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Airway Pathology in Chronic Obstructive Pulmonary Disease | GeneGlobe

Airway Pathology in Chronic Obstructive Pulmonary Disease

Pathway

Pathway Description

Chronic inhalation of cigarette smoke alters a wide range of immunological functions, including innate and adaptive immune responses. Cigarette smoking significantly increases the risk of heart disease, lung cancer and microbial infections (such as respiratory infections, periodontitis and bacterial meningitis). Tobacco use is also associated with delayed recovery from injuries and a higher incidence of atherosclerosis, COPD (Chronic Obstructive Pulmonary Disease), Crohn's disease, Rheumatoid Arthritis and cancers of the lung, mouth, larynx, oesophagus and bladder. COPD is a widespread chronic lung disorder which includes (a) chronic obstructive bronchitis with fibrosis and obstruction of small airways and (b) emphysema with enlargement of airspaces and destruction of lung parenchyma, loss of lung elasticity, and closure of small airways. The most important cause of chronic bronchitis and emphysema is cigarette smoking.

The lungs are an important route of exposure to environmental pathogens and antigens. Specific and nonspecific defence mechanisms are involved in clearing these foreign substances from the lungs. In COPD, chronic inflammation leads to fixed narrowing of small airways and alveolar wall destruction (emphysema) in the lungs. This is characterized by increased numbers of alveolar macrophages, neutrophils, and cytotoxic T lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). There is also a high level of oxidative stress, which may amplify this inflammation. Alveolar macrophages, neutrophils, and cytotoxic T lymphocytes accumulate in the lungs of smokers, leading to inflammation and the release of cellular products, such as enzymes that break down collagen and elastin in the lung and/or stimulate mucus production, resulting in emphysema and/or chronic bronchitis. Cigarette smoking increases the number of alveolar macrophages by several folds, and these cells express increased levels of lysosomal enzymes and secrete elastase. These enzymes might damage connective tissue and parenchymal cells of the lung, which contribute to the pathogenesis of COPD (for example, chronic bronchitis and emphysema). IL-8 is released from active monocytes and plays a primary role in the activation of both neutrophils and eosinophils in the airways of COPD patients and serves as a marker in evaluating the severity of airway inflammation. In addition, alveolar macrophages from smokers produce significantly higher levels of oxygen radicals and have higher myeloperoxidase activity; these are important mediators of the killing of intracellular pathogens. Chronic exposure to cigarette smoke inhibits the clearance of Pseudomonas aeruginosa from the lung, and these animals develop COPD-like lesions in the lung. Thus, smoking produces various morphological, physiological, biochemical and enzymatic changes in alveolar macrophages that might impair antibacterial defences, cellular regulatory activity and inflammatory responses in the lung, leading to lung pathogenesis.

The cause of pulmonary hypertension in COPD is generally assumed to be hypoxic pulmonary vasoconstriction leading to permanent medial hypertrophy. In addition to its adverse effects in cardiovascular disease, lung cancer and COPD, cigarette smoke suppresses the immune system. There are diverse medical and surgical treatments employed to alleviate and manage the symptoms of COPD. Some of the more recent developments include HFCWO (High-Frequency Chest Wall Oscillation) therapy and the combining of spirometry and pulse oximetry.