Abstract
Background Proposed criteria for progressive fibrosing interstitial lung disease (PF-ILD) have been linked to increased mortality risk, but lung function trajectory after satisfying individual criteria remains unknown. Because survival is rarely employed as the primary end-point in therapeutic trials, identifying PF-ILD criteria that best predict subsequent change in forced vital capacity (FVC) could improve clinical trial design.
Methods A retrospective, multicentre longitudinal cohort analysis was performed in consecutive patients with fibrotic connective tissue disease-associated ILD (CTD-ILD), chronic hypersensitivity pneumonitis and idiopathic interstitial pneumonia at three US centres (test cohort) and one UK centre (validation cohort). 1-year change in FVC after satisfying proposed PF-ILD criteria was estimated using joint modelling. Subgroup analyses were performed to determine whether results varied across key subgroups.
Results 1227 patients were included, with CTD-ILD predominating. Six out of nine PF-ILD criteria were associated with differential 1-year change in FVC, with radiological progression of fibrosis, alone and in combination with other features, associated with the largest subsequent decline in FVC. Findings varied significantly by ILD subtype, with CTD-ILD demonstrating little change in FVC after satisfying most PF-ILD criteria, while other ILDs showed significantly larger changes. Findings did not vary after stratification by radiological pattern or exposure to immunosuppressant therapy. Near-term change in FVC after satisfying proposed PF-ILD criteria was heterogeneous depending on the criterion assessed and was strongly influenced by ILD subtype.
Conclusions These findings may inform future clinical trial design and suggest ILD subtype should be taken into consideration when applying PF-ILD criteria.
Abstract
Lung function trajectory varies considerably following ILD diagnosis and after satisfying proposed PF-ILD criteria according to ILD diagnosis. These findings suggest diagnosis should be taken into consideration when designing ILD clinical trials. https://bit.ly/2ZF8C7V
Footnotes
Author contributions: Study design: J.M. Oldham, C.T. Lee, C.A. Newton and P.L. Molyneaux. Data collection: J.M. Oldham, C.T. Lee, Z. Wu, W.S. Bowman, J.V. Pugashetti, N. Dao, J. Tonkin, H. Seede, G. Echt, A. Adegunsoye, C.K. Garcia, C.A. Newton and P.L. Molyneaux. Data analysis: J.M. Oldham and P.L. Molyneaux. Interpretation of results: J.M. Oldham, C.T. Lee, W.S. Bowman, J.V. Pugashetti, A. Adegunsoye, F. Chua, T.M. Maher, C.K. Garcia, M.E. Strek, C.A. Newton and P.L. Molyneaux. Manuscript preparation: J.M. Oldham, C.T. Lee, J.V. Pugashetti, T.M. Maher, M.E. Strek, C.A. Newton and P.L. Molyneaux.
This article has supplementary material available from erj.ersjournals.com
Conflict of interest: J.M. Oldham reports grants from the National Institutes of Health, during the conduct of the study; personal fees from Boehringer Ingelheim, Genentech, Lupin, Gatehouse Bio and AmMax Bio, outside the submitted work.
Conflict of interest: C.T. Lee has nothing to disclose.
Conflict of interest: Z. Wu has nothing to disclose.
Conflict of interest: W.S. Bowman has nothing to disclose.
Conflict of interest: J.V. Pugashetti has nothing to disclose.
Conflict of interest: N. Dao has nothing to disclose.
Conflict of interest: J. Tonkin has nothing to disclose.
Conflict of interest: H. Seede has nothing to disclose.
Conflict of interest: G. Echt has nothing to disclose.
Conflict of interest: A. Adegunsoye reports grants from the National Institutes of Health, personal fees for lectures and consultancy from Boehringer Ingelheim, personal fees for consultancy from Genentech, outside the submitted work.
Conflict of interest: F. Chua has nothing to disclose.
Conflict of interest: T.M. Maher has, via his institution, received industry-academic funding from AstraZeneca and GlaxoSmithKline R&D, and has received consultancy or lecture fees from AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Galapagos, Galecto, GlaxoSmithKline R&D, IQVIA, Pliant, Respivant, Roche and Theravance.
Conflict of interest: C.K. Garcia has received institutional funding for research from the National Institutes of Health, Dept of Defense and Boehringer Ingelheim, as well as prior compensation from Pliant Therapeutics Inc. for advisory board service.
Conflict of interest: M.E. Strek reports grants, personal fees and non-financial support from Boehringer Ingelheim, grants from Novartis, outside the submitted work.
Conflict of interest: C.A. Newton reports grants from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (K23HL148498) and NIH National Centre for Advancing Translational Sciences (UL1TR001105), during the conduct of the study; personal fees for consultancy from Boehringer Ingelheim, outside the submitted work.
Conflict of interest: P.L. Molyneaux, via his institution, received industry-academic funding from AstraZeneca, and has received speaker and consultancy fees from Boehringer Ingelheim and Hoffman-La Roche, outside the submitted work.
Support statement: This work was supported by the National Heart, Lung, and Blood Institute (K23HL138190 (J.M. Oldham); T32HL007605 (C.T. Lee); K23HL146942 (A. Adegunsoye); R01HL093096 (C.K. Garcia); T32HL007013 (W.S. Bowman and J.V. Pugashetti); K23HL148498 (C.A. Newton)) and National Center for Advancing Translational Sciences (UL1TR001105 (C.A. Newton)). P.L. Molyneaux is supported by an Action for Pulmonary Fibrosis Mike Bray fellowship. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received May 18, 2021.
- Accepted October 20, 2021.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org
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