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Diagnosis and Management of Pulmonary Hypertension pp 67–92Cite as

Hypoxic Pulmonary Hypertension

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  • 2016 Accesses

Part of the book series: Respiratory Medicine ((RM,volume 12))

Abstract

Elevation in pulmonary arterial pressure is a common occurrence in patients with chronic lung disease. Hypoxic pulmonary vasoconstriction, parenchymal lung disease, and inflammation contribute to increased pulmonary vascular tone and remodeling. Diagnosis of pulmonary vascular disease in patients with lung disease may be especially challenging due to the lack of specificity of common complaints of dyspnea and inaccuracy of echocardiographic estimates such as pulmonary arterial pressure in this group of patients. The presence of pulmonary hypertension (PH) in chronic lung disease is associated with increased morbidity and mortality, but the efficacy of pharmacologic treatment of PH in this population has not been established. This chapter will review the epidemiology and pathogenesis of PH associated with chronic lung disease and provide an approach to evaluation and management including the identification and selection of some patients who may benefit from currently available pulmonary vasodilator therapies.

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References

  1. Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S43–54.

    PubMed  Google Scholar 

  2. Hoeper MM, Barbera JA, Channick RN, et al. Diagnosis, assessment, and treatment of non-pulmonary arterial hypertension pulmonary hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S85–96.

    PubMed  Google Scholar 

  3. Stenmark KR, Fagan KA, Frid MG. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res. 2006;99(7):675–91.

    CAS  PubMed  Google Scholar 

  4. Stenmark KR, Meyrick B, Galie N, Mooi WJ, McMurtry IF. Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure. Am J Physiol. 2009;297(6):L1013–32.

    CAS  Google Scholar 

  5. Strange G, Playford D, Stewart S, et al. Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort. Heart. 2012;98(24):1805–11.

    PubMed Central  PubMed  Google Scholar 

  6. Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in COPD. Eur Respir J. 2008;32(5):1371–85.

    CAS  PubMed  Google Scholar 

  7. Andersen KH, Iversen M, Kjaergaard J, et al. Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease. J Heart Lung Transplant. 2012;31(4):373–80.

    PubMed  Google Scholar 

  8. 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.

    PubMed  Google Scholar 

  9. Shorr AF, Wainright JL, Cors CS, Lettieri CJ, Nathan SD. Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant. Eur Respir J. 2007;30(4):715–21.

    CAS  PubMed  Google Scholar 

  10. Lettieri CJ, Nathan SD, Barnett SD, Ahmad S, Shorr AF. Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest. 2006;129(3):746–52.

    PubMed  Google Scholar 

  11. Nathan SD, Shlobin OA, Ahmad S, et al. Serial development of pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Respiration. 2008;76(3):288–94.

    CAS  PubMed  Google Scholar 

  12. Cottin V, Nunes H, Brillet PY, et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J. 2005;26(4):586–93.

    CAS  PubMed  Google Scholar 

  13. Bady E, Achkar A, Pascal S, Orvoen-Frija E, Laaban JP. Pulmonary arterial hypertension in patients with sleep apnoea syndrome. Thorax. 2000;55(11):934–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Laks L, Lehrhaft B, Grunstein RR, Sullivan CE. Pulmonary hypertension in obstructive sleep apnoea. Eur Respir J. 1995;8(4):537–41.

    CAS  PubMed  Google Scholar 

  15. Sophocles Jr AM. High-altitude pulmonary edema in Vail, Colorado, 1975-1982. West J Med. 1986;144(5):569–73.

    PubMed Central  PubMed  Google Scholar 

  16. Hochstrasser J, Nanzer A, Oelz O. [Altitude edema in the Swiss Alps. Observations on the incidence and clinical course in 50 patients 1980–1984]. Schweiz Med Wochenschr. 1986;116(26):866–73.

    CAS  PubMed  Google Scholar 

  17. Maggiorini M. High altitude-induced pulmonary oedema. Cardiovasc Res. 2006;72(1):41–50.

    CAS  PubMed  Google Scholar 

  18. Aldashev AA, Sarybaev AS, Sydykov AS, et al. Characterization of high-altitude pulmonary hypertension in the Kyrgyz: association with angiotensin-converting enzyme genotype. Am J Respir Crit Care Med. 2002;166(10):1396–402.

    PubMed  Google Scholar 

  19. Xu XQ, Jing ZC. High-altitude pulmonary hypertension. Eur Respir Rev. 2009;18(111):13–7.

    PubMed  Google Scholar 

  20. 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.

    PubMed  Google Scholar 

  21. Eddahibi S, Chaouat A, Morrell N, et al. Polymorphism of the serotonin transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease. Circulation. 2003;108(15):1839–44.

    CAS  PubMed  Google Scholar 

  22. Chaouat A, Savale L, Chouaid C, et al. Role for interleukin-6 in COPD-related pulmonary hypertension. Chest. 2009;136(3):678–87.

    CAS  PubMed  Google Scholar 

  23. Tuder RM, Abman SH, Braun T, et al. Development and pathology of pulmonary hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S3–9.

    CAS  PubMed  Google Scholar 

  24. Li M, Riddle SR, Frid MG, et al. Emergence of fibroblasts with a proinflammatory epigenetically altered phenotype in severe hypoxic pulmonary hypertension. J Immunol. 2011;187(5):2711–22.

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Sylvester JT, Shimoda LA, Aaronson PI, Ward JP. Hypoxic pulmonary vasoconstriction. Physiol Rev. 2012;92(1):367–520.

    CAS  PubMed  Google Scholar 

  26. Sommer N, Dietrich A, Schermuly RT, et al. Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms. Eur Respir J. 2008;32(6):1639–51.

    CAS  PubMed  Google Scholar 

  27. Hultgren HN, Lopez CE, Lundberg E, Miller H. Physiologic studies of pulmonary edema at high altitude. Circulation. 1964;29:393–408.

    CAS  PubMed  Google Scholar 

  28. Hultgren HN, Grover RF, Hartley LH. Abnormal circulatory responses to high altitude in subjects with a previous history of high-altitude pulmonary edema. Circulation. 1971;44(5):759–70.

    CAS  PubMed  Google Scholar 

  29. Tsukimoto K, Mathieu-Costello O, Prediletto R, Elliott AR, West JB. Ultrastructural appearances of pulmonary capillaries at high transmural pressures. J Appl Physiol. 1991;71(2):573–82.

    CAS  PubMed  Google Scholar 

  30. West JB, Tsukimoto K, Mathieu-Costello O, Prediletto R. Stress failure in pulmonary capillaries. J Appl Physiol. 1991;70(4):1731–42.

    CAS  PubMed  Google Scholar 

  31. Hultgren HN. High-altitude pulmonary edema: current concepts. Annu Rev Med. 1996;47:267–84.

    CAS  PubMed  Google Scholar 

  32. Bärtsch P, Mairbäurl H, Maggiorini M, Swenson ER. Physiological aspects of high-altitude pulmonary edema. J Appl Physiol. 2005;98:1101–10.

    PubMed  Google Scholar 

  33. Houston CS. Acute pulmonary edema of high altitude. N Engl J Med. 1960;263:478–80.

    CAS  PubMed  Google Scholar 

  34. Hackett PH, Creagh CE, Grover RF, et al. High-altitude pulmonary edema in persons without the right pulmonary artery. N Engl J Med. 1980;302(19):1070–3.

    CAS  PubMed  Google Scholar 

  35. Schumacker PT. Lung cell hypoxia: role of mitochondrial reactive oxygen species signaling in triggering responses. Proc Am Thorac Soc. 2011;8(6):477–84.

    PubMed Central  CAS  PubMed  Google Scholar 

  36. Archer SL, Huang J, Henry T, Peterson D, Weir EK. A redox-based O2 sensor in rat pulmonary vasculature. Circ Res. 1993;73(6):1100–12.

