Pub Date : 2020-01-01DOI: 10.1007/978-3-030-52787-7_6
B. Levarge, D. Montani, M. Humbert
{"title":"Pulmonary Veno-occlusive Disease and Pulmonary Capillary Hemangiomatosis","authors":"B. Levarge, D. Montani, M. Humbert","doi":"10.1007/978-3-030-52787-7_6","DOIUrl":"https://doi.org/10.1007/978-3-030-52787-7_6","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82735530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01DOI: 10.1007/978-3-030-52787-7_9
H. Ford, Ahmed Sesay, E. Sonntag, S. Krishnan
{"title":"Sarcoidosis-Associated Pulmonary Hypertension","authors":"H. Ford, Ahmed Sesay, E. Sonntag, S. Krishnan","doi":"10.1007/978-3-030-52787-7_9","DOIUrl":"https://doi.org/10.1007/978-3-030-52787-7_9","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73006780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa5049
Camilla Udjus, B. Halvorsen, P. Aukrust, G. Christensen, O. Skjønsberg, K. Larsen
Background: Pulmonary hypertension is a serious complication to chronic lung diseases, often with alveolar hypoxia. Mechanisms for hypoxia-induced pulmonary hypertension are suggested to be initial vasoconstriction, followed by inflammation, proliferation of smooth muscle cells (SMCs) and fibrosis in pulmonary arteries. Elevated levels of Interleukin (IL)-18, IL-1β and IL-6 are found in patients with pulmonary hypertension. IL-18 and IL-1β are proinflammatory cytokines activated by the enzyme caspase-1. We have documented that caspase-1 deficient mice have reduced hypoxia-induced pulmonary hypertension and reduced muscularization in pulmonary arteries compared to wild-type (WT) mice. Objective: To study mechanisms of SMC proliferation in hypoxic pulmonary hypertension initiated by the enzyme caspase-1. Methods: Pulmonary arteries from WT and caspase-1-/- mice were harvested and grown “ex vivo”. Human SMCs were exposed to hypoxia and treated with caspase-1 inhibitor. Proliferation of SMCs was measured by cell count, BrdU incorporation, Ki67 and cyclin D1 mRNA. Results: Caspase-1 abrogated arteries showed reduced SMC proliferation, together with lowered levels of IL-18, IL-1β and IL-6. Supply of IL-18 or IL-1β rescued SMC proliferation in caspase-1 deficient arteries, and the level of IL-6 protein was restored. Hypoxic stimulation of human SMCs showed increased BrdU incorporation and Ki67 protein levels, indicating hypoxia-induced cell proliferation. Cell count, BrdU incorporation and cyclin D1 mRNA levels were reduced by adding a caspase-1 inhibitor. Conclusions: The enzyme caspase-1 regulates smooth muscle cell proliferation through IL-18/IL-1β and IL-6, being novel targets in pulmonary hypertension.
{"title":"Caspase-1 triggers smooth muscle cell proliferation in hypoxic pulmonary hypertension","authors":"Camilla Udjus, B. Halvorsen, P. Aukrust, G. Christensen, O. Skjønsberg, K. Larsen","doi":"10.1183/13993003.congress-2019.pa5049","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5049","url":null,"abstract":"Background: Pulmonary hypertension is a serious complication to chronic lung diseases, often with alveolar hypoxia. Mechanisms for hypoxia-induced pulmonary hypertension are suggested to be initial vasoconstriction, followed by inflammation, proliferation of smooth muscle cells (SMCs) and fibrosis in pulmonary arteries. Elevated levels of Interleukin (IL)-18, IL-1β and IL-6 are found in patients with pulmonary hypertension. IL-18 and IL-1β are proinflammatory cytokines activated by the enzyme caspase-1. We have documented that caspase-1 deficient mice have reduced hypoxia-induced pulmonary hypertension and reduced muscularization in pulmonary arteries compared to wild-type (WT) mice. Objective: To study mechanisms of SMC proliferation in hypoxic pulmonary hypertension initiated by the enzyme caspase-1. Methods: Pulmonary arteries from WT and caspase-1-/- mice were harvested and grown “ex vivo”. Human SMCs were exposed to hypoxia and treated with caspase-1 inhibitor. Proliferation of SMCs was measured by cell count, BrdU incorporation, Ki67 and cyclin D1 mRNA. Results: Caspase-1 abrogated arteries showed reduced SMC proliferation, together with lowered levels of IL-18, IL-1β and IL-6. Supply of IL-18 or IL-1β rescued SMC proliferation in caspase-1 deficient arteries, and the level of IL-6 protein was restored. Hypoxic stimulation of human SMCs showed increased BrdU incorporation and Ki67 protein levels, indicating hypoxia-induced cell proliferation. Cell count, BrdU incorporation and cyclin D1 mRNA levels were reduced by adding a caspase-1 inhibitor. Conclusions: The enzyme caspase-1 regulates smooth muscle cell proliferation through IL-18/IL-1β and IL-6, being novel targets in pulmonary hypertension.","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74424545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa4749
