sampling of enlarged mediastinal nodes, or

the biopsy of involved extrathoracic sites.

iii. Oral corticosteroid treatment should be considered in patients with severe,

persistent, or progressively worsening respiratory symptoms that interfere with

daily life. Treatment should also be instituted if lung function progressively

deteriorates over 6 months. A fall in VC of 10-15% and/or transfer factor for

carbon monoxide of >20%, confirmed on more than one occasion, is considered

significant. Treatment should not be commenced in asymptomatic patients in the

absence of other organ involvement.

68 i. This is a normal-shaped curve.

ii. The expiratory limb is triangular in shape. Following a full inspiration, the lung’s

recoil pressure is maximal, as is the pleural pressure, because the thoracic muscles

are stretched to provide maximal expiratory force. The onset of expiratory flow is

explosive and reaches its peak rate within 0.01 s, i.e. at point A. This is the PEFR

and is usually measured with a peak flow meter.

iii. The expiratory curve decreases its flow gradually as the lung volume drops from

TLC to RV. This graded decline reflects the gradual drop in the lung’s elastic recoil

as the lung gets smaller, as well as the gradual reduction in airway calibre during

expiration; also, muscular force on the lung (pleural pressure) slowly decreases as

the thoracic cage changes position during expiration and the respiratory muscles

shorten.

iv. Inspiration does not reach an instant maximal flow, in contrast to expiration,

which does so owing to the inspiratory recruitment of dynamic forces. On

expiration, the respiratory muscles contract, and the power increases almost

instantly from the start of expiration to achieve a maximal flow within milliseconds.

This process takes much longer at the start of inspiration as the muscle forces that

generate flow take longer to develop, and maximal inspiratory flow is only achieved

by the midpoint of the inspiratory VC. It then slows again as the maximum inspired

volume is reached as a consequence of muscular contraction slowing at the higher

lung volumes (TLC). This causes the semicircular appearance of the inspiratory

flow-volume curve.

69, 70: Answers

Criteria for long-term oxygen therapy

FEV₁ < 1.5 l

and

PaO₂ less than 7.3 kPa when stable*

PaO₂ greater than 7.3 kPa and less than 8 kPa when stable,* as well as one of:

• Secondary polycythaemia

• Nocturnal hypoxaemia (SaO₂ less than 90% for more than 30% of the time)

• Peripheral oedema

• Pulmonary hypertension

*Measurement of arterial blood gases on two occasions at least 3 weeks apart in

patients who have a definitive diagnosis of COPD and who are receiving optimum

medical management

69 i. An oxygen concentrator. Room air is entrained into the machine, and nitrogen

is adsorbed by zeolite material, resulting in high-concentration oxygen.

Concentrators are typically able to deliver concentrations between 50% and 95%

at a flow rate of up to 5 l/min. Long-term oxygen therapy should be prescribed for

patients in respiratory failure (defined as a PaO₂ <8 kPa).

ii. The specific criteria for long-term oxygen therapy in patients with COPD are

summarised in the Box.

iii. In patients who qualify for long-term oxygen therapy, oxygen should be

prescribed for at least 15 hr/day, although survival may be augmented when used

for more than 20 hr/day.

70 The chest radiograph shows moderate bilateral pleural effusions. The absence

of cardiac enlargement and significant dyspnoea should exclude left ventricular

failure, although cardiac failure can occur with a normal cardiac silhouette in

patients with mitral stenosis or constrictive pericarditis. It is most likely that the

patient has an inflammatory pleurisy, probably due to autoimmune disease such as

systemic lupus erythematosus or rheumatoid arthritis. The patient shown here

suffered from chronic rheumatoid arthritis. Other possible causes include

vasculitides such as polyarteritis nodosa, Wegener’s granulomatosis and

polyserositis, drug reactions, e.g. hydralazine, phenytoin, phenothiazines, and

practolol, lymphatic hypoplasia (yellow nail syndrome) and hypothyroidism. In

general, bilateral effusions suggest a systemic cause and unilateral fluid a local

cause.

71, 72: Answers

71 i. The chest X-ray shows left basal consolidation with an associated pleural

effusion.

ii. Although most effusions associated with CAP are simple parapneumonic

effusions that will resolve without intervention, significant pleural effusions should

be tapped to exclude an complicated parapneumonic effusion (defined as pleural

fluid pH <7.2, lactase dehydrogenase >1000 IU/l or glucose <2.2 mmol/l) or

empyema (visibly turbid fluid or a positive Gram stain or culture for bacteria). If

these are present, the fluid should be drained. Persisting fever or blood tests showing

high inflammatory markers or a raised platelet or white cell count would be a

further indication that the fluid should be drained to exclude pleural infection as a

cause for the failure of the patient to improve.

72 i. The history is suggestive of severe bronchiectasis, and the chest radiograph

shows a large number of ring shadows suggestive of dilated, thick-walled bronchi,

compatible with this diagnosis. Bronchiectasis can be confirmed by HRCT scans of

the lungs, which will show dilated bronchi (>110% of the diameter of the

accompanying artery) that are thick walled. There may be ‘tree-in-bud’ changes,

especially during active disease, due to mucous filling the small airways.

ii. There are a large number of causes of bronchiectasis, although in industrialized

nations most cases are idiopathic. Worldwide, the most common cause is severe

childhood infection (e.g. whooping cough, measles, pneumonia, TB). Other

important causes are cystic fibrosis, primary ciliary dyskinesia, immunoglobulin

deficiency, focal bronchial obstruction, atypical mycobacterial infection (especially

Mycobacterium avium-intracellulare), and allergic bronchopulmonary aspergillosis.

Bronchiectasis has recently been increasing recognized in patients with severe

COPD, being present on CT scans in 25% of these patients, and in long-term

survivors with HIV infection.

iii. The patient will need an HRCT of the thorax, lung function testing

(bronchiectasis is associated with asthma or fixed small airways obstruction that

can be severe), total IgG and IgE levels, Aspergillus antibodies and skin testing, as

well as sputum culture for bacteria, fungi

(to look for Aspergillus), and

mycobacteria (to exclude atypical mycobacterial infection that can both cause and

complicate cases of bronchiectasis). The bacteria present in bronchiectasis include

Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and

Staphylococcus aureus (especially in cystic fibrosis). In severe bronchiectasis,

patients almost invariably become colonized with Pseudomonas aeruginosa and

can acquire more unusual environmental bacteria such as Burkholderia cepacia and

Stenotrophomonas.

73, 74: Questions

73 This is the chest radiograph (73) of a

teenager who has had a lifetime history

of cough productive of frequently

purulent sputum and needs enzyme

supplementation of her diet to prevent

malabsorption.

i. What is the condition?

ii. How is it inherited, and what is the

genetic defect?

iii. How is the diagnosis confirmed?

iv. What are the main respiratory

complications, and which pathogens are

likely to be isolated from her sputum?

74 This scan (74) was taken 5 years

after the patient, a 55-year-old man,

presented with a blood-stained pleural

effusion. At that time examination of

the fluid and bronchoscopy were

negative. What is the abnormality

shown, and what are the possible

causes?

73, 74: Answers

73 i. Cystic fibrosis leading to bronchiectasis and impaired exocrine (and in some

patients endocrine) pancreatic function requiring pancreatic enzyme

supplementation. The basic pathophysiology is excessively thick mucous

production, leading to a failure to clear bacterial infection from the lungs, airway

inflammation, and blockage of the pancreatic ducts.

ii. This is an autosomal recessive gene defect affecting the CFTR protein, an ATP-

binding cassette (ABC) transporter ion channel in epithelial cell membranes. A very

large number (>1400) of different mutations have been described, but the most

common in Western populations is the deletion of phenylalanine at position 508

(F508Δ), which is present in approximately 66% of cases. Most cases of cystic fibrosis

result in fatal disease, although with improved medical care, the median age of death

has risen to 37 years. Exactly how impaired function of the CFTR leads to an inability

to clear respiratory secretions and chronic bronchial infection is not, however, clear.

iii. The diagnosis is confirmed by an elevated sweat chloride level (>60 mmol/l) on

a sweat test. In patients with equivocal results (30-60 mmol/l), nasal potential

difference can be used, but this is a technically difficult test. CFTR genotyping will

help as long as the patient has one of the 50 or so more common mutations, which

are responsible for 80-90% of cases.

iv. Cystic fibrosis causes severe, mainly upper lobe bronchiectasis (in contrast to

non-cystic fibrosis bronchiectiasis, which tends to affect the lower or middle lobes)

with a distal progressive small airways obstruction, resulting in respiratory failure,

cor pulmonale, and death. Haemoptysis and pneumothorax are common

complications, and patients can be colonized with Aspergillus and develop allergic

bronchopulmonary aspergillosis or semi-invasive chronic necrotizing aspergillosis.

The common pathogens are Staphylococcus aureus (which is relatively rare in non-

cystic fibrosis bronchectasis) Haemophilus influenzae, Moraxella catarrhalis, and

Streptococcus pneumoniae in early disease, but most patients are eventually colonized

with Pseudomonas aeruginosa. Severely affected patients can also be colonized with

Burkholderia cepacia, which can be associated with a rapid deterioration in lung

function (the ‘cepacia syndrome’). Recently, Streptococcus milleri species have been

identified as common pathogens in patients with cystic fibrosis, and they can also

develop superinfection with non-tuberculous mycobacteria.

Benign pleural thickening. In contrast to the scan of malignant pleural

mesothelioma, the pleural thickening is smooth and diffuse, with only slight

constriction of the hemithorax. A blood-stained pleural effusion is always

suggestive of malignancy, but the long history makes this unlikely and this case

was, in fact, due to benign asbestos-related pleurisy.

75, 76: Questions

75 A 65-year-old male is a smoker and

has a history of seropositive rheumatoid

arthritis. Following a short history of

cough, a chest X-ray

(75) was

performed.

i. Describe the image.

ii. What are the possible causes of the

lesions?

iii. What investigations would you

perform?

76a

76b

76 These are the chest radiographic (76a) and bronchoscopic (76b) appearance of

a 24-year-old female in whom systemic lupus erythematosus had been diagnosed 6

months earlier. Her initial joint symptoms and rash had been successfully controlled

on steroids, but 4 weeks before admission to ICU she developed symptoms

suggestive of cerebral involvement, and the steroid dose was increased. She was

admitted with respiratory distress, circulatory collapse, and disseminated

intravascular coagulation. Gram-negative sepsis was confirmed, and she improved

with antibiotic and standard supportive therapy. Pulsed cyclophosphamide was

subsequently started for lupus cerebritis diagnosed on MRI scanning. Several weeks

later, she suffered a massive haemoptysis, and the chest radiograph and

bronchoscopy were performed at this time. Lesions similar to those pictured were

present throughout the bronchial tree.

i. Describe the bronchoscopic appearances.

ii. Which organism is likely to be responsible for the respiratory problems?

75, 76: Answers

75 i. The chest X-ray shows multiple 1-2 cm soft tissue nodules in both lungs, one

of which is clearly peripheral in the left apex, with a further lesion in the right lower

lobe. These lesions are cavitating, as seen in the right lower lobe.

ii. Possible causes of each lesion include malignancy, rheumatoid nodules, and

infection.

iii. A CT/PET scan may differentiate malignancy from other causes. However,

infection and rheumatoid nodules may also exhibit low-grade uptake on a PET

scan. Rheumatoid lesions are always peripheral on the radiograph, may cavitate,

and are seldom more than 1.5 cm in diameter. If there is doubt concerning the

aetiology, a biopsy is recommended, particularly if the PET scan is positive.

76 i. The chest radiograph (76a) shows a densely consolidated right upper lobe

with infiltrates in the middle and lower lobes. The bronchoscopy (76b) shows

mucosal infiltration with white, nodular lesions, suggestive of a fungal infection.

ii. Histology of the bronchial biopsies showed extensive infiltration with fungal

hyphae but minimal inflammatory infiltrate. Aspergillus fumigatus was

subsequently isolated. The diagnosis is invasive aspergillosis, an important

complication in immunocompromised patients. It usually presents as a necrotizing

cavitating pneumonia unresponsive to standard antibiotics. The pulmonary features

in this case are rare, but a wide variety of presentations have been described.

Diagnosis may be difficult, with both sputum culture and serology frequently being

negative. Biopsy specimens are usually required to make the diagnosis.

Extrapulmonary dissemination to the liver, kidney, gastrointestinal tract, and brain

occurs in about 25% of cases.

Treatment was with intravenous liposomal and nebulized amphotericin followed

by oral itraconazole. The patient recovered, and a follow-up chest radiograph at 3

months was normal.

Aspergillus species can affect the lungs in several ways:

• Allergic bronchopulmonary aspergillosis in asthma.

• Aspergilloma, i.e. a fungus ball infects pre-existing cavities.

• Chronic necrotizing pulmonary aspergillosis.

• Aspergillus tracheobronchitis.

• Invasive aspergillosis, as in this case.

The last two develop in immunocompromised hosts.

77-79: Questions

77 i. What is this (77)?

ii. For which patients may it be

prescribed?

iii. What are the benefits of the treat-

ment, and how long does treatment last?

78 A 45-year-old female has a 5-year history of asthma. She has been well controlled

on low doses of inhaled corticosteroids. Over the last 4 months, she has noticed that

she has required the use of her short-acting bronchodilator several times per week,

has awoken at night due to coughing, and has had two exacerbations of her asthma

requiring oral steroids. How would you manage her case?

79 i. What is the abnormality here (79)?

ii. How do you know which lobe is

affected?

iii. What are the likely causes?

77-79: Answers

77 i. This is a portable oxygen cylinder.

ii. It allows patients with severe COPD or other lung disease to maintain exercise.

People already on long-term oxygen therapy who wish to continue their oxygen

therapy outside the home should have ambulatory oxygen provided. Ambulatory

oxygen is also commonly prescribed in the context of short-burst oxygen therapy

for patients who have documented exercise desaturation and improvement with

oxygen therapy to maintain saturations above 90%.

iii. Despite the high cost of short-burst oxygen, there is very limited evidence to

support its use. Various products are available. Oxygen cylinders may contain

compressed gas or liquid oxygen and may be used with an oxygen-conserving

device. When used at 2 l/min, a small oxygen cylinder that can be carried by the

patient will last approximately 90 min. An oxygen-conserving device (allowing flow

only during inspiration) can prolong this up to 4 hr.

78 This lady has symptoms suggesting that her asthma is uncontrolled. The first

steps would be to ensure adherence to her inhaled corticosteroids and to check her

inhaler technique. A careful history, enquiring about new allergen exposure, e.g. a

new pet, is important. She is currently at step 2 of the GINA/BTS guidelines for

asthma management (see Question 1). Once other potential causes of her worsening

symptoms have been excluded, her pharmacological management should be stepped

up. Step 3 of the GINA/BTS guidelines favours adding a long-acting beta-agonist,

e.g. salmeterol or formoterol, to her current regime. This is most commonly done by

switching to a combination of steroid + long-acting beta-agonist inhaler. This

strategy has been shown to be more effective than just increasing the dose of the

inhaled steroids alone.

79 i. The chest X-ray is of a collapsed right middle lobe.

ii. Middle lobe collapse causes the right border of the heart to be obscured. Unlike

in lower lobe collapse, the diaphragmatic contour is preserved. As the lobe is

relatively small, collapse does not result in mediastinal deviation.

iii. The common causes are lobar pneumonia, a lung tumour with occlusion of the

middle lobe orifice, and post-tuberculous occlusion of the middle lobe airway as old

TB glands at the hilum from a primary infection cause external compression

(Brock’s syndrome). A slow-growing benign tumour, e.g. carcinoid, can occasionally

cause the recurrent collapse of an airway, which will become permanent in time.

80, 81: Questions

80 Sand-blasting carries an occupational hazard.

i. Which pneumoconiosis is associated with this occupational exposure?

ii. What other occupations pose similar risks?

81a

81b

81 A 20-year-old female presented with 1-week of haemoptysis and shortness of

breath. She had a three pack-year history of smoking a hookah nightly at a Middle

Eastern restaurant. Physical examination revealed bilateral inspiratory crackles.

