Respiratory disease


The main function of the lungs is to provide continuous gas exchange between inspired air (supplying oxygen) and blood in the pulmonary circula-tion (removing carbon dioxide). The lungs are each enclosed within a double membrane; visceral pleura covers the surface of the lung and is continuous at the hilum with the parietal pleura, which lines the inside of the thoracic cavity. The interpleural space between these layers normally contains only a tiny amount of lubricating fluid. The right lung is divided into three lobes, whereas the left lung has two. The trachea divides at the carina (lying under the junction of manubrium sterni and second right costal cartilage) into right and left main bronchi. Within the lungs the bronchi branch again, forming secondary and tertiary bronchi, then smaller bronchioles, and finally terminal bronchioles ending at the alveoli.

The airways are lined by epithelium containing ciliated columnar cells and mucous (goblet) cells - fewer of the latter in the smaller airways. Mucus traps macrophages, inhaled particles and bacteria, and is moved by the cilia in a cephalad direction thus clearing the lungs (the mucociliary escalator). Gas exchange occurs in the alveolus where capillary blood flow and inspired air are separated only by a thin wall composed mainly of type 1 pneumocytes and capillary endothelial cells and the capillary and alveolar basement mem-branes are fused as one.


The lung has a dual blood supply: pulmonary (venous blood) and systemic (arterial blood). The pulmonary circulation delivers deoxygenated blood to the lungs from the right side of the heart Via the pulmonary artery. Oxygen from inhaled air passes through the alveoli into the bloodstream and oxygenated blood is returned to the left heart Via the pulmonary veins. The bronchial (systemic) system carries arterial blood from the descending aorta to oxygen-ate lung tissue primarily along the larger conducting airways. In contrast, carbon dioxide passes from the capillaries which surround the alveoli, into the alveolar spaces, and is breathed out.

Inspiratory airflow is achieved by creating a sub-atmospheric pressure in the alveoli by increasing the volume of the thoracic cavity under the action of the inspiratory muscles: descent of the diaphragm (innervated by the phrenic nerve, C3-C5) and contraction of the intercostal muscles with move-ment of the ribs upwards and outwards. The accessory muscles of respiration are also recruited (sternomastoids and scalenes) during exercise or respira-tory distress. Expiration is a passive process, relying on the elastic recoil of the lung and chest wall. During exercise ventilation is increased and expira-tion becomes active, with contraction of the muscles of the abdominal wall and the internal intercostals.


Common symptoms of respiratory disease are cough, sputum production, chest pain (p. 407), breathlessness, haemoptysis and wheeze.

Cough is the most common manifestation of lower respiratory tract disease. It is initiated by mechanical (e.g. touch and displacement) or chemi-cal (e.g. noxious fumes) stimulation of specialized cough receptors on the epithelium of the upper and lower respiratory tract. Impulses are carried by afferent nerves to a ‘cough centre' in the medulla. This generates efferent signals (via phrenic nerve and efferent branches of the vagus) to expiratory musculature to generate a cough.

Cough lasting only a few weeks is most commonly due to an acute respira-tory tract infection. Asthma, gastro-oesophageal reflux disease and postnasal drip are the most common causes of a persistent cough (Table 11.1). A postnasal drip is due to rhinitis, acute nasopharyngitis or sinusitis and symp-toms, other than cough, are nasal discharge, a sensation of liquid dripping back into the throat, and frequent throat clearing. Cough may be the only symptom of asthma when it is typically worse at night, on waking and after

Table 11.1 Causes of persistent cough
*Postnasal drip
*Gastro-oesophageal reflux disease
Post-viral cough
Lung airway disease: COPD, bronchiectasis, tumour, foreign body
Lung parenchymal disease: interstitial lung disease, lung abscess
Drugs: ACE inhibitors
*Commonest causes and responsible for 99% of cases who are non-smokers, not taking ACE inhibitors and with a normal chest X-ray.
COPD, chronic obstructive pulmonary disease; ACE, angiotensin-converting enzyme

exercise. A chronic cough, sometimes accompanied by sputum production, is common in smokers. However, a worsening cough may be the presenting symptom of bronchial carcinoma and needs investigation.

Breathlessness Dyspnoea is the subjective sensation of shortness of breath. Orthopnoea is breathlessness that occurs when lying flat and is the result of abdominal contents pushing the diaphragm into the thorax and of redistribution of blood from the lower extremities to the lungs. Paroxysmal nocturnal dyspnoea is a manifestation of left heart failure: the patient wakes up gasping for breath and finds some relief by sitting upright. The mechanism is similar to orthopnoea, but because sensory awareness is depressed during sleep, severe interstitial pulmonary oedema can accumulate.

The cause of breathlessness (Table 11.2) is often apparent from the clini-cal history and examination, particularly with sudden and acute breathless-ness. In acute breathlessness, appropriate initial investigations include a chest X-ray, pulse oximetry and sometimes arterial blood gases. ECG, full blood count, serum electrolytes, blood glucose, serum troponin (suspected cardiac cause) and D-dimers (suspected pulmonary embolism) may be indi-cated depending on the clinical circumstances. Pulmonary embolism can be a difficult diagnosis to make and chest X-ray, blood gases and ECG may be normal (p. 472). Simple lung function tests, pulse oximetry, a full blood count and a chest X-ray are the initial investigations for most patients with chronic breathlessness. Echocardiography is indicated if a cardiac cause is suspected.

Table 11.2 Causes of breathlessness

Acute (onset over minutes/hours)

Chronic (onset over days/months)

Acute asthma


Exacerbation COPD



Diffuse parenchymal lung disease

Pulmonary embolism

Pleural effusion


Cancer of the bronchus/trachea

Hypersensitivity pneumonitis

Heart failure

Upper airway obstruction:

Inhaled foreign body


Severe anaemia

Left heart failure

Cardiac tamponade

Panic with hyperventilation

COPD, chronic obstructive pulmonary disease

Psychogenic breathlessness is usually described as ‘inability to take a deep breath' and rarely disturbs sleep and may be better with exercise.

Wheezing is the result of airflow limitation and due to localized (e.g. cancer, foreign body) or generalized (e.g. asthma and chronic obstructive pulmonary disease) obstruction of the airways. Asthma is a common cause of wheezing and is likely when patients present with episodic wheezing, cough and dyspnoea which responds favourably to inhaled bronchodilators. Wheeze should be distinguished from stridor which is a harsh inspiratory wheezing sound caused by obstruction of the trachea or major bronchi, e.g. by tumour.

Haemoptysis (coughing blood) always requires investigation. Common causes are bronchiectasis, bronchial carcinoma, pulmonary embolism, bron-chitis and lung infections including pneumonia (rust coloured sputum), abscess and tuberculosis. Pulmonary oedema is associated with the produc-tion of pink frothy sputum. Rarer causes are benign tumours, bleeding dis-orders, Wegener's granulomatosis (p. 549) and Goodpasture's syndrome (p. 552). A chest X-ray should be performed in all patients, and subsequent investigations (e.g. bronchoscopy, CT of the thorax, ventilation-perfusion scan) decided from the history and examination.

MassiVe haemoptysis (>200 mL in 24 hours) is most often due to pulmo-nary TB, bronchiectasis, lung abscess or malignancy (primary or secondary). It may be life-threatening due to asphyxiation and is an indication for hospital admission. Initial management includes administration of oxygen, placement of a large-bore intravenous catheter, blood samples (full blood count, clotting screen, urea and electrolytes), arterial blood gases and chest X-ray. There should be early referral to a respiratory physician and thoracic surgeon.

Chest pain (p. 407) due to respiratory disease is often a localized sharp pain made worse by deep breathing or coughing (referred to as pleuritic pain) and is most commonly caused by infection or by pleural irritation from a pulmonary embolism.



Sputum is commonly sent for microbiology (Gram stain and culture in pneu-monia, auramine stain in suspected tuberculosis) and cytology for malignant cells but may be falsely negatiVe. A 5% saline nebulizer will encourage productive coughing if sputum is difficult to obtain. Yellow/green sputum indicates inflammation (infection or allergy). Haemoptysis is discussed aboVe.

Respiratory function tests

Respiratory function tests include simple outpatient investigations to assess airflow limitation and lung volumes. Normal values vary for age, sex and height, and between indiViduals.

Peak expiratory flow rate (PEFR)

This records the maximum expiratory flow rate during a forced expiration after full inspiration and is measured with a peak flow meter. It is useful in monitoring the response to treatment of asthma and many patients will monitor their own PEFR at home.

