Skip to main content
SpringerLink
Log in
Book cover

Pulmonary Hypertension and Interstitial Lung Disease pp 103–128Cite as

Pulmonary Hypertension in Idiopathic Interstitial Pneumonias

  • Chapter
  • First Online:

  • 874 Accesses

Abstract

The classification of the idiopathic interstitial pneumonias (IIPs) has recently been updated by the ATS and ERS [1] (Table 6.1). Idiopathic pulmonary fibrosis (IPF) is the most common of the IIPs, and data from existing registries suggest that IPF accounts for 17–37% of all interstitial lung disease (ILD) diagnoses [2, 3]. Although estimates of the true incidence and prevalence of IPF are hampered by different methodologies used in epidemiological studies. IPF is a heterogeneous disease with some patients experiencing slow progressive disease, others a much more rapidly progressive disease and others still experiencing periods of stability punctuated by accelerated decline within acute exacerbations. Median survival is just 2–3 years [4]. It is appreciated that the development of pulmonary hypertension (PH) within IPF is common and its development has a dramatic effect both on morbidity and mortality. The desire to improve prognosis and quality of life in patients with IIP-associated PH (IIP–PH) who unfortunately at present have no clinically proven intervention to do so drives clinical research within this difficult area. The study of PH within IIP has predominantly focused upon IPF or mixed patient groups with IIP (which are predominantly made up of IPF patients). Therefore, this chapter focuses predominantly on PH within the IPF population.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   119.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Travis WD et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733–48.

    Article  PubMed  Google Scholar 

  2. Thomeer M, Demedts M, Vandeurzen K. Registration of interstitial lung diseases by 20 centres of respiratory medicine in Flanders. Acta Clin Belg. 2001;56(3):163–72.

    Article  CAS  PubMed  Google Scholar 

  3. Tinelli C et al. The Italian register for diffuse infiltrative lung disorders (RIPID): a four-year report. Sarcoidosis Vasc Diffuse Lung Dis. 2005;22(Suppl 1):S4–8.

    PubMed  Google Scholar 

  4. Raghu G et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183(6):788–824.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lettieri CJ et al. Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest. 2006;129(3):746–52.

    Article  PubMed  Google Scholar 

  6. Nathan SD et al. Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis. Chest. 2007;131(3):657–63.

    Article  PubMed  Google Scholar 

  7. Arcasoy SM et al. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. Am J Respir Crit Care Med. 2003;167(5):735–40.

    Article  PubMed  Google Scholar 

  8. Nathan SD et al. Serial development of pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Respiration. 2008;76(3):288–94.

    Article  CAS  PubMed  Google Scholar 

  9. Raghu G et al. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med. 2013;158(9):641–9.

    Article  PubMed  Google Scholar 

  10. The effect of diffuse fibrosis on reliability of ct signs of ph.pdf.

    Google Scholar 

  11. Zisman DA et al. High-resolution chest computed tomography findings do not predict the presence of pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Chest. 2007;132(3):773–9.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Nihtyanova SI et al. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheumatol. 2014;66(6):1625–35.

    Article  PubMed  Google Scholar 

  13. Fischer A et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015;46(4):976–87.

    Article  CAS  PubMed  Google Scholar 

  14. Handa T et al. Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis. Chest. 2006;129(5):1246–52.

    Article  PubMed  Google Scholar 

  15. Baughman RP, Engel PJ, Nathan S. Pulmonary hypertension in sarcoidosis. Clin Chest Med. 2015;36(4):703–14.

    Article  PubMed  Google Scholar 

  16. Nadrous HF et al. Pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Chest. 2005;128(4):2393–9.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. Mejia M et al. Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with severe pulmonary arterial hypertension. Chest. 2009;136(1):10–5.

    Article  PubMed  Google Scholar 

  19. Rivera-Lebron BN et al. Echocardiographic and hemodynamic predictors of mortality in idiopathic pulmonary fibrosis. Chest. 2013;144(2):564–70.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Corte TJ et al. Pulmonary vascular resistance predicts early mortality in patients with diffuse fibrotic lung disease and suspected pulmonary hypertension. Thorax. 2009;64(10):883–8.

