Cellular and Structural Bases of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by poorly reversible airflow limitation that is usually both progressive and associated with an abnormal inflammatory response of the lung. Cigarette smoking is the most important risk factor for the development of COPD. However, only a minority of smokers develop COPD and the reason is still unknown. The pathological hallmarks of COPD are inflammation of the peripheral airways and destruction of lung parenchyma or emphysema. The functional consequence of these abnormalities is expiratory airflow limitation. Since the major determinants of expiratory flow are a driving pressure that promotes flow (elastic recoil of the lung) and an opposing resistance that inhibits flow (airway obstruction), the reduction in flow occurring in COPD is more correctly defined as airflow limitation rather than airflow obstruction, since both loss of elastic recoil and increase in airway resistance play an important role in the observed decrease in flow. Emphysema will contribute to the airflow limitation by reducing the elastic recoil of the lung through parenchymal destruction, as well as by reducing the elastic load applied to the airways through destruction of alveolar attachments. On the other hand, inflammation of the peripheral airways will contribute to the airflow limitation by increasing the thickness of the airway wall which, together with fibrosis and smooth muscle hypertrophy, may cause airway narrowing. The role of mucus hypersecretion in the development of chronic airflow limitation is still controversial. The main site of mucus hypersecretion, expressed clinically as chronic bronchitis, is the central airways, and there is increasing evidence that the central airways are inflamed in patients with COPD. Pulmonary hypertension is a common feature in patients with advanced COPD, but the precise mechanisms of increased vascular resistance are unclear. For many years, it has been regarded as a consequence of the hypoxic vasoconstriction that may occur in advanced stages of the disease. However, the lack of reversibility of pulmonary hypertension after hypoxemia correction suggests that it might be due at least in part to the development of pulmonary vascular inflammation and remodeling. In summary, in subjects with COPD, pathological changes can be found in the central airways, the peripheral airways, the lung parenchyma, and pulmonary arteries. Interestingly, some of these changes can already be present in the lungs of "normal" smokers, i.e. smokers with normal lung function, indicating that smoking itself is able to damage the lung even before airflow limitation occurs. In the present article we will focus on the cellular and structural changes present in the lungs of "normal" smokers and on those present in the lungs of smokers with COPD, in an attempt to underline the possible mechanisms contributing to airflow limitation in these patients. We will then review the few studies that described the cellular and structural changes that occur in severe COPD and those that occur during an exacerbation of the disease. Finally, we will address the effect of smoking cessation or antiiflammatory treatment in an attempt to investigate the potential reversibility of the pathologic lesions characteristic of COPD. In advanced COPD, changes in the right heart, the respiratory muscles, and the skeletal non-respiratory muscles as well as cachexia may also occur, but these systemic changes will not be discussed in this article.