The spirometer

This is used to measure forced expiratory volume (FEV) and forced vital capacity (FVC). The patient exhales as fast and as long as possible from a full inspiration; the volume expired in the first second is the FEV1 and the total volume expired is the FVC. The FEV1/FVC ratio is a measure of airflow limitation and is normally about 75%:

■ Airflow limitation: FEV1/FVC < 75%

■ Restrictive lung disease: FEV1/FVC > 75%.

More sophisticated techniques allow the measurement of total lung capacity (TLC) and residual volume (RV). These are increased in obstructive lung disease such as asthma or COPD, because of air trapping, and reduced in lung fibrosis. Transfer factor (Teo) measures the transfer of a low concen-tration of added carbon monoxide in the inspired air to haemoglobin. The transfer coefficient (Keo) is the value corrected for differences in lung volume. Gas transfer is reduced early on in emphysema and lung fibrosis.

Arterial blood gas sampling This is used to measure partial pressures of oxygen and carbon dioxide within arterial blood (p. 583), the values of which are used in the assessment of the breathless patient and the manage-ment of respiratory failure and acute asthma. Arterial oxygen saturation (Sa0ị) can be continuously measured non-invasively using an oximeter with either ear or finger probes. Normal ranges are from 94 to 98%. However, carbon dioxide levels are not measured and hypoventilation with carbon dioxide retention would go undetected.

Walking distance

A 6-minute period is also used to assess lung function.


Chest X-ray

Routine films are taken postero-anteriorly (PA), i.e. the film is placed in front of the patient with the X-ray source behind. AP films are taken only in patients who are unable to stand; the cardiac outline appears bigger and the scapulae cannot be moved out of the way. Figure 11.1 shows a normal chest X-ray and suggests a systematic approach to read a film. The solitary pulmonary nodule detected on chest X-ray is a common clinical problem (Table 11.3). Risk factors for malignancy in this situation are older age, smoker, occupa-tional exposure to carcinogens, increasing size of lesion (80% > 3 cm), irregular border, eccentric calcification of the lesion and increasing size

Fig. 11.1 A normal chest X-ray and suggested checklist for review of a film.

Check list
Patient name and date of film
View – ?PA or AP
Film centring – ?equal distance between each clavicular head and spinal
Trachea – ?deviated from midline
Soft tissues: neck, shoulders, breast
Bony outline: ribs, clavicles, spine
Diaphragms – right diaphragm usually 2–3 cm higher than left
Cardiothoracic ratio – maximum transverse diameter of the heart normally less than 50% maximum transverse diameter of the thorax measured from inside of ribs on PA film
Mediastinum – ?widened (>6 cm on upright film or >25% of thoracic width at aortic knob)
Hilar region – ? lymphadenopathy, ?enlarged pulmonary arteries and veins
Lungs – ?opacities, consolidation, fluid, nodules.

compared to an old X-ray. CT scan is usually necessary for further evaluation

Computed tomography (CT scan, p. 822)

The initial imaging tool for the lung parenchyma is the chest X-ray. However, a CT scan can detect lung disease in symptomatic patients with a normal chest X-ray. It can be used as a guide to the type and site of lung or pleural biopsy, and is used in the staging of bronchial carcinoma. Multi-slice (high resolution) CT scanning (sampling lung parenchyma with scans of 1-2 mm

thickness at intervals of 10-20 mm) is particularly useful in the detection and eValuation of diffuse parenchymal lung disease and in diagnosis of bronchiectasis. CT angiography (helical CT using intraVenous contrast) is used in the diagnosis of pulmonary emboli.

Magnetic resonance imaging (MRI, p. 826)

MRI is used in the staging of lung cancer to assess tumour invasion in the mediastinum, lung apex and chest wall. It also provides accurate images of the heart and aorta. MRI is less useful than CT scanning in the assessment of the lung parenchyma.

Positron emission tomography (PET, p. 828)

PET scanning is used in the investigation of pulmonary nodules to different-iate benign from malignant, and in the staging of lung cancer.

Scintigraphic imaging

Ventilation-perfusion (V/Q) scanning is used in the diagnosis of pulmonary emboli. Xenon-133 gas is inhaled (the ventilation scan) and microaggregates of albumin labelled with technetium-99m are injected intravenously (the perfusion scan). Pulmonary emboli are detected as ‘cold areas' on the per-fusion scan relative to the ventilation scan. However, many lung diseases affect pulmonary blood flow as well as ventilation and the V/Q scan is only diagnostic when it is reported as normal (excluding PE) or high probability (diagnostic of pulmonary emboli).

Pleural aspiration and biopsy

Pleural aspiration is used for both diagnostic and therapeutic reasons (to drain large effusions for symptom relief, to instil therapeutic agents such as sclerosants). A diagnostic fluid sample is obtained with a fine bore needle and a 50 mL syringe to investigate the cause of a pleural effusion (p. 559).

Complications of pleural aspiration include pneumothorax, damage to the neurovascular bundle which lies in the subcostal groove, infection and seeding of malignant cells along the tract with a malignant effusion. Pulmo-nary oedema may occur when large quantities of fluid (>1 L) are removed rapidly for therapeutic purposes.


A flexible bronchoscope is passed through the nose and the airways as far as the subsegmental bronchi are inspected under intravenous midazolam sedation, topical lidocaine anaesthesia and pre-medication with an antimus-carinic agent such as atropine (to reduce bronchial secretions). Biopsies and brushings are taken of macroscopic abnormalities and washings for appropri-ate microbiological staining and culture and cytological examination for malignant cells. Diffuse parenchymal lung disease is investigated by trans-bronchial biopsy. Complications of bronchoscopy ± biopsy include respiratory depression, pneumothorax, respiratory obstruction, cardiac arrhythmias and haemorrhage.


A mediastinoscopy is used in the diagnosis of mediastinal masses and in staging nodal disease in carcinoma of the bronchus. An incision is made just above the sternum and a mediastinoscope inserted by blunt dissection.

Video-assisted thoracoscopic (VATS) lung biopsy

This technique is less invasive than open thoracotomy for obtaining a lung biopsy. It is used in the investigation of diffuse and localized lung disease.


Cigarette smoking has declined in recent years in the Western world, but is on the increase in many developing countries. Tobacco smoke contains over 40 different carcinogens and is associated with an increased risk of cancer in the gastrointestinal tract (oral cavity, oesophagus, stomach and pancreas), respiratory (larynx and bronchus) and urogenital system (bladder, kidney, cervix). Cigarette smoking is a risk factor for ischaemic heart disease and peripheral vascular disease and is the major cause of chronic obstructive pulmonary disease (COPD) (p. 516). Environmental tobacco smoke (‘passive' smoking) also increases the risk of lung cancer and COPD. Persuading an individual to stop smoking is an essential part of the management of many respiratory diseases and has a preventative role in the ‘well' person. Popula-tion targeted approaches such as advertising and banning smoking in public places has reduced smoking prevalence. Individually targeted smoking ces-sation strategies are best delivered by a smoking cessation clinic and are non-pharmacological (behavioural therapy, self-help programmes, group counselling) and pharmacological:

■ Nicotine replacement therapy as gum, lozenges, patches, tablets, nasal spray

■ Bupropion tablets - mode of action in smoking cessation is not clear

■ Varenicline tablets - partial agonist at the nicotinic acid acetylcholine receptor.

The pharmacological therapies all require the smoker to commit to a target stop date.


The common cold (acute coryza)

The common cold is usually caused by infection with one of the rhinoviruses. Spread is by droplets and close personal contact. After an incubation period of 12 hours to 5 days there is malaise, slight pyrexia, a sore throat and a watery nasal discharge, which becomes mucopurulent after a few days. Treatment is symptomatic. The differential diagnosis is mainly from rhinitis (see below).

Sinusitis (see p. 707)


Rhinitis is defined clinically as sneezing attacks, nasal discharge or blockage occurring for more than 1 hour on most days:

■ For a limited period of the year (seasonal or intermiữent rhinitis)

■ Throughout the whole year (perennial or persistent rhinitis).

Seasonal rhinitis is often called ‘hay fever' and occurs during the summer months. It is caused by allergy to grass and tree pollen and a variety of mould spores (e.g. Aspergillus fumigatus) which grow on cultivated plants. In addition to the nasal symptoms there may be itching of the eyes and soft palate.

