{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:36:21Z","timestamp":1791502581494,"version":"4.3.4"},"reference-count":54,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1 F32 HL164090-01"],"award-info":[{"award-number":["1 F32 HL164090-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2024,2,15]]},"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Clinical trials repurposing pulmonary arterial hypertension (PAH) therapies to patients with lung disease- or hypoxia-pulmonary hypertension (PH) (classified as World Health Organization Group 3 PH) have failed to show a consistent benefit. However, Group 3 PH clinical heterogeneity suggests robust phenotyping may inform detection of treatment-responsive subgroups. We hypothesised that cluster analysis would identify subphenotypes with differential responses to oral PAH therapy.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Two k-means analyses were performed on a national cohort of US veterans with Group 3 PH; an inclusive model (I) of all treated patients (n=196) and a haemodynamic model (H) limited to patients with right heart catheterisations (n=112). The primary outcome was organ failure or all-cause mortality by cluster. An exploratory analysis evaluated within-cluster treatment effects.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Three distinct clusters of Group 3 PH patients were identified. In the inclusive model (C1\n<jats:sup>I<\/jats:sup>\nn=43, 21.9%; C2\n<jats:sup>I<\/jats:sup>\nn=102, 52.0%; C3\n<jats:sup>I<\/jats:sup>\nn=51, 26.0%), lung disease and spirometry drove cluster assignment. By contrast, in the haemodynamic model (C1\n<jats:sup>H<\/jats:sup>\nn=44, 39.3%; C2\n<jats:sup>H<\/jats:sup>\nn=43, 38.4%; C3\n<jats:sup>H<\/jats:sup>\nn=25, 22.3%), right heart catheterisation data surpassed the importance of lung disease and spirometry. In the haemodynamic model, compared to C3\n<jats:sup>H<\/jats:sup>\n, C1\n<jats:sup>H<\/jats:sup>\nexperienced the greatest hazard for respiratory failure or death (HR 6.1, 95% CI 3.2\ufffd11.8). In an exploratory analysis, cluster determined treatment response (p=0.006). Conclusions regarding within-cluster treatment responses were limited by significant differences between select variables in the treated and untreated groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Cluster analysis identifies novel real-world subphenotypes of Group 3 PH patients with distinct clinical trajectories. Future studies may consider this methodological approach to identify subgroups of heterogeneous patients that may be responsive to existing pulmonary vasodilatory therapies.<\/jats:p>\n<\/jats:sec>","DOI":"10.1183\/23120541.00959-2023","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T17:18:13Z","timestamp":1709227093000},"page":"00959-2023","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cluster analysis identifies novel real-world lung disease\ufffdpulmonary hypertension subphenotypes: implications for treatment response"],"prefix":"10.1183","volume":"10","author":[{"given":"Shelsey W.","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Sheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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