Evidence map›Paper›PMID 41738192›Full record

Observational studyAmerican journal of respiratory and critical care medicine2026

Molecular endotypes predict differential response to immunosuppressant therapy in non-idiopathic pulmonary fibrosis interstitial lung disease.

Manoj V Maddali, Janelle V Pugashetti, Shaun M Pienkos, Andrew R Moore, Samuel B Konkol, John S Kim, Shwu-Fan Ma, Chad A Newton, Christine K Garcia, Ayodeji Adegunsoye and 12 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in American journal of respiratory and critical care medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Mycophenolate and azathioprine in fibrotic interstitial lung disease.American journal of respiratory and critical care medicine · 2026
    Observational
  2. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Manoj V MaddaliDivision of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA, United States.
Janelle V PugashettiDivision of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, United States.
Shaun M PienkosDivision of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA, United States.ORCID 0009-0001-8409-4803
Andrew R MooreDivision of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA, United States.
Samuel B KonkolDivision of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA, United States.
John S KimDivision of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA, United States.
Shwu-Fan MaDivision of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA, United States.
Chad A NewtonDivision of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Christine K GarciaDivision of Pulmonary and Critical Care Medicine, Columbia University, New York, NY, United States.
Ayodeji AdegunsoyeDivision of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, United States.
Mary E StrekDivision of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, United States.
Ching-Hsien ChenDivision of Pulmonary and Critical Care Medicine, University of California-Davis, Davis, CA, United States.
Angela L LinderholmDivision of Pulmonary and Critical Care Medicine, University of California-Davis, Davis, CA, United States.
Rachel L ZemansDivision of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, United States.
Bethany B MooreDivision of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, United States.
Paul J WoltersDivision of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California San Francisco, San Francisco, CA, United States.
Rishi RajDivision of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA, United States.
Jonathan H ChenDepartment of Biomedical Data Science, Stanford University, Stanford, CA, United States.
Fernando J MartinezDivision of Pulmonary and Critical Care Medicine, University of Massachusetts, Worcester, MA, United States.
Imre NothDivision of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA, United States.
Angela J RogersDivision of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA, United States.
Justin M OldhamDivision of Pulmonary and Critical Care Medicine, University of California-Davis, Davis, CA, United States.

