靶向药物在缺氧性肺动脉高压中的研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

刘贵香 ¹ , 孙媛媛 ¹ , 李琪 ² , 刘明洁 ¹ , 温静 ¹ , 王华蕊 ¹ ,  朱玲 ¹

1. ;
2. ;

Corresponding author：

朱玲, Email: 18263802832@163.com

Keywords：

DOI：

10.7507/1671-6205.202304034

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Citation： 刘贵香, 孙媛媛, 李琪, 刘明洁, 温静, 王华蕊, 朱玲. 靶向药物在缺氧性肺动脉高压中的研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2024, 23(3): 221-228. doi: 10.7507/1671-6205.202304034 Copy

1.	Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol, 2013, 62(25 Suppl): D42-D50.
2.	Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J, 2022, 43(38): 3618-3731.
3.	Howell K, Ooi H, Preston R, et al. Structural basis of hypoxic pulmonary hypertension: the modifying effect of chronic hypercapnia. Exp Physiol, 2004, 89(1): 66-72.
4.	Jiang Y, Dai A, Li Q, et al. Hypoxia induces transforming growth factor-beta1 gene expression in the pulmonary artery of rats via hypoxia-inducible factor-1alpha. Acta Biochim Biophys Sin (Shanghai), 2007, 39(1): 73-80.
5.	Gu S, Goel K, Forbes LM, et al. Tensions in taxonomies: current understanding and future directions in the pathobiologic basis and treatment of group 1 and group 3 pulmonary hypertension. Compr Physiol, 2023, 13(1): 4295-4319.
6.	Weatherald J, Boucly A, Peters A, et al. The evolving landscape of pulmonary arterial hypertension clinical trials. Lancet, 2022, 400(10366): 1884-1898.
7.	Clozel M, Maresta A, Humbert M. Endothelin receptor antagonists. Handb Exp Pharmacol, 2013, 218: 199-227.
8.	Ghofrani HA, Osterloh IH, Grimminger F. Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov, 2006, 5(8): 689-702.
9.	Jones DA, Benjamin CW, Linseman DA. Activation of thromboxane and prostacyclin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades. Mol Pharmacol, 1995, 48(5): 890-896.
10.	Lazarus HM, Denning J, Wring S, et al. A trial design to maximize knowledge of the effects of rodatristat ethyl in the treatment of pulmonary arterial hypertension (ELEVATE 2). Pulm Circ, 2022, 12(2): e12088.
11.	Humbert M, McLaughlin V, Gibbs JSR, et al. Sotatercept for the treatment of pulmonary arterial hypertension. N Engl J Med, 2021, 384(13): 1204-1215.
12.	Humbert M, McLaughlin V, Gibbs JSR, et al. Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Eur Respir J, 2023, 61(1): 2201347.
13.	Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med, 2023, 388(16): 1478-1490.
14.	Frantz RP, Benza RL, Channick RN, et al. TORREY, a Phase 2 study to evaluate the efficacy and safety of inhaled seralutinib for the treatment of pulmonary arterial hypertension. Pulm Circ, 2021, 11(4): 20458940211057071.
15.	Pullamsetti SS, Sitapara R, Osterhout R, et al. Pharmacology and rationale for seralutinib in the treatment of pulmonary arterial hypertension. Int J Mol Sci, 2023, 24(16): 12653.
16.	朱建勇, 曾玉琴, 胡清, 等. 西地那非联合波生坦治疗结缔组织病相关中重度肺动脉高压的临床疗效. 中国呼吸与危重监护杂志, 2018, 17(4): 369-372.
17.	Nydegger C, Martinelli C, Di Marco F, et al. Phosphodiesterase-5 inhibition alleviates pulmonary hypertension and basal lamina thickening in rats challenged by chronic hypoxia. Front Physiol, 2018, 9: 289.
18.	Strange G, Playford D, Stewart S, et al. Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort. Heart, 2012, 98(24): 1805-1811.
19.	Wijeratne DT, Lajkosz K, Brogly SB, et al. Increasing incidence and prevalence of World Health Organization Groups 1 to 4 Pulmonary Hypertension: a population-based cohort study in Ontario, Canada. Circ Cardiovasc Qual Outcomes, 2018, 11(2): e003973.
20.	雷思, 唐豆豆, 许念茹, 等. 肺动脉高压患者的现状调查及病因构成. 中南大学学报(医学版), 2017, 42(6): 641-646.
21.	Chaouat A, Bugnet AS, Kadaoui N, et al. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005, 172(2): 189-194.
22.	Oswald-Mammosser M, Weitzenblum E, Quoix E, et al. Prognostic factors in COPD patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure. Chest, 1995, 107(5): 1193-1198.
23.	Andersen CU, Mellemkjær S, Hilberg O, et al. Pulmonary hypertension in interstitial lung disease: prevalence, prognosis and 6 min walk test. Respir Med, 2012, 106(6): 875-882.