Her chest CT is shown in 81a. Sequential BALs were increasingly bloody

(72,000 cells/cm³, 181,000 cells/cm³, and 540,000 cells/cm³, respectively). All

serologies were negative, including ANCA, antinuclear antibodies, rheumatoid

factor, antiglomerular basement membrane antibodies, scleroderma, and

cryoglobulin. The patient’s lung biopsy is shown in 81b.

i. What does the lung biopsy show?

ii. What is the diagnosis?

iii. Is it related to smoking?

80, 81: Answers

80 i. Silicosis is a chronic, fibronodular interstitial lung disease caused by the

inhalation of free crystalline silica (SiO₂). Silica occurs both complexed with other

elements and in isolation as a ‘free’ form. The latter, occurring primarily as quartz,

tridymite, and cristobalite, is associated with fibrotic lung disease. Tridymite and

cristobalite are more fibrogenic than quartz.

ii. Sand-blasting is widely used to clean and etch stone and metal surfaces. Highly

pressurized air or water drives a stream of abrasive sand into the workpiece. Very

high concentrations of respirable silica are present in the resulting dust cloud. Non-

siliceous particulates are increasingly used to minimize this risk, but if the target

surface (e.g. stone) contains silica, significant exposure may still occur. Because

silica is a major constituent of the earth’s crust, mining, tunnelling, quarrying, and

stone cutting may also entail significant exposure to silica-containing dust. Finely

powdered quartz, known as silica flour or tripoli, is another common source of

exposure as it is used as a polishing agent, as a dry lubricant in the rubber industry,

and as a thickening agent in paints and plastics.

81 i. The lung biopsy shows areas of linear antibody deposition.

ii. Goodpasture’s syndrome. Goodpasture’s syndrome results from autoantibodies

directed against the non-collagenous domain of the alpha-3 chain of type IV

collagen on the alveolar and glomerular basement membranes, leading to alveolar

haemorrhage and/or nephritis. Approximately 50% of patients present with

nephritis alone, 45% present with nephritis and alveolar haemorrhage, and 5%

present with alveolar haemorrhage alone (although in these, renal involvement may

be seen on biopsy). In a small series, four of 10 patients with Goodpasture’s

localized to the lung subsequently developed renal dysfunction.

As many as 40% of patients with Goodpasture’s syndrome may be seronegative

for anti-basement membrane antibodies at the time of presentation. This

phenomenon is attributed to the insensitivity of the ELISA assay for very low levels

of circulating antibody (as the bulk of the antibody is deposited on the basement

membranes). In some patients, circulating antibodies can be detected with a novel,

highly sensitive biosensor assay system. Patients who are seronegative at

presentation may become seropositive later in their course.

iii. Many irritants (e.g. tobacco smoke) have been found to potentiate anti-basement

membrane antibody deposition in rabbit lungs. In patients with Goodpasture’s

syndrome, smoking is independently predictive of alveolar haemorrhage.

82, 83: Questions

82 A 47-year-old Latina female presented with a 2-week history of shortness of

breath. She had recently gained weight. Examination showed dullness at the right

lung base, and a full abdomen, which was non-tender. Blood tests were

unremarkable, and the chest X-ray showed a very large right pleural effusion. Pleural

aspiration showed a protein of 5.2 g/dl, with lactate dehydrogenase of 137 IU/dl

and normal cells. Her abdominal CT (82) is shown. What is the possible diagnosis?

83 i. How would you manage

a young man presenting with

this chest radiograph (83) for

the first time?

ii.

What is the risk of

recurrence?

iii. How would you manage

this?

82, 83: Answers

82 A biopsy of a pelvic mass was performed, which showed a lipoleiomyoma with

prominent vascularity and degenerative changes. There was focal serositis with

mesothelial hyperplasia involving the tumour surface. Focal infarction with sclerosis

and oedema was seen, but there was no evidence of malignancy. This is pseudo-

Meigs’ syndrome.

Meigs’ syndrome is the triad of ascites and pleural effusion that develops in

association with benign ovarian tumours

(most commonly fibromas). The

syndrome is called pseudo-Meigs’ when the ascites and pleural effusions develop in

association with other ovarian or uterine pathology (most commonly malignant

tumours). As with Meigs’ syndrome, the pleural effusion resolves after removal of

the pelvic mass. Benign pathologies included in Meigs’ syndrome include fibromas

(91%), granulosa cell tumours (5%), and cystadenomas. Pseudo-Meigs’ was

initially described in a patient with a uterine leiomyoma in 1909. Findings on

thoracentesis are consistent with either transudative or exudative effusion. Rarely,

the effusion will be haemorrhagic. Diagnosis is made by exploratory laparotomy

with sampling of the pelvic pathology.

83 i. The majority of spontaneous pneumothoraces occur as a result of rupture of

subpleural apical blebs in otherwise fit and healthy individuals. Rarely there is an

underlying inflammatory or degenerative disease process such as TB, scleroderma

or interstitial pulmonary fibrosis that requires attention. If the rupture of a small

bleb results in a small pneumothorax (<20%) and the patient is asymptomatic, then

often nothing needs to be done other than advising the patient to reduce activities.

In larger pneumothoraces where the patient is breathless, the pneumothorax should

be aspirated via a small cannula attached to a 50 ml syringe via a three-way tap

introduced into the second anterior intercostal space. A volume of air up to 2.5 l

can be aspirated, but the procedure should be stopped earlier if lung is blocking the

needle or no more air is coming out with ease. A chest radiograph taken 1 hr later

will show if the procedure has been successful. If the lung has not re-expanded,

intercostal tube drainage should be undertaken. Most patients will have their lung

re-expanded rapidly and will leave hospital within 5 days. If there is a persistent air

leak after this time, surgery should be considered.

ii. The risk of recurrence after a first, conservatively treated pneumothorax is of the

order of 30-40%.

iii. A second pneumothorax should lead to consideration of surgery. The operation

of choice is a pleurectomy using VATS. VATS may also be used to resect or staple

subpleural bullae that may have been responsible for the pneumothorax.

Mechanical pleurodesis by pleural abrasion may also be carried out.

84, 85: Questions

84a

84 A 35-year-old male was referred by his family physician, who noted that he was

centrally cyanosed but otherwise well. The following respiratory function test

results were obtained:

• Oxygen saturation on air: lying 94%, standing 89%.

• FEV₁ 93% expected.

• FVC 97% expected.

• DL_CO normal.

The chest X-ray (84a) showed a large, well-defined, rounded lesion in the left lower

zone. The patient had been treated 10 years previously for a brain abscess.

i. What is the term that describes the oxygen saturation results?

ii. What is the likely diagnosis?

iii. What other problems may occur?

iv. How can the pulmonary lesions be treated?

85 i. What are the main causes of central sleep apnoea?

ii. What are the main symptoms?

iii. How would you treat this condition?

84, 85: Answers

84 i. Orthodeoxia.

84b

ii. PAVM. An upright posture increases the

right-to-left shunt through the PAVM and

therefore results in a fall in oxygen

saturation. A PAVM also allow minor

episodes of bacteraemia to reach the arterial

circulation and can therefore occasionally

lead to brain abscesses. A CT pulmonary

angiogram demonstrates a feeding

pulmonary artery as the cause of the patient’s

shunt (84b).

iii. Iron deficiency anaemia due to blood loss

from mucosal arteriovenous malformations

in the gut.

iv. PAVMs can be effectively treated by embolization of the feeding vessel.

85 i. The most common causes of central sleep apnoea are congestive heart failure

and neurological diseases. Central hypoventilation is caused by:

• Primary central hypoventilation.

• Brainstem infarction.

• Encephalitis.

• Arnold-Chiari malformation.

• Chronic opioid treatment.

Causes of neuromuscular respiratory dysfunction include:

• Muscular dystrophy.

• Spinal atrophy.

• Amyotrophic lateral sclerosis.

• Acid maltase deficiency.

Causes of unstable respiratory drive include:

• Sleep onset (transient).

• Hyperventilation-induced hypocapnia.

• Hypoxia (pulmonary disease, high altitude).

• Congestive heart failure.

• Disorders of the CNS.

• Chronic opioid treatment.

ii. Patients may have a diminished sense of breathlessness when hypercapnic.

Restless sleep is common, as is daytime somnolence and morning headache. Right-

sided heart failure and polycythaemia occur in advanced cases.

iii. Treatment for central apnoea includes supplemental oxygen, nasal CPAP, BiPAP,

and respiratory stimulant medications. Nocturnal ventilatory assistance may

become necessary by face mask or via a tracheostomy.

86, 87: Answers

86 i. There has been re-expansion of a totally collapsed lung due to removal of the

endobronchial part of the tumour. Improved breathlessness and lung function occur,

and improved ventilation and perfusion of the previously collapsed lung can be

demonstrated by radionuclide scans. It may also permit the drainage of infected

retained secretions.

ii. It is difficult to predict which patients will have such an improvement. Where a

tumour has progressed radiographically from the periphery towards the hilum, the

obstruction is unlikely to respond to a removal of the proximal part of the tumour

by laser. A shorter duration of collapse (up to 3 months) is more likely to respond

to attempts at re-expansion. During the procedure, it may be difficult to know how

far distally an obstruction extends; a CT scan can sometimes help in this regard. An

attempt should be made early in the procedure to pass through the obstruction and

assess the patency of the distal airways. If these are occluded, the likelihood of a

favourable outcome is small.

87 i. Left thoracoplasty. The most common indication for this operation was TB in

the pre-chemotherapy area to collapse the lung in the face of progressive or

uncontrolled advance of the TB. The patient would initially have been treated by

an artificial pneumothorax, often for up to 1 or 2 years - also reducing the aerobic

environment that the Mycobacterium tuberculosis organism enjoys. It was

performed in 1-3 stages developed to discern the extent of patient tolerance of the

procedure.

Other methods used to achieve the same result were plombage (plastic spheres

inserted extrapleurally inside the chest) and oleothorax (installation of paraffin

wax). Thoracoplasty may rarely be performed now in patients who have chronic

lung cavities with ongoing systemic symptoms, usually due to infection by resistant

organisms, or in patent pleural spaces with failure of the lung to expand and fill the

space.

ii. Scoliosis can develop after thoracoplasty in prepubertal patients, and its severity

is related to the number of ribs removed. The scoliosis is convex to the side of the

surgery. Spinal TB may also have been a concomitant feature in such patients.

Patients with this type of chest wall deformity are at risk of nocturnal

hypoventilation, particularly when there is accompanying chronic obstructive

airways disease (as many of these patients continue to smoke). Ultimately,

hypercapnic respiratory failure (hypoxaemia with hypercapnia) and pulmonary

hypertension develop, requiring oxygen at night and non-invasive ventilatory

support often just at night.

88, 89: Questions

A 51-year-old male with severe

COPD had an FEV₁ 24% of that

predicted, an exercise tolerance of only a

few yards on the flat, and a resting PO₂

of 6 kPa. He underwent a procedure to

improve his survival and quality of life.

i. Describe his chest X-ray appearances

(88).

ii. What procedure has he had done?

iii.

What are the most common

indications for this treatment?

89 A 28-year-old male had chemo-

therapy for relapsed acute myeloid

leukaemia 25 days before presenting

with a several day history of coryzal

symptoms followed by a dry cough. On

examination, he was pyrexial at 37.5°C,

and had bilateral widespread inspiratory

squeaks and crepitations. His oxygen

saturation was 92% on air. This is a

representative slice of the CT scan (89)

performed to identify the cause of the

patient’s fever, cough, and hypoxia.

i. What does the CT scan show?

ii. What is the likely diagnosis?

iii. What investigations need to be

performed?

iv. How should the patient be managed?

88, 89: Answers

88 i. The chest X-ray shows a marked asymmetry in appearance of the lung fields.

The right lung is hyperinflated with a paucity of lung markings. The left lung

appears normal. There is also evidence of a previous sternotomy.

ii. The patient has undergone a single (right) lung transplant.

iii. The most common conditions that require lung transplantation are

COPD/emphysema (particularly due to α₁-antitrypsin deficiency), cystic fibrosis,

bronchiectasis, pulmonary fibrosis, and primary pulmonary hypertension.

Patients must be below the age of 60 and meet stringent criteria. In the case of

COPD, the patient’s post-bronchodilator FEV₁ must be <25% and the resting PO₂

<7.5 kPa. Hypercapnia and secondary pulmonary hypertension are often present.

Many patients have a rapid decline in FEV₁ or life-threatening exacerbations

necessitating transplant. In practice, most transplants are for patients with

emphysema, cystic fibrosis, or primary pulmonary hypertension, because of their

younger age, better resilience, and lesser co-morbidity.

89 i. The CT scan shows ‘tree-in-bud’ changes suggestive of a small airways

inflammatory process, i.e. a bronchiolitis.

ii. These appearances in this context suggest the patient has a respiratory virus

infection, which can cause more severe and prolonged disease in an

immunocompromised host than in a healthy host. Bronchiolitis is common and can

develop into a pneumonia. The viruses seen in this context are respiratory syncytial

virus, parainfluenza, influenza, adenovirus, rhinovirus, coronavirus, and the

recently identified and characterized respiratory virus metapneumovirus. Similar

appearances can occur with Mycoplasma pneumoniae and Chlamydophila

pneumoniae infection, and Aspergillus can cause a tracheobronchitis with localized

‘tree-in-bud’ areas on the CT scan.

iii. Along with routine blood tests, and sputum and blood cultures, tests to identify

respiratory viruses are necessary. These can be cultures from nasopharyngeal

aspirates or BAL fluid, but a much more rapid diagnosis can be achieved by direct

immunofluorescence or PCR of the same samples. This patient had parainfluenza-

3 infection confirmed by direct immunofluorescence of a nasopharyngeal aspirate.

iv. Effective antiviral therapies against respiratory viruses are limited. Influenza can

be treated with amantidine and the neuraminidase inhibitors zanamivir and

oseltamivir, and respiratory syncytial virus with ribavirin or the monoclonal

antibody palivizumab, but the efficacy of most treatments is debatable. Treatment

is often just supportive with oxygen and antibiotics against associated bacterial

infections. The patient needs to be isolated from other immunocompromised

patients to avoid patient-to-patient spread.

90: Question

90 A 58-year-old male with a history of asthma had developed progressive fatigue,

malaise, dyspnoea, fever, chills, night sweats, and decreased intake over the previous

few weeks. He denied cough, chest pain, haemoptysis, orthopnoea, and paroxysmal

nocturnal dyspnoea. Two days prior to admission, he had developed a non-pruritic

rash on his forearms, buttock, and groin. Current medications included

montelukast, rabeprazole, ranitidine, digoxin, betamethasone nasal spray, and

tiotropium. On examination, he had bilateral cervical and inguinal

lymphadenopathy, and a non-blanching, erythematous macular rash over the groin,

buttock, and both forearms. His white cell count showed 23% eosinophils. His

chest X-ray is shown in 90. He underwent a VATS biopsy that showed eosinophilic

vasculitis, hyperinflation, and mild, medial hypertrophy of the pulmonary arteries.

i. What is the likely diagnosis?

ii. What are the causes of this?

iii. Describe the treatment and prognosis.

90: Answer

90 i. This is Churg-Strauss syndrome. Churg-Strauss syndrome is an uncommon

condition that shares certain clinical and pathological features with Wegener’s

granulomatosis and polyarteritis nodosa. It is characterized by granulomatous

inflammation and a necrotizing eosinophilic vasculitis and necrosis that can affect

any organ system but most commonly involves the heart, lungs, skin, nervous

system, and kidneys.

ii. The cause of Churg-Strauss syndrome is not known. Its development after

allergic hyposensitization, vaccination, exposure to certain drugs, the withdrawal

of corticosteroids, and pulmonary infections suggests that these events may initiate

the inflammatory cascade. The use of leukotriene antagonists in patients with

asthma has been associated with the development of Churg-Strauss syndrome

perhaps because it allows for a tapering of corticosteroids and thereby unmasks

the syndrome. Other suggested explanations include that it might be an allergic

response to the leukotriene antagonist itself or that the use of antagonist produces

an imbalance in leukotriene receptor stimulation.

