Pulmonary Hypertension Associated with Chronic Lung Disease

Yuanchen      Wang; Rodolfo   A.   Estrada; Khushboo      Goel; Rodney   J.   Folz; Sandeep      Sahay
doi:10.2174/011573398X266440240408080251
Abstract

Patients with Chronic Lung Disease (CLD) are frequently burdened by pulmonary hypertension (PH), which is associated with reduced functional capacity, poor quality of life, increased oxygen requirements, and increased morbidity and mortality. The development of PH associated with chronic lung disease (PH-CLD) is complex and multifactorial and varies between different types of CLD. In this review, we provide an update on PH-CLD, with a particular focus on Interstitial Lung Disease (ILD), chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), and obesity hypoventilation syndrome (OHS). We discussed epidemiology, histopathology, pathophysiology, diagnostic evaluation, and treatment approaches. There are limited data on the use of pulmonary arterial hypertension-specific treatments in PH-CLD, so it has been proposed to phenotype patients based on their degree of pulmonary vascular disease to guide individualized care. The heterogeneity within PH-CLD highlights the importance of identifying novel molecular pathways unique to each subgroup to ultimately achieve precision medicine.
« Previous Next »
Graphical Abstract

[1]
Strange, G.; Playford, D.; Stewart, S.; Deague, J.A.; Nelson, H.; Kent, A.; Gabbay, E. Pulmonary hypertension: Prevalence and mortality in the Armadale echocardiography cohort. Heart,  2012, 98(24), 1805-1811.
 [http://dx.doi.org/10.1136/heartjnl-2012-301992] [PMID: 22760869]

[2]
Hayes, D., Jr; Black, S.M.; Tobias, J.D.; Kirkby, S.; Mansour, H.M.; Whitson, B.A. Influence of pulmonary hypertension on patients with idiopathic pulmonary fibrosis awaiting lung transplantation. Ann. Thorac. Surg.,  2016, 101(1), 246-252.
 [http://dx.doi.org/10.1016/j.athoracsur.2015.06.024] [PMID: 26319484]

[3]
Judge, E.P.; Fabre, A.; Adamali, H.I.; Egan, J.J. Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Eur. Respir. J.,  2012, 40(1), 93-100.
 [http://dx.doi.org/10.1183/09031936.00115511] [PMID: 22135282]

[4]
Kimura, M.; Taniguchi, H.; Kondoh, Y.; Kimura, T.; Kataoka, K.; Nishiyama, O.; Aso, H.; Sakamoto, K.; Hasegawa, Y. Pulmonary hypertension as a prognostic indicator at the initial evaluation in idiopathic pulmonary fibrosis. Respiration,  2013, 85(6), 456-463.
 [http://dx.doi.org/10.1159/000345221] [PMID: 23257350]

[5]
Hoeper, M.M.; Behr, J.; Held, M.; Grunig, E.; Vizza, C.D.; Vonk-Noordegraaf, A.; Lange, T.J.; Claussen, M.; Grohé, C.; Klose, H.; Olsson, K.M.; Zelniker, T.; Neurohr, C.; Distler, O.; Wirtz, H.; Opitz, C.; Huscher, D.; Pittrow, D.; Gibbs, J.S.R. Pulmonary hypertension in patients with chronic fibrosing idiopathic interstitial pneumonias. PLoS One,  2015, 10(12), e0141911.
 [http://dx.doi.org/10.1371/journal.pone.0141911] [PMID: 26630396]

[6]
Nikkho, S.M.; Richter, M.J.; Shen, E.; Abman, S.H.; Antoniou, K.; Chung, J.; Fernandes, P.; Hassoun, P.; Lazarus, H.M.; Olschewski, H.; Piccari, L.; Psotka, M.; Saggar, R.; Shlobin, O.A.; Stockbridge, N.; Vitulo, P.; Vizza, C.D.; Wort, S.J.; Nathan, S.D. Clinical significance of pulmonary hypertension in interstitial lung disease: A consensus statement from the pulmonary vascular research institute’s innovative drug development initiative—group 3 pulmonary hypertension. Pulm. Circ.,  2022, 12(3), e12127.
 [http://dx.doi.org/10.1002/pul2.12127] [PMID: 36016668]

[7]
Nathan, S.D.; Barbera, J.A.; Gaine, S.P.; Harari, S.; Martinez, F.J.; Olschewski, H.; Olsson, K.M.; Peacock, A.J.; Pepke-Zaba, J.; Provencher, S.; Weissmann, N.; Seeger, W. Pulmonary hypertension in chronic lung disease and hypoxia. Eur. Respir. J.,  2019, 53(1), 1801914.
 [http://dx.doi.org/10.1183/13993003.01914-2018] [PMID: 30545980]

[8]
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), 158-164.
 [http://dx.doi.org/10.1164/ajrccm.159.1.9803117] [PMID: 9872834]

[9]
Wells, J.M.; Washko, G.R.; Han, M.K.; Abbas, N.; Nath, H.; Mamary, A.J.; Regan, E.; Bailey, W.C.; Martinez, F.J.; Westfall, E.; Beaty, T.H.; Curran-Everett, D.; Curtis, J.L.; Hokanson, J.E.; Lynch, D.A.; Make, B.J.; Crapo, J.D.; Silverman, E.K.; Bowler, R.P.; Dransfield, M.T. Pulmonary arterial enlargement and acute exacerbations of COPD. N. Engl. J. Med.,  2012, 367(10), 913-921.
 [http://dx.doi.org/10.1056/NEJMoa1203830] [PMID: 22938715]

[10]
Zeder, K.; Avian, A.; Bachmaier, G.; Douschan, P.; Foris, V.; Sassmann, T.; Troester, N.; Brcic, L.; Fuchsjaeger, M.; Marsh, L.M.; Maron, B.A.; Olschewski, H.; Kovacs, G. Elevated pulmonary vascular resistance predicts mortality in COPD patients. Eur. Respir. J.,  2021, 58(2), 2100944.
 [http://dx.doi.org/10.1183/13993003.00944-2021] [PMID: 33986032]

[11]
Gall, H.; Felix, J.F.; Schneck, F.K.; Milger, K.; Sommer, N.; Voswinckel, R.; Franco, O.H.; Hofman, A.; Schermuly, R.T.; Weissmann, N.; Grimminger, F.; Seeger, W.; Ghofrani, H.A. The giessen pulmonary hypertension registry: Survival in pulmonary hypertension subgroups. J. Heart Lung Transplant.,  2017, 36(9), 957-967.
 [http://dx.doi.org/10.1016/j.healun.2017.02.016] [PMID: 28302503]

[12]
Hurdman, J.; Condliffe, R.; Elliot, C.A.; Davies, C.; Hill, C.; Wild, J.M.; Capener, D.; Sephton, P.; Hamilton, N.; Armstrong, I.J.; Billings, C.; Lawrie, A.; Sabroe, I.; Akil, M.; O’Toole, L.; Kiely, D.G. ASPIRE registry: Assessing the spectrum of pulmonary hypertension identified at a referral centre. Eur. Respir. J.,  2012, 39(4), 945-955.
 [http://dx.doi.org/10.1183/09031936.00078411] [PMID: 21885399]

[13]
Minai, O.A.; Ricaurte, B.; Kaw, R.; Hammel, J.; Mansour, M.; McCarthy, K.; Golish, J.A.; Stoller, J.K. Frequency and impact of pulmonary hypertension in patients with obstructive sleep apnea syndrome. Am. J. Cardiol.,  2009, 104(9), 1300-1306.
 [http://dx.doi.org/10.1016/j.amjcard.2009.06.048] [PMID: 19840581]

[14]
Prins, K.W.; Rose, L.; Archer, S.L.; Pritzker, M.; Weir, E.K.; Kazmirczak, F.; Misialek, J.R.; Thenappan, T. Disproportionate right ventricular dysfunction and poor survival in group 3 pulmonary hypertension. Am. J. Respir. Crit. Care Med.,  2018, 197(11), 1496-1499.
 [http://dx.doi.org/10.1164/rccm.201712-2405LE] [PMID: 29360393]

[15]
Shorr, A.F.; Wainright, J.L.; Cors, C.S.; Lettieri, C.J.; Nathan, S.D. Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant. Eur. Respir. J.,  2007, 30(4), 715-721.
 [http://dx.doi.org/10.1183/09031936.00107206] [PMID: 17626111]

[16]
Andersen, K.H.; Iversen, M.; Kjaergaard, J.; Mortensen, J.; Nielsen-Kudsk, J.E.; Bendstrup, E.; Videbaek, R.; Carlsen, J. Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease. J. Heart Lung Transplant.,  2012, 31(4), 373-380.
 [http://dx.doi.org/10.1016/j.healun.2011.11.020] [PMID: 22226804]

[17]
Portillo, K.; Torralba, Y.; Blanco, I.; Burgos, F.; Rodriguez -Roisin, R.; Rios, J.; Roca, J.; Barberà, J.A. Pulmonary hemodynamic profile in chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis.,  2015, 10, 1313-1320.
 [http://dx.doi.org/10.2147/COPD.S78180] [PMID: 26203238]

[18]
Scharf, S.M.; Iqbal, M.; Keller, C.; Criner, G.; Lee, S.; Fessler, H.E. Hemodynamic characterization of patients with severe emphysema. Am. J. Respir. Crit. Care Med.,  2002, 166(3), 314-322.
 [http://dx.doi.org/10.1164/rccm.2107027] [PMID: 12153963]

[19]
Boerrigter, B.G.; Bogaard, H.J.; Trip, P.; Groepenhoff, H.; Rietema, H.; Holverda, S.; Boonstra, A.; Postmus, P.E.; Westerhof, N.; Vonk-Noordegraaf, A. Ventilatory and cardiocirculatory exercise profiles in COPD: The role of pulmonary hypertension. Chest,  2012, 142(5), 1166-1174.
 [http://dx.doi.org/10.1378/chest.11-2798] [PMID: 22556320]

[20]
Atwood, C.W., Jr; McCrory, D.; Garcia, J.G.N.; Abman, S.H.; Ahearn, G.S. Pulmonary artery hypertension and sleep-disordered breathing: ACCP evidence-based clinical practice guidelines. Chest,  2004, 126(1)(Suppl.), 72S-77S.
 [http://dx.doi.org/10.1378/chest.126.1_suppl.72S] [PMID: 15249496]