    CAS  PubMed  Google Scholar 

  37. Waypa GB, Chandel NS, Schumacker PT. Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing. Circ Res. 2001;88(12):1259–66.

    CAS  PubMed  Google Scholar 

  38. Moudgil R, Michelakis ED, Archer SL. Hypoxic pulmonary vasoconstriction. J Appl Physiol. 2005;98(1):390–403.

    CAS  PubMed  Google Scholar 

  39. Pozeg ZI, Michelakis ED, McMurtry MS, et al. In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation. 2003;107(15):2037–44.

    CAS  PubMed  Google Scholar 

  40. Arias-Stella J, Saldana M. The terminal portion of the pulmonary arterial tree in people native to high altitudes. Circulation. 1963;28:915–25.

    CAS  PubMed  Google Scholar 

  41. West JB. High-altitude medicine. Am J Respir Crit Care Med. 2012;186(12):1229–37.

    PubMed  Google Scholar 

  42. Groves BM, Reeves JT, Sutton JR, et al. Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen. J Appl Physiol. 1987;63(2):521–30.

    CAS  PubMed  Google Scholar 

  43. Maggiorini M, Leon-Velarde F. High-altitude pulmonary hypertension: a pathophysiological entity to different diseases. Eur Respir J. 2003;22(6):1019–25.

    CAS  PubMed  Google Scholar 

  44. Shimoda LA, Semenza GL. HIF and the lung: role of hypoxia-inducible factors in pulmonary development and disease. Am J Respir Crit Care Med. 2011;183(2):152–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  45. Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148(3):399–408.

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Yu AY, Shimoda LA, Iyer NV, et al. Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alpha. J Clin Invest. 1999;103(5):691–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Beall CM, Cavalleri GL, Deng L, et al. Natural selection on EPAS1 (HIF2alpha) associated with low hemoglobin concentration in Tibetan highlanders. Proc Natl Acad Sci U S A. 2010;107(25):11459–64.

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Bigham A, Bauchet M, Pinto D, et al. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data. PLoS Genet. 2010;6(9):e1001116.

    PubMed Central  PubMed  Google Scholar 

  49. Peng Y, Yang Z, Zhang H, et al. Genetic variations in Tibetan populations and high-altitude adaptation at the Himalayas. Mol Biol Evol. 2011;28(2):1075–81.

    CAS  PubMed  Google Scholar 

  50. Pak O, Aldashev A, Welsh D, Peacock A. The effects of hypoxia on the cells of the pulmonary vasculature. Eur Respir J. 2007;30(2):364–72.

    CAS  PubMed  Google Scholar 

  51. Platoshyn O, Golovina VA, Bailey CL, et al. Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation. Am J Physiol. 2000;279(5):C1540–9.

    CAS  Google Scholar 

  52. Frid MG, Brunetti JA, Burke DL, et al. Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage. Am J Pathol. 2006;168(2):659–69.

    PubMed Central  CAS  PubMed  Google Scholar 

  53. Lee C, Mitsialis SA, Aslam M, et al. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation. 2012;126(22):2601–11.

    PubMed Central  CAS  PubMed  Google Scholar 

  54. Vergadi E, Chang MS, Lee C, et al. Early macrophage recruitment and alternative activation are critical for the later development of hypoxia-induced pulmonary hypertension. Circulation. 2011;123(18):1986–95.

    PubMed Central  CAS  PubMed  Google Scholar 

  55. Balanos GM, Talbot NP, Dorrington KL, Robbins PA. Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography. J Appl Physiol. 2003;94(4):1543–51.

    PubMed  Google Scholar 

  56. Thannickal VJ, Toews GB, White ES, Lynch 3rd JP, Martinez FJ. Mechanisms of pulmonary fibrosis. Annu Rev Med. 2004;55:395–417.

    CAS  PubMed  Google Scholar 

  57. Corte TJ, Wort SJ, Wells AU. Pulmonary hypertension in idiopathic pulmonary fibrosis: a review. Sarcoidosis Vasc Diffuse Lung Dis. 2009;26(1):7–19.