Diagnosis is suggested when a previously healthy patient presents with allergic

rhinitis or recurrent sinusitis associated with asthma, followed by signs and

symptoms of a systemic vasculitis. The diagnosis is often initially missed as asthma

and sinus disease are common in the population. The mean latency between the

development of asthma and/or sinusitis and Churg-Strauss syndrome is 8 years.

The 1990 American College of Rheumatology Diagnostic Criteria are:

1. Asthma.

2. Eosinophilia >10% in peripheral blood.

3. Neuropathy, mononeuropathy, or polyneuropathy.

4. Pulmonary infiltrates.

5. Paranasal sinus abnormalities.

6. Extravascular eosinophil infiltration on biopsy.

ANCA positivity is seen in up to 70% of patients, usually with a perinuclear

staining pattern. The cytoplasmic pattern has been observed but is rare.

iii. Corticosteroids are the first-line treatment and are usually sufficient for those

who do not have severe organ involvement. Cyclophosphamide is generally used

when patients relapse or for those with severe necrotizing disease. Plasma exchange,

intravenous immunoglobulin, and alpha-interferon have been posited as adjunctive

therapies, but no randomized trials inform their use in Churg-Strauss syndrome.

Prior to the use of corticosteroids, mortality was approximately 50% within 3

months from vasculitis. The survival rate with corticosteroid therapy approaches

90% at 1 year, 62 to 75% at 5 years, and 50% at 7 years. Factors that define a poor

prognosis and increased mortality include renal disease, gastrointestinal

involvement, cardiomyopathy, CNS involvement, a weight loss of over 10% body

weight, and age over 50 years.

91, 92: Questions

Test

Before treatment

8 hr after treatment

FiO₂

0.4

0.6

7.31

7.29

PaCO₂

7.2 kPa

7.9 kPa

PaO₂

8.9 kPa

8.6 kPa

HCO₃

22 mmol/l

21 mmol/l

91 A 70-year-old female with known COPD has been admitted with a fever,

purulent sputum, and disorientation.

i. Describe her arterial blood gases before and after

8 hr of nebulized

bronchodilators, steroids, and antibiotics (Table).

ii. What should be the next step in her management, and what is the physiology

behind this intervention?

iii. How successful is it?

92 This 45-year-old white female presented with bilateral hilar lymphadenopathy

on chest radiograph and this painful rash (92).

i. What is this syndrome called?

ii. What is her prognosis?

iii. What other cutaneous manifestations may occur in this disease?

91, 92: Answers

91 i. The arterial blood gases demonstrate an acute respiratory acidosis (low pH

and raised PaCO₂). Despite treatment with bronchodilators, steroids, and

antibiotics, she has deteriorated. The PaO₂ has dropped even though the inspired

oxygen concentration has been increased.

ii. Non-invasive ventilation should be the treatment of choice. The PaCO₂ is

inversely proportional to the patient’s minute volume (tidal volume x respiratory

rate). Non-invasive ventilation improves the patient’s minute volume, reducing

PaCO₂ and therefore improving the pH.

iii. Non-invasive ventilation is successful in approximately 80% of cases but fails

in 20%, in particular in those with evidence of pneumonia on chest X-ray. When

instituting non-invasive ventilation, it is therefore important to make a clear plan

covering what to do in the event of deterioration, and ceilings of therapy should be

agreed. The assessment of whether patients with COPD are suitable for elective

endotracheal intubation and invasive ventilation is complex and should include

functional status, BMI, oxygen requirement when stable, previous admissions to

intensive care, age, lung function, and, whenever possible, a careful discussion with

other family members.

92 i. Löfgren’s syndrome, after a Swedish physician who described it in 1946. It

consists of bilateral hilar lymphadenopathy and the rash of erythema nodosum.

Lymphoma and granulomatous infections should be considered. An elevated serum

ACE may reduce the need for a biopsy confirmation in the absence of atypical

features. The syndrome usually occurs in young females who often present with

fever, malaise, arthralgias, and painful lesions on their legs (probably due to

circulating immune complexes). The condition occasionally relapses and is

uncommon in males.

ii. This female is in the best prognostic group of white individuals, with a 90%

chance of spontaneous remission of her sarcoidosis within 2 years without

corticosteroids. The erythema nodosum should fade within weeks.

iii. Cutaneous involvement with sarcoidosis may occur on the anterior surface of

the legs with erythema nodosum. The most common additional skin manifestations

are papulonodular lesions. Nodules are smooth reddish-brown and often solitary

or in small groups, whereas papules are often numerous and often occur on the

face or neck. Lupus pernio occurs mainly in older females and more commonly in

black individuals, and is associated with chronic fibrotic sarcoidosis. Although

often located across the nose and cheeks, these violaceous plaques may be found on

the arms, buttocks, and thighs. Nasal septal perforation may occur. The condition

is treated with prednisolone and weekly methotrexate. Sarcoidosis also has a

predilection for scars and tattoos and can cause subcutaneous nodules.

93, 94: Answers

93 i. This is a face mask used for non-invasive ventilation. It is tight-fitting, and

when attached to a ventilator can provide bi-level (different inspiratory and

expiratory) respiratory support. There is a separate port via which oxygen can be

entrained.

ii. In the acute setting, it should be considered in patients with hypercapnic

respiratory failure and respiratory acidosis due to an exacerbation of COPD. The

patient should be conscious and able to co-operate and maintain his or her airway.

iii. An undrained pneumothorax is an absolute contraindication to this treatment.

Relative contraindications include copious upper airway secretions, confusion,

upper gastrointestinal surgery, bowel obstruction, and haemodynamic instability.

BiPAP is commonly employed in patients who are deemed unsuitable for intensive

care admission and patients with heart failure or pneumonia in whom standard

treatment has failed.

94 i. Eosinophilic granuloma. The major findings on chest CT are irregular, cystic

structures of variable size, most being 3-5 cm in diameter (94a), suggestive of

eosinophilic granuloma. The chest radiograph in this disorder is characterized by

diffusely increased interstitial markings. A nodular or reticular nodular infiltrate is

present, sometimes accompanied by cystic lesions (94b). The infiltrate is most

commonly found in the lung periphery and in the upper lobes. Volume loss is

characteristically absent on both the chest radiograph and the CT.

ii. Primary pulmonary histiocytosis X or eosinophilic granuloma of the lung can

present at any age but is most frequently seen in the third and fourth decades of life.

Patients complain of cough and exertional dyspnoea but may be asymptomatic.

Spontaneous pneumothorax is a classical association. A progressive decline in lung

function and the occurrence of multiple pneumothoraces implies a poor long-term

prognosis. Pleurodesis may be of use in these patients. Immunosuppressive

treatment is of unproven value. The eosinophilic granulomas can also occur in the

pituitary gland, causing diabetes insipidus, and may cause asymptomatic bone cysts,

detected on a radiological skeletal survey.

iii. The classical pathological findings are discrete parenchymal nodules composed

of fibrous tissue, eosinophils, and ‘histiocytosis X’ cells, which resemble the

Langerhans cells of the skin. The histiocytosis cells are characterized by

intracytoplasmic X bodies, which can be visualized by electron microscopy.

95, 96: Questions

95 Shown here is the chest radiograph

(95) of a 56-year-old female from south-

east Asia with chronic cough, malaise,

and weight loss. Multiple sputum

specimens submitted for mycobacterial

and fungal culture have yielded negative

results.

i. What are the radiographic findings?

ii. What is the most likely diagnosis, and

how can this be established?

iii. What is the appropriate treatment?

96 A 60-year-old male presents with a

mucoid cough that has lasted for 4

months and increasing dyspnoea. He

has never smoked. The chest X-ray (96)

is abnormal.

i. What is the likely diagnosis?

ii. How would you make the diagnosis?

iii. What is the best treatment?

95, 96: Answers

95 i. There is a cavitating infiltrate in the apical segment of the left upper lobe.

ii. Melioidosis is an important cause of respiratory infection in tropical regions,

especially south-east Asia. It is caused by the Gram-negative bacterial pathogen

Burkholderia pseudomallei, acquired by cutaneous inoculation with

haematogenous spread to the lungs.

Melioidosis may present acutely, with evidence of cellulitis at the inoculation site,

prominent systemic and respiratory symptoms, and diffuse pulmonary infiltrates.

A more insidious or chronic form of the disease may develop long after an infected

patient has left the endemic area. The presentation of chronic melioidosis is

characterized by indolent wasting symptoms, cough, and apical infiltrates that may

become fibrotic or cavitating, features indistinguishable from those of pulmonary

TB. The diagnosis of melioidosis should be considered whenever a compatible

syndrome develops in a patient who has been in an endemic area. The organism can

readily be cultured from respiratory secretions or other sites, and infection can be

confirmed by serological testing.

iii. B. pseudomallei is sensitive to a variety of antimicrobial agents, but resistance

is variable and antibiotic selection should be based on in vitro sensitivity testing. For

acute disease, combination intravenous therapy including an aminoglycoside is

recommended for 1 month, followed by several months of oral treatment. For

chronic disease, a 3-6-month course of an oral agent such as trimethoprim/

sulfamethoxazole (co-trimoxazole) or amoxicillin-clavulanate may be used.

96 i. The chest X-ray shows a reasonably well-defined infiltrate, which lacks density

in the right lower lobe. This appearance is compatible with an alveolar cell

carcinoma.

ii. Many patients with this tumour produce sputum, often in large quantities.

Sputum cytology is therefore often positive. Alternatively, a bronchoscopic

transbronchial biopsy will yield the diagnosis.

iii. Alveolar cell carcinomas are a variant of adenocarcinoma, and their histology

is often a mixture of these cell types. The tumour can be localized and peripheral,

and classically shows air bronchograms. This presentation may be resectable and

will in general have a better survival, stage for stage, than an adenocarcinoma.

However, if the tumour appears more diffuse on staging CT, it rapidly spreads to

the lung lymphatics, to the hilar glands, and to the other lung. At presentation, CT

may reveal small areas of contralateral ground-glass shadowing that are likely to

be tumour spread. Resection will not be possible. The tumour responds poorly to

chemotherapy, despite having a less aggressive nature and, classically, a low

standardized uptake value on PET scans.

100

97, 98: Questions

97 A 65-year-old lorry driver is seen in

Accident & Emergency with a 5-hr

history of progressive weakness of his

arms and legs, along with a dry mouth

and some difficulty swallowing. He has

a 40 pack-year smoking history and

was previously well. Routine blood tests

are normal, but the chest X-ray (97) is

abnormal.

i. What is the likely diagnosis from the

chest X-ray?

ii. What are the presenting symptoms

due to?

iii. How would you treat this condition?

Test

Result

Reference range

FiO₂

0.6

7.44

7.35-7.45

PCO₂

4.9 kPa (37 mmHg)

4.6-6.0 kPa (35-46 mmHg)

PO₂

11.1 kPa (83 mmHg)

12 - 16 kPa (91-122 mmHg)

HCO₃ 19 mmol/l

22-30 mmol/l

98 A 21-year-old female with a history of asthma presents to the Accident &

Emergency department with severe breathlessness.

i. Interpret these arterial blood gas tensions (Table).

ii. How should the patient be managed?

101

97, 98: Answers

97 i. The chest X-ray shows a large centrally placed mass that is in fact situated

behind the hilum in the apical segment of the right lower lobe. This is a tumour

mass.

ii. The patient has a proximal myopathy with absent tendon reflexes. This, together

with the dry mouth and abnormal chest X-ray, makes LEMS likely. This

paramalignant syndrome is rare and occurs with small-cell lung cancer; it may

precede the clinical or radiological appearance of the tumour by several months.

The reflexes can return for some minutes after forced repetitive contracture of the

affected muscle groups. An electromyogram will show post-tetanic potentiation.

iii. Treatment is aimed both at the underlying carcinoma, which should be treated

by cytotoxic chemotherapy, and at the symptoms of LEMS. The tumour’s response

to chemotherapy will often, by itself, cause the myopathy to improve. Specific

treatment is with high-dose oral prednisolone, 40-60 mg/day, and 2-4 mg/day

aminopyridine, which is an anticholinergic antagonist. These drugs can be reduced

as a response is seen. The return of LEMS usually heralds the relapse of the primary

tumour. It is thought that LEMS carries a better prognosis for survival from the

small-cell cancer.

98 i. The patient has a severe exacerbation of asthma causing the PaO₂ to be much

lower than expected for an FiO2 of 60%. The arterial blood gases show a very

wide alveolar-arterial oxygen gradient. This is calculated by applying the alveolar

air equation, which gives an assessment of oxygen shunt. The equation is PaO₂ =

FiO₂ - PaCO₂/R (where R is assumed to be 0.8). So, here PaO₂ = 60 - 4.9/0.8,

which = 60 - 6 = 54. And therefore PAO₂ (54 kPa) - PaO₂ (11.1 kPa) = 42.9 kPa.

The normal alveolar-arterial oxygen gradient breathing room air is 2 kPa, and a

subject breathing 60% oxygen would have a PaO₂ of approximately 45-50 kPa.

Applying a PaO₂ of 45 kPa to the alveolar air equation gives an alveolar-arterial

oxygen gradient of 2-3 kPa; i.e. normal gas exchange is occurring. The pCO₂ is

within the normal range, which suggests that the exacerbation is severe as one

expects a low pCO₂ in patients with acute asthma due to the increased ventilatory

drive.

ii. The patient is best managed on a high-dependency unit. Treatment should

include high-flow oxygen, continuous nebulized bronchodilators, intravenous

hydrocortisone followed by oral prednisolone 60 mg daily, and intravenous

magnesium. If the condition does not improve, intravenous aminophylline should

be considered. A chest X-ray should be performed to exclude a pneumothorax and

pneumonia.

102

99, 100: Answers

99 i. The photo shows discrete, raised red-purple patches resulting from Kaposi’s

sarcoma. AIDS-related Kaposi’s sarcoma occurs principally in homosexual or

bisexual men infected with the recently identified human herpes virus-8. Unlike

classical forms of the disease, AIDS-associated Kaposi’s sarcoma frequently involves

lymph nodes, gastrointestinal tract, and lung, commonly in the setting of extensive

cutaneous disease and very rarely as an isolated event. Kaposi’s sarcoma typically

occurs in advanced HIV disease when the CD4-positive count is below 100 cells/μl.

ii. Pulmonary Kaposi’s sarcoma may cause radiographic infiltrates and respiratory

symptoms that mimic a variety of other infectious and neoplastic processes.

Dyspnoea and cough are the most common presenting symptoms. Fever and night

sweats may be present and commonly suggest a concomitant infection.

Haemoptysis may also occur and heralds a poor prognosis. Evidence of

parenchymal infiltrates on a CT scan in the presence of visceral Kaposi’s sarcoma

may be sufficient for the diagnosis. The lesions of Kaposi’s sarcoma may also be

readily identified endobronchially. However, biopsy is not recommended due to a

high risk of haemorrhage. In selected cases, open lung biopsy may be necessary.

100 i. There are large spherical lesions with smooth margins in both lungs. CT

scanning confirms that these are thin-walled, fluid-filled cysts.

ii. Cystic abnormalities of this size are most likely the result of hydatid infection.

Pulmonary sequestrations may occasionally manifest in this fashion, as may infected

bullae or bronchogenic cysts. Sequestrations are almost always in the lower lobes.

iii. Hydatid disease results from the ingestion of eggs of the ubiquitous carnivore

tapeworms Echinococcus granulosa or E. multilocularis, prevalent in areas where

dogs coexist with the natural intermediate hosts (i.e. sheep and cattle). Oncospheres

released in the gut enter the portal circulation, and larvae then develop in the liver,

lungs or, less commonly, other systemic sites. E. granulosa larvae form encapsulated

cysts (cystic hydatid disease) that grow slowly and cause symptoms only if they

rupture, become secondarily infected, or reach sufficient size to compress adjacent

structures. The chest radiograph typically shows one or more homogenous masses

with sharply defined margins. The ‘lily pad’ sign may be present if air enters the

cyst. This results from collapsed cyst walls and debris floating on the surface of the

fluid. Eosinophilia may be present, but serological tests are not always positive

unless a cyst has ruptured. CT, and particularly MRI scanning, can reveal the cystic

nature of these lesions and can identify coexistent hepatic cysts. Needle biopsy of

suspected hydatid cysts should be avoided, and treatment by intact surgical excision

is desirable because a spillage of cyst contents can cause anaphylaxis and may lead

to larval dissemination. E. multilocularis cysts fail to mature, and the invading

scolices cause continued inflammation and tissue destruction (alveolar hydatid

disease). Pulmonary involvement is focal or diffuse and treatment with systemic

antihelminthic drugs (e.g. praziquantel or mebendazole) is recommended.

