Update on Pediatric Pulmonary Arterial Hypertension

Saji, Tsutomu

doi:10.1253/circj.cj-13-1180

Cited by 16 publications

(7 citation statements)

References 60 publications

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“…Estimated incidence rates for IPAH vary from 0.47 to 1–2 cases per million children, with estimated prevalence rates from 2.1 to 4.4 cases per million children [5–9].…”

Section: Updates In Paediatric Ph Epidemiology and Classificationmentioning

confidence: 99%

Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management

et al. 2019

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Paediatric pulmonary arterial hypertension (PAH) shares common features of adult disease, but is associated with several additional disorders and challenges that require unique approaches. This article discusses recent advances, ongoing challenges and distinct approaches for the care of children with PAH, as presented by the Paediatric Task Force of the 6th World Symposium on Pulmonary Hypertension. We provide updates of the current definition, epidemiology, classification, diagnostics and treatment of paediatric PAH, and identify critical knowledge gaps. Several features of paediatric PAH including the prominence of neonatal PAH, especially in pre-term infants with developmental lung diseases, and novel genetic causes of paediatric PAH are highlighted. The use of cardiac catheterisation as a diagnostic modality and haemodynamic definitions of PAH, including acute vasoreactivity, are addressed. Updates are provided on issues related to utility of the previous classification system to reflect paediatric-specific aetiologies and approaches to medical and interventional management of PAH, including the Potts shunt. Although a lack of clinical trial data for the use of PAH-targeted therapy persists, emerging data are improving the identification of appropriate targets for goal-oriented therapy in children. Such data will likely improve future clinical trial design to enhance outcomes in paediatric PAH.

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“…Estimated incidence rates for IPAH vary from 0.47 to 1–2 cases per million children, with estimated prevalence rates from 2.1 to 4.4 cases per million children [5–9].…”

Section: Updates In Paediatric Ph Epidemiology and Classificationmentioning

confidence: 99%

Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management

et al. 2019

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“…Pediatric PAH differs from the adult-onset disease in several important aspects, including sex bias, clinical presentation, etiology, and response to therapy [ 7 , 8 , 9 ]. The frequency of PAH is ~3–4-fold higher in females relative to males for adult-onset disease.…”

Section: Introductionmentioning

confidence: 99%

Genetics and Genomics of Pediatric Pulmonary Arterial Hypertension

Welch

Chung

2020

Genes

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Pulmonary arterial hypertension (PAH) is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors and likely gene–environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to ~42% of pediatric-onset PAH compared to ~12.5% of adult-onset PAH. De novo variants are frequently associated with PAH in children and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, increased etiologic heterogeneity, poorer prognosis, and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

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“…Prognosis has been poor because of the eventual development of right heart failure caused by progression of pulmonary vascular resistance [2]. The recent development of disease-modifying drugs such as the prostaglandin I 2 analogs, endothelin receptor antagonists, and phosphodiesterase type-5 inhibitors has dramatically improved outcomes for patients with pulmonary arterial hypertension (PAH); however, most patients still develop chronic right heart failure, for which the only curative treatment is lung transplantation [3]. …”

Section: Introductionmentioning

confidence: 99%

Implication of overexpression of dishevelled-associated activator of morphogenesis 1 (Daam-1) for the pathogenesis of human Idiopathic Pulmonary Arterial Hypertension (IPAH)

et al. 2017

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BackgroundIdiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis. Evidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell polarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins—namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated activator of morphogenesis 1 (Daam-1)—in pulmonary arteries.MethodsWe analyzed sections of formalin-fixed and paraffin-embedded autopsied lung tissues obtained from 9 IPAH cases, 7 associated pulmonary arterial hypertension cases, and 16 age-matched controls without pulmonary arterial abnormalities. Results of microscopic observation were analyzed in relation to the cellular components and size of pulmonary arteries.ResultsVarying rates of positive reactivity to Dvl-2 and Daam-1 were confirmed in all cellular components of pulmonary arteries, namely, endothelial cells, myofibroblasts, and medial smooth muscle cells. In contrast, none of these components was reactive to Wnt-11. No specific expression patterns were observed for endothelial cells or myofibroblasts under any experimental conditions. However, marked expression of Dvl-2 and Daam-1 was confirmed in smooth muscle cells. In addition, Dvl-2 was depleted while Daam-1 expression was elevated in IPAH, in contrast with specimens from associated pulmonary arterial hypertension cases and controls.ConclusionsHigh Daam-1 expression may upregulate the Wnt/PCP pathway and cause IPAH.

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Update on Pediatric Pulmonary Arterial Hypertension

Cited by 16 publications

References 60 publications

Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management

Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management

Genetics and Genomics of Pediatric Pulmonary Arterial Hypertension

Implication of overexpression of dishevelled-associated activator of morphogenesis 1 (Daam-1) for the pathogenesis of human Idiopathic Pulmonary Arterial Hypertension (IPAH)

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