Examination Medicine: A Guide to Physician Training, 7th Edition

CHAPTER 6. The respiratory long case

I here present the reader with a new sign, which I have discovered for detecting diseases of the chest. This consists in percussion …

Leopold Auenbrugger (1760)

Bronchiectasis

Bronchiectasis is a reasonably common subject for a long case and usually poses a management problem. It is defined as pathological and permanent dilatation of the bronchi. There are associated destructive and inflammatory changes in the walls of the segmental and subsegmental bronchi. The diagnosis is not always straightforward because there are overlap syndromes, e.g. COPD, asthma and chronic bronchitis (Table 6.1).

Table 6.1

Features suggesting predominate bronchiectasis

image

The history

1. Find out when the patient’s respiratory problems began. Classically the cough and sputum begin in childhood, although adult onset is becoming more common. Ask about childhood whooping cough or measles. Lower respiratory tract infection with influenza and adenoviruses is an increasingly common cause of the disease. Potentially necrotising bacteria are also a cause if antibiotic treatment is inadequate – these include Staphylococcus aureus and Klebsiella organisms. The abnormal pulmonary defence mechanisms, or mucus clearance, associated with cystic fibrosis, tuberculosis, immunoglobulin deficiency, HIV infection and primary ciliary dyskinesia (immotile cilia syndrome) make these important causes of the condition. Localised bronchiectasis can occur in association with a space-occupying lesion, which can be endobronchial or external.

  Symptoms include:

a. recurrent haemoptysis

b. dyspnoea and wheeze

c. chronic sinusitis (70%)

d. recurrent pneumonia and pleurisy

e. systemic symptoms of weight loss, fever and anorexia

f. symptoms of right heart failure – a late event.

2. Ask about recent precipitating causes of admissions to hospital (e.g. infection, haemoptysis).

3. Enquire about treatment – physiotherapy, postural drainage, antibiotics (as prophylaxis or treatment), bronchodilators, lung resection.

4. Determine whether the patient had childhood immunisations (e.g. MMR).

5. Ask about investigations in the past (e.g. CT scanning, ciliary function studies, sweat test, bronchograms (memorable!)).

6. Establish aetiology, such as childhood or early adult infections (e.g. pneumonia, measles, whooping cough) (Table 6.2). The majority of cases have no obvious cause if those due to cystic fibrosis are excluded.

Table 6.2

Causes of bronchiectasis

image

Notes: Lung carcinoma rarely causes bronchiectasis as death tends to intervene first.

Aboriginal Australians who grew up in remote areas are at particular risk.

7. Ask how the disease interferes with the patient’s life (e.g. work). Infertility is usual in men with primary ciliary dyskinesia and is variable in affected women.

The examination

Examine the respiratory system carefully (see Table 16.10, p. 342).

1. Particularly note the unpleasant purulent sputum.

2. Examine carefully for clubbing, the yellow nail syndrome and localised crackles and wheezes.

3. Look for the position of the apex beat (don’t miss dextrocardia – Kartagener’s syndrome) and for the signs of right heart failure.

4. Consider the complications and look for them. These include:

a. pneumonia

b. pleurisy

c. empyema

d. lung abscess

e. cor pulmonale

f. cerebral abscess (very rare)

g. amyloid (rare, but an important topic in the examination).

Investigations

Investigations should include:

• chest X-ray film (see Fig 6.1a), which may be normal, or it may show 1–2 cm cystic lesions or, more often, streaky infiltration and thickened bronchial walls (tram tracking), especially in the lower lobes

image

image

FIGURE 6.1 (a) Right middle lobe bronchiectasis. Note the increased lung markings and the thickened bronchial walls (arrow).

(b) CT scan of the chest of a patient with bronchiectasis. Note the thickened bronchial walls (arrow). Figures reproduced courtesy of The Canberra Hospital.

• sputum microscopy and culture; the common organisms are Haemophilus influenzaePseudomonasEscherichia coli, pneumococcus, mycobacteria and Staphylococcus aureus

• immunoglobulin (IgG, IgM, IgA) levels (hypogammaglobulinaemia)

• tests for cystic fibrosis and immotile cilia syndrome in young adults

• blood film for eosinophilia, which may indicate allergic bronchopulmonary aspergillosis or asthma

• ventilatory function tests, which may show a restrictive defect or an obstructive pattern. It is therefore more useful in assessing severity than in making the diagnosis. A patient with bronchiectasis with a forced expiratory volume in 1 second (FEV1) of <40% predicted is said to have severe disease

• arterial blood gas estimations, which may show mild or moderate hypoxia and, later, respiratory failure – defined as an arterial oxygen tension (PaO2) <60 mmHg or an arterial carbon dioxide tension (PaCO2) >50 mmHg

• high-resolution CT scanning of the chest (see Fig 6.1b), which has replaced bronchography and is indicated in most patients to confirm the diagnosis. The typical findings are of airway dilatation (usually defined as a diameter greater than that of the accompanying branch of the pulmonary artery). Temporary dilatation can occur during acute infections so the scan should be performed when the patient is stable. Remember the radiation dose of an HRCT is about 8mSv and the test should be used sparingly, especially in children and young adults.

The extent of the disease is usually generalised. If the bronchiectasis is localised, resection may be indicated as long as the underlying cause is not systemic.

Treatment

The principles of treatment are as follows.

1. The facilitation (or maximisation) of clearance of sputum and the treatment of infection with antibiotics and of bronchoconstriction with bronchodilators.

2. Inhaled steroids may be of value if there is bronchial reactivity.

3. Twice-daily postural drainage (20 minutes morning and night) or newer physiotherapy techniques should be recommended (e.g. use of a flutter valve). Head-down drainage is now discouraged because of the risk of aspiration.

4. The use of antibiotics during exacerbations is routine, though of unproven benefit, and prednisone in tapered doses may be useful. The use of prophylactic nebulised antibiotics is a controversial treatment. Problem pathogens include Mycobacterium avium complex (MAC), Pseudomonas and Aspergillus. Patients with frequent infections may benefit from long-term antibiotic treatment with macrolides. Recombinant deoxyribonuclease is useful for cystic fibrosis patients but may be harmful for other patients with bronchiectasis.

5. Influenza and pneumococcal vaccines are advisable for all patients.

6. Treatment of heart failure should go pari passu with that of the lung disease.

7. Immunoglobulin deficiency can be treated with monthly IV injections of immunoglobulin, which decrease the incidence of infection and the need for hospitalisation.

8. Massive haemoptysis may occur as a result of bronchial wall erosion and the increased vascularity of the bronchial walls. It may respond to bronchial artery embolisation.

9. Smoking (including of marijuana) cessation is always essential.

10. Home oxygen is of unproven benefit but often prescribed (to non-smoking patients) with severe disease (FEV1 <40%). A screening test for eligibility is an oxygen saturation of 93% or less on room air.

11. Surgery should be considered for localised disease to prevent progression or as treatment of intractable haemorrhage.

12. Transplant is occasionally appropriate for end-stage disease.

Lung carcinoma

Lung carcinoma is a common disease that candidates often encounter in the examination. It can pose a diagnostic and management problem, and remains a leading cause of cancer death in men and women. At diagnosis only 20% of patients will have local disease and half will have disseminated disease. The overall 5-year survival rate is less than 15%. The major cell types are set out in Table 6.3. Over the last 20 years, adenocarcinoma has become more common than squamous cell carcinoma.

Table 6.3

Carcinoma of the lung – cell types

image

The history

1. Find out how the diagnosis was made or suspected – a proportion of patients are asymptomatic and were diagnosed after a routine chest X-ray or scan.

2. Ask about the duration of illness and respiratory symptoms (e.g. haemoptysis, dyspnoea, increasing cough, chest pain).

3. Enquire about a history of unresolved pneumonia, pleural eff usion or lung abscess.

4. Ask about systemic symptoms (e.g. weight loss, loss of appetite, lethargy).

5. Determine metastatic and non-metastatic symptoms (Table 6.4).

Table 6.4

Metastatic and non-metastatic manifestations of lung carcinoma

image

image

6. Ask about aetiology:

a. smoking and exposure to the cigarette smoke of others (a dose-response relationship – long-term smokers have a 10- to 30-fold risk; discontinuation of smoking reduces the risk over 10–15 years, but the relative risk does not return to 1.0); women have a higher risk for a given level of exposure to cigarette smoke than men (1.5:1); there is a familial association for first-degree relatives

b. occupational history (e.g. asbestos exposure, uranium miners); remember, the effect of asbestos plus smoking is synergistic, not additive

c. chronic scarring (e.g. tuberculosis, scleroderma, interstitial lung disease (ILD) may be associated with adenocarcinoma).

7. Ask about investigations performed, such as chest X-ray changes (the only abnormal finding in 5% of cases), CT scans, bronchoscopy, sputum cytology, needle biopsy and thoracotomy. The finding of a solitary nodule on a chest X-ray must be investigated but benign causes include a post-infection granuloma or a hamartoma.

8. Enquire about the patient’s work and home environments, including the number of dependants and the patient’s ability to work.

9. Ask about treatment off ered and begun.

10. Find out the patient’s understanding of the condition and the likely prognosis.

The examination

1. Finger clubbing is a most important sign (Table 16.11). This is very rare in small cell carcinoma.

2. Chest signs will vary – listen carefully for a fixed inspiratory wheeze over a large bronchus.

3. Recurrent laryngeal nerve palsy may have caused hoarseness, and phrenic nerve paralysis may have caused an elevation of a hemidiaphragm.

4. An apical tumour may be responsible for Pancoast’s syndrome (C8, T1 thoracic nerve destruction or compression, or Horner’s syndrome, or both).

5. Look for metastatic (e.g. supraclavicular lymphadenopathy and hepatomegaly) and non-metastatic manifestations, especially the neurological and endocrinological changes (Table 6.4).

Investigations

Screening of high-risk patients with chest X-ray or CT scanning may lead to an early diagnosis, but has not been shown to affect survival. The diagnosis may be difficult, even when suspected.

1. Sputum cytology may be helpful in centrally located lesions, but fibre-optic bronchoscopy is now more often done first.

2. The chest X-ray or CT may suggest the cell type: for example, peripheral nodule adenocarcinoma; central lesion with obstructive pneumonitis – squamous; mediastinal or hilar mass – small cell; or alveolar infiltrate – bronchoalveolar cell.

3. A suspect shadow on the chest X-ray film should be investigated by fibre-optic bronchoscopy and biopsy or fine-needle aspiration (see Fig 6.2a and b). Bronchial brushings and washings, taken at bronchoscopy, should also be sent for cytological examination but have a lower yield than biopsy.

image

image

FIGURE 6.2 (a) PA film. A round opacity is visible in the right middle lobe (arrow).

(b) Lateral film. A round opacity is visible in the right middle lobe (arrow). Figure reproduced courtesy of The Canberra Hospital.

4. For peripheral lesions, especially those less than 2 cm in size, transthoracic fine-needle biopsy with CT guidance is very useful, but complications (e.g. pneumothorax, significant bleeding) can occur.

