Download PDF
Semin Respir Crit Care Med 2024; 45(05): 574-581
DOI: 10.1055/s-0044-1791824
Review Article

Pulmonary Vascular Disease in Chronic Obstructive Pulmonary Disease

Dana Kay
1   College of Medicine, University of Cincinnati, Cincinnati, Ohio
,
Roberto Bernardo
2   Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio
,
Jean Elwing
2   Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio
› Author Affiliations Funding None.
› Further Information
    Permissions and Reprints

Abstract

Pulmonary hypertension (PH) is a vascular disease characterized by pulmonary artery remodeling and right heart failure. PH related to COPD is a precapillary form of the disease, with hemodynamic measurements including a mean pulmonary artery pressure of greater than 20 mm Hg, a wedge pressure of less than 15 mm Hg, and a pulmonary vascular resistance of greater than 3 WU (Woods units), categorized under the World Health Organization classification as group 3. The presence of PH in COPD has been known to increase morbidity and mortality. Limited studies have evaluated treatment options for PH related to COPD.

Keywords

pulmonary hypertension - pulmonary vascular disease - pulmonary artery remodeling - right heart failure


Publication History

Article published online:
12 November 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Scharf SM, Iqbal M, Keller C, Criner G, Lee S, Fessler HE. National Emphysema Treatment Trial (NETT) Group. Hemodynamic characterization of patients with severe emphysema. Am J Respir Crit Care Med 2002; 166 (03) 314-322
    CrossrefPubMedSearch in Google Scholar
  • 2 Weitzenblum E, Hirth C, Ducolone A, Mirhom R, Rasaholinjanahary J, Ehrhart M. Prognostic value of pulmonary artery pressure in chronic obstructive pulmonary disease. Thorax 1981; 36 (10) 752-758
    CrossrefPubMedSearch in Google Scholar
  • 3 Thabut G, Dauriat G, Stern JB. et al. Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation. Chest 2005; 127 (05) 1531-1536
    CrossrefPubMedSearch in Google Scholar
  • 4 Oswald-Mammosser M, Apprill M, Bachez P, Ehrhart M, Weitzenblum E. Pulmonary hemodynamics in chronic obstructive pulmonary disease of the emphysematous type. Respiration 1991; 58 (5-6): 304-310
    CrossrefPubMedSearch in Google Scholar
  • 5 Magee F, Wright JL, Wiggs BR, Paré PD, Hogg JC. Pulmonary vascular structure and function in chronic obstructive pulmonary disease. Thorax 1988; 43 (03) 183-189
    CrossrefPubMedSearch in Google Scholar
  • 6 Voelkel NF, Quaife RA, Leinwand LA. et al; National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 2006; 114 (17) 1883-1891
    CrossrefPubMedSearch in Google Scholar
  • 7 Fishman AP, McClement J, Himmelstein A, Cournand A. Effects of acute anoxia on the circulation and respiration in patients with chronic pulmonary disease studied during the steady state. J Clin Invest 1952; 31 (08) 770-781
    CrossrefPubMedSearch in Google Scholar
  • 8 Weir EK, Archer SL. The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels. FASEB J 1995; 9 (02) 183-189
    CrossrefPubMedSearch in Google Scholar
  • 9 Nakamura A, Kasamatsu N, Hashizume I. et al. Effects of hemoglobin on pulmonary arterial pressure and pulmonary vascular resistance in patients with chronic emphysema. Respiration 2000; 67 (05) 502-506
    CrossrefPubMedSearch in Google Scholar
  • 10 Joppa P, Petrasova D, Stancak B, Tkacova R. Systemic inflammation in patients with COPD and pulmonary hypertension. Chest 2006; 130 (02) 326-333
