Pulmonale Hypertonie assoziiert mit Lungenerkrankungen

Zusammenfassung

Die pulmonale Hypertonie bei chronischen Lungenerkrankungen (PH-CLD) ist eine der häufigsten, jedoch häufig unterdiagnostizierten Formen der pulmonalen Hypertonie (PH). Ihr Auftreten verschlechtert nachweislich Prognose und Lebensqualität der betroffenen Patient*innen. Neue epidemiologische Daten betonen die Heterogenität dieser Patientengruppe und zeigen, dass sowohl die zugrunde liegende Lungenerkrankung als auch der Schweregrad der PH für Prognose und Therapie entscheidend sind. Der 7. Weltkongress für pulmonale Hypertonie (WSPH) hat daher die Bedeutung einer systematischen Diagnostik und differenzierten Phänotypisierung von PH-CLD unterstrichen. Während einzelne Studien einen potenziellen Nutzen PH-spezifischer Therapien zeigen, berichten andere, etwa bei COPD, auch von negativen Effekten. Die vorliegende Stellungnahme der PH-DACH-Arbeitsgruppe fasst die wesentlichen Empfehlungen der 11. Task Force des 7. WSPH zusammen, bewertet die Evidenzlage kritisch und kommentiert gezielt Abweichungen vom Originaltext. Ziel ist es, einen Beitrag zur Entwicklung praxisnaher Diagnose- und Therapiealgorithmen für PH-CLD-Patienten zu leisten.

Abstract

Pulmonary hypertension associated with chronic lung diseases (PH-CLD) is one of the most common but frequently underdiagnosed forms of pulmonary hypertension (PH). Its presence has been consistently associated with worse prognosis and reduced quality of life for affected patients. Recent epidemiological data highlight the heterogeneity of this patient population, demonstrating that both the underlying lung disease and the severity of PH are critical determinants of prognosis and therapeutic decisions. The 7th World Symposium on Pulmonary Hypertension (WSPH) emphasized the importance of systematic diagnostic approaches and detailed phenotyping of PH-CLD. While some studies have shown potential benefits of PH-targeted therapies, others – particularly in COPD – have reported adverse outcomes. This position statement by the PH-DACH working group summarizes the key recommendations of the 11th Task Force of the 7th WSPH, critically assesses the current evidence, and comments specifically on deviations from the original text. The aim is to contribute to the development of practical diagnostic and therapeutic algorithms for patients with PH-CLD.

