13 Respiratory disease

Approach to the patient

• A productive cough is a feature of chronic obstructive pulmonary disease (COPD) or bronchiectasis (large volumes). Yellow sputum does not always indicate infection, as eosinophils in the sputum can give the same appearance, e.g. in asthma. Green sputum usually implies infection.

Haemoptysis should always be investigated. Often, the diagnosis can be made from a CXR, but a normal CXR does not exclude disease. Bronchoscopy is only diagnostic in about 5% of patients with haemoptysis and a normal CXR.

For management of a massive haemoptysis, see Box 13.1.

Treatment of cough is the treatment of the underlying cause and often symptomatic. Anti-tussives include codeine linctus 5–10 mL 3–4 times daily or pholcodine 5 mL 3–4 times daily. There is no evidence that expectorants work but simple linctus 5 mL 3–4 times daily is comforting.

Shortness of breath

Most people get breathless on exertion; exercise tolerance should be documented. Breathlessness can be of sudden onset, e.g. in acute left ventricular failure, or more progressive, as in COPD. It may vary at different times of the day, e.g. in asthma it is usually worse in the morning.

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.

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.

• 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.

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.

Fig. 13.1 Algorithm for the treatment of respiratory failure in chronic obstructive pulmonary disease. BiPAP, bilevel positive airways pressure; CPAP, continuous positive airways pressure; LVF, left ventricular failure; NIV, non-invasive ventilation

(Calvaley & Walter 2008, with permission).

• Non-invasive ventilation (NIV)

This is the treatment of choice in patients with exacerbations of COPD who, despite maximal medical therapy and controlled oxygen therapy, have a persistent respiratory acidosis (pH 7.25–7.35, [H+] 45–56 nmol/L).

A tight-fitting facial mask delivers bi-level positive airway pressure ventilatory support (BiPAP). Continuous positive airway pressure (CPAP, p. 542) is also used. NIV can avoid the need for endotracheal intubation.

• Patients with pH < 7.25 respond less well to NIV and should be referred directly for tracheal intubation or a trial of NIV in an intensive care setting.

• NIV results in a reduced need for endotracheal intubation and thus the associated complications. There is improved acidaemia, a reduction in mortality and a shortening of hospital stay. NIV allows better communication, and nutrition and physiotherapy to continue as normal.

• Contraindications to NIV include impaired consciousness, recent facial or upper airway surgery, facial abnormalities such as burns or trauma, undrained pneumothorax, hypoxaemia, cardiovascular instability, inability to protect the airway, recent gastrointestinal surgery, vomiting and copious respiratory secretions.

• Endotracheal intubation

Endotracheal intubation and mechanical ventilation are used in patients with acidaemia or with persistent or worsening hypoxia despite NIV, and when NIV is contraindicated.

• Mortality in patients with COPD who are intubated for an exacerbation is about 20%.

• Assessment for suitability for intubation and ventilation includes functional status, requirement for oxygen when stable, BMI, co-morbidities, previous admissions to the ICU, FEV₁ and age. Weaning from a ventilator can be difficult and NIV can be used post extubation to shorten weaning time.

• Other therapies

Although there is no proven benefit, chest physiotherapy, particularly with the use of positive expiratory pressure masks, can be helpful in patients with copious secretions. Currently, there is no evidence showing benefit for the use of heliox (helium and oxygen mixture) in patients with exacerbations of COPD.

Prognosis of COPD

The predictors of a poor prognosis are increasing age and worsening airflow limitation, i.e. a fall in FEV₁. A predictive index (BODE = body mass index, degree of airflow obstruction, dyspnoea and exercise capacity) has recently been modified, improving prediction of outcome, and is shown in Table 13.2. A patient with a BODE index of 0–2 has a mortality rate of 10% and with 7–10 it rises to 80% at 4 years. A simpler index using age, dyspnoea and airflow obstruction (ADO) gives a similar prognosis.

Table 13.2 Assignment of points for the updated BODE index

Obstructive sleep apnoea/hypopnoea syndrome

• Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) affects 1–2% of the population and is commonly seen in overweight, middle-aged men.

• It is a syndrome caused by abnormal size and/or collapsibility of the pharynx during sleep, which disrupts sleep and causes symptoms.

• During sleep, activity of the respiratory muscles is reduced and in OSAHS this results in collapse of the upper airways intermittently and repeatedly. If there is complete collapse, there is total obstruction of the airway and no respiratory flow (apnoea); partial collapse may cause snoring; and if there is critical collapse, there is reduced flow (hypopnoea).