    Article  CAS  PubMed  Google Scholar 

  21. Yasui K et al. Pulmonary vascular resistance estimated by Doppler echocardiography predicts mortality in patients with interstitial lung disease. J Cardiol. 2016;68(4):300–7.

    Article  PubMed  Google Scholar 

  22. Baughman RP et al. Survival in sarcoidosis-associated pulmonary hypertension: the importance of hemodynamic evaluation. Chest. 2010;138(5):1078–85.

    Article  PubMed  Google Scholar 

  23. Raghu G et al. Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction. Eur Respir J. 2015;46(5):1370–7.

    Article  PubMed  CAS  Google Scholar 

  24. Leuchte HH et al. Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med. 2006;173(7):744–50.

    Article  CAS  PubMed  Google Scholar 

  25. Corte TJ et al. Elevated brain natriuretic peptide predicts mortality in interstitial lung disease. Eur Respir J. 2010;36(4):819–25.

    Article  CAS  PubMed  Google Scholar 

  26. Song JW, Song JK, Kim DS. Echocardiography and brain natriuretic peptide as prognostic indicators in idiopathic pulmonary fibrosis. Respir Med. 2009;103(2):180–6.

    Article  PubMed  Google Scholar 

  27. Shin S et al. Pulmonary artery size as a predictor of outcomes in idiopathic pulmonary fibrosis. Eur Respir J. 2016;47(5):1445–51.

    Article  PubMed  Google Scholar 

  28. Corte TJ et al. Pulmonary function vascular index predicts prognosis in idiopathic interstitial pneumonia. Respirology. 2012;17(4):674–80.

    Article  PubMed  Google Scholar 

  29. Peelen L et al. Fibrotic idiopathic interstitial pneumonias: mortality is linked to a decline in gas transfer. Respirology. 2010;15(8):1233–43.

    Article  PubMed  Google Scholar 

  30. Lama VN et al. Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2003;168(9):1084–90.

    Article  PubMed  Google Scholar 

  31. Eaton T et al. Six-minute walk, maximal exercise tests: reproducibility in fibrotic interstitial pneumonia. Am J Respir Crit Care Med. 2005;171(10):1150–7.

    Article  PubMed  Google Scholar 

  32. Nathan SD et al. Right ventricular systolic pressure by echocardiography as a predictor of pulmonary hypertension in idiopathic pulmonary fibrosis. Respir Med. 2008;102(9):1305–10.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Andersen C et al. NT-proBNP <95 ng/l can exclude pulmonary hypertension on echocardiography at diagnostic workup in patients with interstitial lung disease. Eur Clin Respir J. 2016;3:32027.

    Article  PubMed  Google Scholar 

  34. Kuriyama K et al. CT-determined pulmonary artery diameters in predicting pulmonary hypertension. Investig Radiol. 1984;19(1):16–22.

    Article  CAS  Google Scholar 

  35. Edwards PD, Bull RK, Coulden R. CT measurement of main pulmonary artery diameter. Br J Radiol. 1998;71(850):1018–20.

    Article  CAS  PubMed  Google Scholar 

  36. Ng CS, Wells AU, Padley SP. A CT sign of chronic pulmonary arterial hypertension: the ratio of main pulmonary artery to aortic diameter. J Thorac Imaging. 1999;14(4):270–8.

    Article  CAS  PubMed  Google Scholar 

  37. Devaraj A et al. Detection of pulmonary hypertension with multidetector CT and echocardiography alone and in combination. Radiology. 2010;254(2):609–16.

    Article  PubMed  Google Scholar 

  38. Steen V et al. Exercise-induced pulmonary arterial hypertension in patients with systemic sclerosis. Chest. 2008;134(1):146–51.

    Article  PubMed  Google Scholar 

  39. Hsu VM et al. Assessment of pulmonary arterial hypertension in patients with systemic sclerosis: comparison of noninvasive tests with results of right-heart catheterization. J Rheumatol. 2008;35(3):458–65.

