Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease and Interstitial Lung Diseases

Emmanuel Weitzenblum; Ari Chaouat; Matthieu Canuet; Romain Kessler

doi:10.1055/s-0029-1233315

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2009; 30(4): 458-470
DOI: 10.1055/s-0029-1233315

Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease and Interstitial Lung Diseases

Emmanuel Weitzenblum¹ , Ari Chaouat² , Matthieu Canuet¹ , Romain Kessler¹

¹Department of Pulmonology, Nouvel Hôpital Civil, Strasbourg France
²Department of Respiratory Diseases and Respiratory Intensive Care, CHU de Nancy, Nancy, France

Abstract

ABSTRACT

Pulmonary hypertension (PH) is a common complication of chronic respiratory diseases and particularly of chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD). Owing to its frequency COPD is by far the most common cause of PH. It is generally a mild to moderate PH, pulmonary artery mean pressure (PAP) usually ranging between 20 and 25 mm Hg, but PH may worsen during exercise, sleep, and particularly during exacerbations of the disease. These acute increases in PAP may lead to the development of right heart failure. A small proportion of COPD patients may present “disproportionate” PH defined by a resting PAP >35 to 40 mm Hg. The prognosis is particularly poor in these patients. PH is relatively frequent in advanced ILD and particularly in idiopathic pulmonary fibrosis. As in COPD the diagnosis is suggested by Doppler echocardiography, but the confirmation still requires right heart catheterization. As in COPD, functional (alveolar hypoxia) and morphological factors (vascular remodeling, destruction of the pulmonary parenchyma) explain the elevation of pulmonary vascular resistance that leads to PH. Also as in COPD PH is most often mild to moderate. In ILD the presence of PH predicts a poor prognosis. The treatment of PH relies on long-term oxygen therapy. “New” vasodilator drugs have rarely been used in COPD and ILD patients exhibiting severe PH. In advanced ILD the presence of PH is a supplemental argument for considering lung transplantation.

KEYWORDS

Pulmonary hypertension - chronic obstructive pulmonary disease - idiopathic pulmonary fibrosis - interstitial lung diseases - pulmonary artery pressure