104

101, 102: Answers

101 i. The different types of apparatus used for progressive exercise tests are a

stepping test, or more commonly a treadmill test, and a cycle ergometer test. During

these tests, the workload is increased by small increments at regular time intervals.

The workload will gradually increase until the patient reaches his or her maximum

exercise capacity or maximal oxygen uptake.

ii. The main purpose of a progressive exercise test is to measure the work capacity

achievable by the individual. Several measurements can be made, including heart

rate, minute ventilation, and mixed expired gas concentration by capturing the

expired gases with the patient breathing through a two-way valve box via a mouth

piece. It is mandatory to measure the ECG during exercise and, from it, the heart

rate. Minute ventilation can be measured by collecting expired gas volumes or by

sampling the expired gas volumes for the expired carbon dioxide and oxygen

concentration; from this, the oxygen uptake per unit time (usually minute by

minute) is measured.

The progressive exercise test is commonly used in the investigation of heart

disease (e.g. the Bruce protocol), looking for chest pain, ECG abnormalities, and

breathlessness. In patients with lung disease, exercise is usually stopped by

maximum exercise ventilation being achieved, causing breathlessness. It is also

possible to measure arterial blood gases during exercise, either by an indwelling

arterial cannula or from arterialized capillary blood collected from an earlobe.

Measurements of arterial/arterialized blood gas tensions will allow the alveolar

arterial oxygen gradient to be calculated.

102 i. This encapsulated intracellular yeast is typical of Cryptococcus neoformans.

This can be confirmed by antigen testing of the blood and the culture of blood and

BAL fluid. Other yeasts that cause lung disease include Candida sp. and

Histoplasma capsulatum, but these can be distinguished on morphology and

culture.

ii. A subacute meningitis would be the most common presentation of illness caused

by this organism in AIDS.

iii. Cryptococcal infection is treated with intravenous amphotericin B, sometimes

with the addition of flucytosine in more severe cases. Alternatively, fluconazole

(orally or intravenously) is used for less severe cases. High-dose treatment is given

for 4-6 weeks, followed by long-term secondary prophylaxis - usually with oral

fluconazole. The response to treatment response in usually monitored by clinical

parameters and falling cryptococcal antigen titres. Respiratory disease may lead to

respiratory failure, and meningitis can progress to widespread involvement of the

brain (cryptococcomas) and hydrocephalus.

106

103, 104: Questions

103a

103b

103 A 25-year-old Eritrean female presented with a 6-month history of continual

back pain, but no other symptoms. These are her chest radiograph and the MRI of

her spine.

i. What are the abnormalities present on the chest radiograph and on the spinal

MRI?

ii. What is the likely diagnosis?

iii. How should the patient be managed?

104 This male patient has a tender lump

104

in his chest wall (104) that has appeared

over the past 2 weeks. He had a VATS

pleurodesis for a malignant pleural

effusion 2 months ago.

i. What is the likely diagnosis of the

underlying malignancy, and what is the

lesion?

ii. How would this now be treated, and

could it have been prevented?

107

103, 104: Answers

103 i. The chest radiograph shows a left paravertebral mass parallel to the thoracic

vertebrae behind the heart. The MRI scan shows destruction of the T8/T9 disc

space, the presence of a large prevertebral abscess and a posterior extradural mass

and oedema of the T8 and T9 vertebral bodies. There is also a distinct angulation

of the spine at this point but no overt cord compression.

ii. This is Pott’s disease, i.e. TB of the spine. The patient comes from a high-risk

population, and the combination of disc involvement, spinal angulation, and an

associated soft tissue mass are very suggestive of TB infection.

iii. The patient needs a biopsy/aspiration of the soft tissue mass to prove the

diagnosis and obtain material for microscopy and culture for Mycobacterium

tuberculosis to help confirm the diagnosis and allow antibiotic sensitivity testing.

She should be started on standard antituberculous therapy, and neurosurgical

advice should be sought to ensure her spine is stable and to minimize the risk of

cord compression. As tuberculous masses can swell when treatment is initiated and

the tuberculous lesions are very close to her spinal cord, there is a case for

combining antituberculous treatment with oral corticosteroids (e.g. prednisolone 60

mg once daily initially, which is roughly equivalent to 30 mg due to the effects of

rifampicin [rifampin] on the metabolism of corticosteroids) to prevent neurological

deterioration on starting treatment.

104 i. The lesion is a skin metastasis from either an adenocarcinoma of the lung or

a mesothelioma. Both these diseases commonly present with breathlessness due to

a large pleural effusion. This is best treated with pleurodesis and, at the same time,

biopsy under VATS. Pleurodesis is effective in preventing a recurrence of the

effusion in 80% of cases. An alternative would be a medical (or intercostal drainage

and instillation of talc) pleurodesis after an initial pleural aspiration has revealed

malignant cells. However, medical pleurodesis is successful in only 50% of

individuals.

ii. The treatment of the skin nodule will be by one or two fractions of radiotherapy.

Skin metastases are a frequent complication of penetration of the chest wall in the

presence of a malignant pleural condition. These lesions can be painful and may not

be adequately controlled by radiotherapy. It is now routine practice to administer

radiotherapy prophylactically to any drain, needle, or VATS scar as soon as

possible, which prevents this complication.

108

105, 106: Questions

105

105 This is the chest radiograph (105) of a 39-year-old male who is known to be

HIV positive. He has presented with fever, headache, and a dry cough. The patient

was born in Arizona but moved to the Pacific North-West at age 27 years.

i. What does the chest X-ray show?

ii. What is the significance of the geographical history?

iii. How would you investigate this patient to exclude the diseases associated with

his geographical history?

106 A 28-year-old male with asthma is brought to Accident & Emergency by

ambulance. He has the following features:

• An inability to complete sentences.

• Pulse 120 beats/min.

• PEFR 40% of that predicted.

• Respiratory rate 28 breaths/min.

What additional features would be present in a life-threatening attack?

109

105, 106: Answers

105 i. The chest X-ray shows widespread military nodular shadowing in both lungs,

with hilar lymphadenopathy.

ii. The appearances on the chest radiograph would suggest TB, but with this

geographical history endemic fungal pathogens could also cause this presentation.

In particular, for people who have lived in the south-west of the USA or northern

Mexico, infection with Coccidioides immitis should be considered.

The inhalation of fungal spores is usually asymptomatic but can cause a (usually)

self-limiting illness termed ‘valley fever’ with fever, cough, arthralgia, and a rash.

However, even the asymptomatic inhalation of spores can result in latent infection

for many years, which can, if the patient becomes immunosuppressed, e.g. HIV

infection, develop into active disease. This can then disseminate, with widespread

infection affecting the lungs, joints, skin, and CNS. Treatment requires systemic

antifungal therapy with amphotericin B or itraconazole.

Similar diseases occur with Histoplasma capsulatum (associated with central

USA, Mexico, Puerto Rica, and parts of South Asia), Paracoccidioides braziliensis

(South and Central America), and Blastomyces dermatitidis

(central North

America, Mexico, Middle East, Africa, and South Asia).

iii. Latent infection with endemic mycoses can be diagnosed by serological testing.

Infection requires the identification of fungal spores in sputum, CSF, joint effusions,

or histopathology specimens by microscopy (silver or PAS staining) or prolonged

culture.

106 These features alone suggest a severe exacerbation of asthma. The clinical

features of a life-threatening attack are shown in the Box.

If an attack is not adequately relieved, the patient can become exhausted and be

unable to sustain adequate minute ventilation. The silent chest may be due to

exhaustion, causing inadequate pleural pressure generation to inspire. Lack of

wheeze therefore may be a sinister and not a reassuring sign. Cyanosis, especially

when receiving high-flow oxygen, is potentially catastrophic. Bradycardia and

confusion can also indicate incipient collapse.

Features of a life-threatening asthma attack

• Silent chest

• Cyanosis

• Bradycardia

• Exhaustion, confusion

• Respiratory acidosis

• PEFR <33% predicted

110

107, 108: Answers

107 i. The back pain is mostly

107b

likely to be due to metastatic

disease. The vertebral column is

one of the most common sites of

metastatic spread.

ii. The numbness of the thigh

may indicate a root lesion

(lower

motor

neurone)

compatible with early corda

equina compression. Enquiries

into bladder and other sphincter

function is essential. The patient

needs plain radiographs of the

lower thoracic and lumbar

spine. Even if these are normal,

further investigation is needed,

and this should be by urgent

MRI scan to visualize the cord and surrounding bony structures. Tumour is best

identified by MRI, as would be a soft tissue mass of other cause, e.g. TB (107b).

iii. Suspected paraparesis needs urgent treatment. Paraplegia, once established, rarely

improves. The primary treatment is radiotherapy together with steroid cover. There

is no advantage from surgical decompression. In patients with small-cell lung cancer

for whom a cord lesion is the presenting symptom, chemotherapy can be added

following radiotherapy if the clinical response appears adequate.

108 i. This plot shows the rates of decline of FEV₁ in healthy individuals and in

smokers.

ii. FEV₁ is a strong predictor of survival in COPD. The normal rate of decline is about

27 ml/year, i.e. 1,000 ml in 40 years. The rate is generally accelerated in smokers, up

to a maximum of 140 ml/year. The plot shows how the rates of decline allow disability

to manifest at younger ages, depending on both the rate of decline and individual

habitual activity. Whereas a healthy person will never develop pulmonary disability,

the heavy, susceptible smoker will become affected in his 50s or 60s. Note that quitting

may result in the rate of decline reverting to that of a never-smoker, delaying or

preventing the onset of disabling symptoms. The plot shows premature death due to

loss of lung function at a considerably earlier age than normal.

It is also likely that an impaired growth of lung function in childhood and

adolescence as a result of recurrent infections or passive exposure to tobacco smoke

may lead to lowered maximally attained lung function in adulthood, such that the

individual starts to decline from a lower threshold than normal.

112

109, 110: Questions

109 A 57-year-old male has persisting

exertional dyspnoea and hypoxia

Lung function results:

weeks after discharge from intensive

FEV₁

2.14 (70% expected)

care. He had been admitted to the

FVC

2.59 (67% expected)

intensive care department with a severe

DL_CO

38% expected

right upper lobe pneumonia that was

K_CO

64% expected

complicated by ARDS and required

ventilation for 22 days. These are his

lung function test results.

i. What could be causing this patient’s persisting dyspnoea?

ii. What investigations are necessary?

iii. What is the natural history of this problem?

110

110 A 44-year-old, non-smoking male presented with several weeks’ cough,

dyspnoea, and purulent sputum on the background of longstanding asthma. He

was apyrexial and not systemically unwell. 110 is the chest X-ray on presentation.

His FEV₁ was 1.9 l/s (expected 4.2 l/s) and his FVC 3.6 l (expected 5.4 l). No acid-

fast bacilli were seen on microscopy of multiple sputum samples, all of which were

negative for acid-fast bacilli and remained negative for mycobacteria after 8 weeks

of culture of culture. A full blood count and blood chemistry were normal except

for a total IgE level of 7143 kIU/ml.

i. What does the X-ray show, and what possible diagnoses need to be considered?

ii. How should the patient be investigated?

iii. What is the treatment of the most likely diagnosis?

113

109, 110: Answers

109 i. The lung function tests show a restrictive spirometric defect and a markedly

reduced transfer factor, which would be compatible with post-ARDS lung fibrosis.

Another cause of dyspnoea, usually after more prolonged ventilation, is a tracheal

stenosis caused by intubation and tracheostomy, but this would cause an obstructive

defect and a characteristic flattened appearance to the inspiratory part of the

flow-volume loop.

ii. As well as lung function tests and a chest X-ray, an HRCT scan is necessary and

should show the characteristic subpleural changes of interstitial fibrosis. In contrast

to the distribution of the airspace shadowing in early ARDS, which is gravity

dependent and therefore often most marked posteriorly in patients ventilated

supine, post-ARDS fibrosis is often more marked anteriorly.

iii. In up to 70% of those who survive an episode of ARDS, lung function returns

to within the normal range.

110 i. The chest X-ray shows hyperinflated lungs, ring shadowing with associated pat-

chy shadowing in the right middle zone, and a streaky infiltrate in the left upper zone.

ii. Opacities in the upper zones can be due to primary lung cancer, TB, and non-

tuberculous mycobacterial infections, lung abscesses, unusual infections such as

Nocardia, actinomycosis, endemic fungi, melioidosis and Aspergillus, and

inflammatory conditions such as vasculitis or necrotizing granuloma. However, the

combination of poorly controlled asthma, massively elevated total IgE levels, ring

shadows suggestive of bronchiectasis, and pulmonary opacities indicate that allergic

bronchopulmonary aspergillosis is the likely diagnosis.

Investigations should be directed to identifying allergic bronchopulmonary

aspergillosis and excluding the other causes. Patients with allergic bronchopulmonary

aspergillosis can have a moderate eosinophilia (>1000/mm³), almost always have

positive skin prick tests to Aspergillus and a markedly raised IgE level (>1000 IU/ml),

and usually have positive Aspergillus-specific IgE in their serum (although less often

positive Aspergillus precipitins, e.g. IgG). Aspergillus can be identified by culture or

cytology in sputum or bronchial washings, and the patient may expectorate

characteristic plugs of sputum shaped like casts of the bronchi. A CT scan can, in

advanced cases, demonstrate bronchiectasis, usually proximal, and mucous plugging

of the large and small airways (the latter giving a ‘tree-in-bud’ appearance).

iii. The treatment of allergic bronchopulmonary aspergillosis requires treatment of

the asthma and airways obstruction component using high-dose inhaled and often

oral corticosteroids, as well as bronchodilators. In addition, infective exacerbations

of the bronchiectasis require treatment with 10-14 days of appropriate antibiotics.

Prolonged treatment with the antifungal agent itraconazole 200 mg twice a day

can reduce the dose of oral prednisolone for patients on long-term corticosteroids.

Itraconazole is poorly absorbed, especially in patients with achlorhydria, and drug

levels should be monitored.

114

111-113: Answers

111 i. OSA raises the mean 24-hr blood pressure by at least 4-6 mmHg in those

with an apnoea-hypopnoea index of >20/hr. OSA has been demonstrated in several

studies to be associated with a 20% greater risk of myocardial infarction and a

40% increase in stroke. However, the effect of OSA on mortality has not been well

measured. One study has demonstrated that conservatively treated patients,

compared with those treated by tracheostomy, had nearly a five times the risk of

cardiovascular- or stroke-related death. The effects of OSA on mortality are not

clear. In diabetes, increased apnoeas and hypopnoeas are associated with an increase

in insulin resistance independent of obesity.

ii. The lack of autonomic nervous system control during rapid eye movement sleep

may represent a risk period for health and may be a precipitating factor in nocturnal

death.

112 i. The average dose entering the lungs from a well co-ordinated inspired breath

with the MDI is about 10%. The rest are either large particles that impact on the

throat, or particles less than 5 μm size that do not deposit in the lung airways or

alveoli and are exhaled. Deposition patterns using depot DPIs are similar. The ideal

particle size for optimal lung deposition is around 5 μm.

ii. The advantages of using a spacer is that patient co-ordination with the firing of

the MDI becomes less important. Also, as the drug leaves the MDI at 97 km/hr

(60 mph), timing the inhalation is more important than when the chamber is used

to ‘collect’ the actuation. There is better deposition in the lung from a spacer, rising

to 12-14%, and with more going to the lung periphery than with the MDI alone.

Fewer large particles leave the chamber, and oral thrush rates are far less.