    PubMed  Google Scholar 

  40. Launay D et al. Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease. Chest. 2011;140(4):1016–24.

    Article  PubMed  Google Scholar 

  41. Coghlan JG et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73(7):1340–9.

    Article  PubMed  Google Scholar 

  42. Antoniou KM et al. Combined pulmonary fibrosis and emphysema in scleroderma-related lung disease has a major confounding effect on lung physiology and screening for pulmonary hypertension. Arthritis Rheumatol. 2016;68(4):1004–12.

    Article  CAS  PubMed  Google Scholar 

  43. Kawut SM et al. Exercise testing determines survival in patients with diffuse parenchymal lung disease evaluated for lung transplantation. Respir Med. 2005;99(11):1431–9.

    Article  PubMed  Google Scholar 

  44. Swigris JJ et al. Heart rate recovery after six-minute walk test predicts pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Respirology. 2011;16(3):439–45.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Galiè N et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2015;46(4):903–75.

    Article  PubMed  CAS  Google Scholar 

  46. Hamada K et al. Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis. Chest. 2007;131(3):650–6.

    Article  PubMed  Google Scholar 

  47. Turner-Warwick M. Precapillary systemic-pulmonary anastomoses. Thorax. 1963;18:225–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Renzoni EA et al. Interstitial vascularity in fibrosing alveolitis. Am J Respir Crit Care Med. 2003;167(3):438–43.

    Article  PubMed  Google Scholar 

  49. Ebina M et al. Heterogeneous increase in CD34-positive alveolar capillaries in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2004;169(11):1203–8.

    Article  PubMed  Google Scholar 

  50. Cosgrove GP et al. Pigment epithelium–derived factor in idiopathic pulmonary fibrosis a role in aberrant angiogenesis. Am J Respir Crit Care Med. 2004;170:242–51.

    Article  PubMed  Google Scholar 

  51. Kwon KY, Park KK, Chang ES. Scanning electron microscopic study of capillary change in bleomycin-induced pulmonary fibrosis. J Korean Med Sci. 1991;6(3):234–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tzouvelekis A et al. Comparative expression profiling in pulmonary fibrosis suggests a role of hypoxia-inducible factor-1alpha in disease pathogenesis. Am J Respir Crit Care Med. 2007;176(11):1108–19.

    Article  PubMed  Google Scholar 

  53. Strieter RM. Masters of angiogenesis. Nat Med. 2005;11(9):925–7.

    Article  CAS  PubMed  Google Scholar 

  54. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9(6):669–76.

    Article  CAS  PubMed  Google Scholar 

  55. Margaritopoulos GA et al. Investigation of angiogenetic axis Angiopoietin-1 and -2/Tie-2 in fibrotic lung diseases: a bronchoalveolar lavage study. Int J Mol Med. 2010;26(6):919–23.

    CAS  PubMed  Google Scholar 

  56. Pertovaara L et al. Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J Biol Chem. 1994;269(9):6271–4.

    CAS  PubMed  Google Scholar 

  57. Hanumegowda C, Farkas L, Kolb M. Angiogenesis in pulmonary fibrosis: too much or not enough? Chest. 2012;142(1):200–7.

    Article  CAS  PubMed  Google Scholar 

  58. Sumi M et al. Increased serum levels of endostatin in patients with idiopathic pulmonary fibrosis. J Clin Lab Anal. 2005;19(4):146–9.

    Article  CAS  PubMed  Google Scholar 

  59. Pascaud MA et al. Lung overexpression of angiostatin aggravates pulmonary hypertension in chronically hypoxic mice. Am J Respir Cell Mol Biol. 2003;29(4):449–57.

    Article  CAS  PubMed  Google Scholar 

  60. Partovian C et al. Adenovirus-mediated lung vascular endothelial growth factor overexpression protects against hypoxic pulmonary hypertension in rats. Am J Respir Cell Mol Biol. 2000;23(6):762–71.

    Article  CAS  PubMed  Google Scholar 

  61. Farkas L et al. VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J Clin Invest. 2009;119(5):1298–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sakao S et al. Apoptosis of pulmonary microvascular endothelial cells stimulates vascular smooth muscle cell growth. Am J Physiol Lung Cell Mol Physiol. 2006;291(3):L362–8.