[21]
Chaouat, A.; Weitzenblum, E.; Krieger, J.; Oswald, M.; Kessler, R. Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients. Chest,  1996, 109(2), 380-386.
 [http://dx.doi.org/10.1378/chest.109.2.380] [PMID: 8620709]

[22]
Bady, E.; Achkar, A.; Pascal, S.; Orvoen-Frija, E.; Laaban, J.P. Pulmonary arterial hypertension in patients with sleep apnoea syndrome. Thorax,  2000, 55(11), 934-939.
 [http://dx.doi.org/10.1136/thorax.55.11.934] [PMID: 11050263]

[23]
Kessler, R.; Chaouat, A.; Schinkewitch, P.; Faller, M.; Casel, S.; Krieger, J.; Weitzenblum, E. The obesity-hypoventilation syndrome revisited: A prospective study of 34 consecutive cases. Chest,  2001, 120(2), 369-376.
 [http://dx.doi.org/10.1378/chest.120.2.369] [PMID: 11502631]

[24]
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(3), 183-189.
 [http://dx.doi.org/10.1136/thx.43.3.183] [PMID: 3406902]

[25]
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(2), 109-124.
 [http://dx.doi.org/10.1007/BF00175982] [PMID: 1501507]

[26]
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(249), 65-85.
 [PMID: 3174923]

[27]
Sakao, S.; Voelkel, N.F.; Tatsumi, K. The vascular bed in COPD: Pulmonary hypertension and pulmonary vascular alterations. Eur. Respir. Rev.,  2014, 23(133), 350-355.
 [http://dx.doi.org/10.1183/09059180.00007913] [PMID: 25176971]

[28]
Tuder, RM; Marecki, JC; Richter, A; Fijalkowska, I; Flores, S Pathology of pulmonary hypertension. Clin Chest Med,  2007, 28(1), 23-42.
 [http://dx.doi.org/10.1016/j.ccm.2006.11.010]

[29]
Ruffenach, G.; Hong, J.; Vaillancourt, M.; Medzikovic, L.; Eghbali, M. Pulmonary hypertension secondary to pulmonary fibrosis: Clinical data, histopathology and molecular insights. Respir. Res.,  2020, 21(1), 303.
 [http://dx.doi.org/10.1186/s12931-020-01570-2] [PMID: 33208169]

[30]
Piccari, L.; Allwood, B.; Antoniou, K.; Chung, J.H.; Hassoun, P.M.; Nikkho, S.M.; Saggar, R.; Shlobin, O.A.; Vitulo, P.; Nathan, S.D.; Wort, S.J. Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the pulmonary vascular research institute’s innovative drug development initiative - group 3 pulmonary hypertension. Pulm. Circ.,  2023, 13(2), e12213.
 [http://dx.doi.org/10.1002/pul2.12213] [PMID: 37025209]

[31]
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(11), 1203-1208.
 [http://dx.doi.org/10.1164/rccm.200308-1111OC] [PMID: 14754760]

[32]
Renzoni, E.A.; Walsh, D.A.; Salmon, M.; Wells, A.U.; Sestini, P.; Nicholson, A.G.; Veeraraghavan, S.; Bishop, A.E.; Romanska, H.M.; Pantelidis, P.; Black, C.M.; du Bois, R.M. Interstitial vascularity in fibrosing alveolitis. Am. J. Respir. Crit. Care Med.,  2003, 167(3), 438-443.
 [http://dx.doi.org/10.1164/rccm.200202-135OC] [PMID: 12406847]

[33]
Colombat, M.; Mal, H.; Groussard, O.; Capron, F.; Thabut, G.; Jebrak, G.; Brugière, O.; Dauriat, G.; Castier, Y.; Lesèche, G.; Fournier, M. Pulmonary vascular lesions in end-stage idiopathic pulmonary fibrosis: Histopathologic study on lung explant specimens and correlations with pulmonary hemodynamics. Hum. Pathol.,  2007, 38(1), 60-65.
 [http://dx.doi.org/10.1016/j.humpath.2006.06.007] [PMID: 16949908]

[34]
Bunel, V.; Guyard, A.; Dauriat, G.; Danel, C.; Montani, D.; Gauvain, C.; Thabut, G.; Humbert, M.; Castier, Y.; Dorfmüller, P.; Mal, H. Pulmonary arterial histologic lesions in patients with COPD with severe pulmonary hypertension. Chest,  2019, 156(1), 33-44.
 [http://dx.doi.org/10.1016/j.chest.2019.02.333] [PMID: 30872017]

[35]
Washko, G.R.; Nardelli, P.; Ash, S.Y.; Vegas Sanchez-Ferrero, G.; Rahaghi, F.N.; Come, C.E.; Dransfield, M.T.; Kalhan, R.; Han, M.K.; Bhatt, S.P.; Wells, J.M.; Aaron, C.P.; Diaz, A.A.; Ross, J.C.; Cuttica, M.J.; Labaki, W.W.; Querejeta Roca, G.; Shah, A.M.; Young, K.; Kinney, G.L.; Hokanson, J.E.; Agustí, A.; San José Estépar, R. Arterial vascular pruning, right ventricular size, and clinical outcomes in chronic obstructive pulmonary disease. A longitudinal observational study. Am. J. Respir. Crit. Care Med.,  2019, 200(4), 454-461.
 [http://dx.doi.org/10.1164/rccm.201811-2063OC] [PMID: 30758975]

[36]
Seimetz, M.; Parajuli, N.; Pichl, A.; Veit, F.; Kwapiszewska, G.; Weisel, F.C.; 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, R.T.; Grimminger, F.; Ghofrani, H.A.; Weissmann, N. Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice. Cell,  2011, 147(2), 293-305.
 [http://dx.doi.org/10.1016/j.cell.2011.08.035] [PMID: 22000010]

[37]
Weissmann, N.; Lobo, B.; Pichl, A.; Parajuli, N.; Seimetz, M.; Puig-Pey, R.; Ferrer, E.; Peinado, V.I.; Domínguez-Fandos, D.; Fysikopoulos, A.; Stasch, J.P.; Ghofrani, H.A.; Coll-Bonfill, N.; Frey, R.; Schermuly, R.T.; García-Lucio, J.; Blanco, I.; Bednorz, M.; Tura-Ceide, O.; Tadele, E.; Brandes, R.P.; Grimminger, J.; Klepetko, W.; Jaksch, P.; Rodriguez-Roisin, R.; Seeger, W.; Grimminger, F.; Barberà, J.A. Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced pulmonary hypertension and emphysema. Am. J. Respir. Crit. Care Med.,  2014, 189(11), 1359-1373.
 [http://dx.doi.org/10.1164/rccm.201311-2037OC] [PMID: 24738736]

[38]
Hoeper, M.M.; Vonk-Noordegraaf, A. Is there a vanishing pulmonary capillary syndrome? Lancet Respir. Med.,  2017, 5(9), 676-678.
 [http://dx.doi.org/10.1016/S2213-2600(17)30291-6] [PMID: 28734824]

[39]
Synn, A.J.; De Margerie-Mellon, C.; Jeong, S.Y.; Rahaghi, F.N.; Jhun, I.; Washko, G.R.; Estépar, R.S.J.; Bankier, A.A.; Mittleman, M.A.; VanderLaan, P.A.; Rice, M.B. Vascular remodeling of the small pulmonary arteries and measures of vascular pruning on computed tomography. Pulm. Circ.,  2021, 11(4), 1-9.
 [http://dx.doi.org/10.1177/20458940211061284] [PMID: 34881020]

[40]
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), 364-372.
 [http://dx.doi.org/10.1183/09031936.00128706] [PMID: 17666559]

[41]
Wu, W.H.; Bonnet, S.; Shimauchi, T.; Toro, V.; Grobs, Y.; Romanet, C.; Bourgeois, A.; Vitry, G.; Omura, J.; Tremblay, E.; Nadeau, V.; Orcholski, M.; Breuils-Bonnet, S.; Martineau, S.; Ferraro, P.; Potus, F.; Paulin, R.; Provencher, S.; Boucherat, O. Potential for inhibition of checkpoint kinases 1/2 in pulmonary fibrosis and secondary pulmonary hypertension. Thorax,  2022, 77(3), 247-258.
 [http://dx.doi.org/10.1136/thoraxjnl-2021-217377] [PMID: 34226205]

[42]
Mura, M.; Anraku, M.; Yun, Z.; McRae, K.; Liu, M.; Waddell, T.K.; Singer, L.G.; Granton, J.T.; Keshavjee, S.; de Perrot, M. Gene expression profiling in the lungs of patients with pulmonary hypertension associated with pulmonary fibrosis. Chest,  2012, 141(3), 661-673.
 [http://dx.doi.org/10.1378/chest.11-0449] [PMID: 21835902]

[43]
Newman, J.H. Molecular rescue in pulmonary arterial hypertension. N. Engl. J. Med.,  2021, 384(13), 1271-1272.
 [http://dx.doi.org/10.1056/NEJMe2036314] [PMID: 33789018]

[44]
Shimoda, L.A. Cellular pathways promoting pulmonary vascular remodeling by hypoxia. Physiology,  2020, 35(4), 222-233.
 [http://dx.doi.org/10.1152/physiol.00039.2019] [PMID: 32490752]

[45]
Stenmark, K.R.; Fagan, K.A.; Frid, M.G. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ. Res.,  2006, 99(7), 675-691.
 [http://dx.doi.org/10.1161/01.RES.0000243584.45145.3f] [PMID: 17008597]

[46]
Moudgil, R; Michelakis, ED; Archer, SL Hypoxic pulmonary vasoconstriction. J Appl Physiol Bethesda Md 1985,  2005, 98(1), 390-403.
 [http://dx.doi.org/10.1152/japplphysiol.00733.2004]

[47]
Brito, J.; Siques, P.; López, R.; Romero, R.; León-Velarde, F.; Flores, K.; Lüneburg, N.; Hannemann, J.; Böger, R.H. Long-term intermittent work at high altitude: Right heart functional and morphological status and associated cardiometabolic factors. Front. Physiol.,  2018, 9, 248.
 [http://dx.doi.org/10.3389/fphys.2018.00248] [PMID: 29623044]

