Prior to 1979, patients presenting with lung destruction and airflow obstruction were often classified by symptoms (Chronic asthma and Chronic bronchitis), or by pathological changes (Emphysema).
Chronic bronchitis is defined clinically as the presence of a chronic productive cough for 3 months during each of 2 consecutive years.
Emphysema, onthe other hand, is defined histopathologically as an abnormal, permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis.
Airflow limitation in emphysema is due to loss of elastic recoil and due to reduction of the surface area available for the exchange of gases during breathing, whereas in chronic bronchitishyperplasia and hypertrophy of the goblet cells and mucous glands of the airway result in more mucus than usual in the airways, contributing to narrowing of the airways and causing a cough with sputum. Microscopically there is infiltration of the airway walls with inflammatory cells. Inflammation is followed by scarring and remodeling that thickens the walls further. As chronic bronchitisprogresses, there is squamous metaplasia and fibrosis. All these changes lead to narrowing of airway caliber and increase in airway resistance. Although some patients predominantly display signs of one or the other, most fall somewhere in the middle of the spectrum. Recognition that these entities overlapped and often coexisted led to the term COPD.
Recent definition of COPD
‘COPD is a disease statecharacterized 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’.
The pathogenic mechanisms are not clear but most likely involve diverse mechanisms. The increased number of activated polymorphonuclearleukocytes and macrophages will infiltrate the walls of bronchi and bronchioles and release elastases in a manner that cannot be counteracted effectively by antiproteases, resulting in lung destruction. Additionally, increased oxidative stress caused by free radicals in cigarette smoke, the oxidants released by phagocytes, and polymorphonuclear leukocytes all may lead to apoptosis or necrosis ofexposed cells. Accelerated aging and autoimmune mechanisms have also been proposed as having roles in the pathogenesis of COPD.
The epithelial layer may become ulcerated and, when the ulcers heal, squamous epithelium replaces the columnar cells. The inflammation is followed by scarring and thickening of the walls which leads to widespread narrowing in the small airways. The small airways (< 2 mmin diameter) 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 airways disease leads toprogressive 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 expiration) the resulting airflow limitation is even more severe.
The loss of lung elastic recoilresults in an increase in total lung capacity, and premature closure of airways limits expiratory flow while the loss of alveoli results in decreased capacity for gas transfer. V/Q mismatch occurs partly because of damage and mucus plugging of smaller airways from chronic inflammation, and partly because of the rapid expiratory closure of the smaller airways owing to loss of elastic recoil from...