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Original research
Longitudinal assessment of lung clearance index to monitor disease progression in children and adults with cystic fibrosis
  1. Alex R Horsley1,2,
  2. John Belcher3,
  3. Katie Bayfield4,
  4. Brooke Bianco2,
  5. Steve Cunningham5,
  6. Catherine Fullwood6,7,
  7. Andrew Jones2,
  8. Anna Shawcross8,
  9. Jaclyn A Smith1,
  10. Anirban Maitra8,
  11. Francis J Gilchrist9,10
  1. 1Division of Infection, Immunity and Respiratory Medicine, The University of Manchester Faculty of Biology, Medicine and Health, Manchester, UK
  2. 2Manchester Adult Cystic Fibrosis Centre, Manchester University NHS Foundation Trust, Manchester, UK
  3. 3School of Medicine, Keele University, Keele, UK
  4. 4Respiratory Medicine, Children's Hospital at Westmead, Westmead, New South Wales, Australia
  5. 5MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
  6. 6Statistics, Research and Innovation, Manchester University NHS Foundation Trust, Manchester, UK
  7. 7MAHSC Centre for Biostatistics, University of Manchester, Manchester, UK
  8. 8Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester, UK
  9. 9Academic Department of Child Health, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
  10. 10Institute of Applied Clinical Sciences, Keele University, Keele, UK
  1. Correspondence to Dr Alex R Horsley, Division of Infection, Immunity and Respiratory Medicine, The University of Manchester Faculty of Biology Medicine and Health, Manchester, UK; alexander.horsley{at}manchester.ac.uk

Abstract

Background Lung clearance index (LCI) is a valuable research tool in cystic fibrosis (CF) but clinical application has been limited by technical challenges and uncertainty about how to interpret longitudinal change. In order to help inform clinical practice, this study aimed to assess feasibility, repeatability and longitudinal LCI change in children and adults with CF with predominantly mild baseline disease.

Methods Prospective, 3-year, multicentre, observational study of repeated LCI measurement at time of clinical review in patients with CF >5 years, delivered using a rapid wash-in system.

Results 112 patients completed at least one LCI assessment and 98 (90%) were still under follow-up at study end. The median (IQR) age was 14.7 (8.6–22.2) years and the mean (SD) FEV1 z-score was −1.2 (1.3). Of 81 subjects with normal FEV1 (>−2 z-scores), 63% had raised LCI (indicating worse lung function). For repeat stable measurements within 6 months, the mean (limits of agreement) change in LCI was 0.9% (−18.8% to 20.7%). A latent class growth model analysis identified four discrete clusters with high accuracy, differentiated by baseline LCI and FEV1. Baseline LCI was the strongest factor associated with longitudinal change. The median total test time was under 19 min.

Conclusions Most patients with CF with well-preserved lung function show stable LCI over time. Cluster behaviours can be identified and baseline LCI is a risk factor for future progression. These results support the use of LCI in clinical practice in identifying patients at risk of lung function decline.

  • cystic fibrosis
  • lung physiology

Data availability statement

Data are available upon reasonable request to the corresponding author.

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Data availability statement

Data are available upon reasonable request to the corresponding author.

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Footnotes

  • Twitter @alexrhorsley

  • Contributors ARH, JAS, AJ conceived the study. ARH led the study. ARH, KB, BB, AS, AM and FJG were responsible for data acquisition. JB, CF and ARH carried out the data analyses, and together with SC, AJ and FJG were responsible for data interpretation and drafting of the work. All authors have approved the final manuscript.

  • Funding This research was funded by the National Institute for Health Research (NIHR), under grant code NIHRCS012-13. Additional support was provided by the NIHR Manchester Clinical Research Facility, the NIHR Manchester Biomedical Research Centre and the NIHR Clinical Research Network. ARH and JAS are supported by the NIHR Manchester Biomedical Research Centre. JAS is funded by a Wellcome Investigator Award (207504/B/17/Z) and is an NIHR Senior Investigator.

  • Disclaimer The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests ARH reports grants from the National Institute for Health Research and non-financial support from Innovision ApS during the conduct of the study, as well as personal fees from Mylan Pharmaceuticals and Vertex Pharmaceuticals and non-financial support from Innovision ApS outside of the submitted work. AM reports personal fees from AbbVie and a travel award from Gilead Sciences.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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