113 This is thoracic actinomycosis. It is a subacute-to-chronic bacterial infection

caused by filamentous, Gram-positive, anaerobic bacteria that are not acid fast. It

is characterized by the formation of multiple abscesses and sinus tracts that may

discharge sulphur granules and commonly invade the pleura and chest wall. The

condition arises following the aspiration of oropharyngeal secretions that contain

actinomycetes. The chest X-ray shows dense consolidation in the right upper lobe

with volume loss. It mimics the appearance of lung cancer but may be cured with

a prolonged course of penicillin of at least 6 months.

116

114, 115: Questions

114

(a) SF Male 49 year old

(b) SF Male 49 year old

PaO₂

PaCO₂A-aDO₂

PaO₂

PaCO₂A-aDO₂

Rest

7.50

12.2

4.3

2.2

Rest

7.41

12.9

5.9

2.4

Exercise

7.51

8.1

3.9

7.2

Exercise

7.33

13.0

5.1

1.5

Heart Rate (bt/min)

160

140

Ventilation

(l min^-1)

120

(l min^-1)

120

100

Heart Rate

100

Heart Rate

Ventilation

(mmol

min^-1)

0.5

1.0

1.5

2.0

(l min^-1)

0.5

1.0

1.5

2.0

(l min^-1)

Oxygen uptake

114 Shown (114) is the response of heart rate and ventilation to increasing oxygen

uptake during a progressive work rate test in a male with alveolar proteinosis.

Exercise has stopped with the heart rate at the upper limit of normal and a

ventilation that was higher than normal but not at predicted maximum, and the

patient was complaining of breathlessness. The subsequent exercise test followed a

procedure that improved the patient’s breathlessness.

i. Comment on the two exercise test results.

ii. What was the procedure that improved the patient?

115 i. What are the symptoms of OSA?

ii. What is the Epworth Sleepiness Score, and how predictive of the severity of OSA

is it?

117

114, 115: Answers

114 i. 114a shows excessively high ventilation from the beginning of exercise to the

completion of the test. Arterial blood gases show hypoxaemia with increasing

hypoxia at the end of exercise and a widened alveolar arterial oxygen gradient

(A-aDO₂, from 2.2 to 7.2 kPa). The post-treatment exercise test (114b) shows a

considerable improvement in resting heart rate and the heart rate response during

exercise, and the ventilatory response remained within the normal range. The

arterial PO₂ and the alveolar arterial oxygen gradients were considerably improved.

ii. The procedure that improved the patient was a BAL of 10 l, which is the

treatment of choice in flushing out the abnormal protein from the alveolar spaces

in these patients.

115 i. The main symptoms of OSA are: excessive daytime sleepiness, difficulty

concentrating, daytime fatigue, unrefreshing sleep, nocturia, depression, nocturnal

choking, and decreased libido. They occur especially in overweight, middle-aged

males who have often snored for years. OSA is also related to collar size, and

increasing neck circumference with weight gain is more common in males because

females who gain weight tend to accumulate it around their hips.

ii. The Epworth Sleepiness Score (Box) is a useful guide to detecting OSA but is in

itself insufficient. Partners will often score the patient differently, and the highest score

should then be recorded. Many sleepy patients do not score very highly. However,

there is a good relationship between greater scores on the Epworth Sleepiness Score

and CPAP compliance. A score greater than 12 is very suggestive of OSA.

Epworth Sleepiness Score: How often are you likely to doze off or fall asleep in

the following situations, in contrast to feeling just tired? This refers to your

usual way of life in recent times. Even if you have not done some of these

things recently, try to work out how they would have affected you. Use the

following scale to choose the most appropriate number for each situation:

0.Would never doze

1.Slight chance of dozing

2.Moderate chance of dozing

3.High chance of dozing

• Sitting and reading

• Watching TV

• Sitting, inactive in a public place (e.g. a theatre or a meeting)

• As a passenger in a car for an hour without a break

• Lying down to rest in the afternoon when circumstances permit

• Sitting and talking to someone

• Sitting quietly after lunch without alcohol

• In a car, while stopped for a few minutes in traffic

Total

/24

118

116, 117: Answers

116 i. The dichotomous branching hyphae of an Aspergillus species invading lung

tissue - the diagnosis is invasive aspergillosis. The morphology of the fungus helps to

identify the species as an Aspergillus, but precise identification requires culture. The

most common Aspergillus species causing lung infection is A. fumigatus, which is

responsible for about 70% of infections. Other Aspergillus species that cause lung

disease include A. flavus, A. terreus, and A. niger. Less common moulds that have a

presentation similar to that of invasive aspergillosis include Fusarium, Scedosporium,

and Penicillium.

ii. Invasive aspergillosis is largely a disease affecting those who are immunosuppressed,

especially those who have prolonged and profound neutropenia. It is therefore

especially common in patients with haematological malignancies or aplastic anaemia,

and in bone marrow transplant recipients. It is also common in lung transplant patients

and occurs in other organ transplant patients as well as patients with AIDS with very

low CD4-positive cell counts. A less aggressive indolent form can affect patients with

pre-existing lung disease and lesser degrees of immunosuppression such as those with

diabetes or patients on corticosteroids.

iii. Treatment is with systemic antifungal agents such as amphotericin, caspofungin,

and voriconazole. Although effective, amphotericin frequently has to be discontinued

due to toxicity (especially renal) and has been largely superseded by liposomal

formulations, which are much better tolerated. The introduction of caspofungin and

the newer azoles such as voriconazole has improved treatment options for invasive

fungal infections enormously. However, recovery from invasive aspergillosis is highly

dependent on the patient’s immune status improving, and mortality is up to 50%.

117

• Because males and females of similar ages have different lung capacities, and

because these are also affected by height and weight, all predictions of

postoperative lung function from preoperative values should be expressed and

considered as a percentage of that predicted.

• If the preoperative FEV₁ and DL_CO are both >80% predicted, a

pneumonectomy is possible. If either is <80%, an exercise test measuring

VO₂max is necessary. If the VO₂max is <10 ml/kg/l and the FEV₁ or DL_CO is

<40% predicted, a lobectomy will not be possible.

• If the VO₂max is >20 ml/kg/l or the FEV₁ or DL_CO is >75% predicted, a

pneumonectomy will still be safe.

• However, for those with intermediate results, i.e. FEV₁ or DL_CO 40-75% of

that predicted and VO₂max 10-20 ml/kg/l, split lung function tests are needed,

e.g. a V/Q scan. This will determine the distribution of blood and air to the

lung tissue planned for resection. If the lung tissue remaining after resection

would contain <40% of function, no resection is possible. Above 40% a

lobectomy is possible.

120

118-120: Answers

118 i. The hands show clubbing with a loss of the nailfold angles. This is associated

with non-small-cell lung cancers. It can be associated with pain and swelling of the

distal forearm and shins, which can become red and oedematous, and the bones

themselves very tender to pressure. Radiography will show new bone formation or

periostitis. The condition is known as HPOA. Bone scintigraphy with Tc-99m-

methylene diphosphonate may reveal increased tracer uptake along the distal fingers

and toes owing to clubbing. Treatment is with non-steroidal anti-inflammatory

medication, with, if possible, treatment of the primary tumour.

ii. HPOA occurs primarily with lung cancer but has also been reported in

association with pulmonary sepsis, thymic carcinoma, chronic myeloid leukaemia,

thyroid carcinoma, Hodgkin’s disease, adenocarcinoma of the oesophagus, primary

lymphocarcinoma of the lung, and bronchial carcinoid tumour. Benign associations

include cyanotic congenital heart disease, pleural fibroma, Graves’ disease,

oesophageal achalasia, portal cirrhosis, inflammatory bowel disease, leioma of the

oesophagus, cystic fibrosis, and idiopathic or familial HPOA.

119 In late pregnancy, the diaphragm is pushed cephalad by up to 4 cm. The

potential loss of lung capacity is partially offset by increased anteroposterior and

transverse diameters. However FRC and RV are reduced, and TLC may fall a little.

Diaphragmatic and maximal mouth pressures remain normal.

Minute ventilation increases markedly from the first trimester and reaches

20-40% above baseline at term. This is mainly due to an increase in tidal volume.

A respiratory alkalosis with compensated renal excretion of bicarbonate results,

with PaCO₂ falling (3.8-4.3 kPa). The PaO₂ remains normal.

120 i. Hospital-acquired pneumonia with or without atelectasis

(areas of

subsegmental pulmonary collapse).

ii. A full blood count, arterial blood gases, blood and sputum cultures, and blood

biochemistry are necessary.

iii. The patient should be given oxygen, kept well hydrated, and encouraged to sit

up rather than lie in bed to help respiration and minimize basal atelectasis, which

will impair gas exchange. Physiotherapy may help the patient to clear tenacious

sputum. She will need empirical antibiotics to cover the usual organisms that cause

hospital-acquired pneumonia, which are initially Streptococcus pneumoniae,

Staphylococcus aureus, and Gram-negative coliforms. However, in patients who

have been in hospital for a long period or in intensive care, the spectrum of

causative organisms extends to include antibiotic-resistant coliforms and

Pseudomonas aeruginosa.

122

121, 122: Answers

121 i. The chest X-ray shows larger than normal lung fields with darker than

normal bases, cystic bi-basal shadowing, and vascular pruning in both lower lobes,

suggestive of basal emphysema.

ii. This condition α₁-antitrypsin deficiency emphysema is an autosomally recessive

inherited disease. It occurs in 1 in 5,000 children in the UK and 1 in 2,700 in the

USA. More than 75 biochemical variants of α₁-antitrypsin have been described.

They have given rise to the Pi inhibitor nomenclature. The most common allele is

PiM, and the most common genotype is PiMM, which occurs in 86% of the normal

UK population. PiMZ and PiS are the next two most common genotypes and are

associated with α₁-antitrypsin levels of 15% and 75% of normal PiMM levels. The

threshold point for developing emphysema is 35-50% of normal level. The

homogygous PiZZ type shows levels that are 10-20% of the average normal value,

and this is the strongest genetic risk factor for panacinar emphysema.

iii. α₁-Antitrypsin is a major inhibitor of serine proteases, including neutrophil

elastase, and has its greatest affinity for the enzyme neutrophil elastase. It is

synthesized in the liver, and in cases of deficiency, it remains entrapped in the liver

as PAS-staining granules. A deficiency of the enzyme leads to unrestrained

proteolytic damage to the lungs, leading to emphysema, which develops at an earlier

age than the common variety seen in COPD. The damage occurs at the lung bases

as this is where blood flow and air (plus tobacco irritants) mix maximally. Cigarette

smoking is a co-factor for α₁-antitrypsin deficiency emphysema, probably as a result

of oxidation and hence inactivation of the remaining functional α₁-antitrypsin by

oxidants of cigarette smoke.

iv. The most important advice is to stop smoking. The family should be screened

by measuring α₁-antitrypsin serum levels, and homogyzotes and heterozygotes

should be identified and advised never to smoke. Heterozygotes usually do not get

the disease even if they do smoke, but advice should be given about having children

if the partner is also a heterozygote.

122 i. The lateral chest X-ray shows pectus excavatum, an inward displacement of

the sternum that has probably been present from birth. Despite being what is

occasionally a striking physical abnormality, it does not cause reduction of the VC

except in a minority of cases. In addition, such patients do not have breathlessness

due to the sternal deformity.

ii. Associated features include thoracic kyphosis and scoliosis. Cardiac effects

include right axis deviation on ECG (due to leftward displacement of the heart),

supraventricular tachycardias, mitral valve prolapse, and, rarely, reduction of right

ventricular filling due to cardiac compression.

124

123-125: Questions

123

123 A 50-year-old male has a 9-month history of a dry cough. He is otherwise well.

Lung function and chest radiology are within normal limits.

i. What is this investigation (123)?

ii. What does it show?

iii. List the common causes of chronic cough

124

125

124 i. The material in 124 was obtained

125 i. What is the diagnosis of this

from whole-lung lavage of a patient

transbronchial biopsy (125), and what

with what disorder?

is the differential diagnosis?

ii. What is the appropriate treatment for

ii. Why is this condition easy to

this condition?

diagnose by transbronchial biopsy?

iii. Do corticosteroids have a therapeutic

iii. Which other conditions may be

role?

confidently diagnosed by transbronchial

biopsy?

125

123-125: Answers

123 i. The investigation is ambulatory

oesophageal pH monitoring, which is the most

Causes of chronic cough with a

sensitive and specific investigation for the

normal chest X-ray

diagnosis of gastro-oesophageal reflux.

• Gastro-oesophageal reflux

ii. The test demonstrates low pH in the

• Oesophageal dysmotility

oesophagus consistent with gastro-oesophageal

• Asthma syndromes

reflux disease, which is an important cause of

• COPD

chronic cough and occurs in up to 40% of

• Rhinitis

individuals with a cough lasting more than 3

• Drugs, e.g. ACE inhibitors

months.

iii. The Box shows the common causes of

chronic cough.

124 i. The lavage fluid shown is characteristic of pulmonary alveolar proteinosis,

a disorder in which a phospholipid-rich proteinaceous material is deposited in the

alveoli and bronchioles without associated lung fibrosis. Lung fluid obtained from

whole-lung lavage or BAL is milky in appearance and contains large macrophages

with prominent cytoplasm.

ii. Whole-lung lavage is the only treatment that is consistently successful. Lavages

of as much as 20 l total fluid washed in are often performed at one session under

general anaesthesia. The procedure is generally well tolerated and may be repeated

as necessary, generally at 6-12-month intervals.

iii. Corticosteroids have not been shown to have a beneficial effect in this disorder

and may be harmful. Inflammation does not appear to play a role in the

pathogenesis. The condition is often self-limiting, with spontaneous remission on

radiography after lavage clearance.

125 i. The compact granulomas with a paucity of interstitial inflammation are

typical of sarcoidosis.

ii. The granulomas are situated adjacent to the bronchi, making them amenable to

diagnosis by bronchial or transbronchial biopsy. Only four separate biopsies are

usually needed to obtain typical granulomas. A transbronchial lung biopsy may be

positive even when the chest radiograph shows only hilar lymphadenopathy

without parenchymal shadowing. The main differential diagnosis is EAA, although

in that condition the granulomas are not as tightly formed and are overshadowed

by an interstitial inflammatory cell infiltrate.

iii. Other conditions that can be readily diagnosed with transbronchial lung biopsy

include lymphangitis carcinomatosa and alveolar proteinosis. Conditions such as

idiopathic pulmonary fibrosis may be suggested by transbronchial biopsy, but the

definitive diagnosis usually requires large samples such as from an open lung biopsy.

126

126-128: Answers

126 i. No, although there should be increased vigilance over asthma control,

especially close to the time of delivery. Delivery is usually uncomplicated if control

is good. As with all asthmatics, inhaled therapy is preferred. No increased

teratogenesis has been reported when mothers receive beta-agonists, inhaled

steroids, sodium cromoglicate (cromolyn), or theophylline. When systemic steroids

are used, neonatal hypoadrenalism is very rare.

ii. A prospective study of 504 pregnant asthmatic women showed that, of 177

patients not initially treated with inhaled corticosteroids, 17% had an acute attack,

in contrast to 4% of the 257 patients who had been on inhaled anti-inflammatory

treatment from the start of the pregnancy. No differences were observed between

the two groups in terms of length of gestation, length of the third stage of labour,

or amount of haemorrhage after delivery. Nor were any differences observed

between these groups with regard to relative birthweight, incidence of

malformations, hypoglycaemia, or need for phototherapy for jaundice in the

neonatal period. In an earlier smaller prospective study of 198 pregnant women,

there was a small increase in pre-eclampsia and a higher incidence of caesarean

section in asthmatic patients compared with those without asthma.

iii. There is no specific effect. In about 40-50% of females, asthma remains

unchanged, in 25% it improves, and in another 25% it deteriorates.