24.	Kimura M, Taniguchi H, Kondoh Y, et al. Pulmonary hypertension as a prognostic indicator at the initial evaluation in idiopathic pulmonary fibrosis. Respiration, 2013, 85(6): 456-463.
25.	Cottin V, Le Pavec J, Prévot G, et al. Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome. Eur Respir J, 2010, 35(1): 105-111.
26.	吴苏佶, 魏毅, 石俊青, 等. 肺纤维化合并肺气肿综合征的临床特征与危险因素分析. 中国呼吸与危重监护杂志, 2021, 20(1): 4-11.
27.	缪莉莉, 杨楠, 张锦. 睡眠呼吸暂停低通气综合征与肺动脉高压的相关研究. 中国呼吸与危重监护杂志, 2014, 13(2): 146-149.
28.	Simonson JL, Pandya D, Khan S, et al. Comparison of obstructive sleep apnoea prevalence and severity across WHO pulmonary hypertension groups. BMJ Open Respir Res, 2022, 9(1): e001304.
29.	Dumitrascu R, Tiede H, Eckermann J, et al. Sleep apnea in precapillary pulmonary hypertension. Sleep Med, 2013, 14(3): 247-251.
30.	Prins KW, Rose L, Archer SL, et al. Disproportionate right ventricular dysfunction and poor survival in group 3 pulmonary hypertension. Am J Respir Crit Care Med, 2018, 197(11): 1496-1499.
31.	Barberà JA, Blanco I. Management of pulmonary hypertension in patients with chronic lung disease. Curr Hypertens Rep, 2015, 17(8): 62.
32.	Chebib N, Mornex JF, Traclet J, et al. Pulmonary hypertension in chronic lung diseases: comparison to other pulmonary hypertension groups. Pulm Circ, 2018, 8(2): 2045894018775056.
33.	Seeger W, Adir Y, Barberà JA, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol, 2013, 62(25 Suppl): D109-D116.
34.	Ozben B, Eryuksel E, Tanrikulu AM, et al. Acute exacerbation impairs right ventricular function in COPD patients. Hellenic J Cardiol, 2015, 56(4): 324-331.
35.	Olschewski H, Ghofrani HA, Walmrath D, et al. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am J Respir Crit Care Med, 1999, 160(2): 600-607.
36.	Blanco I, Ribas J, Xaubet A, et al. Effects of inhaled nitric oxide at rest and during exercise in idiopathic pulmonary fibrosis. J Appl Physiol (1985), 2011, 110(3): 638-645.
37.	Lasota B, Skoczyński S, Mizia-Stec K, et al. The use of iloprost in the treatment of 'out of proportion' pulmonary hypertension in chronic obstructive pulmonary disease. Int J Clin Pharm, 2013, 35(3): 313-315.
38.	Nydegger C, Corno AF, von Segesser LK, et al. Effects of PDE-5 inhibition on the cardiopulmonary system after 2 or 4 weeks of chronic hypoxia. Cardiovasc Drugs Ther, 2019, 33(4): 407-414.
39.	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(3): 262-272.
40.	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(1): 145-155.
41.	Keen JL, Thenappan T. Shifting gears: the search for group 3 pulmonary hypertension treatment. Curr Opin Pulm Med, 2021, 27(5): 296-302.
42.	Zhao N, Chen J, Zhang M, et al. PAH-specific therapy for pulmonary hypertension and interstitial lung disease: a systemic review and meta-analysis. Front Cardiovasc Med, 2022, 9: 992879.
43.	Waxman AB, Elia D, Adir Y, et al. Recent advances in the management of pulmonary hypertension with interstitial lung disease. Eur Respir Rev, 2022, 31(165): 210220.
44.	Piccari L, Aguilar-Colindres R, Rodríguez-Chiaradía DA. Pulmonary hypertension in interstitial lung disease and in chronic obstructive pulmonary disease: different entities? Curr Opin Pulm Med, 2023, 29(5): 370-379.
45.	崔建华. 缺氧性肺动脉高压形成机制的研究进展. 西北国防医学杂志, 2013, 34(3): 251-255.
46.	Liu R, Yuan T, Wang R, et al. Insights into endothelin receptors in pulmonary hypertension. Int J Mol Sci, 2023, 24(12): 10206.
47.	Yang Z, Li P, Yuan Q, et al. Inhibition of miR-4640-5p alleviates pulmonary hypertension in chronic obstructive pulmonary disease patients by regulating nitric oxide synthase 1. Respir Res, 2023, 24(1): 92.
48.	Ozen G, Amgoud Y, Abdelazeem H, et al. Downregulation of PGI(2) pathway in Pulmonary Hypertension Group-III patients. Prostaglandins Leukot Essent Fatty Acids, 2020, 160: 102158.
49.	Goudie AR, Lipworth BJ, Hopkinson PJ, et al. Tadalafil in patients with chronic obstructive pulmonary disease: a randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med, 2014, 2(4): 293-300.
50.	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(1): e12043.