    Article  CAS  PubMed  Google Scholar 

  63. Nathan SD, Noble PW, Tuder RM. Idiopathic pulmonary fibrosis and pulmonary hypertension: connecting the dots. Am J Respir Crit Care Med. 2007;175(9):875–80.

    Article  PubMed  Google Scholar 

  64. Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004;109(2):159–65.

    Article  PubMed  Google Scholar 

  65. Ask K et al. Targeting genes for treatment in idiopathic pulmonary fibrosis: challenges and opportunities, promises and pitfalls. Proc Am Thorac Soc. 2006;3(4):389–93.

    Article  CAS  PubMed  Google Scholar 

  66. Teng RJ et al. Increased superoxide production contributes to the impaired angiogenesis of fetal pulmonary arteries with in utero pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2009;297(1):L184–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Smith AP, Demoncheaux EA, Higenbottam TW. Nitric oxide gas decreases endothelin-1 mRNA in cultured pulmonary artery endothelial cells. Nitric Oxide. 2002;6(2):153–9.

    Article  CAS  PubMed  Google Scholar 

  68. Hashimoto N et al. Endothelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 2010;43(2):161–72.

    Article  CAS  PubMed  Google Scholar 

  69. Arciniegas E et al. Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2007;293(1):L1–8.

    Article  CAS  PubMed  Google Scholar 

  70. Sakao S et al. VEGF-R blockade causes endothelial cell apoptosis, expansion of surviving CD34+ precursor cells and transdifferentiation to smooth muscle-like and neuronal-like cells. FASEB J. 2007;21(13):3640–52.

    Article  CAS  PubMed  Google Scholar 

  71. Giaid A et al. Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis. Lancet. 1993;341(8860):1550–4.

    Article  CAS  PubMed  Google Scholar 

  72. Saleh D et al. Elevated expression of endothelin-1 and endothelin-converting enzyme-1 in idiopathic pulmonary fibrosis: possible involvement of proinflammatory cytokines. Am J Respir Cell Mol Biol. 1997;16(2):187–93.

    Article  CAS  PubMed  Google Scholar 

  73. Trakada G, Spiropoulos K. Arterial endothelin-1 in interstitial lung disease patients with pulmonary hypertension. Monaldi Arch Chest Dis. 2001;56(5):379–83.

    CAS  PubMed  Google Scholar 

  74. Voelkel NF, Vandivier RW, Tuder RM. Vascular endothelial growth factor in the lung. Am J Physiol Lung Cell Mol Physiol. 2006;290(2):L209–21.

    Article  CAS  PubMed  Google Scholar 

  75. Ramirez-Bergeron DL et al. HIF -dependent hematopoietic factors regulate the development of the embryonic vasculature. Dev Cell. 2006;11(1):81–92.

    Google Scholar 

  76. Meyer KC, Cardoni A, Xiang ZZ. Vascular endothelial growth factor in bronchoalveolar lavage from normal subjects and patients with diffuse parenchymal lung disease. J Lab Clin Med. 2000;135(4):332–8.

    Article  CAS  PubMed  Google Scholar 

  77. Farkas L et al. Pulmonary hypertension and idiopathic pulmonary fibrosis: a tale of angiogenesis, apoptosis, and growth factors. Am J Respir Cell Mol Biol. 2011;45(1):1–15.

    Article  CAS  PubMed  Google Scholar 

  78. Khalil N et al. Enhanced expression and immunohistochemical distribution of transforming growth factor-beta in idiopathic pulmonary fibrosis. Chest. 1991;99(3 Suppl):65s–6s.

    Article  CAS  PubMed  Google Scholar 

  79. Bergeron A et al. Cytokine profiles in idiopathic pulmonary fibrosis suggest an important role for TGF-beta and IL-10. Eur Respir J. 2003;22(1):69–76.

    Article  CAS  PubMed  Google Scholar 

  80. Zaiman AL et al. Role of the TGF-beta/Alk5 signaling pathway in monocrotaline-induced pulmonary hypertension. Am J Respir Crit Care Med. 2008;177(8):896–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Fredriksson L, Li H, Eriksson U. The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev. 2004;15(4):197–204.

