Valerie J Waters1, Sanja Stanojevic2, Nicole Sonneveld3, Michelle Klingel4, Hartmut Grasemann5, Yvonne C W Yau6, Elizabeth Tullis7, Pearce Wilcox8, Andreas Freitag9, Mark Chilvers10, Felix A Ratjen11. 1. Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Valerie.Waters@sickkids.ca. 2. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Sanja.Stanojevic@sickkids.ca. 3. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: n.sonneveld@erasmusmc.nl. 4. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: michelle.klingel@sickkids.ca. 5. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Hartmut.Grasemann@sickkids.ca. 6. Division of Microbiology, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Yvonne.Yau@sickkids.ca. 7. Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto. Electronic address: Tullise@smh.ca. 8. Division of Respiratory Medicine, Department of Medicine, St Paul's Hospital, University of British Columbia, Vancouver. Electronic address: PWilcox@providencehealth.bc.ca. 9. Division of Respiratory Medicine, Department of Medicine, Hamilton Health Sciences Center, McMaster University, Hamilton. Electronic address: freitaga@mcmaster.ca. 10. Division of Respiratory Medicine, Department of Pediatrics, British Columbia Children's Hospital, Vancouver. Electronic address: mchilvers@cw.bc.ca. 11. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto. Electronic address: Felix.Ratjen@sickkids.ca.
Abstract
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.
RCT Entities:
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.
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