Perennial rhinitis may be allergic (the allergens are similar to those for asthma) or non-allergic (triggered by cold air, smoke and perfume). Patients rarely have symptoms affecting the eyes or soft palate. Some develop nasal polyps which may cause nasal obstruction, loss of smell and taste, and mouth breathing.


The diagnosis of rhinitis is clinical. Skin-prick testing or measurement of specific serum IgE antibody against the particular antigen (RAST test) in conjunction with a detailed clinical history will identify causal antigens.


This involves avoidance of allergens, if practical, antihistamines, e.g. ceti-rizine or loratidine tablets, decongestants and topical steroids, e.g. beclo-metasone spray twice daily. A 2-week course of low-dose oral prednisolone (5-10 mg daily) is used when other treatments fail.

Acute pharyngitis

Viruses, particularly from the adenovirus group, are the most common cause of acute pharyngitis. Symptoms are a sore throat and fever which are self-limiting and only require symptomatic treatment. More persistent and severe pharyngitis may imply bacterial infection, often secondary invaders, of which the most common organisms are haemolytic Streptococcus, Haemophilus influenzae and Stephylococcus aureus. This is treated with penicillin V 500 mg four times a day for 10 days (erythromycin if allergic).

Acute laryngotracheobronchitis (croup)

This is usually the result of infection with one of the parainfluenza viruses or measles virus. Symptoms are most severe in children under 3 years of age. Inflammatory oedema involving the larynx causes a hoarse voice, barking cough (croup) and stridor (p. 508). Tracheitis produces a burning retrosternal pain. Treatment is with oxygen therapy, oral or intramuscular corticosteroids and nebulized adrenaline. Endotracheal intubation is occasionally necessary and rarely tracheostomy.


The influenza virus exists in two main forms, A and B. The surface of the Virion is coated with haemagglutinin (H) and an enzyme, neuraminidase (N), which are necessary for attachment to the host respiratory epithelium. Human immunity develops against the H and N antigens. Influenza A has the capacity to undergo antigenic ‘shift', and major changes in the H and N antigens are associated with pandemic infections which may cause millions of deaths world-wide. The H5N1 strain is passed from birds to humans (avian flu) and the H1N1 strain is endemic in pigs and birds. A new strain of swine-origin H1N1 is responsible for the latest pandemic, declared June 2009. Minor antigenic ‘drifts' are associated with less severe epidemics.

Clinical features

The incubation period is 1-3 days. There is then an abrupt onset of fever, generalized aching in the limbs, severe headache, sore throat and dry cough, all of which may last several weeks. Influenza and the common cold (p. 513) can have similar symptoms. In general flu symptoms are worse than a common cold, fever, generalized aching and dry cough are more common with flu, and a runny and stuffy nose are more common with a cold.


Laboratory diagnosis is not always necessary, but serology shows a fourfold rise in antibody titre over a 2-week period, or the virus can be demonstrated in throat or nasal secretion.


Treatment is symptomatic (paracetamol, bed rest, maintenance of fluid intake), together with antibiotics to prevent secondary infection for individuals with chronic bronchitis, heart or renal disease. In the current pandemic (H1N1), neuraminidase inhibitors, e.g. zanamivir and oseltamivir, are offered to all patients with suspicious symptoms without the need for testing for infection.


Pneumonia is the most common complication. This is either viral or the result of secondary infection with bacteria, of which Staphylococcus aureus is the most serious, with a mortality rate of up to 20%.


Influenza vaccine is prepared from current strains. It is effective in 70% of people and lasts for about a year. It is recommended in individuals over 65 years of age or people under 65 years of age who are more likely to acquire the infection or suffer from a severe illness (see National Formulary for a detailed list).

Inhalation of foreign bodies

Children inhale foreign bodies - frequently peanuts - more often than do adults. In adults inhalation is usually associated with a depressed conscious level, such as after an alcoholic binge. A large object may totally occlude the airways and rapidly result in death. Smaller objects impact more peripherally (usually in the right main bronchus, because it is more vertical than the left) and cause choking or persistent wheeze, presentation at a later stage with persistent suppurative pneumonia or lung abscess. In an emergency the foreign body is dislodged from the airway using the Heimlich manoeuvre: the subject is gripped from behind with the arms around the upper abdomen, a sharp forceful squeeze pushes the diaphragm into the thorax and the rapid airflow generated may be sufficient to force the foreign body out of the trachea or bronchus. In the non-emergency situation bronchoscopy is used to remove the foreign body.


Acute bronchitis

Acute bronchitis is usually viral but may be complicated by bacterial infection, particularly in smokers and in patients with chronic airflow limitation. Symp-toms are cough, retrosternal discomfort, chest tightness and wheezing, which usually resolve spontaneously over 4-8 days.

Chronic obstructive pulmonary disease (COPD)

COPD is characterized by poorly reversible airflow limitation that is usually Progressive and associated with a persistent inflammatory response of the lungs. COPD is now the preferred term for patients previously diagnosed as having chronic bronchitis or emphysema.

Epidemiology and aetiology

Cigarette smoking is the major cause of COPD and is related to the daily average of cigarettes smoked and years spent smoking. Most smokers will eventually develop abnormal lung function if they continue to smoke. Chronic exposure to pollutants at work (mining, building and chemical industries), outdoor air pollution, and inhalation of smoke from biomass fuels used in heating and cooking in poorly ventilated areas play a role, particularly in developing countries. Alpha-1 antitrypsin deficiency (p. 174) causes early onset COPD but otherwise patients are rarely symptomatic before middle age. The cost of COPD is considerable due to direct (hospital admissions, outpatient visits, drug costs) and indirect costs (loss of working days).


In chronic bronchitis, there is airway narrowing, and hence airflow limitation, as a result of hypertrophy and hyperplasia of mucus secreting glands of the bronchial tree, bronchial wall inflammation and mucosal oedema. The epithelial cell layer may ulcerate and, when the ulcers heal, squamous epithelium may replace columnar epithelium (squamous metaplasia). Emphy-sema is defined pathologically as dilatation and destruction of the lung tissue distal to the terminal bronchioles. Emphysematous changes lead to loss of elastic recoil, which normally keeps airways open during expiration; this is associated with expiratory airflow limitation and air trapping. Although it has been suggested that these definitions separate patients into two different clinical groups (the ‘pink puffers' with predominant emphysema and the ‘blue bloaters' with predominant chronic bronchitis), most have both emphysema and chronic bronchitis, irrespective of the clinical signs.


■ Cigarette smoke causes mucous gland hypertrophy in the larger airways and leads to an increase in neutrophils, macrophages and lymphocyes in the airways and walls of the bronchi and bronchioles. These cells release inflammatory mediators (elastases, proteases, IL-1 and -8 and TNF-a) that attract inflammatory cells (and further amplify the process), induce structural changes and break down connective tissue (protease-antiprotease imbalance) in the lung parenchyma resulting in emphysema. a1-Antitrypsin is a major protease inhibitor and is inactivated by cigarette smoke.

■ Respiratory infections are a precipitating cause of acute exacerbations of COPD, but it is not known if they contribute to the Progressive airflow limitation that characterizes COPD.

■ α1-Antitrypsin deficiency (p. 174) is a cause of early-onset emphysema.

Clinical features

Symptoms and signs help to distinguish COPD from asthma (Table 11.4). The characteristic symptoms of COPD are cough with the production of sputum, wheeze and breathlessness following many years of a smoker's cough. Frequent infective exacerbations occur, giving purulent sputum. On examina-tion the patient with severe disease is breathless at rest, with prolonged expiration, chest expansion is poor and the lungs are hyperinflated (loss of

Table 11.4 Differentiating features of COPD and asthma



Smoker or ex-smoker



Symptoms under age 35



Atopic features (rhinitis, eczema)



Cellular iníiltrate

Macrophages, neutrophils, CD8+ T cells

Eosinophils, CD4+ T cells

Cough and sputum




Persistent and Progressive


Night-time symptoms



Signiíicant diurnal or day-to-day variability of symptoms



Bronchodilator response (FEV1 & PEFR)



Corticosteroid response



Fig. 11.2 Some clinical signs in a patient with COPD.

normal cardiac and liver dullness, ‘barrel-shaped chest, protruding abdomen). Pursed lips on expiration help to prevent alveolar and airway collapse. Use of the accessory muscles of respiration (scalene and sternocleidomastoid) reflect the increased work of breathing (Fig. 11.2). There may be a wheeze or quiet breath sounds. In ‘pink puffers' breathlessness is the predominant problem; they are not cyanosed. ‘Blue bloaters' hypoventilate; they are cyanosed, may be oedematous and have features of CO2 retention (warm peripheries with a bounding pulse, flapping tremor of the outstretched hands and confusion in severe cases).

