1. بسم الله الرحمن الرحيم

2. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)  Lecture by:  Dr. Zaidan Jayed Zaidan

3.  COPD is a heterogeneous condition embracing several overlapping pathological processes including chronic bronchitis, chronic bronchiolitis (small airway disease) and emphysema. Many patients also exhibit a systemic component characterised by impaired nutrition, weight loss and skeletal muscle dysfunction. COPD is defined by the presence of airways obstruction, which does not change markedly over several months and, unlike asthma, is not fully reversible.

4. Epidemiology  The prevalence of COPD in the UK is estimated to be between 1 and 2% but is probably greater because airflow limitation is present in 10% of the general population. Exacerbations of COPD account for 10% of hospital admissions in the UK and with around 30 000 deaths/year it represents the sixth most common cause of death in the UK. Following the marked increase in tobacco consumption in developing countries COPD is gaining global importance; if current trends continue, it will become the fifth leading cause of lost disability-adjusted life years and the third most important cause of death world- wide by 2020.

5. Risk factors  cigarette smoking remains the most important. Susceptibility to cigarette smoke varies but both the dose and duration of smoking appear to be important, and it is unusual to develop COPD with less than 10 pack years (1 pack year = 20 cigarettes/day/year).

7. Pathophysiology

10. Clinical features  COPD should be suspected in any patient over the age of 40 years who presents with symptoms of persistent cough and sputum production and/or breathlessness. Depending on the presentation important differential diagnoses include asthma, tuberculosis, bronchiectasis and congestive cardiac failure. Chronic severe asthma may be difficult to distinguish from COPD.

11.  Cough is usually the first symptom but seldom prompts the patient to consult a doctor. It is characteristically accompanied by small amounts of mucoid sputum. Chronic bronchitis is formally defined when a cough and sputum occur on most days for at least 3 consecutive months for at least 2 successive years. Haemoptysis may complicate exacerbations of COPD but should not be attributed to COPD without thorough investigation. Breathlessness usually heralds the first presentation to the health professional. The level should be quantified for future reference; scales such as the modified MRC dyspnoea scale may be of assistance. In advanced disease enquiry should be made as to the presence of oedema (which may be seen for the first time during an exacerbation) and morning headaches indicative of hypercapnia.

13.  Physical signs are non-specific, correlate poorly with lung function, and are seldom obvious until the disease is advanced. The presence of pitting oedema should be documented and the body mass index (BMI) recorded. Crackles may accompany infection but if persistent raise the possibility of bronchiectasis. Finger clubbing is not consistent with COPD and should alert the physician to potentially more serious pathology.  Two classical phenotypes have been described: 'pink puffers' and 'blue bloaters'. The former are typically thin and breathless, and maintain a normal PaCO2 until the late stage of disease. The latter develop (or tolerate) hypercapnia earlier and may develop oedema and secondary polycythaemia. In practice, these phenotypes often overlap.

14. Investigations  Although there are no reliable radiographic signs that correlate with the severity of airflow limitation, a chest X-ray is essential to identify alternative diagnoses such as cardiac failure, other complications of smoking such as lung cancer, and the presence of large bullae. A blood count is useful to exclude anaemia or document polycythaemia, and in younger patients with predominantly basal emphysema, α1- antiproteinase should be assayed.

15.  The diagnosis of COPD requires objective demonstration of airflow obstruction by spirometry and is established when the post-bronchodilator FEV1 is less than 80% of the predicted value and accompanied by FEV1/ FVC < 70%. The presence of an FEV1 / FVC < 70% in the presence of an FEV1 of 80% or more suggests the presence of mild disease. Particular attention should be paid to vital capacity, as this is dependent on the technique and effort employed by the patient. The severity of COPD may be defined in relation to the post- bronchodilator FEV1. A low peak flow is consistent with COPD but it is not sufficiently specific to confirm the diagnosis, is unable to discriminate between obstructive and restrictive disorders, and may underestimate the severity of airflow limitation in COPD.

