Breathlessness on lying flat occurs in, for example, pulmonary oedema (p. 425). Breathlessness with a wheeze occurring on exposure to an allergen is seen in asthma (e.g. horse riding). It can occur many hours after exposure to an allergen (p. 520) in, for example, hypersensitivity pneumonitis.

Inhalation of foreign bodies can cause choking and acute shortage of breath. Treatment is with the Heimlich manoeuvre. See Emergencies in Medicine p. 714.

Chest pain

Chest pain in respiratory disease is usually pleuritic. Pain can be due to other causes, e.g. localized pain in costochondritis. Shoulder tip pain suggests irritation of the diaphragmatic pleura. Retrosternal soreness occurs with tracheitis but also in other conditions, e.g. oesophagitis, when it is usually burning. Chest pain should always be differentiated from cardiac pain, which is usually a central crushing chest pain radiating to the jaw, neck and left arm (p. 431).

Respiratory investigations

These are discussed under specific diseases.

Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition predominantly caused by smoking and is the sixth commonest cause of death worldwide; its incidence is increasing. It is characterized by airflow limitation, which is not fully reversible. The lungs have an abnormal inflammatory response to inhaled particles or gases, resulting in airflow limitation. The GOLD (Global Initiative for Chronic Obstructive Lung Disease, WHO) criteria for the diagnosis of lung disease are shown in Table 13.1.

Table 13.1 COPD — Global Initiative in Obstructive Lung Disease (GOLD) criteria

Causes

Tobacco smoking, indoor air pollution from biomass fuel and environmental pollution are the major causes for COPD in the world, although only 10–20% of heavy smokers develop COPD.

Pathogenesis

• Inflammation, infection, scarring, loss of elasticity and increased secretion of mucus (which blocks airways) all play a role. There is also an imbalance of protease and antiprotease activity (α₁-antitrypsin being the major antiprotease).

• Small airways are particularly affected early in the process (obstructive bronchiolitis).

• If airway narrowing is combined with emphysema (loss of elastic recoil of the lung with collapse of small airways during expiration), airflow limitation is even more severe.

• Microscopically, there is infiltration of the walls of bronchi and bronchioles by acute and chronic inflammatory cells, with ulceration of epithelial layers leading to squamous metaplasia, scarring and thickening of walls.

• Systemic sequelae including skeletal muscle dysfunction (see below).

Thus, the characteristic physiological effects include airflow limitation and abnormal alveolar gas exchange, leading to cor pulmonale (pulmonary vascular disease).

Clinical features

COPD is suspected on the basis of chronic progressive symptoms, usually with a smoking history of more than 20 pack years (1 pack year = 20 cigarettes per day for 1 year). It is supported by objective evidence of airflow limitation (or obstruction), usually with spirometry, which does not return to normal with treatment.

• Patients are usually over the age of 35, have a risk factor and present with one or more of exertional breathlessness, chronic cough, regular sputum production, frequent winter ‘exacerbations/bronchitis’ or wheeze.

• Effort intolerance, ankle swelling and fatigue also occur.

• Chest pain and haemoptysis are uncommon and an alternative diagnosis should be looked for.

• Extrapulmonary features occur, e.g. osteoporosis, depression and metabolic problems leading to weight loss, loss of muscle mass and weakness.

Signs

• In mild COPD, signs are absent, except for a wheeze.

• In more severe COPD, tachypnoea, prolonged expiration, pursed lip breathing, use of accessory muscles and intercostal in-drawing on inspiration are seen. Hypercapnic patients will be vasodilated with a bounding pulse and a coarse flapping tremor of the outstretched hands. Severe hypercapnia causes confusion and progressive drowsiness. Clubbing is not a sign of COPD and should alert the physician to the possibility of bronchiectasis or lung cancer.

• In advanced COPD, patients develop cor pulmonale.

Pulmonary hypertension/cor pulmonale

Pulmonary hypertension/cor pulmonale (p. 520) is defined as heart disease secondary to disease of the lung. It occurs in hypoxic patients with COPD. Pulmonary hypertension can be present for years without causing symptoms.