• Apnoea results in hypoxia and increasingly strenuous respiratory efforts until the patient overcomes the resistance and there is termination of the apnoea and resumption of breathing.

• The patient wakes up as a result of the combination of this increased respiratory effort and central hypoxic stimulation. Patients may wake up hundreds of times per night, resulting in reduced rapid eye movement (REM) sleep and sleep deprivation. Patients are usually unaware of these night-time awakenings.

Factors predisposing to OSAH include increasing age, male gender, obesity, sedative drugs, smoking and alcohol consumption.

• Differential diagnosis. Central sleep apnoea is due to impairment of central ventilatory control secondary to brainstem pathology. It occurs at the onset of sleep and is seen in non-obese patients with no history of snoring.

Diagnosis

Symptoms

These include excessive daytime somnolence (90%), impaired concentration and loud snoring (95%). Patients may fall asleep at work, whilst driving or in mid-conversation.

If patients present with typical symptoms, they should be asked to complete an Epworth Sleepiness Scale (ESS). The maximum score is 24, normal range is < 11, mild daytime sleepiness 11–14, moderate subjective daytime sleepiness 15–18 and severe daytime sleepiness > 18. Patients and their partners should fill out the Epworth Sleepiness Scale independently, as patients often under-estimate the severity of their symptoms because onset is often gradual and there may be concerns over driving.

Examination

Examination includes a recording of weight, height, neck circumference and BP. Mandible size should be noted. There should be a full examination of the nose, oral cavity and upper airways, and a complete respiratory, cardiovascular and neurological assessment.

Complications

OSAHS has been associated with hypertension, hypothyroidism, diabetes and lipid abnormalities, and there is increasing evidence of an association with increased cerebrovascular events. Patients with OSAHS may decompensate with hypercapnic respiratory failure or cor pulmonale, especially if there is co-existent COPD.

Referrals

Patients with an abnormal Epworth Sleepiness Scale; those with symptoms suggestive of OSAHS with sleepiness in dangerous situations, such as driving or operating hazardous equipment, even if the ESS is normal; and those with likely OSAHS and COPD should be referred to a specialist sleep centre.

Investigations

Sleep studies

The primary aims of sleep studies are to assess sleep fragmentation, to establish whether a respiratory problem is responsible and to decide if upper airway obstruction is the primary cause.

• Oximetry is cheap and widely available. It can be used to measure the number of oxygen desaturations per hour or the time spent below an agreed SpO₂ level during the study. Oximetry has a role in initial assessment but limited sleep studies or polysomnography are usually required for diagnosis of OSAHS.

• Polysomnography records sleep and breathing patterns simultaneously. Full polysomnography monitors sleep stage, oxygen saturation, respiratory effort, airflow, thoraco-abdominal movement, snoring, ECG, body position and limb movements. This is an expensive technique, as the patient needs to spend the night in a sleep centre and a technician must be available throughout. Full polysomnography is not necessary for diagnosis in most cases.

• Limited sleep studies can measure thoraco-abdominal movement, oximetry, flow and heart rate. The limited sleep studies can be performed at home, although there is reduced sensitivity and specificity, compared to full polysomnography.

Treatment

Treatment depends on the severity of disease, underlying medical conditions and patient compliance. Management should consist firstly of correction of treatable and potentially reversible factors.

• Who to treat. Patients who have a sleep study showing a > 4% oxygen saturation dip more than 10 times an hour should be referred for treatment. Treatment is also necessary in those with mild OSAHS who are symptomatic or have complications.

Behavioural interventions

Weight loss can reduce symptoms, as can smoking cessation and avoidance of alcohol, sedatives and sleeping tablets. Some patients may benefit from sleeping on their side. Keeping the nose as clear as possible, with the use of nasal decongestants if required, may improve symptoms.

Treatment of underlying conditions such as hypothyroidism may greatly improve symptoms of OSAHS.

The above measures may alleviate symptoms in patients who snore or have mild OSAHS. However, in those with more severe disease, additional treatment, as well as behavioural change, is likely to be required and should not be delayed.