Schlüsselwörter

pulmonale Hypertonie - COPD - ILD - Lungenerkrankungen

Keywords

pulmonary hypertension - COPD - ILD - lung diseases

^* geteilte Letztautorenschaft

Publication History

Article published online:
06 October 2025

• Literatur

• 1 Shlobin OA, Adir Y, Barbera JA. et al. Pulmonary hypertension associated with lung diseases. Eur Respir J 2024; 64: 2401200
• 2 Hollingworth K, Davis K, Landis S. et al. Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012–2013. COPD 2014; 9: 597-611
• 3 Washko GR, Nardelli P, Ash SY. et al. Arterial Vascular Pruning, Right Ventricular Size, and Clinical Outcomes in Chronic Obstructive Pulmonary Disease. A Longitudinal Observational Study. Am J Respir Crit Care Med 2019; 200: 454-461
• 4 Nathan SD, Barbera JA, Gaine SP. et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J 2019; 53: 1801914
• 5 Vizza CD, Hoeper MM, Huscher D. et al. Pulmonary Hypertension in Patients With COPD: Results From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA). Chest 2021; 160: 678-689
• 6 Waxman A, Restrepo-Jaramillo R, Thenappan T. et al. Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study. Eur Respir J 2023; 61: 2202414
• 7 Tello K, Yogeswaran A, Majeed RW. et al. Association of Phosphodiesterase-5 Inhibitor Treatment With Improved Survival in Pulmonary Hypertension Associated With COPD in the Pulmonary Vascular Research Institute GoDeep Meta-Registry. Chest 2025; 167: 224-240
• 8 Agustí A, Celli BR, Criner GJ. et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Eur Respir J 2023; 61: 2300239
• 9 El Kaddouri B, Strand MJ, Baraghoshi D. et al. Fleischner Society Visual Emphysema CT Patterns Help Predict Progression of Emphysema in Current and Former Smokers: Results from the COPDGene Study. Radiology 2021; 298: 441-449
• 10 Zhang L, Liu Y, Zhao S. et al. The Incidence and Prevalence of Pulmonary Hypertension in the COPD Population: A Systematic Review and Meta-Analysis. Int J Chron Obstruct Pulmon Dis 2022; 17: 1365-1379
• 11 Fabbri LM, Celli BR, Agustí A. et al. COPD and multimorbidity: recognising and addressing a syndemic occurrence. The Lancet Respiratory Medicine 2023; 11: 1020-1034
• 12 Divo M, Cote C, De Torres JP. et al. Comorbidities and Risk of Mortality in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2012; 186: 155-161
• 13 Torres-Castro R, Gimeno-Santos E, Vilaró J. et al. Effect of pulmonary hypertension on exercise tolerance in patients with COPD: a prognostic systematic review and meta-analysis. Eur Respir Rev 2021; 30: 200321
• 14 Klinger JR, Wu B, Morland K. et al. Burden of pulmonary hypertension due to chronic obstructive pulmonary disease: Analysis of exacerbations and healthcare resource utilization in the United States. Respir Med 2023; 219: 107412
• 15 Weiss T, Near AM, Zhao X. et al. Healthcare resource utilization in patients with pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD): a real-world data analysis. BMC Pulm Med 2023; 23: 455
• 16 Zeder K, Avian A, Bachmaier G. et al. Elevated pulmonary vascular resistance predicts mortality in COPD patients. Eur Respir J 2021; 58: 2100944
• 17 Simonneau G, Montani D, Celermajer DS. et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 2019; 53: 1801913
• 18 Roversi S, Fabbri LM, Sin DD. et al. Chronic Obstructive Pulmonary Disease and Cardiac Diseases. An Urgent Need for Integrated Care. Am J Respir Crit Care Med 2016; 194: 1319-1336
• 19 Piccari L, Del Pozo R, Blanco I. et al. Association Between Systemic and Pulmonary Vascular Dysfunction in COPD. COPD 2020; 15: 2037-2047
• 20 Nathan SD, Barnett SD, King CS. et al. Impact of the new definition for pulmonary hypertension in patients with lung disease: an analysis of the United Network for Organ Sharing database. Pulm Circ 2021; 11: 1-7
• 21 Kovacs G, Agusti A, Barberà JA. et al. Pulmonary Vascular Involvement in Chronic Obstructive Pulmonary Disease. Is There a Pulmonary Vascular Phenotype?. Am J Respir Crit Care Med 2018; 198: 1000-1011
• 22 Hoeper MM, Dwivedi K, Pausch C. et al. Phenotyping of idiopathic pulmonary arterial hypertension: a registry analysis. Lancet Respir Med 2022; 10: 937-948
• 23 Piccari L, Wort SJ, Meloni F. et al. The Effect of Borderline Pulmonary Hypertension on Survival in Chronic Lung Disease. Respiration 2022; 101: 717-727