5. In patients with a malignant pleural effusion, thoracocentesis and pleural biopsy provide a high diagnostic yield (Table 16.12).

6. Other investigations may include bone marrow biopsy, mediastinoscopy and thoracotomy. Video-assisted thoracoscopy has replaced open biopsy in many centres.

7. Other possible causes (e.g. of a coin lesion) must be excluded. For this purpose CT is helpful; demonstration of central or lamellar calcification usually indicates that a coin lesion is benign. Follow-up scans to confirm a lesion is unchanged are helpful. Positron emission tomography (PET) scans may be of value in these cases.

8. Once the diagnosis is made and the cell type identified, further investigations may be indicated to stage the disease.

• Symptoms and signs that suggest central nervous system, liver, bone, chest wall or mediastinal involvement need to be sought carefully.

• Full blood count (Table 6.5), serum calcium and liver function tests may suggest tumour spread.

Table 6.5

Full blood count and liver function tests from a female patient with carcinoma of the lung

PARAMETER

VALUE

NORMAL VALUE

Haemoglobin

84 g/L

115–165 g/L (female)

Mean corpuscular volume (MCV)

95 fL

80–100 fL

White cell count (WCC)

4.0 × 109/L

4.5–13.5 × 109/L

Platelets

95 × 109/L

150–400 × 109/L

Erythrocyte sedimentation rate (ESR)

70 mm/h

3–19 mm/h (female <50 years)

Bilirubin

84 mmol/L

<20 mmol/L (total)

Aspartate aminotransferase (AST)

57 U/L

<40 U/L

Alanine aminotransferase (ALT)

50 U/L

<35 U/L

Lactate dehydrogenase (LDH)

780 U/L

110–230 U/L

Protein

60 g/L

62–80 g/L (total)

Albumin

33 g/L

32–45 g/L

Blood film: normochromic red cells, poikilocytosis, tear drop cells. Some nucleated red cells (normoblasts) and myeloid cells (metamyelocytes and myelocytes). Some rouleaux formation. Comment: The combination of normochromic anaemia and the presence of marrow precursors in the peripheral blood is called a leucoerythroblastic reaction. It is typical of bone marrow infiltration by carcinoma or fibrosis. The abnormal liver function tests are non-specific, but suggest liver involvement in this setting. The elevated LDH level probably indicates liver damage, but can also occur when there is haemolysis.

• CT scanning of the chest and abdomen with contrast is an important aid in determining whether disease is localised.

• In small cell carcinoma, stage the disease into limited disease (lung primary, ipsilateral and contralateral hilar, mediastinal and supraclavicular nodes) or extensive disease −70% of patients (contralateral lung, distant metastases).

• Non-small cell carcinoma is staged according to the tumour node metastases (TNM) international staging system (Table 6.6). In general, disease confined to one hemi-thorax and the ipsilateral cervical nodes is called limited and further involvement is described as extensive disease.

Table 6.6

TNM international staging system for carcinoma of the lung (non-small cell)

image

T1–T4 = ascending degrees of increase in tumour size and involvement; N0 = no lymph nodes;

N1–4 = ascending degrees of nodal involvement; M0 = no metastases; M1–4 = ascending degrees of metastatic involvement.

9. Assessment for resectability should include respiratory function tests. If the forced expiratory volume (FEV1) is 1.5 L or more, this indicates that the patient could tolerate a pneumonectomy (a postoperative FEV1 of 1 L or more is usually considered the minimum that will be tolerated). Otherwise, a patient who can climb three flights of stairs is usually considered well enough to tolerate surgery.

Treatment

The average 5-year survival rate for all types of carcinoma of the lung is about 15%.

Small cell carcinomas

1. These are only occasionally resected as they have usually metastasised at the time of diagnosis. They are, however, sensitive to chemotherapy and radiotherapy.

2. In patients with limited disease, chemotherapy and concurrent radiotherapy improve the prognosis. Untreated, the median survival is only about 4 months. Treatment often includes platinum-based drugs – etoposide and cisplatin or carboplatin.

3. Prophylactic cranial irradiation may be given to patients with complete responses. There is a risk of leukaemia, central nervous system metastases, dementia and second primary malignancies with treatment.

Limited small cell carcinoma has a median survival with treatment of 11–18 months; 10–20% are disease-free at 2 years. Extensive small cell carcinoma has a median survival of 6–12 months with therapy.

Non-small cell carcinomas

1. These may be resectable – unless tumour has spread to the contralateral lung or outside the thorax or there is significant cardiopulmonary disease.

2. The most important prognostic factor is the stage of disease. Staging usually involves bronchoscopy and CT scanning of the chest, abdomen and brain, (PET scanning is useful but not covered by Medicare for this indication), as well as a physiological assessment of the patient’s fitness for surgery, from the point of view of both lung function and general health. One-third of patients have disease sufficiently localised for an attempt at resection.

3. Radiotherapy with ‘curative intent’ may be offered to patients if they refuse surgery or are unfit for surgery for other reasons. About 6% are alive after 5 years. Radiotherapy is not useful for patients who have had surgical resection of a peripheral tumour.

4. Adjuvant chemotherapy is not routine for surgical patients, but regimens including cisplatin may provide a small survival advantage (5% at 5 years). A common regime involves four cycles over 12–16 weeks. Median survival is only a few months in patients with intracranial metastases or bone involvement.

5. Chemotherapy and radiotherapy are used for stage IV disease. Although these patients will succumb to the disease, there is evidence that this can prolong life and improve symptoms. Treatment is often guided by tumour characteristics – pemetrexed-based chemotherapy is preferred for non-squamous tumours. Some tumours have mutations at the tyrosine kinase domain and the use of oral tyrosine kinase inhibitors (gefitnib and erlotib) has been associated with an initial improved response. Resistance usually develops after about a year of treatment.

6. Airway obstruction as a result of carcinoma may be relieved by using Nd-YAG laser or brachytherapy for palliation.

7. Combination chemotherapy is sometimes appropriate. Survival benefit is only 1 or 2 months.

For many of these patients the prognosis is poor. Sensitive questions about the patient’s expectations and plans for the future are important. Has there been adequate pain relief? How is the family coping? Does the patient plan to stay at home when things deteriorate? The examiners will expect a mature approach to the problem of an incurable disease and to the provision of palliative treatment.

Chronic obstructive pulmonary disease

This general term is usually applied to patients with chronic bronchitis and emphysema. Although these two conditions are different, they usually occur together. Chronic obstructive pulmonary disease (COPD) is common and presents major management problems. However, in the examination it is unusual for it to be the patient’s only medical problem. The vast majority of patients with COPD (more than 95%) are orhave been smokers. However, only about one-fifth of smokers experience a rapid enough decline in FEV1 ever to develop COPD.

The history

1. Find out about symptoms, such as cough and sputum, dyspnoea, wheeze, impaired exercise tolerance, ankle oedema and weight loss. Remember that the diagnosis of chronic bronchitis is made largely from the history.

2. Ask about precipitating causes of disease exacerbation, such as an upper respiratory tract infection, pneumonia, omission of drugs, symptoms of right ventricular failure, resumption of smoking, pneumothorax, sleep apnoea, oropharyngeal aspiration and gastro-oesophageal reflux disease.

3. Enquire about smoking habits. Ask about the number of cigarettes smoked per day and the length of use (10 packet years of smoking is usually a prerequisite), as well as exposure to other people’s cigarette smoke – passive smoking. Absence of a smoking history weighs heavily against the diagnosis unless chronic asthma or alpha1-antitrypsin deficiency is present, or exposure to dust or fumes. Find out at what age the patient began to smoke. Commencement in adolescence when lung development is incomplete may lead to a more rapid decline in lung function.

4. Ask about occupational history. This may be important, particularly as an additive feature if the patient has pneumoconiosis or has been exposed to toluene in plastics factories. Exposure to the fumes of solid fuel fires and to air pollution is also a risk factor.

5. Ask about medications, especially steroids, home oxygen and bronchodilators.

6. Enquire about management at home and work and the social effects of the disease. Find out in detail how limited the patient is physically and whether ADLs are managed. Ask about financial problems associated with chronic illness and symptoms of depression caused by chronic disability and loss of self-esteem.

7. Ask about family history, such as alpha1-antitrypsin deficiency causing emphysema (autosomal codominant inheritance; the most common variant associated with severe deficiency of alpha1-antitrypsin (<11 mmol/L) is the ZZ allele, responsible for 2% of cases of emphysema in smokers). The condition should be suspected when COPD develops early or after minimal smoking exposure.

The examination

Examine the respiratory system carefully (see Ch 16). The examination may be normal until airway obstruction is moderately severe. Look particularly for:

1. pursed-lip breathing (prolongs the expiratory time and may limit over-inflation) and use of accessory muscles

2. cyanosis and polycythaemia (note: clubbing does not occur unless another disease such as carcinoma has supervened)

3. intercostal recession

4. prolonged forced expiratory time (reduced in both obstructive and restrictive lung disease)

5. tracheal tug

6. reduced diaphragmatic movements, over-inflation, reduced chest wall movement and expansion, Hoover’s sign (paradoxical inward movement of the lower costal margin during inspiration)

7. reduced breath sounds with or without wheezes (rhonchi) and early coarse inspiratory crackles

8. sputum

9. signs of right heart failure

10. signs of cachexia in patients with advanced disease (this is probably related to the increase in tumour necrosis factor alpha associated with chronic hypoxia rather than to the increased work of breathing)

11. side-effects of treatment (e.g. tremor as a result of the use of beta-agonists, or the various changes caused by steroids).

Investigations

1. Chest X-ray film (see Fig 6.3) – look for signs of hyperinflation (flat diaphragms and a vertical heart shadow) and cor pulmonale and exclude pneumonia. Radiolucent bullae may be visible; they are very specific for emphysema. The X-ray may be normal if the patient has mild disease. High resolution CT of the chest is more often performed and is more specific for emphysema.

image

FIGURE 6.3 COPD. Note the overinflated lungs, flat hemi-diaphragms and prominent pulmonary arteries (arrows), a sign of pulmonary hypertension. Figure reproduced courtesy of The Canberra Hospital.

2. Ventilatory function tests – look for a considerable reduction of the FEV1/FVC (forced vital capacity) ratio (<0.70). A normal FEV1 excludes the condition. The amount of reversibility should be tested with bronchodilators. An increase in FEV1 or FVC of more than 15% and of at least 200 mL is considered significant. Complete, or almost complete, reversibility means that the diagnosis is asthma rather than COPD. Some asthmatics smoke and have both conditions; many smokers claim to have asthma but have only COPD. Vital capacity or total lung capacity may be falsely decreased if measured by gas dilution techniques because of the non-homogeneity of ventilation in COPD. The diffusing capacity for carbon monoxide is reduced in emphysema – a value of <50% is associated with exertion-induced hypoxia.

3. Arterial blood gas levels – look for respiratory failure at rest. The demonstration of significant hypoxia (usually a PaO2 of <55 mmHg, or <59 mmHg if the patient has cor pulmonale) is required for the prescription of home oxygen treatment. Ventilatory failure is defined as PaCO2 of >45 mmHg.

