{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:19:04Z","timestamp":1787548744675,"version":"build-2736575974"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474499"],"award-info":[{"award-number":["82474499"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2024MH319"],"award-info":[{"award-number":["ZR2024MH319"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Acute exacerbation of idiopathic pulmonary fibrosis is a fatal acute-on-chronic respiratory event with limited evidence-based treatment options. Systemic corticosteroids remain widely used, yet their benefit in unselected patients is uncertain, and indiscriminate immunosuppression may expose some patients to harm. A major translational gap is that most available biomarkers describe diagnosis, risk, or prognosis, but do not identify whether corticosteroids actually modify patient outcomes. This Hypothesis and Theory article proposes a testable, biomarker-guided conceptual framework that reframes corticosteroid treatment in acute exacerbation of idiopathic pulmonary fibrosis\u2014from the question of average benefit in unselected patients to the hypothesis that corticosteroid effects differ across corticosteroid-responsive, corticosteroid-neutral, and corticosteroid-harm-prone biological states. We synthesise evidence on disease biology, corticosteroid outcome data, and candidate circulating, imaging, microbiological, and physiological biomarkers. Epithelial injury, inflammatory activation, fibroproliferation, endothelial and coagulation injury, infection or other trigger burden, radiological extent, oxygenation, and early clinical trajectory are evaluated as components of a treatment-stratification framework. We emphasise that these markers currently function mainly as diagnostic, risk, prognostic, safety, or dynamic-response markers rather than validated predictors of corticosteroid response. To bridge this gap, we propose a translational framework that integrates baseline biological signals with structured reassessment at 72\u201396\u00a0h. This framework separates three decision domains: inflammatory reversibility (the likelihood of corticosteroid-modifiable sterile inflammation), irreversible epithelial\/fibroproliferative injury (the burden of structural damage unlikely to be modified by corticosteroids), and infection- or host vulnerability-related harm risk (the probability that immunosuppression is unsafe). It is intended to guide prospective treatment-aware cohorts, biomarker-by-treatment interaction analyses, target-trial emulation, and biomarker-enriched or adaptive trials.<\/jats:p>","DOI":"10.3389\/fphar.2026.1934548","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T04:23:26Z","timestamp":1787545406000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A biomarker-guided framework for corticosteroid treatment stratification in acute exacerbation of idiopathic pulmonary fibrosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Qinglong","family":"Chen","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Li","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]},{"name":"Shandong Key Laboratory of Innovation and Application Research in Basic Theory of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyue","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wen","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1164\/rccm.200709-1365OC","article-title":"Computed tomography findings in acute exacerbation of idiopathic pulmonary fibrosis","volume":"178","author":"Akira","year":"2008","journal-title":"Am. 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