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Eosinophilic and Neutrophilic Inflammation in Asthma

Insights from Clinical Studies

¹ Cardiovascular Research Institute, and ² Department of Medicine, University of California, San Francisco, California

Correspondence and requests for reprints should be addressed to John V. Fahy, M.D., M.Sc., University of California at San Francisco, Box 0130, 505 Parnassus Avenue, San Francisco, CA 94143. E-mail: john.fahy{at}ucsf.edu

ABSTRACT

Cellular inflammation of the airways with eosinophils and neutrophils is a characteristic feature of asthma and is considered relevant to the pathogenesis of the disease. Studies of large numbers of subjects with well-characterized asthma in recent years has resulted in new insights about the clinical and pathologic correlates of eosinophilic and neutrophilic inflammation in asthma. For example, eosinophilic asthma is a distinct phenotype of asthma that is associated pathologically by thickening of the basement membrane zone and pharmacologically by corticosteroid responsiveness. In contrast, noneosinophilic asthma, a sizeable subgroup of asthma that includes patients with severe disease, is not characterized by thickening of the basement membrane zone, and it appears to be relatively corticosteroid resistant. Eosinophilic and neutrophilic asthma are not mutually exclusive subtypes of asthma. Rather, neutrophils accumulate in the airways in patients with asthma with more severe airflow obstruction, where eosinophils may also be present in excess. In addition, neutrophils are prominent in airway secretions during acute severe asthma exacerbations, where it is possible that they have roles in both the initiation and resolution of attacks. These insights about the relationships between cellular inflammation and disease phenotypes of asthma support the concept that different subgroups of patients with asthma, despite clinically similar features, can be defined by specific cellular and molecular markers. The promise now is that these markers will ultimately guide personalized treatment programs.

Key Words: eosinophils • neutrophils • asthma