Peter Smith, C. Watkins, K. Kraft, M. Grant
Rationale: United Therapeutics is developing a new drug-device product comprising a dry powder formulation of treprostinil inhalation powder (TreT) and a small, portable, dry powder inhaler, to treat pulmonary arterial hypertension (PAH). Objectives: The primary objective was to evaluate the pharmacokinetics (PK), safety and tolerability of TreT in healthy normal volunteers (HNVs). Methods: This was an open-label, single ascending dose study in 36 HNVs, assigned to 6 single dose cohorts of TreT (30, 60, 90, 120, 150, and 180 µg). Safety and tolerability of TreT was evaluated in each cohort prior to escalating the dose for the next cohort. Blood samples were obtained before TreT administration and at selected times through 480 minutes post‑dose. Blood samples were analyzed for treprostinil using a validated analytical method and PK parameters were calculated using noncompartmental methods. Results: A total of 36 HNVs were randomized and dosed. There were no severe adverse events (AEs), serious AEs, or deaths during the study. No AEs led to a subject’s early termination. The most frequently reported AEs were cough (n=11, 30.6%) and headache (n=8, 22.2%). Bioanalysis confirmed that the treprostinil plasma concentrations and exposure for TreT, achieved clinically relevant concentrations comparable to those observed in historical Tyvaso single dose clinical studies. Cmax and AUC for treprostinil, increased in a linear manner with increasing dose. Conclusion: Overall, TreT was safe and well-tolerated and produced clinically relevant concentrations of treprostinil when inhaled as a dry powder.
{"title":"A phase 1, single-center, open-label, dose-rising clinical trial to evaluate the pharmacokinetics, safety and tolerability of treprostinil inhalation powder (TreT) in healthy normal volunteers","authors":"Peter Smith, C. Watkins, K. Kraft, M. Grant","doi":"10.1183/13993003.congress-2019.pa4749","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa4749","url":null,"abstract":"Rationale: United Therapeutics is developing a new drug-device product comprising a dry powder formulation of treprostinil inhalation powder (TreT) and a small, portable, dry powder inhaler, to treat pulmonary arterial hypertension (PAH). Objectives: The primary objective was to evaluate the pharmacokinetics (PK), safety and tolerability of TreT in healthy normal volunteers (HNVs). Methods: This was an open-label, single ascending dose study in 36 HNVs, assigned to 6 single dose cohorts of TreT (30, 60, 90, 120, 150, and 180 µg). Safety and tolerability of TreT was evaluated in each cohort prior to escalating the dose for the next cohort. Blood samples were obtained before TreT administration and at selected times through 480 minutes post‑dose. Blood samples were analyzed for treprostinil using a validated analytical method and PK parameters were calculated using noncompartmental methods. Results: A total of 36 HNVs were randomized and dosed. There were no severe adverse events (AEs), serious AEs, or deaths during the study. No AEs led to a subject’s early termination. The most frequently reported AEs were cough (n=11, 30.6%) and headache (n=8, 22.2%). Bioanalysis confirmed that the treprostinil plasma concentrations and exposure for TreT, achieved clinically relevant concentrations comparable to those observed in historical Tyvaso single dose clinical studies. Cmax and AUC for treprostinil, increased in a linear manner with increasing dose. Conclusion: Overall, TreT was safe and well-tolerated and produced clinically relevant concentrations of treprostinil when inhaled as a dry powder.","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77272447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.oa496
D. Kiely, A. Swift, Marcella Cogliano, L. Kendall, C. Oram, D. Capener, A. Rothman, P. Garg, C. Johns, M. Austin, J. Pickworth, P. Hickey, Tony Kahn, A. Lawrie, R. Condliffe, Fred Wilson, J. Wild
{"title":"A prospective study comparing the repeatability and sensitivity to change of non-invasive endpoints in pulmonary arterial hypertension: the RESPIRE study","authors":"D. Kiely, A. Swift, Marcella Cogliano, L. Kendall, C. Oram, D. Capener, A. Rothman, P. Garg, C. Johns, M. Austin, J. Pickworth, P. Hickey, Tony Kahn, A. Lawrie, R. Condliffe, Fred Wilson, J. Wild","doi":"10.1183/13993003.congress-2019.oa496","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.oa496","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85100299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1436
N. Braams, O. Spruijt, F. Oosterveer, B. Westerhof, A. Noordegraaf, L. Meijboom, F. S. D. Man, H. Bogaard
