Therapeutic significance of distal airway inflammation in asthma

Abstract

Inflammation in asthma is not merely confined to the large central airways but also extends to the small peripheral airways. Distal lung inflammation can be observed even in patients with asthma with mild disease and normal spirometric readings. Subjects with asymptomatic asthma can exhibit significant increases in peripheral airway resistance, likely the result of distal lung inflammation. As determined from measurements of eosinophilic and other cellular infiltrates, the inflammatory response in the distal lung can exceed that in the large airways. Nocturnal asthma, a natural model of cyclic asthma worsening, is associated with an increase in nighttime distal lung inflammation, as evidenced by the accumulation of alveolar tissue eosinophils. Distal lung disease appears to increase the risk of recurrent asthma exacerbation, whereas disease-related anatomic changes in the small airways of the distal lung are prominent in fatal asthma. The clinical significance of distal lung disease makes this region an important therapeutic target. Chlorofluorocarbon (CFC)-based preparations of inhaled corticosteroids used to treat airway inflammation produce aerosols of relatively large particle size (approximately 4 microm); such aerosols have poor access to the distal lung. New formulations of inhaled corticosteroids that use hydrofluoroalkane (HFA) propellants can have smaller particle sizes (approximately 1 microm). Extrafine HFA aerosols have better access to the distal lung, with less oropharyngeal deposition. Imaging studies suggest that anti-inflammatory medication delivered as an extrafine aerosol produces beneficial changes in distal lung function. In one study, an HFA formulation of an inhaled corticosteroid reduced air trapping to a greater degree than a CFC formulation of the same corticosteroid. By extending the delivery of anti-inflammatory medication to the distal lung, the new HFA-based corticosteroids have the potential to treat asthma more effectively and at reduced steroid doses.