4. Haemoglobin value – look for polycythaemia.

5. Sputum culture – will usually grow Haemophilus influenzaeStreptococcus pneumoniae or Moraxella catarrhalis during exacerbations and remissions.

6. Electrocardiogram (ECG) – look for signs of right ventricular hypertrophy and multifocal atrial tachycardia, which can complicate chronic lung disease (see Figs 6.4 and 6.5).

image

FIGURE 6.4 COPD. There is atrial fibrillation with a moderately rapid ventricular response rate. There are prominent R waves in V1 and there is marked RAD (right-axis deviation) (+110°). The right precordial T wave inversion suggests right ventricular ‘strain’.

image

FIGURE 6.5 Multifocal atrial tachycardia L2 strip.

7. Alpha1-antitrypsin measurement – this is now generally recommended. It should particularly be considered if the patient has never smoked or has associated cirrhosis or basilar emphysema, or rarely subcutaneous nodules from panniculitis.

8. Assessment of nutrition – body mass index (BMI = weight in kg/height in cm2), grip strength, serum albumin, calcium and phosphate levels.

9. Exercise testing – to assess the need for ambulatory oxygen therapy and the degree of disability if there are discrepancies.

Differential diagnosis

1. Asthma

  Features suggesting asthma:

a. non-smoker

b. onset in childhood

c. family history of allergy

d. episodic attacks and also nocturnal symptoms

e. a rapid response to treatment, especially steroids

f. eosinophilia in the sputum

g. atopic diathesis

h. reversibility of obstruction.

2. Bronchiectasis

  Features suggesting bronchiectasis:

a. daily sputum production with or without haemoptysis

b. onset in childhood

c. recurrent chest infection

d. clubbing.

Treatment

1. The patient should stop smoking, as this decreases sputum production and bronchospasm and may reduce the rate of decline in lung function to that of a non-smoker (smoking cessation has been shown to prolong life). The candidate should have an approach to the treatment of nicotine addiction. This may involve the temporary use of nicotine substitutes, psychological counselling and encouragement, or the use of drugs such as bupropion.

2. Antibiotics can be used to shorten exacerbations (long-term chemoprophylaxis is indicated if there are four or more episodes a year), such as amoxycillin or doxycycline, given as a course at home at the first sign of purulent sputum. Remember that 25% of H. influenzae and 75% of M. catarrhalis infections are ampicillin-resistant.

3. Regular bronchodilators are of value:

• Beta2-agonists from metered-dose inhalers form the basis of treatment. A small change in FEV1 and FVC may produce considerable subjective improvement. Some patients find the inhaler devices difficult to use.

• Inhaled long-acting anticholinergic drugs, such as tiotropium bromide, provide symptomatic improvement and reduce exacerbations, but do not prolong life.

• Inhaled steroids in high doses (e.g. 400 μg beclomethasone) reduce the rate of episodes of exacerbation, but should be discontinued if after a trial of 4–8 weeks of treatment there is no clinical or spirometric improvement.

  Candidates should have a strategy to ensure effective use of the best device for a particular patient. Long-acting drugs, such as salmeterol, provide longer acting bronchodilatation and are at least more convenient. Oral theophylline derivatives may have an additive effect with beta2-agonists, perhaps because they improve respiratory muscle function. They are prescribed much less often now, partly because they cause oesophageal reflux, cardiac arrhythmias, nausea and insomnia, and partly because they are not very effective. Antitussives and mucolytics are controversial, but may be useful to prevent exacerbations.

  When patients do not improve, consider problems with adherence or technique.

4. Pursed lip breathing and postural changes may be of value. Maintain adequate hydration.

5. Steroid use may be effective in an acute exacerbation and as a way of excluding asthma if there is persisting doubt. A trial of high doses for 2 weeks may be beneficial when bronchodilators are insufficient. Maintenance steroid treatment should be given only if a short course has been shown objectively to be effective (i.e. improved respiratory function test results). Use the lowest dose possible. The associated weight gain, loss of muscle strength and osteoporosis may make things worse.

6. Annual influenza vaccine and 5-yearly pneumococcal vaccine are useful. Always know the immunisation status!

7. Pulmonary rehabilitation programs have been demonstrated in randomised controlled trials to improve symptoms and quality of life, but not to prolong life. Exercise and weight reduction increase patients’ wellbeing, but not their lung function.

8. Domiciliary oxygen is indicated for patients with a PaO2 of <55 mmHg or cor pulmonale and a PaO2 of <59 mmHg. There is evidence that mortality rates are decreased by the use of domiciliary low-flow oxygen given for 19 hours per day (especially during sleep). This may work by reducing the progression of pulmonary hypertension. Find out what type of oxygen supplementation the patient uses (e.g. concentrator, cylinders) and how this is managed with regard to convenience and cost.

9. Consider treatment of cor pulmonale. Heart failure is likely to improve with successful treatment of the lung disease. Spironolactone and diuretics may be useful.

10. Alpha1-antitrypsin deficiency can be treated by replenishing the missing antiprotease, which re-establishes antineutrophil elastase protection for the lower lung zones. An IV preparation can be administered weekly or monthly. This expensive treatment is indicated only if alpha1-antitrypsin levels are below 11 μmol/L. Only a small proportion of people with alpha1-antitrypsin deficiency develop COPD and the treatment is not recommended unless there is demonstrated disease.

11. Lung transplantation is an option for younger (<65 years) patients with end-stage disease and without serious co-morbidity who have not had previous thoracic surgery. The 1-year survival rate is more than 80% for this group.

12. Lung reduction surgery is an option for some severely symptomatic patients who have stopped smoking. Those with predominately upper lobe emphysema were thought more likely to benefit. Thorascopic removal of the worst lung segments did seem to give symptomatic improvement to many patients. However, the procedure has lost favour and is now rarely performed. This is partly because lung function continues to decline. Symptomatic benefit may be lost within a year and accelerated decline in lung function may occur. Pulmonary hypertension is a contraindication and air leaks from the stapled lung are the most important postoperative problem. This operation was combined with an intensive rehabilitation and exercise program, which may in itself account for some of the postoperative improvement.

13. The use of positive pressure ventilation (CPAP) is a possible option for long-term management.

14. The management of severe exacerbations is difficult, particularly when these are associated with severe carbon dioxide retention and a reduced level of consciousness. Steroids and theophylline are both used commonly for these patients. Evidence for their effectiveness is not strong. Non-invasive ventilation (BiPAP) via a mask may improve symptoms and avoid the need for intubation. Intensive care units usually require some evidence of a potentially reversible problem before allowing intubation and mechanical ventilation. The patient’s own wishes are important and should be obtained before he or she is too sick to make a decision.

Sleep apnoea

Sleep apnoea is an increasingly recognised clinical syndrome that should be suspected in patients who have obesity, hypertension, fatigue, excessive snoring or unexplained respiratory failure. Obstructive sleep apnoea is a common cause of sleep disturbance, but by no means the only explanation for it. Sleep apnoea patients commonly have some combination of these symptoms.

The history

1. Classically, in obstructive sleep apnoea, anyone else in the house will describe a history of loud snoring at night, associated with multiple periods of cessation of respiratory movement and waking and gasping for breath. Apnoeas of more than 10 seconds are considered significant, but for patients with this condition pauses of up to 2 or 3 minutes can occur and pauses of 30 seconds are common. Remember, though, that the majority of people who snore (40% of middle-aged men and 20% of middle-aged women) do not have sleep apnoea and brief apnoeas not associated with signs of arousal are normal for many people.

2. Ask the patient whether there have been problems with excessive daytime sleepiness and with working during the day.

3. Enquire whether the patient drinks alcohol and, if so, how much. Alcohol consumption is a common exacerbating factor.

4. Calculate the patient’s Epworth sleepiness score (Table 6.7).

Table 6.7

The Epworth sleepiness scale

image

5. Ask whether there is a history of hypertension and whether this has been treated (50% of these patients have hypertension). Find out whether the patient has had angina or arrhythmias at night; both of these may be precipitated by the hypoxia associated with apnoea. Heartburn and non-cardiac chest pain caused by gastro-oesophageal reflux are also common.

6. Enquire about medications, such as hypnotics, that may have been prescribed for poor sleeping, but actually aggravate sleep apnoea.

7. Ask about a previous diagnosis of COPD or symptoms of heart failure. The recurrent increase in afterload that occurs during apnoeic episodes can precipitate or exacerbate left ventricular failure. Fewer than 10% of patients develop right heart failure and significant pulmonary hypertension.

8. Ask about a history of tonsillar enlargement or throat surgery. In a few sleep apnoea patients there is a clear anatomical cause for the obstruction.

9. In the absence of excessive snoring, central sleep apnoea needs to be considered for a patient with the other symptoms.

10. Ask about symptoms suggestive of narcolepsy rather than sleep apnoea (Table 6.8). The sudden sleep attacks of narcolepsy can occur at any time, including during meals, conversation or driving. Patients may also report sudden loss of muscle tone from emotion (e.g. laughter). The result is an unexpected dropping of an object or a sudden buckling at the knees and falling down; cataplexy should be considered. Cataplexy is usually associated with narcolepsy, although it may precede narcolepsy by several years.

Table 6.8

Differential diagnosis of daytime sleepiness

image

11. Ask about symptoms of the restless legs syndrome (RLS), which may also lead to daytime sleepiness (remember, RLS is associated with iron deficiency).

12. The use of diuretics or insulin may predispose patients to inadequate sleep and should not be confused with sleep apnoea.

13. Ask whether the patient drives a motor car and whether the risks of driving have been discussed. Also ask whether it has been recommended that the anaesthetist be informed of the patient’s sleep apnoea before the administration of an anaesthetic.

14. Find out whether a CPAP mask has been prescribed and whether the patient finds it comfortable enough to use. Up to 50% of patients are unable to tolerate the device. If the treatment is tolerated, find out whether it has made a difference – many patients report a dramatic reduction in daytime sleepiness and improvement in wellbeing.

15. Find out how this chronic condition has affected the patient’s family and work.

The examination

1. Assess the BMI, but remember that up to 50% of patients with obstructive sleep apnoea and most patients with central sleep apnoea are not obese.

2. Respiratory examination is usually normal.

3. Measure the blood pressure and look in the fundi for signs of hypertension.

4. The cardiovascular system should be examined carefully for evidence of pulmonary hypertension.

5. Inspect the head, neck and mouth for signs of uvular enlargement and macroglossia or tonsillar hypertrophy – ‘pharyngeal crowding’. Look at and measure the neck circumference.

6. Perform a neurological examination to look for signs of autonomic neuropathy (e.g. diabetes mellitus, Shy-Drager syndrome), brain stem lesions or spinal cord disease (e.g. tumour, demyelination), which can cause central sleep apnoea.

7. Examine for neurological causes of obstructive sleep apnoea, such as myasthenia gravis or muscular dystrophy.

8. Look for signs of hypothyroidism or acromegaly.

Investigations

1. Consider sleep study monitoring (polysomnography) with the electroencephalogram, chin electromyogram, electro-ocular monitoring (to detect rapid eye movement (REM) sleep), oximetry, PaCO2monitoring and, if indicated, ECG monitoring (for arrhythmias).