    Article  CAS  PubMed  Google Scholar 

  82. Antoniades HN et al. Platelet-derived growth factor in idiopathic pulmonary fibrosis. J Clin Invest. 1990;86(4):1055–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Welsh DJ, Peacock AJ. Cellular responses to hypoxia in the pulmonary circulation. High Alt Med Biol. 2013;14(2):111–6.

    Article  PubMed  Google Scholar 

  84. Kolilekas L et al. Sleep oxygen desaturation predicts survival in idiopathic pulmonary fibrosis. J Clin Sleep Med. 2013;9(6):593–601.

    Google Scholar 

  85. Pihtili A et al. Obstructive sleep apnea is common in patients with interstitial lung disease. Sleep Breath. 2013;17(4):1281–8.

    Article  PubMed  Google Scholar 

  86. Mermigkis C et al. How common is sleep-disordered breathing in patients with idiopathic pulmonary fibrosis? Sleep Breath. 2010;14(4):387–90.

    Article  PubMed  Google Scholar 

  87. Perez-Padilla R et al. Breathing during sleep in patients with interstitial lung disease. Am Rev Respir Dis. 1985;132(2):224–9.

    CAS  PubMed  Google Scholar 

  88. Midgren B et al. Oxygen desaturation during sleep and exercise in patients with interstitial lung disease. Thorax. 1987;42(5):353–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Clark M et al. A survey of nocturnal hypoxaemia and health related quality of life in patients with cryptogenic fibrosing alveolitis. Thorax. 2001;56(6):482–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Midgren B. Oxygen desaturation during sleep as a function of the underlying respiratory disease. Am Rev Respir Dis. 1990;141(1):43–6.

    Article  CAS  PubMed  Google Scholar 

  91. Fletcher EC et al. Pulmonary vascular hemodynamics in chronic lung disease patients with and without oxyhemoglobin desaturation during sleep. Chest. 1989;95(4):757–64.

    Article  CAS  PubMed  Google Scholar 

  92. Corte TJ et al. Elevated nocturnal desaturation index predicts mortality in interstitial lung disease. Sarcoidosis Vasc Diffuse Lung Dis. 2012;29(1):41–50.

    CAS  PubMed  Google Scholar 

  93. Trakada G et al. Endothelin-1 levels in interstitial lung disease patients during sleep. Sleep Breath. 2003;7(3):111–8.

    Article  PubMed  Google Scholar 

  94. Talbot NP et al. Two temporal components within the human pulmonary vascular response to approximately 2 h of isocapnic hypoxia. J Appl Physiol (1985). 2005;98(3):1125–39.

    Article  Google Scholar 

  95. van Riet EE et al. Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail. 2016;18(3):242–52.

    Article  PubMed  Google Scholar 

  96. Papadopoulos CE et al. Left ventricular diastolic dysfunction in idiopathic pulmonary fibrosis: a tissue Doppler echocardiographic [corrected] study. Eur Respir J. 2008;31(4):701–6.

    Article  CAS  PubMed  Google Scholar 

  97. Nathan SD et al. Prevalence and impact of coronary artery disease in idiopathic pulmonary fibrosis. Respir Med. 2010;104(7):1035–41.

    Article  PubMed  Google Scholar 

  98. Hubbard RB et al. The association between idiopathic pulmonary fibrosis and vascular disease: a population-based study. Am J Respir Crit Care Med. 2008;178(12):1257–61.

    Article  PubMed  Google Scholar 

  99. Sode BF et al. Venous thromboembolism and risk of idiopathic interstitial pneumonia: a nationwide study. Am J Respir Crit Care Med. 2010;181(10):1085–92.

    Article  PubMed  Google Scholar 

  100. Sprunger DB et al. Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease. Eur Respir J. 2012;39(1):125–32.

    Article  CAS  PubMed  Google Scholar 

  101. Wygrecka M et al. Cellular origin of pro-coagulant and (anti)-fibrinolytic factors in bleomycin-injured lungs. Eur Respir J. 2007;29(6):1105–14.

    Article  CAS  PubMed  Google Scholar 

  102. Fujii M et al. Relevance of tissue factor and tissue factor pathway inhibitor for hypercoagulable state in the lungs of patients with idiopathic pulmonary fibrosis. Thromb Res. 2000;99(2):111–7.