Cor pulmonale is enlargement of the right ventricle secondary to increased afterload due to primary lung disease in patients who have no other cause of ventricular dysfunction. Symptoms include worsening exertional dyspnoea, fatigue and chest pain. On examination JVP is raised and there is a right ventricular parasternal heave, a loud pulmonary component of the second heart sound, fluid retention and peripheral oedema.

Diagnosis and investigations

The diagnosis of COPD is usually clinical, supported by the presence of airflow obstruction on spirometry.

Lung function tests

• Spirometry shows evidence of airflow obstruction, with a reduced forced expiratory volume in 1 second (FEV₁) of < 80%, a reduced FEV₁ to forced vital capacity (FVC) ratio of < 70% and a reduced peak expiratory flow rate (PEFR). In COPD reversibility is less than in asthmatic patients (usually a change in FEV₁ of < 15%). Clinically significant COPD is not present if the FEV₁ and FEV₁/FVC ratio return to normal following treatment. FEV₁ determines severity (Table 13.1) and can also be used to monitor the course of the disease and response to therapy. In addition, FEV₁ can be used to test reversibility and is a predictor of mortality. Five-year survival is about 50% when FEV₁ falls to < 1 L.

• Serial home PEF measurements can be useful to exclude asthma. Reversibility to bronchodilators is also helpful in distinguishing patients who have asthma and to aid further management.

Other tests

• Haemoglobin level and packed cell volume (PCV) can be elevated as a result of persistent hypoxaemia causing secondary polycythaemia.

• Arterial blood gases (ABGs) determine the degree of hypoxia and hypercapnia. A baseline should always be taken for assessment of patients in acute exacerbations and will help in assessing the need for long-term oxygen therapy (LTOT).

• Pulse oximetry measures oxyhaemoglobin concentration but remember that it does not give information about the CO₂ (PaCO₂ or arterial carbon dioxide tension) and hence alveolar ventilation.

• CXR can be normal or show hyper-expanded lung fields with low flattened diaphragms and the presence of bullae.

• Sputum culture is usually unnecessary.

• ECG is not necessary in routine assessment of COPD but can show advanced cor pulmonale; it is insensitive.

• Alpha₁-antitrypsin level and phenotype may be helpful (young non-smokers, lower lobe emphysema, a family history of chest problems). The normal range for α₁-antitrypsin is 2–4 g/L.

Management

With the exception of smoking cessation, the aims of COPD treatment are symptomatic relief and the prevention of exacerbations and complications. No existing medication has been shown to modify decline in lung function.

Smoking cessation

This is vital at any age or stage of the disease. An aggressive smoking cessation programme has been shown to reduce the age-related decline in FEV₁, significantly in middle-aged smokers with mild airways obstruction, and also lead to a decrease in cardiovascular and lung cancer mortality. Smokers should be told to stop and an agreed target date set. Nicotine replacement therapy (NRT) or bupropion is given, unless contraindicated, in addition to a support programme to improve the chances of success.

• NRT aims to replace nicotine and thus reduce the craving for a cigarette. Chewing gum 2 mg and 4 mg, transdermal patches 16-hour and 24-hour in varying doses, nasal spray 0.5 mg per spray, inhalational 10 mg inhalation cartridge, sublingual tablets 2 mg and lozenges 1, 2 and 4 mg are available. Nicotine patches should be limited to 3 months’ usage. NRT should be stopped if the patient restarts smoking. Common side-effects are localized reactions, such as skin irritation with patches, and minor sleep disturbances. Contradictions include vascular disease and allergy to the drug; NRT should not be used in pregnancy or breast feeding.

• Bupropion sustained release is a weak, selective inhibitor of the neuronal re-uptake of dopamine and noradrenaline (norepinephrine). The exact mechanism by which it aids smoking cessation is unclear. The dose is 150 mg once a day for 1 week prior to stopping smoking and then 300 mg a day for a further 6–8 weeks, provided the patient abstains from further cigarettes. Side-effects include seizures in about 1 in 1000 patients. Avoid in patients with a previous history of seizures, or a concomitant administration of other medication that lowers the seizure threshold. Other side-effects include hypersensitivity reactions (0.1%), insomnia and dry mouth.

