Background: The impact of pulmonary hypertension (PH) on survival has been demonstrated in severe cases with idiopathic pulmonary fibrosis (IPF) who were referred for transplantation. However, whether PH is a predictor of survival remains unclear in milder cases. Objectives: To evaluate the survival impact of pulmonary artery pressure measured during the initial evaluation in patients with IPF. Methods: We retrospectively analyzed the initial evaluation data of 101 consecutive IPF patients undergoing right heart catheterization. Patients evaluated with supplemental oxygen were excluded. Predictors of 5-year survival were analyzed using the Cox proportional model. Results: The mean forced vital capacity (FVC) % predicted, diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, and mean pulmonary artery pressure (MPAP) were 70.2 ± 20.1%, 47.9 ± 19.5%, and 19.2 ± 6.5 mm Hg, respectively. A univariate Cox proportional hazard model showed that the body mass index, %FVC, %DLCO, baseline PaO2, modified Medical Research Council score, 6-min walk distance, and lowest SpO2 of the 6-min walk test were significantly predictive of survival. The MPAP and pulmonary vascular resistance of right heart catheterization were also significant. With stepwise, multivariate Cox proportional analysis, MPAP (HR = 1.064; 95% CI 1.015-1.116, p = 0.010) and %FVC (HR = 0.965, 95% CI 0.949-0.982, p < 0.001) were independent determinants of survival. Analysis of the receiver operating curve revealed MPAP >20 mm Hg to be optimal for predicting the prognosis. Conclusions: Higher MPAP and lower %FVC at the initial evaluation were significant independent prognostic factors of IPF. The current results suggested the importance of the initial evaluation of PH for patients with IPF.

Keywords:
Idiopathic pulmonary fibrosis, Mortality, Pulmonary hypertension
1.
American Thoracic Society: Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement - American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 2000;161:646-664.
2.
King TE Jr, Tooze JA, Schwarz MI, Brown KR, Cherniack RM: Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med 2001;164:1171-1181.
3.
King TE Jr, Schwarz MI, Brown K, Tooze JA, Colby TV, Waldron JA Jr, Flint A, Thurlbeck W, Cherniack RM: Idiopathic pulmonary fibrosis: relationship between histopathologic features and mortality. Am J Respir Crit Care Med 2001;164:1025-1032.
4.
Flaherty KR, Toews GB, Travis WD, Colby TV, Kazerooni EA, Gross BH, Jain A, Strawderman RL 3rd, Paine R, Flint A, Lynch JP 3rd, Martinez FJ: Clinical significance of histological classification of idiopathic interstitial pneumonia. Eur Respir J 2002;19:275-283.
5.
Collard HR, King TE Jr, Bartelson BB, Vourlekis JS, Schwarz MI, Brown KK: Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2003;168:538-542.
6.
Lama VN, Flaherty KR, Toews GB, Colby TV, Travis WD, Long Q, Murray S, Kazerooni EA, Gross BH, Lynch JP 3rd, Martinez FJ: Prognostic value of desaturation during a 6-min walk test in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003;168:1084-1090.
7.
Flaherty KR, Mumford JA, Murray S, Kazerooni EA, Gross BH, Colby TV, Travis WD, Flint A, Toews GB, Lynch JP 3rd, Martinez FJ: Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003;168:543-548.
8.
Jegal Y, Kim DS, Shim TS, Lim CM, Do Lee S, Koh Y, Kim WS, Kim WD, Lee JS, Travis WD, Kitaichi M, Colby TV: Physiology is a stronger predictor of survival than pathology in fibrotic interstitial pneumonia. Am J Respir Crit Care Med 2005;171:639-644.
9.
Alakhras M, Decker PA, Nadrous HF, Collazo-Clavell M, Ryu JH: Body mass index and mortality in patients with idiopathic pulmonary fibrosis. Chest 2007;131:1448-1453.
10.
Nishiyama O, Taniguchi H, Kondoh Y, Kimura T, Kato K, Kataoka K, Ogawa T, Watanabe F, Arizono S: A simple assessment of dyspnoea as a prognostic indicator in idiopathic pulmonary fibrosis. Eur Respir J 2010;36:1067-1072.
11.
Nadrous HF, Pellikka PA, Krowka MJ, Swanson KL, Chaowalit N, Decker PA, Ryu JH: Pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Chest 2005;128:2393-2399.
12.
Leuchte HH, Baumgartner RA, Nounou ME, Vogeser M, Neurohr C, Trautnitz M, Behr J: Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med 2006;173:744-750.
13.
Lettieri CJ, Nathan SD, Barnett SD, Ahmad S, Shorr AF: Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest 2006;129:746-752.
14.
Nathan SD, Noble PW, Tuder RM: Idiopathic pulmonary fibrosis and pulmonary hypertension: connecting the dots. Am J Respir Crit Care Med 2007;175:875-880.
15.
Shorr AF, Wainright JL, Cors CS, Lettieri CJ, Nathan SD: Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant. Eur Respir J 2007;30:715-721.
16.