    Article  CAS  PubMed  Google Scholar 

  103. Kotani I et al. Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis. Thromb Res. 1995;77(6):493–504.

    Article  CAS  PubMed  Google Scholar 

  104. Fahim A et al. Increased platelet binding to circulating monocytes in idiopathic pulmonary fibrosis. Lung. 2014;192(2):277–84.

    Article  CAS  PubMed  Google Scholar 

  105. Kinder BW, Collard HR, King Jr TE. Anticoagulant therapy and idiopathic pulmonary fibrosis. Chest. 2006;130(1):302–3.

    Article  PubMed  Google Scholar 

  106. Noth I et al. A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012;186(1):88–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Luo Q et al. Prevalence of venous thromboembolic events and diagnostic performance of the wells score and revised geneva scores for pulmonary embolism in patients with interstitial lung disease: a prospective study. Heart Lung Circ. 2014;23(8):778–85.

    Article  PubMed  Google Scholar 

  108. Noble PW et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377(9779):1760–9.

    Article  CAS  PubMed  Google Scholar 

  109. Richeldi L et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosi. N Engl J Med. 365(12):1079–87.

    Google Scholar 

  110. Nathan SD et al. Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis. Thorax. 2016;71(5):429–35.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Raghu G et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3–19.

    Article  PubMed  Google Scholar 

  112. 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):681–6.

    Google Scholar 

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

    Google Scholar 

  114. Hardinge M et al. British Thoracic Society guidelines for home oxygen use in adults. Thorax. 2015;70(Suppl 1):i1–43.

    Article  PubMed  Google Scholar 

  115. Kim DS et al. Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features. Eur Respir J. 2006;27(1):143–50.

    Article  CAS  PubMed  Google Scholar 

  116. Song JW et al. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011;37(2):356–63.

    Article  CAS  PubMed  Google Scholar 

  117. Judge EP et al. Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Eur Respir J. 2012;40(1):93–100.

    Article  PubMed  Google Scholar 

  118. Huie TJ et al. A detailed evaluation of acute respiratory decline in patients with fibrotic lung disease: aetiology and outcomes. Respirology. 2010;15(6):909–17.

    Article  PubMed  Google Scholar 

  119. Johannson KA et al. Acute exacerbation of idiopathic pulmonary fibrosis associated with air pollution exposure. Eur Respir J. 2014;43(4):1124–31.

    Article  PubMed  Google Scholar 

  120. Lee JS et al. Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J. 2012;39(2):352–8.

    Article  CAS  PubMed  Google Scholar 

  121. Maher TM et al. Development of a consensus statement for the definition, diagnosis, and treatment of acute exacerbations of idiopathic pulmonary fibrosis using the delphi technique. Adv Ther. 2015;32(10):929–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Shen JH et al. Comparison of the Wells score with the revised Geneva score for assessing suspected pulmonary embolism: a systematic review and meta-analysis. J Thromb Thrombolysis. 2016;41(3):482–92.

    Article  PubMed  Google Scholar 

  123. Wijesekera NT et al. Image quality of computed tomographic pulmonary angiography for suspected pulmonary embolus in patients with diffuse interstitial lung disease. J Thorac Imaging. 2012;27(3):156–63.

    Article  PubMed  Google Scholar 

  124. Leuschner G et al. Suspected pulmonary embolism in patients with pulmonary fibrosis: discordance between ventilation/perfusion SPECT and CT pulmonary angiography. Respirology. 2016;21(6):1081–7.

    Article  PubMed  Google Scholar 

  125. Strickland NH et al. Cause of regional ventilation-perfusion mismatching in patients with idiopathic pulmonary fibrosis: a combined CT and scintigraphic study. AJR Am J Roentgenol. 1993;161(4):719–25.

