# New approaches to uncover COPD pathobiology and develop therapies

**Authors:** Yohannes Tesfaigzi, Ali Önder Yildirim, Francesca Polverino, Thomas M. Conlon, Venkataramana Sidhaye, Maor Sauler, S. Vamsee Raju, Renata Z. Jurkowska, Divay Chandra, Michael H. Cho, Edwin K. Silverman, Ramon C. Sun, Peter Castaldi, Purushothama Rao Tata, Kambez H. Benam, Linto Antony, Mareike Lehmann, Beata Kosmider, Karim Bahmed, Zerihun H. Negasi, Kamakshi Bankoti, Carter Swaby, Dave A. Lagowala, Yeşim Vural, Hasan Bayram, Rosa Faner, George Washko, Dinh Son Bui, Bartolome Celli, Roxana Maria Wasnick, Enid Neptune

PMC · DOI: 10.1172/jci.insight.199693 · JCI Insight · 2026-02-23

## TL;DR

This review discusses new research on COPD's causes and therapies, aiming to improve understanding and treatment.

## Contribution

The paper summarizes recent advances in COPD research, emphasizing collaboration through the COPD-iNET consortium.

## Key findings

- COPD risk factors include genetic and epigenetic determinants interacting with the microbiome and environment.
- New technologies like single-cell transcriptomics are being used to study COPD progression.
- Biomarker research and pre-COPD diagnosis are critical for developing effective therapies.

## Abstract

Chronic obstructive pulmonary disease (COPD) was the third leading cause of global mortality in 2011 but receives limited attention and research funding. This Review describes the current knowledge on COPD risk factors, including genetic and epigenetic determinants and their interactions with the microbiome and environmental exposures. Preclinical models are being refined and single-cell transcriptomic, metabolomic, and proteomic technologies are being implemented to investigate the molecular mechanisms of disease progression. Patient cohorts to define biomarkers of early disease and the latest approaches to diagnose pre-COPD are essential to accelerate the development of novel and effective therapeutic interventions and translate new findings into clinical trials. This Review is a summary of topics covered by a symposium organized by the COPD-iNET consortium, an international network of researchers who have established a platform that facilitates collaboration of this multidisciplinary group of preclinical, translational, and clinical researchers.

## Linked entities

- **Diseases:** Chronic obstructive pulmonary disease (MONDO:0005002), COPD (MONDO:0005002)