[48]
Wright, J.K.; Kim, L.T.; Rogers, T.E.; Nguyen, H.; Turnage, R.H. Nitric oxide and thromboxane A2-mediated pulmonary microvascular dysfunction. Arch. Surg.,  1999, 134(3), 293-298.
 [http://dx.doi.org/10.1001/archsurg.134.3.293] [PMID: 10088571]

[49]
Berger, M.M.; Dehnert, C.; Bailey, D.M.; Luks, A.M.; Menold, E.; Castell, C.; Schendler, G.; Faoro, V.; Mairbäurl, H.; Bärtsch, P.; Swenson, E.R. Transpulmonary plasma ET-1 and nitrite differences in high altitude pulmonary hypertension. High Alt. Med. Biol.,  2009, 10(1), 17-24.
 [http://dx.doi.org/10.1089/ham.2008.1053] [PMID: 19326597]

[50]
Sylvester, J.T.; Shimoda, L.A.; Aaronson, P.I.; Ward, J.P.T. Hypoxic pulmonary vasoconstriction. Physiol. Rev.,  2012, 92(1), 367-520.
 [http://dx.doi.org/10.1152/physrev.00041.2010] [PMID: 22298659]

[51]
Rabinovitch, M.; Konstam, M.A.; Gamble, W.J.; Papanicolaou, N.; Aronovitz, M.J.; Treves, S.; Reid, L. Changes in pulmonary blood flow affect vascular response to chronic hypoxia in rats. Circ. Res.,  1983, 52(4), 432-441.
 [http://dx.doi.org/10.1161/01.RES.52.4.432] [PMID: 6831659]

[52]
Rabinovitch, M.; Gamble, W.J.; Miettinen, O.S.; Reid, L. Age and sex influence on pulmonary hypertension of chronic hypoxia and on recovery. Am. J. Physiol. Heart Circ. Physiol.,  1981, 240(1), H62-H72.
 [http://dx.doi.org/10.1152/ajpheart.1981.240.1.H62] [PMID: 6450541]

[53]
Davie, N.J.; Crossno, J.T., Jr; Frid, M.G.; Hofmeister, S.E.; Reeves, J.T.; Hyde, D.M.; Carpenter, T.C.; Brunetti, J.A.; McNiece, I.K.; Stenmark, K.R. Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells. Am. J. Physiol. Lung Cell. Mol. Physiol.,  2004, 286(4), L668-L678.
 [http://dx.doi.org/10.1152/ajplung.00108.2003] [PMID: 12754186]

[54]
Dierick, F.; Solinc, J.; Bignard, J.; Soubrier, F.; Nadaud, S. Progenitor/stem cells in vascular remodeling during pulmonary arterial hypertension. Cells,  2021, 10(6), 1338.
 [http://dx.doi.org/10.3390/cells10061338] [PMID: 34071347]

[55]
Frid, M.G.; Brunetti, J.A.; Burke, D.L.; Carpenter, T.C.; Davie, N.J.; Reeves, J.T.; Roedersheimer, M.T.; van Rooijen, N.; Stenmark, K.R. Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage. Am. J. Pathol.,  2006, 168(2), 659-669.
 [http://dx.doi.org/10.2353/ajpath.2006.050599] [PMID: 16436679]

[56]
Sheikh, A.Q.; Saddouk, F.Z.; Ntokou, A.; Mazurek, R.; Greif, D.M. Cell autonomous and non-cell autonomous regulation of smc progenitors in pulmonary hypertension. Cell Rep.,  2018, 23(4), 1152-1165.
 [http://dx.doi.org/10.1016/j.celrep.2018.03.043] [PMID: 29694892]

[57]
Fadini, G.P.; Avogaro, A.; Ferraccioli, G.; Agostini, C. Endothelial progenitors in pulmonary hypertension: New pathophysiology and therapeutic implications. Eur. Respir. J.,  2010, 35(2), 418-425.
 [http://dx.doi.org/10.1183/09031936.00112809] [PMID: 20123847]

[58]
Wang, X.; Guo, Z.; Ding, Z.; Mehta, J.L. Inflammation, autophagy, and apoptosis after myocardial infarction. J. Am. Heart Assoc.,  2018, 7(9), e008024.
 [http://dx.doi.org/10.1161/JAHA.117.008024] [PMID: 29680826]

[59]
Yuan, K.; Liu, Y.; Zhang, Y.; Nathan, A.; Tian, W.; Yu, J.; Sweatt, A.J.; Shamshou, E.A.; Condon, D.; Chakraborty, A.; Agarwal, S.; Auer, N.; Zhang, S.; Wu, J.C.; Zamanian, R.T.; Nicolls, M.R.; de Jesus Perez, V.A. Mural cell SDF1 signaling is associated with the pathogenesis of pulmonary arterial hypertension. Am. J. Respir. Cell Mol. Biol.,  2020, 62(6), 747-759.
 [http://dx.doi.org/10.1165/rcmb.2019-0401OC] [PMID: 32084325]

[60]
Kumar, R.; Mickael, C.; Kassa, B.; Sanders, L.; Hernandez-Saavedra, D.; Koyanagi, D.E.; Kumar, S.; Pugliese, S.C.; Thomas, S.; McClendon, J.; Maloney, J.P.; Janssen, W.J.; Stenmark, K.R.; Tuder, R.M.; Graham, B.B. Interstitial macrophage-derived thrombospondin-1 contributes to hypoxia-induced pulmonary hypertension. Cardiovasc. Res.,  2020, 116(12), 2021-2030.
 [http://dx.doi.org/10.1093/cvr/cvz304] [PMID: 31710666]

[61]
Bailey, D.M.; Dehnert, C.; Luks, A.M.; Menold, E.; Castell, C.; Schendler, G.; Faoro, V.; Gutowski, M.; Evans, K.A.; Taudorf, S.; James, P.E.; McEneny, J.; Young, I.S.; Swenson, E.R.; Mairbäurl, H.; Bärtsch, P.; Berger, M.M. High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability. J. Physiol.,  2010, 588(23), 4837-4847.
 [http://dx.doi.org/10.1113/jphysiol.2010.194704] [PMID: 20876202]

[62]
Sturrock, A.; Cahill, B.; Norman, K.; Huecksteadt, T.P.; Hill, K.; Sanders, K.; Karwande, S.V.; Stringham, J.C.; Bull, D.A.; Gleich, M.; Kennedy, T.P.; Hoidal, J.R. Transforming growth factor-β1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol.,  2006, 290(4), L661-L673.
 [http://dx.doi.org/10.1152/ajplung.00269.2005] [PMID: 16227320]

[63]
Maston, L.D.; Jones, D.T.; Giermakowska, W.; Resta, T.C.; Ramiro-Diaz, J.; Howard, T.A.; Jernigan, N.L.; Herbert, L.; Maurice, A.A.; Gonzalez Bosc, L.V. Interleukin-6 trans-signaling contributes to chronic hypoxia-induced pulmonary hypertension. Pulm. Circ.,  2018, 8(3), 1-11.
 [http://dx.doi.org/10.1177/2045894018780734] [PMID: 29767573]

[64]
Savale, L.; Tu, L.; Rideau, D.; Izziki, M.; Maitre, B.; Adnot, S.; Eddahibi, S. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice. Respir. Res.,  2009, 10(1), 6.
 [http://dx.doi.org/10.1186/1465-9921-10-6] [PMID: 19173740]

[65]
Pu, X.; Lin, X.; Duan, X.; Wang, J.; Shang, J.; Yun, H.; Chen, Z. Oxidative and endoplasmic reticulum stress responses to chronic high-altitude exposure during the development of high-altitude pulmonary hypertension. High Alt. Med. Biol.,  2020, 21(4), 378-387.
 [http://dx.doi.org/10.1089/ham.2019.0143] [PMID: 33090046]

[66]
Siques, P.; Pena, E.; Brito, J.; El Alam, S. Oxidative stress, kinase activation, and inflammatory pathways involved in effects on smooth muscle cells during pulmonary artery hypertension under hypobaric hypoxia exposure. Front. Physiol.,  2021, 12, 690341.
 [http://dx.doi.org/10.3389/fphys.2021.690341] [PMID: 34434114]

[67]
Zhang, Y.; Talwar, A.; Tsang, D.; Bruchfeld, A.; Sadoughi, A.; Hu, M.; Omonuwa, K.; Cheng, K.F.; Al-Abed, Y.; Miller, E.J. Macrophage migration inhibitory factor mediates hypoxia-induced pulmonary hypertension. Mol. Med.,  2012, 18(2), 215-223.
 [http://dx.doi.org/10.2119/molmed.2011.00094] [PMID: 22113497]

[68]
McGetterick, M.; Peacock, A. Group 3 pulmonary hypertension: Challenges and opportunities. Glob. Cardiol. Sci. Pract.,  2020, 2020(1), e202006.
 [http://dx.doi.org/10.21542/gcsp.2020.6] [PMID: 33150151]

[69]
Kylhammar, D.; Rådegran, G. The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension. Acta Physiol.,  2017, 219(4), 728-756.
 [http://dx.doi.org/10.1111/apha.12749] [PMID: 27381367]

[70]
Sobin, S.S.; Tremer, H.M.; Hardy, J.D.; Chiodi, H.P. Changes in arteriole in acute and chronic hypoxic pulmonary hypertension and recovery in rat. J. Appl. Physiol.,  1983, 55(5), 1445-1455.
 [http://dx.doi.org/10.1152/jappl.1983.55.5.1445] [PMID: 6643182]

[71]
De Cunto, G.; Cardini, S.; Cirino, G.; Geppetti, P.; Lungarella, G.; Lucattelli, M. Pulmonary hypertension in smoking mice over-expressing protease-activated receptor-2. Eur. Respir. J.,  2011, 37(4), 823-834.
 [http://dx.doi.org/10.1183/09031936.00060210] [PMID: 20693251]

[72]
Tuder, R.M.; Petrache, I. Pathogenesis of chronic obstructive pulmonary disease. J. Clin. Invest.,  2012, 122(8), 2749-2755.
 [http://dx.doi.org/10.1172/JCI60324] [PMID: 22850885]

[73]
Barberà, J.A.; Peinado, V.; Santos, S.; Ramirez, J.; Roca, J.; Rodriguez-Roisin, R. Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of smokers. Am. J. Respir. Crit. Care Med.,  2001, 164(4), 709-713.
 [http://dx.doi.org/10.1164/ajrccm.164.4.2101023] [PMID: 11520741]