Full Text

References

REFERENCES

1 Simonneau G, Galiè N, Rubin L J et al.. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004; 43(12, Suppl S) 5S-12S
2 Bishop J M. Cardiovascular complications of chronic bronchitis and emphysema. Med Clin North Am. 1973; 57 771-780
3 Hatano S, Strasser T Primary Pulmonary Hypertension Report on a WHO Meeting. Geneva; World Health Organization 1975: 7-45
4 Thabut G, Dauriat G, Stern J B et al.. Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation. Chest. 2005; 127 1531-1536
5 Fisher M R, Criner G J, Fishman A P NETT Research Group et al. Estimating pulmonary artery pressures by echocardiography in patients with emphysema. Eur Respir J. 2007; 30 914-921
6 Fishman A P. Primary pulmonary arterial hypertension: a look back. J Am Coll Cardiol. 2004; 43(12, Suppl S) 2S-4S
7 Tartulier M, Bourret M, Deyrieux F. Pulmonary arterial pressures in normal subjects: effects of age and muscular exercise. Bull Physiopathol Respir (Nancy). 1972; 8 1295-1321
8 Naeije R. Pulmonary vascular function. In: Peacock AJ, Rubin LJ Pulmonary Circulation: Diseases and Their Treatment. London; Arnold 2004: 3-13
9 Chaouat A, Bugnet A S, Kadaoui N et al.. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005; 172 189-194
10 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; 164 219-224
11 Naeije R, Torbicki A. More on the noninvasive diagnosis of pulmonary hypertension: Doppler echocardiography revisited. Eur Respir J. 1995; 8 1445-1449
12 Arcasoy S M, Christie J D, Ferrari V A et al.. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. Am J Respir Crit Care Med. 2003; 167 735-740
13 Burrows B, Kettel L J, Niden A H, Rabinowitz M, Diener C F. Patterns of cardiovascular dysfunction in chronic obstructive lung disease. N Engl J Med. 1972; 286 912-918
14 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; 36 752-758
15 Scharf S M, Iqbal M, Keller C, Criner G, Lee S, Fessler H E. National Emphysema Treatment Trial (NETT) Group . Hemodynamic characterization of patients with severe emphysema. Am J Respir Crit Care Med. 2002; 166 314-322
16 Williams B T, Nicholl J P. Prevalence of hypoxaemic chronic obstructive lung disease with reference to long-term oxygen therapy. Lancet. 1985; 2 369-372
17 Boutin-Forzano S, Moreau D, Kalaboka S et al.. Reported prevalence and co-morbidity of asthma, chronic bronchitis and emphysema: a pan-European estimation. Int J Tuberc Lung Dis. 2007; 11 695-702
18 Wilkinson M, Langhorne C A, Heath D, Barer G R, Howard P. A pathophysiological study of 10 cases of hypoxic cor pulmonale. Q J Med. 1988; 66 65-85
19 Magee F, Wright J L, Wiggs B R, Paré P D, Hogg J C. Pulmonary vascular structure and function in chronic obstructive pulmonary disease. Thorax. 1988; 43 183-189
20 Hale K A, Niewoehner D E, Cosio M G. Morphologic changes in the muscular pulmonary arteries: relationship to cigarette smoking, airway disease, and emphysema. Am Rev Respir Dis. 1980; 122 273-278
21 Wright J L, Lawson L, Paré P D et al.. The structure and function of the pulmonary vasculature in mild chronic obstructive pulmonary disease: the effect of oxygen and exercise. Am Rev Respir Dis. 1983; 128 702-707
22 Santos S, Peinado V I, Ramírez J et al.. Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD. Eur Respir J. 2002; 19 632-638
23 Lockhart A, Tzareva M, Schrijen F et al.. Etudes hémodynamiques des décompensations respiratoires aiguës des bronchopneumopathies chroniques. Bull Physiopathol Respir. 1967; 3 645-667
24 Lockhart A, Tzareva M, Nader F, Leblanc P, Schrijen F, Sadoul P. Elevated pulmonary artery wedge pressure at rest and during exercise in chronic bronchitis: fact or fancy. Clin Sci. 1969; 37 503-517
25 Butler J, Schrijen F, Henriquez A, Polu J M, Albert R K. Cause of the raised wedge pressure on exercise in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1988; 138 350-354
26 Weitzenblum E. Chronic cor pulmonale. Heart. 2003; 89 225-230
27 Barberà J A, Peinado V I, Santos S. Pulmonary hypertension in chronic obstructive pulmonary disease. Eur Respir J. 2003; 21 892-905
28 Fishman A P. Hypoxia on the pulmonary circulation. How and where it acts. Circ Res. 1976; 38 221-231
29 Heath D. Remodeling of the pulmonary vasculature in hypoxic lung disease. In: Peacock AJ Pulmonary Circulation. London; Chapman & Hall 1996: 71-79
