Factors associated with response to treatment of pulmonary exacerbations in cystic fibrosis patients

BACKGROUND: Pulmonary exacerbations are associated with significant lung function decline from baseline in cystic fibrosis (CF) and it is not well understood why some patients do not respond to antibiotic therapy. The objective of this study was to identify factors associated with lung function response to antibiotic treatment of pulmonary exacerbations. METHODS: As a secondary analysis of a randomized, controlled trial of intravenous antibiotic treatment for pulmonary exacerbations in CF patients, we investigated whether baseline factors and changes in sputum bacterial density, serum or sputum inflammatory markers were associated with recovery of lung function and risk of subsequent exacerbation. RESULTS: In 36 of the 70 exacerbations (51%), patients' lung function returned to >100% of their baseline at day 14 of antibiotic treatment; 34 exacerbations were classified as non-responders. Baseline characteristics were not significantly different between responders and non-responders. Less of a drop in FEV1 from baseline to exacerbation (OR 1.09, 95% CI 1.0, 1.18, p=0.04) as well as a greater decrease in sputum neutrophil elastase (OR 2.94, 95% CI 1.07, 8.06, p=0.04) were associated with response to antibiotic treatment at day 14. In addition, higher CRP (HR 1.35 (95% CI: 1.01, 1.78), p=0.04) and sputum neutrophil elastase (HR 1.71 (95% CI: 1.02, 2.88), p=0.04) at day 14 of antibiotic therapy were associated with an increased risk of subsequent exacerbation. CONCLUSIONS: Inadequate reduction of inflammation during an exacerbation is associated with failure to recover lung function and increased risk of subsequent re-exacerbation in CF patients.