A Nationwide multicenter registry and biobank program for deep phenotyping of idiopathic and hereditary pulmonary arterial hypertension in Korea: the PAH platform for deep phenotyping in Korean subjects (PHOENIKS) cohort

Albert Youngwoo Jang, Sungseek Kim, Su Jung Park, Hanul Choi, Pyung Chun Oh, Seyeon Oh, Kyung-Hee Kim, Kye Hun Kim, Kyunghee Byun, Wook-Jin Chung, PHOENIKS Investigators, Wook-Jin Chung, Kyung-Hee Kim, Kye Hun Kim, In-Cheol Kim, Gee Hee Kim, Gi-Beom Kim, Jae-Hyeong Park, Jung-Woo Son, Jong-Min Song, Sang Jae Rhee, Ju-Hee Lee, Jo Won Jung, Hae Ok Jung, Goo-Yeong Cho, Jeong Hyun Choi, Sun-Hwa Lee, Soo Yong Lee, Albert Youngwoo Jang, Sungseek Kim, Su Jung Park, Hanul Choi, Pyung Chun Oh, Seyeon Oh, Kyung-Hee Kim, Kye Hun Kim, Kyunghee Byun, Wook-Jin Chung, PHOENIKS Investigators, Wook-Jin Chung, Kyung-Hee Kim, Kye Hun Kim, In-Cheol Kim, Gee Hee Kim, Gi-Beom Kim, Jae-Hyeong Park, Jung-Woo Son, Jong-Min Song, Sang Jae Rhee, Ju-Hee Lee, Jo Won Jung, Hae Ok Jung, Goo-Yeong Cho, Jeong Hyun Choi, Sun-Hwa Lee, Soo Yong Lee

Abstract

Background: Pulmonary arterial hypertension (PAH) is a progressive, chronic disease without curative treatment. Large registry data of these patient populations have been published, although, phenotypic variants within each subtype of PAH have not been elucidated. As interest towards personalized medicine grows, the need for a PAH cohort with a comprehensive understanding of patient phenotypes through multiomics approaches, called deep phenotyping, is on the rise. The PAH Platform for Deep Phenotyping in Korean Subjects (PHOENIKS) cohort is designed to collect clinical data as well as biological specimens for deep phenotyping in patients with idiopathic PAH (IPAH) and heritable PAH (HPAH) in Korea.

Methods: A total of 17 regional hospitals are currently working on enrolling up to 100 consecutive IPAH/HPAH patients for obtaining clinical data and biological specimens across Korea. The diagnosis of PAH is based on right heart catheterization. All clinical data is stored in a government-based online database. Each participating hospitals collect a whole blood sample from each patient, through which DNA, RNA, serum, plasma, and peripheral blood mononuclear cells will be extracted from the buffy coat layer for further multiomics analysis.

Results: Not applicable.

Conclusions: The PHOENIKS cohort is enrolling IPAH and HPAH patients across Korea to determine the prognosis and drug response in different phenotypic variant. The data generated by this cohort are expected to open new doors for personalized medicine in PAH patients of South Korea.

Trial registration: ClinicalTrials.gov NCT03933579. Registered on May 1st, 2019.

Keywords: Blood bank, registries; Precision medicine; Pulmonary arterial hypertension.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

