title: Physiological mechanisms of dyspnea relief following ivacaftor in cystic fibrosis: a case report.
abstract: Ivacaftor is a novel oral pharmacologic agent that specifically targets the genetic defect of cystic fibrosis (CF) by augmenting chloride conductance through the CF transmembrane regulator (CFTR) protein. For individuals with CF and at least one copy of the G551D gating mutation, improvements in sweat chloride, nutritional parameters, lung function, respiratory symptoms, and exercise tolerance (i.e., 6-min walk distance) are attained within 2 weeks of initiating ivacaftor. However, there are no reports detailing the physiological and sensory implications of these improvements and their underlying mechanisms. We performed detailed cardiopulmonary exercise testing pre- and post-initiation of ivacaftor in a 27-year old male with CF (CFTR genotype F508del/G551D) and chronic airflow obstruction (FEV1/FVC=0.44). An improvement of FEV1 (by 16%) following ivacaftor was accompanied by clinically significant improvements in exercise capacity (by 14%) and exertional dyspnea (by up to 5 Borg scale units). These improvements were attributable, at least in part, to favorable alterations in the ventilatory response to exercise, including improvements in breathing patterns (e.g., increased tidal volume and reduced breathing frequency) and dynamic operating lung volumes (e.g., increased inspiratory reserve volume and inspiratory capacity) and decreases in dynamic mechanical ventilatory constraints.
authors.affiliation: Division of Respirology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Quon
authors.affiliation: Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada; Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Michele R
authors.initials: MR
authors.lastname: Schaeffer
authors.affiliation: Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada; School of Kinesiology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Molgat-Seon
authors.affiliation: Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Sabrina S
authors.initials: SS
authors.lastname: Wilkie
authors.affiliation: Division of Respirology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada; Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Pearce G
authors.initials: PG
authors.lastname: Wilcox
authors.affiliation: Centre for Heart Lung Innovation, Providence Health Care Research Institute, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada; Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada. Electronic address: jordan.guenette@hli.ubc.ca.
authors.forename: Jordan A
authors.initials: JA
authors.lastname: Guenette
mesh_terms: D000328:Adult; D000627:Aminophenols / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy*; D004417:Dyspnea / Q000188:drug therapy* / Q000209:etiology; D017079:Exercise Tolerance / Q000187:drug effects*; D006801:Humans; D008297:Male; D015363:Quinolones / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*
chemical_list: D000627:Aminophenols; D015363:Quinolones; C545203:ivacaftor
keywords: Cystic fibrosis; Dyspnea; Ivacaftor