[74]
Gredic, M.; Wu, C.Y.; Hadzic, S.; Pak, O.; Savai, R.; Kojonazarov, B.; Doswada, S.; Weiss, A.; Weigert, A.; Guenther, A.; Brandes, R.P.; Schermuly, R.T.; Grimminger, F.; Seeger, W.; Sommer, N.; Kraut, S.; Weissmann, N. Myeloid-cell-specific deletion of inducible nitric oxide synthase protects against smoke-induced pulmonary hypertension in mice. Eur. Respir. J.,  2022, 59(4), 2101153.
 [http://dx.doi.org/10.1183/13993003.01153-2021] [PMID: 34475225]

[75]
Liu, X.; Zhang, S.; Wang, X.; Wang, Y.; Song, J.; Sun, C.; Chen, G.; Yang, G.; Tao, Y.; Hu, Y.; Bu, D.; Huang, Y.; Du, J.; Jin, H. Endothelial cell-derived SO2 controls endothelial cell inflammation, smooth muscle cell proliferation, and collagen synthesis to inhibit hypoxic pulmonary vascular remodelling. Oxid. Med. Cell. Longev.,  2021, 2021, 1-14.
 [http://dx.doi.org/10.1155/2021/5577634] [PMID: 33953829]

[76]
Patel, N.M.; Kawut, S.M.; Jelic, S.; Arcasoy, S.M.; Lederer, D.J.; Borczuk, A.C. Pulmonary arteriole gene expression signature in idiopathic pulmonary fibrosis. Eur. Respir. J.,  2013, 41(6), 1324-1330.
 [http://dx.doi.org/10.1183/09031936.0084112] [PMID: 23728404]

[77]
Coccagna, G.; Mantovani, M.; Brignani, F.; Parchi, C.; Lugaresi, E. Continuous recording of the pulmonary and systemic arterial pressure during sleep in syndromes of hypersomnia with periodic breathing. Bull. Physiopathol. Respir.,  1972, 8(5), 1159-1172.
 [PMID: 4348639]

[78]
Ismail, K; Roberts, K; Manning, P; Manley, C; Hill, NS OSA and pulmonary hypertension: Time for a new look. Chest,  2015, 143(7), 847-861.

[79]
Shah, F.A.; Moronta, S.; Braford, M.; Greene, N. Obstructive sleep apnea and pulmonary hypertension: A review of literature. Cureus,  2021, 13(4), e14575.
 [http://dx.doi.org/10.7759/cureus.14575] [PMID: 34035997]

[80]
Phillips, B.G.; Narkiewicz, K.; Pesek, C.A.; Haynes, W.G.; Dyken, M.E.; Somers, V.K. Effects of obstructive sleep apnea on endothelin-1 and blood pressure. J. Hypertens.,  1999, 17(1), 61-66.
 [http://dx.doi.org/10.1097/00004872-199917010-00010] [PMID: 10100095]

[81]
Schulz, R.; Hummel, C.; Heinemann, S.; Seeger, W.; Grimminger, F. Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia. Am. J. Respir. Crit. Care Med.,  2002, 165(1), 67-70.
 [http://dx.doi.org/10.1164/ajrccm.165.1.2101062] [PMID: 11779732]

[82]
Yokoe, T.; Minoguchi, K.; Matsuo, H.; Oda, N.; Minoguchi, H.; Yoshino, G.; Hirano, T.; Adachi, M. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation,  2003, 107(8), 1129-1134.
 [http://dx.doi.org/10.1161/01.CIR.0000052627.99976.18] [PMID: 12615790]

[83]
Cahan, C; Decker, MJ; Arnold, JL; Washington, LH; Veldhuis, JD; Goldwasser, E Diurnal variations in serum erythropoietin levels in healthy subjects and sleep apnea patients. J Appl Physiol ,  1992, 72(6), 2112-2117.

[84]
Rångemark, C.; Hedner, J.A.; Carlson, J.T.; Gleerup, G.; Winther, K. Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients. Sleep,  1995, 18(3), 188-194.
 [http://dx.doi.org/10.1093/sleep/18.3.188] [PMID: 7610315]

[85]
Bokinsky, G.; Miller, M.; Ault, K.; Husband, P.; Mitchell, J. Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure. A preliminary investigation. Chest,  1995, 108(3), 625-630.
 [http://dx.doi.org/10.1378/chest.108.3.625] [PMID: 7656607]

[86]
Behr, J.; Nathan, S.D. Pulmonary hypertension in interstitial lung disease: Screening, diagnosis and treatment. Curr. Opin. Pulm. Med.,  2021, 27(5), 396-404.
 [http://dx.doi.org/10.1097/MCP.0000000000000790] [PMID: 34127619]

[87]
Rahaghi, F.F.; Kolaitis, N.A.; Adegunsoye, A.; de Andrade, J.A.; Flaherty, K.R.; Lancaster, L.H.; Lee, J.S.; Levine, D.J.; Preston, I.R.; Safdar, Z.; Saggar, R.; Sahay, S.; Scholand, M.B.; Shlobin, O.A.; Zisman, D.A.; Nathan, S.D. Screening strategies for pulmonary hypertension in patients with interstitial lung disease. Chest,  2022, 162(1), 145-155.
 [http://dx.doi.org/10.1016/j.chest.2022.02.012] [PMID: 35176276]

[88]
Singh, N.; Dorfmüller, P.; Shlobin, O.A.; Ventetuolo, C.E. Group 3 pulmonary hypertension: From bench to bedside. Circ. Res.,  2022, 130(9), 1404-1422.
 [http://dx.doi.org/10.1161/CIRCRESAHA.121.319970] [PMID: 35482836]

[89]
Yu, S.; Wang, Y.; Fan, Y.; Ma, R.; Wang, Y.; Ye, Q. Pulmonary hypertension in patients with pneumoconiosis with progressive massive fibrosis. Occup. Environ. Med.,  2022, 79(11), 723-728.
 [http://dx.doi.org/10.1136/oemed-2021-108095] [PMID: 35654579]

[90]
Trushenko, N.V.; Suvorova, O.A.; Nekludova, G.V.; Levina, I.A.; Chikina, S.Y.; Nikolenko, A.M.; Tsareva, N.A.; Volkov, A.V.; Yaroshetskiy, A.I.; Merzhoeva, Z.M.; Nuralieva, G.S.; Avdeev, S.N. Predictors of pulmonary hypertension and right ventricular dysfunction in patients with hypersensitivity pneumonitis. Life ,  2023, 13(6), 1348.
 [http://dx.doi.org/10.3390/life13061348] [PMID: 37374130]

[91]
Bush, D.; Galambos, C.; Ivy, D.D.; Abman, S.H.; Wolter-Warmerdam, K.; Hickey, F. Clinical characteristics and risk factors for developing pulmonary hypertension in children with down syndrome. J. Pediatr.,  2018, 202, 212-219.e2.
 [http://dx.doi.org/10.1016/j.jpeds.2018.06.031] [PMID: 30025669]

[92]
Jacob, J.; Bartholmai, B.J.; Rajagopalan, S.; Karwoski, R.; Nair, A.; Walsh, S.L.F.; Barnett, J.; Cross, G.; Judge, E.P.; Kokosi, M.; Renzoni, E.; Maher, T.M.; Wells, A.U. Likelihood of pulmonary hypertension in patients with idiopathic pulmonary fibrosis and emphysema. Respirology,  2018, 23(6), 593-599.
 [http://dx.doi.org/10.1111/resp.13231] [PMID: 29237236]

[93]
Greiner, S.; Jud, A.; Aurich, M.; Hess, A.; Hilbel, T.; Hardt, S.; Katus, H.A.; Mereles, D. Reliability of noninvasive assessment of systolic pulmonary artery pressure by Doppler echocardiography compared to right heart catheterization: Analysis in a large patient population. J. Am. Heart Assoc.,  2014, 3(4), e001103.
 [http://dx.doi.org/10.1161/JAHA.114.001103] [PMID: 25146706]

[94]
D’Andrea, A.; Stanziola, A.; Di Palma, E.; Martino, M.; D’Alto, M.; Dellegrottaglie, S.; Cocchia, R.; Riegler, L.; Betancourt Cordido, M.V.; Lanza, M.; Maglione, M.; Diana, V.; Calabrò, R.; Russo, M.G.; Vannan, M.; Bossone, E. Right ventricular structure and function in idiopathic pulmonary fibrosis with or without pulmonary hypertension. Echocardiography,  2016, 33(1), 57-65.
 [http://dx.doi.org/10.1111/echo.12992] [PMID: 26096076]

[95]
Nowak, J.; Hudzik, B.; Jastrzȩbski, D.; Niedziela, J.T.; Rozentryt, P.; Wojarski, J.; Ochman, M.; Karolak, W.; Żegleń, S.; Gierlotka, M.; Gąsior, M. Pulmonary hypertension in advanced lung diseases: Echocardiography as an important part of patient evaluation for lung transplantation. Clin. Respir. J.,  2018, 12(3), 930-938.
 [http://dx.doi.org/10.1111/crj.12608] [PMID: 28052583]

[96]
Kiely, D.G.; Levin, D.L.; Hassoun, P.M.; Ivy, D.; Jone, P.N.; Bwika, J.; Kawut, S.M.; Lordan, J.; Lungu, A.; Mazurek, J.A.; Moledina, S.; Olschewski, H.; Peacock, A.J.; Puri, G.D.; Rahaghi, F.N.; Schafer, M.; Schiebler, M.; Screaton, N.; Tawhai, M.; van Beek, E.J.R.; Vonk-Noordegraaf, A.; Vandepool, R.; Wort, S.J.; Zhao, L.; Wild, J.M.; Vogel-Claussen, J.; Swift, A.J. Statement on imaging and pulmonary hypertension from the pulmonary vascular research institute (PVRI). Pulm. Circ.,  2019, 9(3), 1-32. Epub ahead of print
 [http://dx.doi.org/10.1177/2045894019841990] [PMID: 30880632]

[97]
Alkukhun, L.; Wang, X.F.; Ahmed, M.K.; Baumgartner, M.; Budev, M.M.; Dweik, R.A.; Tonelli, A.R. Non-invasive screening for pulmonary hypertension in idiopathic pulmonary fibrosis. Respir. Med.,  2016, 117, 65-72.
 [http://dx.doi.org/10.1016/j.rmed.2016.06.001] [PMID: 27492515]

