Abstract
Pulmonary hypertension (PH) is an important complication in the natural history of chronic obstructive pulmonary disease (COPD). Its presence is associated with reduced survival and greater use of healthcare resources. The prevalence of PH is high in patients with advanced COPD, whereas in milder forms it might not be present at rest but may develop during exercise. In COPD, PH is usually of moderate severity and progresses slowly, without altering right ventricular function in the majority of patients. Nevertheless, a small subgroup of patients (1–3%) may present with out-of-proportion PH, that is, with pulmonary arterial pressure largely exceeding the severity of airway impairment. These patients depict a clinical picture similar to more severe forms of PH and have higher mortality rates.
PH in COPD is caused by the remodelling of pulmonary arteries, which is characterized by the intimal proliferation of poorly differentiated smooth muscle cells and the deposition of elastic and collagen fibres. The sequence of changes that lead to PH in COPD begins at early disease stages by the impairment of endothelial function, which is associated with impaired release of endothelium-derived vasodilating agents (nitric oxide, prostacyclin) and increased expression of growth factors. Products contained in cigarette smoke play a critical role in the initiation of pulmonary endothelial cell alterations.
Recognition of PH can be difficult because symptoms due to PH are not easy to differentiate from the clinical picture of COPD. Suspicion of PH should be high if clinical deterioration is not matched by the decline in pulmonary function, and in the presence of profound hypoxaemia or markedly reduced carbon monoxide diffusing capacity. Patients with suspected PH should be evaluated by Doppler echocardiography and, if confirmed, undergo right-heart catheterization in those circumstances where the result of the procedure can determine clinical management.
To date, long-term oxygen therapy is the treatment of choice in COPD patients with PH and hypoxaemia because it slows or reverses its progression. Conventional vasodilators are not recommended because of their potential detrimental effects on gas exchange, produced by the inhibition of hypoxic pulmonary vasoconstriction and their lack of effectiveness after long-term treatment. In the subgroup of patients with out-of-proportion PH, new specific therapy available for pulmonary arterial hypertension (PAH) [prostanoids, endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors] may be considered in the setting of clinical trials. The use of specific PAH therapy in COPD patients with moderate PH is discouraged because of the potential detrimental effect of some of these drugs on gas exchange and there are no data demonstrating their efficacy.
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References
Barberà JA, Peinado VI, Santos S. Pulmonary hypertension in chronic obstructive pulmonary disease. Eur Respir J 2003; 21(5): 892–905
Barberà JA, Riverola A, Roca J, et al. Pulmonary vascular abnormalities and ventilation-perfusion relationships in mild chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1994; 149 (2 Pt 1): 423–9
Peinado VI, Barberà JA, Ramirez J, et al. Endothelial dysfunction in pulmonary arteries of patients with mild COPD. Am J Physiol 1998; 274 (6 Pt 1): L908–13
Santos S, Peinado VI, Ramirez J, et al. Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD. Eur Respir J 2002; 19: 632–8
Galie N, Torbicki A, Barst R, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 2004; 25(24): 2243–78
Kovacs G, Scheidl S, Olschewski H. Pulmonary arterial pressure at rest and during exercise in normal controls. Eur Respir J 2008; 32: 261
Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007; 176(6): 532–55
Scharf SM, Iqbal M, Keller C, et al. Hemodynamic characterization of patients with severe emphysema. Am J Respir Crit Care Med 2002; 166(3): 314–22
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): 189–94
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(5): 1531–6
Kessler R, Faller M, Weitzenblum E, et al. “Natural history” of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease. Am J Respir Crit Care Med 2001; 164: 219–24
Peinado VI, Barberà 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): 1605–11
Weitzenblum E, Hirth C, Ducolone A, et al. Prognostic value of pulmonary artery pressure in chronic obstructive pulmonary disease. Thorax 1981; 36: 752–8
