The effect of ivacaftor treatment on airway microbial community dynamics in patients with G551D (the “cELTIC” mutation)

G G Einarsson, N J Ronan, L McIlreavey, G O'Callaghan, D M Murphy, M M Tunney, J Elborn, B J Plant

Research output: Contribution to journalMeeting abstract

26 Citations (Scopus)

Abstract

Introduction and Aim: Ivacaftor (Kalydeco), a CFTR potentiator for cystic fibrosis (CF) patients with the G551D mutation, improves lung function and reduces pulmonary exacerbations. However, the impact of ivacaftor on airway microbial community composition and structure is poorly defined. The aim of this study was to determine if ivacaftor treatment is associated with changes in the lower airway microbiota. Methods: Sputum samples (n=64) were collected from adult CF patients (n=21) at a single centre; samples were collected at initiation of ivacaftor treatment before and after 3, 6, 9 and 12 months of treatment. FEV1 (% predicted) was recorded at each timepoint. Molecular-based analysis (Illumina MiSeq) was performed to assess differences in the lower airway microbiota. This included differences in taxonomic richness, community diversity (Shannon-Wiener index), relative abundance and co-occurrence. We considered a valid correlation between specific taxa and changes in lung function, community richness and diversity based on the Spearman's correlation coefficient (p) of >0.5 and adjusted P0.5 and adjusted P0.05]. However, significant intra-individual differences were observed for the majority of samples over the course of the study. The mean percent predicted FEV1 increase between pre-treatment and the last available post-treatment visit was 12% (range-9% to 58%). For 14 patients, we observed changes in percent predicted FEV1 that paralleled changes in both taxonomic richness and diversity. In a number of cases, a reduction in Pseudomonas spp. and an increase in Streptococcus spp. and a number of anaerobic taxa was apparent. The observed community richness and diversity negatively correlated with a higher proportion of Pseudomonas spp. [p=-0.65; P0.5; P0.5; P0.5; P
Original languageEnglish
Pages (from-to)302-303
Number of pages2
JournalPediatric Pulmonology
Volume50
DOIs
Publication statusPublished - 04 Sep 2015

Keywords

  • Actinomyces
  • Fusobacterium
  • North American
  • Prevotella
  • Pseudomonas
  • Staphylococcus
  • Stenotrophomonas
  • Streptococcus
  • Veillonella
  • adult
  • airway
  • community
  • community dynamics
  • correlation coefficient
  • cystic fibrosis
  • human
  • ivacaftor
  • lower respiratory tract
  • lung function
  • microbial community
  • microflora
  • mutation
  • patient
  • sputum
  • taxon

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