[98]
Yagi, M.; Taniguchi, H.; Kondoh, Y.; Ando, M.; Kimura, T.; Kataoka, K.; Furukawa, T.; Suzuki, A.; Johkoh, T.; Hasegawa, Y. CT -determined pulmonary artery to aorta ratio as a predictor of elevated pulmonary artery pressure and survival in idiopathic pulmonary fibrosis. Respirology,  2017, 22(7), 1393-1399.
 [http://dx.doi.org/10.1111/resp.13066] [PMID: 28488784]

[99]
Remy-Jardin, M.; Ryerson, C.J.; Schiebler, M.L.; Leung, A.N.C.; Wild, J.M.; Hoeper, M.M.; Alderson, P.O.; Goodman, L.R.; Mayo, J.; Haramati, L.B.; Ohno, Y.; Thistlethwaite, P.; van Beek, E.J.R.; Knight, S.L.; Lynch, D.A.; Rubin, G.D.; Humbert, M. Imaging of pulmonary hypertension in adults: A position paper from the Fleischner Society. Eur. Respir. J.,  2021, 57(1), 2004455.
 [http://dx.doi.org/10.1183/13993003.04455-2020] [PMID: 33402372]

[100]
Tan, R.T.; Kuzo, R.; Goodman, L.R.; Siegel, R.; Haasler, G.R.; Presberg, K.W. Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease. Chest,  1998, 113(5), 1250-1256.
 [http://dx.doi.org/10.1378/chest.113.5.1250] [PMID: 9596302]

[101]
Devaraj, A.; Wells, A.U.; Meister, M.G.; Corte, T.J.; Hansell, D.M. The effect of diffuse pulmonary fibrosis on the reliability of CT signs of pulmonary hypertension. Radiology,  2008, 249(3), 1042-1049.
 [http://dx.doi.org/10.1148/radiol.2492080269] [PMID: 19011195]

[102]
Kato, S.; Sekine, A.; Kusakawa, Y.; Ogura, T.; Futaki, M.; Iwasawa, T.; Kirigaya, H.; Gyotoku, D.; Iinuma, N.; Iguchi, K.; Nakachi, T.; Fukui, K.; Kimura, K.; Umemura, S. Prognostic value of cardiovascular magnetic resonance derived right ventricular function in patients with interstitial lung disease. J. Cardiovasc. Magn. Reson.,  2015, 17(1), 10.
 [http://dx.doi.org/10.1186/s12968-015-0113-5] [PMID: 25871501]

[103]
Kamide, H.; Kato, S.; Hayakawa, K.; Fukui, K.; Kitamura, H.; Ogura, T.; Iwasawa, T.; Kimura, K.; Tamura, K.; Utsunomiya, D. Impairment of right ventricular strain evaluated by cardiovascular magnetic resonance feature tracking in patients with interstitial lung disease. Int. J. Cardiovasc. Imaging,  2021, 37(3), 1073-1083.
 [http://dx.doi.org/10.1007/s10554-020-02079-x] [PMID: 33113068]

[104]
Mirza, H.; Hashmi, M.F. Lung ventilation perfusion scan (VQ Scan). In: StatPearls; StatPearls Publishing, 2023. 

[105]
Raghu, G.; Nathan, S.D.; Behr, J.; Brown, K.K.; Egan, J.J.; Kawut, S.M.; Flaherty, K.R.; Martinez, F.J.; Wells, A.U.; Shao, L.; Zhou, H.; Henig, N.; Szwarcberg, J.; Gillies, H.; Montgomery, A.B.; O’Riordan, T.G. Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction. Eur. Respir. J.,  2015, 46(5), 1370-1377.
 [http://dx.doi.org/10.1183/13993003.01537-2014] [PMID: 26250495]

[106]
Nadrous, H.F.; Pellikka, P.A.; Krowka, M.J.; Swanson, K.L.; Chaowalit, N.; Decker, P.A.; Ryu, J.H. Pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Chest,  2005, 128(4), 2393-2399.
 [http://dx.doi.org/10.1378/chest.128.4.2393] [PMID: 16236900]

[107]
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(3), 746-752.
 [http://dx.doi.org/10.1378/chest.129.3.746] [PMID: 16537877]

[108]
Furukawa, T.; Kondoh, Y.; Taniguchi, H.; Yagi, M.; Matsuda, T.; Kimura, T.; Kataoka, K.; Johkoh, T.; Ando, M.; Hashimoto, N.; Sakamoto, K.; Hasegawa, Y. A scoring system to predict the elevation of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis. Eur. Respir. J.,  2018, 51(1), 1701311.
 [http://dx.doi.org/10.1183/13993003.01311-2017] [PMID: 29348178]

[109]
Gläser, S.; Obst, A.; Koch, B.; Henkel, B.; Grieger, A.; Felix, S.B.; Halank, M.; Bruch, L.; Bollmann, T.; Warnke, C.; Schäper, C.; Ewert, R. Pulmonary hypertension in patients with idiopathic pulmonary fibrosis - the predictive value of exercise capacity and gas exchange efficiency. PLoS One,  2013, 8(6), e65643.
 [http://dx.doi.org/10.1371/journal.pone.0065643] [PMID: 23840349]

[110]
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(3), 657-663.
 [http://dx.doi.org/10.1378/chest.06-2485] [PMID: 17356077]

[111]
Swigris, J.J.; Olson, A.L.; Shlobin, O.A.; Ahmad, S.; Brown, K.K.; Nathan, S.D. Heart rate recovery after six-minute walk test predicts pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Respirology,  2011, 16(3), 439-445.
 [http://dx.doi.org/10.1111/j.1440-1843.2010.01877.x] [PMID: 20946337]

[112]
Alhamad, E.H.; Cal, J.G.; Alrajhi, N.N.; Alharbi, W.M. Predictors of mortality in patients with interstitial lung disease-associated pulmonary hypertension. J. Clin. Med.,  2020, 9(12), 3828.
 [http://dx.doi.org/10.3390/jcm9123828] [PMID: 33255999]

[113]
Sun, X.G.; Hansen, J.E.; Oudiz, R.J.; Wasserman, K. Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation,  2001, 104(4), 429-435.
 [http://dx.doi.org/10.1161/hc2901.093198] [PMID: 11468205]

[114]
Boutou, A.K.; Pitsiou, G.G.; Trigonis, I.; Papakosta, D.; Kontou, P.K.; Chavouzis, N.; Nakou, C.; Argyropoulou, P.; Wasserman, K.; Stanopoulos, I. Exercise capacity in idiopathic pulmonary fibrosis: The effect of pulmonary hypertension. Respirology,  2011, 16(3), 451-458.
 [http://dx.doi.org/10.1111/j.1440-1843.2010.01909.x] [PMID: 21122030]

[115]
Gille, T.; Laveneziana, P. Cardiopulmonary exercise testing in interstitial lung diseases and the value of ventilatory efficiency. Eur. Respir. Rev.,  2021, 30(162), 200355.
 [http://dx.doi.org/10.1183/16000617.0355-2020] [PMID: 34853093]

[116]
Degani-Costa, L.H.; Levarge, B.; Digumarthy, S.R.; Eisman, A.S.; Harris, R.S.; Lewis, G.D. Pulmonary vascular response patterns during exercise in interstitial lung disease. Eur. Respir. J.,  2015, 46(3), 738-749.
 [http://dx.doi.org/10.1183/09031936.00191014] [PMID: 25976688]

[117]
Humbert, M.; Kovacs, G.; Hoeper, M.M. ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur. Respir. J., 2022.
 [http://dx.doi.org/10.1183/13993003.00879-2022] [PMID: 36028254]

[118]
Kovacs, G.; Agusti, A.; Barberà, J.A.; Celli, B.; Criner, G.; Humbert, M.; Sin, D.D.; Voelkel, N.; Olschewski, H. Pulmonary vascular involvement in chronic obstructive pulmonary disease. Is there a pulmonary vascular phenotype? Am. J. Respir. Crit. Care Med.,  2018, 198(8), 1000-1011.
 [http://dx.doi.org/10.1164/rccm.201801-0095PP] [PMID: 29746142]

[119]
Deaño, R.C.; Glassner-Kolmin, C.; Rubenfire, M.; Frost, A.; Visovatti, S.; McLaughlin, V.V.; Gomberg-Maitland, M. Referral of patients with pulmonary hypertension diagnoses to tertiary pulmonary hypertension centers: The multicenter RePHerral study. JAMA Intern. Med.,  2013, 173(10), 887-893.
 [http://dx.doi.org/10.1001/jamainternmed.2013.319] [PMID: 23568223]

[120]
Mereles, D.; Ehlken, N.; Kreuscher, S.; Ghofrani, S.; Hoeper, M.M.; Halank, M.; Meyer, F.J.; Karger, G.; Buss, J.; Juenger, J.; Holzapfel, N.; Opitz, C.; Winkler, J.; Herth, F.F.J.; Wilkens, H.; Katus, H.A.; Olschewski, H.; Grünig, E. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation,  2006, 114(14), 1482-1489.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.106.618397] [PMID: 16982941]

[121]
Chan, L.; Chin, L.M.K.; Kennedy, M.; Woolstenhulme, J.G.; Nathan, S.D.; Weinstein, A.A.; Connors, G.; Weir, N.A.; Drinkard, B.; Lamberti, J.; Keyser, R.E. Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension. Chest,  2013, 143(2), 333-343.
 [http://dx.doi.org/10.1378/chest.12-0993] [PMID: 22922554]

[122]
Sajkov, D.; Wang, T.; Saunders, N.A.; Bune, A.J.; DOUGLAS McEVOY, R. Continuous positive airway pressure treatment improves pulmonary hemodynamics in patients with obstructive sleep apnea. Am. J. Respir. Crit. Care Med.,  2002, 165(2), 152-158.
 [http://dx.doi.org/10.1164/ajrccm.165.2.2010092] [PMID: 11790646]

[123]
Alchanatis, M.; Tourkohoriti, G.; Kakouros, S.; Kosmas, E.; Podaras, S.; Jordanoglou, J.B. Daytime pulmonary hypertension in patients with obstructive sleep apnea: The effect of continuous positive airway pressure on pulmonary hemodynamics. Respiration,  2001, 68(6), 566-572.
 [http://dx.doi.org/10.1159/000050574] [PMID: 11786710]

