{ "abstract": "Purpose\n\nAsthma is heterogeneous in its molecular and clinical manifestations, complicating treatment. In this study, we investigated the molecular phenotypes of asthma using RNA-sequencing (RNA-seq) of peripheral blood mononuclear cells to advance precision medicine approaches.Methods\n\nWe analyzed peripheral blood RNA-seq data from 456 participants from the Cohort for Reality and Evolution of Adult Asthma in Korea, including 23 patients with severe asthma and 433 with non-severe asthma to identify blood transcriptome-associated clusters (B-TACs) that correlate with distinct inflammatory processes. This included a meta-analysis of differentially expressed genes to refine gene selection for defining B-TACs. Gene Set Variation Analysis was used to assess the differential activation of biological pathways across B-TACs. We validated these findings in the Precision Medicine Intervention in Severe Asthma cohort of 122 patients, focusing on cluster stability, clinical correlates, and treatment responsiveness.Results\n\nOur analysis identified 3 B-TACs (B-TAC1, B-TAC2 and B-TAC3) with B-TAC1 and B-TAC2 showing higher blood eosinophil levels than B-TAC3. B-TAC1 was characterized by a clear T2-high inflammatory profile, whereas B-TAC2 exhibited a mixed molecular phenotype with both T2-high and non-T2 features. B-TAC3 was associated with low T2 and inflammasome-related inflammation profiles. Validation using the PRISM cohort underscored the stability of B-TAC1 and B-TAC2. Notably, patients with B-TAC2 molecular phenotype had lower biologics use and tended to have less favorable treatment outcomes than those with B-TAC1.Conclusions\n\nWe discovered and validated 3 B-TACs, with B-TAC2 displaying a mixed T2-high and non-T2 phenotype, suggesting a potential reduction in responsiveness to biologic treatments. These findings provide molecular insights that may guide the development of personalized treatment strategies for asthma.", "abstract_shown": true, "affiliations": [ "Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea.", "Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea.", "Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.", "Department of Internal Medicine, Korea University Medical Center Anam Hospital, Seoul, Korea.", "Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea.", "Department of Internal Medicine, Konkuk University College of Medicine, Seoul, Korea.", "DNA Link, Seoul, Korea.", "Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.", "Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea.", "Department of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.", "Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.", "Department of Internal Medicine, Nowon Eulji Hospital, Eulji University School of Medicine, Seoul, Korea.", "Department of Internal Medicine, Pusan National University Hospital, Pusan National University College of Medicine, Busan, Korea.", "Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.", "Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.", "Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.", "Department of Allergy and Clinical Immunology, Kangwon National University School of Medicine, Chuncheon, Korea.", "Department of Allergy and Clinical Immunology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Korea.", "Division of Allergy, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.", "National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK.", "Interdisciplinary Program of Bioinformatics, College of Natural Science, Seoul National University, Seoul, Korea. sunghow@gmail.com.", "Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, Ulsan University School of Medicine, Seoul, Korea. tbkim@amc.seoul.kr." ], "article_type": "research article", "arxiv": null, "author_total": 25, "authors": [ { "affs": [ 0 ], "name": "Eunse Kim", "orcid": "0000-0003-2915-1497" }, { "affs": [ 1, 2 ], "name": "So-Young Park", "orcid": "0000-0002-5224-3077" }, { "affs": [ 3 ], "name": "Byung Keun Kim", "orcid": "0000-0001-5147-6306" }, { "affs": [ 4 ], "name": "Min-Hye Kim", "orcid": "0000-0002-1775-3733" }, { "affs": [ 5 ], "name": "Ji-Yong Moon", "orcid": "0000-0003-2459-3448" }, { "affs": [ 6 ], "name": "Jong Eun Lee", "orcid": "0000-0001-8115-3743" }, { "affs": [ 6 ], "name": "Hye Yoon Jang", "orcid": "0000-0002-2864-4997" }, { "affs": [ 6 ], "name": "Eunsoon Shin", "orcid": "0000-0001-8408-2696" }, { "affs": [ 2 ], "name": "Jae-Woo Jung", "orcid": "0000-0002-3411-735X" }, { "affs": [ 7 ], "name": "Taehoon Lee", "orcid": "0000-0002-9224-0866" }, { "affs": [ 8 ], "name": "Chan Sun Park", "orcid": "0000-0003-0113-8354" }, { "affs": [ 9 ], "name": "Jeong-Hee Choi", "orcid": "0000-0002-0599-875X" }, { "affs": [ 10 ], "name": "Sujeong Kim", "orcid": "0000-0002-2494-9216" }, { "affs": [ 11 ], "name": "Sang-Hoon Kim", "orcid": "0000-0002-4105-0552" }, { "affs": [ 12 ], "name": "Hye-Kyung Park", "orcid": "0000-0003-4065-2962" }, { "affs": [ 13 ], "name": "Sae-Hoon Kim", "orcid": "0000-0002-2572-5302" }, { "affs": [ 14 ], "name": "Sang-Ha Kim", "orcid": "0000-0002-1763-5366" }, { "affs": [ 15 ], "name": "Joo-Hee Kim", "orcid": "0000-0002-1572-5149" }, { "affs": [ 16 ], "name": "Jae-Woo Kwon", "orcid": "0000-0003-1639-3606" }, { "affs": [ 17 ], "name": "Young-Joo Cho", "orcid": "0000-0002-9414-5934" }, { "affs": [ 18 ], "name": "Byung-Jae Lee", "orcid": "0000-0001-6940-0836" }, { "affs": [ 19 ], "name": "Ian M Adcock", "orcid": "0000-0003-4106-8469" }, { "affs": [ 19 ], "name": "Kian Fan Chung", "orcid": "0000-0001-7101-1426" }, { "affs": [ 0, 20 ], "name": "Sungho Won", "orcid": "0000-0001-5751-5089" }, { "affs": [ 21 ], "name": "Tae-Bum Kim", "orcid": "0000-0001-5663-0640" } ], "bibtex": "https://research.draconitic.com/paper/6td6j710ghsrq.bib", "cited_by": 0, "doi": "10.4168/aair.2026.18.5.652", "fulltext_url": "https://europepmc.org/articles/PMC13655406", "id": "6td6j710ghsrq", "issns": [ "2092-7355", "2092-7363" ], "landing_url": "https://europepmc.org/article/MED/42845223", "language": "eng", "licence": "CC-BY-NC", "licence_label": "CC BY-NC", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2737|Asthma and respiratory diseases" ] ], "openalex": "W7214743506", "pdf_url": "https://europepmc.org/articles/PMC13655406?pdf=render", "pmcid": "PMC13655406", "pmid": "42845223", "published": "2026-09-01", "publisher": null, "ris": "https://research.draconitic.com/paper/6td6j710ghsrq.ris", "sources": [ { "first_seen": "2026-10-30T12:18:10Z", "native_id": "MED:42845223", "source": "europepmc", "url": "https://europepmc.org/article/MED/42845223" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2737|Asthma and respiratory diseases", "subfield": "physiology" } ], "title": "Molecular Phenotyping Based on Blood Transcriptome-Associated Clusters in Asthma: Findings From Two Korean Asthma Cohorts.", "title_text": "Molecular Phenotyping Based on Blood Transcriptome-Associated Clusters in Asthma: Findings From Two Korean Asthma Cohorts.", "type": "peer-reviewed", "updated_at": "2026-10-30T12:18:10Z", "url": "https://research.draconitic.com/paper/6td6j710ghsrq", "venue": "Allergy, asthma & immunology research", "versions": [] }