2. For a definitive diagnosis, the apnoeic spells must be 10 seconds or longer in duration and at least five per hour must be recorded over several hours. The apnoea hypopnoea index (AHI) is the total number of episodes of apnoea or hypopnoea per night divided by the number of hours of sleep (mild 5–15; moderate 6–30; severe >30). A value of 5 or greater is considered abnormal, but is probably not diagnostic in the absence of symptoms.

3. For patients with typical features of the condition, home PaO2 monitoring overnight may be an option. A positive test (several significant desaturation episodes per hour) is enough evidence to justify treatment. A negative test, however, does not exclude the diagnosis.

4. Narcolepsy can also be diagnosed by a sleep study.

5. Hypothyroidism should be excluded with thyroid function tests if there is any clinical suspicion.

6. Check for proteinuria (uncommon, but may reach nephrotic levels in severe obesity).

7. Look at ECG for arrhythmias. Echocardiography may be indicated to enable estimation of pulmonary artery pressures and to assess right ventricular function.

Treatment

1. If the patient has hypothyroidism, thyroid hormone replacement may reverse sleep apnoea.

2. Concomitant diseases such as cardiac failure, hypertension and asthma need to be treated vigorously. Nasal decongestants may be helpful. Weight loss is of value, but may be difficult to achieve. Respiratory depressants, such as tranquillisers, should be withdrawn.

3. CPAP is of value for long-term treatment of irreversible obstructive sleep apnoea (Table 6.9). CPAP devices are not always well tolerated, but the devices are improving steadily in comfort and portability. Nasal CPAP is effective in the majority of patients who can adjust to it. If there is residual sleepiness despite regular use of CPAP, modafinil may be a useful adjunct.

Table 6.9

The effects of treatment for sleep apnoea from randomised clinical trials

image

4. Surgical correction of upper airways narrowing caused by polyps, enlarged tonsils or macroglossia can lead to significant improvement, but may not fully reverse the problem. Excision of soft tissue in the oropharynx is of value for well-selected patients.

5. If there has been a recent stroke, observation may be all that is required, since respiratory function may improve with time. Patients with central sleep apnoea can often be successfully treated with bilevel positive airways pressure (BiPAP) ventilation.

Interstitial lung disease, including idiopathic pulmonary fibrosis

Interstitial lung disease (ILD) may have a prolonged course, so patients are often available for the examinations. Discovering the aetiology may be difficult.

The history

The diagnosis may not be obvious until you examine the patient, at which stage you may have to ask further questions about the following:

1. presenting respiratory symptoms (e.g. dry cough, dyspnoea, lethargy, malaise)

2. whether the patient knows the cause of the respiratory symptoms

3. the onset and duration of symptoms (these are clues) – pulmonary fibrosis has a very slow onset and patients are not acutely ill; if there is the insidious onset of cough, fever, malaise and myalgias over weeks to months, think about cryptogenic organising pneumonia (COP), which has a better prognosis and responds to steroids

4. the patient’s gender and age (also clues) – for example, lymphangioleiomyomatosis (LAM) occurs essentially only in premenopausal women who often have a history of recurrent pneumothorax

5. systemic symptoms – for example, weight loss, fatigue, fever, rash and arthralgia, which may indicate a systemic disease, particularly a connective tissue disease (scleroderma, systemic lupus, Sjögren’s syndrome or rheumatoid arthritis) or sarcoidosis (Table 6.10)

Table 6.10

Fibrotic and granulomatous lung disease

image

6. pre-existing asthma – which may suggest Churg Strauss syndrome (ask about renal disease)

7. whether there is a history of haemoptysis and renal disease – which may indicate Goodpasture’s syndrome or SLE

8. drug use – cardiac (e.g. amiodarone, hydralazine, procainamide), rheumatological (e.g. methotrexate, d-penicillamine), chemotherapeutic (e.g. busulphan, bleomycin, cyclophosphamide) and others (e.g. nitrofurantoin, bromocriptine)

9. any history of radiotherapy

10. a detailed lifetime occupational history, such as exposure to mineral dust (silicosis, asbestosis, coal worker’s pneumoconiosis), chemical fumes (nitrogen dioxide, chlorine, ammonia) or organic dusts (Table 6.11)

Table 6.11

Asbestos and the lung

image

11. occupational history consistent with hypersensitivity pneumonitis (e.g. bird fancier’s lung, farmer’s lung from mouldy hay or grain dust in grain elevators); ask about recurrent Monday chest tightness (e.g. byssinosis from cotton, flax or hemp dust)

12. infections (e.g. aspiration pneumonia, miliary tuberculosis)

13. investigations (e.g. high-resolution CT of the thorax, lung biopsy or bronchial lavage)

14. treatment, if any

15. social problems as a result of the chronic disability.

The examination

1. Clubbing (consider idiopathic pulmonary fibrosis, but also asbestosis); cyanosis and lower lobe crackles (fine, late, inspiratory) make the diagnosis of idiopathic pulmonary fibrosis (IPF) likely.

2. If the signs suggest upper lobe pulmonary fibrosis, consider in your differential diagnosis silicosis, sarcoidosis, beryllium, cystic fibrosis, coal worker’s pneumoconiosis, eosinophilic granuloma, ankylosing spondylitis and tuberculosis. Lower lobe pulmonary fibrosis may be due to IPF, scleroderma, asbestosis, aspiration or drugs.

3. Look for signs of associated systemic disease, as well as sarcoidosis and connective tissue disease that would rule out IPF. For example, erythema nodosum and anterior uveitis would suggest looking for evidence of sarcoidosis.

4. Assess the severity of the disease (signs of pulmonary hypertension).

5. Look for signs of drug side-effects (especially steroids).

Investigations

The goals of investigations are to find the aetiology, establish the severity of the disease and look for signs of active inflammation. If active inflammation is present, the condition may respond to immunotherapy (steroids or cyclophosphamide). If established fibrosis is present, such treatment is unlikely to help.

1. Chest radiography is the initial investigation, but may be normal (see Fig 16.24).

2. High-resolution CT of the thorax is the investigation of choice (see Fig 6.6). It is the most sensitive non-invasive test. The changes of ILD are characteristic. Note whether there is a localised or diffuse abnormality or progressive massive fibrosis (caused by silicosis and coal worker’s pneumoconiosis).

image

FIGURE 6.6 CT scan of the thorax. There are increased lung markings posteriorly, more prominent on the right than on the left (arrows). Figure reproduced courtesy of The Canberra Hospital.

3. Pulmonary function tests usually reveal a restrictive pattern, with reduction of lung volumes and reduced transfer factor. An obstructive pattern may be seen in sarcoidosis, histiocytosis X (typically found in men who smoke and have a history of pneumothorax) and LAM.

4. Blood gas levels will show hypoxia with a normal or low PaCO2.

5. The erythrocyte sedimentation rate is often raised.

6. There may be hypergammaglobulinaemia and a raised lactate dehydrogenase (LDH) level. Eosinophilia may be a useful clue (Table 6.12). Serological testing for connective tissue diseases is routine.

Table 6.12

Causes of pulmonary infiltrate and eosinophilia (PIE)

Prolonged pulmonary eosinophilia. This may be caused by: drugs (e.g. sulfonamides, sulfasalazine, salicylates, nitrofurantoin, penicillin, isoniazid, methotrexate, carbamazepine, imipramine, L-tryptophan); parasites (e.g. Ascaris); idiopathic

Loeffler’s syndrome (benign and acute)

Allergic bronchopulmonary aspergillosis (always associated with asthma)

Tropical (e.g. microfilaria)

Eosinophilic pneumonia and vasculitis (e.g. polyarteritis nodosa, Wegener’s granulomatosis)

7. A positive gallium-67 lung scan may indicate disease activity. Lung clearance studies using pertechnate may also be helpful (rapid clearance suggests active alveolitis).

8. Bronchoalveolar lavage can be performed and is most helpful if there is haemophtysis or an acute disease onset. It is suggested that fibrosis on a transbronchial biopsy associated with a lavage showing a predominance of polymorphonuclear cells is less responsive to treatment. Lymphocytosis on lavage suggests drug-induced or granulomatous disease.

9. Diagnoses likely to be made by transbronchial lung biopsy include sarcoidosis and lymphangitic spread of carcinoma; infection can be ruled out. Other specific diagnoses are not usually apparent.

10. Open lung biopsy or video-assisted thoracoscopic biopsy may be required to confirm the presence of idiopathic ILD, but only if there is clinical uncertainty and the test result could change treatment.

Treatment

This depends on the cause (Table 6.13).

Table 6.13

Classification of interstitial lung disease (ILD)

image

SLE = systemic lupus erythematosus.

1. Remove exposure, if appropriate.

2. Treatment will not reverse established fibrosis.

3. Steroids may help in COP, chemical injuries, hypersensitivity pneumonias (acute disease only), sarcoidosis (severe disease), histiocytosis X (controversial) and connective tissue disease. However, there is no evidence that steroids improve survival in these conditions and they are of no value in dust diseases.

4. Treatment with prednisolone is usually begun at 1 mg/kg/day and reduced to half this dose after 4–12 weeks. Follow-up with measurement of spirometry, lung volumes and transfer factor is important to document response to treatment. Consider maintenance steroids in lower dose for patients who are improving or stabilised.

5. Immunosuppressive agents, and especially azathioprine, may sometimes be of benefit and can be used in combination with low-dose steroids. Cyclophosphamide is now controversial. Antifibrotic agents are under trial – pirfenidone reduces lung decline. Colchicine in doses of 0.6 mg daily inhibits macrophage production of fibroblast growth factors, but its efficacy is controversial.

6. N-acetylcysteine in combination with immunosuppression reduces deterioration of lung function. Treat any associated gastro-oesophageal reflux as it may aggrevate disease.

7. General measures, such as administration of pneumococcal and influenza vaccines, may be indicated.

8. Home oxygen therapy may provide symptomatic relief for hypoxaemic patients.

9. Unilateral lung transplantation may be considered for some patients in the final stage of their disease.

Pulmonary hypertension

Many patients with this chronic and often severe illness will have raised pulmonary artery pressures as a result of a cardiac or respiratory illness. The patient may or may not be aware of this complication of the underlying disease, but it is essential for the candidate to know when to look for it. Idiopathic pulmonary hypertension (IPH) is a rare but important condition, which is diagnosed when other causes of pulmonary hypertension have been excluded. By definition, pulmonary hypertension is present when the mean pulmonary artery pressure (PAP) exceeds 25 mmHg at rest or 30 mmHg during exercise.

The classification of pulmonary hypertension was revised in 2008. The Venice classification is now called the Dana Point classification. The term ‘primary pulmonary hypertension’ has been replaced with ‘idiopathic pulmonary hypertension’ (see Table 6.14).

Table 6.14

The Dana Point classification for pulmonary hypertension (2008)

image

ALK1 = activin receptor-like kinase type 1

BMPR = bone morphogenetic protein receptor type 2

HIV = human immunodeficiency virus

Adapted from G Simonneau, IM Robbins, M Beghetti, RN Channick et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009;54: S43–54.