[124]
Timms, R.M.; Khaja, F.U.; Williams, G.W. Hemodynamic response to oxygen therapy in chronic obstructive pulmonary disease. Ann. Intern. Med.,  1985, 102(1), 29-36.
 [http://dx.doi.org/10.7326/0003-4819-102-1-29] [PMID: 3966742]

[125]
Waxman, A.; Restrepo-Jaramillo, R.; Thenappan, T.; Ravichandran, A.; Engel, P.; Bajwa, A.; Allen, R.; Feldman, J.; Argula, R.; Smith, P.; Rollins, K.; Deng, C.; Peterson, L.; Bell, H.; Tapson, V.; Nathan, S.D. Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease. N. Engl. J. Med.,  2021, 384(4), 325-334.
 [http://dx.doi.org/10.1056/NEJMoa2008470] [PMID: 33440084]

[126]
King, T.E., Jr; Behr, J.; Brown, K.K.; du Bois, R.M.; Lancaster, L.; de Andrade, J.A.; Stähler, G.; Leconte, I.; Roux, S.; Raghu, G. BUILD-1: A randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med.,  2008, 177(1), 75-81.
 [http://dx.doi.org/10.1164/rccm.200705-732OC] [PMID: 17901413]

[127]
King, T.E., Jr; Brown, K.K.; Raghu, G.; du Bois, R.M.; Lynch, D.A.; Martinez, F.; Valeyre, D.; Leconte, I.; Morganti, A.; Roux, S.; Behr, J. BUILD-3: A randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med.,  2011, 184(1), 92-99.
 [http://dx.doi.org/10.1164/rccm.201011-1874OC] [PMID: 21474646]

[128]
Raghu, G.; Million-Rousseau, R.; Morganti, A.; Perchenet, L.; Behr, J. Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial. Eur. Respir. J.,  2013, 42(6), 1622-1632.
 [http://dx.doi.org/10.1183/09031936.00104612] [PMID: 23682110]

[129]
Raghu, G.; Behr, J.; Brown, K.K.; Egan, J.J.; Kawut, S.M.; Flaherty, K.R.; Martinez, F.J.; Nathan, S.D.; Wells, A.U.; Collard, H.R.; Costabel, U.; Richeldi, L.; de Andrade, J.; Khalil, N.; Morrison, L.D.; Lederer, D.J.; Shao, L.; Li, X.; Pedersen, P.S.; Montgomery, A.B.; Chien, J.W.; O’Riordan, T.G. Treatment of idiopathic pulmonary fibrosis with ambrisentan: A parallel, randomized trial. Ann. Intern. Med.,  2013, 158(9), 641-649.
 [http://dx.doi.org/10.7326/0003-4819-158-9-201305070-00003] [PMID: 23648946]

[130]
Nathan, S.D.; Behr, J.; Collard, H.R.; Cottin, V.; Hoeper, M.M.; Martinez, F.J.; Corte, T.J.; Keogh, A.M.; Leuchte, H.; Mogulkoc, N.; Ulrich, S.; Wuyts, W.A.; Yao, Z.; Boateng, F.; Wells, A.U. Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): A randomised, placebo-controlled phase 2b study. Lancet Respir. Med.,  2019, 7(9), 780-790.
 [http://dx.doi.org/10.1016/S2213-2600(19)30250-4] [PMID: 31416769]

[131]
Zisman, D.A.; Schwarz, M.; Anstrom, K.J.; Collard, H.R.; Flaherty, K.R.; Hunninghake, G.W. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N. Engl. J. Med.,  2010, 363(7), 620-628.
 [http://dx.doi.org/10.1056/NEJMoa1002110] [PMID: 20484178]

[132]
Behr, J.; Nathan, S.D.; Wuyts, W.A.; Mogulkoc Bishop, N.; Bouros, D.E.; Antoniou, K.; Guiot, J.; Kramer, M.R.; Kirchgaessler, K.U.; Bengus, M.; Gilberg, F.; Perjesi, A.; Harari, S.; Wells, A.U. Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: A double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir. Med.,  2021, 9(1), 85-95.
 [http://dx.doi.org/10.1016/S2213-2600(20)30356-8] [PMID: 32822614]

[133]
Han, M.K.; Bach, D.S.; Hagan, P.G.; Yow, E.; Flaherty, K.R.; Toews, G.B.; Anstrom, K.J.; Martinez, F.J. Sildenafil preserves exercise capacity in patients with idiopathic pulmonary fibrosis and right-sided ventricular dysfunction. Chest,  2013, 143(6), 1699-1708.
 [http://dx.doi.org/10.1378/chest.12-1594] [PMID: 23732584]

[134]
Nathan, S.D.; Flaherty, K.R.; Glassberg, M.K.; Raghu, G.; Swigris, J.; Alvarez, R.; Ettinger, N.; Loyd, J.; Fernandes, P.; Gillies, H.; Kim, B.; Shah, P.; Lancaster, L. A randomized, double-blind, placebo-controlled study of pulsed, inhaled nitric oxide in subjects at risk of pulmonary hypertension associated with pulmonary fibrosis. Chest,  2020, 158(2), 637-645.
 [http://dx.doi.org/10.1016/j.chest.2020.02.016] [PMID: 32092321]

[135]
Nathan, S.D.; Waxman, A.; Rajagopal, S.; Case, A.; Johri, S.; DuBrock, H.; De La Zerda, D.J.; Sahay, S.; King, C.; Melendres-Groves, L.; Smith, P.; Shen, E.; Edwards, L.D.; Nelsen, A.; Tapson, V.F. Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension: A post-hoc analysis of the INCREASE study. Lancet Respir. Med.,  2021, 9(11), 1266-1274.
 [http://dx.doi.org/10.1016/S2213-2600(21)00165-X] [PMID: 34214475]

[136]
Vonbank, K.; Ziesche, R.; Higenbottam, T.W.; Stiebellehner, L.; Petkov, V.; Schenk, P.; Germann, P.; Block, L.H. Controlled prospective randomised trial on the effects on pulmonary haemodynamics of the ambulatory long term use of nitric oxide and oxygen in patients with severe COPD. Thorax,  2003, 58(4), 289-293.
 [http://dx.doi.org/10.1136/thorax.58.4.289] [PMID: 12668787]

[137]
Stolz, D.; Rasch, H.; Linka, A.; Di Valentino, M.; Meyer, A.; Brutsche, M.; Tamm, M. A randomised, controlled trial of bosentan in severe COPD. Eur. Respir. J.,  2008, 32(3), 619-628.
 [http://dx.doi.org/10.1183/09031936.00011308] [PMID: 18448495]

[138]
Valerio, G.; Bracciale, P.; Grazia D’Agostino, A. Effect of bosentan upon pulmonary hypertension in chronic obstructive pulmonary disease. Ther. Adv. Respir. Dis.,  2009, 3(1), 15-21.
 [http://dx.doi.org/10.1177/1753465808103499] [PMID: 19293199]

[139]
Vitulo, P.; Stanziola, A.; Confalonieri, M.; Libertucci, D.; Oggionni, T.; Rottoli, P.; Paciocco, G.; Tuzzolino, F.; Martino, L.; Beretta, M.; Callari, A.; Amaducci, A.; Badagliacca, R.; Poscia, R.; Meloni, F.; Refini, R.M.; Geri, P.; Baldi, S.; Ghio, S.; D’Alto, M.; Argiento, P.; Sofia, M.; Guardamagna, M.; Pezzuto, B.; Vizza, C.D. Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A randomized controlled multicenter clinical trial. J. Heart Lung Transplant.,  2017, 36(2), 166-174.
 [http://dx.doi.org/10.1016/j.healun.2016.04.010] [PMID: 27329400]

[140]
Blanco, I.; Santos, S.; Gea, J.; Güell, R.; Torres, F.; Gimeno-Santos, E.; Rodriguez, D.A.; Vilaró, J.; Gómez, B.; Roca, J.; Barberà, J.A. Sildenafil to improve respiratory rehabilitation outcomes in COPD: a controlled trial. Eur. Respir. J.,  2013, 42(4), 982-992.
 [http://dx.doi.org/10.1183/09031936.00176312] [PMID: 23429918]

[141]
Rao, R.S.; Singh, S.; Sharma, B.B.; Agarwal, V.V.; Singh, V. Sildenafil improves six-minute walk distance in chronic obstructive pulmonary disease: A randomised, double-blind, placebo-controlled trial. Indian J. Chest Dis. Allied Sci.,  2011, 53(2), 81-85.
 [PMID: 21545068]

[142]
Goudie, A.R.; Lipworth, B.J.; Hopkinson, P.J.; Wei, L.; Struthers, A.D. Tadalafil in patients with chronic obstructive pulmonary disease: A randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir. Med.,  2014, 2(4), 293-300.
 [http://dx.doi.org/10.1016/S2213-2600(14)70013-X] [PMID: 24717626]

[143]
Shujaat, A.; Bellardini, J.; Girdhar, A.; Bajwa, A.A. Use of pulmonary arterial hypertension-specific therapy in overweight or obese patients with obstructive sleep apnea and pulmonary hypertension. Pulm. Circ.,  2014, 4(2), 244-249.
 [http://dx.doi.org/10.1086/675987] [PMID: 25006443]

[144]
Ghofrani, H.A.; Wiedemann, R.; Rose, F.; Schermuly, R.T.; Olschewski, H.; Weissmann, N.; Gunther, A.; Walmrath, D.; Seeger, W.; Grimminger, F. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: A randomised controlled trial. Lancet,  2002, 360(9337), 895-900.
 [http://dx.doi.org/10.1016/S0140-6736(02)11024-5] [PMID: 12354470]

[145]
Olschewski, H.; Simonneau, G.; Galiè, N.; Higenbottam, T.; Naeije, R.; Rubin, L.J.; Nikkho, S.; Speich, R.; Hoeper, M.M.; Behr, J.; Winkler, J.; Sitbon, O.; Popov, W.; Ghofrani, H.A.; Manes, A.; Kiely, D.G.; Ewert, R.; Meyer, A.; Corris, P.A.; Delcroix, M.; Gomez-Sanchez, M.; Siedentop, H.; Seeger, W. Inhaled iloprost for severe pulmonary hypertension. N. Engl. J. Med.,  2002, 347(5), 322-329.
 [http://dx.doi.org/10.1056/NEJMoa020204] [PMID: 12151469]