References

    1. Hoeper MM, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–D50. doi: 10.1016/j.jacc.2013.10.032.
    1. Hoeper MM, et al. A global view of pulmonary hypertension. Lancet Respir Med. 2016;4(4):306–322. doi: 10.1016/S2213-2600(15)00543-3.
    1. Hoeper MM, et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol. 2013;168(2):871–880. doi: 10.1016/j.ijcard.2012.10.026.
    1. McGoon MD, Miller DP. REVEAL: a contemporary US pulmonary arterial hypertension registry. Eur Respir Rev. 2012;21(123):8–18. doi: 10.1183/09059180.00008211.
    1. Chung WJ, et al. Baseline characteristics of the Korean registry of pulmonary arterial hypertension. J Korean Med Sci. 2015;30(10):1429–1438. doi: 10.3346/jkms.2015.30.10.1429.
    1. Jing ZC, et al. Registry and survival study in chinese patients with idiopathic and familial pulmonary arterial hypertension. Chest. 2007;132(2):373–379. doi: 10.1378/chest.06-2913.
    1. Delude CM. Deep phenotyping: the details of disease. Nature. 2015;527(7576):S14–S15. doi: 10.1038/527S14a.
    1. Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation. 1987;76(1):135–141. doi: 10.1161/01.CIR.76.1.135.
    1. Rhee RL, et al. Comparison of treatment response in idiopathic and connective tissue disease-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2015;192(9):1111–1117. doi: 10.1164/rccm.201507-1456OC.
    1. Sweatt AJ, et al. Discovery of distinct immune phenotypes using machine learning in pulmonary arterial hypertension. Circ Res. 2019;124(6):904–919. doi: 10.1161/CIRCRESAHA.118.313911.
    1. Hemnes AR, et al. Critical genomic networks and Vasoreactive variants in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2016;194(4):464–475. doi: 10.1164/rccm.201508-1678OC.
    1. Graf S, Bleda M, Haddinapola C, Haimel M, Bogaard HJ, Coglan G, Corris PA, Gibbs JS, Humbert M, Kiely DG, Laurie A, Machado RD, Peacock AJ, Pepke Zaba J, Toshner M, Trembath RC, Noordegraaf AV, Wharton J, Wilkins M, Wort SJ, Morrell NW, and on behalf of the NIHR BioResource – Rare Diseases(BRIDGE) PAH Consortium , and the UK National PAH Cohort Study Consortium, Whole Genome Sequencing in Idiopathic and Familial Pulmonary Arterial Hypertension Reveals Causal Rare Coding and Non-coding Sequence Variation. in: vascular disease session title: dickinson w. richards memorial lecture. Circulation, 2018. . Accessed 10 July 2019.
    1. Nichols WC, Pauciulo MW, Lutz K, Winslow C, Walsworth A, Gygi A, Marsolo K, Harley JB, Martin LJ National Biologic Sample and Data Repository for PAH Update. in: c58. Clinical pulmonary vascular disease. Am J Respir Crit Care Med, 2015. . Accessed 10 July 2019.
    1. Simonneau Gérald, Montani David, Celermajer David S., Denton Christopher P., Gatzoulis Michael A., Krowka Michael, Williams Paul G., Souza Rogerio. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. European Respiratory Journal. 2019;53(1):1801913. doi: 10.1183/13993003.01913-2018.
    1. Humbert M, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122(2):156–163. doi: 10.1161/CIRCULATIONAHA.109.911818.
    1. Ling Y, et al. Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland. Am J Respir Crit Care Med. 2012;186(8):790–796. doi: 10.1164/rccm.201203-0383OC.
    1. Benza RL, et al. Endothelin-1 pathway polymorphisms and outcomes in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2015;192(11):1345–1354. doi: 10.1164/rccm.201501-0196OC.
    1. Rhodes CJ, et al. Plasma metabolomics implicates modified transfer RNAs and altered bioenergetics in the outcomes of pulmonary arterial hypertension. Circulation. 2017;135(5):460–475. doi: 10.1161/CIRCULATIONAHA.116.024602.
    1. Li M, et al. Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1. Circulation. 2016;134(15):1105–1121. doi: 10.1161/CIRCULATIONAHA.116.023171.
    1. Caruso P, et al. Identification of MicroRNA-124 as a major regulator of enhanced endothelial cell glycolysis in pulmonary arterial hypertension via PTBP1 (Polypyrimidine tract binding protein) and pyruvate kinase M2. Circulation. 2017;136(25):2451–2467. doi: 10.1161/CIRCULATIONAHA.117.028034.
    1. Lau EMT, et al. Epidemiology and treatment of pulmonary arterial hypertension. Nat Rev Cardiol. 2017;14(10):603–614. doi: 10.1038/nrcardio.2017.84.
    1. Savale Laurent, Guignabert Christophe, Weatherald Jason, Humbert Marc. Precision medicine and personalising therapy in pulmonary hypertension: seeing the light from the dawn of a new era. European Respiratory Review. 2018;27(148):180004. doi: 10.1183/16000617.0004-2018.
    1. Satoh Kimio, Kikuchi Nobuhiro, Satoh Taijyu, Kurosawa Ryo, Sunamura Shinichiro, Siddique Mohammad, Omura Junichi, Yaoita Nobuhiro, Shimokawa Hiroaki. Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension. International Journal of Molecular Sciences. 2018;19(12):4081. doi: 10.3390/ijms19124081.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren