Blood mRNA biomarkers distinguish variable systemic and sputum inflammation at treatment initiation of inhaled antibiotics in cystic fibrosis: A prospective non-randomized trial
Abstract
Inhaled antibiotics control chronic airway infection and maintain respiratory health in cystic fibrosis (CF). Given variation in patient responses to inhaled antibiotics, the ability to identify distinct responder phenotypes would facilitate the delivery of personalized care. Previously, a 10-gene panel was identified, measured directly from blood leukocytes, which predicted host response to intravenous antibiotic treatment during pulmonary exacerbations. In the current study, we tested whether the same panel predicted clinical response in subjects receiving a month of inhaled antibiotic therapy with aztreonam lysine (AZLI; Cayston®). A small cohort of CF subjects infected with Pseudomonas aeruginosa were enrolled at baseline health, prior to initiating one month’s treatment with AZLI using the Altera® nebulizer system. Eighteen CF subjects underwent blood leukocyte gene panel measurements, sputum quantitative microbiology, spirometry, and C-reactive protein (CRP) measurement prior to onset and at completion of 4 weeks of AZLI therapy. Mean absolute improvement in percent predicted Forced Expiratory Volume in one second (ppFEV1) was 3%. Significant reductions in sputum bacterial colony counts were detected with treatment. CRP increased following treatment. While single genes within the panel did not change significantly following treatment, the analysis of multigene panel data demonstrated that HCA112 gene predicted ppFEV1 improvement. Hierarchical clustering based on gene…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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