In addition to pulmonary manifestations, patients with COPD develop sys-temic problems, including skeletal muscle dysfunction (loss of muscle bulk and skeletal muscle strength), nutritional abnormalities, weight loss, and depression. Skeletal muscle dysfunction is due to a combination of factors (aging, malnutrition, systemic inflammation, inactivity, hypoxia) and affects both respiratory and limb muscles. It contributes to reduced exercise toler-ance independently of the reduced lung function.


■ Respiratory failure (p. 582)

■ Cor pulmonale, i.e. heart disease secondary to disease of the lung (p. 471).


The diagnosis is made on the basis of history (breathlessness and sputum production in a lifetime smoker), physical examination and confirmation of airflow limitation with lung function testing:

■ Lung function tests show Progressive airflow limitation with increasing disease severity and breathlessness (Table 11.5). Some patients have partially reversible airflow limitation with an increase in FEV1 (but usually < 15%) following inhalation of a β2-agonist. Serial peak flow measure-ments may be necessary to exclude asthma (Table 11.4). Additional testing of lung function is necessary if there is diagnostic uncertainty. Lung volumes are normal or increased, and the loss of alveoli with emphysema results in a decreased gas transfer coefficient of carbon monoxide.

■ Chest X-ray may be normal or show evidence of hyperinflated lungs indicated by low, flattened diaphragms and a long narrow heart shadow. There are reduced peripheral lung markings and bullae (complete destruction of lung tissue producing an airspace greater than 1 cm).

■ High resolution CT scans are used, particularly to show emphysematous bullae.

■ Haemoglobin and PCV may be high as a result of persistent hypoxaemia and secondary polycythaemia (p. 217).

■ Arterìal blood gases may be normal or show hypoxia ± hypercapnia in advanced cases.

Table 11.5 Classification of severity (GOLD criteria)

Stage of COPD



Stage I, Mild

FEV1/FVC < 70%
FEV1 ≥ 80% predicted

Chronic cough, none/ mild breathlessness

Stage II, Moderate

FEV1/FVC < 70%
50% ≤ FEV1< 80% predicted

Breathlessness on exertion

Stage III, Severe

FEVi/FVC < 70%
30% ≤ FEV1< 50% predicted

Breathless on minimal exertion. May be weight loss and depression

Stage IV, Very severe

FEV1/FVC < 70%
FEV1 < 30% predicted or
FEV1 < 50% predicted plus respiratory failure

Breathless at rest

(Modiíled from the Global Strategy for the Diagnosis, Management and Prevention of COPD,

■ α1-Antitrypsin serum levels and genotype are measured in early onset disease (<40 years) or family history.

■ ECG and echocardiography is used to assess cardiac status if clinical features of cor pulmonale (p. 471).


COPD care should be delivered by a multidisciplinary team to include GP and respiratory physicians, respiratory nurse specialists, physiotherapy, occupa-tional therapy, dietetics and palliative care in end-stage COPD.

Cessation of smoking It is essential to persuade the patient to stop smoking (p. 520). This may slow the rate of deterioration.

Bronchodilators A stepwise approach to drug therapy is used similar to that used in asthma (p. 526). Inhaled (with spacer device if necessary) tio-tropium bromide, a long-acting once-daily antimuscarinic agent, is used as initial maintenance therapy with a rescue short-acting β2-agonist (p. 564) to prevent or reduce acute symptoms. A long-acting β2-agonist is added in patients with persistent dyspnoea. Dry powder inhalers are simpler to use than metered dose inhalers but technique still needs to be checked. Neb-ulized therapy may be useful for patients with disabling breathlessness despite inhalers.

Corticosteroids Assessment of reversibility is made with a 2-week course of oral prednisolone (30 mg daily), with measurement of lung function before and after the treatment period. If there is objective evidence of benefit (>15% improvement in FEV1), oral steroids are gradually reduced and replaced with inhaled corticosteroids.

Prevention of infection Acute exacerbations of COPD are commonly due to bacterial or viral infection. Patients should receive pneumococcal vaccine and annual influenza vaccination and receive prompt antibiotic treatment for acute exacerbations.

Oxygen Long-term domiciliary oxygen therapy is provided by oxygen concentrators and has a survival benefit in selected groups of patients:

■ PaO2 < 7.3 kPa when breathing room air

■ PaP2 < 8.0 kPa with secondary polycythaemia, nocturnal hypoxaemia, peripheral oedema or evidence of pulmonary hypertension.

Assessment for home oxygen should include blood gas measurements made 3 weeks apart in a stable patient receiving bronchodilator treatment. It is prescribed to patients who no longer smoke (supported by a carboxyhaemo-globin concentration < 3%). Oxygen is given for 19 hours per day (every day) at a flow rate of 1-3 L/min via nasal prongs to increase arterial oxygen satu-ration to >90%.

Additional treatments include mucolytics to reduce sputum viscosity, venesection for polycythaemia, diuretics for oedema, exercise training to improve sense of well-being and breathlessness, and high-calorie dietary supplements in those with low BMI. Surgery is beneficial for a minority of patients: bullectomy for patients with large emphysematous bullae and lung volume reduction surgery for selected patients with severe COPD

(FeV1 < 1 L).

Acute exacerbation of COPD

Diagnosis is made on the basis of increased breathlessness or an increase in sputum volume or purulence. The major complication is respiratory failure. Exacerbations are usually the result of a superimposed viral or bacterial respiratory tract infection and are investigated and treated in a similar manner to asthma but with some essential modifications (see below) (p. 533). Some patients with mild exacerbations may be managed at home by a dedicated multidisciplinary team (including nurses, physiotherapists and occupational therapists). Management of patients admitted to hospital:

■ Controlled oxygen is given with the aim of maintaining SaO2 > 88-92% and PaO2 > 8 kPa without increasing PaCO2. These patients often depend on a degree of hypoxaemia to maintain respiratory drive and therefore, if oxygen is necessary, low concentrations (24%) are given via a Venturi mask (fixed oxygen concentration mask), so as not to reduce respiratory drive and precipitate worsening hypercapnia and respiratory acidosis. The oxygen concentration is increased in increments (28% and then 35%) if clinical examination and arterial blood gases (repeated at 30-60 minute intervals) do not show hypoventilation, carbon dioxide retention and wors-ening acidosis.

■ Bronchodilators (salbutamol and ipratropium bromide) are given 4-6 hourly together with oral prednisolone 40 mg. In the presence of type 2 respiratory failure, nebulizers should be air driven and controlled oxygen given by nasal cannulae simultaneously.

■ Antibiotics, e.g. cefaclor or co-amoxiclav, are given if there is a history of more purulent sputum production or with chest X-ray changes. Patients should be encouraged to cough up sputum, initially with the help of a physiotherapist. Antibiotic treatment is modified depending on sputum culture results.

■ Aminophylline use is controversial because of its modest benefits and high incidence of side-effects. It is used for patients with moderate to severe exacerbations who are not responding to standard treatment as above. It is given intravenously with cardiac monitoring as a loading dose (5 mg/kg over 20 minutes) and then maintenance of 0.5 mg/kg/hour. Plasma theophylline levels are measured daily to maintain concentration of 10-20 mg/L (55-110 μmol/L). In patients already taking oral theo-phylline omit the loading dose and check plasma levels before starting the maintenance infusion.

■ Patients with life-threatening respiratory failure require ventilatory assist-ance. Bilevel positive airway pressure (BiPAP, p. 584) avoids the need for intubation and mechanical ventilation in some patients. It is indicated in patients with signs of worsening respiratory distress (respiratory rate > 30/min) and respiratory acidosis (blood pH < 7.35, PaCO2 > 6 kPa) who have failed to respond to optimal medical treatment and controlled oxygen.

■ Low molecular weight heparin is given to prevent thromboembolism.

■ Respiratory stimulants are rarely used due to the increasing availability of non-invasive ventilatory support. Doxapram, 1.5-4.0 mg/min by slow i.v. infusion, may help in the short term to arouse the patient and to stimulate coughing, with clearance of some secretions.

■ Exacerbations of COPD are occasionally the result of pneumothorax, heart failure or pulmonary embolism, and these must be excluded.

