Biomarkers associated with clinical response to cystic fibrosis pulmonary exacerbation treatment and adjuvant prednisone therapy

Cystic fibrosis (CF) pulmonary exacerbations are characterized by increased inflammation. The objectives of this study were to identify inflammatory biomarkers associated with 1) early clinical response to IV antibiotics (by day 7); and 2) response to the delayed use of prednisone (from day 7 to 14). This was a secondary analysis of a clinical trial evaluating the adjunctive use of prednisone in pwCF. We studied blood and sputum inflammatory markers at Day 0 that were associated with early response to IV antibiotics at Day 7 (early responder analysis). In non-responders to IV antibiotics alone, we examined biomarkers at Day 7 that were associated with response to oral prednisone at Day 14. Clinical outcomes included: 1) absolute change in ppFEV1; 2) absolute change in chronic respiratory infection symptom score (CRISS); and 3) composite outcome of absolute improvement in ppFEV1 of ≥ 8 % and CRISS score decrease by ≥ 11 (early responder analysis only). Higher Day 0 sputum IFN-γ and lower blood calprotectin were associated with improved Day 7 lung function response; lower Day 0 sputum IL-8 and blood eotaxin were associated with improved symptom scores. In non-responders at Day 7, higher blood eotaxin was associated with better lung function response and higher blood CRP was associated with worse symptom score response at Day 14 in those treated with prednisone versus placebo. Sputum and blood inflammatory markers are associated with early response to IV antibiotics and change with prednisone treatment during PEx.