{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:01:27Z","timestamp":1785229287936,"version":"3.55.0"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Pulmonary hypertension associated with idiopathic pulmonary fibrosis (PH-IPF) is a frequent and clinically relevant complication that worsens exercise capacity, quality of life, and survival. This narrative review summarizes the epidemiology, pathophysiology, diagnostic approach, and therapeutic landscape of PH-IPF. The development of PH in IPF reflects the combined effects of fibrotic parenchymal destruction, pulmonary vascular remodeling, hypoxic vasoconstriction, endothelial dysfunction, and altered vascular signaling. Diagnosis remains challenging because symptoms often overlap with those of advanced fibrotic lung disease and non-invasive tools have limited sensitivity; right heart catheterization remains the diagnostic gold standard. Antifibrotic agents are central to IPF management but have no established role as PH-targeted therapies. Most pulmonary arterial hypertension therapies have failed to show benefit in PH-IPF or have raised safety concerns, with ambrisentan and riociguat associated with harm. Inhaled treprostinil is currently the only approved therapy with randomized evidence of efficacy in PH associated with interstitial lung disease, including IPF. Supportive care, optimization of comorbidities, referral to expert centers, and timely lung transplantation evaluation remain essential components of management.<\/jats:p>","DOI":"10.3389\/fphar.2026.1865787","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:28:42Z","timestamp":1784780922000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the therapeutic landscape of pulmonary hypertension associated with interstitial lung disease, with a focus on idiopathic pulmonary fibrosis: a narrative review"],"prefix":"10.3389","volume":"17","author":[{"given":"Nicol\u00f2","family":"Reccardini","sequence":"first","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste","place":["Trieste, Italy"]},{"name":"Department of Pulmonary Rehabilitation, Azienda Sanitaria Universitaria Friuli Centrale","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Da Re","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste","place":["Trieste, Italy"]},{"name":"Department of Pulmonology, Santa Maria Degli Angeli Hospital","place":["Pordenone, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Mondini","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Spedali Civili","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Salton","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste","place":["Trieste, Italy"]},{"name":"Department of Pulmonology, University Hospital of Cattinara","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Confalonieri","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste","place":["Trieste, Italy"]},{"name":"Department of Pulmonology, University Hospital of Cattinara","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Confalonieri","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste","place":["Trieste, Italy"]},{"name":"Department of Pulmonology, University Hospital of Cattinara","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hughes","sequence":"additional","affiliation":[{"name":"Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre","place":["Manchester, United Kingdom"]},{"name":"Department of Rheumatology, Salford Care Organisation, Northern Care Alliance NHS Foundation Trust","place":["Salford, United Kingdom"]},{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Monteleone","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Ruhrlandklinik, University Hospital Essen, University of Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Ruaro","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste","place":["Trieste, Italy"]},{"name":"Department of Pulmonology, University Hospital of Cattinara","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"61","DOI":"10.4103\/1817-1737.203742","article-title":"A review of imaging modalities in pulmonary hypertension","volume":"12","author":"Ascha","year":"2017","journal-title":"Ann. Thorac. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.repc.2024.03.004","article-title":"Pulmonary arterial hypertension: navigating the pathways of progress in diagnosis, treatment, and patient care","volume":"43","author":"Azaredo Raposo","year":"2024","journal-title":"Rev. Port. Cardiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1164\/rccm.201302-0302OC","article-title":"Regulation of hypoxia-induced pulmonary hypertension by vascular smooth muscle hypoxia-inducible factor-1\u03b1","volume":"189","author":"Ball","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"CD012621","DOI":"10.1002\/14651858.CD012621.pub2","article-title":"Phosphodiesterase 5 inhibitors for pulmonary hypertension","volume":"1","author":"Barnes","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1902279","DOI":"10.1183\/13993003.02279-2019","article-title":"Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: long-term results of the INSIGHTS-IPF registry","volume":"56","author":"Behr","year":"2020","journal-title":"Eur. Respir. J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S2213-2600(20)30356-8","article-title":"Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: a double-blind, randomised, placebo-controlled, phase 2b trial","volume":"9","author":"Behr","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1701857","DOI":"10.1183\/13993003.01857-2017","article-title":"Macitentan reduces progression of TGF-\u03b21-induced pulmonary fibrosis and pulmonary hypertension","volume":"52","author":"Bellaye","year":"2018","journal-title":"Eur. Respir. J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"22038","DOI":"10.1038\/s41598-024-70650-w","article-title":"Long-term oxygen therapy in precapillary pulmonary hypertension - SOPHA study","volume":"14","author":"Benjamin","year":"2024","journal-title":"Sci. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"L249","DOI":"10.1152\/ajplung.00258.2015","article-title":"Endothelial HIF signaling regulates pulmonary fibrosis-associated pulmonary hypertension","volume":"310","author":"Bryant","year":"2016","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1161\/01.CIR.0000102381.57477.50","article-title":"Endothelial dysfunction in pulmonary hypertension","volume":"109","author":"Budhiraja","year":"2004","journal-title":"Circulation"},{"key":"B11","doi-asserted-by":"publisher","first-page":"101","DOI":"10.18553\/jmcp.2023.29.1.101","article-title":"Inhaled treprostinil vs iloprost: comparison of adherence, persistence, and health care resource utilization in patients with pulmonary arterial hypertension","volume":"29","author":"Burger","year":"2023","journal-title":"J. Manag. Care Spec. Pharm."},{"key":"B12","doi-asserted-by":"publisher","first-page":"230138","DOI":"10.1183\/16000617.0138-2023","article-title":"Clinical-radiological-pathological correlation in pulmonary arterial hypertension","volume":"32","author":"Condliffe","year":"2023","journal-title":"Eur. Respir. Rev."},{"key":"B13","first-page":"7","article-title":"Pulmonary hypertension in idiopathic pulmonary fibrosis: a review","volume":"26","author":"Corte","year":"2009","journal-title":"Sarcoidosis Vasc. Diffuse Lung Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1164\/rccm.201403-0446OC","article-title":"Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia","volume":"190","author":"Corte","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s10741-016-9551-x","article-title":"Pulmonary hypertension associated with lung diseases and hypoxemia","volume":"21","author":"Cuttica","year":"2016","journal-title":"Heart Fail Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5177","DOI":"10.3390\/jcm14155177","article-title":"Sotatercept for connective tissue disease-associated pulmonary arterial hypertension with concomitant interstitial lung disease: efficacy and safety insights","volume":"14","author":"Dagher","year":"2025","journal-title":"J. Clin. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1111\/resp.14378","article-title":"Phosphodiesterase 5 inhibitor treatment and survival in interstitial lung disease pulmonary hypertension: a Bayesian retrospective observational cohort study","volume":"28","author":"Dawes","year":"2023","journal-title":"Respirology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"170039","DOI":"10.1183\/16000617.0039-2017","article-title":"Exertional dyspnoea in pulmonary arterial hypertension","volume":"26","author":"Dumitrescu","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1172\/JCI36136","article-title":"VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats","volume":"119","author":"Farkas","year":"2009","journal-title":"J. Clin. Invest."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1165\/rcmb.2010-0365TR","article-title":"Pulmonary hypertension and idiopathic pulmonary fibrosis: a tale of angiogenesis, apoptosis, and growth factors","volume":"45","author":"Farkas","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"00571","DOI":"10.1183\/23120541.00571-2021","article-title":"Vascular remodelling in idiopathic pulmonary fibrosis patients and its detrimental effect on lung physiology: potential role of endothelial-to-mesenchymal transition","volume":"8","author":"Gaikwad","year":"2022","journal-title":"ERJ Open Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"00487","DOI":"10.1183\/23120541.00487-2022","article-title":"Endothelial-to-mesenchymal transition: a precursor to pulmonary arterial remodelling in patients with idiopathic pulmonary fibrosis","volume":"9","author":"Gaikwad","year":"2023","journal-title":"ERJ Open Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1183\/13993003.01032-2015","article-title":"2015 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the european society of cardiology (ESC) and the european respiratory society (ERS): endorsed by: association for european paediatric and congenital cardiology (AEPC), international society for heart and lung transplantation (ISHLT)","volume":"46","author":"Gali\u00e8","year":"2015","journal-title":"Eur. Respir. J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1165\/rcmb.2015-0145OC","article-title":"Altered hypoxic-adenosine axis and metabolism in group III pulmonary hypertension","volume":"54","author":"Garcia-Morales","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/S2213-2600(18)30502-2","article-title":"Lung transplantation for idiopathic pulmonary fibrosis","volume":"7","author":"George","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/S0140-6736(02)11024-5","article-title":"Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial","volume":"360","author":"Ghofrani","year":"2002","journal-title":"Lancet"},{"key":"B27","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41569-024-01064-4","article-title":"Mechanisms and treatment of pulmonary arterial hypertension","volume":"22","author":"Ghofrani","year":"2025","journal-title":"Nat. Rev. Cardiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S2213-2600(14)70013-X","article-title":"Tadalafil in patients with chronic obstructive pulmonary disease: a randomised, double-blind, parallel-group, placebo-controlled trial","volume":"2","author":"Goudie","year":"2014","journal-title":"Lancet Respir. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1378\/chest.12-1594","article-title":"Sildenafil preserves exercise capacity in patients with idiopathic pulmonary fibrosis and right-sided ventricular dysfunction","volume":"143","author":"Han","year":"2013","journal-title":"Chest"},{"key":"B30","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.healun.2014.09.004","article-title":"Effect of pulmonary hypertension on survival in patients with idiopathic pulmonary fibrosis after lung transplantation: an analysis of the united network of organ sharing registry","volume":"34","author":"Hayes","year":"2015","journal-title":"J. Heart Lung Transpl."},{"key":"B31","doi-asserted-by":"publisher","first-page":"D42","DOI":"10.1016\/j.jacc.2013.10.032","article-title":"Definitions and diagnosis of pulmonary hypertension","volume":"62","author":"Hoeper","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/S2213-2600(15)00543-3","article-title":"A global view of pulmonary hypertension","volume":"4","author":"Hoeper","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/S2213-2600(22)00097-2","article-title":"Phenotyping of idiopathic pulmonary arterial hypertension: a registry analysis","volume":"10","author":"Hoeper","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1056\/NEJMoa2213558","article-title":"Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension","volume":"388","author":"Hoeper","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"2200879","DOI":"10.1183\/13993003.00879-2022","article-title":"2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"61","author":"Humbert","year":"2023","journal-title":"Eur. Respir. J."},{"key":"B36","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1056\/NEJMoa1002110","article-title":"A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis","volume":"363","author":"Zisman","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e121","DOI":"10.1164\/rccm.202009-3608ST","article-title":"Home oxygen therapy for adults with chronic lung disease. An official American thoracic society clinical practice guideline","volume":"202","author":"Jacobs","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.3390\/life14091068","article-title":"A case of interstitial lung disease-related pulmonary hypertension successfully treated with inhaled iloprost","volume":"14","author":"Jang","year":"2024","journal-title":"Life (Basel)"},{"key":"B39","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s12931-022-02033-6","article-title":"Comorbidity burden and survival in patients with idiopathic pulmonary fibrosis: the EMPIRE registry study","volume":"23","author":"Jovanovic","year":"2022","journal-title":"Respir. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1111\/resp.13250","article-title":"Pulmonary hypertension in interstitial lung disease: limitations of echocardiography compared to cardiac catheterization","volume":"23","author":"Keir","year":"2018","journal-title":"Respirology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1159\/000345221","article-title":"Pulmonary hypertension as a prognostic indicator at the initial evaluation in idiopathic pulmonary fibrosis","volume":"85","author":"Kimura","year":"2013","journal-title":"Respiration"},{"key":"B42","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/S2213-2600(16)30222-3","article-title":"Idiopathic pulmonary fibrosis: effects and optimal management of comorbidities","volume":"5","author":"King","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1164\/rccm.201011-1874OC","article-title":"BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis","volume":"184","author":"King","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1056\/NEJMoa1811737","article-title":"Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis","volume":"379","author":"Kolb","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B45","doi-asserted-by":"crossref","first-page":"633A","DOI":"10.1378\/chest.132.4_MeetingAbstracts.633a","article-title":"A randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of iloprost inhalation in adults with abnormal pulmonary arterial pressure and exercise limitation associated with idiopathic pulmonary fibrosis","volume":"132","author":"Krowka","year":"2007","journal-title":"Chest"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.3390\/life14091203","article-title":"Converging pathways: a review of pulmonary hypertension in interstitial lung disease","volume":"14","author":"Lawrence","year":"2024","journal-title":"Life (Basel)"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1056\/NEJMra1705751","article-title":"Idiopathic pulmonary fibrosis","volume":"378","author":"Lederer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1378\/chest.129.3.746","article-title":"Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis","volume":"129","author":"Lettieri","year":"2006","journal-title":"Chest"},{"key":"B49","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1186\/s12931-021-01791-z","article-title":"Global incidence and prevalence of idiopathic pulmonary fibrosis","volume":"22","author":"Maher","year":"2021","journal-title":"Respir. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1056\/NEJMoa2503643","article-title":"Nerandomilast in patients with progressive pulmonary fibrosis","volume":"392","author":"Maher","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"00550","DOI":"10.1183\/23120541.00550-2024","article-title":"Vascular involvement in idiopathic pulmonary fibrosis","volume":"10","author":"Mondoni","year":"2024","journal-title":"ERJ Open Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1513\/AnnalsATS.202005-451OC","article-title":"Longitudinal changes in clinical features, management, and outcomes of idiopathic pulmonary fibrosis. A nationwide cohort study","volume":"18","author":"Moon","year":"2021","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.3390\/jcm14041317","article-title":"Non-pharmacological management of idiopathic pulmonary fibrosis","volume":"14","author":"Mullholand","year":"2025","journal-title":"J. Clin. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"S107","DOI":"10.37765\/ajmc.2024.89632","article-title":"Real-world data on the course of idiopathic pulmonary fibrosis","volume":"30","author":"Nathan","year":"2024","journal-title":"Am. J. Manag. Care"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1801914","DOI":"10.1183\/13993003.01914-2018","article-title":"Pulmonary hypertension in chronic lung disease and hypoxia","volume":"53","author":"Nathan","year":"","journal-title":"Eur. Respir. J."},{"key":"B56","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/S2213-2600(19)30250-4","article-title":"Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study","volume":"7","author":"Nathan","year":"","journal-title":"Lancet Respir. Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.healun.2021.02.006","article-title":"Impact of lung morphology on clinical outcomes with riociguat in patients with pulmonary hypertension and idiopathic interstitial pneumonia: a post hoc subgroup analysis of the RISE-IIP study","volume":"40","author":"Nathan","year":"","journal-title":"J. Heart Lung Transpl."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1016\/S2213-2600(21)00165-X","article-title":"Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension: a post-hoc analysis of the INCREASE study","volume":"9","author":"Nathan","year":"","journal-title":"Lancet Respir. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1164\/rccm.202107-1766OC","article-title":"Efficacy of inhaled treprostinil on multiple disease progression events in patients with pulmonary hypertension due to parenchymal lung disease in the INCREASE trial","volume":"205","author":"Nathan","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.chest.2022.09.007","article-title":"Inhaled treprostinil dosage in pulmonary hypertension associated with interstitial lung disease and its effects on clinical outcomes","volume":"163","author":"Nathan","year":"","journal-title":"Chest"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1513\/AnnalsATS.202303-229RL","article-title":"A novel approach to clinical change endpoints: a win ratio analysis of the INCREASE trial","volume":"20","author":"Nathan","year":"","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B62","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1136\/thorax-2023-220821","article-title":"Survival analysis from the INCREASE study in PH-ILD: evaluating the impact of treatment crossover on overall mortality","volume":"79","author":"Nathan","year":"2024","journal-title":"Thorax"},{"key":"B63","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1056\/NEJMoa2512911","article-title":"Inhaled treprostinil for idiopathic pulmonary fibrosis","volume":"11","author":"Nathan","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1164\/ajrccm.160.2.9810008","article-title":"Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis","volume":"160","author":"Olschewski","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2101483","DOI":"10.1183\/13993003.01483-2021","article-title":"Pulmonary vascular resistance predicts mortality in patients with pulmonary hypertension associated with interstitial lung disease: results from the COMPERA registry","volume":"58","author":"Olsson","year":"2021","journal-title":"Eur. Respir. J."},{"key":"B66","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/S2213-2600(23)00259-X","article-title":"Pulmonary hypertension associated with lung disease: new insights into pathomechanisms, diagnosis, and management","volume":"11","author":"Olsson","year":"2023","journal-title":"Lancet Respir. Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1165\/rcmb.2020-0373PS","article-title":"The interplay of the genetic architecture, aging, and environmental factors in the pathogenesis of idiopathic pulmonary fibrosis","volume":"64","author":"Pardo","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s00408-004-2542-z","article-title":"Heterogeneous remodeling of lung vessels in idiopathic pulmonary fibrosis","volume":"183","author":"Parra","year":"2005","journal-title":"Lung"},{"key":"B69","doi-asserted-by":"publisher","first-page":"3472","DOI":"10.3390\/jcm13123472","article-title":"Predictors of mortality in pulmonary hypertension-associated chronic lung disease","volume":"13","author":"Pescatore","year":"2024","journal-title":"J. Clin. Med."},{"key":"B70","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1159\/000327918","article-title":"Pulmonary hypertension in idiopathic pulmonary fibrosis: a reviews","volume":"82","author":"Pitsiou","year":"2011","journal-title":"Respiration"},{"key":"B71","doi-asserted-by":"publisher","first-page":"3670","DOI":"10.1096\/fj.201801659R","article-title":"Therapeutic effect of pirfenidone in the sugen\/hypoxia rat model of severe pulmonary hypertension","volume":"33","author":"Poble","year":"2019","journal-title":"FASEB J."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.neurom.2025.08.411","article-title":"Noncontact midair ultrasonic neuromodulation of the median and ulnar nerves induces frequency-specific parasympathetic and cortical network responses in healthy adults","volume":"28","author":"Pryer","year":"2025","journal-title":"Neuromodulation"},{"key":"B73","doi-asserted-by":"publisher","first-page":"L229","DOI":"10.1152\/ajplung.00238.2014","article-title":"The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes","volume":"308","author":"Pugliese","year":"2015","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1111\/crj.12631","article-title":"Risk factors for acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis","volume":"12","author":"Qiu","year":"2018","journal-title":"Clin. Respir. J."},{"key":"B75","doi-asserted-by":"publisher","first-page":"641","DOI":"10.7326\/0003-4819-158-9-201305070-00003","article-title":"Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial","volume":"158","author":"Raghu","year":"","journal-title":"Ann. Intern Med."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1183\/09031936.00104612","article-title":"Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial","volume":"42","author":"Raghu","year":"","journal-title":"Eur. Respir. J."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1183\/13993003.02316-2014","article-title":"Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review","volume":"46","author":"Raghu","year":"","journal-title":"Eur. Respir. J."},{"key":"B78","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1183\/13993003.01537-2014","article-title":"Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction","volume":"46","author":"Raghu","year":"","journal-title":"Eur. Respir. J."},{"key":"B79","doi-asserted-by":"publisher","first-page":"e18","DOI":"10.1164\/rccm.202202-0399ST","article-title":"Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS\/ERS\/JRS\/ALAT clinical practice guideline","volume":"205","author":"Raghu","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B80","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1111\/bph.15036","article-title":"Idiopathic pulmonary fibrosis and pulmonary hypertension: heracles meets the hydra","volume":"178","author":"Rajagopal","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"930","DOI":"10.3390\/ph17070930","article-title":"Pirfenidone in idiopathic pulmonary fibrosis: real-world observation on efficacy and safety, focus on patients undergoing antithrombotic and anticoagulant","volume":"17","author":"Reccardini","year":"2024","journal-title":"Pharm. (Basel)"},{"key":"B82","doi-asserted-by":"publisher","first-page":"2004455","DOI":"10.1183\/13993003.04455-2020","article-title":"Imaging of pulmonary hypertension in adults: a position paper from the fleischner society","volume":"57","author":"Remy-Jardin","year":"2021","journal-title":"Eur. Respir. J."},{"key":"B83","doi-asserted-by":"publisher","first-page":"216","DOI":"10.7326\/0003-4819-107-2-216","article-title":"Primary pulmonary hypertension. A national prospective study","volume":"107","author":"Rich","year":"1987","journal-title":"Ann. Intern Med."},{"key":"B84","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.1056\/NEJMoa2414108","article-title":"Nerandomilast in patients with idiopathic pulmonary fibrosis","volume":"392","author":"Richeldi","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"B85","doi-asserted-by":"publisher","first-page":"176547","DOI":"10.1016\/j.ejphar.2024.176547","article-title":"Pirfenidone and nintedanib attenuates pulmonary artery endothelial and smooth muscle cells transformations induced by IL-11","volume":"972","author":"Roger","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"235","DOI":"10.3390\/diagnostics12020235","article-title":"Chronic thromboembolic pulmonary hypertension: an update","volume":"12","author":"Ruaro","year":"","journal-title":"Diagn. (Basel)"},{"key":"B87","doi-asserted-by":"publisher","first-page":"616","DOI":"10.3390\/diagnostics12030616","article-title":"An overview of different techniques for improving the treatment of pulmonary hypertension secondary in systemic sclerosis patients","volume":"12","author":"Ruaro","year":"","journal-title":"Diagn. (Basel)"},{"key":"B88","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1186\/s12931-020-01570-2","article-title":"Pulmonary hypertension secondary to pulmonary fibrosis: clinical data, histopathology and molecular insights","volume":"21","author":"Ruffenach","year":"2020","journal-title":"Respir. Res."