Long term prognosis

This is assessed by the BODE predictive index (body mass index, degree of airflow obstruction - FEV1, dyspnoea, exercise capacity). In the most severe category, a patient with BMI < 21, FEV1 < 35% predicted, shortness of breath on dressing, and walking distance < 149 m in 6 minutes has a mortality rate of 80% at 4 years.

Obstructive sleep apnoea (OSA)

There is repeated apnoea (cessation of breathing for 10 seconds or more) as a result of obstruction of the upper airway during sleep. It affects about 2% of the population and is most common in overweight middle-aged men. It can also occur in children, particularly those with enlarged tonsils.


Apnoea occurs if the upper airway at the back of the throat is sucked closed when the patient breathes in. This occurs during sleep because the muscles that hold the airway open are hypotonic. Airway closure continues until the patient is woken up by the struggle to breathe against a blocked throat. These awakenings are so brief that the patient remains unaware of them but may be woken hundreds of times at night leading to sleep deprivation and daytime sleepiness. Contributing factors include alcohol ingestion before sleep, obesity and COPD. It is more common in patients with hypothyroidism and acromegaly.

Clinical features

Loud snoring and excessive daytime sleepiness (leading to impairment of work performance and driving) occur in the majority of patients. Apnoeas may be witnessed by bed partners. Other symptoms are irritability, personal-ity change, morning headaches, impotence and nocturnal choking. Patients with OSA have an increased risk of hypertension, heart failure, myocardial infarction and stroke.


The Epworth sleepiness scale is a simple tool that helps discriminate OSA from simple snoring. The patient is asked how likely, or not, they would be to fall asleep in eight specified situations - watching television, and sitting and talking to someone are two examples. A high score equates with signifi-cant excess sleepiness. Frequent falls in arterial oxygen saturation during sleep (measured by oximetry at home) may confirm the diagnosis. If this is normal or equivocal inpatient sleep studies are indicated. This usually involves oximetry supplemented by video-recording in a room specifically adapted for sleep studies. The diagnosis of sleep apnoea/hypopnoea is confirmed if there are more than 15 apnoeas or hypopnoeas in any 1 hour of sleep.


■ Weight loss, removal of markedly enlarged tonsils and correction of facial deformities may help.

■ CPAP (continuous positive airway pressure, p. 584) to the airway via a tight-fitting nasal mask - nasal CPAP - during sleep keeps the pharyngeal walls open and is an effective treatment.


Bronchiectasis is abnormal and permanent dilatation of the central and medium-sized airways. This in turn leads to impaired clearance of bronchial secretions with secondary bacterial infection and bronchial inflammation. It may be localized to a lobe or generalized throughout the bronchial tree.


Cystic fibrosis and post-infectious (bronchial damage following pneumonia, whooping cough, TB) are the common causes. Many cases are idiopathic. Rarer causes are immunodeficiency (AIDS and immunoglobulin deficiency), congenital ciliary defect (e.g. Kartagener's syndrome: immotile cilia, situs invertus, chronic sinusitis) and airway obstruction (e.g. inhaled foreign body).

Clinical features

There is usually a history of a chronic productive cough and recurrent chest infections. In severe disease there is production of copious amounts of thick, foul-smelling green sputum. Other symptoms are haemoptysis (which may be massive and life-threatening), breathlessness and wheeze. On examination there is clubbing and coarse crackles over the affected area, usually the lung bases.


■ Chest X-ray may be normal or show dilated bronchi with thickened bronchial walls, and sometimes multiple cysts containing fluid.

■ High-resolution CT scanning (p. 510) is the gold standard for diagnosis. It shows airway dilatation, bronchial wall thickening and bronchial wall cysts that are not shown on a standard chest X-ray.

■ Sputum culture is essential during an infective exacerbation. The common organisms are Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae.

■ Further investigations, e.g. serum immunoglobulins, sweat test (p. 525), in patients where an underlying cause is suspected.


Patients should be advised on smoking cessation (p. 512) and physiotherapy techniques to improve sputum clearance. They should receive annual influ-enza vaccination, pneumococcal vaccination and prompt antibiotic treatment for exacerbations:

■ Respiratory physiotherapy promotes mucociliary clearance and sputum production. Techniques are the active cycle of breathing technique (ACBT), postural drainage and chest percussion.

■ Antibiotics are given to patients presenting with increased cough, sputum production or purulence. In mild cases intermittent chemotherapy with cefaclor 500 mg three times daily may be the only therapy needed. Flucloxacillin is the best treatment if Staph. aureus is isolated on sputum culture. If the sputum remains yellow or green despite regular physio-therapy and antibiotics it is probable that there is infection with P. aeru-ginosa. Specific antibiotics, e.g. ceftazidime, are required and are administered by aerosol or parenterally. Oral ciprofloxacin is an alterna-tive. Long-term antibiotics are given to patients with frequent exacerbations.

■ Bronchodilators (β2 agonists and/or anticholinergics) may provide symptomatic relief even without an objective improvement in FEV1.

■ Inhaled or oral steroids can decrease the rate of progression.

■ Surgery is reserved for the very small minority with localized disease. Severe disease sometimes requires lung or heart-lung transplantation.


These are listed in Table 11.6.

Table 11.6 Complications of bronchiectasis

Haemoptysis – may be massive
Metastatic cerebral abscess
Respiratory failure

Cystic fibrosis

Cystic fibrosis (CF) is an autosomal recessive condition occurring in 1 : 2000 live births in the UK. It is much less common in Afro-Caribbean and Asian people. It is caused by mutations in a single gene on chromosome 7 that encodes the CF transmembrane conductance regulator (CFTR) protein, a chloride channel and regulatory protein found in epithelial cell membranes in the lungs, pancreas, gastrointestinal and reproductive tract. The most common mutation is ΔF508 (deletion, phenylalanine at position 508). Deranged transport of chloride and/or other CFTR-affected ions, such as sodium and bicarbonate, leads to an alteration in the viscosity and tenacity of mucus produced at these epithelial surfaces and to increased salt content in sweat gland secretions.

Clinical features

Although the lungs of babies born with CF are structurally normal at birth, frequent respiratory infections soon develop and are the presenting feature. The resultant inflammatory response damages the airway, leading to Progressive bronchiectasis, airflow limitation and eventually respiratory failure. Finger clubbing is present in most patients particularly with more advanced disease. Sinusitis and nasal PolyPs occur in most Patients. In the newborn, thick tenacious intestinal secretions cause small bowel obstruction (meco-nium ileus), an early manifestation of CF. Meconium ileus equivalent syn-drome presents in later life with small bowel obstruction. There may be steatorrhoea and diabetes mellitus as a result of pancreatic insufficiency. Males are infertile because of failure of develoPment of the vas deferens. Chronic ill-health in children leads to imPaired growth and delayed Puberty. Many Patients are undernourished.


Evaulation for CF is indicated in Patients with suggestive symPtoms or signs, or a sibling with the disease:

■ Sweat sodium measurement is the initial investigation. This must be performed in a laboratory regularly undertaking testing. A value ≥ 60 mmol/L is diagnostic. Lower values but above the normal range still require DNA analysis

■ Blood DNA analysis of the gene defect

■ Radiology showing features of CF.

Genetic screening for the carrier state together with counselling should be offered to persons or couples with a family history of CF.


Management of bronchiectasis and exocrine pancreatic insufficiency is described on pages 190 and 524. Lung damage associated with persistent infection with P. aeruginosa is a major cause of morbidity and mortality in patients with CF. Nebulized anti-pseudomonal antibiotic therapy, e.g. tobramycin, improves lung function, slows the rate of respiratory decline and decreases the risk of infective exacerbations and hospitalization in these patients. Regular sputum culture for Pseudomonas allows early detection and treatment. Inhalation of recombinant DNAase (donase alfa) improves FEV1. Some patients with severe respiratory disease have received lung or heart-lung transplantations.


Ninety per cent of children now survive into their teens and the median survival for those born after 1990 is about 40 years. Most mortality is the result of pulmonary disease. A major problem is sputum infection with Burkholderia cepacia. It is associated with accelerated lung disease and resistance to antibiotics in some strains. Close contact promotes cross-infection, so siblings and fellow sufferers with CF may pass the organism from one to another.


Asthma is a common chronic inflammatory condition of the lung airways the cause of which is incompletely understood. It has three characteristics: airflow limitation, airway hyperresponsiveness to a range of stimuli, and inflammation of the bronchi. Airflow limitation is usually reversible, either spontaneously or with treatment; in chronic asthma it may be irreversible as a result of airway wall remodeling and mucus impaction.