17.  Measurement of lung volumes provides an assessment of hyperinflation. This is generally performed by helium dilution technique; however, in patients with severe COPD, and in particular large bullae, body plethysmography is preferred because the use of helium may underestimate lung volumes. The presence of emphysema is suggested by a low gas transfer. Exercise tests provide an objective assessment of exercise tolerance and provide a baseline on which to judge the response to bronchodilator therapy or rehabilitation programmes; they may also be valuable when assessing prognosis. Pulse oximetry may prompt referral for a domiciliary oxygen assessment if less than 93%.

18.  The assessment of health status provides valuable clinical information but currently available questionnaires are too cumbersome for day-to-day practice.  CT is likely to play an increasing role in the assessment of COPD as it allows the detection, characterisation and quantification of emphysema and is more sensitive than the chest X-ray at detecting bullae.

20. Management  The management of COPD has been the subject of unjustified pessimism. It is usually possible to improve breathlessness, reduce the frequency and severity of exacerbations, and improve health status and prognosis

21.  Smoking cessation: Every attempt should be made to highlight the role of smoking in the development and progress of the disease and encourage, advise and assist the patient toward smoking cessation. On cessation, patients should be warned to expect an apparent worsening of chest symptoms and reassured that this is temporary. Cessation is difficult but highly rewarding and remains the only intervention proven to decelerate the decline in FEV1.

23. Bronchodilators  Bronchodilator therapy is central to the management of breathlessness in patients with COPD. The inhaled route is preferred and a number of different agents delivered by a variety of devices are available. Choice should be informed by patient preference and inhaler assessment. Short-acting bronchodilators may be used for patients with mild disease but longer-acting bronchodilators are more appropriate for patients with moderate to severe disease. It is important to realise that significant improvements in breathlessness may be reported despite minimal changes in FEV1, probably reflecting improvements in lung emptying that reduce dynamic hyperinflation and ease the work of breathing.

24.  Oral bronchodilator therapy may be contemplated in patients who cannot use inhaled devices efficiently. Theophylline preparations improve breathlessness and quality of life, but their use has been limited by side-effects, unpredictable metabolism and drug interactions. Bambuterol-a pro-drug of terbutaline-is used on occasion. Orally active highly selective phosphodiesterase inhibitors are currently being developed.

25. Corticosteroids  Inhaled corticosteroids (ICS) reduce the frequency and severity of exacerbations; they are currently recommended in patients with severe disease (FEV1less than 50%) who report two or more exacerbations requiring antibiotics or oral steroids per year. Regular use is associated with a small improvement in FEV1, but there is no impact on the accelerated decline in lung function. The combination of ICS with long-acting β2 -agonists produces further improvement in breathlessness and reduces the frequency and severity of exacerbations.

26.  Oral corticosteroids are useful during exacerbations but maintenance therapy contributes to osteoporosis and impaired skeletal muscle function and should be avoided. Oral corticosteroid trials may assist in the diagnosis of asthma but do not predict response to inhaled steroids in COPD.

27. Pulmonary rehabilitation  Exercise should be encouraged at all stages and patients reassured that breathlessness, whilst distressing, is not dangerous. Multidisciplinary programmes that incorporate physical training, disease education and nutritional counselling reduce symptoms, improve health status and enhance confidence. Most programmes include two to three sessions per week, last between 6 and 12 weeks, and are accompanied by demonstrable and sustained improvements.

28. Oxygen therapy  Long-term domiciliary oxygen therapy (LTOT) has been shown to improve survival, prevent progression of pulmonary hypertension, decrease the incidence of secondary polycythaemia, and improve neuropsychological health. It is most conveniently provided by an oxygen concentrator via nasal prongs and patients should be instructed to use oxygen for a minimum of 15 hours/day; greater benefits are seen in patients who receive > 20 hours/day. The aim of therapy is to increase the PaO2 to at least 8 kPa (60 mmHg) or SaO2 at least 90%. Ambulatory oxygen therapy should be considered in patients who desaturate on exercise and show objective improvement in exercise capacity and/or dyspnoea with oxygen. Oxygen flow rates should be adjusted to maintain SaO2 above 90%. Short-burst oxygen therapy is widely prescribed but is expensive and of unproven benefit.