51.	Stolz D, Rasch H, Linka A, et al. A randomised, controlled trial of bosentan in severe COPD. Eur Respir J, 2008, 32(3): 619-628.
52.	Lederer DJ, Bartels MN, Schluger NW, et al. Sildenafil for chronic obstructive pulmonary disease: a randomized crossover trial. Copd, 2012, 9(3): 268-275.
53.	Sharif-Kashani B, Hamraghani A, Salamzadeh J, et al. The effect of amlodipine and sildenafil on the NT-ProBNP level of patients with COPD-induced pulmonary hypertension. Iran J Pharm Res, 2014, 13(Suppl): 161-168.
54.	Hao Y, Zhu Y, Mao Y, et al. Efficacy and safety of Sildenafil treatment in pulmonary hypertension caused by chronic obstructive pulmonary disease: a meta-analysis. Life Sci, 2020, 257: 118001.
55.	张春艳, 方翔, 候聪霞, 等. 波生坦在老年慢性阻塞性肺疾病稳定期合并肺动脉高压治疗中的临床效果. 临床研究, 2021, 29(3): 36-38.
56.	尹义平, 张敏. 波生坦治疗老年慢性阻塞性肺疾病稳定期合并肺动脉高压的临床效果及对患者右心功能的影响. 中国医药, 2019, 14(12): 1788-1791.
57.	Chen X, Tang S, Liu K, et al. Therapy in stable chronic obstructive pulmonary disease patients with pulmonary hypertension: a systematic review and meta-analysis. J Thorac Dis, 2015, 7(3): 309-319.
58.	Rao RS, Singh S, Sharma BB, et al. Sildenafil improves six-minute walk distance in chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Indian J Chest Dis Allied Sci, 2011, 53(2): 81-85.
59.	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(2): 678-689.
60.	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(2): 166-174.
61.	Ren Z, Li J, Shen J, et al. Therapeutic sildenafil inhibits pulmonary damage induced by cigarette smoke exposure and bacterial inhalation in rats. Pharm Biol, 2020, 58(1): 116-123.
62.	Blanco I, Gimeno E, Munoz PA, et al. Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Am J Respir Crit Care Med, 2010, 181(3): 270-278.
63.	Blanco I, Santos S, Gea J, et al. Sildenafil to improve respiratory rehabilitation outcomes in COPD: a controlled trial. Eur Respir J, 2013, 42(4): 982-992.
64.	Pichl A, Sommer N, Bednorz M, et al. Riociguat for treatment of pulmonary hypertension in COPD: a translational study. Eur Respir J, 2019, 53(6): 1802445.
65.	Bajwa AA, Shujaat A, Patel M, et al. The safety and tolerability of inhaled treprostinil in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Pulm Circ, 2017, 7(1): 82-88.
66.	Wang L, Jin YZ, Zhao QH, et al. Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension. Int J Chron Obstruct Pulmon Dis, 2017, 12: 3353-3360.
67.	Wu X, Bos IST, Conlon TM, et al. A transcriptomics-guided drug target discovery strategy identifies receptor ligands for lung regeneration. Sci Adv, 2022, 8(12): eabj9949.
68.	Lammi MR, Ghonim MA, Pyakurel K, et al. Treatment with intranasal iloprost reduces disease manifestations in a murine model of previously established COPD. Am J Physiol Lung Cell Mol Physiol, 2016, 310(7): L630-638.
69.	王瑞, 武云. 肺动脉高压靶向药物治疗的研究进展. 医学综述, 2022, 28(9): 1776-1783.
70.	Li Y, Wang Y, Liu S. Bosentan combined with sildenafil in the treatment of COPD patients with pulmonary arterial hypertension. Am J Transl Res, 2021, 13(10): 11522-11530.
71.	冼倩, 庞浩文, 吴旭. 贝前列素钠、西地那非起始联合与序贯治疗慢性阻塞性肺疾病合并肺动脉高压的效果比较. 广东医科大学学报, 2022, 40(4): 408-411.
72.	Raghu G, Behr J, Brown KK, et al. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med, 2013, 158(9): 641-649.
73.	Raghu G, Nathan SD, Behr J, et al. Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction. Eur Respir J, 2015, 46(5): 1370-1377.
74.	King TE Jr, Behr J, Brown KK, et al. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2008, 177(1): 75-81.
75.	King TE Jr, Brown KK, Raghu G, et al. BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2011, 184(1): 92-99.
76.	Corte TJ, Keir GJ, Dimopoulos K, et al. Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia. Am J Respir Crit Care Med, 2014, 190(2): 208-217.
77.	Tanaka Y, Hino M, Gemma A. Potential benefit of bosentan therapy in borderline or less severe pulmonary hypertension secondary to idiopathic pulmonary fibrosis-an interim analysis of results from a prospective, single-center, randomized, parallel-group study. BMC Pulm Med, 2017, 17(1): 200.