• Combination therapy with NRT or bupropion has so far shown no significant benefit.

• Varenicline is an oral partial agonist on the α₄β₂ subtype of nicotinic acetylcholine receptor. A 12-week course increases the chances of stopping smoking four-fold; its main side-effect is nausea but severe depression has been recorded.

Drug therapy

This is used both for the short-term management of exacerbations and for the long-term relief of symptoms in patients with an FEV₁ < 80% predicted.

Bronchodilator therapy

Inhaler therapy remains the mainstay of treatment, despite the fact that COPD is characterized by irreversible airway obstruction. It causes relaxation of the smooth muscle and thus decreases airway resistance. Patients with mild COPD feel less breathless.

• Inhaler technique. Patients should be taught a good technique for using inhalers; this should be rechecked regularly. COPD patients may have problems in effective coordination and find it hard to use simple metered-dose inhalers (MDIs). This can be improved by offering different types of inhaler and/or a spacer.

• Beta₂-adrenoceptor agonists act directly on the smooth muscle, have a relatively rapid onset of action and can therefore be used for symptomatic relief and prior to exercise. They can be used on an ‘as required’ or a ‘regular’ basis.

• Short-acting β₂-adrenoceptor agonists. Salbutamol is usually given by pressurized aerosol inhalation 100–200 mcg (1–2 puffs) up to 4–6 times a day. Terbutaline is prescribed at a dose of 250–500 mcg (1–2 puffs) up to 3–4 times a day.

• Long-acting β₂-adrenoceptor agonists. These are used in more severe airway limitation (moderate and severe COPD). They include salmeterol 50–100 mcg (2–4 puffs) twice a day and formoterol 12 mcg inhaled twice a day (depending on formulation and severity).

Side-effects include fine tremor, nervous tension, tachycardia, arrhythmias and hypokalaemia.

• Antimuscarinic agents are used for achieving greater and more prolonged bronchodilatation.

• Short-acting antimuscarinics. These cause bronchodilatation by blocking the bronchoconstrictor effects of cholinergic nerves. They have a longer onset of action and a more prolonged and greater bronchodilatory effect than β₂ agonists, and are associated with less toxicity. Ipratropium bromide is given by aerosol inhalation at a dose of 20–40 mcg 3–4 times a day or by nebulized solution 250–500 mcg 3–4 times a day.

• Long-acting antimuscarinics. Inhaled tiotropium 18 mcg once daily improves the duration of bronchodilatation and the frequency of acute exacerbations in patients with moderate to severe COPD.

Side-effects include dry mouth, nausea, constipation, bladder outlet obstruction, exacerbation of acute-angle glaucoma and headache.

In mild disease short-acting β₂ agonists or short-acting antimuscarinic bronchodilators should be prescribed as required. Their effects are additive and once airflow becomes more severe a regular antimuscarinic can be added to a β agonist. Some patients prefer to use just one combined inhaler ipratropium bromide 20 mcg and salbutamol 100 mcg/metered dose 2 puffs 4 times a day.

Patients who remain symptomatic despite being treated with a combination of two short-acting bronchodilators or patients who have two or more exacerbations a year should be prescribed a long-acting bronchodilator and an inhaled corticosteroid should be added (see below).

Objective evidence of improvement in peak flow or FEV₁ may be small and the decision on whether to continue or stop therapy should be based on the patient’s reported symptoms.

Corticosteroids

Corticosteroids are given to patients in the community with increasing shortness of breath that interferes with daily activities. Inhaled corticosteroids are usually reserved for stable COPD, but if already prescribed, should be continued throughout exacerbations.

• Oral corticosteroids The use of corticosteroids in patients with COPD remains contentious but a subgroup of patients respond to these drugs with improvement of lung function. Therefore in symptomatic patients a trial of prednisolone of 30 mg a day for 2 weeks can be given, with spirometry measurements before and after the treatment period. If patients show a response (FEV₁ increases > 15%), prednisolone should be stopped and an inhaled steroid such as beclometasone 400 mcg twice daily started. Regular oral corticosteroids are not recommended, but in advanced COPD, patients may require a maintenance dose when steroids cannot be withdrawn after an exacerbation.