30. Surgical intervention  Selected patients with COPD may benefit from surgical intervention. Young patients with minimal airflow limitation and a lack of generalised emphysema, but in whom large bullae compress surrounding normal lung tissue, may be considered for bullectomy. Lung volume reduction surgery (LVRS) removes peripheral emphysematous lung tissue reducing hyperinflation and decreasing the work of breathing. In carefully selected patients LVRS results in improvements in FEV1, lung volumes, exercise tolerance and quality of life. Effects last for at least 2 years but long-term outcomes are unknown. Both bullectomy and LVRS can be performed thorascopically, minimising morbidity. Lung transplantation may benefit highly selected patients with advanced disease but is limited by shortages in donor organs.

31. Other measures  Patients with COPD should be offered an annual influenza vaccination and, as appropriate, pneumococcal vaccination. Obesity, poor nutrition, depression and social isolation should be identified and, if possible, improved. Mucolytic therapy (e.g. acetylcysteine 200 mg orally 8-hourly for 8 weeks in the first instance) may be recommended in patients with chronic cough and sputum production and should be continued if symptomatic benefit is reported.

32. Prognosis  COPD has a variable natural history. The prognosis is inversely related to age and directly related to the post-bronchodilator FEV1. Additional poor prognostic indicators include weight loss (survival is negatively correlated with BMI) and pulmonary hypertension. A recent study has suggested that a composite score comprising the body mass index (B), the degree of airflow obstruction (O), a measurement of dyspnoea (D) and exercise capacity (E) may assist in predicting death from respiratory and other causes.

34. Acute exacerbations of COPD  Acute exacerbations of COPD are characterised by an increase in symptoms and deterioration in lung function and health status. They become more common as the disease progresses and may be caused by bacteria, viruses or a change in air quality. They may be accompanied by the development of respiratory failure and/or fluid retention and represent an important cause of death.

35.  Many patients can be managed at home with the use of increased bronchodilator therapy, a short course of oral corticosteroids, and if appropriate, antibiotics. The presence of cyanosis, peripheral oedema or an alteration in consciousness should prompt referral to hospital. In other patients consideration of comorbidity and social circumstances may influence decisions regarding placement.

36. Oxygen therapy  In patients with an exacerbation of severe COPD, high concentrations of oxygen may cause respiratory depression and worsening acidosis. Controlled oxygen at 24% or 28% should be used with the aim of maintaining a PaO2 more than 8 Kpa ( 60 mmHg) (or an SO2 more than 90%) without worsening acidosis.

37. Bronchodilators  Nebulised short-acting β2- agonists combined with an anticholinergic agent should be administered. Provided patients are properly supervised it is usually safe to drive nebulisers with oxygen, but if concern exists regarding oxygen sensitivity nebulisers may be driven by compressed air and supplemental oxygen delivered by nasal cannula.

38. Corticosteroids  Oral prednisolone reduces symptoms and improves lung function. Currently doses of 30 mg for 10 days are recommended but shorter courses may be acceptable. Prophylaxis against osteoporosis should be considered in patients who receive repeated courses of steroids

39. Antibiotic therapy  The role of bacteria in exacerbations remains controversial and there is little evidence for the routine administration of antibiotics. They are currently recommended for patients reporting an increase in sputum purulence, sputum volume or breathlessness. In most cases simple regimens are advised such as an aminopenicillin or a macrolide. Co-amoxiclav is only required in regions where β-lactamase-producing organisms are known to be common.

40. Non-invasive ventilation  If, despite the above measures, the patient remains tachypnoeic and acidotic ( PH less than 7.35) then NIV should be commenced. Several studies have shown that its use is associated with reduced requirements for mechanical ventilation and reductions in mortality. It is not useful in patients who cannot protect their airway. Mechanical ventilation may be contemplated in those with a reversible cause for deterioration (e.g. pneumonia), or when no prior history of respiratory failure has been noted.

41. Additional therapy  There has been a vogue for using an infusion of intravenous aminophylline but evidence for benefit is limited and attention must be paid to the risk of inducing arrhythmias and drug interactions. The use of the respiratory stimulant doxapram has been largely superseded by the development of NIV, but it may be useful for a limited period in selected patients with a low respiratory rate. Diuretics should be administered if peripheral oedema has developed.

42. Discharge  Discharge from hospital may be contemplated once the patient is clinically stable on his or her usual maintenance medication. The provision of a nurse-led 'hospital at home' team providing short-term nebuliser loan improves discharge rates and provides additional support for the patient.

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