title: Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations.
abstract: Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response.A systematic literature search was performed to identify prospective observational studies. Factors predicting the relative change in LCI and spirometry were evaluated while adjusting for within-study clustering.Six previously reported studies and one unpublished study, which included 176 pulmonary exacerbations in both paediatric and adult patients, were included. Overall, LCI significantly decreased by 0.40 units (95% CI -0.60- -0.19, p=0.004) or 2.5% following treatment. The relative change in LCI was significantly correlated with the relative change in forced expiratory volume in 1 s (FEV1), but results were discordant in 42.5% of subjects (80 out of 188). Higher (worse) baseline LCI was associated with a greater improvement in LCI (slope: -0.9%, 95% CI -1.0- -0.4%).LCI response to therapy for pulmonary exacerbations is heterogeneous in CF patients; the overall effect size is small and results are often discordant with FEV1.
authors.affiliation: Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada Both authors contributed equally.
authors.forename: Nicole
authors.initials: N
authors.lastname: Sonneveld
authors.affiliation: Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada Both authors contributed equally sanja.stanojevic@sickkids.ca.
authors.forename: Sanja
authors.initials: S
authors.lastname: Stanojevic
authors.affiliation: Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
authors.forename: Reshma
authors.initials: R
authors.lastname: Amin
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Aurora
authors.affiliation: Royal Brompton Hospital, London, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Davies
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Elborn
authors.affiliation: Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Horsley
authors.affiliation: University Children's Hospital Bern, Bern, Switzerland University Children's Hospital Basel (UKBB), Basel, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Latzin
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: O'Neill
authors.affiliation: Dept of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Robinson
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Scrase
authors.affiliation: Dept of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, Australia Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Hiran
authors.initials: H
authors.lastname: Selvadurai
authors.affiliation: Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
authors.forename: Padmaja
authors.initials: P
authors.lastname: Subbarao
authors.affiliation: Royal Children's Hospital, Melbourne, Australia Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: Liam
authors.initials: L
authors.lastname: Welsh
authors.affiliation: University Children's Hospital Bern, Bern, Switzerland University Children's Hospital Basel (UKBB), Basel, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Yammine
authors.affiliation: Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada Physiology and Experimental Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada Faculty of Medicine, Dept of Paediatrics, University of Toronto, Toronto, ON, Canada.
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001944:Breath Tests / Q000379:methods; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007262:Infusions, Intravenous; D008168:Lung / Q000382:microbiology / Q000503:physiopathology*; D008171:Lung Diseases / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D013147:Spirometry / Q000379:methods; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents