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. 2023 Apr 1;61(4):2201245.
doi: 10.1183/13993003.01245-2022. Print 2023 Apr.

Interstitial lung disease progression after genomic usual interstitial pneumonia testing

Sachin Chaudhary  1 , S Sam Weigt  2 , Manuel L Ribeiro Neto  3 , Bryan S Benn  4 , Janelle Vu Pugashetti  5 , Rebecca Keith  6 , Arista Chand  1 , Scott Oh  2 , Fayez Kheir  7 , Vijaya Ramalingam  4   8 , Joshua J Solomon  6 , Richart Harper  5 , Joseph A Lasky  9 , Justin M Oldham  10   11
Affiliations

Interstitial lung disease progression after genomic usual interstitial pneumonia testing

Sachin Chaudhary et al. Eur Respir J. .

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.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Strobe diagram
Figure 2.
Figure 2.
Genomic UIP classification stratified by baseline HRCT pattern
Figure 3.
Figure 3.
ILD diagnosis following gUIP testing stratified by baseline HRCT pattern
Figure 4.
Figure 4.
Kaplan-Meier survival curve comparing progression-free survival between groups stratified by genomic UIP classification.
See this image and copyright information in PMC

Comment in

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