30 Von Euler U S, Liljestrand G. Observation of the pulmonary arterial blood pressure in the cat. Acta Physiol Scand. 1946; 12 301-320
31 Motley H L, Cournand A, Werko L et al.. The influence of short periods of induced acute hypoxia upon pulmonary artery pressure in man. Am J Physiol. 1947; 150 315-320
32 Fishman A P, 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; 31 770-781
33 Archer S, Michelakis E. The mechanism(s) of hypoxic pulmonary vasoconstriction: potassium channels, redox O(2) sensors, and controversies. News Physiol Sci. 2002; 17 131-137
34 Grover R F. Chronic hypoxic pulmonary hypertension. In: Fishman A The Pulmonary Circulation: Normal and Abnormal. Philadelphia; University of Pennsylvania Press 1990: 283-299
35 Weitzenblum E, Schrijen F, Mohan-Kumar T, Colas des Francs V, Lockhart A. Variability of the pulmonary vascular response to acute hypoxia in chronic bronchitis. Chest. 1988; 94 772-778
36 Penaloza D, Sime F, Banchero N et al.. Pulmonary hypertension in healthy men born and living at high altitude. Med Thorac. 1962; 19 449-460
37 Harris P, Heath D. The pulmonary circulation at high altitude. In: Harris P, Heath D The Human Pulmonary Circulation. Edinburgh; Churchill Livingstone 1986: 493-506
38 Wright J L, Petty T, Thurlbeck W M. 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; 170 109-124
39 Wright J L, Levy R D, Churg A. Pulmonary hypertension in chronic obstructive pulmonary disease: current theories of pathogenesis and their implications for treatment. Thorax. 2005; 60 605-609
40 Weitzenblum E, Ehrhart M, Rasaholinjanahary J, Hirth C. Pulmonary hemodynamics in idiopathic pulmonary fibrosis and other interstitial pulmonary diseases. Respiration. 1983; 44 118-127
41 Kessler R, Chaouat A, Schinkewitch P et al.. The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases. Chest. 2001; 120 369-376
42 Humbert M, Sitbon O, Chaouat A et al.. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006; 173 1023-1030
43 Jamieson S W, Kapelanski D P, Sakakibara N et al.. Pulmonary endarterectomy: experience and lessons learned in 1,500 cases. Ann Thorac Surg. 2003; 76(5) 1457-1462 discussion 1462-1464
44 Abraham A S, Cole R B, Green I D, Hedworth-Whitty R B, Clarke S W, Bishop J M. Factors contributing to the reversible pulmonary hypertension of patients with acute respiratory failure studies by serial observations during recovery. Circ Res. 1969; 24 51-60
45 Weitzenblum E, Hirth C, Roeslin N, Vandevenne A, Oudet P. Pulmonary hemodynamic changes during the acute respiratory insufficiency of chronic bronchopneumopathies. Respiration. 1971; 28 539-554
46 Horsfield K, Segel N, Bishop J M. The pulmonary circulation in chronic bronchitis at rest and during exercise breathing air and 80% oxygen. Clin Sci. 1968; 34 473-483
47 Weitzenblum E, el-Gharbi T, Vandevenne A et al.. Pulmonary hemodynamic changes during muscular exercise in non-decompensated chronic bronchitis. Bull Physiopathol Respir (Nancy). 1972; 8 49-71
48 Jezek V, Schrijen F, Sadoul P. Right ventricular function and pulmonary hemodynamics during exercise in patients with chronic obstructive bronchopulmonary disease. Cardiology. 1973; 58 20-31
49 Raeside D A, Brown A, Patel K R, Welsh D, Peacock A J. Ambulatory pulmonary artery pressure monitoring during sleep and exercise in normal individuals and patients with COPD. Thorax. 2002; 57 1050-1053
50 Catterall J R, Douglas N J, Calverley P MA et al.. Transient hypoxemia during sleep in chronic obstructive pulmonary disease is not a sleep apnea syndrome. Am Rev Respir Dis. 1983; 128 24-29
51 Hudgel D W, Martin R J, Capehart M, Johnson B, Hill P. Contribution of hypoventilation to sleep oxygen desaturation in chronic obstructive pulmonary disease. J Appl Physiol. 1983; 55 669-677
52 Fletcher E C, Gray B A, Levin D C. Nonapneic mechanisms of arterial oxygen desaturation during rapid-eye-movement sleep. J Appl Physiol. 1983; 54 632-639
53 Coccagna G, Lugaresi E. Arterial blood gases and pulmonary and systemic arterial pressure during sleep in chronic obstructive pulmonary disease. Sleep. 1978; 1 117-124
54 Boysen P G, Block A J, Wynne J W, Hunt L A, Flick M R. Nocturnal pulmonary hypertension in patients with chronic obstructive pulmonary disease. Chest. 1979; 76 536-542
55 Weitzenblum E, Muzet A, Ehrhart M et al.. Nocturnal changes in blood gases and pulmonary arterial pressure in chronic bronchitis patients with respiratory insufficiency. Nouv Presse Med. 1982; 11 1119-1122
56 Fletcher E C, Levin D C. Cardiopulmonary hemodynamics during sleep in subjects with chronic obstructive pulmonary disease. The effect of short- and long-term oxygen. Chest. 1984; 85 6-14
57 Weitzenblum E, Apprill M, Oswald M, Chaouat A, Imbs J L. Pulmonary hemodynamics in patients with chronic obstructive pulmonary disease before and during an episode of peripheral edema. Chest. 1994; 105 1377-1382
58 MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease, I. Am J Respir Crit Care Med. 1994; 150 833-852 1158-1168
59 Edema in cor pulmonale. Lancet. 1975; ii 1289-1290
60 Richens J M, Howard P. Oedema in cor pulmonale. Clin Sci (Lond). 1982; 62 255-259
61 Vizza C D, Lynch J P, Ochoa L L, Richardson G, Trulock E P. Right and left ventricular dysfunction in patients with severe pulmonary disease. Chest. 1998; 113 576-583
62 Brent B N, Berger H J, Matthay R A, Mahler D, Pytlik L, Zaret B L. Physiologic correlates of right ventricular ejection fraction in chronic obstructive pulmonary disease: a combined radionuclide and hemodynamic study. Am J Cardiol. 1982; 50 255-262
63 Biernacki W, Flenley D C, Muir A L, MacNee W. Pulmonary hypertension and right ventricular function in patients with COPD. Chest. 1988; 94 1169-1175
64 Weitzenblum E, Chaouat A. Right ventricular function in COPD: can it be assessed reliably by the measurement of right ventricular ejection fraction?. Chest. 1998; 113 567-569
65 Burghuber O C, Bergmann H. Right-ventricular contractility in chronic obstructive pulmonary disease: a combined radionuclide and hemodynamic study. Respiration. 1988; 53 1-12
66 MacNee W, Wathen C G, Flenley D C, Muir A D. The effects of controlled oxygen therapy on ventricular function in patients with stable and decompensated cor pulmonale. Am Rev Respir Dis. 1988; 137 1289-1295
67 Aber G M, Bishop J M. Serial changes in renal function, arterial gas tensions and the acid-base state in patients with chronic bronchitis and oedema. Clin Sci. 1965; 28 511-525
68 Oswald-Mammosser M, Oswald T, Nyankiye E, Dickele M C, Grange D, Weitzenblum E. Non-invasive diagnosis of pulmonary hypertension in chronic obstructive pulmonary disease: comparison of ECG, radiological measurements, echocardiography and myocardial scintigraphy. Eur J Respir Dis. 1987; 71 419-429
69 Tramarin R, Torbicki A, Marchandise B, Laaban J P, Morpurgo M. Doppler echocardiographic evaluation of pulmonary artery pressure in chronic obstructive pulmonary disease. A European multicentre study. Working Group on Noninvasive Evaluation of Pulmonary Artery Pressure. European Office of the World Health Organization, Copenhagen. Eur Heart J. 1991; 12 103-111
70 Torbicki A, Skwarski K, Hawrylkiewicz I, Pasierski T, Miskiewicz Z, Zielinski J. Attempts at measuring pulmonary arterial pressure by means of Doppler echocardiography in patients with chronic lung disease. Eur Respir J. 1989; 2 856-860
71 Leuchte H H, Baumgartner R A, Nounou M E et al.. Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med. 2006; 173 744-750
72 Schrijen F, Uffholtz H, Polu J M, Poincelot F. Pulmonary and systemic hemodynamic evolution in chronic bronchitis. Am Rev Respir Dis. 1978; 117 25-31
73 Weitzenblum E, Loiseau A, Hirth C, Mirhom R, Rasaholinjanahary J. Course of pulmonary hemodynamics in patients with chronic obstructive pulmonary disease. Chest. 1979; 75 656-662
74 Weitzenblum E, Sautegeau A, Ehrhart M, Mammosser M, Hirth C, Roegel E. Long-term course of pulmonary arterial pressure in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1984; 130 993-998
75 Bishop J M, Cross K W. Physiological variables and mortality in patients with various categories of chronic respiratory disease. Bull Eur Physiopathol Respir. 1984; 20 495-500
76 Cooper C B, Waterhouse J, Howard P. Twelve year clinical study of patients with hypoxic cor pulmonale given long term domiciliary oxygen therapy. Thorax. 1987; 42 105-110
77 Skwarski K, MacNee W, Wraith P K, Sliwinski P, Zielinski J. Predictors of survival in patients with chronic obstructive pulmonary disease treated with long-term oxygen therapy. Chest. 1991; 100 1522-1527