Burrows B, Kettel LJ, Niden AH, et al. Patterns of cardiovascular dysfunction in chronic obstructive lung disease. N Engl J Med 1972; 286(17): 912–8
Traver GA, Cline MG, Burrows B. Predictors of mortality in chronic obstructive pulmonary disease: a 15-year follow-up study. Am Rev Respir Dis 1979; 119(6): 895–902
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: 1193–8
Burgess MI, Mogulkoc N, Bright-Thomas RJ, et al. Comparison of echocardiographic markers of right ventricular function in determining prognosis in chronic pulmonary disease. J Am Soc Echocardiogr 2002; 15(6): 633–9
Incalzi RA, Fuso L, De Rosa M, et al. Electrocardiographic signs of chronic cor pulmonale: a negative prognostic finding in chronic obstructive pulmonary disease. Circulation 1999; 99(12): 1600–5
Kessler R, Faller M, Fourgaut G, et al. Predictive factors of hospitalization for acute exacerbation in a series of 64 patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 159: 158–64
Wilkinson M, Langhorne CA, Heath D, et al. A pathophysiological study of 10 cases of hypoxic cor pulmonale. Q J Med 1988; 249: 65–85
Wright JL, Petty T, Thurlbeck WM. Analysis of the structure of the muscular pulmonary arteries in patients with pulmonary hypertension and COPD: National Institutes of Health nocturnal oxygen therapy trial. Lung 1992; 170(2): 109–24
Santos S, Peinado VI, Ramirez J, et al. Enhanced expression of vascular endothelial growth factor in pulmonary arteries of smokers and patients with moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003; 167(9): 1250–6
Magee F, Wright JL, Wiggs BR, et al. Paré Pulmonary vascular structure and function in chronic obstructive pulmonary disease. Thorax 1988; 43: 183–9
Hale KA, Ewing SL, Gosnell BA, et al. Lung disease in long-term cigarette smokers with and without chronic airflow obstruction. Am Rev Respir Dis 1984; 130: 716–21
Saetta M, Baraldo S, Corbino L, et al. CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 160(2): 711–7
Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288(5789): 373–6
Stamler JS, Loh E, Roddy MA, et al. Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 1994; 89: 2035–40
Cremona G, Wood AM, Hall LW, et al. Effect of inhibitors of nitric oxide release and action on vascular tone in isolated lungs of pig, sheep, dog and man. J Physiol 1994; 481: 185–95
Greenberg B, Kishiyama S. Endothelium-dependent and -independent responses to severe hypoxia in rat pulmonary artery. Am J Physiol 1993; 349: H1712–20
Barberà JA, Roger N, Roca J, et al. Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease. Lancet 1996; 347(8999): 436–40
Dinh-Xuan AT, Higenbottam T, Clelland C, et al. Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive pulmonary disease. N Engl J Med 1991; 324: 1539–47
Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. N Engl J Med 1995; 333: 214–21
Melgosa M, Peinado VI, Santos S, et al. Expression of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) in pulmonary arteries of patients with severe COPD. Eur Respir J 2003; 22: 20
Barberà JA, Peinado VI, Santos S, et al. Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of smokers. Am J Respir Crit Care Med 2001; 164(4): 709–13
Nana-Sinkam SP, Lee JD, Sotto-Santiago S, et al. Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke. Am J Respir Crit Care Med 2007; 175(7): 676–85
Tuder RM, Cool CD, Geraci MW, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 1999; 159(6): 1925–32
Giaid A, Yanagisawa M, Langblen D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993; 328: 1732–9
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: 493–8
Wright JL, Churg A. Effect of long-term cigarette smoke exposure on pulmonary vascular structure and function in the guinea pig. Exp Lung Res 1991; 17: 997–1009
Yamato H, Churg A, Wright JL. Guinea pig pulmonary hypertension caused by cigarette smoke cannot be explained by capillary bed destruction. J Appl Physiol 1997; 82: 1644–53
Wright JL, Tai H, Dai J, et al. Cigarette smoke induces rapid changes in gene expression in pulmonary arteries. Lab Invest 2002; 82(10): 1391–8
Su Y, Han W, Giraldo C, et al. Effect of cigarette smoke extract on nitric oxide synthase in pulmonary artery endothelial cells. Am J Respir Cell Mol Biol 1998; 19: 819–25
Peinado VI, Ramirez J, Roca J, et al. Identification of vascular progenitor cells in pulmonary arteries of patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2006; 34(3): 257–63