    CrossrefPubMedSearch in Google Scholar
  • 11 Barberà JA, Peinado VI, Santos S, Ramirez J, Roca J, Rodriguez-Roisin R. Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of smokers. Am J Respir Crit Care Med 2001; 164 (04) 709-713
    CrossrefPubMedSearch in Google Scholar
  • 12 Peinado VI, Barberá JA, Abate P. et al. Inflammatory reaction in pulmonary muscular arteries of patients with mild chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 159 (5 Pt 1): 1605-1611
    CrossrefPubMedSearch in Google Scholar
  • 13 Wright JL, Tai H, Dai J, Churg A. Cigarette smoke induces rapid changes in gene expression in pulmonary arteries. Lab Invest 2002; 82 (10) 1391-1398
    CrossrefPubMedSearch in Google Scholar
  • 14 Brimioulle S, Lejeune P, Vachiery JL, Leeman M, Melot C, Naeije R. Effects of acidosis and alkalosis on hypoxic pulmonary vasoconstriction in dogs. Am J Physiol 1990; 258 (2 Pt 2): H347-H353
    PubMedSearch in Google Scholar
  • 15 Rose Jr CE, Van Benthuysen K, Jackson JT. et al. Right ventricular performance during increased afterload impaired by hypercapnic acidosis in conscious dogs. Circ Res 1983; 52 (01) 76-84
    CrossrefPubMedSearch in Google Scholar
  • 16 McGuire M, Bradford A. Chronic intermittent hypercapnic hypoxia increases pulmonary arterial pressure and haematocrit in rats. Eur Respir J 2001; 18 (02) 279-285
    CrossrefPubMedSearch in Google Scholar
  • 17 Zuoyou L, Shiota S, Morio Y. et al. Borderline pulmonary hypertension associated with chronic hypercapnia in chronic pulmonary disease. Respir Physiol Neurobiol 2019; 262: 20-25
    CrossrefPubMedSearch in Google Scholar
  • 18 Tkácová R, Joppa P, Stancák B, Salagovic J, Misíková S, Kalina I. The link between angiotensin-converting enzyme genotype and pulmonary artery pressure in patients with COPD. Wien Klin Wochenschr 2005; 117 (5-6): 210-214
    CrossrefPubMedSearch in Google Scholar
  • 19 Yildiz P, Oflaz H, Cine N, Erginel-Unaltuna N, Erzengin F, Yilmaz V. Gene polymorphisms of endothelial nitric oxide synthase enzyme associated with pulmonary hypertension in patients with COPD. Respir Med 2003; 97 (12) 1282-1288
    CrossrefPubMedSearch in Google Scholar
  • 20 Eddahibi S, Humbert M, Fadel E. et al. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J Clin Invest 2001; 108 (08) 1141-1150
    CrossrefPubMedSearch in Google Scholar
  • 21 Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in COPD. Eur Respir J 2008; 32 (05) 1371-1385
    CrossrefPubMedSearch in Google Scholar
  • 22 Hassoun PM. Pulmonary Arterial Hypertension. N Engl J Med 2021; 385 (25) 2361-2376
    CrossrefPubMedSearch in Google Scholar
  • 23 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 (02) 20 45894021999960
    CrossrefPubMedSearch in Google Scholar
  • 24 Nathan SD, Barbera JA, Gaine SP. et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J 2019; 53 (01) 53
    CrossrefPubMedSearch in Google Scholar
  • 25 Bernardo RJ, Haddad F, Couture EJ. et al. Mechanics of right ventricular dysfunction in pulmonary arterial hypertension and heart failure with preserved ejection fraction. Cardiovasc Diagn Ther 2020; 10 (05) 1580-1603
    CrossrefPubMedSearch in Google Scholar
  • 26 Amsallem M, Boulate D, Kooreman Z. et al. Investigating the value of right heart echocardiographic metrics for detection of pulmonary hypertension in patients with advanced lung disease. Int J Cardiovasc Imaging 2017; 33 (06) 825-835
    CrossrefPubMedSearch in Google Scholar