{"title":"Right ventricular-arterial coupling in chronic thromboembolic pulmonary hypertension patients during exercise","authors":"N. Braams, O. Spruijt, F. Oosterveer, B. Westerhof, A. Noordegraaf, L. Meijboom, F. S. D. Man, H. Bogaard","doi":"10.1183/13993003.congress-2019.pa1436","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1436","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77994561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1423
A. Alqarni, O. Brand, A. Pasini, Abdulrhman Alghamdi, Wael Alshehri, Mushabbab A Alahmari, L. Pang
{"title":"Role of vasoactive mediators on cigarette smoke extract (CSE)-induced proliferation in human pulmonary artery smooth muscle cells (hPASMCs)","authors":"A. Alqarni, O. Brand, A. Pasini, Abdulrhman Alghamdi, Wael Alshehri, Mushabbab A Alahmari, L. Pang","doi":"10.1183/13993003.congress-2019.pa1423","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1423","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81303445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa1439
F. Rashidi, R. Parvizi, Eisa Bilejani, Ata Koohi
{"title":"Outcome of pulmonary thromboendarterectomy in chronic thromboembolic disease with normal hemodynamic: is it time to change the definition of CTEPH","authors":"F. Rashidi, R. Parvizi, Eisa Bilejani, Ata Koohi","doi":"10.1183/13993003.congress-2019.pa1439","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa1439","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86285108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.oa499
K. Olsson, M. Richter, J. Kamp, H. Gall, A. Heine, H. Ghofrani, J. Fuge, R. Ewert, M. Hoeper
{"title":"Risk assessment and prognosis in patients with pulmonary arterial hypertension receiving intravenous treprostinil","authors":"K. Olsson, M. Richter, J. Kamp, H. Gall, A. Heine, H. Ghofrani, J. Fuge, R. Ewert, M. Hoeper","doi":"10.1183/13993003.congress-2019.oa499","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.oa499","url":null,"abstract":"","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86468631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-28DOI: 10.1183/13993003.congress-2019.pa5467
H. Shimokawahara, H. Matsubara, K. Hayashi, T. Nishihara, M. Tsuji, T. Naito, M. Shigetoshi, I. Tabuchi, M. Munemasa
Background: Pulmonary arterial hypertension (PAH) has a poor prognosis despite the available therapeutic options. Normalization of hemodynamics would be needed to obtain the good prognosis. Aims and Objectives: We aimed to investigate the determinants in PAH patients for normalization of hemodynamics only with oral drugs. Methods: We retrospectively reviewed 190 patients with PAH treated at a single referral center. Hemodynamic parameters were investigated before and after treatments. All the patients were divided into a good control group with mean pulmonary arterial pressure (mPAP)＜30mmHg and a poor control group with mPAP≧30mmHg at follow-up. Results: Eighty-two patients were idiopathic/heritable, 65 patients were connective tissue disease, 22 patients congenital heart disease and 21 patients were portal hypertension. mPAP decreased significantly from baseline to follow-up (51±18.7 mmHg to 34.1±15.2 mmHg, p Conclusions: To achieve normalization of hemodynamics in PAH, parenteral prostanoid should be used in cases with baseline mPAP exceeding 40mmHg.
{"title":"Therapeutic limitations of oral medications to normalize hemodynamics in patients with pulmonary artery hypertension","authors":"H. Shimokawahara, H. Matsubara, K. Hayashi, T. Nishihara, M. Tsuji, T. Naito, M. Shigetoshi, I. Tabuchi, M. Munemasa","doi":"10.1183/13993003.congress-2019.pa5467","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5467","url":null,"abstract":"Background: Pulmonary arterial hypertension (PAH) has a poor prognosis despite the available therapeutic options. Normalization of hemodynamics would be needed to obtain the good prognosis. Aims and Objectives: We aimed to investigate the determinants in PAH patients for normalization of hemodynamics only with oral drugs. Methods: We retrospectively reviewed 190 patients with PAH treated at a single referral center. Hemodynamic parameters were investigated before and after treatments. All the patients were divided into a good control group with mean pulmonary arterial pressure (mPAP)＜30mmHg and a poor control group with mPAP≧30mmHg at follow-up. Results: Eighty-two patients were idiopathic/heritable, 65 patients were connective tissue disease, 22 patients congenital heart disease and 21 patients were portal hypertension. mPAP decreased significantly from baseline to follow-up (51±18.7 mmHg to 34.1±15.2 mmHg, p Conclusions: To achieve normalization of hemodynamics in PAH, parenteral prostanoid should be used in cases with baseline mPAP exceeding 40mmHg.","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90486343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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