Fishman AP. State of the art: chronic cor pulmonale. Am Rev Respir Dis 1976; 114(4): 775–94
Naeije R. Should pulmonary hypertension be treated in chronic obstructive pulmonary disease? In: Weir EK, Archer SL, Reeves JT, editors. The diagnosis and treatment of pulmonary hypertension. Mount Kisco (NY): Futura Publishing, 1992: 209–39
Weitzenblum E, Sautegeau A, Ehrhart M, et al. Long-term course of pulmonary arterial pressure in chronic obstructive pulmonary disease. Am Rev Respir Dis 1984; 130: 993–8
Barberà JA. Chronic obstructive pulmonary disease. In: Roca J, Rodriguez-Roisin R, Wagner PD, editors. Pulmonary and peripheral gas exchange in health and disease. New York (NT): Marcel Dekker, 2000: 229–61
Peinado VI, Santos S, Ramirez J, et al. Response to hypoxia of pulmonary arteries in COPD: an in vitro study. Eur Respir J 2002; 20: 332–8
Agustí AGN, Barberà JA, Roca J, et al. Hypoxic pulmonary vasoconstriction and gas exchange during exercise in chronic obstructive pulmonary disease. Chest 1990; 97(2): 268–75
Naeije R, Melot C, Mols P, et al. Effects of vasodilators on hypoxic pulmonary vasoconstriction in normal man. Chest 1982; 82(4): 404–10
Bratel T, Hedenstierna G, Nyquist O, et al. The use of a vasodilator, felodipine, as an adjuvant to long-term oxygen treatment in COLD patients. Eur Respir J 1990; 3: 46–54
Melot C, Naeije R, Mols P, et al. Effects of nifedipine on ventilation/perfusion matching in primary pulmonary hypertension. Chest 1983; 83(2): 203–7
Andrivet P, Chabrier PE, Defouilloy C, et al. Intravenously administered atrial natriuretic factor in patients with COPD. Effects on ventilation-perfusion relationships and pulmonary hemodynamics. Chest 1994; 106: 118–24
Adnot S, Kouyoumdjian C, Defouilloy C, et al. Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension. Am Rev Respir Dis 1993; 148: 310–6
Frostell C, Blomqvist H, Hedenstierna G, et al. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology 1993; 78: 427–35
Roger N, Barberà JA, Roca J, et al. Nitric oxide inhalation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997; 156 (3 Pt 1): 800–6
Katayama Y, Higenbottam TW, Diaz de Atauri MJ, et al. Inhaled nitric oxide and arterial oxygen tension in patients with chronic obstructive pulmonary disease and severe pulmonary hypertension. Thorax 1997; 52(2): 120–4
Archer SL, Mike D, Crow J, et al. A placebo-controlled trial of prostacyclin in acute respiratory failure in COPD. Chest 1996; 109(3): 750–5
Zhao L, Mason NA, Morrell NW, et al. Sildenafil inhibits hypoxia-induced pulmonary hypertension. Circulation 2001; 104(4): 424–8
Ballester E, Roca J, Ramis L, et al. Pulmonary gas exchange in severe chronic asthma. Response to 100% oxygen and salbutamol. Am Rev Respir Dis 1990; 141: 558–62
Ringsted CV, Eliasen K, Andersen JB, et al. Ventilationperfusion distributions and central hemodynamics in chronic obstructive pulmonary disease: effects of terbutaline administration. Chest 1989; 96: 976–83
Barberà JA, Reyes A, Roca J, et al. Effect of intravenously administered aminophylline on ventilation/perfusion inequality during recovery from exacerbations of chronic obstructive pulmonary disease. Am Rev Respir Dis 1992; 145(6): 1328–33
Brent BN, Berger HJ, Matthay RA, et al. Physiologic correlates of right ventricular ejection fraction in chronic obstructive pulmonary disease: a combined radionuclide and hemodynamic study. Am J Cardiol 1982; 50(2): 255–62
Weitzenblum E, Chaouat A. Right ventricular function in COPD: can it be assessed reliably by the measurement of right ventricular ejection fraction? Chest 1998; 113(3): 567–9
Crottogini AJ, Willshaw P. Calculating the end-systolic pressure-volume relation. Circulation 1991; 83(3): 1121–3
Biernacki W, Flenley DC, Muir AL, et al. Pulmonary hypertension and right ventricular function in patients with COPD. Chest 1988; 94(6): 1169–75
MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part One. Am J Respir Crit Care Med 1994; 150(3): 833–52
MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease: part Two. Am J Respir Crit Care Med 1994; 150(4): 1158–68
Barberà JA, Roca J, Ferrer A, et al. Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease. Eur Respir J 1997; 10(6): 1285–91
Weitzenblum E, Apprill M, Oswald M, et al. Pulmonary hemodynamics in patients with chronic obstructive pulmonary disease before and during an episode of peripheral edema. Chest 1994; 105(5): 1377–82
