Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations

Nicole Sonneveld; Sanja Stanojevic; Reshma Amin; Paul Aurora; Jane Davies; J Stuart Elborn; Alex Horsley; Philipp Latzin; Katherine O'Neill; Paul Robinson; Emma Scrase; Hiran Selvadurai; Padmaja Subbarao; Liam Welsh; Sophie Yammine; Felix Ratjen

doi:10.1183/09031936.00211914

Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations

Eur Respir J. 2015 Oct;46(4):1055-64. doi: 10.1183/09031936.00211914. Epub 2015 Jul 9.

Authors

Nicole Sonneveld¹, Sanja Stanojevic², Reshma Amin³, Paul Aurora⁴, Jane Davies⁵, J Stuart Elborn⁶, Alex Horsley⁷, Philipp Latzin⁸, Katherine O'Neill⁶, Paul Robinson⁹, Emma Scrase⁴, Hiran Selvadurai⁹, Padmaja Subbarao¹⁰, Liam Welsh¹¹, Sophie Yammine⁸, Felix Ratjen¹²

Affiliations

¹ Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada Both authors contributed equally.
² 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.
³ Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁴ Great Ormond Street Hospital, London, UK.
⁵ Royal Brompton Hospital, London, UK.
⁶ Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
⁷ Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
⁸ University Children's Hospital Bern, Bern, Switzerland University Children's Hospital Basel (UKBB), Basel, Switzerland.
⁹ 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.
¹⁰ 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.
¹¹ Royal Children's Hospital, Melbourne, Australia Murdoch Children's Research Institute, Melbourne, Australia.
¹² 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.

PMID: 26160868
DOI: 10.1183/09031936.00211914

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Anti-Bacterial Agents / administration & dosage*
Breath Tests / methods
Child
Child, Preschool
Cluster Analysis
Cystic Fibrosis / drug therapy*
Cystic Fibrosis / physiopathology*
Female
Forced Expiratory Volume
Humans
Infusions, Intravenous
Lung / microbiology
Lung / physiopathology*
Lung Diseases / etiology
Lung Diseases / physiopathology
Male
Middle Aged
Observational Studies as Topic
Prospective Studies
Respiratory Function Tests
Retrospective Studies
Spirometry / methods
Young Adult

Substances

Anti-Bacterial Agents

Grants and funding

NIHR-CS-012-013/DH_/Department of Health/United Kingdom