pulmonary disorders
Chronic Obstructive Pulmonary Disease (COPD)
Pathophysiology of COPD
Various factors cause the airflow limitation and other complications of COPD. Inhalational exposures can trigger an inflammatory response in airways and alveoli that leads to disease in genetically susceptible people. The process is thought to be mediated by an increase in protease activity and a decrease in antiprotease activity. Lung proteases, such as neutrophil elastase, matrix metalloproteinases, and cathepsins, break down elastin and connective tissue in the normal process of tissue repair. Their activity is normally balanced by antiproteases, such as alpha-1 antitrypsin, airway epithelium–derived secretory leukoproteinase inhibitor, elafin, and matrix metalloproteinase tissue inhibitor. In patients with COPD, activated neutrophils and other inflammatory cells release proteases as part of the inflammatory process; protease activity exceeds antiprotease activity, and tissue destruction and mucus hypersecretion result. Neutrophil and macrophage activation also leads to accumulation of free radicals, superoxide anions, andhydrogen peroxide, which inhibit antiproteases and cause bronchoconstriction, mucosal edema, and mucous hypersecretion. Neutrophil-induced oxidative damage, release of profibrotic neuropeptides (eg, bombesin), and reduced levels of vascular endothelial growth factor may contribute to apoptotic destruction of lung parenchyma. The inflammation in COPD increases as disease severity increases, and, in severe (advanced) disease, inflammation does not resolve completely despite smoking cessation. This chronic inflammation does not seem to respond to corticosteroids, particularly in patients who continue to smoke cigarettes ( Pathophysiology reference ). Respiratory infection (which COPD patients are prone to) may amplify progression of lung destruction. Bacteria, especially Haemophilus Infections , colonize the lower airways of about 30% of patients with COPD. In more severely affected patients (eg, those with previous hospitalizations), colonization with The cardinal pathophysiologic feature of COPD is airflow limitation caused by airway narrowing and/or obstruction, loss of elastic recoil, or both. Airway narrowing and obstruction are caused by inflammation-mediated mucus hypersecretion, mucus plugging, mucosal edema, bronchospasm, peribronchial fibrosis, and remodelling of small airways or a combination of these mechanisms. Alveolar septa are destroyed, reducing parenchymal attachments to the airways and thereby facilitating airway closure during expiration. Enlarged alveolar spaces sometimes consolidate into bullae, defined as airspaces≥1 cm in diameter. Bullae may be entirely empty or have strands of lung tissue traversing them in areas of locally severe emphysema; they occasionally occupy the entire hemithorax. These changes lead to loss of elastic recoil and lung hyperinflation. Increased airway resistance increases the work of breathing. Lung hyperinflation, although it decreases airway resistance, also increases the work of breathing. Increased work of breathing may lead to alveolar hypoventilation with hypoxia and hypercapnia, although hypoxia and hypercarbia can also be caused by ventilation/perfusion (V/Q) mismatch. In addition to airflow limitation and sometimes respiratory insufficiency, complications include Pulmonary hypertension Respiratory infection Weight loss and other comorbidities Chronic hypoxemia increases pulmonary vascular tone, which, if diffuse, causes Pulmonary Hypertension and Viral or bacterial respiratory infections are common among patients with COPD and cause a large percentage of acute exacerbations. It is currently thought that acute bacterial infections are due to acquisition of new strains of bacteria rather than overgrowth of chronic colonizing bacteria. Weight loss may occur, perhaps in response to insufficient caloric intake and increased levels of circulating tumor necrosis factor (TNF)-alpha. This weight loss may be due to a mismatch between caloric expenditure and nutritional intake because caloric expenditure can be high in the presence of heightened inflammatory cytokines and hypoxemia. Other coexisting or complicating disorders that adversely affect quality of life and/or survival include Osteoporosis , 1.Pascoe S, Barnes N, Brusselle G, et al: Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial.Lancet Respir Med7(9):745–756 2019. doi: 10.1016/S2213-2600(19)30190-0 