The history

1. Symptoms are usually non-specific but often severe. As usual, begin by asking whether the patient knows what is wrong and the reason for the admission, or visit, to hospital.

2. If pulmonary hypertension seems a possibility, ask about the possible causes (Table 6.14). Remember to ask specifically about appetite-suppressing drugs. The use of fenfluramine and phenermine in combination and for long periods has been associated with the greatest risk.

3. If the patient has an illness that could be a cause, ask detailed questions about that condition, its severity and chronicity. There may be a family history in cases of IPH (6%; autosomal dominant condition with incomplete penetrance, 20–80%). The majority of familial cases are associated with a mutation on the BMPR2 gene.

4. Find out how symptomatic the patient is now. Idiopathic and secondary pulmonary hypertension cause dyspnoea. Almost all patients have dyspnoea at the time of diagnosis. Other less common symptoms include fatigue, chest pain, syncope and oedema. Cough and haemoptysis can be present. Ask about symptoms of connective tissue diseases and especially about scleroderma. Try to work out the patient’s functional class (NYHA I–IV, often called the NYHA-WHO class when related to pulmonary hypertension).

5. Ask about previous or planned investigations. These may relate to the underlying condition; for example, respiratory function tests or scans, echocardiography (often transoesophageal echocardiography) or cardiac catheterisation. A patient who presents with symptoms and signs of pulmonary hypertension needs a number of investigations before IPH can be diagnosed.

6. What general treatment has been recommended? This may be for the underlying cardiac or respiratory condition or for thrombosis. There may be a history of cardiac surgery in childhood for congenital heart disease. Oxygen supplementation is often prescribed. Find out how this is administered (e.g. via nasal prongs or a mask), for how many hours a day and whether it comes from a concentrator or oxygen tanks. Oxygen is very expensive unless subsidised. Ask about the cost and inconvenience of the treatment with regard to portability and noise (oxygen concentrators are noisy and use a lot of electricity). Has the treatment been helpful?

7. What drugs is the patient taking? Heparin and then warfarin are routine for pulmonary embolism, but warfarin is also used for many patients with IPH because of the risk of in situ thrombosis in the pulmonary arteries. Bronchodilators and steroids may have been prescribed for lung disease. The possibility of a heart or lung transplant, or both, may have been raised with the patient. The patient may be on a therapeutic trial or taking an agent, such as bosentan, sildenafil or the inhaled prostacyclin analogue iloprost. Patients involved in trials or taking new drugs are often very well informed about what is going on.

8. As with any chronic and possibly debilitating condition, questions about the patient’s ability to work and manage the activities of daily living need to be detailed and comprehensive.

The examination

1. Try to assess the severity of the patient’s dyspnoea as he or she undresses or by asking the patient to walk around the room.

2. Perform a thorough respiratory and cardiac examination (see Table 16.1, p. 311 and Table 16.10, p. 342). Look particularly for an elevated JVP with a large v wave. Feel for a parasternal impulse (right ventricular heave). Feel for a palpable P2 (and listen for tricuspid regurgitation).

3. Look for signs of chronic lung disease, congenital heart disease and connective tissue disease. Examine for signs of a deep venous thrombosis (DVT).

Investigations

Investigations are directed at finding an underlying reason for pulmonary hypertension – IPH is a diagnosis of exclusion – and at assessing its severity and potential reversibility. These investigations include those detailed below.

1. Chest X-ray – this will be abnormal in 90% of IPH patients. It may show ILD or an abnormal cardiac silhouette – right ventricular dilatation. There may be large proximal pulmonary arteries that appear ‘pruned’ in the periphery, and the right ventricle may appear enlarged on the lateral film (see Fig 6.7a and b).

image

FIGURE 6.7 (a) and (b) Severe pulmonary hypertension. There is pruning of the pulmonary arteries and right ventricular dilatation.

2. Respiratory function tests (normal, restrictive or obstructive pattern) – moderate pulmonary hypertension itself is associated with a reduction in the diffusion capacity for carbon monoxide (DLCO) to about 50% of predicted.

3. ECG – signs of right heart strain or hypertrophy are present in up to 90% of patients (see Fig 6.8).

image

FIGURE 6.8 ECG of a patient with idiopathic pulmonary hypertension. Note RAA (right atrial abnormality), ‘P’ pulmonale, right axis, right ventricular hypertrophy and strain pattern, and sinus tachycardia.

4. Blood gases – hypercapnia in hypoventilation syndromes, but hypocapnia is more common in IPH because of increased alveolar ventilation. Mild hypoxia in IPH, but more severe when pulmonary hypertension is secondary to lung disease.

5. CT pulmonary angiogram or ventilation–perfusion (V/Q) scan and Doppler venograms – DVT and pulmonary embolism – assessment of extent of involvement of the pulmonary bed.

6. High-resolution CT of the lungs – looking for interstitial lung disease.

7. Six-minute walking test – predicts survival and correlates with NYHA-WHO class. Reduction in arterial oxygen concentration of >10% during this test predicts almost threefold mortality risk over 29 months. Patients unable to manage 332 metres in 6 minutes also have an adverse prognosis.

8. Transthoracic or transoesophageal echocardiogram (see Fig 6.9) – a trans-thoracic echocardiogram will usually enable left ventricular failure or severe mitral valve disease to be excluded. One or both will enable the assessment of known congenital heart disease, the detection of a left to right (or reversed) shunting (Eisenmenger’s syndrome) and measurement, in many cases, of pulmonary artery pressures. The presence of tricuspid regurgitation (common in normal people and almost universal in the presence of raised right ventricular pressures) enables estimation of right ventricular, and therefore pulmonary artery, pressures in many patients. The pressure difference across the tricuspid valve can be calculated if the velocity of the regurgitant jet is measured by Doppler. Right atrial pressures are usually close to 5 mmHg; the right ventricular pressure can be estimated by adding 5 to the pressure difference across the tricuspid valve. The normal right ventricular and pulmonary artery systolic pressure is 20–25 mmHg. Assessment of pulmonary artery ejection characteristics can also be used to estimate pulmonary artery pressures. Right ventricular size and function can be assessed. Right ventricular dilatation and abnormal septal motion are useful signs of pulmonary hypertension. The right ventricle appears abnormal on echocardiograms in more than 90% of people with pulmonary hypertension.

image

FIGURE 6.9 Echocardiography report in a patient with pulmonary hypertension.

9. Catheterisation of the right heart – this investigation is the gold standard and should also be performed if other tests have not been definitive. It is usually performed with a multiple-lumen flotation catheter and enables direct measurement of the right heart pressures. Left to right shunting can be detected by the collection of blood samples from the venae cavae, right atrium, right ventricle and pulmonary artery. A ‘step-up’ in the blood oxygen saturation indicates a shunt. The size of the shunt can be calculated if the cardiac output is measured by thermo dilution. Measurement of the pulmonary artery wedge pressure enables the detection of mitral stenosis or the very rare pulmonary veno-occlusive disease. By definition, IPH means the pulmonary capillary wedge pressure is <18 mmHg (i.e. the raised pulmonary pressures are not secondary to left ventricular failure). Pulmonary vascular resistance can be calculated using the cardiac output, pulmonary artery pressure and pulmonary artery wedge pressure measurements. The formula is:

image

This gives a result in mmHg/L/min or Wood units. The normal is 1.7 mmHg/L/ min.

Treatment

1. Treatment of pulmonary hypertension that is secondary to an underlying respiratory or cardiac condition begins with an attempt to optimise treatment or fix the underlying condition.

a. COPD: bronchodilators, steroids, continuous oxygen.

b. ILD: oxygen. Aggressive treatment of an underlying connective tissue disease may halt or slow progression of the pulmonary pressures.

c. Pulmonary embolus: anticoagulation, vena caval filter and occasionally pulmonary embolectomy.

d. Mitral stenosis: valvotomy or replacement.

e. Mitral regurgitation: repair or replacement if left ventricular function remains reasonable.

f. Atrial septal defect: surgery or, if suitable, closure in the catheter laboratory (e.g. with an Amplatzer closure device). There must be evidence of reversibility of the pulmonary pressure if it is close to systemic.

g. Eisenmenger’s syndrome: repair of the defect responsible for the shunt is not usually possible once reversal of shunting has occurred. Consider heart and lung transplant if conservative treatment (diuretics, digoxin and sometimes ACE inhibitors) has failed.

2. General measures include continuous oxygen, diuretics, digoxin and spironolactone for problems with right heart failure. Use of the newer endothelin receptor antagonists (bosentan), prostoglandins (iloprost) or phosphodiesterase inhibitors (sildenafil) is generally indicated for IPH and pulmonary hypertension secondary to connective tissue disease and pulmonary embolism. Bosantan has also been approved for use in Eisenmenger’s syndrome.

IDIOPATHIC (PRIMARY) PULMONARY HYPERTENSION

Treatment of this progressive and debilitating condition involves the general measures outlined above. Untreated patients have a poor survival rate: 2 to 3 years median survival from the time of diagnosis.

1. If a vaso reactivity test is positive (response on right heart catheterisation to a short acting vasodilator), a trial of a calcium channel blocker prior to trying the newer agents in generally recommended.

2. Bosentan has been approved for use for patients with IPH. This drug is an endothelin receptor antagonist. Endothelin-1 is a potent vasoconstrictor whose levels have been shown to be elevated in patients with IPH. Modest improvements in functional capacity and pulmonary artery pressures have been demonstrated after treatment of patients with IPH and those with underlying connective tissue disease. The drug is only available for patients with class III symptoms and a right atrial pressure of >8 mmHg. Its side-effects include teratogenicity, an increase in liver enzyme levels and possibly male infertility. Prostacyclin analogues, such as iloprost, which are taken by inhalation, can also be effective. Continuous IV epoprostenol has been shown to improve symptoms and prognosis in a number of small randomised trials for IPH patients at least. Sildenafil (a phosphodiesterase inhibitor) is a vasodilator that must not be used in combination with nitrates because of the risk of severe and prolonged hypotension.

3. Warfarin is usually recommended because of the demonstrated risk of the formation of in situ thrombus in the pulmonary arteries.

4. Suitable patients (severe unresponsive disease, right heart failure, young patient) should be considered for transplant. Successful outcomes have been shown with heart–lung, double lung or single lung transplants. IPH has not been found to recur in the transplanted lung. The prognosis depends on the NYHA-WHO functional class: class I–II, 6 years; class III, 2.5 years; class IV, 6 months.

Sarcoidosis

This chronic, systemic, granulomatous disease is relatively common and patients occasionally require admission to hospital for investigation or treatment. It is an unusual lung disease in that it is less common in smokers. Although most patients present between the ages of 20 and 40 years, children and elderly people are sometimes affected. There are cases of familial sarcoidosis. At presentation 90% of patients have pulmonary involvement and 40% have other organs affected. The disorder results from an exaggerated T-helper lymphocyte response that occurs for unknown reasons and is responsible for granuloma formation and fibrosis.

