Obstructive Spirometric Index Predicts Lung Function Response to LAMA in asthma: A Post-Hoc Analysis of the CAPTAIN Trial

Abstract

Rationale: The Obstructive Spirometric Index (OSI) integrates the forced expiratory volume in 1 second (FEV₁) and FEV₁/forced vital capacity (FEV₁/FVC) to better capture the risk associated with airflow limitation compared to FEV1 and FEV₁/FVC alone. However, its theragnostic value is unclear. Aim: To assess OSI’s predictive value for response to the long-acting muscarinic antagonist (LAMA) umeclidinium (UMEC). Methods: We conducted a post-hoc analysis of CAPTAIN, a double-blind, 24–52-week randomized controlled trial in uncontrolled moderate-to-severe asthma. Participants were factorially randomised to ICS/LABA inhalers with/without UMEC. The interaction between baseline lung function (FEV₁% or OSI) and UMEC (yes/no) was assessed using multivariable models: negative binomial for asthma attacks and linear for ΔFEV₁ at 52 weeks. Results: Among 2,436 patients, neither FEV₁ nor OSI interacted with UMEC for asthma attack risk. In 543 patients with available FEV₁ at 52 weeks, OSI significantly interacted with UMEC for lung function improvement (p=0.01), while FEV₁ did not. Higher OSI was associated with greater lung function improvement following UMEC (Figure). Conclusions: The OSI, which integrates FEV1 and FEV1/FVC, predicts lung function improvement with UMEC, whereas FEV₁ alone does not. OSI may identify treatment opportunities. Funding: GSK/APQ/FRQS/NIHR ( NCT02924688 ). erj;66/suppl_69/PA5764/F1 F1 F1

Authors 18

1. Samuel Mailhot-Larouche

   Université de Sherbrooke

   Affiliation as printed

   1Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Canada

2. Fleur L. Meulmeester Aachen 2Dept. of Biomedical Data Sciences

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   2Dept. of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, Netherlands

3. Sanjay Ramakrishnan

   The University of Western Australia · Institute for Respiratory Health

   Affiliation as printed

   3lnstitute for Respiratory Health & UWA Medical School, University of Western Australia, Perth, Australia

4. Michael E. Wechsler

   National Jewish Health

   Affiliation as printed

   4National Jewish Health, Denver, United States

5. Guy Brusselle

   Ghent University Hospital

   Affiliation as printed

   5Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium

6. Jonathan Corren

   University of California, Los Angeles

   Affiliation as printed

   6UCLA, Los Angeles, United States

7. Sarah E. Diver

   University of Leicester · NIHR Leicester Biomedical Research Centre

   Affiliation as printed

   7Department of Respiratory Sciences, lnstitute for Lung Health, NIHR Respiratory BRC, University of Leicester, Leicester, United Kingdom

8. Christopher E Brightling

   University of Leicester · NIHR Leicester Biomedical Research Centre

   Affiliation as printed

   7Department of Respiratory Sciences, lnstitute for Lung Health, NIHR Respiratory BRC, University of Leicester, Leicester, United Kingdom

9. Nicola Alexander Hanania

   Baylor College of Medicine

   Affiliation as printed

   9Baylor College of Medicine, Houston, United States

10. Alison Moore

    GlaxoSmithKline (United Kingdom)

    Affiliation as printed

    11GlaxoSmithKline, London, United Kingdom

11. Philippe Lachapelle

    Université de Sherbrooke

    Affiliation as printed

    1Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Canada

12. Timothy Hinks

    University of Oxford

    Affiliation as printed

    12Respiratory Medicine Unit and Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

13. Mark Holliday

    Medical Research Institute of New Zealand

    Affiliation as printed

    13Medical Research lnstitute of New Zealand, Wellington, New Zealand

14. Richard W. Beasley

    Medical Research Institute of New Zealand

    Affiliation as printed

    13Medical Research lnstitute of New Zealand, Wellington, New Zealand

15. Jacob K. Sont Aachen

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    14Dept. of Biomedical Data Sciences. Leiden University Medical Centre, Leiden, Netherlands

16. Ewout Willem Steyerberg

    University Medical Center Utrecht

    Affiliation as printed

    15Julius Center, University Medical Center, Utrecht, Netherlands

17. Ian Douglas Pavord

    University of Oxford

    Affiliation as printed

    12Respiratory Medicine Unit and Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

18. Simon Couillard

    Université de Sherbrooke

    Affiliation as printed

    16Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke Medicine Unit and Oxford Respiratory NIHR BRC, Nuffield Department of Medicine. University of Oxford, Canada