Primary pulmonary hypertension in children: Clinical characterization and survival

Sandoval, Julio; Bauerle, Otto; Gómez, Arturo; Palomar, Andrés; Guerra, María Luisa Martínez; Furuya, María E.Y.

doi:10.1016/0735-1097(94)00391-3

Cited by 123 publications

(64 citation statements)

References 32 publications

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“…Over the past decade, several studies have highlighted successful clinical strategies in the management of children with severe PAH. 136 This may in part be related to the striking physiologic observation by Barst et al 137 and Sandoval et al, 138 which demonstrated that the acute pulmonary vascular response to vasodilators is more common in younger patients than adults (40% in children vs 20% in adults). These findings support the hypothesis that despite past reports of a higher mortality in children than adult patients if untreated, children with IPAH can do quite well with long-term vasodilator therapy.…”

Section: Childrenmentioning

confidence: 92%

Medical Therapy For Pulmonary Arterial Hypertension

Badesch

Abman

Ahearn

et al. 2004

Chest

546

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Section: Childrenmentioning

confidence: 92%

Medical Therapy For Pulmonary Arterial Hypertension

Badesch

Abman

Ahearn

et al. 2004

Chest

546

View full text Add to dashboard Cite

“…The prevalence of acute vasoreactivity is higher in children than in adults, allowing a higher proportion of children to be treated effectively with calcium channel blocker therapy [13][14][15]. In children with IPAH, BARST et al [13] showed that 5-yr survival rates improved significantly in 31 acute vasoreactive responders treated with calcium channel blockers compared with 43 nonresponders (p50.0002).…”

Section: Calcium Channel Blockersmentioning

confidence: 99%

Paediatric pulmonary hypertension: monitoring progress and identifying unmet needs

Beghetti¹

2009

Eur Respir Rev

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Recent advances in the field of pulmonary hypertension (PH) have provided clinicians with a range of treatment options, but effective disease management in children presents a unique challenge. The present article will discuss the steps being taken to address unmet needs in paediatric PH.Understanding the epidemiology of paediatric PH is essential to guide management decisions, but such epidemiological data are scarce. The first international paediatric PH registry, Tracking Outcomes in Paediatric Pulmonary Hypertension (TOPP), promises to become a vital resource.Studies of PH therapies are rare in children, and treatment of paediatric PH is generally guided by the adult treatment algorithm, with some adaptations. However, invasive management options, such as continuous prostacyclin infusion, even if effective, are challenging in children, and further research is required to develop appropriate treatment strategies, formulations and doses for paediatric PH. Measures of treatment success must also be defined, and the applicability of endpoints from adult clinical studies remains an open question.In summary, further epidemiological and treatment data are needed for paediatric pulmonary hypertension. The international TOPP registry will provide a valuable insight, but this must be complemented by research and development of adapted paediatric therapies. Dedicated childhood pulmonary hypertension services would optimise the diagnosis and management of this life-threatening disease.

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“…Untreated, median survival from diagnosis is 2.6 years in adults (1) and 10 months in children (2). Therapeutic interventions include prostacyclin, endothelin antagonists, and phosphodiesterase type 5 inhibitors, all of which improve hemodynamics, exercise tolerance, and clinical status (3).…”

mentioning

confidence: 99%

Smooth Muscle Proliferation and Role of the Prostacyclin (IP) Receptor in Idiopathic Pulmonary Arterial Hypertension

Falcetti¹,

Hall²,

Phillips³

et al. 2010

Am J Respir Crit Care Med

120

129

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Rationale: Prostacyclin analogs, used to treat idiopathic pulmonary arterial hypertension (IPAH), are assumed to work through prostacyclin (IP) receptors linked to cyclic AMP (cAMP) generation, although the potential to signal through peroxisome proliferatoractivated receptor-g (PPARg) exists. Objectives: IP receptor and PPARg expression may be depressed in IPAH. We wished to determine if pathways remain functional and if analogs continue to inhibit smooth muscle proliferation. Methods: We used Western blotting to determine IP receptor expression in peripheral pulmonary arterial smooth muscle cells (PASMCs) from normal and IPAH lungs and immunohistochemistry to evaluate IP receptor and PPARg expression in distal arteries. Measurements and Main Results: Cell proliferation and cAMP assays assessed analog responses in human and mouse PASMCs and HEK-293 cells. Proliferative rates of IPAH cells were greater than normal human PASMCs. IP receptor protein levels were lower in PASMCs from patients with IPAH, but treprostinil reduced replication and treprostinil-induced cAMP elevation appeared normal. Responses to prostacyclin analogs were largely dependent on the IP receptor and cAMP in normal PASMCs, although in IP 2/2 receptor cells analogs inhibited growth in a cAMP-independent, PPARg-dependent manner. In IPAH cells, antiproliferative responses to analogs were insensitive to IP receptor or adenylyl cyclase antagonists but were potentiated by a PPARg agonist and inhibited (z 60%) by the PPARg antagonist GW9662. This coincided with increased PPARg expression in the medial layer of acinar arteries. Conclusions: The antiproliferative effects of prostacyclin analogs are preserved in IPAH despite IP receptor down-regulation and abnormal coupling. PPARg may represent a previously unrecognized pathway by which these agents inhibit smooth muscle proliferation.

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Primary pulmonary hypertension in children: Clinical characterization and survival

Cited by 123 publications

References 32 publications

Medical Therapy For Pulmonary Arterial Hypertension

Medical Therapy For Pulmonary Arterial Hypertension

Paediatric pulmonary hypertension: monitoring progress and identifying unmet needs

Smooth Muscle Proliferation and Role of the Prostacyclin (IP) Receptor in Idiopathic Pulmonary Arterial Hypertension

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