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Original research
Disease monitoring using lung function trajectory in lymphangioleiomyomatosis: assessment in two national cohorts
  1. Jan Johnson1,
  2. Iain Stewart2,
  3. Simon R Johnson3
  1. 1Centre for Respiratory Research, University of Nottingham Faculty of Medicine and Health Sciences, Nottingham, UK
  2. 2National Heart & Lung Institute, Imperial College London, London, UK
  3. 3NIHR BRC and Biodiscovery Institute, University of Nottingham Faculty of Medicine and Health Sciences, Nottingham, UK
  1. Correspondence to Professor Simon R Johnson, NIHR BRC and Biodiscovery Institute, University of Nottingham Faculty of Medicine and Health Sciences, Nottingham NG7 2UH, Nottingham, UK; simon.johnson{at}nottingham.ac.uk

Abstract

Study question In lymphangioleiomyomatosis, airflow obstruction and impairment of gas transfer progress at variable rates and serial lung function is recommended for disease monitoring. As these measurements are variable, recognising subjects needing treatment can be difficult. We used two prospective national cohorts to study change over time and variation in FEV1 to inform clinical decision making.

Patients and methods Clinical and lung function data for 141 UK and 148 American subjects were studied. Multilevel mixed effects modelling, route mean square analysis of errors and Bland-Altman analysis were used to analyse variability in lung function over time.

Results At baseline assessment, DLCO was reduced to a greater degree than FEV1. In untreated patients, FEV1 and DLCO declined at proportionately similar rates independent of initial lung function. In mechanistic target of rapamycin (mTOR) inhibitor treated patients, FEV1 stabilised but DLCO continued to decline. FEV1/DLCO per cent predicted ratio was 1.37 (0.43) at baseline and increased to 1.41 (0.50) after 42 (24) months (p=0.0002). At least five measurements were required before >70% of individuals had estimates of rate of FEV1 loss within 50 mL/year and DLCO loss within 0.1 mmol/min/kPa/year of the final values.

Conclusions While FEV1 and DLCO fall proportionately in most, in early disease and during mTOR inhibitor treatment, DLCO should also be monitored as it may fall independent of FEV1. Since at least five observations over many months are required to make confident estimates of FEV1 and DLCO trajectories, new strategies are needed to measure disease activity and target early treatment appropriately.

  • Respiratory Measurement

Data availability statement

Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. UK data can be made available in an anonymised format, on request from the corresponding author on a collaborative basis for academic research. US data are available with linked, anonymised clinical information from the National Disease Research Interchange (Philadelphia, USA).

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Data availability statement

Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. UK data can be made available in an anonymised format, on request from the corresponding author on a collaborative basis for academic research. US data are available with linked, anonymised clinical information from the National Disease Research Interchange (Philadelphia, USA).

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Footnotes

  • Contributors JJ collected, analysed and reviewed clinical data. IS advised on and performed the data analysis. SRJ collected, analysed and reviewed clinical data and is responsible for study design, data analysis, writing the manuscript and is guarantor for the study. All authors contributed equally to the work.

  • Funding This study was supported by the Nottingham NIHR Biomedical Research Centre, Nottingham University NHS Trust. Nottingham NG7 2UH, UK.

  • Competing interests SRJ reports grants from National Institute for Health Research, grants from The LAM Foundation, grants from LAM Action, during the conduct of the study; personal fees from Pfizer, outside the submitted work.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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