Non-surgical interventions

• NIV

• CPAP. This involves wearing a tight-fitting mask during sleep, which delivers pressure via air tubing from a flow generator in the region of 5–10 mmHg. The pressure splints open the pharynx and prevents collapse, allowing unobstructed breathing and an undisturbed night. Nasal CPAP is currently the treatment of choice. There are machines available that automatically ‘hunt’ the pressure required to overcome the collapse of the airway. Supplemental oxygen can be delivered via the machine if oxygen saturations are low, such as in COPD patients. Treatment with CPAP improves symptoms and may improve BP. Once patients are established on CPAP, they are likely to require it for life. However, compliance is poor because of the discomfort and noise. Other side-effects include rhinitis, nasal congestion, nasal bridge abrasions, claustrophobia and abdominal bloating.

• Intra-oral devices. Mandibular advancement devices may be worn at night; by holding the lower jaw forward, they increase the space behind the tongue and thus pharyngeal volume. This improves airflow. Alternatives include tongue-retaining devices, which hold the tongue forward. These devices need to be made individually and are useful in patients with mild OSAHS and for snorers.

• Pharmacological treatment

• Supplementary oxygen may benefit a small subset of patients, especially those living at altitude.

• Modafinil 200–400 mg daily (100 mg in the elderly) in the morning is a wake-promoting drug that is a potential adjunctive therapy. There are, however, ongoing debates regarding its efficacy.

Surgery

The aims of surgery are to increase the calibre of the pharynx and thus reduce pharyngeal resistance during sleep.

• Uvulopalatopharyngoplasty involves resection of the uvula, redundant retro-lingual soft tissue and palatine tonsillar tissue if present. The outcome is difficult to predict and it is not uniformly successful. Side-effects include post-operative pain, changes in voice and nasal regurgitation of food. In addition, patients are more likely to have difficulty with CPAP following surgery.

• Tonsillectomy may help patients with large tonsils.

• Tracheostomy is only used in patients with life-threatening apnoea in whom all other treatments have failed. It works by bypassing the obstruction.

Mandibular advancement, suprahyoid tensing, weight reduction surgery and nasal surgery have been used but there is insufficient evidence to recommend these treatments.

Driving

It is the doctor’s responsibility to inform the patient of the risks associated with continued driving, even if the diagnosis is clinically suspected but not yet formally diagnosed. Once a diagnosis is made, patients must be told verbally and in writing that it is their responsibility to inform the authorities.

Cystic fibrosis

Cystic fibrosis (CF) is a common recessively inherited disease with an incidence of 1 in 2500 and a calculated carrier frequency of 1 in 25 in the UK. It is more common in the Caucasian population.

Genetics

• CF is caused by a genetic mutation in the cystic fibrosis gene, which codes for a protein known as the cystic fibrosis transmembrane regulator (CFTR) protein. The gene is situated on the long arm of chromosome 7 (7q21.3→7q22.1).

• The commonest mutation in the European population is δF508, which is found in about 70% of affected cases and causes defective synthesis, defective maturation, blocked activation or defective function of the CFTR protein.

Pathophysiology

• The CFTR protein is essential for regulation and transport of electrolytes across the epithelial cell and intracellular membranes. In the presence of a mutant CFTR protein, chloride channels in the epithelial cells fail to open in response to elevated cyclic adenosine monophosphate (cAMP), leading to a decreased excretion of chloride ions and an increased reabsorption of sodium. As a result, less water is secreted into the airways, making the secretions more tenacious and viscous, more difficult to expectorate, and prone to infection. There is a continuous cycle of infection and inflammation, resulting in severe airway damage, bronchiectasis and loss of respiratory function.

• In the sweat ducts a similar process results in increased concentrations of sweat sodium and chloride, which is useful for diagnosis. Other organs involved include the pancreas, liver, biliary tree and gut.

Clinical features

Respiratory

The commonest presentation is with recurrent respiratory infections. A cough productive of purulent sputum in childhood eventually results in bronchiectasis and chronic airway obstruction. Increased breathlessness occurs as the disease develops. Other pulmonary complications include haemoptysis, pneumothorax and allergic bronchopulmonary aspergillosis. Eventually, cor pulmonale and respiratory failure develop. Nasal polyps and purulent sinusitis occur. Physical signs include clubbing, cyanosis, wheeze and scattered coarse crackles.

• Infection is a major problem. The bacteria are described in the treatment section. Colonization with Burkholderia cepacia is an increasing problem. It is multi-resistant and is spread by patient-to-patient contact, resulting in clinic segregation and the end of ‘CF holidays’.