78.	Kolb M, Raghu G, Wells AU, et al. Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis. N Engl J Med, 2018, 379(18): 1722-1731.
79.	Kang J, Song JW. Effect of sildenafil added to antifibrotic treatment in idiopathic pulmonary fibrosis. Sci Rep, 2021, 11(1): 17824.
80.	Han MK, Bach DS, Hagan PG, et al. Sildenafil preserves exercise capacity in patients with idiopathic pulmonary fibrosis and right-sided ventricular dysfunction. Chest, 2013, 143(6): 1699-1708.
81.	Pitre T, Khalid MF, Cui S, et al. Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Pulm Pharmacol Ther, 2022, 73-74: 102128.
82.	Pitre T, Mah J, Helmeczi W, et al. Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis. Thorax, 2022, 77(12): 1243-1250.
83.	Hoeper MM, Behr J, Held M, et al. Pulmonary hypertension in patients with chronic fibrosing idiopathic interstitial pneumonias. PLoS One, 2015, 10(12): e0141911.
84.	Weatherald J, Humbert M. PDE5 to keep them alive: The use of phosphodiesterase type-5 inhibitors in severe pulmonary hypertension associated with interstitial lung disease. Respirology, 2023, 28(3): 212-214.
85.	Collard HR, Anstrom KJ, Schwarz MI, et al. Sildenafil improves walk distance in idiopathic pulmonary fibrosis. Chest, 2007, 131(3): 897-899.
86.	Brewis MJ, Church AC, Johnson MK, et al. Severe pulmonary hypertension in lung disease: phenotypes and response to treatment. Eur Respir J, 2015, 46(5): 1378-1389.
87.	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(1): 85-95.
88.	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(9): 780-790.
89.	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(6): 494-503.
90.	Lambers C, Roth M, Jaksch P, et al. Treprostinil inhibits proliferation and extracellular matrix deposition by fibroblasts through cAMP activation. Sci Rep, 2018, 8(1): 1087.
91.	Nikitopoulou I, Manitsopoulos N, Kotanidou A, et al. Orotracheal treprostinil administration attenuates bleomycin-induced lung injury, vascular remodeling, and fibrosis in mice. Pulm Circ, 2019, 9(4): 2045894019881954.
92.	Corboz MR, Zhang J, LaSala D, et al. Therapeutic administration of inhaled INS1009, a treprostinil prodrug formulation, inhibits bleomycin-induced pulmonary fibrosis in rats. Pulm Pharmacol Ther, 2018, 49: 95-103.
93.	Nathan SD, Tapson VF, Elwing J, et al. Efficacy of inhaled treprostinil on multiple disease progression events in patients with pulmonary hypertension due to parenchymal lung disease in the INCREASE Trial. Am J Respir Crit Care Med, 2022, 205(2): 198-207.
94.	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(2): 398-406.
95.	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(4): 325-334.
96.	Nathan SD, Waxman A, Rajagopal S, et al. Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension: a post-hoc analysis of the INCREASE study. Lancet Respir Med, 2021, 9(11): 1266-1274.
97.	Kolb M, Orfanos SE, Lambers C, et al. The antifibrotic effects of inhaled treprostinil: an emerging option for ILD. Adv Ther, 2022, 39(9): 3881-3895.
98.	Lee C, Hamlyn J, Porcelli J, et al. Practical considerations in the management of inhaled prostacyclin therapy for pulmonary hypertension associated with interstitial lung disease (WHO group 3). Respir Med, 2022, 196: 106806.
99.	Behr J. Inhaled treprostinil in pulmonary hypertension in the context of interstitial lung disease: a success, finally. Am J Respir Crit Care Med, 2022, 205(2): 144-145.
100.	Saggar R, Khanna D, Vaidya A, et al. Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis. Thorax, 2014, 69(2): 123-129.
101.	Roccia F, Campolo B, Gallelli L, et al. Effects of ambrisentan in a patient affected by combined pulmonary fibrosis and emphysema and by severe pulmonary hypertension: clinical, functional, and biomolecular findings. Clin Drug Investig, 2013, 33(6): 451-457.
102.	Kulshrestha R, Singh H, Pandey A, et al. Differential expression of caveolin-1 during pathogenesis of combined pulmonary fibrosis and emphysema: effect of phosphodiesterase-5 inhibitor. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(8): 165802.

1. Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol, 2013, 62(25 Suppl): D42-D50.
2. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J, 2022, 43(38): 3618-3731.
3. Howell K, Ooi H, Preston R, et al. Structural basis of hypoxic pulmonary hypertension: the modifying effect of chronic hypercapnia. Exp Physiol, 2004, 89(1): 66-72.
4. Jiang Y, Dai A, Li Q, et al. Hypoxia induces transforming growth factor-beta1 gene expression in the pulmonary artery of rats via hypoxia-inducible factor-1alpha. Acta Biochim Biophys Sin (Shanghai), 2007, 39(1): 73-80.
5. Gu S, Goel K, Forbes LM, et al. Tensions in taxonomies: current understanding and future directions in the pathobiologic basis and treatment of group 1 and group 3 pulmonary hypertension. Compr Physiol, 2023, 13(1): 4295-4319.
6. Weatherald J, Boucly A, Peters A, et al. The evolving landscape of pulmonary arterial hypertension clinical trials. Lancet, 2022, 400(10366): 1884-1898.
7. Clozel M, Maresta A, Humbert M. Endothelin receptor antagonists. Handb Exp Pharmacol, 2013, 218: 199-227.
8. Ghofrani HA, Osterloh IH, Grimminger F. Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov, 2006, 5(8): 689-702.
9. Jones DA, Benjamin CW, Linseman DA. Activation of thromboxane and prostacyclin receptors elicits opposing effects on vascular smooth muscle cell growth and mitogen-activated protein kinase signaling cascades. Mol Pharmacol, 1995, 48(5): 890-896.
10. Lazarus HM, Denning J, Wring S, et al. A trial design to maximize knowledge of the effects of rodatristat ethyl in the treatment of pulmonary arterial hypertension (ELEVATE 2). Pulm Circ, 2022, 12(2): e12088.
11. Humbert M, McLaughlin V, Gibbs JSR, et al. Sotatercept for the treatment of pulmonary arterial hypertension. N Engl J Med, 2021, 384(13): 1204-1215.
12. Humbert M, McLaughlin V, Gibbs JSR, et al. Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Eur Respir J, 2023, 61(1): 2201347.
13. Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med, 2023, 388(16): 1478-1490.
14. Frantz RP, Benza RL, Channick RN, et al. TORREY, a Phase 2 study to evaluate the efficacy and safety of inhaled seralutinib for the treatment of pulmonary arterial hypertension. Pulm Circ, 2021, 11(4): 20458940211057071.
15. Pullamsetti SS, Sitapara R, Osterhout R, et al. Pharmacology and rationale for seralutinib in the treatment of pulmonary arterial hypertension. Int J Mol Sci, 2023, 24(16): 12653.
16. 朱建勇, 曾玉琴, 胡清, 等. 西地那非联合波生坦治疗结缔组织病相关中重度肺动脉高压的临床疗效. 中国呼吸与危重监护杂志, 2018, 17(4): 369-372.
17. Nydegger C, Martinelli C, Di Marco F, et al. Phosphodiesterase-5 inhibition alleviates pulmonary hypertension and basal lamina thickening in rats challenged by chronic hypoxia. Front Physiol, 2018, 9: 289.
18. Strange G, Playford D, Stewart S, et al. Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort. Heart, 2012, 98(24): 1805-1811.
19. Wijeratne DT, Lajkosz K, Brogly SB, et al. Increasing incidence and prevalence of World Health Organization Groups 1 to 4 Pulmonary Hypertension: a population-based cohort study in Ontario, Canada. Circ Cardiovasc Qual Outcomes, 2018, 11(2): e003973.
20. 雷思, 唐豆豆, 许念茹, 等. 肺动脉高压患者的现状调查及病因构成. 中南大学学报(医学版), 2017, 42(6): 641-646.
21. Chaouat A, Bugnet AS, Kadaoui N, et al. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005, 172(2): 189-194.
22. Oswald-Mammosser M, Weitzenblum E, Quoix E, et al. Prognostic factors in COPD patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure. Chest, 1995, 107(5): 1193-1198.
23. Andersen CU, Mellemkjær S, Hilberg O, et al. Pulmonary hypertension in interstitial lung disease: prevalence, prognosis and 6 min walk test. Respir Med, 2012, 106(6): 875-882.
24. Kimura M, Taniguchi H, Kondoh Y, et al. Pulmonary hypertension as a prognostic indicator at the initial evaluation in idiopathic pulmonary fibrosis. Respiration, 2013, 85(6): 456-463.
25. Cottin V, Le Pavec J, Prévot G, et al. Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome. Eur Respir J, 2010, 35(1): 105-111.