• 24 Hoeper MM, Behr J, Held M. et al. Pulmonary Hypertension in Patients with Chronic Fibrosing Idiopathic Interstitial Pneumonias. PLoS One 2015; 10: e0141911
• 25 Gall H, Felix JF, Schneck FK. et al. The Giessen Pulmonary Hypertension Registry: Survival in pulmonary hypertension subgroups. The Journal of Heart and Lung Transplantation 2017; 36: 957-967
• 26 Brewis MJ, Church AC, Johnson MK. et al. Severe pulmonary hypertension in lung disease: phenotypes and response to treatment. Eur Respir J 2015; 46: 1378-1389
• 27 Chebib N, Mornex J, Traclet J. et al. Pulmonary hypertension in chronic lung diseases: comparison to other pulmonary hypertension groups. Pulm Circ 2018; 8: 1-10
• 28 Alhamad EH, Cal JG, Alrajhi NN. et al. Predictors of Mortality in Patients with Interstitial Lung Disease-Associated Pulmonary Hypertension. JCM 2020; 9: 3828
• 29 Prins KW, Rose L, Archer SL. et al. Clinical Determinants and Prognostic Implications of Right Ventricular Dysfunction in Pulmonary Hypertension Caused by Chronic Lung Disease. JAHA 2019; 8: e011464
• 30 Sonaglioni A, Caminati A, Nicolosi GL. et al. Incremental prognostic value of arterial elastance in mild-to-moderate idiopathic pulmonary fibrosis. Int J Cardiovasc Imaging 2022; 38: 1473-1485
• 31 Kamide H, Kato S, Hayakawa K. et al. Impairment of right ventricular strain evaluated by cardiovascular magnetic resonance feature tracking in patients with interstitial lung disease. Int J Cardiovasc Imaging 2021; 37: 1073-1083
• 32 Tello K, Ghofrani HA, Heinze C. et al. A simple echocardiographic estimate of right ventricular-arterial coupling to assess severity and outcome in pulmonary hypertension on chronic lung disease. Eur Respir J 2019; 54: 1802435
• 33 Moinzadeh P, Bonella F, Oberste M. et al. Impact of Systemic Sclerosis-Associated Interstitial Lung Disease With and Without Pulmonary Hypertension on Survival. Chest 2024; 165: 132-145
• 34 Young A, Vummidi D, Visovatti S. et al. Prevalence, Treatment, and Outcomes of Coexistent Pulmonary Hypertension and Interstitial Lung Disease in Systemic Sclerosis. Arthritis & Rheumatology 2019; 71: 1339-1349
• 35 Guillén-Del-Castillo A, Meseguer ML, Fonollosa-Pla V. et al. Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension. Sci Rep 2022; 12: 5289
• 36 Launay D, Montani D, Hassoun PM. et al. Clinical phenotypes and survival of pre-capillary pulmonary hypertension in systemic sclerosis. PLoS One 2018; 13: e0197112
• 37 Chauvelot L, Gamondes D, Berthiller J. et al. Hemodynamic Response to Treatment and Outcomes in Pulmonary Hypertension Associated With Interstitial Lung Disease Versus Pulmonary Arterial Hypertension in Systemic Sclerosis: Data From a Study Identifying Prognostic Factors in Pulmonary Hypertension Associated With Interstitial Lung Disease. Arthritis & Rheumatology 2021; 73: 295-304
• 38 Cottin V, Selman M, Inoue Y. et al. Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement. Am J Respir Crit Care Med 2022; 206: e7-e41
• 39 Jacob J, Bartholmai BJ, Rajagopalan S. et al. Functional and prognostic effects when emphysema complicates idiopathic pulmonary fibrosis. Eur Respir J 2017; 50: 1700379
• 40 Jacob J, Bartholmai BJ, Rajagopalan S. et al. Likelihood of pulmonary hypertension in patients with idiopathic pulmonary fibrosis and emphysema. Respirology 2018; 23: 593-599
• 41 Zhao A, Gudmundsson E, Mogulkoc N. et al. Mortality surrogates in combined pulmonary fibrosis and emphysema. Eur Respir J 2024; 63: 2300127
• 42 Zou RH, Wallace WD, Nouraie SM. et al. Lower DLco% identifies exercise pulmonary hypertension in patients with parenchymal lung disease referred for dyspnea. Pulm Circ 2020; 10: 2045894019891912
• 43 Furukawa T, Kondoh Y, Taniguchi H. et al. A scoring system to predict the elevation of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis. Eur Respir J 2018; 51: 1701311
• 44 Armstrong HF, Thirapatarapong W, Dussault NE. et al. Distinguishing Pulmonary Hypertension in Interstitial Lung Disease by Ventilation and Perfusion Defects Measured by Cardiopulmonary Exercise Testing. Respiration 2013; 86: 407-413
• 45 Boerrigter BG, Bogaard HJ, Trip P. et al. Ventilatory and Cardiocirculatory Exercise Profiles in COPD. Chest 2012; 142: 1166-1174
• 46 Yogeswaran A, Kuhnert S, Gall H. et al. Relevance of Cor Pulmonale in COPD With and Without Pulmonary Hypertension: A Retrospective Cohort Study. Front Cardiovasc Med 2022; 9: 826369
• 47 Yagi M, Taniguchi H, Kondoh Y. et al. CT -determined pulmonary artery to aorta ratio as a predictor of elevated pulmonary artery pressure and survival in idiopathic pulmonary fibrosis. Respirology 2017; 22: 1393-11399
• 48 Wu X, Shi Y, Wang X. et al. Diagnostic value of computed tomography-based pulmonary artery to aorta ratio measurement in chronic obstructive pulmonary disease with pulmonary hypertension: A systematic review and meta-analysis. Clin Respir J 2022; 16: 276-283
• 49 Choi JS, Lee SH, Leem AhY. et al. Prognostic impact of the ratio of the main pulmonary artery to that of the aorta on chest computed tomography in patients with idiopathic pulmonary fibrosis. BMC Pulm Med 2019; 19: 81
• 50 Alkukhun L, Wang XF, Ahmed MK. et al. Non-invasive screening for pulmonary hypertension in idiopathic pulmonary fibrosis. Respir Med 2016; 117: 65-72
• 51 Ratanawatkul P, Oh A, Richards JC. et al. Performance of pulmonary artery dimensions measured on high-resolution computed tomography scan for identifying pulmonary hypertension. ERJ Open Res 2020; 6: 00232-2019
• 52 Cheng Y, Li L, Tu X. et al. The Main Pulmonary Artery to the Ascending Aorta Diameter Ratio (PA/A) as a Predictor of Worse Outcomes in Hospitalized Patients with AECOPD. COPD 2022; 17: 1157-1165
• 53 Agoston-Coldea L, Lupu S, Mocan T. Pulmonary Artery Stiffness by Cardiac Magnetic Resonance Imaging Predicts Major Adverse Cardiovascular Events in patients with Chronic Obstructive Pulmonary Disease. Sci Rep 2018; 8: 14447
• 54 Johns CS, Rajaram S, Capener DA. et al. Non-invasive methods for estimating mPAP in COPD using cardiovascular magnetic resonance imaging. Eur Radiol 2018; 28: 1438-1448
• 55 Winterbottom CJ, Shah RJ, Patterson KC. et al. Exposure to Ambient Particulate Matter Is Associated With Accelerated Functional Decline in Idiopathic Pulmonary Fibrosis. Chest 2018; 153: 1221-1228
• 56 Grünig E, MacKenzie A, Peacock AJ. et al. Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial. Eur Heart J 2021; 42: 2284-2295
• 57 Morris NR, Kermeen FD, Jones AW. et al. Exercise-based rehabilitation programmes for pulmonary hypertension. Cochrane Database Sys Rev 2023; 3: CD011285
• 58 Arif R, Pandey A, Zhao Y. et al. Treatment of pulmonary hypertension associated with COPD: a systematic review. ERJ Open Res 2022; 8: 00348-2021
• 59 Timms RM, Khaja FU, Williams GW. Hemodynamic Response to Oxygen Therapy in Chronic Obstructive Pulmonary Disease. Ann Intern Med 1985; 102: 29-36
• 60 Weitzenblum E, Sautegeau A, Ehrhart M. et al. Long-Term Oxygen Therapy Can Reverse the Progression of Pulmonary Hypertension in Patients with Chronic Obstructive Pulmonary Disease. Am Rev Respir Dis 1985; 131: 493-498
• 61 Castro-Añón O, Golpe R, Pérez-De-Llano LA. et al. Haemodynamic effects of non-invasive ventilation in patients with obesity-hypoventilation syndrome. Respirology 2012; 17: 1269-1274
• 62 Held M, Walthelm J, Baron S. et al. Functional impact of pulmonary hypertension due to hypoventilation and changes under noninvasive ventilation. Eur Respir J 2014; 43: 156-165
• 63 Lewis RA, Thompson AAR, Billings CG. et al. Mild parenchymal lung disease and/or low diffusion capacity impacts survival and treatment response in patients diagnosed with idiopathic pulmonary arterial hypertension. Eur Respir J 2020; 55: 2000041
• 64 Dwivedi K, Condliffe R, Sharkey M. et al. Computed tomography lung parenchymal descriptions in routine radiological reporting have diagnostic and prognostic utility in patients with idiopathic pulmonary arterial hypertension and pulmonary hypertension associated with lung disease. ERJ Open Res 2022; 8: 00549-2021
• 65 Elkhapery A, Hammami MB, Sulica R. et al. Pulmonary Vasodilator Therapy in Severe Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (Severe PH-COPD): A Systematic Review and Meta-Analysis. J Cardiovasc Dev Dis 2023; 10: 498
• 66 Nathan SD, Argula R, Trivieri MG. et al. Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results. Eur Respir J 2024; 63: 2400172
• 67 Prins KW, Duval S, Markowitz J. et al. Chronic use of PAH-specific therapy in World Health Organization Group III Pulmonary Hypertension: a systematic review and meta-analysis. Pulm Circ 2017; 7: 145-155
• 68 Nathan SD, Behr J, Collard HR. et al. Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study. Lancet Respir Med 2019; 7: 780-790