78 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 1193-1198
79 Nocturnal Oxygen Therapy Trial Group . Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med. 1980; 93 391-398
80 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; 1 681-686
81 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; 131 493-498
82 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 65-70
83 Vonbank K, Ziesche R, Higenbottam T W 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; 58 289-293
84 Stolz D, Rasch H, Linka A et al.. A randomised, controlled trial of bosentan in severe COPD. Eur Respir J. 2008; 32 619-628
85 Baldwin Ede F, Cournand A, Richards D W. Pulmonary insufficiency; a study of 39 cases of pulmonary fibrosis. Medicine (Baltimore). 1949; 28 1-25
86 Bradley B, Branley H M, Egan J J et al.. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax. 2008; 63(Suppl 5) v1-v58
87 Nadrous H F, Pellikka P A, Krowka M J et al.. Pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Chest. 2005; 128 2393-2399
88 Lettieri C J, Nathan S D, Barnett S D, Ahmad S, Shorr A F. Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest. 2006; 129 746-752
89 Hamada K, Nagai S, Tanaka S et al.. Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis. Chest. 2007; 131 650-656
90 Han M K, McLaughlin V V, Criner G J, Martinez F J. Pulmonary diseases and the heart. Circulation. 2007; 116 2992-3005
91 Nathan S D, Shlobin O A, Ahmad S, Urbanek S, Barnett S D. Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis. Chest. 2007; 131 657-663
92 Handa T, Nagai S, Miki S et al.. Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis. Chest. 2006; 129 1246-1252
93 Shorr A F, Helman D L, Davies D B, Nathan S D. Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics. Eur Respir J. 2005; 25 783-788
94 Hachulla E, Gressin V, Guillevin L et al.. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum. 2005; 52 3792-3800
95 Luchsinger P C, Moser K M, Buhlmann A, Rossier P H. The interrelationship between cor pulmonale, capillary bed restriction and diffusion insufficiency for oxygen in the lung. Am Heart J. 1957; 54 106-117
96 Enson Y, Thomas H M, Bosken C H et al.. Pulmonary hypertension in interstitial lung disease: relation of vascular resistance to abnormal lung structure. Trans Assoc Am Physicians. 1975; 88 248-255
97 Nathan S D, Noble P W, Tuder R M. Idiopathic pulmonary fibrosis and pulmonary hypertension: connecting the dots. Am J Respir Crit Care Med. 2007; 175 875-880
98 Lupi-Herrera E, Sandoval J, Bialostozky D et al.. Extrinsic allergic alveolitis caused by pigeon breeding at a high altitude (2,240 meters): hemodynamic behavior of pulmonary circulation. Am Rev Respir Dis. 1981; 124 602-607
99 Nunes H, Humbert M, Capron F et al.. Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax. 2006; 61 68-74
100 Leuchte H H, Neurohr C, Baumgartner R et al.. Brain natriuretic peptide and exercise capacity in lung fibrosis and pulmonary hypertension. Am J Respir Crit Care Med. 2004; 170 360-365
101 Nadrous H F, Pellikka P A, Krowka M J et al.. The impact of pulmonary hypertension on survival in patients with idiopathic pulmonary fibrosis. Chest. 2005; 128(6, Suppl) 616S-617S
102 Demedts M, Behr J, Buhl R IFIGENIA Study Group et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005; 353 2229-2242
103 Gluskowski J, Hawrylkiewicz I, Zych D, Zieliński J. Effects of corticosteroid treatment on pulmonary haemodynamics in patients with sarcoidosis. Eur Respir J. 1990; 3 403-407
104 Rodman D M, Lindenfeld J. Successful treatment of sarcoidosis-associated pulmonary hypertension with corticosteroids. Chest. 1990; 97 500-502
105 Olschewski H, Ghofrani H A, Walmrath D et al.. Inhaled prostacyclin and iloprost in severe pulmonary hypertension secondary to lung fibrosis. Am J Respir Crit Care Med. 1999; 160 600-607
106 Ghofrani H A, Wiedemann R, Rose F et al.. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet. 2002; 360 895-900
107 Behr J, Ryu J H. Pulmonary hypertension in interstitial lung disease. Eur Respir J. 2008; 31 1357-1367

Emmanuel WeitzenblumM.D.

Department of Pulmonology, Nouvel Hôpital Civil

67091 Strasbourg, France

Email: Emmanuel.weitzenblum@chru-strasbourg.fr