    CAS  PubMed  Google Scholar 

  58. Patel NM, Lederer DJ, Borczuk AC, Kawut SM. Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest. 2007;132(3):998–1006.

    PubMed  Google Scholar 

  59. Guazzi M, Galie N. Pulmonary hypertension in left heart disease. Eur Respir Rev. 2012;21(126):338–46.

    PubMed  Google Scholar 

  60. Segers VF, Brutsaert DL, De Keulenaer GW. Pulmonary hypertension and right heart failure in heart failure with preserved left ventricular ejection fraction: pathophysiology and natural history. Curr Opin Cardiol. 2012;27(3):273–80.

    PubMed  Google Scholar 

  61. Grau M, Barr RG, Lima JA, et al. Percent emphysema and right ventricular structure and function: the MESA lung and MESA-RV studies. Chest. 2013;144(1):136–44.

    Google Scholar 

  62. Barr RG, Bluemke DA, Ahmed FS, et al. Percent emphysema, airflow obstruction, and impaired left ventricular filling. N Engl J Med. 2010;362(3):217–27.

    PubMed Central  PubMed  Google Scholar 

  63. Noureddine H, Gary-Bobo G, Alifano M, et al. Pulmonary artery smooth muscle cell senescence is a pathogenic mechanism for pulmonary hypertension in chronic lung disease. Circ Res. 2011;109(5):543–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  64. Amsellem V, Gary-Bobo G, Marcos E, et al. Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;184(12):1358–66.

    CAS  PubMed  Google Scholar 

  65. Wright JL, Churg A. Animal models of cigarette smoke-induced chronic obstructive pulmonary disease. Exp Rev Respir Med. 2010;4(6):723–34.

    CAS  Google Scholar 

  66. Voelkel NF, Gomez-Arroyo J, Mizuno S. COPD/emphysema: the vascular story. Pulm Circ. 2011;1(3):320–6.

    PubMed Central  PubMed  Google Scholar 

  67. Peinado VI, Pizarro S, Barbera JA. Pulmonary vascular involvement in COPD. Chest. 2008;134(4):808–14.

    CAS  PubMed  Google Scholar 

  68. Barbera J. Mechanisms of development of chronic obstructive pulmonary disease-associated pulmonary hypertension. Pulm Circ. 2013;3(1):160–4.

    PubMed Central  PubMed  Google Scholar 

  69. Ryan JJ, Rehman J, Archer SL. Paracrine proliferative signaling by senescent cells in world health organization group 3 pulmonary hypertension: age corrupting youth? Circ Res. 2011;109(5):476–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  70. Seimetz M, Parajuli N, Pichl A, et al. Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice. Cell. 2011;147(2):293–305.

    CAS  PubMed  Google Scholar 

  71. Churg A, Zhou S, Wright JL. Series “matrix metalloproteinases in lung health and disease”: matrix metalloproteinases in COPD. Eur Respir J. 2012;39(1):197–209.

    CAS  PubMed  Google Scholar 

  72. Wright JL, Zhou S, Churg A. Pulmonary hypertension and vascular oxidative damage in cigarette smoke exposed eNOS(−/−) mice and human smokers. Inhal Toxicol. 2012;24(11):732–40.

    CAS  PubMed  Google Scholar 

  73. Mahapatra S, Nishimura RA, Sorajja P, Cha S, McGoon MD. Relationship of pulmonary arterial capacitance and mortality in idiopathic pulmonary arterial hypertension. J Am Coll Cardiol. 2006;47(4):799–803.

    PubMed  Google Scholar 

  74. Lahm T, Albrecht M, Fisher AJ, et al. 17beta-Estradiol attenuates hypoxic pulmonary hypertension via estrogen receptor-mediated effects. Am J Respir Crit Care Med. 2012;185(9):965–80.