• 69 Raghu G, Behr J, Brown KK. et al. Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan: A Parallel, Randomized Trial. Ann Intern Med 2013; 158: 641-649
• 70 Dawes TJW, McCabe C, Dimopoulos K. et al. Phosphodiesterase 5 inhibitor treatment and survival in interstitial lung disease pulmonary hypertension: A Bayesian retrospective observational cohort study. Respirology 2023; 28: 262-272
• 71 Waxman A, Restrepo-Jaramillo R, Thenappan T. et al. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. N Engl J Med 2021; 384: 325-334
• 72 Nathan SD, Deng C, King CS. et al. Inhaled Treprostinil Dosage in Pulmonary Hypertension Associated With Interstitial Lung Disease and Its Effects on Clinical Outcomes. Chest 2023; 163: 398-406
• 73 Nathan SD, Johri S, Joly JM. et al. Survival analysis from the INCREASE study in PH-ILD: evaluating the impact of treatment crossover on overall mortality. Thorax 2024; 79: 301-306
• 74 Nathan SD, Cottin V, Behr J. et al. 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. J Heart Lung Transplant 2021; 40: 494-503
• 75 Vitulo P, Stanziola A, Confalonieri M. et al. Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A randomized controlled multicenter clinical trial. J Heart Lung Transplant 2017; 36: 166-174
• 76 Valerio G, Bracciale P, Grazia D’Agostino A. Effect of bosentan upon pulmonary hypertension in chronic obstructive pulmonary disease. Ther Adv Respir Dis 2009; 3: 15-21
• 77 Weatherald J, Nathan SD, El-Kersh K. et al. Inhaled treprostinil in patients with pulmonary hypertension associated with interstitial lung disease with less severe haemodynamics: a post hoc analysis of the INCREASE study. BMJ Open Respir Res 2024; 11: e002116
• 78 Maron BA, Choudhary G, Goldstein RL. et al. Tadalafil for veterans with chronic obstructive pulmonary disease-pulmonary hypertension: A multicenter, placebo-controlled randomized trial. Pulm Circ 2022; 12: e12043
• 79 Kolb M, Raghu G, Wells AU. et al. Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med 2018; 379: 1722-1731
• 80 Behr J, Nathan SD, Wuyts WA. et al. 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. Lancet Respir Med 2021; 9: 85-95
• 81 Nathan SD, Flaherty KR, Glassberg MK. et al. A Randomized, Double-Blind, Placebo-Controlled Study of Pulsed, Inhaled Nitric Oxide in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis. Chest 2020; 158: 637-645
• 82 A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects with Pulmonary Fibrosis at Risk for Pulmonary Hypertension (REBUILD). [Internet]. [cited 2025 Sep 3]. Available from: https://clinicaltrials.gov/study/NCT03267108
• 83 Faria-Urbina M, Oliveira RKF, Agarwal M. et al. Inhaled Treprostinil in Pulmonary Hypertension Associated with Lung Disease. Lung 2018; 196: 139-146
• 84 MK-5475-013 INSIGNIA-PH-COPD: a study of the efficacy and safety of MK-5475 (an inhaled sGC stimulator) in adults with PH-COPD. [Internet]. [cited 2025 Sep 3]. Available from: https://clinicaltrials.gov/study/NCT05612035
• 85 Tadalafil for severe pulmonary hypertension due to chronic obstructive pulmonary disease (ERASE PH-COPD). [Internet]. [cited 2025 Sep 3]. Available from: https://clinicaltrials.gov/study/NCT05844462
• 86 A study to evaluate the safety and tolerability of treprostinil palmitil inhalation powder in participants with pulmonary hypertension associated with interstitial lung disease. [Internet]. [cited 2025 Sep 3]. Available from: https://clinicaltrials.gov/study/NCT05176951
• 87 An Open-Label ProSpective MultiCENTer Study to Evaluate Safety and Tolerability of Dry Powder Inhaled Treprostinil in PH (ASCENT). [Internet]. [cited 2025 Sep 3]. Available from: https://clinicaltrials.gov/study/NCT06129240
• 88 A phase 3 study to evaluate the safety and tolerability of L606 in subjects with PAH or PH-ILD. [Internet]. [cited 2025 Sep 3]. Available from: https://clinicaltrials.gov/study/NCT04691154
• 89 Investigation of H01 in adults with pulmonary hypertension including interstitial lung disease (the SATURN study). [Internet]. [cited 2025 Sep 3]. Available from: https://clinicaltrials.gov/study/NCT05128929
• 90 Extended Access Program to Assess Long-term Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension RANGER (RANGER). [Internet]. [cited 2025 Sep 3]. Available from: https://clinicaltrials.gov/study/NCT03068130