Patel NM, Lederer DJ, Borczuk AC, Kawut SM: Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest 2007;132:998-1006.
17.
Pitsiou G, Papakosta D, Bouros D: Pulmonary hypertension in idiopathic pulmonary fibrosis: a review. Respiration 2011;82:294-304.
18.
Hamada K, Nagai S, Tanaka S, Handa T, Shigematsu M, Nagao T, Mishima M, Kitaichi M, Izumi T: Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis. Chest 2007;131:650-656.
19.
Nathan SD, Shlobin OA, Ahmad S, Urbanek S, Barnett SD: Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis. Chest 2007;131:657-663.
20.
Badesch DB, Champion HC, Sanchez MA, Hoeper MM, Loyd JE, Manes A, McGoon M, Naeije R, Olschewski H, Oudiz RJ, Torbicki A: Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2009;54:S55-S66.
21.
Chaouat A, Naeije R, Weitzenblum E: Pulmonary hypertension in COPD. Eur Respir J 2008;32:1371-1385.
22.
Standardization of Spirometry, 1994 update: American Thoracic Society. Am J Respir Crit Care Med 1995;152:1107-1136.
23.
Guideline of respiratory function tests-spirometry, flow-volume curve, diffusion capacity of the lung. Nihon Kokyuki Gakkai Zasshi 2004;suppl:1-56.
24.
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories: ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111-117.
25.
Mahler DA, Wells CK: Evaluation of clinical methods for rating dyspnea. Chest 1988;93:580-586.
26.
Kawut SM, O'Shea MK, Bartels MN, Wilt JS, Sonett JR, Arcasoy SM: Exercise testing determines survival in patients with diffuse parenchymal lung disease evaluated for lung transplantation. Respir Med 2005;99:1431-1439.
27.
Corte TJ, Wort SJ, Gatzoulis MA, Macdonald P, Hansell DM, Wells AU: Pulmonary vascular resistance predicts early mortality in patients with diffuse fibrotic lung disease and suspected pulmonary hypertension. Thorax 2009;64:883-888.
28.
Renzoni EA, Walsh DA, Salmon M, Wells AU, Sestini P, Nicholson AG, Veeraraghavan S, Bishop AE, Romanska HM, Pantelidis P, Black CM, Du Bois RM: Interstitial vascularity in fibrosing alveolitis. Am J Respir Crit Care Med 2003;167:438-443.
29.
Ebina M, Shimizukawa M, Shibata N, Kimura Y, Suzuki T, Endo M, Sasano H, Kondo T, Nukiwa T: Heterogeneous increase in CD34-positive alveolar capillaries in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2004;169:1203-1208.
30.
Judge EP, Fabre A, Adamali HI, Egan JJ: Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Eur Respir J 2012;40:93-100.
31.
Farkas L, Gauldie J, Voelkel NF, Kolb M: Pulmonary hypertension and idiopathic pulmonary fibrosis: a tale of angiogenesis, apoptosis, and growth factors. Am J Respir Cell Mol Biol 2011;45:1-15.
32.
Farkas L, Farkas D, Ask K, Möller A, Gauldie J, Margetts P, Inman M, Kolb M: VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats. J Clin Invest 2009;119:1298-1311.
33.
Seimetz M, Parajuli N, Pichl A, Veit F, Kwapiszewska G, Weisel FC, Milger K, Egemnazarov B, Turowska A, Fuchs B, Nikam S, Roth M, Sydykov A, Medebach T, Klepetko W, Jaksch P, Dumitrascu R, Garn H, Voswinckel R, Kostin S, Seeger W, Schermuly RT, Grimminger F, Ghofrani HA, Weissmann N: Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice. Cell 2011;147:293-305.
34.
Henno P, Boitiaux JF, Douvry B, Cazes A, Lévy M, Devillier P, Delclaux C, Israël-Biet D: Tobacco-associated pulmonary vascular dysfunction in smokers: role of the ET-1 pathway. Am J Physiol Lung Cell Mol Physiol 2011;300:L831-L839.
35.
Pak O, Aldashev A, Welsh D, Peacock A: The effects of hypoxia on the cells of the pulmonary vasculature. Eur Respir J 2007;30:364-372.
36.
Sumikawa H, Johkoh T, Colby TV, Ichikado K, Suga M, Taniguchi H, Kondoh Y, Ogura T, Arakawa H, Fujimoto K, Inoue A, Mihara N, Honda O, Tomiyama N, Nakamura H, Muller NL: Computed tomography findings in pathological usual interstitial pneumonia: relationship to survival. Am J Respir Crit Care Med 2008;177:433-439.
37.
Cottin V, Le Pavec J, Prevot G, Mal H, Humbert M, Simonneau G, Cordier JF: Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome. Eur Respir J 2010;35:105-111.
38.
Mejia M, Carrillo G, Rojas-Serrano J, Estrada A, Suarez T, Alonso D, Barrientos E, Gaxiola M, Navarro C, Selman M: Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with severe pulmonary arterial hypertension. Chest 2009;136:10-15.
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