127 i. The CT image demonstrates multiple small nodules on a background of

emphysema.

ii. The appearances are typical of non-tuberculous mycobacteria. Pulmonary

metastases, vasculitis, and septic emboli are other possible causes. Non-tuberculous

mycobacteria, in particular Mycobacterium avium complex, may be confirmed

from BAL. Mycobacterium avium complex is an uncommon but important cause

of morbidity in patients with COPD. DNA probe testing on lavage samples may

establish the diagnosis rapidly and exclude TB.

iii. Treatment is with clarithromycin, rifampicin (rifampin), and ethambutol with

consideration of additional intravenous amikacin in severe cases. Treatment should

continue until the patient has been culture negative on therapy for 1 year. The

mortality can be as high as 50% despite good compliance with therapy.

128 i. Endobronchial brachytherapy. Its role is primarily palliative for

breathlessness but also for cough and haemoptysis. It is indicated for an

endobronchial tumour with a mural and/or endobronchial component, preferably

without extrinsic compression. Occasionally, it may be used with curative intent in

patients with small endobronchial tumours.

ii. The procedure is performed under local anaesthetic with intravenous sedation

and is generally well tolerated.

128

129, 130: Answers

129 i. The picture shows a typical wheal and flare reaction.

ii. This is a type 1 (immediate) hypersensitivity reaction. It results from the IgE-

mediated release of histamine and other inflammatory cytokines from mast cells

and basophils. This process in the skin results in urticaria, characterized by hives

or wheals that cause significant pruritis. Angio-oedema is localized tissue swelling

that may occur in tissues throughout the body. If it occurs in the upper airway, e.g.

larynx or tongue, it can cause life-threatening airway obstruction. IgE-mediated

cytokine release in the airways results in asthma, and if the mast cell and basophil

products are released systemically, anaphylactic shock can occur.

iii. The most common allergens are peanuts, bee stings, latex, pollen, animal dander,

and drugs, e.g. penicillin. Once the causative agent has been identified, meticulous

allergen avoidance is the most important intervention. Anaphylactoid reactions are

clinically similar to anaphylaxis and are due to mast cell degranulation but are not IgE

mediated. Common examples include the reactions to radiocontrast dyes and opiates.

130 i. The chest X-ray shows a left-sided pleural effusion with increased density at

the left hilum. The most likely diagnosis is TB.

ii. Pleural aspiration will reveal a lymphocytic exudate with a low glucose level.

Samples should be sent for culture for Mycobacterium tuberculosis. However, the

yield from PCR and culture from tuberculous pleural effusions is relatively low, at

40%. Higher diagnostic yields of over 90% may be obtained with blind pleural

biopsy using an Abram’s needle. In cases where malignancy is more likely,

ultrasound-guided pleural biopsy is the investigation of choice if cytological

examination of pleural fluid does not provide the diagnosis. The causes of a

lymphocytic pleural effusion are given in the Box.

A tuberculous pleural effusion is most commonly caused by a delayed

hypersensitivity reaction to the presence of mycobacterial antigens, which responds

to antituberculous therapy usually within a few weeks. This should be distinguished

from a tuberculous empyema in which pus with a high mycobacterial load occupies

the pleural space; this usually requires percutaneous drainage.

Causes of a lymphocytic pleural effusion

Malignancy

Infection

• Primary lung cancer

• TB

• Mesothelioma

• Amyloidosis (rare)

• Pleural metastases

• Sarcoidosis (rare)

• Lymphoma (rare)

130

131-133: Questions

131 As well as dyspnoea, this male

131a

patient also complains that he has had

multiple floating spots across his field of

vision for several weeks, and on

examination he has retinal haemorr-

hages and exudates (131a).

i. How commonly would such eye and

pulmonary problems be connected?

ii. What is the appropriate management

of this situation?

132 A 70-year-old male who is known to have a squamous cell carcinoma of the

lung is admitted with a 2-day history of confusion, abdominal pains, vomiting, and

constipation.

i. What is the differential diagnosis for his confusion?

ii. What is the likely metabolic cause, and how would you treat it?

133

133 i. What does the CT scan (133) show?

ii. What is the differential diagnosis?

131

131-133: Answers

131 i. The retinal problem (131a) is due

131b

to CMV. The differential diagnosis of

interstitial pneumonitis is as in the answer

173, with Pneumocystis jirovecii

pneumonia

(formerly Pneumocystis

carinii pneumonia, or PCP) still being the

most likely cause (131b). Other than the

eye, this organism also causes disease of

the gut, nervous system, and biliary tree.

Rarely, CMV may be implicated in HIV-

related pneumonitis when other

pathogens, such as P. jirovecii, have been excluded as a cause.

ii. The initial management would be as in 13, that is, therapy for presumed P.

jirovecii pneumonia until the result of bronchoscopy has been obtained. In the rare

case of CMV pneumonitis, the patient will be treated with intravenous ganciclovir

at high dose for 2-3 weeks. If the CMV pneumonitis occurs without concomitant

eye involvement, no further therapy is necessary.

132 i. The common causes of confusion in a patient with known lung cancer are

cerebral metastases, poor attention to pain control leading to opiate excess, uraemia,

pneumonia, and hypercalcaemia. This patient has a squamous cell carcinoma in

which hypercalcaemia can present as a paramalignant syndrome due to the secretion

of a cyclic AMP stimulating factor. He does not appear to complain of bony pains,

making the hypercalcaemia unlikely to be due to increased bone turnover from

multiple metastases.

ii. Hypercalcaemia presents with thirst, polyuria, dehydration, confusion,

constipation, and eventually coma. Treatment is by intravenous rehydration,

intravenous hydrocortisone, and intravenous bisphosphonate. The latter can be very

effective and needs repeating every 4-6 weeks. Treatment of the primary tumour

whenever possible is also likely to be beneficial.

133 i. The CT scan shows two darker areas within the liver that are of differing size

and likely to be metastases.

ii. The differential diagnosis can often be between malignancy and benign cysts, which

are usually smooth in outline and non-contrast-enhancing. An ultrasound scan will

discover whether they are fluid-filled cysts or malignant deposits. Liver metastases are

usually asymptomatic in newly diagnosed cases of lung cancer, and are found in about

5% of cases of non-small-cell lung cancer thought to be operable. Their presence is

more common late in the course of the disease, with up to 60% of autopsy cases

having liver deposits.

132

134, 135: Questions

134a

134b

134 A 62-year-old female with a 100 pack-year history had a chest X-ray taken to

evaluate her complaint of a chronic, non-productive cough. Pulse oximetry showed

an oxygen saturation of 85% when breathing air. Spirometry showed moderate

airflow limitation. A left upper lobe nodule was found, leading to a chest CT

(134a). BAL was negative, and a transbronchial lung biopsy was obtained (134b).

i. What does the histology show?

ii. What is the diagnosis?

iii. What is the appropriate treatment?

135 A 55-year-old female presents with

135

a 6-week history of a non-productive

cough, fevers, malaise, and some weight

loss. There is no improvement with a

course of amoxicillin and clarithro-

mycin. Her HRCT scan is shown (135).

A bronchoscopy is normal and shows

no evidence of an obstructing lesion, TB,

eosinophilia, or bronchoalveolar cell

carcinoma.

i. Describe the HRCT appearances.

ii. There is clinical and radiological

improvement with oral steroids. What is the diagnosis, how may it be confirmed,

and what are the possible causes?

133

134, 135: Answers

134 i. Neuroendocrine tumors can show a variety of histological abnormalities

including diffuse hyperplasia, neuroepithelial bodies, carcinoid tumourlets, and

typical carcinoid tumour, any or all of which can be associated with airway wall

thickening and fibrosis. Neuroendocrine cells are confirmed by their staining with

bombesin or chromogranin.

ii. Finding diffuse small nodules (i.e. 2 mm, seen in the right upper lobe on the slice)

indicates diffuse involvement, which, in addition to the large carcinoid tumor in

the left upper lobe, indicates diffuse idiopathic pulmonary neuroendocrine cell

hyperplasia with carcinoid. Diffuse idiopathic pulmonary neuroendocrine cell

hyperplasia is felt to be a preneoplastic condition, and the most common

physiological deficit observed with it is airway obstruction; several investigators

have reported an association with BO.

iii. Treatment is difficult. Cytotoxic agents are ineffective. Octreotide has been tried

as it binds to carcinoid tumour cells and inhibits growth as well as the release of

hormones. Agents targeting the epidermal growth factor receptor transduction

pathway have also been tried since neuroendocrine cells overexpress epidermal

growth factor receptors.

135 i. The HRCT shows patchy alveolar opacities that are bilateral and peripheral.

ii. The diagnosis is organizing pneumonia. Inflammatory indices are often raised, but

no specific blood tests exist. BAL shows a mixed pattern with increased neutrophils

and lymphocytes. The diagnosis may be confirmed by transbronchial or lung biopsy

that shows intra-alveolar buds of granulation tissue. The causes of organizing

pneumonia are listed in the Box and must be excluded. Cryptogenic organizing

pneumonia for which no cause is found responds well to oral corticosteroids, usually

within 48 hours. The dose may be tapered after 4-6 weeks, but the condition often

relapses. Prolonged treatment of 6-12 months is usually required.

Causes of organizing pneumonia

Infection

• Bacteria, e.g. mycobacteria

• Viruses, e.g. influenza

• Parasites, e.g. Plasmodium vivax

• Fungi, e.g. Pneumocystis jirovecii

Drugs, e.g. amiodarone, methotrexate, phenytoin

Connective tissue disorders, e.g. rheumatoid arthritis, Sjögren’s syndrome

Wegener’s granulomatosis

Post bone-marrow transplant

Previous exposure of the lungs to radiotherapy (e.g. for breast cancer)

134

136, 137: Answers

136 i. The blood results suggest the syndrome of syndrome of inappropriate ADH

secretion. If the chest X-ray shows a mass, a small-cell lung cancer is the most

common association of this syndrome with malignancy. The ectopic secretion of

ADH causes waterlogging, confusion, and haemodilution of electrolytes with a low

serum osmolality (<275 mOsm/kg), together with a concentrated urine and

osmolality >200 mOsm/kg. This syndrome is present with abnormal electrolytes in

10% of new presentations of small-cell lung cancer, and 50% will not excrete a

waterload. Other causes of this syndrome include pulmonary infections, CNS

disorders, and some drugs.

ii. The treatment will include treatment of the primary tumour with chemotherapy

and oral demeclocycline, which competes for ADH binding sites in the kidney.

Renal function should be monitored and the demeclocycline reduced or stopped

once the tumour is responding to therapy.

137 i. A nasal polyp, a red mass in the region of the middle turbinate. These occur

when oedematous sinus mucosa prolapses into the nasal cavity. They are often

associated with perennial rhinitis and low-grade sinusitis.

ii. Nasal polyposis should be treated medically with a short course of oral steroids

or local steroid drops followed by topical steroid sprays. If this is not successful,

intranasal or endoscopic polypectomy can be considered for polyps that occlude the

nasal cavity. Surgery is not curative, however, and the recurrence rate is greater

than 40%. For polyposis that occurs in the setting of chronic rhinosinusitis, the

allergic disease should be treated with antihistamines, topical nasal corticosteroids,

and immunotherapy.

iii. Some 20-40% of patients with asthma have nasal polyps, and many of these

patients are allergic to aspirin (acetylsalicylic acid); 10% of all chronic asthmatics

respond to aspirin or other non-steroidal anti-inflammatory drugs with an

exacerbation of asthma and acute rhinoconjunctivitis. Some 30% of asthmatics

with polypoid rhinosinusitis have aspirin sensitivity. Other allergic causes include

fungal infestations, sinusitis and Churg-Strauss syndrome. There can also be

infective causes, as well as underlying cystic fibrosis or immune deficiency states.

Malignancy is rare.

136

138-140: Questions

138 A 29-year-old male was in a motor vehicle

138

accident in which he fractured his femur, right

humerus, and liver. No abdominal surgery was

needed. On day three of his hospitalization, he

developed haemoptysis. His chest CT is shown

in 138. What is the diagnosis?

139 A 60-year-old male with a 20 pack-year smoking history has a small

haemoptysis on 3 consecutive days.

i. What are the common causes of this, and how often is a diagnosis made?

ii. What tests should be carried out?

140 A 60-year-old male who has never

140

smoked has a longstanding history of a

dry cough. Over the last few months, he

has become increasingly breathless on

exertion.

i. Describe the appearances on the chest

X-ray (140).

ii. What is the most likely cause of these

appearances?

iii. What complications may occur?

137

138-140: Answers

138 Post-traumatic pseudocyst. Blunt chest trauma can result in tears of the lung

parenchyma termed post-traumatic pseudocysts or pneumatoceles (pseudocyst being

the preferred term since these are epithelium-lined cavities). Post-traumatic pseudocysts

are, not surprisingly, more common in young males (average age 17-30 years, with the

male:female incidence ratio being as high as 11:1). The most common symptoms are

chest pain, dyspnoea, and haemoptysis. Treatment is conservative unless substantial

bleeding occurs, in which case wedge resection may be needed. The pseudocysts

generally resolve in 1-4 months, larger cysts taking longer.

139 i. In published series, the causes of haemoptysis are neoplasm (12-24% of

cases), bronchiectasis (1-40%), bronchitis (7-40%), pneumonia (3-16%), TB

(3-6%), unknown (3-22%), and miscellaneous causes (11-26%).

ii. In a male of this age and smoking history, a carcinoma must be excluded.

Assuming that the chest X-ray is normal, he should proceed to a CT of the thorax

and a bronchoscopy. A chest X-ray may be abnormal in up to 40% of individuals

with this type of history. Most neoplasms seen at bronchoscopy will be noted on

CT scan, but CT scanning may identify up to 20% of tumours not visible on

bronchoscopy because they are peripheral.

140 i. The chest X-ray shows evidence of mid and upper zone fibrosis. The hila are

pulled up. The process may also result in lung cavities in the mid-zones.

ii. The most common cause of upper zone fibrosis is sarcoid. However,

pneumoconiosis, hypersensitivity pneumonitis, previous TB, histoplasmosis, and

seronegative arthropathies must be excluded. Sarcoidosis may be staged by the

radiographic appearances (Box).

iii. Any lung cavities may be complicated by the development of an aspergilloma.

Aspergillomas predispose to life-threatening haemorrhage. The incidence of lung

cancer is also increased in the context of pulmonary fibrosis.

Radiographic staging of sarcoidosis

Stage 0: Normal chest radiograph

Stage I: Hilar and mediastinal lymph node enlargement

Stage II: Lymphadenopathy and parenchymal disease

Stage III: Parenchymal disease only

Stage IV: Pulmonary fibrosis

138

141, 142: Questions

141

Ventilation

(l min^-1)

PaO2

Ventilatory capacity

Normal V_E

FEV₁ 1.5l

V_A

110

(mmol min^-1)

0.5

1.0

1.5

2.0

2.5 ( min^-1)

Oxygen uptake

141 i. How is the maximum exercise ventilation predicted in patients with chronic

airflow obstruction?

ii. Ventilation for a given oxygen uptake is often excessive in patients with airflow

obstruction. What factors contribute to an excessively high ventilation during

exercise in these patients and others with pulmonary disease?

142 A 69-year-old female who has been

142

treated with chemotherapy and

mediastinal radiotherapy for non-

Hodgkin’s lymphoma presents with a 4-

month history of dry cough and

dyspnoea. On examination, she is

apyrexial and has no respiratory signs.

She is known to have longstanding

pleural thickening of unknown origin.

142 is her chest X ray.

i. What new changes does the chest X-

ray show?

ii. What is the likely diagnosis, and how

can this be confirmed?

iii. What is the management and outlook?

139

141, 142: Answers

141 i. The maximum exercise ventilation is predicted as the FEV₁ x 35 in litres.

ii. The ventilatory response to exercise is linear until anaerobic metabolism

stimulates ventilation further by a decrease in the pH.

Minute ventilation is a combination of alveolar ventilation and dead space

ventilation. In patients with airflow obstruction, the contribution from the dead

space, both anatomical and physiological, increases. The worse the airflow

obstruction, the higher the minute ventilation has to be in order to maintain a

normal alveolar ventilation and rate of gas exchange.

Other factors that will increase minute ventilation are:

• Hypoxia: which will add to ventilatory drive, and ventilation will rise.

• Respiratory exchange ratio: if the patient makes an anaerobic contribution to

exercise, either due to an abnormal diet, e.g. high fat or low carbohydrate, or

because the anaerobic mechanisms ‘kick in’ early due to poor aerobic metabolism.

141 shows an idealized scheme where minute ventilation (V_E) comprises alveolar

ventilation (V_A), dead space ventilation (VD), and contributions due to hypoxia

(PaO₂) and an increase in respiratory exchange ratio (respiratory quotient, RQ).

The horizontal line shows the predicted maximum exercise ventilation for an FEV₁

of 1.5 l, and it can be seen that as the various factors cause the minute ventilation

to rise, the curves will move to the left, prematurely limiting exercise.

142 i. The chest X-ray shows dense bilateral shadowing adjacent to the

mediastinum with sparing of the rest of the lungs. The shadowing has a linear edge.

ii. These appearances are characteristic of post-radiotherapy fibrosis in patients

who have been treated with radiotherapy for mediastinal malignancy (e.g.

lymphomatous involvement of the mediastinal nodes). The radiological

abnormalities have a straight border parallel to the mediastinum with almost

complete sparing of the more distal lung. A CT scan will clarify the distribution of

the changes and will show ground-glass infiltration with nodules in the early phase,

evolving to fibrotic changes with traction bronchiectasis. Radiotherapy pneumonitis

usually develops within 3 months of the radiotherapy but can occur much later and

is also often exacerbated by subsequent cycles of chemotherapy (so called ‘recall’

pneumonitis). The patient may have characteristic areas of pigmentation and

telangiectasia of the skin overlying the affected area.

iii. Patients with radiotherapy-induced pneumonitis are treated with oral

corticosteoroids, which may decrease the risk and severity of significant permanent

fibrotic damage. However, patients are often left with residual dyspnoea and can

in severe cases die from progressive respiratory failure. Disease progress or

improvement is best monitored by lung function testing, which will show restrictive

lung function impairment with a reduced transfer factor.

140

143, 144: Questions

143 A 69-year-old male, previously a pipe-fitter, presents with a 4-month history

of exertional breathlessness and a dry cough. On examination, he has evidence of

digital clubbing and fine inspiratory crackles at both bases.

i. What is the diagnosis?

ii. What aspects in the history and what investigations would confirm your

diagnosis?

iii. What management options are available?

144a

144b

144 An elderly female complained of

shortness of breath on exertion but was

otherwise in good health.

i. What abnormalities are evident on the

chest radiograph (144a) and CT film

(144b), and what is the likely diagnosis?

ii. What further diagnostic tests are likely to be of value?

iii. What risks are associated with this condition?

iv. What management is advisable, and what specific risks should be mentioned to

the patient?

141

143, 144: Answers

143 i. The most likely diagnosis is asbestosis.

ii. In the history, previous exposure to asbestos should be confirmed. Connective

tissue disorders should also be excluded, and a detailed drug history should be

taken. Pulmonary function tests will show a restrictive defect and reduced transfer

factor. An HRCT would show reticulonodular infiltrates at the lung bases. The

presence of calcified pleural plaques on the diaphragmatic surface make the

diagnosis most likely to be asbestosis. Autoantibody tests will be negative. The

diagnosis of asbestosis is usually made clinically, in the absence of other causes of

fibrosis, and lung biopsy is not generally required.

iii. Corticosteroids and other immunosuppressants are ineffective, and no other

treatments are beneficial. Patients should be advised to stop smoking in view of the

markedly increased risk of lung cancer in this situation. Infections should be treated

promptly. Patients with a diagnosis of asbestosis should also be informed that they

may qualify for financial compensation.

144 i. There is an upper mediastinal mass that is exhibiting areas of calcification

(poorly seen on the radiograph). The trachea is markedly deviated. The features

are those of a retrosternal thyroid goitre.

ii. None. Radio-iodine scanning is frequently performed but is almost never of value

as the goitre will not take up the iodine. Bronchoscopy is non-contributory. Needle

biopsy might reveal a thyroid carcinoma, but this would be unlikely to exhibit

calcification, and a negative core would not exclude this diagnosis.

iii. Any airway obstruction can worsen with deteriorating exercise tolerance.

Haemorrhage can occur into the gland, causing acute enlargement and an airway

emergency. Malignant degeneration has very rarely been reported.

iv. Subtotal thyroidectomy is indicated to relieve airway compression. This is usually

possible through a collar incision. The chief hazards are damage to the recurrent

laryngeal nerves and transient postoperative hypocalcaemia from parathyroid

injury. Very occasionally, tracheomalacia may exist, which results in instability of

the tracheal wall postoperatively and difficulty with respiration.

142

145, 146: Questions

145 A 55-year-old, non-smoking female presented with a 6-week history of

progressive exertional dyspnoea associated with a dry cough. Nine months

previously, she had undergone haematopoietic stem cell transplant for chronic

lymphocytic leukaemia, receiving a graft from an unrelated donor. The post-

transplant period was complicated by graft-versus-host disease affecting her

oropharynx and skin. She was apyrexial. Chest radiographs and CT scans of the

lungs were unremarkable. Spirometry showed an FEV₁ of 1.0 l/min and an FVC of

2.0 l. Her transfer factor was normal when adjusted for lung volumes. Prior to the

stem cell transplant, her FEV₁ had been close to the expected values for her age

and height, at 2.3 l/min and 3.0 l, respectively.

i. What is the likely diagnosis?

ii. How should the patient be managed?

Predicted

Actual

PEFR (l/min)

590

490

FEV₁ (l)

4.41

3.10

FVC (l)

5.20

4.20

DL_CO (mmol/min/kPa)

12.01

11.50

K_CO (mmol/min/kPa/l)

1.72

1.69

146 The pulmonary function tests (Table) were obtained on a 23-year-old, 225 kg

male before a laparoscopic gastrojejunal bypass planned for obesity.

i. What is the pulmonary function test abnormality?

ii. Does the patient have an intrapulmonary cause for a restrictive pulmonary

disease (e.g. pulmonary fibrosis)?

iii. What pathophysiological processes contribute to the restrictive pattern seen?

iv. Will these tests improve with weight loss?

143

145, 146: Answers

145 i. The spirometry values show a marked obstructive defect that had occurred

since her allograft bone marrow transplant, a situation that is highly suggestive of

BO. BO is a progressive small airways obstructive disorder sometimes associated

with bronchiectasis that occurs in 5-10% of bone marrow allograft patients,

especially those with graft-versus-host disease affecting other parts of the body. It

is thought to be caused by graft-versus-host disease affecting the respiratory

epithelium.

ii. The diagnosis is usually clinical as definitive confirmation would require VATS

lung biopsy. CT scans of the lungs can be normal or show changes suggestive of

small airways disease, with a mosaic pattern, especially on expiratory films. CT

evidence of mild bronchiectasis is not uncommon. Active viral infections should be

excluded using a nasopharyngeal aspirate or BAL. Treatment is with increased

immunosuppression including inhaled steroids, as well as bronchodilators, although

the disease is often poorly reversible and can progress to respiratory failure and

death. A clinically identical disease is seen in up to 50% of lung transplant

recipients, and is a common cause of late death in patients who survive the initial

transplant period.

146 i. A restrictive pattern of disease.

ii. These tests are consistent with obesity, i.e. an extrathoracic cause. They would

also be compatible with other forms of chest wall disease, such as scoliosis,

muscular weakness, or paralysis of the diaphragm. Without further clinical

information, no other diagnosis, including that of pulmonary fibrosis, need be

sought. For obesity to cause a reduced TLC, the ratio between the weight (in kg)

and the height (in cm) must generally exceed 1.0. Reductions in FRC, VC, and RV

can occur with lesser degrees of obesity. The gas transfer (DL_CO) is normal, but it

can also be reduced in the presence of gross reduction of lung volume, although it

will correct to normal when alveolar volume is incorporated (K_CO). This implies

normal pulmonary gas exchange, and a low DL_CO is probably due to basal

hypoventilation as a direct consequence of the obesity.

iii. Obese individuals have increased chest wall mass, resulting in a reduction in net

outward elastic recoil pressure. The compliance of the lung and chest wall falls as

weight increases. The increased mass of the abdominal wall and abdominal contents

reduces the FRC. Accordingly, these patients develop airway closure in dependent

lung zones that becomes most pronounced when the patient lies supine. The

changes in PaO₂ observed when these patients lie supine can be great.

iv. Pulmonary function tests improve toward normal as weight is lost.

144

147, 148: Answers

147 i. The chest X-ray shows collapse and consolidation of the left upper lobe

characterized by loss of the cardiac outline and increasing opacification and density

towards the apex of the lung. There also is evidence of lymphangitis in the right

lower lobe, shown as septal lines reaching the periphery.

ii. The likely diagnosis is a lung cancer with the primary in the upper lobe and

metastatic spread to the nodes in the left hilum and subaortic fossa, where the left

recurrent nerve loops under the aortic arch and is destroyed in that region by

tumour. Bronchoscopy will confirm that the left vocal cord is paralysed and often

partially adducted, contributing to breathlessness by causing some obstruction to

airflow in the trachea. If the primary tumour is seen in the left upper lode orifice,

it can be biopsied. If not, a CT scan may show nodes accessible by EBUS-guided

transbronchial node biopsy.

iii. Approximately 3-5% of lung cancers can present with hoarseness, and this

signifies mediastinal involvement either by direct invasion of the recurrent laryngeal

nerve by the primary tumour, or, more commonly, by metastatic nodal involvement.

In both circumstances, the tumour will be inoperable, with mediastinal spread of

the cancer.

148 Nasal prongs are useful at flow rates of 2-3 l/min for mild hypoxaemia (SaO₂

88-90%). These allow the patient to eat or drink, and there is no carbon dioxide

rebreathing. Higher flow rates can be achieved, although this may cause discomfort

and dry the nasal mucosa. In addition, the inspiration of oxygen delivered is

variable and uncontrolled and therefore potentially harmful.

A Hudson or MC face mask. These can deliver oxygen at flow rates up to

15 l/min, corresponding to an approximate FiO₂ of 0.7. The amount of delivered

oxygen is dependent on the rate and depth of the patient’s respiration, and the mask

is not safe in patients with a reduced hypoxic drive who require controlled oxygen

therapy.

A Venturi mask. This enables controlled oxygen (24%, 28%, or 35%) to be

delivered at high flow rates. Entrainment of air occurs through the holes in the

coloured fittings at the neck of the mask to give the high total flow rate, which may

be needed in severely dyspnoeic patients. It is indicated for hypoxaemic patients

with a reduced hypoxic drive whose oxygen delivery must be constant to prevent

uncontrolled respiratory depression with subsequent hypercapnia. A range of

fittings is available, giving a range of inspired oxygen concentrations. Each fitting

requires a different oxygen flow rate from the wall oxygen outlet.

146

149, 150: Answers

149 Mediastinal involvement includes the following:

• Left recurrent laryngeal nerve palsy presents as hoarseness and poor cough. It

is due to metastases in the subaortic fossa.

• Superior vena caval obstruction is caused by tumour compression by the right

paratracheal lymph nodes.

• Dysphagia can be due to mediastinal lymphadenopathy of the subcarinal modes.

A barium swallow will identify the location of the obstruction (shown here).

• Arrhythmias, usually atrial fibrillation, can be caused by direct pericardial

invasion by tumour, particularly from the left lower lobe.

• Pericardial effusion - as above, this is due to direct invasion by tumour.

Tamponade can ensue with dyspnoea and appropriate physical signs.

• High hemidiaphragm can occur, which is due to phrenic nerve entrapment in

the mediastinum.

Horner’s syndrome results, usually, from a primary apical tumour extending onto

the posterior mediastinal surface and entrapping the sympathetic chain. It is

characterized by a small pupil with enophthalmos on the affected side. There is

partial ptosis due to paralysis of the sympathetically innervated portion of the

orbicularis oculis muscle (Müller’s muscle).There is also a unilateral absence of

sweating on the face and forehead.

150 i. Paranasal sinusitis. There is bilateral mucosal thickening and air-fluid levels

in the maxillary sinuses, worse on the left. Symptoms include headache, pain, and

tenderness over the affected sinuses, periorbital swelling in children, nasal

congestion and obstruction, purulent nasal secretions, postnasal drainage, cough,

sore throat, and purulent sputum. A CT scan of the paranasal sinuses is a very

sensitive and specific means of showing sinus disease.

ii. Predisposing factors include acute viral, bacterial, mycoplasmal, or other

respiratory tract infections, foreign bodies, nasogastric or nasotracheal tubes, nasal

packing, exposures to respiratory tract irritants, and barotrauma associated with

flying, swimming, and diving. More longstanding risk factors include allergic

rhinitis, nasal polyposis, immunoglobulin deficiencies, AIDS, anatomical disorders,

cystic fibrosis, or ciliary dyskinesia syndrome.

iii. Sinusitis is a frequent finding in patients with asthma and can lead to a

worsening of asthma. Sinusitis with nasal mucosal congestion and oedema results

in decreased humidification and temperature rectification of inhaled air. Sinusitis is

associated with postnasal drainage, which can carry bacteria and/or inflammatory

material to the lower respiratory tract. Asthma and sinusitis are also linked through

a common allergic response pathway or aspirin sensitivity.

148

151, 152: Answers

151 i. Fundoscopy shows blurring of the optic disc consistent with papilloedema.

ii. The most likely diagnosis is neurosarcoidosis.

iii. An MRI scan of the brain with gadolinium would show leptomeningeal

enhancement and periventricular high-signal lesions on T2-weighted images. A

lumbar puncture (after raised intracranial pressure has been excluded) would show

lymphocytes and a raised CSF protein level, often greater than 1 g/l. CSF ACE may

be raised, and oligoclonal bands should be absent. Serum ACE is also often raised

but is not sufficiently sensitive or specific to be useful for diagnosis, although it is

commonly used to monitor the disease response to treatment. A CT scan of the

chest is required to elucidate the bilateral hilar lymphadenopathy and identify

mediastinal nodes and any parenchymal disease. The pathological diagnosis of

sarcoid is made from non-caseating granulomas. The thoracic disease may be

diagnosed by bronchoscopy, transbronchial biopsies, endoscopic/endobronchial

ultrasound, or mediastinoscopy.

An important differential diagnosis is TB, which may also cause bilateral hilar

lymphadenopathy and lymphocytic meningitis. CSF findings include lymphocytes

and very high protein levels. Although the CSF is usually smear negative for acid-

fast bacilli, TB is commonly identified by PCR or culture. TB is characterized by

caseating granulomas that are obtained from mediastinal lymph node biopsy, or

by identifying or culturing the organism from sputum or lung lavage.

152 i. This is a PET scan using an intravenous tracer of 18-fluoro-deoxyglucose,

which is taken up by cells rapidly metabolizing glucose, such as tumours and

infections. The more aggressive the tumour, the higher the uptake (standardized

uptake value). The PET scan shows the primary tumour uptake and hilar plus right

paratracheal node uptake.

ii. This test should follow CT and diagnosis if a tumour appears resectable.

iii. It is extremely useful as it is much superior to CT at identifying hitherto occult

lesions. The resolution of PET is limited to lesions greater than 7 mm in size, but it

will identify metastatic disease in up to 30% of cases staged by CT scanning alone.

PET can give a false-positive result in up to 10% of cases, and apparently positive

lesions should be biopsied. False-negative PET is rare and does not need biopsy

confirmation. Slow-growing tumours, including alveolar cell carcinoma and

carcinoid tumours, can be falsely negative, however. False positives are seen with

distal infection, TB, sarcoid, fungal infections, and rheumatoid nodules.

iv. PET changes the staging of the cancer usually by downstaging it, i.e. assigning

it a worse stage, in up to 35% of subjects and will save a thoracotomy in up to

20% of individuals as assessed by CT and isotope scanning alone.

150

153-155: Questions

153a

153b

153 This 70-year-old patient has had haemoptysis with recurrent episodes of

pneumonia in the left lower lobe for 15 years. A mass (153a, 153b) was seen at

bronchoscopy to be partially occluding the left lower lobe and was removed by

laser resection. What is the likely diagnosis?

