Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction

Abstract

Asthma exacerbations are associated with subsequent deficits in lung function. Here, we tested the hypothesis that a specific pattern of inflammatory responses during acute exacerbations may be associated with chronic airway obstruction. Gene coexpression networks were characterized in induced sputum obtained during an acute exacerbation, from asthmatic children with or without chronic airflow limitation. The data showed that activation of Th1-like/cytotoxic and interferon signaling pathways during acute exacerbations was decreased in asthmatic children with deficits in baseline lung function. These associations were independent of the identification of picornaviruses in nasal secretions or the use of medications at the time of the exacerbation. Th2-related pathways were also detected in the responses, but variations in these pathways were not related to chronic airways obstruction. Our findings show that decreased activation of Th1-like/cytotoxic and interferon pathways is a hallmark of acute exacerbation responses in asthmatic children with evidence of chronic airways obstruction.