• Inhaled corticosteroids. An inhaled corticosteroid should be given, in addition to a bronchodilator, in patients with an FEV₁ < 50% or with two or more exacerbations a year requiring treatment with antibiotics or oral corticosteroids. In addition, a trial of high-dose inhaled corticosteroid for 3 weeks in patients with moderate airflow obstruction can distinguish those patients who actually have a diagnosis of asthma and not COPD. There are a number of different formulations and inhalers available. The dose varies from 200 mcg to 800 mcg a day.

There are many side-effects associated with corticosteroids (see Box 15.2, p. 585). Inhaled steroids cause considerably fewer systemic side-effects, although at high doses adverse effects have been reported.

Box 13.2 Guidelines for domiciliary oxygen (Royal College of Physicians, 1999)

• Chronic obstructive pulmonary disease with PaO₂ < 7.3 kPa when breathing air during a period of clinical stability

• Chronic obstructive pulmonary disease with PaO₂ 7.3–8 kPa in the presence of secondary polycythaemia, nocturnal hypoxaemia, peripheral oedema or evidence of pulmonary hypertension

• Severe chronic asthma with PaCO₂ < 7.3 kPa or persistent disabling breathlessness

• Diffuse lung disease with PaO₂ < 8 kPa and in patients with PaO₂ > 8 kPa with disabling dyspnoea

• Cystic fibrosis when PaO₂ < 7.3 kPa or if PaO₂ 7.3–8 kPa in the presence of secondary polycythaemia, nocturnal hypoxaemia, pulmonary hypertension or peripheral oedema

• Pulmonary hypertension without parenchymal lung involvement when PaO₂ < 8 kPa

• Neuromuscular or skeletal disorders, after specialist assessment

• Obstructive sleep apnoea despite continuous positive airways pressure therapy, after specialist assessment

• Pulmonary malignancy or other terminal disease with disabling dyspnoea

• Heart failure with daytime PaO₂ < 7.3 kPa (on air) or with nocturnal hypoxaemia

Patients requiring LTOT will need an oxygen concentrator and education regarding its use. They should use the oxygen for at least 15 hours per day or, if possible, 20 hours per day. Once established, they should be reviewed at least once a year by a practitioner familiar with LTOT. They should be warned about the risks of explosion and fire if they continue to smoke. Short-burst oxygen should be reserved for patients with episodes of severe breathlessness that is not relieved by other treatment.

An oxygen alert card stating the oxygen saturation should be given to all patients who have had hypercapnic respiratory failure.

Non-invasive ventilation (NIV)

This is mainly used for exacerbations of COPD — see p. 485. The ventilators are small and can be used at home. Patients should be considered for home NIV if, despite maximal treatment, they have hypercapnic respiratory failure and have required ventilatory support during an exacerbation, or are acidotic or hypercapnic on LTOT.

Diuretic therapy (p. 420)

This is necessary for all oedematous patients. Patients should be weighed daily.

Other agents

• Oral mucolytic drugs. Mucolytics increase the expectoration of sputum by reducing its viscosity. Regular use of mucolytics for at least 2 months can reduce the number of exacerbations of COPD and days of illness. They should be used in patients with a chronic productive cough but only continued if there is continual symptomatic improvement.

• Carbocisteine 2.25 g a day in divided doses, then 1.5 g daily in divided doses. Erdosteine 300 mg twice daily is also used.

• Mecysteine hydrochloride 200 mg 4 times a day for 2 days, followed by 200 mg 3 times a day for 6 weeks, then 200 mg twice daily.

• Anti-oxidants. N-acetylcysteine has both anti-oxidant and mucolytic properties, and has been shown to reduce frequency of exacerbations. However, it and other anti-oxidants, such as α-tocopherol and β-carotene supplements, are currently not recommended.

• Anti-tussives. Regular use of anti-tussive medication is not recommended in COPD, as there is insufficient evidence for its benefit, and although cough is a problematic symptom, it has a protective role.

• Antibiotics

• There is no evidence for the use of prophylactic antibiotics.

