The distal airways: are they important in asthma?

Although the airways of <2 mm in diameter have been dubbed the "quiet zone", they do not appear to be so in asthma. Physiological and pathological evidence suggests that the small airways and lung parenchyma participate in asthma pathogenesis, and may explain many of the clinical observations noted. This review presents this evidence, beginning with physiological evidence, followed by pathology and last by imaging studies that evaluate the distal lung. Seminal physiological studies date back to the 1960s, with significant progress in the area of airway smooth muscle and its contribution to airways responsiveness noted over the last several years. The use of bronchoscopy in clinical studies has complemented the autopsy studies in advancing knowledge about airway structural changes appreciated in asthma in the small airways and lung parenchyma. These pathological studies have allowed validation of the physiological, and more recently the imaging studies performed to evaluate this compartment of the lung in asthma. Thus, the evidence suggests that the small airways and parenchyma contribute significantly to asthma pathogenesis. The challenge now lies in evaluating this compartment in the context of its value as a therapeutic target in asthma.