The prevalence of asthma is increasing, particularly in the second decade of life, when 10-15% of the population is affected. Asthma is more common in developed countries (particularly the UK, Australia and New Zealand) than Far Eastern countries and Eastern Europe.


Asthma is classified as:

■ Extrinsic (atopic) - allergens can be identified by positive skin-prick reac-tions to common inhaled allergens, e,g, dust mite, pollens and fungi. In adults sensitization to chemicals or biological Products in the workplace may be the cause.

■ Intrinsic often starts in middle age and no definite external cause can be identified. However, many patients do show a degree of atopy and on close questioning give a history of respiratory symptoms consistent with childhood asthma.


Two major factors are involved in the development of asthma:

■ Atopy is the term used in individuals who readily develop immunoglobulin E (IgE) antibodies against common environmental antigens such as the house-dust mite, grass pollen and fungal spores from Aspergillus fumiga-tus. Genetic and environmental factors affect serum IgE levels. Included in the genetic influence is the interleukin-4 (IL-4) gene cluster on chromo-some 5 which Controls the production of the cytokines, IL-3, IL-4, IL-5 and IL-13 which in turn affect mast and eosinophil cell development and longevity, and IgE production. Environmental factors include childhood exposure to allergens and maternal smoking, and intestinal bacterial and childhood infections. Growing up in a relatively clean environment may predispose towards an IgE response to allergens.

■ Increased responsiveness of the airways of the lung to stimuli such as inhaled histamine and methacholine (bronchial provocation tests, see below).


The primary abnormality in asthma is narrowing of the airway, which is due to smooth muscle contraction, thickening of the airway wall by cellular infiltration and inflammation, and the presence of secretions within the airway lumen. The pathogenesis of asthma is complex and not fully understood. It involves a number of cells, mediators, nerves and vascular leakage which can be activated by several mechanisms, of which exposure to allergens is the most relevant.

Intlammation Mast cells, eosinophils, T lymphocytes and dentritic cells are increased in the bronchial wall, mucous membranes and secretions of asthmatics. Dentritic cells may play a role in the initial uptake and pres-entation of allergens to lymphocytes, predominantly of the T-helper 2 (Th2) phenotype. These lymphocytes, when stimulated by the appropriate antigen, release a restricted panel of cytokines (IL-3, IL-4, IL-5, IL-9 and IL-13, GM-CSF), which play a part in the migration and activation of mast cells and eosinophils. In addition, production of IL-4 and IL-13 helps maintain the Proallergic Th2 PhenotyPe, favouring switching of antibody Production by B lymphocytes to IgE. These IgE molecules attach to mast cells via high-affinity recePtors which in turn release a number of Powerful mediators acting on smooth muscle and small blood vessels, such as histamine, tryPtase, Pros-taglandin D2 and leukotriene C4, which cause the immediate asthmatic reac-tion. Activation of eosinophils, by IgE binding, leads to release of a variety of mediators, such as eosinoPhilic cationic Protein, which are Predominantly toxic to airway cells.

Remodelling Airway smooth muscle undergoes hypertrophy and hyper-Plasia leading to a larger fraction of the wall being occuPied by smooth muscle tissue. The airway wall is further thickened by deposition of repair collagens and matrix Proteins below the basement membrane. The airway epithelium is damaged, with loss of the ciliated columnar cells into the lumen. The ePithelium undergoes metaPlasia with an increase in the number of mucus-secreting goblet cells.

Precipitating factors

The major allergen is the house dust mite and its faeces. Non-specific factors causing wheezing are viral infections, cold air, exercise, irritant dusts, vaPours and fumes (cigarette smoke, Perfume, exhaust fumes), emotion and drugs (NSAIDs, aspirin and p-blockers).

Over 250 materials encountered at the workplace give rise to occuPational asthma, which tyPically imProves on days away from work and during holidays. Common occuPations associated with asthma are veterinary medicine and animal handling (allergens from mouse, rat and rabbit urine and fur), bakery (wheat, rye) and laundry work (biological enzymes).

A rare cause of asthma is the airborne spores of Aspergillus fumigatus, a soil mould. There are fleeting shadows on the chest X-ray and peripheral blood eosinoPhilia (allergic bronchoPulmonary asPergillosis), not to be confused with the severe asPergillus Pneumonia occurring in the immunocomPromised.

Clinical features

The principal symptoms of asthma are wheezing attacks, shortness of breath, chest tightness and cough (may be the only symptom). Symptoms tend to be intermittent, worse at night and in the early morning and provoked by triggers as above. Some patients have just one or two attacks a year, whereas others have chronic symptoms. On examination, during an attack, there is reduced chest expansion, prolonged expiratory time and bilateral expiratory poly-Phonic wheezes.


The diagnosis of asthma is made on the history and evidence of airflow obstruction (by spirometry or PEF) when symptomatic. There is no single satisfactory diagnostic test for all asthmatic patients:

■ Demonstration of variable (at least 15%) airflow limitation by measure-ment of PEFR or FEV1:

■ Measurement of PEFR by the patient on waking, during the day and before bed - most asthmatic individuals will show obvious diurnal variation, with lowest values occurring in the early morning (the ‘morning dip', Fig. 11.3)

■ An increase after inhalation of a bronchodilator, e.g. salbutamol

■ A decrease after 6 minutes of exercise, e.g. running.

■ Histamine or methacholine challenge in difficult cases. Bronchial hyper-reactivity is demonstrated by asking the patient to inhale gradually increasing doses of histamine or methacholine and demonstrating a fall in FEV1. The test should not be períormed on individuals who have poor lung function (FEV1 < 1.5 L) or a history of ‘brittle' asthma.

■ Skin-prick tests should be períormed in all cases of asthma to help identify allergic causes. A weal develops 15 minutes after allergen injec-tion in the epidermis of the forearm. Measurement of allergen-specific IgE in the serum is also sometimes used.

■ Chest X-ray is períormed during an acute attack (see later) or to identify the pulmonary shadows associated with allergic bronchopulmonary aspergillosis.

Fig. 11.3 Diurnal variability in PEFR in asthma, showing the effect of steroids.The arrows indicate the morning ‘dips’. M, morning; N, noon; E, evening.


The effective management of asthma centres on patient and family educa-tion, antismoking advice (p. 512), the avoidance of precipitating factors and specific drug treatment. Self-management programmes have been incorpo-rated into patient care and involve individualized self-treatment plans based on self-monitoring of PEFR and symptoms and a written action plan showing patients how to act early in exacerbations. Patients should be offered influ-enza immunization.

Avoidance of precipitating factors Patients should be discouraged from smoking and avoid allergens, e.g. household pets, which have been identified as extrinsic causes. Occupational asthma should be identified early because removal of the Patient from exPosure may cure the asthma and continued exPosure may become self PerPetuating even when exPosure ceases. P-Blockers in any form are absolutely contraindicated in patients with asthma. Individuals intolerant of asPirin should avoid all NSAIDs.

Drug treatment Most drugs are delivered directly into the lungs as aero-sols (metered-dose inhaler ± spacer, p. 566) or dry powder inhalers, which means that lower doses can be used and systemic side-effects are reduced comPared to oral treatment. Asthma is managed with a stePwise aPProach which depends partly on repeated measurements of PEFR by the patient (Fig. 11.4). The aim is that the patient starts treatment at the step most appropriate to the initial severity, and when control of symPtoms is achieved, treatment is gradually reduced to the previous step over a period of 1-3 months. The aim of treatment is to have control of the disease, i.e. no day or night symp-toms, no exacerbations, no need for relieving bronchodilators and normal lung function (FEV1 or PEF > 80% predicted):

■ β2-Adrenoceptor agonists (p. 564), e.g. salbutamol, terbutaline and the longer-acting, salmeterol and formoterol, relax bronchial smooth muscle and cause bronchial dilatation.

■ Antimuscarinic bronchodilators (p. 564), e.g. ipratropium bromide or oxitroPium bromide, cause bronchodilatation and may be additive to adrenocePtor stimulants.

■ Corticosteroids are powerful anti-inflammatory agents. Inhaled steroids (p. 568), e.g. beclometasone dipropionate, budesonide and fluticasone ProPionate, are used as maintenance treatment in all but very mild asthmatic individuals. Side-effects of inhaled steroids are oral candidia-sis, hoarseness and rarely cataract formation. Oral steroids are occasion-ally necessary in those Patients not controlled on inhaled steroids. Side-effects are listed on page 665.