The history

1. Ask whether the patient has been admitted to hospital and if so, why. The patient may already know the diagnosis and be an outpatient undergoing further investigations or treatment, or the diagnosis may be suspected because of lymphadenopathy or changes on chest X-ray (see Fig 6.10). Most patients present with asymptomatic hilar adenopathy (see Table 6.15).

Table 6.15

Clinical presentation of sarcoidosis

image

image

FIGURE 6.10 Massive bilateral hilar lymphadenopathy (arrows). Figure reproduced courtesy of The Canberra Hospital.

2. Ask about acute or subacute symptoms, as sarcoidosis develops in this way in about one-third of cases. The patient may have fever, weight loss, loss of appetite and malaise. The occurrence of erythema nodosum, joint symptoms and bilateral hilar adenopathy on the chest X-ray suggests an acute presentation. A combination of fever, facial nerve palsy, parotid enlargement and anterior uveitis may occur.

3. Symptoms suggesting a more insidious onset include persistent cough and dyspnoea. If the patient has chronic sarcoidosis, it is still important to find out how he or she originally presented, as the insidious onset is more often associated with chronic sarcoidosis and the development of damage to the lungs (up to 15% develop progressive pulmonary fibrosis – ILD) and other organs.

4. Ask about skin eruptions (e.g. erythema nodosum, plaques, maculopapular lesions and subcutaneous nodules). Erythema nodosum, fever and migratory polyarthralgias, when found in combination with hilar lymphadenopathy, may indicate Lofgren’s syndrome.

5. Eye symptoms occur in about one-quarter of patients. The patient may have noticed blurred vision, excess tears and light sensitivity as a result of uveitis. Involvement of the lacrimal glands can cause the sicca syndrome, resulting in dry, sore eyes.

6. Ask about nasal stuffiness, as the nasal mucosa is involved in about one-fifth of patients. Occasionally, a hoarse voice or even stridor may result from sarcoid involving the larynx.

7. Renal involvement is uncommon but occasionally nephrolithiasis can result because of hypercalcaemia.

8. Ask about neurological symptoms – facial nerve palsy is the most common manifestation, but psychiatric disturbances and fits may occur.

9. Almost half the patients at some time in the course of the disease have arthralgia; even frank arthritis can occur.

10. The patient may be aware of cardiac abnormalities. Conduction problems, including complete heart block and ventricular arrhythmias, occur in about 5% of patients. Cardioverter defibrillators are occasionally required.

11. If the patient is female, ask about pregnancies. Sarcoidosis tends to abate in pregnancy but then flare up in the postpartum period.

12. Enquire about gastrointestinal symptoms (e.g. dysphagia from hilar adenopathy), although these are very rare. Liver involvement is common but rarely causes symptoms. The patient may know about abnormal liver function tests (usually a cholestatic picture).

13. Ask how the diagnosis was made. The CT scan has a characteristic appearance and may have been the only investigation performed, although in most cases the diagnosis is confirmed by biopsy. Specifically determine whether a lymph node biopsy or lung biopsy has been performed. Sometimes a skin or conjunctival biopsy may have been obtained to make the diagnosis. Bronchial or transbronchial lung biopsies are used to make the diagnosis in most cases. Occasionally, mediastinoscopy with lymph node biopsy is needed to make the diagnosis. Cardiac MRI can be used to look for myocardial involvement.

14. Ask about treatment. Find out whether the patient has been receiving steroids and what dose is currently being taken. Various other treatments may have been tried, including NSAIDs, cyclosporin and cyclophosphamide.

The examination

1. Begin with an examination of the skin.

a. You might be lucky enough to find erythema nodosum. These raised red or purple lesions are most commonly found on the lower limbs. They resolve spontaneously after 3 or 4 weeks.

b. Look at the face, back and extremities for maculopapular eruptions. These are elevated spots less than 1 cm in diameter that have a waxy, flat top. There may also be lupus pernio on the face (see Fig 6.11). These are purple swollen nodules with a shiny surface, which particularly affect the nose, cheeks, eyelids and ears. They may make the nose appear bulbous; occasionally the mucosa of the nose may be involved and the underlying bone can be destroyed. Lupus pernio sometimes also involves the fingers and knees. Pink nodules may be found in old scars.

image

FIGURE 6.11 Lupus pernio. The nose shows typical scaly violaceous swelling. F Ferri, Sarcoidosi–lupus perni. Ferri’s color atlas and text of clinical medicine. Fig 11.4. Elsevier, 2009, with permission.

2. Examine the eyes for signs of uveitis. Yellow conjunctival nodules may be present. Examine the fundi for papilloedema. Feel the parotids. Uveoparotid fever presents with uveitis, parotid swelling and seventh cranial nerve palsy.

3. Next examine the respiratory system. Most commonly, physical examination of the chest reveals no abnormality. Look particularly for signs of interstitial lung disease; basal end-inspiratory crackles may be present. Pleural effusions occur rarely.

4. Next examine all the lymph nodes. Lymphadenopathy is sometimes generalised.

5. Now examine the abdomen for hepatomegaly (20%) and splenomegaly (up to 40%).

6. Examine the joints for signs of arthritis, which is almost always non-deforming.

7. Examine the nervous system. Look particularly for facial nerve palsy.

8. Feel the pulse (heart block or arrhythmia) and look for signs of right ventricular failure or cardiomyopathy. Note the presence of a pacemaker or defibrillator box.

Investigations

1. A full blood count may reveal lymphocytopenia and sometimes eosinophilia.

2. The ESR is often raised. There may be hyperglobulinaemia.

3. The ACE level is raised in about two-thirds of patients with active sarcoidosis but unfortunately is not diagnostic; ACE is also sometimes elevated (5%) in healthy persons or those with primary biliary cirrhosis, leprosy, atypical mycobacterial infection, miliary tuberculosis, silicosis, acute histoplasmosis and hyperparathyroidism. ACE is not elevated in patients with malignancies (e.g. lymphoma). Hypercalcaemia and, more commonly, hypercalciuria may be present.

4. The chest X-ray is usually abnormal (Table 6.16) and the changes can be classified into three stages:

Table 6.16

Chest X-ray changes in sarcoidosis

image

• Stage 1 Bilateral hilar lymphadenopathy alone

• Stage 2 Bilateral hilar lymphadenopathy and pulmonary infiltration

• Stage 3 Pulmonary infiltration without hilar lymphadenopathy

  Patients with stage 1 X-rays are considered to have an acute reversible form of the disease, whereas the other stages tend to be more chronic. The chest X-ray may show paratracheal lymphadenopathy; cavitation and pleural effusions are rare. Cavities may become colonised with Aspergillus. CT scans of the chest may show a ground-glass appearance when active alveolitis is present. Always think about excluding tuberculosis and histoplasmosis.

5. If there is parenchymal granulomatous involvement, respiratory function tests reveal the changes that are typical of interstitial lung disease, with reduced lung volumes and diffusing capacity, but a normal FEV1/FVC ratio. Occasionally, a mixed pattern of obstruction and restriction is seen.

6. Blood gas estimations may show mild hypoxaemia.

7. A gallium-67 lung scan usually shows a pattern of diffuse uptake, but increased uptake in the lacrimal and parotid glands (panda sign) or in the right paratracheal and left hilar areas (lambda sign) is more specific for sarcoidosis. Enlarged nodes also tend to show up on the scans.

8. Bronchoscopy with transbronchial biopsy will usually establish the pathological diagnosis. Bronchioalveolar lavage will show an increase in the number of CD4+ T-helper lymphocytes. However, this is not diagnostic of the condition.

9. Biopsy of lymph nodes, skin or liver may be diagnostic. The non-caseating granulomas found in sarcoidosis are non-specific; they are also found in berylliosis, leprosy, hypersensitivity pneumonitis and granulomatous infection, and in lymph nodes that drain adjacent carcinomas.

Treatment

Indications for treatment are lack of resolution of active pulmonary sarcoidosis with increasing symptoms or worsening lung function; neurological, renal or cardiac complications; major eye disease; and occasionally severe systemic symptoms (e.g. fever and weight loss).

1. The drug of choice is prednisolone. This is begun in high dose (1 mg/kg) for up to 6 weeks and then tapered over the following few months. Treatment is continued for 12 months. The prognosis is good. About 50% of patients develop some permanent organ damage but, in most, this is mild.

2. Patients who require longer treatment may be offered steroid-sparing drugs, including chlorambucil, methotrexate or azathioprine.

3. Hydroxychloroquine may be useful for skin disease.

4. Infliximab (a monoclonal antibody directed at tumour necrosis factor (TNF)) has been shown to improve lung function for patients already being treated with steroids and cytotoxics.

Cystic fibrosis

The survival of children with cystic fibrosis into adult life is now common. More than 50% of patients reach the age of 30 years and the prognosis is improving all the time. Although paediatricians are often reluctant to give up these patients, they are increasingly coming under the care of adult physicians. A small number of cases are diagnosed in adult life. They, unfortunately, tend to spend long periods in hospital and are thus readily available for clinical examinations.

Cystic fibrosis is a common, serious, congenital inherited defect in Caucasian people. It has an autosomal recessive inheritance and the gene has been identified. The mutation is in the cystic fibrosis transmembrane conductance regulator protein gene on chromosome 7. The trait is present in about 1 in 25 Caucasians and 1 in 3000 has the condition. It is rare in other races. It is a chronic disease that can affect the lungs, pancreas, bowel, liver and sweat glands.

The history

1. Ask about presentation:

a. age at diagnosis – milder forms are sometimes not diagnosed until adult life

b. presenting symptoms – the patient may have been told that he or she had meconium ileus as a baby or recurrent respiratory infections in early life; failure to thrive may suggest the diagnosis

c. pulmonary symptoms – cough and sputum, haemoptysis, wheeze, dyspnoea

d. nasal polyps and sinusitis – relatively common

e. gastrointestinal symptoms – problems maintaining weight; diarrhoea and steatorrhoea (pancreatic malabsorption); constipation and abdominal distension and bowel obstruction (defective water excretion into the bowel)

f. heat exhaustion in hot weather – patients with cystic fibrosis can lose large amounts of salt in their sweat, which sometimes causes problems, particularly in the tropics

g. cardiac symptoms – the patient may know of cardiac involvement (cor pulmonale is a late development)

h. jaundice and variceal bleeding – focal biliary cirrhosis and portal hypertension occur occasionally

i. diabetes mellitus – occurs in 10% of patients with cystic fibrosis.

2. Ask about diagnosis. The patient may know whether a sweat test was performed. Collection of sweat and measurement of the chloride concentration is still the accepted method of diagnosing the condition. A sweat chloride concentration of more than 70 mmol/L suggests cystic fibrosis in an adult. Otherwise, a combination of respiratory and malabsorptive problems may be considered enough to make the diagnosis. A list of the major and minor diagnostic criteria is presented in Table 6.17. DNA markers are likely to be used increasingly in the diagnosis. At the moment this is difficult because there are a large number (over 1300) of abnormal genotypes that can result in the disease. Screening for the most common mutations is especially helpful for those patients who have the clinical syndrome but a negative sweat test (1–2%).