    PubMed Central  CAS  PubMed  Google Scholar 

  75. Macnee W. Right heart function in COPD. Semin Respir Crit Care Med. 2010;31(3):295–312.

    PubMed  Google Scholar 

  76. Brown RD, Ambler SK, Li M, et al. MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2013;304(2):H269–81.

    PubMed Central  CAS  PubMed  Google Scholar 

  77. MacNee W, Skwarski K. The pathogenesis of peripheral edema in chronic obstructive pulmonary disease. Clin Pulm Med. 1997;4(6):309–15.

    Google Scholar 

  78. Skwarski KM, Morrison D, Barratt A, Lee M, MacNee W. Effects of hypoxia on renal hormonal balance in normal subjects and in patients with COPD. Respir Med. 1998;92:1331–6.

    CAS  PubMed  Google Scholar 

  79. 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(2):219–24.

    CAS  PubMed  Google Scholar 

  80. Carlsen J, Andersen HK, Boesgaard S, et al. Pulmonary arterial lesions in explanted lungs after transplantation correlate with severity of pulmonary hypertension in chronic obstructive pulmonary disease. J Heart Lung Transplant. 2013;32:347–54.

    PubMed  Google Scholar 

  81. Lederer DJ, Arcasoy SM, Wilt JS, D’Ovidio F, Sonett JR, Kawut SM. Six-minute-walk distance predicts waiting list survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006;174(6):659–64.

    PubMed Central  PubMed  Google Scholar 

  82. Cottin V, Le Pavec J, Prevot G, et al. Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome. Eur Respir J. 2010;35(1):105–11.

    CAS  PubMed  Google Scholar 

  83. Sugerman HJ, Baron PL, Fairman RP, Evans CR, Vetrovec GW. Hemodynamic dysfunction in obesity hypoventilation syndrome and the effects of treatment with surgically induced weight loss. Ann Surg. 1988;207(5):604–13.

    PubMed Central  CAS  PubMed  Google Scholar 

  84. Kessler R, Faller M, Fourgaut G, Mennecier B, Weitzenblum E. 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(1):158–64.

    CAS  PubMed  Google Scholar 

  85. Boerrigter BG, Bogaard HJ, Trip P, et al. Ventilatory and cardiocirculatory exercise profiles in COPD: the role of pulmonary hypertension. Chest. 2012;142(5):1166–74.

    PubMed  Google Scholar 

  86. Fang A, Studer S, Kawut SM, et al. Elevated pulmonary artery pressure is a risk factor for primary graft dysfunction following lung transplantation for idiopathic pulmonary fibrosis. Chest. 2011;139(4):782–7.

    PubMed Central  PubMed  Google Scholar 

  87. Diamond JM, Lee JC, Kawut SM, et al. Clinical risk factors for primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2013;187(5):527–34.

    PubMed Central  PubMed  Google Scholar 

  88. Rivera-Lebron BN, Forfia PR, Kreider M, Lee J, Holmes JH, Kawut SM. Echocardiographic and hemodynamic predictors of mortality in idiopathic pulmonary fibrosis. Chest. 2013;144(2):564–70.

    PubMed Central  PubMed  Google Scholar 

  89. 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):1193–8.

    CAS  PubMed  Google Scholar 

  90. 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.

    CAS  PubMed  Google Scholar 

  91. Wells JM, Washko GR, Han MK, et al. Pulmonary arterial enlargement and acute exacerbations of COPD. N Engl J Med. 2012;367(10):913–21.

    PubMed Central  CAS  PubMed  Google Scholar 

  92. Stanbrook MB. The pulmonary artery in COPD—does size matter? N Engl J Med. 2012;367(10):946–8.

    CAS  PubMed  Google Scholar 

  93. 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.

    PubMed  Google Scholar 

  94. Forfia PR, Vachiery JL. Echocardiography in pulmonary arterial hypertension. Am J Cardiol. 2012;110(6 Suppl):16S–24.

    PubMed  Google Scholar 

  95. Pirat B, McCulloch ML, Zoghbi WA. Evaluation of global and regional right ventricular systolic function in patients with pulmonary hypertension using a novel speckle tracking method. Am J Cardiol. 2006;98(5):699–704.

