{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:34:14Z","timestamp":1791614054760,"version":"4.3.4"},"reference-count":22,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"unspecified","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007150","name":"United Therapeutics Corporation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007150","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Resp Res"],"accepted":{"date-parts":[[2024,3,14]]},"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Inhaled treprostinil (iTre) is the only treatment approved for pulmonary hypertension due to interstitial lung disease (PH-ILD) to improve exercise capacity. This post hoc analysis evaluated clinical worsening and PH-ILD exacerbations from the 16-week INCREASE study and change in 6-minute walking distance (6MWD) in the INCREASE open-label extension (OLE) in patients with less severe haemodynamics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients were stratified by baseline pulmonary vascular resistance (PVR) of &lt;4 Wood units (WU) versus \u22654 WU and \u22645 WU versus &gt;5 WU. Exacerbations of underlying lung disease, clinical worsening and change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in INCREASE were evaluated. For the OLE, patients previously assigned to placebo were considered to have a 16-week treatment delay. 6MWD and clinical events in the OLE were evaluated by PVR subgroup.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 326 patients enrolled in INCREASE, patients with less severe haemodynamics receiving iTre had fewer exacerbations of underlying lung disease and clinical worsening events. This was supported by the Bayesian analysis of the risk of disease progression (HR&lt;1), and significant decreases in NT-proBNP levels. In the OLE, patients without a treatment delay had improved exercise capacity after 1-year compared with those with a 16-week treatment delay (22.1\u2009m vs \u221210.3\u2009m). Patients with a PVR of \u22645 WU without a treatment delay had a change of 5.5\u2009m compared with \u22128.2\u2009m for those with a treatment delay. Patients without a treatment delay had a prolonged time to hospitalisation, lung disease exacerbation and death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Treatment with iTre led to consistent benefits in clinical outcomes in patients with PH-ILD and less severe haemodynamics. Earlier treatment in less severe PH-ILD may lead to better exercise capacity long-term, however, the subgroup analyses in this post hoc study were underpowered and confirmation of these findings is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjresp-2023-002116","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T13:06:07Z","timestamp":1711112767000},"page":"e002116","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Inhaled treprostinil in patients with pulmonary hypertension associated with interstitial lung disease with less severe haemodynamics: a post hoc analysis of the INCREASE study"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02630316","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Jason","family":"Weatherald","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D","family":"Nathan","sequence":"additional","affiliation":[{"name":"Inova Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"El-Kersh","sequence":"additional","affiliation":[{"name":"University of Arizona College of Medicine, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul G","family":"Argula","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary M","family":"DuBrock","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz P","family":"Rischard","sequence":"additional","affiliation":[{"name":"University of Arizona College of Medicine, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J","family":"Cassady","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Tarver","sequence":"additional","affiliation":[{"name":"AdventHealth Central Florida, Orlando, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J","family":"Levine","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor F","family":"Tapson","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunqin","family":"Deng","sequence":"additional","affiliation":[{"name":"United Therapeutics Corp Research Triangle Park, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Shen","sequence":"additional","affiliation":[{"name":"United Therapeutics Corp Research Triangle Park, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisit","family":"Das","sequence":"additional","affiliation":[{"name":"United Therapeutics Corp Research Triangle Park, Research Triangle Park, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron B","family":"Waxman","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"2025083112385894000_11.1.e002116.1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac237"},{"key":"2025083112385894000_11.1.e002116.2","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01914-2018","article-title":"Pulmonary hypertension in chronic lung disease and hypoxia","volume":"53","author":"Nathan","year":"2019","journal-title":"Eur Respir J"},{"key":"2025083112385894000_11.1.e002116.3","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur Respir 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