Table 6.17

Diagnosis of cystic fibrosis

image

3. Ask about family history – the autosomal recessive inheritance means siblings and other close relatives may be affected.

4. Ask about treatment. Pulmonary disease is the main determinant of mortality. Aggressive treatment of the pulmonary complications has had the greatest effect on the improvement in life expectancy. The patients are usually well aware of this and are largely responsible for their own treatment. The condition is a chronic suppurative progressive one causing bronchiolitis, bronchitis, pneumonia and eventually bronchiectasis. The pathology is probably the result of the formation of viscous mucous plugs, which lead to distal infection and lung damage.

a. The mainstay of treatment is physiotherapy, which the patient, with help from family and a physiotherapist, performs. Ask about deep breathing, percussion, postural drainage, the use of a flutter valve and the forced expiratory technique called ‘huffing’.

b. Mucolytic drugs are of doubtful benefit and may even be harmful.

c. The patient should also know what antibiotics have been used and whether continuously or intermittently. Nebulised bronchodilators and antibiotics are commonly prescribed. Staphylococcus aureus and Pseudomonas aeruginosa are common pathogens because of their ability to grow on the abnormal bronchial mucus of cystic fibrotic lungs. The patient may know if the pseudomonas is antibiotic resistant.

d. Ask whether treatment for complications, such as haemoptysis, cor pulmonale or pneumothorax, has been required. Minor haemoptysis, where less than 250 mL of blood is lost, occurs in about 60% of patients. Major haemoptysis occurs in about 7% of patients and bronchial artery embolisation may be required. Cor pulmonale may require treatment with diuretics, spironolactone and possibly vasodilators, but aggressive treatment of the lung disease and supplementary oxygen are more important in the long term. Pleurodesis used to be the treatment of choice for recurrent pneumothorax, but this may result in a contraindication to lung transplantation. Macrolide antibiotics, especially azithromycin, are being used because of their anti-inflammatory properties.

5. Enquire about gastrointestinal symptoms. These tend to be less of a problem, but malabsorption may make weight gain very difficult for these patients. Ask what pancreatic enzyme replacement the patient uses and how often.

6. Ask about the number of admissions to hospital over the past 12 months and the length of each stay. Routine admission to hospital three or four times a year for intensive physiotherapy and nebulised antibiotics and bronchodilators is not advantageous.

7. Enquire about social support. Ask whether the patient knows about or belongs to the local cystic fibrosis association and whether he or she has been in touch with other affected patients. Try to find out tactfully whether the patient understands the inheritance of the disease; male patients may know that azoospermia is usually present due to destruction of the vas deferens by abnormal secretions (95%). Eighty per cent of women are fertile, and pregnancy and breastfeeding are often successful. Find out in some detail how a young adult copes with this debilitating and life-shortening disease.

The examination

1. Look at the patient’s size and physique. Muscle bulk is considered a good indicator of the severity and prognosis in a particular patient. Measure the patient’s height and weight.

2. Ask the patient to cough. Listen for a loose cough and examine any sputum for the degree of purulence.

3. Now examine the respiratory system carefully. Note clubbing, which is present in the majority of patients. Look for abnormal chest wall development. Estimate forced expiratory time and examine the chest, listening particularly for crackles, wheezes and reduced breath sounds.

4. Examine the heart for signs of cor pulmonale and right ventricular failure.

5. Examine the abdomen for signs of faecal loading, especially in the right iliac fossa.

Investigations

1. Sputum culture is most important. Colonisation with H. influenzae and S. aureus tends to occur in young patients and this is often followed by nosocomial E. coli and Proteus spp. By the age of 10 years, Pseudomonas is the main pathogen in most patients, but usually it does not cause systemic infection.

2. A full blood count should be asked for to look for anaemia, which may be caused by malabsorption or chronic disease; the white cell count may indicate acute infection. Polycythaemia is rare, despite chronic hypoxia.

3. The electrolyte levels and liver function tests should be looked at. There may be evidence of deficiencies of fat-soluble vitamins (A, D, E and K). The creatinine level should be known before aminoglycosides are used.

4. The chest X-ray (see Fig 6.12a and b) should be looked at carefully and should be compared with previous films if these are available. Increased lung markings are present in 98% of patients. These occur particularly in the upper lobes. Cystic bronchiectatic changes occur in more than 60% of patients. Mucous plugs may be seen in one-third and atelectasis occurs in just over 10% of patients. Look also for pneumothorax and pleural changes at the site of previous pneumothoraces or pleurodesis.

image

FIGURE 6.12 (a) Cystic fibrosis PA and (b) lateral films in a young patient. Note increased lung markings in the right middle lobe with ‘tram tracking’ – increased bronchial wall thickness (arrows). Figures reproduced courtesy of The Canberra Hospital.

5. Chest CT is not routine but may help define focal areas of bronchiectasis that are amenable to resection.

6. Spirometry readings may fluctuate because of airway inflammation. An FEV1 that is persistently less than 40% indicates a poor prognosis.

Management

Try to form an idea of the patient’s ability to cope with the illness, as so much of the management depends on this.

1. Intensive and repetitive physiotherapy is the mainstay of treatment. Inactivated influenza vaccine and the pneumococcal vaccine should be routine.

2. Intravenous antibiotics may be indicated for acute exacerbations of pulmonary disease if these are severe or fail to respond to oral antibiotic treatment. Intravenous options include tobramycin and ceftazimide for Pseudomonas. Inhaled tobramycin seems useful and bronchodilators can help airway clearance. Nebulised anti-pseudomonas antibiotics improve lung function and prognosis.

3. Malabsorption may require aggressive treatment with pancreatic enzyme supplements, including lipase, and frequent small meals as well as vitamin supplements.

4. Double lung transplantation is now an accepted, although still uncommon, treatment in patients with advanced disease. Cystic fibrosis does not recur in the transplanted lung. The 5-year survival rate is only about 65%.

5. Human recombinant DNAase seems effective in degrading the concentration of DNA in sputum, reducing sputum viscosity and improving the patient’s ability to clear pulmonary secretions. Gene therapy may be the treatment of choice in the future (e.g. ivacaftor for the G551D mutation).

Tuberculosis

The increased incidence of pulmonary tuberculosis (TB) over the past 10 years or so and its association with HIV infection have made it a possible long case. Protection from Mycobacterium tuberculosis is via cell-mediated immunity involving CD4+ T-helper lymphocytes. The defects of these cells in number and effectiveness, which is characteristic of HIV infection, explain this susceptibility. It may be a difficult diagnostic or management problem, or both. It also has important social and public health implications.

The history

The patient is likely to know that the diagnosis has been made or is suspected.

1. Find out whether the patient is a recent immigrant and, if so, from where.

2. Ask whether there has been a previous diagnosis of any other serious medical problem that might interfere with cell-mediated immunity, such as malnutrition, alcoholism or HIV infection.

3. Establish how the diagnosis was made and how long ago.

4. Ask about some of the important symptoms – weight loss, sweats and fever, cough with purulent and blood-stained sputum, and pleuritic chest pain from pleural lesions or uncontrolled coughing.

5. Ask what investigations have been performed or are planned. TB may have been suspected after a chest X-ray was performed because of respiratory symptoms or as a routine screening test. The patient may remember having to give early morning sputum specimens on a number of occasions or having had a bronchocospy with washings, if sputum was not being produced. Bronchoscopy may have been performed to exclude other causes of an abnormal chest X-ray, such as carcinoma of the lung.

  A tuberculin (Mantoux) skin test may have been performed as a screening test or to support the diagnosis where cultures have been negative. A positive tuberculin test is still significant, even if the patient has received a bacille Calmette-Guérin (BCG) vaccination in the past. Remember, if the patient is in a high-risk group (HIV positive, immunosuppressed, in close contact with a clear-cut case of TB or has evidence of prior TB on chest X-ray), the Mantoux test is considered positive with just 5 mm of induration (vs 15 mm in low-risk patients).

6. Find out what treatment regimen the patient is receiving. Considerable detail must be sought about the drugs themselves – doses (if known), how long treatment will continue, how the drugs are administered (supervised or unsupervised) and what side-effects have occurred (Table 6.18). Remember that rifampicin and rifabutin colour body fluids, including urine, orange.

Table 6.18

Common antituberculous drugs and their side-effects

DRUG

MAIN SIDE-EFFECTS

USUAL DOSE/DAY

Rifampicin

Hepatitis, flu-like illness

600 mg

Isoniazid

Hepatitis, fever, peripheral neuropathy

300 mg (reduced to 2 or 3 doses a week in renal failure)

Streptomycin

Ototoxicity, renal impairment

1 g (not safe in pregnancy)

Ethambutol

Optic neuritis

15 mg/kg

Pyrazinamide

Hepatitis

1.5–2 g

PAS

Hepatitis, diarrhoea, hypersensitivity

12 g

PAS = para-aminosalicylic acid.

7. Ask whether there has been a trigger for reactivation of previous infection (diabetes mellitus, old age, HIV infection).

8. Find out what effect this serious and chronic disease has had on the patient’s life. Has the patient been able to work or go to school? Do friends and workmates know the diagnosis? Does the patient’s occupation involve a public health risk?

9. Establish how the problem has been handled from a public health aspect. What screening has been done on the patient’s family and friends? Are any of the family also being treated?

The examination

Early in the course of the illness there may be no specific signs. Of those patients without HIV infection who have TB, 80% have only pulmonary disease. However, the majority of patients with HIV and TB have extrapulmonary and pulmonary disease.

1. Note the patient’s general appearance. Look for wasting and cachexia that may be associated with the risk factors for TB (HIV, alcoholism) or may be a result of the disease (which is also known as consumption for this reason).

2. Examine the lungs for signs of the aggressive primary infection that can occur in immunocompromised patients. These include a pleural effusion or tuberculous empyema and lobar collapse (as a result of lymphadenopathy and bronchial obstruction).

3. Post-primary disease is more common in adults. There is almost always a loose cough and often haemoptysis. There may be no abnormal findings, but you should look especially for upper lobe signs, including coarse crackles and wheezes owing to partial bronchial obstruction caused by lymphadenopathy, and the rare amphoric breath sounds that occur over a cavity.

4. Extrapulmonary disease most commonly involves the lymph nodes (especially in HIV patients). Examine all the palpable lymph node groups. The most often affected are the cervical and supraclavicular. There is usually painless swelling.

5. Involvement of the genitourinary tract can be associated with haematuria and tenderness over the flanks.

6. The bones are involved in a small number of cases. The lumbar spine (Pott’s disease), hips and knees are most affected. Collapse of the vertebral bodies may cause kyphosis and even paraplegia.

7. Tuberculous pericarditis can cause symptoms and signs of pericarditis and occasionally tamponade.

8. Abdominal TB can cause various gastrointestinal signs. There may be a palpable abdominal mass. Severe abdominal tenderness suggests tuberculous peritonitis.