    Article  CAS  PubMed  Google Scholar 

  126. Peiman S et al. Subsegmental pulmonary embolism: a narrative review. Thromb Res. 2016;138:55–60.

    Article  CAS  PubMed  Google Scholar 

  127. Alagha K et al. Warfarin should be banned in ipf.pdf. Am J Respir Crit Care Med. 2015;191:958–60.

    Article  CAS  PubMed  Google Scholar 

  128. Milara J et al. Vascular effects of sildenafil in patients with pulmonary fibrosis and pulmonary hypertension: an ex vivo/in vitro study. Eur Respir J. 2016;47(6):1737–49.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  130. Collard HR, Anstrom KJ, Schwarz MI, Zisman DA. Sildenafil improves walk distance in idiopathic pulmonary fibrosis. Chest. 2007;131(3):897–9.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Corte TJ et al. The use of sildenafil to treat pulmonary hypertension associated with interstitial lung disease. Respirology. 2010;15(8):1226–32.

    Article  PubMed  Google Scholar 

  132. Zimmermann GS et al. Haemodynamic changes in pulmonary hypertension in patients with interstitial lung disease treated with PDE-5 inhibitors. Respirology. 2014;19(5):700–6.

    Article  PubMed  Google Scholar 

  133. Zisman DA et al. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med. 2010;363(7):620–8.

    Article  PubMed  Google Scholar 

  134. Han MK et al. Sildenafil preserves exercise capacity in patients with idiopathic pulmonary fibrosis and right-sided ventricular dysfunction. Chest. 2013;143(6):1699–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. du Bois RM et al. Six-minute-walk test in idiopathic pulmonary fibrosis: test validation and minimal clinically important difference. Am J Respir Crit Care Med. 2011;183(9):1231–7.

    Article  PubMed  Google Scholar 

  136. Hoeper MM et al. Pulmonary hypertension in patients with chronic fibrosing idiopathic interstitial pneumonias. PLoS One. 2015;10(12):e0141911.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Giaid A et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993;328(24):1732–9.

    Article  CAS  PubMed  Google Scholar 

  138. Ross B, D’Orleans-Juste P, Giaid A. Potential role of endothelin-1 in pulmonary fibrosis: from the bench to the clinic. Am J Respir Cell Mol Biol. 2010;42(1):16–20.

    Article  CAS  PubMed  Google Scholar 

  139. Uguccioni M et al. Endothelin-1 in idiopathic pulmonary fibrosis. J Clin Pathol. 1995;48(4):330–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. King Jr TE 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.

    Article  PubMed  Google Scholar 

  141. Raghu G et al. Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial. Eur Respir J. 2013;42(6):1622–32.

    Article  CAS  PubMed  Google Scholar 

  142. Corte TJ et al. Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia. Am J Respir Crit Care Med. 2014;190(2):208–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Olschewski H 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.

    Article  CAS  PubMed  Google Scholar 

  144. Ghofrani HA et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369(4):330–40.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  146. Bayer. Efficacy and safety of riociguat in patients with symptomatic pulmonary hypertension (PH) associated with idiopathic interstitial pneumonia’s (IIP) (RISE-IIP). https://clinicaltrials.gov/ct2/show/, NCT02138825.

  147. King Jr TE et al. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008;177(1):75–81.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Royal Brompton Hospital, National Heart and Lung Institute, Imperial College London, London, UK

    Simon Bax BSc, MBBS, MRCP

  2. Interstitial Lung Disease Unit, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College London, London, UK

    Athol Wells MBChB, MD, FRACP, FRCP, FRCR

  3. Pulmonary Hypertension Service, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College London, London, UK

    Laura Price BSc, MBChB, MRCP, PhD & John Wort MA, MBBS, PhD, FRCP, FFICM

Authors
  1. Simon Bax BSc, MBBS, MRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Athol Wells MBChB, MD, FRACP, FRCP, FRCR
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura Price BSc, MBChB, MRCP, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John Wort MA, MBBS, PhD, FRCP, FFICM
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA

    Robert P. Baughman

  2. Regional Hospital Aosta and University of Genoa, Genoa, Italy

    Roberto G. Carbone

  3. Inova Fairfax Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA

    Steven D. Nathan

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Bax, S., Wells, A., Price, L., Wort, J. (2017). Pulmonary Hypertension in Idiopathic Interstitial Pneumonias. In: Baughman, R., Carbone, R., Nathan, S. (eds) Pulmonary Hypertension and Interstitial Lung Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-49918-5_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-49918-5_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-49916-1

  • Online ISBN: 978-3-319-49918-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation