Evidence map›Paper›PMID 41408261›Full record

ArticleRespiratory research2025

Molecular determinants of lung function decline: a multi-level analysis of gene expression.

Zaid W Elhusseini, Omar Rafique, Min Hyung Ryu, Peter Castaldi, Don D Sin, Ingo Ruczinski, Craig P Hersh

Abstract read
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In one paragraph

Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Zaid W ElhusseiniChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA, USA.
Omar RafiqueChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA, USA.
Min Hyung RyuDivision of Respiratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Peter CastaldiChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA, USA.
Don D SinDivision of Respiratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Ingo RuczinskiDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
Craig P HershChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA, USA. craig.hersh@channing.harvard.edu.

Funding

Defining a gene expression signature of airway disease, COPD exacerbations, and response to treatmentR01HL166231 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CRAIG P HERSH · 2023 to 2026
$3.3M
Defining the Role of Viral Infections and Autoantibodies in Chronic Obstructive Pulmonary Disease ProgressionR01HL168663 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI CRAIG P HERSH, Ingo Ruczinski · 2024 to 2026
$2.0M
NHLBI NIH HHS R01 HL166231NHLBI NIH HHS R01 HL168663
6 · The paper itself

Abstract

backgroundChronic obstructive pulmonary disease (COPD) is characterized by progressive lung function decline, commonly measured by forced expiratory volume in one second (FEV1). Uncovering the genetic basis of FEV1 decline is essential for understanding COPD pathophysiology and for developing therapies. We hypothesized that gene expression patterns in inflammatory pathways are associated with FEV1 decline.

methodsWe analyzed whole blood RNA-sequencing data from the 5 (n = 4,147) and 10 year visits (n = 435) in the COPDGene Study. Gene expression was assessed in three analyses: cross-sectional associations with FEV1 at two separate time points, association between year 5 gene expression and FEV1 changes from year 5–10, and longitudinal changes in both gene expression and FEV1. A gene signature derived from the 5-year visit was linked to FEV1 decline across three intervals (baseline to 5 years, 5 to 10 years, and baseline to 10 years) and tested for validation in the ECLIPSE study.

resultsDistinct gene sets emerged in the three analyses (Cross-sectional: 961 genes; FEV1 Change: 179; Longitudinal: 532). Only two genes (NOV and AC009404.2) overlapped across all analyses, while unique genes (e.g., MMP9, IL1RL1, and CHI3L1) were context-specific. Pathway analysis of genes from the longitudinal analysis highlighted oxidative stress and immune processes. A 20-gene signature was derived, including 17 genes positively and three negatively associated with FEV1. These signatures were significantly associated with FEV1-related traits in COPDGene and ECLIPSE.

conclusionsThese findings reveal molecular markers of FEV1 decline, offering insights into COPD pathophysiology and potential therapeutic targets.

Indexed as

Gene Expression ProfilingLungPulmonary Disease, Chronic ObstructiveAgedCross-Sectional StudiesDisease ProgressionFemaleForced Expiratory VolumeHumansLongitudinal StudiesMaleBiomarkersCOPDLongitudinal analysisPulmonary function testsRNA-sequencing

Identifiers

PMID41408261
PMCPMC12822344

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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 Socratic graph.