Investigations

1. The diagnosis of active disease depends on microscopy of a specimen that shows mycobacteria (e.g. send three morning sputum specimens on separate days, followed by confirmation by culture of the organism). Traditionally, specimens of sputum or gastric or bronchial washings (often useful for children), or a lymph node biopsy, are stained with the Ziehl-Neelsen stain. Modern laboratories are more likely to use auramine-rhodamine stains and fluorescence microscopy. Only about 60% of patients with eventually proven TB have positive microscopy. Culture of the organism takes about 6 weeks, but is needed for the definitive diagnosis. These organisms should then be tested for sensitivity to the main antituberculous drugs. This takes up to 8 more weeks. If multidrug resistance (MDRTB) is suspected, the rpo gene can be tested: it is responsible for 95% of rifampicin resistance. Polymerase chain reaction (PCR) testing can now provide rapid identification of M. tuberculosis, but is not available everywhere and does not distinguish between viable and non-viable organisms.

2. A chest X-ray showing the typical pattern of infiltrates and cavities in the upper lobe strongly suggests the diagnosis, but many other patterns are consistent with TB (Figs 6.136.14 and 6.15).

image

FIGURE 6.13 Right upper lobe scarring; old TB infection (arrow). Figure reproduced courtesy of The Canberra Hospital.

image

FIGURE 6.14 CT scan of the thorax in a patient with TB; note the destructive changes and cavitation. Figure reproduced courtesy of The Canberra Hospital.

image

FIGURE 6.15 Pulmonary tuberculosis. Two small rounded areas of shadowing are seen in the right upper zone (black arrow). The right hilum is enlarged by the enlarged draining lymph nodes (open arrow). This combination of focal shadowing and enlarged lymph nodes is the primary (Ghon) complex of tuberculosis. With healing, calcification may occur in the parenchymal and nodal lesions. In contrast, in tuberculosis reactivation or re-infection, cavitation may occur and there is no lymphadenopathy. The Canberra Hospital X-Ray Library, reproduced with permission.

3. Tuberculin (Mantoux) skin testing is useful for screening for latent TB. The test may be negative in severe disease (e.g. in up to 50% of cases of miliary TB) or if exposure is only recent (repeat in 3 months). IFNλ release assays use a specific tuberculosis antigen to stimulate release of IFNλ from T cells in vitro. These tests are more specific than tuberculin testing and may be useful where rates of TB are low. They are not affected by previous BCG vaccination. A positive screening test should be followed by a chest X-ray to look for active disease.

4. Biopsies of the pleura, lymph nodes or bone marrow may be needed. Bronchoscopy is sometimes necessary to exclude other causes of X-ray changes.

5. The fasting blood sugar level should be taken to rule out diabetes mellitus.

6. HIV patients may have TB despite a completely normal chest X-ray. They may also have less typical chest X-ray findings – often lower lobe changes without cavities. They are more likely to have infection with other mycobacteria, such as MAC. Remember that the diagnosis can be made even when the organism is not isolated. All patients with TB should be tested for HIV infection.

Treatment

There are four first-line drugs for the treatment of TB: isoniazid, rifampicin, ethambutol and pyrazinamide. These are all given orally. Second-line drugs tend to be more toxic and are used only for organisms resistant to the first-line drugs. They include streptomycin, quinolone, kanamycin and amikacin (parenteral), and cycloserine, ethionamide and PAS (para-aminosalicylic acid). The initial isolate should undergo drug susceptibility testing, especially if treatment seems to have failed or there is a relapse of symptoms.

Treatment of latent TB reduces the risk of transmission and the risk of progression to active disease by up to 90%. Nine months of treatment with isoniazid is commonly recommended.

1. Treatment begins with a combination regimen of three drugs (usually isoniazid, rifampicin and pyrazinamide) for 2 months. A fourth drug (usually ethambutol) is often given until the organism’s sensitivities are available. The aim here is to kill the majority of the organisms, improve the patient’s symptoms and render him or her non-infectious. This is followed by 4 months of treatment with two drugs (isoniazid and rifampicin).

2. Adherence to the full course of treatment is very important, but difficult to ensure. Complicated public health arrangements, with monitoring of compliance, may be needed to enforce treatment. Direct observed treatment (DOT) is insisted on by public health authorities if compliance seems doubtful. These patients present as required to be observed taking their treatment.

3. The response to treatment is monitored by repeat sputum cultures until they become negative. Persisting positive cultures after 3 months suggest resistance of the organism or non-adherence on the part of the patient. Patients are probably not an infectious risk if no sputum is produced or if the sputum is consistently acid-fast bacilli (AFB) negative.

4. Patients need to be aware of the most important side-effects of treatment, which include hepatitis (up to 5% in the general population and 30% in HIV patients), deafness and visual disturbance (Table 6.18). Small increases in the transaminases (to three times normal) are no cause for alarm and are poor predictors of significant hepatotoxicity. Treatment should be reviewed immediately if jaundice develops.

5. Multiple drug resistance is increasingly common and should be expected if the infection was acquired from a patient with a known resistant organism or if the infection was acquired in parts of Asia or South America. The addition of a fluoroquinolone to the regimen should be considered while resistance studies are underway.

6. Prevention of infection by vaccination with BCG is not widely practised in Australia; its effectiveness is uncertain. In high-risk areas vaccination of children has been shown to reduce the risk of cerebral TB. The Mantoux test should be interpreted as usual regardless of previous BCG vaccination (15 mm is a positive skin test for low-risk individuals). If the Mantoux test is positive (≥5 mm) in a high-risk group (patients with exposure to TB (especially household contacts), or who are HIV infected, on prolonged steroid treatment (≥15 mg ≥1 month) or have undergone organ transplant), prescribe treatment with isoniazid for latent TB (5 mg/kg/day for 9 months). If close (e.g. household) contacts are negative on the tuberculin test, treat for 12 weeks and repeat the skin test: this reduces the chance of the development of open TB by 90%. If the test is ≥10 mm in an intermediate-risk group (IV drug abusers, prisoners, healthcare workers, nursing-home patients, homeless people or those with diabetes), also treat with isoniazid. Screening of contacts and high-risk patients with tuberculin testing is an important public health measure.

Lung transplantation

Although lung transplantion is an uncommon procedure, transplant patients have chronic management problems that make them very suitable long cases. The examiners will have the opportunity to ask questions about the patient’s underlying pulmonary problem, the general indications for lung transplant, management of the complications of transplant and, of course, the types of social problems associated with a severe chronic illness. Occasionally, patients who are being assessed for possible transplant may be suitable for the clinical examinations.

The history

1. Find out why the patient is in hospital (it may just be for the clinical examinations).

2. Obtain some basic information about the transplant: how long ago, how many lungs were transplanted and whether the patient’s heart was also originally someone else’s.

3. Enquire what the original lung disease was. Emphysema (including that caused by alpha1-antitrypsin deficiency) is the most common indication, accounting for about half the unilateral transplants and one-third of the bilateral transplants. Idiopathic pulmonary hypertension, cystic fibrosis and Eisenmenger’s syndrome are the main indications for heart/lung transplants.

4. Ask how successful the procedure has been from the patient’s point of view. Lung function tests should be normal after bilateral transplant and nearly so after unilateral transplant. A decline in lung function test measurements of more than 10% usually is important.

5. Find out what complications the patient can remember. Ask about known rejection episodes and how they were managed. Have there been difficult infections? The patient may know what organisms have been detected. Stenosis of a bronchial anastomosis site is an occasional early problem. This is often treated with dilatation and stenting.

6. Review what medications the patient is taking. If necessary, prompt for prednisolone, cyclosporin, mycophenolate, azathioprine and tacrolimus. Find out whether blood levels of tacrolimus and cyclosporin are measured regularly. Remember that these two drugs are metabolised via the cytochrome P450 pathway in the liver and blood levels may be affected by other medications (so make sure you review all of the drugs being taken).

7. If the patient is being assessed for transplant, try to find out whether the patient fits the current guidelines for transplant (Tables 6.19 and 6.20). In general, suitable patients are sick enough to require the operation but not too sick to present an intolerable operative risk.

Table 6.19

Age criteria for lung transplant

image

Table 6.20

Indications and contraindications for lung transplant

image

DLCO = diffusion capacity for carbon monoxide; VC = vital capacity; ILD = interstitial lung disease.

8. Establish how the patient has coped with the procedure, its complications and the immunosuppressants. What regular follow-up is carried out? Many transplant units have a transplant nurse available after hours whom the patient can contact directly if there are problems.

The examination

Perform a thorough respiratory examination.

1. Look especially for thoracotomy scars and attempt an assessment of the patient’s functional capacity (e.g. look for signs of breathlessness while the patient is undressing and, if the room is big enough, get the patient to walk backwards and forwards).

2. Listen for end-inspiratory pops and squeaks (bronchiolitis obliterans at an advanced stage can be associated with the development of bronchiectasis).

3. Note signs of infection – fever and areas of bronchial breathing or crackles.

4. Look for sputum and assess the cough.

5. Is the patient Cushingoid?

Management

The detection of complications and their management is likely to dominate the discussion.

1. Rejection. Early rejection episodes are common and treated with boost doses of prednisone. Symptoms of acute rejection include malaise, fever, dyspnoea and cough. Clinical assessment may reveal crackles, decreasing FEV1, hypoxia and a raised white cell count. The chest X-ray may show infiltrates and pleural effusions. A transbronchial biopsy tends to be performed if there is any suspicion of rejection and allows an accurate diagnosis. In some places, routine biopsies are performed to detect asymptomatic rejection. It is not clear, however, whether these should be treated.

2. Infection. Most lung transplant patients develop infections requiring treatment. Infection is the most common cause of death. A combination of immunosuppression and local problems, such as impaired ciliary activity, are relevant. Infections with cytomegalovirus (CMV), adenovirus, influenza A and paramyxovirus are common and associated with a significant mortality. Invasive fungal organisms, such as Aspergillus, result in an even worse prognosis. Patients now receive at least 3 months of routine prophylactic antibiotic, antiviral and antifungal treatment. This approach has improved the early postoperative prognosis.

3. Immunosuppression. The usual problems with immunosuppressive drugs occur in lung transplant patients. Renal impairment, hypertension and hyperlipidaemia are frequent problems. Osteoporosis and peripheral neuropathy are also possible problems. Five per cent of lung transplant patients develop post-transplant lymphoproliferative disorders.

4. Bronchiolitis obliterans. The gradual onset of small airways obstruction is a manifestation of chronic rejection. It does not usually begin until 2 or more years after transplant, but is detectable in at least half of transplant patients within 5 years. It may occur more often in those who have had more frequent acute rejection episodes and in those with a human leucocyte antigen (HLA) mismatch with the donor. There tends to be a very gradual onset of dyspnoea, fatigue and cough. Patients have a slowly decreasing FEV1 but chest X-rays are often normal. CT scans may show a central mottling opacity. Biopsy will establish the diagnosis. The prognosis is not good. Sometimes an aggressive increase in immunosuppression may stabilise the condition, but it cannot be reversed and often the patient deteriorates rapidly.

5. Disease recurrence. Sarcoidosis and some forms of idiopathic ILD can recur in the transplanted lungs.