26. 吴苏佶, 魏毅, 石俊青, 等. 肺纤维化合并肺气肿综合征的临床特征与危险因素分析. 中国呼吸与危重监护杂志, 2021, 20(1): 4-11.
27. 缪莉莉, 杨楠, 张锦. 睡眠呼吸暂停低通气综合征与肺动脉高压的相关研究. 中国呼吸与危重监护杂志, 2014, 13(2): 146-149.
28. Simonson JL, Pandya D, Khan S, et al. Comparison of obstructive sleep apnoea prevalence and severity across WHO pulmonary hypertension groups. BMJ Open Respir Res, 2022, 9(1): e001304.
29. Dumitrascu R, Tiede H, Eckermann J, et al. Sleep apnea in precapillary pulmonary hypertension. Sleep Med, 2013, 14(3): 247-251.
30. Prins KW, Rose L, Archer SL, et al. Disproportionate right ventricular dysfunction and poor survival in group 3 pulmonary hypertension. Am J Respir Crit Care Med, 2018, 197(11): 1496-1499.
31. Barberà JA, Blanco I. Management of pulmonary hypertension in patients with chronic lung disease. Curr Hypertens Rep, 2015, 17(8): 62.
32. Chebib N, Mornex JF, Traclet J, et al. Pulmonary hypertension in chronic lung diseases: comparison to other pulmonary hypertension groups. Pulm Circ, 2018, 8(2): 2045894018775056.
33. Seeger W, Adir Y, Barberà JA, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol, 2013, 62(25 Suppl): D109-D116.
34. Ozben B, Eryuksel E, Tanrikulu AM, et al. Acute exacerbation impairs right ventricular function in COPD patients. Hellenic J Cardiol, 2015, 56(4): 324-331.
35. Olschewski H, Ghofrani HA, Walmrath D, et al. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am J Respir Crit Care Med, 1999, 160(2): 600-607.
36. Blanco I, Ribas J, Xaubet A, et al. Effects of inhaled nitric oxide at rest and during exercise in idiopathic pulmonary fibrosis. J Appl Physiol (1985), 2011, 110(3): 638-645.
37. Lasota B, Skoczyński S, Mizia-Stec K, et al. The use of iloprost in the treatment of 'out of proportion' pulmonary hypertension in chronic obstructive pulmonary disease. Int J Clin Pharm, 2013, 35(3): 313-315.
38. Nydegger C, Corno AF, von Segesser LK, et al. Effects of PDE-5 inhibition on the cardiopulmonary system after 2 or 4 weeks of chronic hypoxia. Cardiovasc Drugs Ther, 2019, 33(4): 407-414.
39. 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(3): 262-272.
40. 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(1): 145-155.
41. Keen JL, Thenappan T. Shifting gears: the search for group 3 pulmonary hypertension treatment. Curr Opin Pulm Med, 2021, 27(5): 296-302.
42. Zhao N, Chen J, Zhang M, et al. PAH-specific therapy for pulmonary hypertension and interstitial lung disease: a systemic review and meta-analysis. Front Cardiovasc Med, 2022, 9: 992879.
43. Waxman AB, Elia D, Adir Y, et al. Recent advances in the management of pulmonary hypertension with interstitial lung disease. Eur Respir Rev, 2022, 31(165): 210220.
44. Piccari L, Aguilar-Colindres R, Rodríguez-Chiaradía DA. Pulmonary hypertension in interstitial lung disease and in chronic obstructive pulmonary disease: different entities? Curr Opin Pulm Med, 2023, 29(5): 370-379.
45. 崔建华. 缺氧性肺动脉高压形成机制的研究进展. 西北国防医学杂志, 2013, 34(3): 251-255.
46. Liu R, Yuan T, Wang R, et al. Insights into endothelin receptors in pulmonary hypertension. Int J Mol Sci, 2023, 24(12): 10206.
47. Yang Z, Li P, Yuan Q, et al. Inhibition of miR-4640-5p alleviates pulmonary hypertension in chronic obstructive pulmonary disease patients by regulating nitric oxide synthase 1. Respir Res, 2023, 24(1): 92.
48. Ozen G, Amgoud Y, Abdelazeem H, et al. Downregulation of PGI(2) pathway in Pulmonary Hypertension Group-III patients. Prostaglandins Leukot Essent Fatty Acids, 2020, 160: 102158.
49. Goudie AR, Lipworth BJ, Hopkinson PJ, et al. Tadalafil in patients with chronic obstructive pulmonary disease: a randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med, 2014, 2(4): 293-300.
50. 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(1): e12043.
51. Stolz D, Rasch H, Linka A, et al. A randomised, controlled trial of bosentan in severe COPD. Eur Respir J, 2008, 32(3): 619-628.
52. Lederer DJ, Bartels MN, Schluger NW, et al. Sildenafil for chronic obstructive pulmonary disease: a randomized crossover trial. Copd, 2012, 9(3): 268-275.
