COPD refers to emphysema, chronic bronchitis, or a combination of the two. These cause severe difficulties in ventilation and in oxygenation of the blood, and are among the major causes of disability and death in the US.
Airway obstruction is not caused by increased smooth muscle contraction in these diseases as it is in asthma. In emphysema the cause of obstruction is destruction and collapse of the smaller airways. Emphysema is characterised by the destruction of the alveolar walls leading to an increase in compliance (compliance = the magnitude of change in lung volume produced by a given change in the transpulmonary pressure). Chronic bronchitis is characterised by excessive mucus production in the bronchi and chronic inflammatory changes in the small airways. Obstruction is caused by accumulation of the mucus in the airways and thickening of the inflamed airways. The same agents that cause emphysema, such as smoking, also cause chronic bronchitis, which is why the two diseases frequently coexist.
[Kumar and Clark]
The global initiative in obstructive lung disease (GOLD) predicts that COPD will become the third most common cause of death and fifth most common cause of disability world-wide by 2020.
The term COPD brings together a variety of syndromes associated with destruction of the lung and airflow obstruction. Chronic asthma, chronic bronchitis, emphysema, pink puffers and blue bloaters. “COPD is a disease state characterised by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.” (GOLD)
- Loss of elasticity and alveolar attachments of airways due to emphysema → reduces elastic recoil and airways collapse during expiration.
- Inflammation and scarring cause the small airways to narrow
- Mucus secretion blocks airways
- Combined these lead to hyperinflation of the lung and breathlessness
COPD is caused by long term exposure to toxic particles and gases. In developed countries, cigarette smoking accounts for 90% of cases. Airflow limitation increases with age, and increases more rapidly in smokers. The rate of increase in someone who has quit smoking is the same as that in someone who never smoked, although it may start from a lower level due to the damage of previous smoking. In developing countries, COPD is caused by cigarette smoking and smoke from cooking fuels. Only 10-20% of heavy smokers develop COPD, indicating individual susceptibility. Risk of death for person smoking 30/day is 20x that of a non-smoker. Autopsy studies have shown that substantial numbers of centri-acinar emphysematous spaces are found in the lungs of 50% of British smokers over the age of 60 years and are unrelated to the diagnosis of significant respiratory disease before death. Climate and air pollution have some affect. Urbanisation, social class and occupation may also have an effect on aetiology but difficult to separate from smoking.
In UK, COPD accounts for 7% of all days off work due to sickness. But the number of patients discharged from hospital with this diagnosis has been falling steadily and the death rate has fallen in the last 25 years from 200 to 70 per 100,000 in the UK.
The most consistent pathological finding is hypertrophy and increase in number of the mucus secreting goblet cells of the bronchial tree, evenly distributed throughout the lung but mainly seen in the larger bronchi. In more advanced cases the bronchi themselves are obviously inflamed and pus is seen in the lumen. Microscopically there is infiltration of the bronchi and bronchioles with acute and chronic inflammatory cells and lymphoid follicles in severe disease. In contrast to asthma, the lymphocytic infiltrate is predominantly CD8+. The epithelial layer may become ulcerated and, when the ulcers heal, squamous epithelium may replace the columnar cells. The inflammation is followed by scarring and a remodelling process that thickens the walls and leads to widespread narrowing in the small airways.
The small airways are particularly affected early in the disease, initially without the development of any significant breathlessness. This initial inflammation of the small airways is reversible and accounts for the improvement in airway function if smoking is stopped early. In later stages the inflammation continues even if smoking is stopped.
Further progression of the disease leads to progressive squamous cell metaplasia, and fibrosis of the bronchial walls. The physiological consequence of these changes is the development of airflow limitation. If the airway narrowing is combined with emphysema (causing loss of the elastic recoil of the lung with collapse of small airways during aspiration) the resulting airflow limitation is even more severe.
Emphysema is defined pathologically as dilation and destruction of the lung tissue distal to the terminal bronchiole:
- Centri-acinar emphysema – damage concentrated around the respiratory bronchioles; extremely common form of emphysema, and when of modest extent it is not normally disabling, but severe Centri-acinar emphysema is associated with substantial airflow limitation.
- Pan-acinar emphysema – less common, damage appears to involve the whole of the acinus, and in the extreme form the lung becomes a mass of bullae. Severe airflow limitation and Va/Q mismatch occur. This type of emphysema occurs in alpha1-antitrypsin deficiency.
- Irregular emphysema produces damage and scarring affecting the lung parenchyma patchily without particular regard for acinar structure.
Emphysema leads to expiratory airflow limitation and air trapping. The loss of lung elastic recoil results in an increase in TLC while the loss of alveoli results in decreased gas transfer.
