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Interstitial lung disease progression after genomic usual interstitial pneumonia testing

Sachin Chaudhary, S. Sam Weigt, Manuel L. Ribeiro Neto, Bryan S. Benn, Janelle Vu Pugashetti, Rebecca Keith, Arista Chand, Scott Oh, Fayez Kheir, Vijaya Ramalingam, Joshua J. Solomon, Richart Harper, Joseph A. Lasky, Justin M. Oldham
European Respiratory Journal 2023 61: 2201245; DOI: 10.1183/13993003.01245-2022
Sachin Chaudhary
1Division of Pulmonary and Critical Care Medicine, University of Arizona, Tucson, AZ, USA
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S. Sam Weigt
2Division of Pulmonary and Critical Care Medicine, University of California at Los Angeles, Los Angeles, CA, USA
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Manuel L. Ribeiro Neto
3Department of Pulmonary Medicine, Cleveland Clinic, Cleveland, OH, USA
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Bryan S. Benn
4Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
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Janelle Vu Pugashetti
5Division of Pulmonary, Critical Care and Sleep Medicine, University of California at Davis, Sacramento, CA, USA
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  • ORCID record for Janelle Vu Pugashetti
Rebecca Keith
6Division of Pulmonary and Critical Care and Sleep Medicine, National Jewish Health, Denver, CO, USA
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Arista Chand
1Division of Pulmonary and Critical Care Medicine, University of Arizona, Tucson, AZ, USA
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Scott Oh
2Division of Pulmonary and Critical Care Medicine, University of California at Los Angeles, Los Angeles, CA, USA
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Fayez Kheir
7Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
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Vijaya Ramalingam
4Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
8Northeast Georgia Physicians Group
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Joshua J. Solomon
6Division of Pulmonary and Critical Care and Sleep Medicine, National Jewish Health, Denver, CO, USA
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Richart Harper
5Division of Pulmonary, Critical Care and Sleep Medicine, University of California at Davis, Sacramento, CA, USA
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Joseph A. Lasky
9Division of Pulmonary and Critical Care Medicine, Tulane University, New Orleans, LA, USA
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Justin M. Oldham
10Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA
11Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA
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  • For correspondence: oldhamj@med.umich.edu
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Abstract

Background A genomic classifier for usual interstitial pneumonia (gUIP) has been shown to predict histological UIP with high specificity, increasing diagnostic confidence for idiopathic pulmonary fibrosis (IPF). Whether those with positive gUIP classification exhibit a progressive, IPF-like phenotype remains unknown.

Methods A pooled, retrospective analysis of patients who underwent clinically indicated diagnostic bronchoscopy with gUIP testing at seven academic medical centres across the USA was performed. We assessed the association between gUIP classification and 18-month progression-free survival (PFS) using Cox proportional hazards regression. PFS was defined as the time from gUIP testing to death from any cause, lung transplant, ≥10% relative decline in forced vital capacity (FVC) or censoring at the time of last available FVC measure. Longitudinal change in FVC was then compared between gUIP classification groups using a joint regression model.

Results Of 238 consecutive patients who underwent gUIP testing, 192 had available follow-up data and were included in the analysis, including 104 with positive gUIP classification and 88 with negative classification. In multivariable analysis, positive gUIP classification was associated with reduced PFS (hazard ratio 1.58, 95% CI 0.86–2.92; p=0.14), but this did not reach statistical significance. Mean annual change in FVC was −101.8 mL (95% CI −142.7– −60.9 mL; p<0.001) for those with positive gUIP classification and −73.2 mL (95% CI −115.2– −31.1 mL; p<0.001) for those with negative classification (difference 28.7 mL, 95% CI −83.2–25.9 mL; p=0.30).

Conclusions gUIP classification was not associated with differential rates of PFS or longitudinal FVC decline in a multicentre interstitial lung disease cohort undergoing bronchoscopy as part of the diagnostic evaluation.