},{"key":"B89","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1183\/13993003.00419-2015","article-title":"Acute exacerbation of idiopathic pulmonary fibrosis: shifting the paradigm","volume":"46","author":"Ryerson","year":"2015","journal-title":"Eur. Respir. J."},{"key":"B90","doi-asserted-by":"publisher","first-page":"2500158","DOI":"10.1183\/13993003.00158-2025","article-title":"Update of the international multidisciplinary classification of the interstitial pneumonias: an ERS\/ATS statement","volume":"66","author":"Ryerson","year":"2025","journal-title":"Eur. Respir. J."},{"key":"B91","doi-asserted-by":"publisher","first-page":"342","DOI":"10.4065\/82.3.342","article-title":"Pulmonary hypertension in patients with interstitial lung diseases","volume":"82","author":"Ryu","year":"2007","journal-title":"Mayo Clin. Proc."},{"key":"B92","doi-asserted-by":"publisher","first-page":"L362","DOI":"10.1152\/ajplung.00111.2005","article-title":"Apoptosis of pulmonary microvascular endothelial cells stimulates vascular smooth muscle cell growth","volume":"291","author":"Sakao","year":"2006","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"2401200","DOI":"10.1183\/13993003.01200-2024","article-title":"Pulmonary hypertension associated with lung diseases","volume":"64","author":"Shlobin","year":"2024","journal-title":"Eur. Respir. J."},{"key":"B94","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1183\/09031936.00107206","article-title":"Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant","volume":"30","author":"Shorr","year":"2007","journal-title":"Eur. Respir. J."},{"key":"B95","doi-asserted-by":"publisher","first-page":"13419","DOI":"10.1038\/srep13419","article-title":"Vagotomy attenuates bleomycin-induced pulmonary fibrosis in mice","volume":"5","author":"Song","year":"2015","journal-title":"Sci. Rep."},{"key":"B96","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/s0735-1097(02)02964-9","article-title":"Pulmonary function in primary pulmonary hypertension","volume":"41","author":"Sun","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s12890-019-0918-3","article-title":"Temporal echocardiographic assessment of pulmonary hypertension in idiopathic pulmonary fibrosis patients treated with nintedanib with or without oxygen therapy","volume":"19","author":"Tahara","year":"2019","journal-title":"BMC Pulm. Med."},{"key":"B98","doi-asserted-by":"publisher","first-page":"e0214697","DOI":"10.1371\/journal.pone.0214697","article-title":"Nintedanib ameliorates experimental pulmonary arterial hypertension via inhibition of endothelial mesenchymal transition and smooth muscle cell proliferation","volume":"14","author":"Tsutsumi","year":"2019","journal-title":"PLoS One"},{"key":"B99","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1056\/NEJMoa2008470","article-title":"Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease","volume":"384","author":"Waxman","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B100","doi-asserted-by":"publisher","first-page":"2202414","DOI":"10.1183\/13993003.02414-2022","article-title":"Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study","volume":"61","author":"Waxman","year":"2023","journal-title":"Eur. Respir. J."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.healun.2004.10.014","article-title":"Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis","volume":"24","author":"Whelan","year":"2005","journal-title":"J. Heart Lung Transpl."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1164\/rccm.202412-2371OC","article-title":"Hemodynamics and Phosphodiesterase-5 inhibitor treatment associated with survival in pulmonary hypertension in interstitial lung disease: a PVRI GoDeep meta-registry analysis","volume":"211","author":"Yogeswaran","year":"2025","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B103","doi-asserted-by":"publisher","first-page":"2604967","DOI":"10.1155\/2020\/2604967","article-title":"Pirfenidone inhibits hypoxic pulmonary hypertension through the NADPH\/ROS\/p38 pathway in adventitial fibroblasts in the pulmonary artery","volume":"2020","author":"Zhang","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"B104","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1111\/resp.12294","article-title":"Haemodynamic changes in pulmonary hypertension in patients with interstitial lung disease treated with PDE-5 inhibitors","volume":"19","author":"Zimmermann","year":"2014","journal-title":"Respirology"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1865787\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:08:39Z","timestamp":1785226119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1865787\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":104,"alternative-id":["10.3389\/fphar.2026.1865787"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1865787","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"article-number":"1865787"}}