Va/Q mismatch occurs partly because of damage and mucus plugging, and partly because of the rapid expiratory closure of the smaller airways owing to loss of elastic recoil. This leads to a decrease in PaO2 and an increase in the work of respiration.
PaCO2 excretion is not impaired to the same extent and many patients will show low normal PaCO2 values – the “pink puffers” who seek to maintain normal blood gases by increasing their respiratory effort. Other patients fail to maintain their respiratory effort and thus their carbon dioxide levels increase. In the short term, the rise in CO2 leads to stimulation of respiration but in the long term these patients often become insensitive to CO2 and come to depend on hypoxaemia to drive their ventilation. These patients appear less breathless, and because they run low O2 values they start to retain fluid and stimulate the production of erythrocytes (polycythemia). So they become bloated, plethoric and cyanosed. Attempts to abolish hypoxaemia by administering oxygen can make the situation much worse by decreasing respiratory drive in these patients who rely on hypoxia to drive their ventilation.
Loss of 50ml/yr FEV1 in COPD compared to 20mL/yr in healthy people.
Bronchoalveolar washes have shown that smokers have neutrophil granulocytes present within the lumen of the bronchial tree that are absent in non-smokers. Also, small airways of smokers are infiltrated by granulocytes capable of releasing elastases and proteases, which possibly help to produce emphysema. It is suggested that imbalance between protease and antiprotease activity may produce the damage. Alpha1-antitrypsin is a major serum antiprotease which can be inactivated by cigarette smoke.
The hypertrophy of mucous glands in the larger airways is thought to be a direct response to persistent irritation resulting from the inhalation of cigarette smoke. The smoke has adverse effect on surfactant, favouring overdistension of the lungs.
alpha1-antitrypsin inhibitor is produced in liver, secreted into blood and diffuses into the lungs where it acts as antiprotesase that inhibits neutrophil elastase, a proteolytic enzyme capable of destroying alveolar wall connective tissue. There are >75 alleles of the alpha1-antitryptin inhibitor gene, of which 3 main phenotypes. ~1in5000 in UK are homozygous deficient, and those who develop chest disease are usually, but not always, smokers. Hereditary alpha1-antitryptin deficiency accounts for ~2% of emphysema cases.
Characteristic symptoms are cough with production of sputum, wheeze and breathlessness following many years of smokers cough and frequent chest infections. Can be worsened by, e.g., cold, foggy weather, pollution. With advanced disease, breathlessness becomes severe even after mild exercise such as dressing.
Only sign in mild disease is wheeze throughout the chest. In severe disease patient is tachypnoeic with prolonged expiration, using accessory muscles to breathe, and may show intercostal indrawing on inspiration and pursing of lips on expiration
More than 40 per cent of smokers aged 61-62 and 50 per cent of those aged 76-77 have COPD
Stopping smoking is the only measure that has been conclusively shown to slow further progression of the disease. After stopping smoking, the rate of decline of lung function slows, approaching that in non-smokers. Preventing a exacerbations of COPD is also important, as it has been found that frequent exacerbations are associated with a more rapid decline in lung function. Respiratory infections are a common cause of such exacerbations, so vaccination against influenza and pneumonia may help protect against accelerated decline in lung function. Combinations of inhaled steroids and bronchodilators used in more advanced COPD reduce the frequency and severity of exacerbations and also the risk of death.
In mild COPD (for example, where breathlessness occurs only on exercising), an inhaled short-acting bronchodilator may be sufficient to control the symptoms. If a single bronchodilator is not sufficient, a combination of two types of shortacting bronchodilators may be tried, or a longacting inhaled bronchodilator can be used instead. In more severe cases, guidelines recommend trying a combination of an inhaled long-acting bronchodilator and an inhaled corticosteroid for an initial period of four weeks. If this combination is still not sufficient to provide relief, theophylline, taken by mouth, may be added. However, this can cause unpleasant side-effects and must be closely monitored
Many other therapies can be used to improve the quality of life of people with COPD. Anxiety or depression can be treated by behavioural therapy and medication. Dietary advice can help prevent weight loss and muscle-wasting. Treatment with a mucolytic medicine may ease sputum production. Pulmonary rehabilitation increases exercise tolerance, promoting independence and emotional well-being. Disease flare-ups due to infections such as pneumonia and flu can be prevented by vaccination.
<h2>Infections as complication of COPD</h2>
Patients with COPD often cope badly with respiratory infections, which can be precipitating cause of acute exacerbations. But its not clear if infections affect the progressive airflow limitation. Prompt use of antibiotics and flu jabs are appropriate.