  • 27 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. J Am Heart Assoc 2019; 8 (02) e011464
    CrossrefPubMedSearch in Google Scholar
  • 28 Smith KA, Waypa GB, Dudley VJ. et al. Role of hypoxia-inducible factors in regulating right ventricular function and remodeling during chronic hypoxia-induced pulmonary hypertension. Am J Respir Cell Mol Biol 2020; 63 (05) 652-664
    CrossrefPubMedSearch in Google Scholar
  • 29 Humbert M, Kovacs G, Hoeper MM. et al; ESC/ERS Scientific Document Group. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2023; 61 (01) 2022
    CrossrefPubMedSearch in Google Scholar
  • 30 Sahay S, Lane J, Sharpe MG. et al. Impact on pulmonary hypertension hemodynamic classification based on the methodology used to measure pulmonary artery wedge pressure and cardiac output. Ann Am Thorac Soc 2023; 20 (12) 1752-1759
    CrossrefPubMedSearch in Google Scholar
  • 31 Naeije R, Chin K. Differentiating precapillary from postcapillary pulmonary hypertension. Circulation 2019; 140 (09) 712-714
    CrossrefPubMedSearch in Google Scholar
  • 32 Vachiéry JL, Tedford RJ, Rosenkranz S. et al. Pulmonary hypertension due to left heart disease. Eur Respir J 2019; 53 (01) 53
    CrossrefPubMedSearch in Google Scholar
  • 33 Shlobin OA, Adir Y, Barbera JA. et al. Pulmonary hypertension associated with lung diseases. Eur Respir J 2024; 2401200
    CrossrefPubMedSearch in Google Scholar
  • 34 Galiè N, Humbert M, Vachiery JL. et al. 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). Eur Respir J 2015; 46 (04) 903-975
    CrossrefPubMedSearch in Google Scholar
  • 35 Chaouat A, Bugnet A-S, Kadaoui N. et al. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 172 (02) 189-194
    CrossrefPubMedSearch in Google Scholar
  • 36 Piccari L, Wort SJ, Meloni F. et al; REHAR Registry Investigators. The effect of borderline pulmonary hypertension on survival in chronic lung disease. Respiration 2022; 101 (08) 717-727
    CrossrefPubMedSearch in Google Scholar
  • 37 Zeder K, Avian A, Bachmaier G. et al. Elevated pulmonary vascular resistance predicts mortality in COPD patients. Eur Respir J 2021; 58 (02) 2100944
    CrossrefPubMedSearch in Google Scholar
  • 38 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 (08) 1000-1011
    CrossrefPubMedSearch in Google Scholar
  • 39 Hoeper MM, Pausch C, Grünig E. et al. Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry. J Heart Lung Transplant 2020; 39 (12) 1435-1444
    CrossrefPubMedSearch in Google Scholar
  • 40 Hale KA, Niewoehner DE, Cosio MG. Morphologic changes in the muscular pulmonary arteries: relationship to cigarette smoking, airway disease, and emphysema. Am Rev Respir Dis 1980; 122 (02) 273-278
    PubMedSearch in Google Scholar
  • 41 Santos S, Peinado VI, Ramírez J. et al. Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD. Eur Respir J 2002; 19 (04) 632-638
    CrossrefPubMedSearch in Google Scholar
  • 42 Estépar RS, Kinney GL, Black-Shinn JL. et al; COPDGene Study. Computed tomographic measures of pulmonary vascular morphology in smokers and their clinical implications. Am J Respir Crit Care Med 2013; 188 (02) 231-239
    CrossrefPubMedSearch in Google Scholar
  • 43 Oakes JM, Xu J, Morris TM. et al. Effects of chronic nicotine inhalation on systemic and pulmonary blood pressure and right ventricular remodeling in mice. Hypertension 2020; 75 (05) 1305-1314
    CrossrefPubMedSearch in Google Scholar
  • 44 Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet 1981; 1 (8222) 681-686