[146]
Hoeper, M.M.; Halank, M.; Wilkens, H.; Günther, A.; Weimann, G.; Gebert, I.; Leuchte, H.H.; Behr, J. Riociguat for interstitial lung disease and pulmonary hypertension: A pilot trial. Eur. Respir. J.,  2013, 41(4), 853-860.
 [http://dx.doi.org/10.1183/09031936.00213911] [PMID: 22936711]

[147]
Corte, T.J.; Gatzoulis, M.A.; Parfitt, L.; Harries, C.; Wells, A.U.; Wort, S.J. The use of sildenafil to treat pulmonary hypertension associated with interstitial lung disease. Respirology,  2010, 15(8), 1226-1232.
 [http://dx.doi.org/10.1111/j.1440-1843.2010.01860.x] [PMID: 20920139]

[148]
Blanco, I.; Gimeno, E.; Munoz, P.A.; Pizarro, S.; Gistau, C.; Rodriguez-Roisin, R.; Roca, J.; Barberà, J.A. 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), 270-278.
 [http://dx.doi.org/10.1164/rccm.200907-0988OC] [PMID: 19875684]

[149]
Barberà, J.A.; Roger, N.; Roca, J.; Rodriguez-Roisin, R.; Rovira, I.; Higenbottam, T.W. Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease. Lancet,  1996, 347(8999), 436-440.
 [http://dx.doi.org/10.1016/S0140-6736(96)90011-2] [PMID: 8618485]

[150]
Lederer, D.J.; Bartels, M.N.; Schluger, N.W.; Brogan, F.; Jellen, P.; Thomashow, B.M.; Kawut, S.M. Sildenafil for chronic obstructive pulmonary disease: A randomized crossover trial. COPD,  2012, 9(3), 268-275.
 [http://dx.doi.org/10.3109/15412555.2011.651180] [PMID: 22360383]

[151]
Pichl, A.; Sommer, N.; Bednorz, M.; Seimetz, M.; Hadzic, S.; Kuhnert, S.; Kraut, S.; Roxlau, E.T.; Kojonazarov, B.; Wilhelm, J.; Gredic, M.; Gall, H.; Tello, K.; Richter, M.J.; Pak, O.; Petrovic, A.; Hecker, M.; Schermuly, R.T.; Grimminger, F.; Seeger, W.; Ghofrani, H.A.; Weissmann, N. Riociguat for treatment of pulmonary hypertension in COPD: A translational study. Eur. Respir. J.,  2019, 53(6), 1802445.
 [http://dx.doi.org/10.1183/13993003.02445-2018] [PMID: 30956210]

[152]
Patel, N.M.; Lederer, D.J.; Borczuk, A.C.; Kawut, S.M. Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest,  2007, 132(3), 998-1006.
 [http://dx.doi.org/10.1378/chest.06-3087] [PMID: 17873194]

[153]
Alhamad, E.H.; Al-Boukai, A.A.; Al-Kassimi, F.A.; Alfaleh, H.F.; Alshamiri, M.Q.; Alzeer, A.H.; Al-Otair, H.A.; Ibrahim, G.F.; Shaik, S.A. Prediction of pulmonary hypertension in patients with or without interstitial lung disease: Reliability of CT findings. Radiology,  2011, 260(3), 875-883.
 [http://dx.doi.org/10.1148/radiol.11103532] [PMID: 21613438]

[154]
Cottin, V.; Nunes, H.; Brillet, P.Y.; Delaval, P.; Devouassoux, G.; Tillie-Leblond, I.; Israel-Biet, D.; Court-Fortune, I.; Valeyre, D.; Cordier, J.F. Combined pulmonary fibrosis and emphysema: A distinct underrecognised entity. Eur. Respir. J.,  2005, 26(4), 586-593.
 [http://dx.doi.org/10.1183/09031936.05.00021005] [PMID: 16204587]

[155]
Cottin, V.; Le Pavec, J.; Prévot, G.; Mal, H.; Humbert, M.; Simonneau, G.; Cordier, J-F. Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome. Eur. Respir. J.,  2010, 35(1), 105-111.
 [http://dx.doi.org/10.1183/09031936.00038709] [PMID: 19643948]

[156]
Mejía, M.; Carrillo, G.; Rojas-Serrano, J.; Estrada, A.; Suárez, 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(1), 10-15.
 [http://dx.doi.org/10.1378/chest.08-2306] [PMID: 19225068]

[157]
Ryerson, C.J.; Hartman, T.; Elicker, B.M.; Ley, B.; Lee, J.S.; Abbritti, M.; Jones, K.D.; King, T.E., Jr; Ryu, J.; Collard, H.R. Clinical features and outcomes in combined pulmonary fibrosis and emphysema in idiopathic pulmonary fibrosis. Chest,  2013, 144(1), 234-240.
 [http://dx.doi.org/10.1378/chest.12-2403] [PMID: 23370641]

[158]
Tomioka, H.; Mamesaya, N.; Yamashita, S.; Kida, Y.; Kaneko, M.; Sakai, H. Combined pulmonary fibrosis and emphysema: Effect of pulmonary rehabilitation in comparison with chronic obstructive pulmonary disease. BMJ Open Respir. Res.,  2016, 3(1), e000099.
 [http://dx.doi.org/10.1136/bmjresp-2015-000099] [PMID: 26933506]

[159]
Launay, D.; Montani, D.; Hassoun, P.M.; Cottin, V.; Le Pavec, J.; Clerson, P.; Sitbon, O.; Jaïs, X.; Savale, L.; Weatherald, J.; Sobanski, V.; Mathai, S.C.; Shafiq, M.; Cordier, J.F.; Hachulla, E.; Simonneau, G.; Humbert, M. Clinical phenotypes and survival of pre-capillary pulmonary hypertension in systemic sclerosis. PLoS One,  2018, 13(5), e0197112.
 [http://dx.doi.org/10.1371/journal.pone.0197112] [PMID: 29763468]

[160]
Saggar, R.; Giri, P.C.; Deng, C.; Johnson, D.; McCloy, M.K.; Liang, L.; Shaikh, F.; Hong, J.; Channick, R.N.; Shapiro, S.S.; Lynch, J.P., III; Belperio, J.A.; Weigt, S.S.; Ramsey, A.L.; Ross, D.J.; Sayah, D.M.; Shino, M.Y.; Derhovanessian, A.; Sherman, A.E.; Saggar, R. Significance of autoimmune disease in severe pulmonary hypertension complicating extensive pulmonary fibrosis: A prospective cohort study. Pulm. Circ.,  2021, 11(2), 1-12.
 [http://dx.doi.org/10.1177/20458940211011329] [PMID: 33996029]

[161]
Chen, W.; Thomas, J.; Sadatsafavi, M.; FitzGerald, J.M. Risk of cardiovascular comorbidity in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis. Lancet Respir. Med.,  2015, 3(8), 631-639.
 [http://dx.doi.org/10.1016/S2213-2600(15)00241-6] [PMID: 26208998]

[162]
Lepida, D.; Papathanasiou, A.; Galiatsou, E.; Nakos, G.; Goudevenos, I.; Koulouras, V. The contribution of left heart disease in COPD patients with pulmonary hypertension. Hellenic J. Cardiol.,  2018, 59(3), 160-165.
 [http://dx.doi.org/10.1016/j.hjc.2018.02.001] [PMID: 29471029]

[163]
Faludi, R.; Hajdu, M.; Vértes, V.; Nógrádi, Á.; Varga, N.; Illés, M.B.; Sárosi, V.; Alexy, G.; Komócsi, A. Diastolic dysfunction is a contributing factor to exercise intolerance in COPD. COPD,  2016, 13(3), 345-351.
 [http://dx.doi.org/10.3109/15412555.2015.1084614] [PMID: 26682932]

[164]
Blanco, I.; Tura-Ceide, O.; Peinado, V.; Barberà, J.A. Updated perspectives on pulmonary hypertension in COPD. Int. J. Chron. Obstruct. Pulmon. Dis.,  2020, 15, 1315-1324.
 [http://dx.doi.org/10.2147/COPD.S211841] [PMID: 32606641]

[165]
Hoeper, M.M.; Dwivedi, K.; Pausch, C.; Lewis, R.A.; Olsson, K.M.; Huscher, D.; Pittrow, D.; Grünig, E.; Staehler, G.; Vizza, C.D.; Gall, H.; Distler, O.; Opitz, C.; Gibbs, J.S.R.; Delcroix, M.; Park, D.H.; Ghofrani, H.A.; Ewert, R.; Kaemmerer, H.; Kabitz, H.J.; Skowasch, D.; Behr, J.; Milger, K.; Lange, T.J.; Wilkens, H.; Seyfarth, H.J.; Held, M.; Dumitrescu, D.; Tsangaris, I.; Vonk-Noordegraaf, A.; Ulrich, S.; Klose, H.; Claussen, M.; Eisenmann, S.; Schmidt, K.H.; Swift, A.J.; Thompson, A.A.R.; Elliot, C.A.; Rosenkranz, S.; Condliffe, R.; Kiely, D.G.; Halank, M. Phenotyping of idiopathic pulmonary arterial hypertension: A registry analysis. Lancet Respir. Med.,  2022, 10(10), 937-948.
 [http://dx.doi.org/10.1016/S2213-2600(22)00097-2] [PMID: 35777416]

[166]
Girard, A.; Jouneau, S.; Chabanne, C.; Khouatra, C.; Lannes, M.; Traclet, J.; Turquier, S.; Delaval, P.; Cordier, J.F.; Cottin, V. Severe pulmonary hypertension associated with COPD: Hemodynamic improvement with specific therapy. Respiration,  2015, 90(3), 220-228.
 [http://dx.doi.org/10.1159/000431380] [PMID: 26277885]