Campbell EJM, Short DS. The cause of oedema in “cor pulmonale”. Lancet 1960; I: 1184–6
Baudouin SV. Oedema and cor pulmonale revisited. Thorax 1997; 52(5): 401–2
MacNee W, Wathen CG, Flenley DC, et al. The effects of controlled oxygen therapy on ventricular function in patients with stable and decompensated cor pulmonale. Am Rev Respir Dis 1988; 137(6): 1289–95
MacNee W, Wathen CG, Hannan WJ, et al. Effects of pirbuterol and sodium nitroprusside on pulmonary haemodynamics in hypoxic cor pulmonale. BMJ (Clin Res Ed) 1983; 287(6400): 1169–72
Lee-Chiong TL, Matthay RA. The heart in the stable COPD patient. In: Similowski T, Whitelaw WA, Derenne JP, editors. Clinical management of chronic obstructive pulmonary disease. New York (NY): Marcel Dekker, 2002: 475–532
Palange P. Renal and hormonal abnormalities in chronic obstructive pulmonary disease (COPD). Thorax 1998; 53: 989–91
Chetty KG, Brown SE, Light RW. Identification of pulmonary hypertension in chronic obstructive pulmonary disease from routine chest radiographs. Am Rev Respir Dis 1982; 126(2): 338–41
Wiedemann HP, Matthay RA. Heart disease. A textbook of cardiovascular medicine. 5th ed. Philadelphia (PA): WB Saunders, 1997
Oswald-Mammosser M, Oswald T, Nyankiye E, et al. Noninvasive diagnosis of pulmonary hypertension in chronic obstructive pulmonary disease. Comparison of ECG, radiological measurements, echocardiography and myocardial scintigraphy. Eur J Respir Dis 1987; 71(5): 419–29
Torbicki A, Skwarski K, Hawrylkiewicz I, et al. Attempts at measuring pulmonary arterial pressure by means of Doppler echocardiography in patients with chronic lung disease. Eur Respir J 1989; 2(9): 856–60
Laaban JP, Diebold B, Zelinski R, et al. Noninvasive estimation of systolic pulmonary artery pressure using Doppler echocardiography in patients with chronic obstructive pulmonary disease. Chest 1989; 96(6): 1258–62
Naeije R, Torbicki A. More on the noninvasive diagnosis of pulmonary hypertension: Doppler echocardiography revisited. Eur Respir J 1995; 8(9): 1445–9
Arcasoy SM, Christie JD, Ferrari VA, et al. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. Am J Respir Crit Care Med 2003; 167(5): 735–40
Fisher MR, Criner GJ, Fishman AP, et al. Estimating pulmonary artery pressures by echocardiography in patients with emphysema. Eur Respir J 2007; 30(5): 914–21
Turhan S, Dincer I, Ozdol C, et al. Value of tissue Doppler myocardial velocities of tricuspid lateral annulus for the diagnosis of right heart failure in patients with COPD. Echocardiography 2007; 24(2): 126–33
Takakura M, Harada T, Fukuno H, et al. Echocardiographic detection of occult cor pulmonale during exercise in patients with chronic obstructive pulmonary disease. Echocardiography 1999; 16(2): 127–34
Leuchte HH, Baumgartner RA, Nounou ME, et al. Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med 2006; 173(7): 744–50
Yusen RD, Lefrak SS, Trulock EP. Evaluation and preoperative management of lung volume reduction surgery candidates. Clin Chest Med 1997; 18(2): 199–224
DeGaute JP, Domenighetti G, Naeije R, et al. Oxygen delivery in acute exacerbation of chronic obstructive pulmonary disease. Effects of controlled oxygen therapy. Am Rev Respir Dis 1981; 124(1): 26–30
Lejeune P, Mols P, Naeije R, et al. Acute hemodynamic effects of controlled oxygen therapy in decompensated chronic obstructive pulmonary disease. Crit Care Med 1984; 12(12): 1032–5
Olvey SK, Reduto LA, Stevens PM, et al. First pass radionuclide assessment of right and left ventricular ejection fraction in chronic pulmonary disease. Effect of oxygen upon exercise response. Chest 1980; 78(1): 4–9
Report of the Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981; I: 681-5
Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease. A clinical trial. Ann Intern Med 1980; 93: 391–8
Timms RM, Khaja FU, Williams GW. Hemodynamic response to oxygen therapy in chronic obstructive pulmonary disease. Ann Intern Med 1985; 102(1): 29–36
Ashutosh K, Mead G, Dunsky M. Early effects of oxygen administration and prognosis in chronic obstructive pulmonary disease and cor pulmonale. Am Rev Respir Dis 1983; 127(4): 399–404
Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med 1992; 327(2): 76–81
Simonneau G, Escourrou P, Duroux P, et al. Inhibition of hypoxic pulmonary vasoconstriction by nifedipine. N Engl J Med 1981; 304(26): 1582–5