    PubMedSearch in Google Scholar
  • 45 Zieliński J, Tobiasz M, Hawryłkiewicz I, Sliwiński P, Pałasiewicz G. Effects of long-term oxygen therapy on pulmonary hemodynamics in COPD patients: a 6-year prospective study. Chest 1998; 113 (01) 65-70
    CrossrefPubMedSearch in Google Scholar
  • 46 Weitzenblum E, Sautegeau A, Ehrhart M, Mammosser M, Pelletier A. Long-term oxygen therapy can reverse the progression of pulmonary hypertension in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1985; 131 (04) 493-498
    CrossrefPubMedSearch in Google Scholar
  • 47 Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med 1980; 93 (03) 391-398
    CrossrefPubMedSearch in Google Scholar
  • 48 Arif R, Pandey A, Zhao Y, Arsenault-Mehta K, Khoujah D, Mehta S. Treatment of pulmonary hypertension associated with COPD: a systematic review. ERJ Open Res 2022; 8 (01) 00348-2021
    CrossrefPubMedSearch in Google Scholar
  • 49 Humbert M, Kovacs G, Hoeper MM. et al. Corrigendum to: 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: Developed by the 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 the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on rare respiratory diseases (ERN-LUNG). Eur Heart J 2023; 44 (15) 1312
    CrossrefPubMedSearch in Google Scholar
  • 50 Agostoni P, Doria E, Galli C, Tamborini G, Guazzi MD. Nifedipine reduces pulmonary pressure and vascular tone during short- but not long-term treatment of pulmonary hypertension in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1989; 139 (01) 120-125
    CrossrefPubMedSearch in Google Scholar
  • 51 Vestri R, Philip-Joet F, Surpas P, Arnaud A, Saadjian A. One-year clinical study on nifedipine in the treatment of pulmonary hypertension in chronic obstructive lung disease. Respiration 1988; 54 (02) 139-144
    CrossrefPubMedSearch in Google Scholar
  • 52 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 (02) 166-174
    CrossrefPubMedSearch in Google Scholar
  • 53 Lederer DJ, Bartels MN, Schluger NW. et al. Sildenafil for chronic obstructive pulmonary disease: a randomized crossover trial. COPD 2012; 9 (03) 268-275
    CrossrefPubMedSearch in Google Scholar
  • 54 Goudie AR, Lipworth BJ, Hopkinson PJ, Wei L, Struthers AD. Tadalafil in patients with chronic obstructive pulmonary disease: a randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med 2014; 2 (04) 293-300
    CrossrefPubMedSearch in Google Scholar
  • 55 Stolz D, Rasch H, Linka A. et al. A randomised, controlled trial of bosentan in severe COPD. Eur Respir J 2008; 32 (03) 619-628
    CrossrefPubMedSearch in Google Scholar
  • 56 Hurdman J, Condliffe R, Elliot CA. et al. Pulmonary hypertension in COPD: results from the ASPIRE registry. Eur Respir J 2013; 41 (06) 1292-1301
    CrossrefPubMedSearch in Google Scholar
  • 57 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 (02) 678-689
    CrossrefPubMedSearch in Google Scholar
  • 58 Tello K, Yogeswaran A, Majeed RW. et al; PVRI-GoDeep-Consortium Imad Al Ghouleh. Phosphodiesterase-5 inhibitor treatment is associated with improved survival in pulmonary hypertension associated with COPD in the PVRI GoDeep meta-registry. Chest 2024; S0012-3692 (24)05046-3
    PubMedSearch in Google Scholar
  • 59 Nathan SD, Argula R, Trivieri MG. et al. Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results. Eur Respir J 2024; 63 (06) 2400172
    CrossrefPubMedSearch in Google Scholar
  • 60 NIH National Library of Medicine. ClinicalTrial.gov. https://clinicaltrials.gov/
    PubMed