Asthma: clinical expression and molecular mechanisms

Abstract

Asthma is a complex disorder that displays heterogeneity and variability in its clinical expression both acutely and chronically. This heterogeneity is influenced by multiple factors including age, sex, socioeconomic status, race and/or ethnicity, and gene by environment interactions. Presently, no precise physiologic, immunologic, or histologic characteristics can be used to definitively make a diagnosis of asthma, and therefore the diagnosis is often made on a clinical basis related to symptom patterns (airways obstruction and hyperresponsiveness) and responses to therapy (partial or complete reversibility) over time. Although current treatment modalities are capable of producing control of symptoms and improvements in pulmonary function in the majority of patients, acute and often severe exacerbations still occur and contribute significantly to both the morbidity and mortality of asthma in all age groups. This review will highlight some of the important clinical features of asthma and emphasize recent advances in both pathophysiology and treatment.

Fig 1

Inflammatory and remodeling responses in asthma with activation of the epithelial mesenchymal trophic unit. The epithelial mesenchymal trophic unit has been defined as bidirectional interaction between the epithelium and underlying mesenchyme involving the release of selective growth factors and cytokines. Epithelial damage alters the set point for communication between bronchial epithelium and underlying mesenchymal cells, leading to myofibroblast activation, an increase in mesenchymal volume, and induction of structural changes throughout airway wall.