Asthma severity: histopathologic correlations

Asthma is a disorder characterized by inflammation of the airways which leads to variable airflow obstruction and symptoms of wheezing, chest tightness, cough, and dyspnea. Decisions concerning the type and intensity of therapy for asthma are generally based on the severity of the disease in a given individual. Guidelines for asthma management classify disease severity on the basis of symptom frequency and intensity as well as the degree of physiological impairment. Because treatment decisions are currently not based on markers of airway inflammation, it is important to know how well the underlying inflammatory pathology correlates with clinical and physiological variables and whether airway inflammation, if undertreated, leads to longer term adverse outcomes such as chronic persistent airway obstruction. Studies of asthma pathology reveal an inflammatory response characterized by infiltration of the airways with eosinophils, mast cells and lymphocytes; disruption of the epithelium; thickening of the reticular basement membrane; and increases in smooth muscle mass. These findings are qualitatively found in mild as well as severe asthmatics, and attempts to draw quantitative correlations between severity and intensity of inflammation have yielded discordant results. Although antiinflammatory therapy with corticosteroids decreases the intensity of the inflammation in association with improved clinical variables, the association is circumstantial and it is unclear which marker of inflammation correlates best with the severity of acute episodes or the severity of the disease in patients who are stable. Problems in relating the underlying pathology to disease severity are largely due to inadequate tissue sampling as bronchoscopically obtained specimens do not permit an evaluation of the outer airway wall or small airways and their surrounding parenchyma.