■ Anti-inflammatory agents, e.g. sodium cromoglicate, prevent activation of inflammatory cells and may be useful in mild asthma. They are not as effective as inhaled steroids, but are free of side-effects, and thus may have some advantages in children.


• Patient measures PEFR at home to guide treatment.

• Short-acting inhaled β agonist taken at any step as needed for symptom relief.

• A rescue of oral steroids (used for shortest time possible) may be needed at any step.

• Decrease treatment after 1-3 months’ stability

LTRa- Leukotriene receptor antagonist

LABa- inhaled long-acting β2 agonist

Fig. 11.4 The stepwise management of asthma in adults.

■ Cysteinyl leukotriene receptor antagonists (LTRAs), e.g. montelukast and zafirlukast, are given orally. Leukotrienes are inflammatory mediators released by mast cells which cause bronchoconstriction and increased production of mucus. LTRAs are particularly useful in patients who still have symptoms despite taking high-dose inhaled or oral corticosteroids, and in patients with asthma induced by aspirin.

■ Steroid-sparing agents. Methotrexate, ciclosporin, anti-IgE monoclonal antibody (omalizumab), intravenous immunoglobulin and etanecerpt are used occasionally.

Acute severe asthma

This is severe progressive asthmatic symptoms over a number of hours or days. It is a medical emergency that must be recognized and treated imme-diately at home with subsequent transfer to hospital (Emergency Box 11.1). In the UK, 1400 patients die from asthma each year and 90% of these deaths are preventable by correct management.

Clinical features

Patients with acute severe asthma typically have:

■ Inability to complete a sentence in one breath

■ Respiratory rate ≥ 25 breaths/min

■ Heart rate ≥ 110 beats/min

■ PEFR 33-50% of predicted normal or patient’s best.

Life-threatening features are any one of the following in a patient with acute severe asthma:

■ Silent chest, cyanosis or feeble respiratory effort

■ Exhaustion, altered conscious level

■ Bradycardia or hypotension

■ PEFR < 33% of predicted or best

■ PaO2 < 8 kPa.

Near fatal asthma is PaCO2 > 6 kPa, and a low or falling arterial pH.

The management of acute severe asthma is shown in Emergency Box 11.1. Patients with moderate asthma (defined as increasing symptoms, PEFR 50-75%, no features of acute severe asthma) who present to hospital are treated with a nebulized β-agonist. Provided they improve and are then stable for at least 1 hour, they may be discharged with oral prednisolone 40 mg daily for 1 week.


Pneumonia is defined as an inflammation of the substance of the lungs and is usually caused by bacteria. Pneumonia can be classified both anatomically,

Emergency Box 11.1
Management of acute severe asthma in hospital
Initial treatment
• Oxygen therapy to maintain oxygen saturation (SpO2) 94–98%.
• Nebulized salbutamol 5 mg or terbutaline 10 mg with oxygen as the driving gas.
• Hydrocortisone 200 mg intravenously.
• Antibiotics if evidence of infection: focal shadowing on the chest X-ray, purulent sputum.
• Fluids, aim for 2.5–3 L/day, intravenously if necessary.
• Chest X-ray to exclude pneumothorax or pneumonia.
• Pulse oximetry (continuous).
• Arterial blood gases if SpO2 < 92%. May need repeat depending
on response.
• PEFR before and after initial treatment.
• Urea and electrolytes – steroids and salbutamol may result in
If improved – continue
Oxygen therapy.
Prednisolone oral, 40–50 mg for 7 days.
Nebulized β2-agonist 4-hourly
After 24 hours
Add in high-dose inhaled corticosteroid
Change nebulized to inhaled β2-agonist
Life-threatening features present or poor response to treatment
Oxygen therapy.
Hydrocortisone 200 mg i.v. 4-hourly.
Nebulized β2-agonist every 10–20 min.
Add nebulized ipratropium bromide 0.5 mg 4-6-hourly.
Magnesium sulphate 1.2–2 g i.v. over 20 min.
If no improvement give:
Salbutamol 3–20 μg/min (5 mg salbutamol in 500 mL 0.9% saline or 5% dextrose, infuse
at 0.3–2 mL/min)
Inform ITU of possible admission for intubation and mechanical ventilation.
Discharge from hospital when:
• Free of SOB or wheeze
• PEFR > 75% predicted & diurnal variability < 25%
• Stable on discharge treatment for 24 h
Before discharge: check inhaler technique, determine reason for exacerbation and issue a written asthma plan discussed with patient.

e.g. lobar (affecting the whole of one lobe) and bronchopneumonia (affecting the lobules and bronchi), or on the basis of aetiology (Table 11.7). Myco-bacterium tuberculosis is a cause of pneumonia and is considered separately, as both mode of Presentation and treatment are different from the other Pneumonias. In about 25% of Patients no organism is isolated. Pneumonia may also result from chemical causes (e.g. aspiration of vomit) and radiotheraPy.

Clinical features

Symptoms and signs vary according to the infecting agent and to the immune state of the patient. Most commonly there is pyrexia, combined with respira-tory symptoms such as cough, sputum production, pleurisy and dyspnoea. Signs of consolidation and a Pleural rub may be Present. There may be a pleural effusion. Elderly patients often have fewer symptoms than younger

Table 11.7 The aetiology of pneumonia in the UK

Infecting agent

Clinical circumstances

Streptococcus pneumonia

Community pneumonia patients usually previously fit

Mycoplasma pneumonia

As above

Influenza A virus (usually with a bacterial component)

As above

Haemophilus influenza

Pre-existing lung disease: COPD

Chlamydia pneumonia

Community-acquired pneumonia

Chlmydia psittaci

Contact with birds (though not inevitable)

Staphylococcus aureus

Children, intravenous drug abusers, associated with influenza virus infections

Legionella pneumophila

nstitutional outbreaks (hospitals and hotels), sporadic, endemic

Coxiella burnetii

Abattoir and animal-hide workers

Pseudomonas aeruginosa

Cystic íibrosis

Enteric Gram-negative bacilli

Pneumocystis jiroveci
Actinomyces israelii
Nocardia asteroids
Aspergillus fumigates

Immunosuppressed (AIDS, lymphomas,
leukaemias, use of cytotoxic drugs and

NB Causes vay in different countries. Streptococcus pneumonia accounts for 35-80% of cases in the UK.

patients or may present with a confusional state. The severity of community-acquired pneumonia is assessed by clinical and laboratory criteria (Table 11.8). Precipitating factors for pneumonia are underlying lung disease, smoking, alcohol abuse, immunosuppression and other chronic illnesses. The clinical history should enquire about contact with birds (possible psittacosis), and farm animals (Coxiella burnetìi, causative organism of Q fever), recent stays in large hotels or institutions (Legionella pneumophila), chronic alcohol abuse (M. tuberculosis, anaerobic organisms), intravenous drug abuse (Staph. aureus, M. tuberculosis) and contact with other patients with pneumonia.


Many otherwise fit patients with mild (Table 11.8) community-acquired pneu-monia are treated as outpatients and the only investigation needed is a chest X-ray. Patients admitted to hospital require investigations to identify the cause and severity of the pneumonia:

■ Chest X-ray confirms the area of consolidation, but these changes may lag behind the clinical course (Fig 11.5). The chest X-ray is repeated at 6 weeks after the acute illness and any persisting abnormalities suggest a bronchial abnormality usually a carcinoma. The chest X-ray is repeated more frequently if the acute illness is not responding to treatment.

Table 11.8 Diagnosis of severe community-acquired pneumonia using CURB-65 and other criteria
Score 1 (maximum score = 6) for each of:
 Confusion – new disorientation in person, place or time
 Urea >7 mmol/L
 Respiratory rate ≥ 30/min
 Blood pressure
Systolic <90
Diastolic ≤ 60 mmHg)
 Age > 65 years
Score 0–1 – Treat as outpatient
Score 2 – Admit to hospital
Score ≥ 3 (severe pneumonia) – often require ITU care
Other markers of severe pneumonia
 Chest X-ray – more than one lobe involved
 PaO2 <8 kPa
 Low albumin (<35 g/L)
 White cell count (<4 × 109/L or >20 × 109/L)
 Blood culture – positive

Fig. 11.5 Chest X-ray showing lobar pneumonia. There is an ill-defined area of opacity in the left lower zone without loss of volume (i.e. no shift of structures such as the mediastinum or trachea). The opacity is caused by the filling of alveolar spaces with fluid instead of air.

