Chronic obstructive pulmonary disease (COPD)
Chronic bronchitis and emphysema (COPD) almost always co-exist to some degree. Together they rank fifth in the global burden of disease; in the UK COPD affects approximately 6% of men and 4% of women over the age of 45. Chronic bronchitis is a clinical term defined as chronic cough and sputum for at least 3 months each year for 2 consecutive years. Emphysema is an anatomical term defined as permanent enlargement of airspaces distal to the terminal bronchioles, together with destruction of their walls.
There is no doubt that chronic bronchitis is almost always entirely due to cigarette smoking. In the United kingdom,before the Clean Air Act of 1956, urban air pollution was a significant factor. However, the incidence of chronic bronchitis over the last 10 years has remained steady in spite of ever-reducing air pollution; the only change has been a small reduction in male chronic bronchitis, undoubtedly resulting from less cigarette smoking in males.
Chronic bronchitis typically affects middle-aged men who are heavy smokers. Clinical episodes are associated with recurrent, low-grade bronchial infections caused by bacteria such as Haemophilus influenzae and Streptococcus pneumoniae, or viruses such as respiratory syncytial virus and adenovirus. Treatment is with antibiotics and physiotherapy and, sometimes, short-term use of oxygen therapy.There may also be a reversible element to the airways obstruction due to local bronchial irritation causing bronchoconstriction; bronchodilators, such as salbutamol, are therefore also used in the treatment of an attack of chronic bronchitis.
Over time, the obstructive airways disease becomes progressively more severe and is accompanied by hypercapnia, hypoxaemia and cyanosis. Such patients have been called ‘blue bloaters’. ‘Pink puffers’are those with more emphysema than bronchial obstruction they therefore hyperventilate to produce a relatively normal blood gas profile. However, it must be emphasised that most patients have a mixture of chronic bronchitis and emphysema, and therefore fall between the above two extremes, showing degrees of hypercapnia, hypoxaemia and hyperventilation. Eventually,right heart failure (cor pulmonale) or respiratory failure ensues.
The earliest abnormality in chronic bronchitis is thought to be a respiratory bronchiolitis, affecting airways of less than 2 mm in diameter. This may lead to destruction of the wall and surrounding parenchymal elastin, with the development of centrilobular emphysema. The reduced airway tension and mural weakness, together with mucus plugging, lead to obstructive clinical features. Bronchioles are so numerous that bronchiolar obstruction must be extensive and widespread to give clinical symptoms.
Bronchial abnormalities are mainly mucus hypersecretion with chronic inflammation; these features produce the typical cough and sputum. Irritation and inflammation in the bronchial epithelium can produce squamous metaplasia with loss of ciliated cells. The metaplastic squamous epithelium may become dysplastic from persistent injury by smoking, and tay even become malignant (squamous cell carcinoma of bronchus).
Although each various has a precise anatomical definition,it must be emphasised that in advanced cases there is usually a mixed picture, and an accurate classification in an individual patient is therefore not possible. Suffice to say that all forms of pulmonaty emphysema show destruction of distal lung parenchyma.
Centrilobular (centriacinar) emphysema involves airspaces in the center of lobules. This lesion is commonest in men,and is closely associated with cigarette smoking, although mild centrilobular emphysema may be seen in patients with coal-worker's pneumoconiosis. In addition, a recent judgement in Britain stated coal mine dust to be a cause of centrilobular emphysema in the absence of coal-worker's pneumoconiosis. The lesions are most common in the upper lobes. As noted above, a respiratory bronchiolitis is also frequently present, together with some large airways disease such as is seen in chronic bronchitis. Dust-laden macrophages and chronic inflammatory cells are often seen in the walls of dilated airways in this type of emphysema. Although the pathogenesis is unknown, it is suggested that respiratory bronchiolitis is the precursor lesion of centrilobular emphysema, with local destruction of airway walls and elastin in adjacent lung parenchyma.
Paulobular (panacinar) emphysema involves all airspaces distal to the terminal bronchioles. Usually, lower lobes are affected, the bases being most severely involved. Grossly,the lungs appear overdistended and voluminous. The aetiology and pathogenesis of panlobular emphysema is largely unknown. However, 70--80% of patients with a1-antitrypsin (al-AT) deficiency in the homozygous state will develop this type of respiratory disease,usually before the age of about 50 years. al-AT is an acute phase serum protein which inhibits the actions of collagenase,elastase and other proteases, including trypsin.One action of al-AT is to inhibit enzymes released from dying neutrophils and macrophages. Any stimulus, such as smoking,that leads to increased numbers of inflammatory cells in the lung will lead to alveolar wall destruction (emphysema) in patients with al-AT deficiency. The enzyme deficiency is inherited as an autosomal dominant trait,and the homozygous deficiency state is said to affect about 1 in 3630 Caucasians; the defect is even rarer in blacks.