321 Changes in lung function and airway microbiology following ivacaftor therapy in an adult G551D homozygote

Abstract

Objectives Ivacaftor has increased lung function and decreased pulmonary exacerbations and intravenous antibiotic use in patients with CF carrying the G551D mutation. This case study describes the effects of ivacaftor on airway microbiology and lung function in a G551D homozygote with chronic Pseudomonas aeruginosa (PA) infection. Methods All sputum culture reports prior to ivacaftor therapy were reviewed. Following ivacaftor initiation sputum samples were sent for standard culture at each clinic visit. 16S gene rRNA pyrosequencing was performed on paired sputum samples collected immediately prior to and after 6 months of ivacaftor therapy. FEV 1 was measured at baseline and at each follow up visit. Sweat chloride was assessed pre-treatment and at 6 months. Results Mucoid PA infection was acquired in 1983. The pre-ivacaftor baseline sputum sample and all preceding 26 samples taken over 8 years were culture positive for PA. 7 consecutive samples collected over 16 months following ivacaftor were culture negative for PA. A later sample was culture positive for the original infecting strain of PA (using variable number tandem repeat profiling). 16S gene rRNA pyrosequencing showed a drop in relative abundance of PA from 98.2% to 4.8% and an increase in microbial diversity over the 6 month sample period. FEV 1 improved from 68% predicted (baseline) to 90% predicted (20 months post ivacaftor). Sweat chloride reduced from 105 mmol/L (baseline) to 52 mmol/L (6months). Conclusion Bacterial diversity and relative abundance of typical CF pathogens may be significantly altered by modulation of both CFTR alleles. Sputum culture clearance of mucoid PA on should be interpreted with caution.