Muramoto A, Caldwell J, Albert RK, et al. Nifedipine dilates the pulmonary vasculature without producing symptomatic systemic hypotension in upright resting and exercising patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease. Am Rev Respir Dis 1985; 132(5): 963–6
Mélot C, Hallemans R, Naeije R, et al. Deleterious effect of nifedipine on pulmonary gas exchange in chronic obstructive pulmonary disease. Am Rev Respir Dis 1984; 130: 612–6
Sturani C, Bassein L, Schiavina M, et al. Oral nifedipine in chronic cor pulmonale secondary to severe chronic obstructive pulmonary disease (COPD). Chest 1983; 84(2): 135–42
Agostoni P, Doria E, Galli C, et al. 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(1): 120–5
Saadjian AY, Philip-Joet FF, Vestri R, et al. Long-term treatment of chronic obstructive lung disease by nifedipine: an 18-month haemodynamic study. Eur Respir J 1988; 1(8): 716–20
Morrell NW, Higham MA, Phillips PG, et al. Pilot study of losartan for pulmonary hypertension in chronic obstructive pulmonary disease. Respir Res 2005; 6: 88
Katayama Y, Higenbottam TW, Cremona G, et al. Minimizing the inhaled dose of NO with breath-by-breath delivery of spikes of concentrated gas. Circulation 1998; 98(22): 2429–32
Yoshida M, Taguchi O, Gabazza EC, et al. Combined inhalation of nitric oxide and oxygen in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997; 155(2): 526–9
Germann P, Ziesche R, Leitner C, et al. Addition of nitric oxide to oxygen improves cardiopulmonary function in patients with severe COPD. Chest 1998; 114(1): 29–35
Vonbank K, Ziesche R, Higenbottam TW, et al. Controlled prospective randomised trial on the effects on pulmonary haemodynamics of the ambulatory long term use of nitric oxide and oxygen in patients with severe COPD. Thorax 2003; 58(4): 289–93
Brijker F, Heijdra YF, van den Elshout FJ, et al. Discontinuation of furosemide decreases PaCO2 in patients with COPD. Chest 2002; 121(2): 377–82
Matthay RA, Berger HJ, Loke J, et al. Effects of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: noninvasive assessment by radionuclide angiocardiography. Am J Med 1978; 65(6): 903–10
Mols P, Ham H, Naeije N, et al. How does salbutamol improve the ventricular performance in patients with chronic obstructive pulmonary disease? J Cardiovasc Pharmacol 1988; 12(2): 127–33
Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004; 351(14): 1425–36
Naeije R, Barberà JA. Pulmonary hypertension associated with COPD. Crit Care 2001; 5(6): 286–9
Higenbottam T. Pulmonary hypertension and chronic obstructive pulmonary disease: a case for treatment. Proc Am Thorac Soc 2005; 2(1): 12–9
Stevens D, Sharma K, Szidon P, et al. Severe pulmonary hypertension associated with COPD. Ann Transplant 2000; 5(3): 8–12
Dernaika TA, Beavin ML, Kinasewitz GT. Iloprost improves gas exchange in COPD patients with pulmonary arterial hypertension (PAH) [abstract]. Am J Respir Crit Care Med 2008; 177: A443
Stolz D, Rasch H, Linka A, et al. A randomised, controlled trial of bosentan in severe COPD. Eur Respir J 2008; 32(3): 619–28
Alp S, Skrygan M, Schmidt WE, et al. Sildenafil improves hemodynamic parameters in COPD: an investigation of six patients. Pulm Pharmacol Ther 2006; 19(6): 386–90
Madden BP, Allenby M, Loke TK, et al. A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease. Vascul Pharmacol 2006; 44(5): 372–6
Rietema H, Holverda S, Bogaard HJ, et al. Sildenafil treatment in COPD does not affect stroke volume or exercise capacity. Eur Respir J 2008; 31(4): 759–64
Blanco I, Gimeno E, Muñoz P, et al. Acute effects of sildenafil in chronic obstructive pulmonary disease (COPD). Eur Respir J 2008; 32: 167
Acknowledgements
This work has been funded by research grants from the EU (6th Framework Programme, LSHM-CT-2005-018725) and the Fondo de Investigación Sanitaria (07/90049) of the Spanish Ministry of Science and Innovation, and a research fellowship grant of the Spanish Society of Respiratory Medicine (SEPAR). Dr Barberà has received consultancy fees from Pfizer, Glaxo SmithKline, Actelion, Praxis and Encysive, and unrestricted research grant funding from Actelion, Schering and Praxis. Dr Blanco has no conflicts of interest to declare.
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Barberà, J.A., Blanco, I. Pulmonary Hypertension in Patients with Chronic Obstructive Pulmonary Disease. Drugs 69, 1153–1171 (2009). https://doi.org/10.2165/00003495-200969090-00002
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DOI: https://doi.org/10.2165/00003495-200969090-00002