[167]
Vizza, C.D.; Hoeper, M.M.; Huscher, D.; Pittrow, D.; Benjamin, N.; Olsson, K.M.; Ghofrani, H.A.; Held, M.; Klose, H.; Lange, T.; Rosenkranz, S.; Dumitrescu, D.; Badagliacca, R.; Claussen, M.; Halank, M.; Vonk-Noordegraaf, A.; Skowasch, D.; Ewert, R.; Gibbs, J.S.R.; Delcroix, M.; Skride, A.; Coghlan, G.; Ulrich, S.; Opitz, C.; Kaemmerer, H.; Distler, O.; Grünig, E. Pulmonary hypertension in patients with COPD. Chest,  2021, 160(2), 678-689.
 [http://dx.doi.org/10.1016/j.chest.2021.02.012] [PMID: 33581097]

[168]
Tanabe, N.; Taniguchi, H.; Tsujino, I.; Sakamaki, F.; Emoto, N.; Kimura, H.; Takamura, K.; Hanaoka, M.; Nishimura, M.; Tatsumi, K. Multi-institutional retrospective cohort study of patients with severe pulmonary hypertension associated with respiratory diseases. Respirology,  2015, 20(5), 805-812.
 [http://dx.doi.org/10.1111/resp.12530] [PMID: 25828844]

[169]
Brewis, M.J.; Church, A.C.; Johnson, M.K.; Peacock, A.J. Severe pulmonary hypertension in lung disease: Phenotypes and response to treatment. Eur. Respir. J.,  2015, 46(5), 1378-1389.
 [http://dx.doi.org/10.1183/13993003.02307-2014] [PMID: 26293503]

[170]
Abuserewa, S.T.; Selim, A.; Youssef, A.; Zolty, R. Role of selexipag in chronic obstructive pulmonary disease (COPD) patients with out-of-proportion pulmonary hypertension. Cureus,  2021, 13(7), e16520.
 [http://dx.doi.org/10.7759/cureus.16520] [PMID: 34430131]

[171]
Calcaianu, G.; Canuet, M.; Schuller, A.; Enache, I.; Chaouat, A.; Kessler, R. Pulmonary arterial hypertension-specific drug therapy in COPD patients with severe pulmonary hypertension and mild-to-moderate airflow limitation. Respiration,  2016, 91(1), 9-17.
 [http://dx.doi.org/10.1159/000441304] [PMID: 26492415]

[172]
Chaouat, A.; Naeije, R.; Weitzenblum, E. Pulmonary hypertension in COPD. Eur. Respir. J.,  2008, 32(5), 1371-1385.
 [http://dx.doi.org/10.1183/09031936.00015608] [PMID: 18978137]

[173]
Hoeper, M.M.; Humbert, M.; Souza, R.; Idrees, M.; Kawut, S.M.; Sliwa-Hahnle, K.; Jing, Z.C.; Gibbs, J.S.R. A global view of pulmonary hypertension. Lancet Respir. Med.,  2016, 4(4), 306-322.
 [http://dx.doi.org/10.1016/S2213-2600(15)00543-3] [PMID: 26975810]

[174]
Kovacs, G.; Avian, A.; Bachmaier, G.; Troester, N.; Tornyos, A.; Douschan, P.; Foris, V.; Sassmann, T.; Zeder, K.; Lindenmann, J.; Brcic, L.; Fuchsjaeger, M.; Agusti, A.; Olschewski, H. Severe pulmonary hypertension in COPD. Chest,  2022, 162(1), 202-212.
 [http://dx.doi.org/10.1016/j.chest.2022.01.031] [PMID: 35092746]

[175]
Dournes, G.; Laurent, F.; Coste, F.; Dromer, C.; Blanchard, E.; Picard, F.; Baldacci, F.; Montaudon, M.; Girodet, P.O.; Marthan, R.; Berger, P. Computed tomographic measurement of airway remodeling and emphysema in advanced chronic obstructive pulmonary disease. Correlation with pulmonary hypertension. Am. J. Respir. Crit. Care Med.,  2015, 191(1), 63-70.
 [http://dx.doi.org/10.1164/rccm.201408-1423OC] [PMID: 25393421]

[176]
Hurdman, J.; Condliffe, R.; Elliot, C.A.; Swift, A.; Rajaram, S.; Davies, C.; Hill, C.; Hamilton, N.; Armstrong, I.J.; Billings, C.; Pollard, L.; Wild, J.M.; Lawrie, A.; Lawson, R.; Sabroe, I.; Kiely, D.G. Pulmonary hypertension in COPD: Results from the ASPIRE registry. Eur. Respir. J.,  2013, 41(6), 1292-1301.
 [http://dx.doi.org/10.1183/09031936.00079512] [PMID: 23018917]

[177]
Chaouat, A.; Bugnet, A.S.; Kadaoui, N.; Schott, R.; Enache, I.; Ducoloné, A.; Ehrhart, M.; Kessler, R.; Weitzenblum, E. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.,  2005, 172(2), 189-194.
 [http://dx.doi.org/10.1164/rccm.200401-006OC] [PMID: 15831842]

[178]
Humbert, M.; McLaughlin, V.; Gibbs, J.S.R.; Gomberg-Maitland, M.; Hoeper, M.M.; Preston, I.R.; Souza, R.; Waxman, A.; Escribano Subias, P.; Feldman, J.; Meyer, G.; Montani, D.; Olsson, K.M.; Manimaran, S.; Barnes, J.; Linde, P.G.; de Oliveira Pena, J.; Badesch, D.B. Sotatercept for the treatment of pulmonary arterial hypertension. N. Engl. J. Med.,  2021, 384(13), 1204-1215.
 [http://dx.doi.org/10.1056/NEJMoa2024277] [PMID: 33789009]

[179]
Hoeper, M.M.; Badesch, D.B.; Ghofrani, H.A.; Gibbs, J.S.R.; Gomberg-Maitland, M.; McLaughlin, V.V.; Preston, I.R.; Souza, R.; Waxman, A.B.; Grünig, E.; Kopeć, G.; Meyer, G.; Olsson, K.M.; Rosenkranz, S.; Xu, Y.; Miller, B.; Fowler, M.; Butler, J.; Koglin, J.; de Oliveira Pena, J.; Humbert, M. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N. Engl. J. Med.,  2023, 388(16), 1478-1490.
 [http://dx.doi.org/10.1056/NEJMoa2213558] [PMID: 36877098]

[180]
Humbert, M.; McLaughlin, V.; Gibbs, J.S.R.; Gomberg-Maitland, M.; Hoeper, M.M.; Preston, I.R.; Souza, R.; Waxman, A.B.; Ghofrani, H.A.; Escribano Subias, P.; Feldman, J.; Meyer, G.; Montani, D.; Olsson, K.M.; Manimaran, S.; de Oliveira Pena, J.; Badesch, D.B. Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension. Eur. Respir. J.,  2023, 61(1), 2201347.
 [http://dx.doi.org/10.1183/13993003.01347-2022] [PMID: 36041750]

[181]
Qaiser, K.N.; Tonelli, A.R. Novel treatment pathways in pulmonary arterial hypertension. Methodist DeBakey Cardiovasc. J.,  2021, 17(2), 29.
 [http://dx.doi.org/10.14797/CBHS2234] [PMID: 34326930]

[182]
Ghofrani, H.A.; Morrell, N.W.; Hoeper, M.M.; Olschewski, H.; Peacock, A.J.; Barst, R.J.; Shapiro, S.; Golpon, H.; Toshner, M.; Grimminger, F.; Pascoe, S. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am. J. Respir. Crit. Care Med.,  2010, 182(9), 1171-1177.
 [http://dx.doi.org/10.1164/rccm.201001-0123OC] [PMID: 20581169]

[183]
Janssen, W.; Schymura, Y.; Novoyatleva, T.; Kojonazarov, B.; Boehm, M.; Wietelmann, A.; Luitel, H.; Murmann, K.; Krompiec, D.R.; Tretyn, A.; Pullamsetti, S.S.; Weissmann, N.; Seeger, W.; Ghofrani, H.A.; Schermuly, R.T. 5-HT2B receptor antagonists inhibit fibrosis and protect from RV heart failure. BioMed Res. Int.,  2015, 2015, 1-8.
 [http://dx.doi.org/10.1155/2015/438403] [PMID: 25667920]

[184]
Wu, D.; Lee, D.; Sung, Y.K. Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: A review. Respir. Res.,  2011, 12(1), 45.
 [http://dx.doi.org/10.1186/1465-9921-12-45] [PMID: 21477377]

[185]
Hamidi, S.A.; Lin, R.Z.; Szema, A.M.; Lyubsky, S.; Jiang, Y.P.; Said, S.I. VIP and endothelin receptor antagonist: An effective combination against experimental pulmonary arterial hypertension. Respir. Res.,  2011, 12(1), 141.
 [http://dx.doi.org/10.1186/1465-9921-12-141] [PMID: 22029879]

[186]
Tofovic, S.P.; Jackson, E.K. Estradiol metabolism: Crossroads in pulmonary arterial hypertension. Int. J. Mol. Sci.,  2019, 21(1), 116.
 [http://dx.doi.org/10.3390/ijms21010116] [PMID: 31877978]

[187]
Kawut, S.M.; Archer-Chicko, C.L.; DeMichele, A.; Fritz, J.S.; Klinger, J.R.; Ky, B.; Palevsky, H.I.; Palmisciano, A.J.; Patel, M.; Pinder, D.; Propert, K.J.; Smith, K.A.; Stanczyk, F.; Tracy, R.; Vaidya, A.; Whittenhall, M.E.; Ventetuolo, C.E. Anastrozole in pulmonary arterial hypertension. A randomized, double-blind, placebo-controlled trial. Am. J. Respir. Crit. Care Med.,  2017, 195(3), 360-368.
 [http://dx.doi.org/10.1164/rccm.201605-1024OC] [PMID: 27602993]

[188]
Houssaini, A.; Abid, S.; Mouraret, N.; Wan, F.; Rideau, D.; Saker, M.; Marcos, E.; Tissot, C.M.; Dubois-Randé, J.L.; Amsellem, V.; Adnot, S. Rapamycin reverses pulmonary artery smooth muscle cell proliferation in pulmonary hypertension. Am. J. Respir. Cell Mol. Biol.,  2013, 48(5), 568-577.
 [http://dx.doi.org/10.1165/rcmb.2012-0429OC] [PMID: 23470622]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/011573398X266440240408080251	Print ISSN 1573-398X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6387
Current Respiratory Medicine Reviews

Pulmonary Hypertension Associated with Chronic Lung Disease

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
