Identification of Inflammatory Gene Expression Patterns Associated with Viral Upper Respiratory Tract Infections (URI) that Cause Asthma Exacerbations
Altman MC, Babineau D, Whalen E, Gill MA, Shao B, Liu AH, Jepson B, Gruchalla RS, O'Connor GT, Pongracic JA, Kercsmar CM, Khurana Hershey G, Zoratti EM, Johnson CC, Teach S, Kattan M, Bacharier LB, Beigelman A, Sigelman S, Gergen PJ, Wheatley LM, Presnell S, Togias A, Gern JE, Busse WW, and Jackson DJ. Identification of inflammatory gene expression patterns associated with viral upper respiratory tract infections (URI) that cause asthma exacerbations. Am J Respir Crit Care Med 2018; 197:A7365.
Am J Respir Crit Care Med
Background: Because establishing immune mechanisms of asthma exacerbations in children is crucial to improved disease control and prevention of these events, we sought to determine cellular and molecular pathways by which URIs lead to exacerbations in vivo using transcriptome profiling and network analysis. Methods: Children (6 to 17 years old) with difficult-to-control, exacerbation-prone asthma (requiring at least 250mcg bid inhaled fluticasone, or equivalency, and history of 2 exacerbations requiring systemic corticosteroids in the past 12 months) and blood eosinophils ≥150/mm3 were enrolled. Nasal lavage samples were collected at baseline during a period of asthma control and then repeated with the onset of URI symptoms at multiple time points within 6 days of the onset of these symptoms, but prior to an initiation of systemic corticosteroids for an exacerbation. Nasal gene expression was assessed by RNA-sequencing and viral infections by PCR. 145 URIs from 104 distinct individuals were analyzed; URIs leading to asthma exacerbations requiring systemic corticosteroids within 10 days of URI onset (cases; n=45) were compared to URIs that resolved without causing an asthma exacerbation (controls; n=100). Differential gene expression was assessed by linear mixed effects modeling and cell deconvolution. Results: There were no differences in the rate of virus detection between cases and controls. Cases demonstrated differential expression of 1516 genes (false discovery rate