53. Sharif-Kashani B, Hamraghani A, Salamzadeh J, et al. The effect of amlodipine and sildenafil on the NT-ProBNP level of patients with COPD-induced pulmonary hypertension. Iran J Pharm Res, 2014, 13(Suppl): 161-168.
54. Hao Y, Zhu Y, Mao Y, et al. Efficacy and safety of Sildenafil treatment in pulmonary hypertension caused by chronic obstructive pulmonary disease: a meta-analysis. Life Sci, 2020, 257: 118001.
55. 张春艳, 方翔, 候聪霞, 等. 波生坦在老年慢性阻塞性肺疾病稳定期合并肺动脉高压治疗中的临床效果. 临床研究, 2021, 29(3): 36-38.
56. 尹义平, 张敏. 波生坦治疗老年慢性阻塞性肺疾病稳定期合并肺动脉高压的临床效果及对患者右心功能的影响. 中国医药, 2019, 14(12): 1788-1791.
57. Chen X, Tang S, Liu K, et al. Therapy in stable chronic obstructive pulmonary disease patients with pulmonary hypertension: a systematic review and meta-analysis. J Thorac Dis, 2015, 7(3): 309-319.
58. Rao RS, Singh S, Sharma BB, et al. Sildenafil improves six-minute walk distance in chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Indian J Chest Dis Allied Sci, 2011, 53(2): 81-85.
59. 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(2): 678-689.
60. 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(2): 166-174.
61. Ren Z, Li J, Shen J, et al. Therapeutic sildenafil inhibits pulmonary damage induced by cigarette smoke exposure and bacterial inhalation in rats. Pharm Biol, 2020, 58(1): 116-123.
62. Blanco I, Gimeno E, Munoz PA, et al. Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Am J Respir Crit Care Med, 2010, 181(3): 270-278.
63. Blanco I, Santos S, Gea J, et al. Sildenafil to improve respiratory rehabilitation outcomes in COPD: a controlled trial. Eur Respir J, 2013, 42(4): 982-992.
64. Pichl A, Sommer N, Bednorz M, et al. Riociguat for treatment of pulmonary hypertension in COPD: a translational study. Eur Respir J, 2019, 53(6): 1802445.
65. Bajwa AA, Shujaat A, Patel M, et al. The safety and tolerability of inhaled treprostinil in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Pulm Circ, 2017, 7(1): 82-88.
66. Wang L, Jin YZ, Zhao QH, et al. Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension. Int J Chron Obstruct Pulmon Dis, 2017, 12: 3353-3360.
67. Wu X, Bos IST, Conlon TM, et al. A transcriptomics-guided drug target discovery strategy identifies receptor ligands for lung regeneration. Sci Adv, 2022, 8(12): eabj9949.
68. Lammi MR, Ghonim MA, Pyakurel K, et al. Treatment with intranasal iloprost reduces disease manifestations in a murine model of previously established COPD. Am J Physiol Lung Cell Mol Physiol, 2016, 310(7): L630-638.
69. 王瑞, 武云. 肺动脉高压靶向药物治疗的研究进展. 医学综述, 2022, 28(9): 1776-1783.
70. Li Y, Wang Y, Liu S. Bosentan combined with sildenafil in the treatment of COPD patients with pulmonary arterial hypertension. Am J Transl Res, 2021, 13(10): 11522-11530.
71. 冼倩, 庞浩文, 吴旭. 贝前列素钠、西地那非起始联合与序贯治疗慢性阻塞性肺疾病合并肺动脉高压的效果比较. 广东医科大学学报, 2022, 40(4): 408-411.
72. Raghu G, Behr J, Brown KK, et al. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med, 2013, 158(9): 641-649.
73. Raghu G, Nathan SD, Behr J, et al. Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction. Eur Respir J, 2015, 46(5): 1370-1377.
74. King TE Jr, Behr J, Brown KK, et al. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2008, 177(1): 75-81.
75. King TE Jr, Brown KK, Raghu G, et al. BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2011, 184(1): 92-99.
76. Corte TJ, Keir GJ, Dimopoulos K, et al. Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia. Am J Respir Crit Care Med, 2014, 190(2): 208-217.
77. Tanaka Y, Hino M, Gemma A. Potential benefit of bosentan therapy in borderline or less severe pulmonary hypertension secondary to idiopathic pulmonary fibrosis-an interim analysis of results from a prospective, single-center, randomized, parallel-group study. BMC Pulm Med, 2017, 17(1): 200.
78. Kolb M, Raghu G, Wells AU, et al. Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis. N Engl J Med, 2018, 379(18): 1722-1731.
79. Kang J, Song JW. Effect of sildenafil added to antifibrotic treatment in idiopathic pulmonary fibrosis. Sci Rep, 2021, 11(1): 17824.