    PubMed  Google Scholar 

  96. Matias C, Isla LP, Vasconcelos M, et al. Speckle-tracking-derived strain and strain-rate analysis: a technique for the evaluation of early alterations in right ventricle systolic function in patients with systemic sclerosis and normal pulmonary artery pressure. J Cardiovasc Med (Hagerstown). 2009;10(2):129–34.

    Google Scholar 

  97. Hardegree EL, Sachdev A, Villarraga HR, et al. Role of serial quantitative assessment of right ventricular function by strain in pulmonary arterial hypertension. Am J Cardiol. 2013;111(1):143–8.

    PubMed  Google Scholar 

  98. Vonk-Noordegraaf A, Souza R. Cardiac magnetic resonance imaging: what can it add to our knowledge of the right ventricle in pulmonary arterial hypertension? Am J Cardiol. 2012;110(6 Suppl):25S–31.

    PubMed  Google Scholar 

  99. Sanz J, Conroy J, Narula J. Imaging of the right ventricle. Cardiol Clin. 2012;30(2):189–203.

    PubMed  Google Scholar 

  100. Halpern SD, Taichman DB. Misclassification of pulmonary hypertension due to reliance on pulmonary capillary wedge pressure rather than left ventricular end-diastolic pressure. Chest. 2009;136(1):37–43.

    PubMed  Google Scholar 

  101. Champion HC, Michelakis ED, Hassoun PM. Comprehensive invasive and noninvasive approach to the right ventricle-pulmonary circulation unit: state of the art and clinical and research implications. Circulation. 2009;120(11):992–1007.

    PubMed  Google Scholar 

  102. Ryan JJ, Rich JD, Thiruvoipati T, Swamy R, Kim GH, Rich S. Current practice for determining pulmonary capillary wedge pressure predisposes to serious errors in the classification of patients with pulmonary hypertension. Am Heart J. 2012;163(4):589–94.

    PubMed  Google Scholar 

  103. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med. 1980;93(3):391–8.

    Google Scholar 

  104. Garvey C. Interstitial lung disease and pulmonary rehabilitation. J Cardiopulm Rehabil Prev. 2010;30(3):141–6.

    PubMed  Google Scholar 

  105. Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med. 2010;182(3):325–31.

    PubMed  Google Scholar 

  106. Colish J, Walker JR, Elmayergi N, et al. Obstructive sleep apnea: effects of continuous positive airway pressure on cardiac remodeling as assessed by cardiac biomarkers, echocardiography, and cardiac MRI. Chest. 2012;141(3):674–81.

    PubMed  Google Scholar 

  107. 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):270–8.

    CAS  PubMed  Google Scholar 

  108. Ghofrani HA, Reichenberger F, Kohstall MG, et al. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. Ann Intern Med. 2004;141(3):169–77.

    CAS  PubMed  Google Scholar 

  109. 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):982–92.

    CAS  PubMed  Google Scholar 

  110. Lederer DJ, Bartels MN, Schluger NW, et al. Sildenafil for chronic obstructive pulmonary disease: a randomized crossover trial. COPD. 2012;9(3):268–75.

    PubMed  Google Scholar 

  111. 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.

    CAS  PubMed  Google Scholar 

  112. Dernaika TA, Beavin M, Kinasewitz GT. Iloprost improves gas exchange and exercise tolerance in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Respiration. 2010;79(5):377–82.

    CAS  PubMed  Google Scholar 

  113. Boeck L, Tamm M, Grendelmeier P, Stolz D. Acute effects of aerosolized iloprost in COPD related pulmonary hypertension—a randomized controlled crossover trial. PLoS One. 2012;7(12):e52248.

    PubMed Central  CAS  PubMed  Google Scholar 

  114. 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):600–7.