Abstract

While genomic UIP classification is not associated with categorical ILD progression, it is associated with modestly higher 1-year rate of FVC decline http://bit.ly/3ii99Gb

Footnotes

  • Author contributions: Study design: S. Chaudhary and J.M. Oldham. Bronchoscopy and sample acquisition: S. Chaudhary, S.S. Weigt, M.L. Ribeiro Neto, B.S. Benn, R. Keith, S. Oh, F. Kheir, V. Ramalingam, J. Solomon, R. Harper, J.A. Lasky and J.M. Oldham. Data collection: S. Chaudhary, S.S. Weigt, M.L. Ribeiro Neto, B.S. Benn, J.V. Pugashetti, R. Keith, AC, F. Kheir, V. Ramalingam, J. Solomon, J.A. Lasky and J.M. Oldham. Data analysis: J.M. Oldham. Interpretation of results: S. Chaudhary, S.S. Weigt, M.L. Ribeiro Neto, B.S. Benn, J. Solomon, J.A. Lasky and J.M. Oldham. Manuscript preparation: S. Chaudhary, S.S. Weigt, M.L. Ribeiro Neto, B.S. Benn, J.V. Pugashetti, J. Solomon, J.A. Lasky and J.M. Oldham.

  • This article has an editorial commentary: https://doi.org/10.1183/13993003.00033-2023

  • Conflict of interest: S. Chaudhary reports consulting fees from Veracyte and Boehringer Ingelheim, outside the submitted work. S.S. Weigt reports consulting fees from Vercyte, and lecture honoraria from Genentech/Roche and Boehringer Ingelheim, outside the submitted work. J.V. Pugashetti is a member of the American Thoracic Society Clinical Problems Planning Committee, outside the submitted work. R. Keith reports lecture honoraria from Envisia, outside the submitted work. S. Oh reports lecture honoraria from Veracyte, outside the submitted work. F. Kheir reports lecture honoraria from Veracyte, Biodesix and UpToDate, and leadership roles with the American College of Chest Physicians and Society of Advanced Bronchoscopy, outside the submitted work. J. Solomon reports grants from Boehringer Ingelheim, Pfizer and NIH, and lecture honoraria from Boehringer Ingelheim, outside the submitted work. J.A. Lasky reports lecture honoraria from Veracyte and Boehringer Ingelheim, advisory board participation with Galecto, United Therapeutics and Genentech, and acts as CMO of the Pulmonary Fibrosis Foundation, outside the submitted work. J.M. Oldham reports grants from the National Institutes of Health (K23HL138190); reports consulting fees from Boehringer Ingelheim, Lupin Pharmaceuticals, AmMax Bio, Roche and Veracyte, a patent “TOLLIP TT genotype for NAC use in IPF” issued, advisory board participation for Endeavor Biomedicines, and acts as Associate Editor for CHEST and Program Committee for the American Thoracic Society, outside the submitted work. All other authors have nothing to disclose.

  • Support statement: This work was supported by the NHLBI (K23HL138190). Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received July 4, 2022.
  • Accepted November 23, 2022.
  • Copyright ©The authors 2023. For reproduction rights and permissions contact permissions{at}ersnet.org
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Interstitial lung disease progression after genomic usual interstitial pneumonia testing
Sachin Chaudhary, S. Sam Weigt, Manuel L. Ribeiro Neto, Bryan S. Benn, Janelle Vu Pugashetti, Rebecca Keith, Arista Chand, Scott Oh, Fayez Kheir, Vijaya Ramalingam, Joshua J. Solomon, Richart Harper, Joseph A. Lasky, Justin M. Oldham
European Respiratory Journal Apr 2023, 61 (4) 2201245; DOI: 10.1183/13993003.01245-2022

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Interstitial lung disease progression after genomic usual interstitial pneumonia testing
Sachin Chaudhary, S. Sam Weigt, Manuel L. Ribeiro Neto, Bryan S. Benn, Janelle Vu Pugashetti, Rebecca Keith, Arista Chand, Scott Oh, Fayez Kheir, Vijaya Ramalingam, Joshua J. Solomon, Richart Harper, Joseph A. Lasky, Justin M. Oldham
European Respiratory Journal Apr 2023, 61 (4) 2201245; DOI: 10.1183/13993003.01245-2022
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