80. Han MK, Bach DS, Hagan PG, et al. Sildenafil preserves exercise capacity in patients with idiopathic pulmonary fibrosis and right-sided ventricular dysfunction. Chest, 2013, 143(6): 1699-1708.
81. Pitre T, Khalid MF, Cui S, et al. Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Pulm Pharmacol Ther, 2022, 73-74: 102128.
82. Pitre T, Mah J, Helmeczi W, et al. Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis. Thorax, 2022, 77(12): 1243-1250.
83. Hoeper MM, Behr J, Held M, et al. Pulmonary hypertension in patients with chronic fibrosing idiopathic interstitial pneumonias. PLoS One, 2015, 10(12): e0141911.
84. Weatherald J, Humbert M. PDE5 to keep them alive: The use of phosphodiesterase type-5 inhibitors in severe pulmonary hypertension associated with interstitial lung disease. Respirology, 2023, 28(3): 212-214.
85. Collard HR, Anstrom KJ, Schwarz MI, et al. Sildenafil improves walk distance in idiopathic pulmonary fibrosis. Chest, 2007, 131(3): 897-899.
86. Brewis MJ, Church AC, Johnson MK, et al. Severe pulmonary hypertension in lung disease: phenotypes and response to treatment. Eur Respir J, 2015, 46(5): 1378-1389.
87. 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(1): 85-95.
88. 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(9): 780-790.
89. 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(6): 494-503.
90. Lambers C, Roth M, Jaksch P, et al. Treprostinil inhibits proliferation and extracellular matrix deposition by fibroblasts through cAMP activation. Sci Rep, 2018, 8(1): 1087.
91. Nikitopoulou I, Manitsopoulos N, Kotanidou A, et al. Orotracheal treprostinil administration attenuates bleomycin-induced lung injury, vascular remodeling, and fibrosis in mice. Pulm Circ, 2019, 9(4): 2045894019881954.
92. Corboz MR, Zhang J, LaSala D, et al. Therapeutic administration of inhaled INS1009, a treprostinil prodrug formulation, inhibits bleomycin-induced pulmonary fibrosis in rats. Pulm Pharmacol Ther, 2018, 49: 95-103.
93. Nathan SD, Tapson VF, Elwing J, et al. Efficacy of inhaled treprostinil on multiple disease progression events in patients with pulmonary hypertension due to parenchymal lung disease in the INCREASE Trial. Am J Respir Crit Care Med, 2022, 205(2): 198-207.
94. 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(2): 398-406.
95. 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(4): 325-334.
96. Nathan SD, Waxman A, Rajagopal S, et al. Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension: a post-hoc analysis of the INCREASE study. Lancet Respir Med, 2021, 9(11): 1266-1274.
97. Kolb M, Orfanos SE, Lambers C, et al. The antifibrotic effects of inhaled treprostinil: an emerging option for ILD. Adv Ther, 2022, 39(9): 3881-3895.
98. Lee C, Hamlyn J, Porcelli J, et al. Practical considerations in the management of inhaled prostacyclin therapy for pulmonary hypertension associated with interstitial lung disease (WHO group 3). Respir Med, 2022, 196: 106806.
99. Behr J. Inhaled treprostinil in pulmonary hypertension in the context of interstitial lung disease: a success, finally. Am J Respir Crit Care Med, 2022, 205(2): 144-145.
100. Saggar R, Khanna D, Vaidya A, et al. Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis. Thorax, 2014, 69(2): 123-129.
101. Roccia F, Campolo B, Gallelli L, et al. Effects of ambrisentan in a patient affected by combined pulmonary fibrosis and emphysema and by severe pulmonary hypertension: clinical, functional, and biomolecular findings. Clin Drug Investig, 2013, 33(6): 451-457.
102. Kulshrestha R, Singh H, Pandey A, et al. Differential expression of caveolin-1 during pathogenesis of combined pulmonary fibrosis and emphysema: effect of phosphodiesterase-5 inhibitor. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(8): 165802.

Previous Article
重组结核杆菌融合蛋白在结核感染中诊断价值的研究进展

Chinese Journal of Respiratory and Critical Care Medicine

靶向药物在缺氧性肺动脉高压中的研究进展

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Format

Content