Funding

POSTDOCTORAL TRAINING IN MEDICAL INFORMATION SCIENCEST15LM007033 · NLM · STANFORD UNIVERSITY · PI SYLVIA KATINA PLEVRITIS · 1985 to 2026
$25.5M
PULMONARY CELLULAR AND MOLECULAR BIOLOGY TRAININGT32HL007749 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Pickett Dickson · 1993 to 2026
$19.9M
Pulmonary Fibrosis and Telomerase DysfunctionR01HL093096 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI GARCIA, CHRISTINE KIM · 2009 to 2024
$6.9M
Lung Remodeling Mediated by Telomere Dysfunction in Alveolar Type II CellsR01HL139897 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Paul j WOLTERS · 2018 to 2026
$5.5M
Proteomic Profiling of Idiopathic Pulmonary Fibrosis Progression TrajectoryR01HL169166 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Justin M Oldham · 2023 to 2026
$2.7M
Prognostic Biomarker Development in Progressive Fibrosing Interstitial Lung DiseaseR01HL166290 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Justin M Oldham · 2024 to 2026
$2.2M
Immune crosstalk in lung injury and fibrosisR35HL176572 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Bethany B. Moore · 2025 to 2026
$2.1M
The Prognostic and Predictive Impact of Telomere Length in Fibrotic Interstitial Lung DiseaseR01HL176839 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI Chad Alan Newton · 2025 to 2026
$1.5M
1/2 Prospective tReatment EffiCacy in IPF uSlng genOtype for Nac Selection (PRECISIONS) trial and Molecular Endophenotyping in Idiopathic Pulmonary Fibrosis and Interstitial Lung Diseases studyUG3HL145266 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI MARTINEZ, FERNANDO J, NOTH, IMRE · 2019 to 2019
$977k
Molecular Markers of Idiopathic Pulmonary Fibrosis ProgressionK23HL148498 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI NEWTON, CHAD ALAN · 2020 to 2024
$891k
Role of polyunsaturated fatty acids in pulmonary fibrosisK23HL150301 · NHLBI · UNIVERSITY OF VIRGINIA · PI KIM, JOHN S · 2021 to 2025
$858k
Improving Pulmonary Fibrosis Classification with Genomics Informed Phenotypic ClustersK23HL146942 · NHLBI · UNIVERSITY OF CHICAGO · PI ADEGUNSOYE, AYODEJI · 2020 to 2024
$810k
A.A. K23HL146942B.B.M. R35HL176572C.A.N. K23HL148498C.A.N. R01HL176839C.K.G. R01HL093096F.J.M., I.N. UG3HL145266J.M.O. R01HL166290J.M.O. R01HL169166J.S.K. K23HL150301J.V.P. T32HL007749M.V.M. T15LM007033NHLBI NIH HHS K23 HL146942NHLBI NIH HHS K23 HL148498NHLBI NIH HHS K23 HL150301NHLBI NIH HHS K23 HL171871NHLBI NIH HHS L30 HL181822NHLBI NIH HHS R01 HL093096NHLBI NIH HHS R01 HL139897NHLBI NIH HHS R01 HL166290NHLBI NIH HHS R01 HL169166NHLBI NIH HHS R01 HL176839NHLBI NIH HHS R35 HL176572NHLBI NIH HHS T32 HL007749NHLBI NIH HHS UG3 HL145266NLM NIH HHS T15 LM007033P.J.W. R01HL139897
6 · The paper itself

Abstract

rationaleInterstitial lung diseases (ILDs) are a clinically and biologically diverse group of disorders characterized by varying inflammation and fibrosis of the lung parenchyma. Immunosuppressant therapy is commonly used to treat non-idiopathic pulmonary fibrosis (non-IPF) ILD, but treatment response is variable and difficult to predict.

objectiveIdentify and validate molecular endotypes of non-IPF ILD.

methodsTwenty plasma proteins associated with inflammation were used to perform latent class analysis in 2 observational non-IPF ILD cohorts (discovery n = 676; validation n = 585). Proteins were measured using a semi-quantitative Olink Explore 3072 platform. The primary outcome was 3-year transplant-free survival. Weighted Cox regression was used to assess differential response to mycophenolate or azathioprine in each cohort according to molecular endotype classification.

resultsA 2-class model best fit both cohorts (P <0.01), with Class 2 comprising ∼30% of patients. Compared to Class 1, Class 2 was associated with significantly lower 3-year transplant-free survival in both discovery (78% vs 36%, P <0.001) and validation (83% vs 46%, P <0.001) cohorts. Significant interaction between molecular endotype and immunosuppressant exposure was observed in both cohorts (discovery Pinteraction = 0.022; validation Pinteraction = 0.019), with survival benefit seen only in Class 2. In pooled analysis, similar trends were observed irrespective of ILD subtype. Pathway analysis supported enrichment of inflammatory signatures in Class 2.

conclusionIn this multicenter observational cohort study, we identified and validated 2 distinct molecular endotypes of non-IPF ILD with divergent outcomes and response to immunosuppressant therapy. These endotypes could inform precision medicine strategies and clinical trial design in ILD.

Indexed as

AzathioprineImmunosuppressive AgentsLung Diseases, InterstitialMycophenolic AcidAgedBiomarkersCohort StudiesFemaleHumansMaleMiddle AgedTreatment OutcomeAzathioprineBiomarkersImmunosuppressive AgentsMycophenolic Acidinterstitial lung diseaselatent class analysismolecular endotypes

Identifiers

PMID41738192
PMCPMC13625607

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.