## Full-text entities

- **Genes:** SERPINA1 (serpin family A member 1) [NCBI Gene 5265] {aka A1A, A1AT, AAT, PI, PI1, PRO2275}, MPO (myeloperoxidase) [NCBI Gene 4353], Fam13a (family with sequence similarity 13, member A) [NCBI Gene 58909] {aka D430015B01Rik, FAM13A1, Precm1}, AGER (advanced glycosylation end-product specific receptor) [NCBI Gene 177] {aka RAGE, SCARJ1, sRAGE}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, Prmt7 (protein arginine N-methyltransferase 7) [NCBI Gene 214572] {aka 4933402B05Rik}, Aatf (apoptosis antagonizing transcription factor) [NCBI Gene 56321] {aka 4933415H02Rik, 5830465M17Rik, Che-1, Trb}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, Abi3bp (ABI family member 3 binding protein) [NCBI Gene 320712] {aka 5033411B22Rik, D930038M13Rik, TARSH, eratin}, ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}, Krt8 (keratin 8) [NCBI Gene 16691] {aka Card2, EndoA, K8, Krt-2.8, Krt2-8, TROMA-1}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Sftpb (surfactant associated protein B) [NCBI Gene 20388] {aka SF-B, SP-B, Sftp-3, Sftp3}, SOD3 (superoxide dismutase 3) [NCBI Gene 6649] {aka EC-SOD}, Krt5 (keratin 5) [NCBI Gene 110308] {aka 3300001P10Rik, CK5, K5, Krt2-5, Tfip8}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, MUC5B (mucin 5B, oligomeric mucus/gel-forming) [NCBI Gene 727897] {aka MG1, MUC-5B, MUC5, MUC9}, TET2 (tet methylcytosine dioxygenase 2) [NCBI Gene 54790] {aka IMD75, KIAA1546, MDS}, Scgb3a2 (secretoglobin, family 3A, member 2) [NCBI Gene 117158] {aka LuLeu1, Pnsp1, UGRP1, Utgrp1}, FAM13A (family with sequence similarity 13 member A) [NCBI Gene 10144] {aka ARHGAP48, FAM13A1}, HHIP (hedgehog interacting protein) [NCBI Gene 64399] {aka HIP}, MFAP2 (microfibril associated protein 2) [NCBI Gene 4237] {aka MAGP, MAGP-1, MAGP1}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, TET1 (tet methylcytosine dioxygenase 1) [NCBI Gene 80312] {aka CXXC6, LCX, bA119F7.1}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, Krt17 (keratin 17) [NCBI Gene 16667] {aka K17, Krt1-17}, MUC5AC (mucin 5AC, oligomeric mucus/gel-forming) [NCBI Gene 4586] {aka MUC5, TBM, leB, mucin}, SCGB1A1 (secretoglobin family 1A member 1) [NCBI Gene 7356] {aka CC10, CC16, CCPBP, CCSP, UGB, UP-1}, MMP12 (matrix metallopeptidase 12) [NCBI Gene 4321] {aka HME, ME, MME, MMP-12}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, ELANE (elastase, neutrophil expressed) [NCBI Gene 1991] {aka ELA2, GE, HLE, HNE, NE, PMN-E}, Prmt1 (protein arginine N-methyltransferase 1) [NCBI Gene 15469] {aka 6720434D09Rik, Hrmt1l2, Mrmt1}
- **Diseases:** cancer (MESH:D009369), hypertrophy (MESH:D006984), chronic bronchitis (MESH:D029481), lung (MESH:D008171), COVID (MESH:D000086382), dysbiosis (MESH:D064806), infections (MESH:D007239), idiopathic pulmonary fibrosis (MESH:D054990), bronchitis (MESH:D001991), function decline (MESH:D060825), RSV (MESH:D018357), lung function (MESH:D055370), emphysema (MESH:D004646), asthma (MESH:D001249), PRISm (MESH:C537758), chronic kidney disease (MESH:D051436), cytotoxic (MESH:D064420), AATD (MESH:D019896), ALS (MESH:D000690), Lung epithelial dysfunction (MESH:D009375), fibrosis (MESH:D005355), Inflammatory (MESH:D007249), respiratory tract infections (MESH:D012141), gastroesophageal reflux (MESH:D005764), viral infection (MESH:D014777), death (MESH:D003643), corticosteroid (MESH:C565152), respiratory disease (MESH:D012140), connective tissue dysfunction (MESH:D003240), hypertension (MESH:D006973), influenza (MESH:D007251), periodontal disease (MESH:D010510), CARDIA (MESH:D004938), underdeveloped lungs (MESH:C000721289), ventilation abnormalities (MESH:D053717), airway obstruction (MESH:D000402), alveolar (MESH:D002282), emphysematous (MESH:D041882), hypoxia (MESH:D000860), frailty (MESH:D000073496), chronic diseases (MESH:D002908), impaired lung function (MESH:D003072), CS (MESH:D015208), wheezing (MESH:D012135), bacterial infections (MESH:D001424), irritable bowel syndrome (MESH:D043183), pneumonia (MESH:D011014), Loeys-Dietz syndrome type 4 (MESH:D055947), dementia (MESH:D003704), COPD (MESH:D029424), cutis laxa (MESH:D003483)
- **Chemicals:** NO2 (MESH:D009585), glycans (MESH:D011134), helium (MESH:D006371), tofersen (MESH:C000709090), O3 (MESH:D010126), CS (-), dupilumab (MESH:C582203), xenon (MESH:D014978), SO2 (MESH:D013458), 5-azacytidine (MESH:D001374), 5-methylcytosine (MESH:D044503), agarose (MESH:D012685), nitrogen oxides (MESH:D009589), lipids (MESH:D008055), LPS (MESH:D008070)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mustela putorius furo (black ferret, subspecies) [taxon 9669], Respiratory syncytial virus (no rank) [taxon 12814], Nicotiana tabacum (American tobacco, species) [taxon 4097], Ovis aries (domestic sheep, species) [taxon 9940]
- **Mutations:** rs28929474, CG-to-TG

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12956016/full.md

## References

269 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956016/full.md

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Source: https://tomesphere.com/paper/PMC12956016