■ Sputum for Gram stain, culture and sensitivity tests.

■ Blood tests. A white cell count above 15 X 109/L suggests bacterial infec-tion. There may be lymphopenia with Legionella pneumonia. Marked red cell agglutination on the blood film suggests the presence of cold agglu-tinins (immunoglobulins that agglutinate reds cells at 4°C), which are raised in 50% of patients with Mycoplasma pneumonia. Liver biochem-istry may be non-specifically abnormal and serum electrolytes may show a raised urea and hyponatraemia. Blood cultures are also taken.

■ Serology. Some organisms, e.g. mycoplasma, causing pneumonia can be diagnosed by detection of a raised IgM antibody by immunofluorescent tests or by a fourfold rise in antibody titre from blood taken early in the clinical course and 10-14 days later.

■ Arterial blood gases. Pao2 < 8 kPa or rising Paco2 indicates severe pneumonia.

■ Urine is sent for legionella and pneumococcal antigen testing in patients with indicators of severe pneumonia (Table 11.8).

Differential diagnosis

This includes pulmonary embolism, pulmonary oedema, pulmonary haemor-rhage, bronchial carcinoma, hypersensitivity pneumonitis and some types of diffuse parenchymal lung disease with acute onset.


Antibiotic treatment of community-acquired pneumonia is summarized in Figure 11.6. In addition, pleuritic pain requires analgesia, and humidified oxygen is given if there is hypoxaemia. Fluids are encouraged, to avoid dehydration. Physiotherapy is needed to help and encourage the patient to cough. Patients with severe pneumonia should be assessed for management on the intensive care unit. Hospital-acquired (nosocomial) pneumonia is often due to infection with Gram-negative organisms and treatment is with co-amoxiclav 500 mg three times daily or in more severe cases a second generation cephalosporin, e.g. cefuroxime and an aminoglycoside (e.g. gen-tamicin). Metronidazole is added in patients at risk of anaerobic infection, e.g. prolonged ITU stay or aspiration in a comatose patient. Antibiotic treat-ment in all cases is adjusted on the basis of the results of sputum microscopy and culture.


Complications of pneumonia include lung abscess (p. 540) and empyema (p. 540).

Specific forms of pneumonia

Mycoplasma pneumoniae commonly presents in young adults with gener-alized features such as headaches and malaise, which may precede chest symptoms by 1-5 days. Physical signs in the chest may be scanty, and chest X-ray appearances frequently do not correlate with the clinical state of the patient. Treatment is with macrolides, e.g. erythromycin 500 mg four times daily (or clarithromycin or azithromycin) for 7-10 days. Extrapulmonary com-plications (myocarditis, erythema multiforme, haemolytic anaemia and meningoencephalitis) will occasionally dominate the clinical picture.

Haemophilus influenzae is commonly the cause of pneumonia in patients with COPD. There are no other features to differentiate it from other causes of bacterial pneumonia. Treatment is with oral amoxicillin 500 mg three times daily.

Chlamydia Chlamydia pneumoniae accounts for 4-13% of cases of community-acquired pneumonia. Patients with C. psifíaci pneumonia may give a history of contact with infected birds, particularly parrots. Symptoms include malaise, fever, cough and muscular pains, which may be low grade and protracted over many months. Occasionally the presentation mimics

Fig. 11.6 Algorithm for the management of community-acquired pneumonia.

■ Severity of pneumonia is assessed using criteria listed in Table 11.8

■ Fluoroquinolones, e.g. ciprofloxacin, are recommended for those intolerant of penicillins or macrolides

■ Choice of antibiotics may be narrowed once microbiological results are available

■ Intravenous antibiotics are switched to oral when the patient has been apyrexial for 24 hours and there is no contraindication to oral treatment

■ Antibiotic treatment is usually for a total of 7-10 days.

meningitis, with a high fever, prostration, photophobia and neck stiffness. Diagnosis of Chlamydia infection is made by demonstrating a rising serum titre of complement-fixing antibody. C. pneumoniae is distinguished from C. psittaci infection by type-specific immunofluorescence tests. Treatment of Chlamydia infection is with macrolides or tetracycline.

Staphylococcus aureus usually causes pneumonia only after a preced-ing influenza viral illness or in staphylococcal septicaemia (occurs in intra-venous drug users or in patients with central venous catheters). It results in patchy areas of consolidation which can break down to form abscesses that appear as cysts on the chest X-ray. Pneumothorax, effusions and empyemas are frequent, and septicaemia may develop with metastatic abscesses in other organs. All patients with this form of pneumonia are extremely ill and the mortality rate is in excess of 25%. Treatment is with intravenous flucloxacillin.

Legionella pneumophila is acquired by the inhalation of aerosols or microaspiration of infected water containing legionella. Infection is linked to contamination of water distribution systems in hotels, hospitals and work-places and may also occur sporadically and in the immunosuppressed. Pneu-monia tends to be more severe than with most other pathogens associated with community-acquired pneumonia.

A strong presumptive diagnosis of L. pneumophila infection is possible in the majority of patients if they have three of the four following features:

■ A prodromal virus-like illness

■ A dry cough, confusion or diarrhoea

■ Lymphopenia without marked leucocytosis

■ Hyponatraemia.

Diagnosis is by specific antigen detection in the urine or by direct fluorescent antibody staining of the organism in the pleural fluid, sputum or bronchial washings. Treatment is with clarithromycin, ciprofloxacin or rifampicin for 14-21 days.

Pseudomonas aeruginosa is seen in the immunocompromised and in patients with CF, in whom its presence is associated with a worsening of the clinical condition and increasing mortality. Treatment includes intravenous ceftazidime, ciprofloxacin, tobramycin or ticarcillin. Inhaled tobramycin is used in CF patients (p. 526).

Pneumocystis jiroveci is the most common opportunistic infection in patients with untreated AIDS. The clinical features and treatment of this and other opportunistic infection are described on page 51.

Aspiration pneumonia Aspiration of gastric contents into the lungs can produce a severe destructive pneumonia as a result of the corrosive effect of gastric acid - Mendelson's syndrome. Aspiration usually occurs into the posterior segment of the right lower lobe because of the bronchial anatomy. It is associated with periods of impaired consciousness, structural abnormali-ties, such as tracheo-oesophageal fistulae or oesophageal strictures, and bulbar palsy. Infection is often due to anaerobes, and treatment must include metronidazole.

Complications of pneumonia: lung abscess and empyema

A lung abscess results from localized suppuration of the lung associated with cavity formation, often with a fluid level on the chest X-ray. Empyema means the presence of pus in the pleural cavity, usually from rupture of a lung abscess into the pleural cavity, or from bacterial spread from a severe pneumonia.

A lung abscess develops in the following circumstances:

■ Complicating aspiration pneumonia or bacterial pneumonia caused by Staph. aureus or Klebsiella pneumoniae

■ Secondary to bronchial obstruction by tumour or foreign body

■ From septic emboli from a focus elsewhere (usually Staph. aureus)

■ Secondary to infarction.

Clinical features

Lung abscess presents with persisting or worsening pneumonia, often with the production of copious amounts of foul-smelling sputum. With empyema the patient is usually very ill, with a high fever and neutrophil leucocytosis. There may be malaise, weight loss and clubbing of the digits.


Bacteriological investigation is best conducted on specimens obtained by transtracheal aspiration, bronchoscopy or percutaneous transthoracic aspiration. Bronchoscopy is helpful to exclude carcinomas and foreign bodies.


Antibiotics are given to cover both aerobic and anaerobic organisms. Intra-venous cefuroxime, and metronidazole are given for 5 days, followed by oral cefaclor and metronidazole for several weeks. Empyemas should be treated by prompt tube drainage or rib resection and drainage of the empyema cavity. Abscesses occasionally require surgery.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease

5. Haematological disease

Haematological disease
Assessment and treatment of suspected neutropenic sepsis

6. Malignant disease

Malignant disease

7. Rheumatology

Clinical features, Investigations

8. Water, electrolytes and acid–base balance


9. Renal disease

Renal disease

10. Cardiovascular disease


11. Respiratory disease

Respiratory disease

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease

15. Diabetes mellitus and other disorders of metabolism


16. The special senses


17. Neurology


18. Dermatology