• Give antibiotics in acute exacerbations, as they shorten exacerbations and may prevent hospital admission.

• Give the patient a supply of antibiotics to keep at home, to start when sputum turns yellow or green.

• Amoxicillin 500 mg 3 times daily is still effective, although resistance to H. influenzae occurs in 10–20%. Resistance is less frequent to cefaclor 500 mg 8-hourly or cefixime 400 mg once daily; co-amoxiclav is an alternative.

Long-term treatment with antibiotics was thought to be of little value but eradication of infection and keeping the lower respiratory tract free of bacteria may help prevent deterioration in lung function.

• Vaccination/antiviral therapy

• Polyvalent pneumococcal polysaccharide vaccine usually provides lifelong immunity after a single dose.

• Annual influenza vaccination should be given, unless patients have a hypersensitivity to eggs.

• Antiviral agents include zanamivir inhalation of 10 mg twice daily for 5 days and oseltamivir 75 mg 12-hourly for 5 days. They are recommended for the treatment of ‘at-risk’ adults who can start therapy within 48 hours of presenting with an influenza-like illness. For side-effects, see p. 91.

• Antidepressants. These may be helpful in COPD, as mood disturbances such as anxiety and depression are common.

• Alpha₁-protease inhibitor augmentation therapy. Young patients with severe hereditary α₁-antitrypsin deficiency with serum levels < 0.31 g/L and abnormal lung function are candidates for α₁-antitrypsin replacement therapy. There is limited evidence for its benefit in modifying the disease in the long term.

Non-pharmacological interventions

• Physiotherapy. Physiotherapy is helpful for patients with excessive sputum. Patients should be encouraged to cough to remove sputum and taught the active cycle of breathing techniques and how to use positive expiratory pressure masks.

• Nutrition. Weight loss is common in patients with COPD and there is an association between low BMI and increased mortality. Patients with a low BMI should be referred for dietary advice and nutritional supplements. Overweight patients should also be offered dietary advice, as obesity puts additional strain on the cardio-respiratory system.

• Pulmonary rehabilitation. Patients with moderate to severe COPD on optimal medical treatment should be put on a pulmonary rehabilitation programme. The aim is to prevent or reverse the deconditioning that occurs in patients with COPD due to lack of exercise and immobility caused by symptoms. The rehabilitation programme is provided by a multi-disciplinary team and includes physical training, disease education, nutritional advice, and psychological, social and behavioural intervention.

Surgery

Surgical treatment for COPD is associated with a high morbidity and mortality, and patients must be carefully selected and be receiving optimal medical management prior to surgery. Bullectomy, lung volume reduction surgery and lung transplantation are used in severe disease.

Acute exacerbations of COPD (type II respiratory failure)

An acute exacerbation is defined as ‘a sustained worsening of the patient’s symptoms from his or her usual stable state that is beyond normal day-to-day variations, and is acute in onset’.

Exacerbations of COPD are among the commonest acute respiratory problems presenting to primary or secondary care.

• They are usually caused by infection, although only 50% of patients will have a positive sputum culture. The commonest organisms are H. influenzae, Strep. pneumoniae and Moraxella catarrhalis.

• Viruses, including rhinovirus, influenza (including H1N1 swine flu variant), coronavirus, adenovirus and respiratory syncytial virus, account for up to 30% of cases.

• Pollutants may also precipitate an exacerbation.

• Some patients with mild exacerbations can be treated at home, but factors such as acute confusion, a decreased level of consciousness, significant co-morbidities, severe breathlessness and acidosis require hospital admission.

Investigations

• CXR for signs of infection or other pathologies, e.g. pneumothorax or pulmonary oedema.

• Baseline ABGs on room air (or a known inspired oxygen concentration) to look for hypoxia or hypercapnia.

• Purulent sputum for culture.

• ECG to look for a cardiac cause for the deterioration.

• Blood cultures if the patient is pyrexial.

• Routine bloods for FBC and U&E.

Treatment

The treatment of respiratory failure in COPD is shown in Fig. 13.1. General care includes prophylaxis against deep vein thrombosis, optimizing fluid status and ensuring adequate nutrition.