• Clinically, one-third of patients have no change in symptoms or lung function, in one-third there is deterioration of lung function, and in one-third there is rapid deterioration resulting in death, even in patients with previous mild disease. The latter is known as ‘cepacia syndrome’.

• Viral infections also occur.

Gastrointestinal

About 85% of patients have pancreatic insufficiency from birth, resulting in malabsorption of fat and protein, and causing steatorrhoea and malnutrition. Infants and children may present with failure to thrive, diarrhoea or acute pancreatitis. Bowel obstruction secondary to meconium ileus (10%) can occur soon after birth; if it occurs later in life, it is known as ‘meconium ileus equivalent’ or ‘distal intestinal obstructive syndrome’ (DIOS). These patients present with volvulus or rectal prolapse. Biliary obstruction may result in cholecystitis, while chronic liver disease and cirrhosis can lead to portal hypertension, varices and splenomegaly. There is an increased prevalence of gallstones (especially cholesterol), reflux oesophagitis, peptic ulceration and gastrointestinal malignancy in CF.

Endocrine

There is gradual loss of pancreatic islet cells with the development of diabetes mellitus in about 11% of adult patients with CF. Diabetic ketoacidosis is rare. Male patients are infertile as a result of failure of the vas deferens and epididymis to develop. Female patients are able to conceive but their fertility may be reduced secondary to thickened cervical mucus.

Other

Puberty and skeletal maturity are delayed in many CF patients. Growth retardation, demineralization and osteoarthropathy may occur. Patients on long-term steroids may develop osteoporosis (p. 585).

Diagnosis and investigations

• Positive family history.

• Sweat test. This is the gold standard test for diagnosis of CF and must be performed in an experienced laboratory. Sweat is collected with pilocarpine iontophoresis; chloride levels with CF are > 60 mmol/L. The test can be repeated the day after receiving fludrocortisone 3 mg/m² for 2 days, when the sweat electrolyte concentration fails to suppress into the normal range in CF patients.

• Nasal potential difference. Normal values are −10 to −30 mV; in CF they are −34 to −60 mV. The test is performed in specialist centres.

• Genotyping. The diagnosis can be confirmed if two abnormal mutations (see above) are found.

• Radiology. A CXR or CT showing enlarged lung volumes and evidence of bronchiectasis supports a diagnosis of CF.

• Pancreatic insufficiency. This is demonstrated by a low stool elastase, abnormal pancreatic stimulation tests or fat malabsorption.

Treatment

The main aims of therapy should be to reduce exacerbations and hospitalization, enhance quality of life, prevent complications (particularly those associated with treatment) and improve mortality.

• Management. Management requires a multi-disciplinary team and is best provided in centres that specialize in CF.

• Clinic visits. Spirometry, blood tests (including vitamins and Aspergillus precipitins), CXR and a physiotherapy and dietician review should be carried out.

• Respiratory management. The aim of respiratory therapy is to decrease the number and pathogenicity of the infecting organism and suppress the lung’s hyper-responsive immune system. This can be achieved with antibiotics, anti-inflammatory agents, bronchodilators and airway clearance techniques. There is no good clinical evidence for the use of oxygen. In hypoxic patients, oxygen may delay or prevent the complications of chronic hypoxia, as it does in COPD. Oxygen may also be used during exercise.

Antibiotics

Routine sputum cultures and sensitivities guide antibiotic therapy. There is no overall consensus on the use of prophylactic antibiotics and duration of treatment.

• Acute respiratory exacerbations. IV antibiotics may be required if there is bacterial resistance to all orally administered antibiotics and if oral antibiotics fail to resolve symptoms. FEV₁ and CRP can be used to monitor response to therapy.

• Staph. aureus. Antibiotics (p. 77) such as continuous twice-daily oral flucloxacillin are usually prescribed if there is evidence of chronic colonization. Continuous prophylactic antibiotics are used in patients with frequent recurrent exacerbations. Despite prophylaxis, isolates of Staph. aureus require high-dose flucloxacillin and an additional antibiotic such as sodium fusidate, azithromycin/erythromycin, clindamycin or rifampicin. Patients with severe exacerbations should receive a second-generation cephalosporin, an aminoglycoside or vancomycin for at least 10–14 days.

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Tags: Kumar & Clarks Medical Management and Therapeutics

Apr 2, 2017 | Posted by admin in GENERAL SURGERY | Comments Off

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