Although cigarette smoking is the most important cause of COPD, only 10-15% of long term smokers develop clinically significant COPD, and approximately half will never develop any symptomatic physiological deficit.²⁸ Why the normal, protective inflammatory response becomes an exaggerated, harmful one in only some smokers is poorly understood, and the precise mechanisms underlying the development of this disorder remain largely unknown. Presumably the inflammation caused by cigarette smoking interacts with other host or environmental factors to produce excess decline in lung function that results in COPD.

It is believed that inhaled noxious particles and gases result in lung inflammation, induce tissue destruction, and impair defense mechanisms that serve to limit or repair this damage. This damage leads to the mucous hypersecretion, airway narrowing and fibrosis, destruction of lung parenchyma and vascular changes. In turn, these pathological changes lead to airflow limitation and other physiological abnormalities characteristic of COPD. It is characterized by an increase in neutrophils, macrophages and T-lymphocytes in various parts of the lung. These activated inflammatory cells release a variety of chemical mediators, many of which (e.g. leukotreine B4, interleukin-8, and tumour necrosis factor) are capable of damaging lung structures and/or sustaining neutrophilic inflammation. In addition to inflammation, two other processes thought to be important in the pathogenesis of COPD are an imbalance of proteinases and antiproteinases in the lung, and oxidative stress.^29-31 Although both these processes may themselves result from ongoing inflammation, they can also arise from genetic (e.g. alpha-1 antitrypsin deficiency) or environmental (e.g. oxidant compounds in cigarette smoke) factors.

The peripheral airways are the major site of airways obstruction in patients of COPD. The structural changes in the airway wall, as well as airway edema and mucus hypersecretion contribute to airway narrowing. The irreversible component of airflow limitation is primarily due to remodelling of the smaller airways; lung parenchymal destruction may also play a role. In advanced COPD, peripheral airways obstruction, parenchymal destruction, and pulmonary vascular abnormalities reduce the lung’s capacity for gas exchange, producing hypoxemia and, later on, hypercapnia. Ventilation-perfusion mismatch is the dominant mechanism of hypoxemia in COPD.