The Role of Small Airway Inflammation in Asthma

Although inflammation in the large central airways has been the subject of numerous asthma studies, inflammation in the small distal airways remained largely unexamined because of the relative inaccessibility of these structures. However, fiberoptic bronchoscopy, combining endobronchial and transbronchial biopsy, now allows specimens to be obtained from both proximal and distal areas of the lung. Newly refined morphometric and immunocytochemical techniques have been applied to both autopsy and lung biopsy specimens. Together, these technological changes have had a profound impact on the study of small airway inflammation. Now, it is understood that the asthma-associated inflammation evident in the large airways occurs in the distal airways as well. The inflammatory process in the two regions has related features: infiltrates contain activated T lymphocytes and eosinophils, increased mucus plugging, and smooth muscle hyperplasia can be observed. Although the similarities are pronounced, inflammation in the small airways differs in important ways from large airway inflammation. The eosinophilic infiltration that occurs throughout the asthmatic lung also is active in the small airways. The contribution of small airway inflammation to deficits in pulmonary function has been clarified by thoracic high-resolution computed tomography imaging. Results of such imaging suggest that the distal airways are a major site of airway obstruction in patients with asthma and may play a significant role in airway hyperresponsiveness; both disorders are cardinal features of asthma. In addition, functional bronchoscopic studies of the small airways in asthma patients have found high peripheral airflow resistance, even when lung function appears normal. Current formulations of inhaled anti-inflammatory medications, particularly corticosteroids administered by metered dose inhalers using chlorofluorocarbon propellants, treat the proximal airways more effectively than the distal airways. However, some new formulations of inhaled steroids that utilize hydrofluoroalkane propellants produce aerosols of smaller average particle size, with greater penetration into the peripheral airways. Their potential to treat inflammation at peripheral sites may account for the significant improvements in asthma outcomes that have been reported in clinical trials of these new formulations.