    CAS  PubMed  Google Scholar 

  115. 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. 2011;110(3):638–45.

    CAS  PubMed  Google Scholar 

  116. Ghofrani HA, Wiedemann R, Rose F, et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet. 2002;360(9337):895–900.

    CAS  PubMed  Google Scholar 

  117. Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR, Hunninghake GW. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med. 2010;363(7):620–8.

    PubMed  Google Scholar 

  118. Han MK, Bach DS, Hagan P, et al. Sildenafil preserves exercise capacity in IPF patients with right ventricular dysfunction. Chest. 2013;143(6):1699–708.

    PubMed Central  CAS  PubMed  Google Scholar 

  119. King Jr TE, 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):92–9.

    PubMed  Google Scholar 

  120. 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):641–9.

    Google Scholar 

  121. Raghu G, Million-Rousseau R, Marganti A, et al. Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial. Eur Respir J. 2013; 42(6):1622–32.

    Google Scholar 

  122. Hoeper MM, Halank M, Wilkens H, et al. Riociguat for interstitial lung disease and pulmonary hypertension: a pilot trial. Eur Respir J. 2013;41(4):853–60.

    PubMed  Google Scholar 

  123. Maggiorini M, Brunner-La Rocca HP, Peth S, et al. Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial. Ann Intern Med. 2006;145(7):497–506.

    PubMed  Google Scholar 

  124. Bates MG, Thompson AA, Baillie JK, et al. Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo-controlled trial. High Alt Med Biol. 2011;12(3):207–14.

    CAS  PubMed  Google Scholar 

  125. Hegewald MJ, Elliott CG. Sustained improvement with iloprost in a COPD patient with severe pulmonary hypertension. Chest. 2009;135(2):536–7.

    PubMed  Google Scholar 

  126. Wang GL, Semenza GL. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood. 1993;82(12):3610–5.

    CAS  PubMed  Google Scholar 

  127. Smith TG, Talbot NP, Privat C, et al. Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA. 2009;302(13):1444–50.

    CAS  PubMed  Google Scholar 

  128. Rhodes CJ, Howard LS, Busbridge M, et al. Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension: clinical prevalence, outcomes, and mechanistic insights. J Am Coll Cardiol. 2011;58(3):300–9.

    CAS  PubMed  Google Scholar 

  129. Zhang H, Qian DZ, Tan YS, et al. Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci U S A. 2008;105(50):19579–86.

    PubMed Central  CAS  PubMed  Google Scholar 

  130. Abud EM, Maylor J, Undem C, et al. Digoxin inhibits development of hypoxic pulmonary hypertension in mice. Proc Natl Acad Sci U S A. 2012;109(4):1239–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  131. Lahm T, Crisostomo PR, Markel TA, et al. Selective estrogen receptor-alpha and estrogen receptor-beta agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism. Am J Physiol. 2008;295(5):R1486–93.

    CAS  Google Scholar 

  132. Resta TC, Kanagy NL, Walker BR. Estradiol-induced attenuation of pulmonary hypertension is not associated with altered eNOS expression. Am J Physiol. 2001;280(1):L88–97.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Pulmonary, Allergy, Critical Care, Occupational and Sleep Medicine, Department of Medicine, Indiana University School of Medicine and Richard L. Roudebush VA Medical Center, 980 W. Walnut Street, Room C-400, Indianapolis, IN, 46202, USA

    Kara Goss M.D. & Tim Lahm M.D.

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  1. Kara Goss M.D.
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  2. Tim Lahm M.D.
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Correspondence to Tim Lahm M.D. .

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Editors and Affiliations

  1. Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA

    James R. Klinger

  2. Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

    Robert P. Frantz

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Goss, K., Lahm, T. (2015). Hypoxic Pulmonary Hypertension. In: Klinger, J., Frantz, R. (eds) Diagnosis and Management of Pulmonary Hypertension. Respiratory Medicine, vol 12. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2636-7_4

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  • DOI: https://doi.org/10.1007/978-1-4939-2636-7_4

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