Heterogeneity in the pathology and treatment of asthma

Asthma is a chronic inflammatory disease of the airways that is characterized by intermittent and at least partially reversible bronchoconstriction, as well as by airway hyperresponsiveness to a wide variety of stimuli. Asthma and other allergic disorders are thought to be due to an imbalance between the T-helper (T(H)) type 2 (T(H)2) and Type 1 (T(H)1) branches of the immune system, which are responsible for allergic inflammatory reactions and delayed hypersensitivity reactions, respectively. Pathologically, asthma is typically characterized by eosinophil activation and infiltration of the airways under the direction of T(H)2 lymphocytes. However, a subset of individuals with asthma lack eosinophils in their airways; instead they exhibit increased neutrophils. This heterogeneity in asthma also applies to treatment; that is, a significant minority of patients with asthma have been shown to be unresponsive to asthma medications, including leukotriene receptor antagonists and inhaled corticosteroids. Such phenotypic differences in asthma are probably due to multiple factors, including differences in individuals' genetic backgrounds and environmental exposures, as well as the presence of associated conditions such as rhinosinusitis and gastroesophageal reflux. Understanding the causes of asthma heterogeneity and their implications for asthma treatment is a major challenge for the new millennium.