154

155

154 i. What does the CT scan (154)

155 The patient whose hands are shown

show?

in the radiograph (155) suffers from

ii. Why is this important?

difficulty swallowing, arthralgias, and a

iii. How would you make the diagnosis?

waxy appearance of the skin on her face

and distal extremities.

i. What disorder accounts for these

abnormalities?

ii. What are the two general types of

pulmonary disease associated with this

disorder?

151

153-155: Answers

153 Given the long history, the polypoid mass is likely to be a benign endobronchial

tumour. The majority of these are carcinoid tumours, although they may be locally

invasive, and metastases to the hilar lymph nodes may be seen at resection. These

tumours show neuroendocrine differentiation, but the carcinoid syndrome is rare

in bronchial carcinoids. Other benign bronchial tumours are of mesenchymal origin

and include lipomas, leiomyomas, and fibromas. This tumour was a mixed

fibrolipoma, and the laser resection line can be seen at the base of the polyp. Rigid

bronchoscopy and laser were used because significant haemorrhage may occur with

the removal of these tumours, particularly carcinoid tumours.

Endobronchial obstruction should be suspected in cases of recurrent pneumonia,

particularly when associated with haemoptysis. Inhaled foreign bodies may cause

the same syndrome. Foreign bodies may not be visible on chest radiographs. Other

non-malignant causes of endobronchial obstruction include amyloidosis and

tracheopathia osteoplastica, a cartilaginous proliferation in the major airways. The

latter may be a long-term sequel of amyloidosis. Both of these conditions may be

resected using laser if the obstruction is symptomatic.

154 i. The scan shows a left-sided adrenal metastasis with enlargement of the

adrenal gland, which is bulky and has lost its triangular shape.

ii. If an adrenal mass is found during the staging of a lung cancer, the concern is that

it is a metastasis. One series found that of 330 patients with apparently operable

tumours, 7.5% (25) had an adrenal mass, of which eight (2.4) were malignant, i.e.

only about 30% of the masses.

iii. Taking into account the information from (ii), either a biopsy should be

performed to confirm the nature of the mass, or a PET scan should be undertaken.

If the latter is negative, no further investigation if needed, but if it is positive, a

biopsy is needed, usually under CT control. Adrenal metastases are found in up to

40% of cases of lung cancer at autopsy.

155 i. Progressive systemic sclerosis (or scleroderma) is a connective tissue disease

in which progressive fibrosis and collagen replacement affects multiple organs,

including the skin, oesophagus, joints, and lung. The hand radiograph depicts acro-

osteolysis or erosion of the distal phalanges. Pulmonary symptoms include

dyspnoea and cough.

ii. The most common pulmonary manifestation of systemic sclerosis is fibrosing

alveolitis, the pattern of which is indistinguishable from idiopathic pulmonary

fibrosis (cryptogenic fibrosing alveolitis). A second, less common pulmonary

manifestation is pulmonary hypertension. The severity of the pulmonary

hypertension of progressive systemic sclerosis is not predicted by the degree of

restrictive interstitial disease.

152

156, 157: Answers

156 i. The chest radiograph shows hilar and paratracheal adenopathy, and diffusely

scattered, small, calcified parenchymal lung nodules. This appearance suggests a

remote and now ‘healed’ disseminated infection.

ii. The differential diagnosis includes previous infection

(e.g. varicella,

histoplasmosis) or, less likely, sarcoidosis. Miliary TB or disseminated

coccidioidomycosis is unlikely to have resolved spontaneously, and transbronchial

lung biopsies in the patient failed to demonstrate active peribronchial

granulomatous inflammation. Thus,

‘old’ histoplasmosis is the most likely

explanation for these radiographic abnormalities.

Histoplasmosis results from the inhalation of spores of the dimorphic soil fungus

Histoplasma capsulatum, which is endemic to the central river valleys of North

America. Acute infection is often asymptomatic but can occasionally result in a

pneumonia-like illness or even ARDS. Parenchymal infiltrates and hilar adenopathy

may be seen even in asymptomatic patients. Fibrosis and calcification often

accompany the resolution of these infections, and hepatosplenic calcification may

also be present. Most patients recover without medical intervention.

Some patients (generally those with underlying lung disease) fail to clear the initial

infection and develop chronic pulmonary histoplasmosis, which clinically and

radiologically resembles TB. Progressive disseminated histoplasmosis can be life-

threatening, especially in patients with defective cell-mediated immunity. This may

occur during progressive primary infection but more often results from reactivation in

previously infected patients. Both chronic and disseminated histoplasmosis should be

treated with amphotericin B, although oral itraconazole may be used in milder cases.

Immunocompromised patients require chronic suppressive itraconazole therapy.

157 i. The lymphatic channels next to the large vessel are infiltrated by tumour

cells. There is some vascular congestion. Both are typical of lymphangitis

carcinomatosa.

ii. Tumour enters the lungs via the pulmonary arteries and embeds in the vessel

wall, from where it penetrates into the adjacent lymphatics with subsequent

permeation throughout the lung. Some patients only have spread within the

vascular tree. A marked reduction in carbon monoxide gas transfer may be

demonstrated in these cases of vascular permeation.

iii. The most common tumour that gives rise to this condition is adenocarcinoma;

primary sites include breast, stomach, prostate, ovary, endometrium, pancreas, and

colon. When these tumours are known to be present, the diagnosis is relatively

simple. However, lymphangitis carcinomatosa may be the presenting symptoms of

these tumours so the cause of breathlessness may be confused with pulmonary

oedema or benign causes of interstitial lung disease until transbronchial or open

lung biopsy is performed.

154

158, 159: Questions

Observed

Predicted

Measurement

maximum

Heart rate (beats/min)

162

160

Ventilation (l/min)

VO₂max (l/min)

1.9

158 The data shown in the Table were obtained at maximal exercise testing in a 45-

year-old male with breathlessness on exertion.

i. What does VO₂max measure, and what parameters are needed to measure it?

ii. Would this patient be capable of performing a job involving packing shelves with

lightweight boxes?

159

159 i. What is the cause of this patient’s OSA?

ii. How would you treat this condition?

iii. How would you make the diagnosis?

iv. If the sleep apnoea is severe, what precaution would you take prior to and after

surgery?

155

158, 159: Answers

158 i. VO₂ measures the amount of oxygen extracted by the tissues during exercise

and is directly related to the amount of work performed. VO₂ = cardiac output (Q)

x oxygen content difference of arterial and mixed venous blood (CaO₂ - CvO₂), or

VO₂ = Q x (SaO₂- SvO₂) x 1.34.

SvO₂ (the saturation of mixed venous blood) reflects the ability of the exercising

muscles to extract oxygen from the blood. VO₂max is defined as the plateau of

oxygen uptake where attempting to go beyond that work capacity is associated

with increasing ventilation but no increase in cardiac output. This is the point at

which the subject has reached maximal aerobic power. Many subjects do not reach

this point as it requires considerable effort and determination with unpleasant

sensations of breathlessness and muscle soreness. Therefore what is often reported

is the maximum VO₂ achieved and not the true VO₂max. VO₂ can be obtained

from work performed on a cycle ergometer, treadmill, or even stepping exercise,

provided that measures of minute ventilation and mixed expired oxygen and carbon

dioxide tensions are available.

ii. To be able to perform heavy physical labour throughout an 8-hr shift, subjects

should achieve a VO₂max of

>25 ml/kg/min. Subjects whose VO₂max is

<15 ml/kg/min would be unable to walk at more than a normal pace. Therefore the

result here suggests he should be able to perform his relatively light tasks.

159 i. Acromegaly - there is typical frontal bossing with prominent supraorbital

ridges, prognathism, coarse skin, and thickened lips. Another endocrinological

cause of OSA is myxoedema.

ii. Transsphenoidal removal of the pituitary gland. Octreotide, which is a

somatostatin analogue, has also been reported to improve OSA in some patients

with acromegaly. Despite successful surgery, most acromegalic patients continue to

have significant sleep apnoea, which requires treatment with nasal CPAP.

iii. OSA is likely to be severe as the tongue is enlarged in this condition, and

oropharyngeal blockage during sleep likely to be severe. Therefore a simple

screening sleep test with an oximeter will record successive dips of SaO₂ throughout

sleep.

iv. The patient should be put on nasal CPAP before and immediately after surgery,

even if the surgery is potentially curative. This is because anaesthesia and opiates

can cause a further reduction in upper airway tone and a suppression of the arousal

response to obstruction. Once the patient has recovered from the surgery, a repeat

sleep study should check whether there is still significant OSA.

156

160, 161: Questions

Test

Range

Result

% Predicted

FEV₁ (l)

1.79-2.42

1.1

FVC (l)

2.42-3.26

1.25

FEV₁/FVC (%)

70-84

119

TLC (l)

4.4-5.96

3.5

RV (l)

1.62-2.19

1.8

DL_CO (mmol/

6.15-8.31

2.75

min/kPa)

Alveolar volume (l)

2.0

K_CO (mmol/

1.4-1.9

1.35

min/kPa/l)

160 A 28-year-old male is wheelchair bound and presents with morning headaches.

His lung function tests are shown in the Table.

i. What type of underlying condition does he have?

ii. Explain the lung function results.

iii. What other lung function tests may be useful?

161

150

100

}dV/dP

Pressure (cm H

2O)

161 The figure (161) shows three pressure-volume curves of the lung and also lung

compliance (dV/dP).

i. Which is the normal curve, and which are those of disease?

ii. Which types of disease do the abnormal curves (a, b, or c) depict and why?

157

160, 161: Answers

160 i. Neuromuscular disorder, e.g. myotonic dystrophy causing respiratory muscle

weakness. Morning headaches may be due to hypercapnia and suggest type II

respiratory failure.

ii. Lung function tests demonstrate a restrictive FEV₁/FVC ratio with a reduced

TLC. The DL_CO is significantly reduced at 38% predicted, but when corrected for

the alveolar volume the K_CO is preserved. This implies a chest wall or muscle

abnormality (rather than a parenchymal abnormality, in which the K_CO would also

be reduced). The RV may be normal or even increased in severe respiratory muscle

weakness.

iii. Other tests may be useful in establishing a diagnosis of respiratory muscle

weakness. The fall in VC between the upright and supine positions has been used

to assess diaphragmatic weakness and is a more sensitive indicator of respiratory

muscle weakness than upright measures of VC and TLC. Normally, there is less

than a 10% drop in VC when changing from the upright to the supine position.

With bilateral diaphragm paralysis or weakness, VC may be reduced by more than

30% in the supine position.

Maximal inspiratory and expiratory pressures are also abnormal in respiratory

muscle weakness. Generalized neuromuscular weakness reduces both maximum

inspiratory and maximum expiratory pressure, whereas isolated involvement of the

diaphragm, such as with idiopathic diaphragm paralysis or the early stages of

amyotrophic lateral sclerosis, may reduce only maximum inspiratory pressure. The

sniff test is another test of global respiratory muscle function.

161 i. The normal curve is curve B. The lung is most compliant at an FRC that is

approximately at 40% that of TLC in normal individuals. This is the most

compliant part of the pressure-volume curve, where breathing in occurs with least

effort for the greatest expansion.

ii. Curve A is from a patient with emphysema. The loss of elastic recoil caused by

the destructive emphysema means that the maximum recoil pressure of the lung (at

TLC) is reduced compared with normal. Therefore the lung remains more expanded

than normal at any given lung volume owing to its poor recoil presssures. In

addition, the lung is more compliant, so breathing in at FRC (at a greater lung

volume than normal) remains easy, but expiration will be more difficult due to the

ready collapsibility of the lungs.

Curve C is from a patient with interstitial lung disease. The lung is less compliant

and stiffer due to the increased intrinsic fibrosis. Owing to the loss of compliance,

inspiration, even at FRC, is harder than normal, increasing the work of breathing.

The total elastic recoil pressure at TLC is greater than normal. These stiff, inelastic

lungs suffer pneumotharaces more readily than normal lungs, and any such

pneumothorax is slow to heal because of the high elastic recoil pressures

encouraging the lung to collapse.

158

162, 163: Answers

Pulmonary manifestations of rheumatoid arthritis

Pleurisy

Usual interstitial pneumonitis

Pleural thickening

Non-specific interstitial

Pleural effusion

pneumonitis

• Exudate

Organizing pneumonia

• High cholesterol

Bronchiectasis

• Low glucose <1.5 mmol/l, low pH <7.2

• Low C3 and C4; positive rheumatoid

Mediastinal lymphadenopathy

factor

Cricoarytenoid arthritis

Rheumatoid nodules

Rheumatoid nodules of the

• Typically subpleural distribution

larynx

• May rupture into the pleural space,

causing pneumothorax and bronchopleural

fistula

162 i. The hands demonstrate the swelling of the metacarpophalangeal joints and

ulnar deviation characteristic of rheumatoid arthritis.

ii. The pulmonary manifestations are listed in the Box.

163 i. The patient has a typical vasculitic rash with small haemorrhagic lesions on

his forearms and shins.

ii. Vasculitis can affect the lungs as part of a systemic condition. The more common

conditions include:

• Wegener’s granulomatosis.

• Allergic granulomatosis and angiitis (Churg-Strauss syndrome). This comprises

asthma, hypereosinophilia with eosinophilic infiltrates, vasculitis, and

granulomas in various organs. It can be controlled by oral steroids, but the

vasculitis can be life-threatening. The condition usually begins with asthma at

about 35 years of age, and is of equal sex incidence; the vasculitis follows some

years later. Upper airway lesions, usually as allergic rhinitis, are common. The

ANCA test, predominantly perinuclear ANCA, is positive in 50% of patients.

• Polyarteritis nodosa, which affects medium-sized arteries, while Churg-Strauss

syndrome affects small ones. There is usually no history of allergic illness in

polyarteritis nodosa, and pulmonary involvement is not common. Pulmonary

involvement includes asthma, pulmonary infiltrates, fibrosis, and effusions.

The cytoplasmic ANCA test is negative.

160

164, 165: Answers

164 i. Obstructive apnoeas (164a) are characterized by a cessation of airflow with

continued evidence of respiratory effort on the chest and abdominal traces, often in a

paradoxical fashion. SaO₂ decreases during these episodes, periodically reaching a

nadir at the end of or just after the reinitiation of airflow.

ii. Central apnoeas (164c) result in a cessation of airflow with no evidence of

respiratory effort on the chest and abdominal traces. This event was terminated by an

EEG arousal.

iii. Mixed apnoeas (164b), a variant of OSA, consist of a central event followed by an

obstructive portion (respiratory effort begins before airflow does).

165 It is a method of grading the size of opacities on chest radiography due to

pneumoconiosis, primarily for epidemiological reporting. The number of opacities

correlates with the quantity of dust in the lungs. The opacities may be the dust itself

or the consequent fibrosis. There is a broad division between opacities of up to 1 cm

(simple pneumoconiosis), and those over 1 cm diameter (complicated pneumoconiosis,

or progressive massive fibrosis). Progressive massive fibrosis arises on a background

of simple pneumoconiosis.

Profusion gives an estimate of the density of the nodules, and is determined

by comparison with a set of standardized radiographs

(Table). Each

profusion category can be subdivided into three, to give a 12-point scale; p nodules

are mostly seen in coal-worker’s pneumoconiosis, whereas r nodules are associated

with silicosis.

Lung function changes with simple coal-worker’s pneumoconiosis are usually

minimal and often overshadowed by the effects of cigarette smoking, although coal

dust does contribute to the development of emphysema. Radiographic changes do not

progress after the miner leaves the coal face with simple pneumoconiosis, but they can

occur with progressive massive

fibrosis. With silica exposure,

simple changes may, however,

Simple

progress despite removal from the

Nodule size

Rounded

Irregular

Profusion

offending agent. Those developing

nodules

of nodules

progressive massive fibrosis have

<1.5 mm

0, 1, 2 or 3

usually been exposed to a high dust

1.5-3 mm

0, 1, 2 or 3

burden. Progressive hypoxaemia

3-10 mm

0, 1, 2 or 3

usually occurs. It is important to

exclude other causes of large

irregular opacities such as tumours

Complicated

and infection.

Nodule size