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Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections
Journal article   Open access   Peer reviewed

Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections

Katherine B Hisert, Sonya L Heltshe, Christopher Pope, Peter Jorth, Xia Wu, Rachael M Edwards, Matthew Radey, Frank J Accurso, Daniel J Wolter, Gordon Cooke, …
American journal of respiratory and critical care medicine, Vol.195(12), pp.1617-1628
06/15/2017
DOI: 10.1164/rccm.201609-1954OC
PMCID: PMC5476912
PMID: 28222269
url
https://doi.org/10.1164/rccm.201609-1954OCView
Published (Version of record) Open Access

Abstract

Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.
 Respiratory Tract Infections - metabolism Cystic Fibrosis - metabolism Humans Respiratory Tract Infections - prevention & control Chloride Channel Agonists - therapeutic use Male Tomography, X-Ray Computed Aminophenols - therapeutic use Cystic Fibrosis Transmembrane Conductance Regulator - metabolism Lung - diagnostic imaging Cystic Fibrosis - diagnostic imaging Sputum - metabolism Cystic Fibrosis Transmembrane Conductance Regulator - drug effects Inflammation - metabolism Sputum - drug effects Quinolones - therapeutic use Adult Female Inflammation - prevention & control Lung - metabolism Cystic Fibrosis - drug therapy

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