• Controlled oxygen. A fixed performance mask can deliver 24%, 28% and 35% oxygen. It is given to correct hypoxia and maintain oxygen saturations > 90%. In a minority of patients respiratory drive is hypoxic and high oxygen concentrations can result in increasing levels of carbon dioxide, decreasing consciousness, and respiratory acidosis and arrest. Pulse oximetry should always be available to measure oxygen saturations. An ABG is performed on arrival in hospital to monitor CO₂ levels. Oxygen concentrations should never be reduced in patients who are hypoxic, even if CO₂ levels are high.

• Bronchodilators (p. 478). There is no benefit in delivering bronchodilators via a nebulizer over an inhaler in acute exacerbations of COPD. Bronchodilators are, however, given via a nebulizer with a face mask or mouth piece delivering higher doses if patients are too breathless to coordinate the use of an inhaler/spacer. If the patient is hypercapnic, the nebulizer should be driven with air and not oxygen. Oxygen can be given at the same time via nasal cannulae.

• Inhaled β₂ short-acting adrenergic agonists (p. 478). The frequency and dose of inhaled β₂-agonists can be increased in an acute exacerbation. They reach peak activity between 10 and 30 mins, and remain effective for about 4–6 hours. Salbutamol (via inhaler or nebulizer) is the most commonly used. Nebulizers are given at a dose of 2.5–5 mg, usually 4 times daily, although this can be increased provided side-effects are tolerated. Currently, there is no evidence to support the use of IV β₂-agonists in acute exacerbations of COPD.

• Inhaled short-acting antimuscarinics. These agents are often used in combination with inhaled β₂-agonists in acute exacerbations of COPD and are associated with fewer side-effects. They have a less rapid onset of action but a longer duration of action. They can be delivered via an inhaler as ipratropium bromide 20–40 mcg, or via a nebulizer ipratropium bromide 500 mcg, salbutamol 2.5 mg/2.5 mL vial, 1 vial 4 times a day.

• Systemic corticosteroids. These drugs reduce the increased airway inflammation in patients with acute exacerbations of COPD. Short courses of corticosteroids have been shown to reduce FEV₁, improve hypoxia and shorten duration of hospital stay compared to placebo. All patients admitted to hospital with an acute exacerbation should receive a course of oral corticosteroids 30 mg for 7–14 days, in addition to other therapies, provided there are no contraindications. The first dose of corticosteroids can be given intravenously as hydrocortisone or methylprednisolone. If patients do receive a prolonged course of corticosteroids, the dose should be gradually tapered down.

• Antibiotics (p. 482). There is some evidence for a small but significant benefit with antibiotics in acute exacerbations of COPD, especially in those with more severe disease. The use of antibiotics is recommended in patients with a history of increased purulence or production of sputum or in those with consolidation on CXR or clinical signs of pneumonia. Initially, treatment is empirical, with an aminopenicillin, a macrolide or a tetracycline, and then changed when culture results and sensitivities become available. Antibiotic use should be guided by local policy. Commonly used antibiotics include amoxicillin 250–500 mg 3 times daily (15% of Haemophilus strains may be resistant), doxycycline 200 mg then 100 mg daily, or erythromycin 250–500 mg every 6 hours or 0.5–1 g every 12 hours. Ampicillin can be used instead of amoxicillin.

• Methylxanthines. The use of methylxanthines such as theophylline (p. 501) remains controversial, as there is currently no clear evidence of benefit in acute exacerbations of COPD. IV theophylline should only be used in patients refractory to nebulized bronchodilators, and levels should be monitored within 24 hours of treatment and regularly after this period. Patients already taking oral methylxanthines should continue on this medication during an exacerbation and should not receive additional IV methylxanthines. IV methylxanthines are usually prescribed as aminophylline loading dose 5 mg/kg (250–500 mg) over at least 20 mins, followed by 0.5 mg/kg/hour over 24 hours adjusted according to plasma levels. Patients should be closely monitored throughout.

• Respiratory stimulants. These (e.g. Doxapram 1.5–4.0 mg/min) are only recommended for use when NIV is unavailable or considered inappropriate.