Pulmonary Artery Hypertension in Formerly Premature Infants With Bronchopulmonary Dysplasia: Clinical Features and Outcomes in the Surfactant Era

Khemani, Ekta; McElhinney, Doff B.; Rhein, Lawrence; Andrade, Olyn; Lacro, Ronald V.; Thomas, Kristin C.; Mullen, Mary P.

doi:10.1542/peds.2007-0971

Cited by 490 publications

(488 citation statements)

References 36 publications

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“…1 However, little evidence exists to support pharmacological management of PH in pulmonary disorders. 2 Medications that target the nitric oxide (NO) signaling pathway have been approved for use in adults, but these medications have not been approved or even extensively tested in PH that arises in infancy.…”

Section: Introductionmentioning

confidence: 99%

Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits?

et al. 2011

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Objective: The objective of this study is to determine the effects that sildenafil citrate has on gas exchange in infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH).Study Design: A retrospective review was performed from 2005 to 2009. Infants treated with sildenafil citrate for greater than 48 h were included. Standard patient data was collected, including echocardiogram, inspired oxygen and systemic blood pressure, before and during administration of sildenafil citrate.Result: Sildenafil citrate was used in 21 preterm infants with BPDassociated PH. A significant reduction in estimated right ventricular peak systolic pressure was seen after initiation of sildenafil citrate, with the majority of infants showing no improvement in gas exchange at 48 h of treatment. Four infants died during treatment. Conclusion:Sildenafil citrate reduced estimated pulmonary artery pressures, but this reduction was not reflected in improved gas exchange within the first 48 h.

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Section: Introductionmentioning

confidence: 99%

Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits?

et al. 2011

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“…PH is often associated with severe BPD. Despite widespread availability and use of pulmonary vasodilators such as nitric oxide, the mortality rate of infants with BPD complicated by PH continues to remain as high as 50% (3,38). Therapeutic agents that target distinct pathogenic mechanisms of pulmonary vascular remodeling and growth in severe BPD may provide additional relief on PH and decrease mortality.…”

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confidence: 99%

Inhibition of β-catenin signaling protects against CTGF-induced alveolar and vascular pathology in neonatal mouse lung

et al. 2016

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Background: Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease of premature infants. Connective tissue growth factor (CTGF) plays an important role in tissue development and remodeling. We have previously shown that targeted overexpression of CTGF in alveolar type II epithelial cells results in BPD-like pathology and activates β-catenin in neonatal mice. Methods: Utilizing this transgenic mouse model and ICG001, a specific pharmacological inhibitor of β-catenin, we tested the hypothesis that β-catenin signaling mediates the effects of CTGF in the neonatal lung. Newborn CTGF mice and control littermates received ICG001 (10 mg/kg/dose) or placebo (dimethyl sulfoxide, equal volume) by daily i.p. injection from postnatal day 5 to 15. Alveolarization, vascular development, and pulmonary hypertension (PH) were analyzed. results: Administration of ICG001 significantly downregulated expression of cyclin D1, collagen 1a1, and fibronectin, which are the known target genes of β-catenin signaling in CTGF lungs. Inhibition of β-catenin signaling improved alveolar and vascular development and decreased pulmonary vascular remodeling. More importantly, the improved vascular development and vascular remodeling led to a decrease in PH. conclusion: β-Catenin signaling mediates the autocrine and paracrine effects of CTGF in the neonatal lung. Inhibition of CTGF-β-catenin signaling may provide a novel therapy for BPD. INTRODUCTIONBronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease of premature infants (1). Over the past four decades, the incidence of this disease has significantly increased as a result of improved survival of extremely-low-birthweight infants (2). The pathology of BPD is increasingly being recognized as a developmental arrest of the immature lung caused by injurious stimuli such as mechanical ventilation, oxygen exposure, and intrauterine or postnatal infections. Larger and simplified alveoli, decreased vascular growth, and variable interstitial fibrosis are the key pathological features observed in lungs of infants who died of BPD (1). The combination of decreased vascular growth and excessive pulmonary vascular remodeling leads to pulmonary hypertension (PH) which significantly contributes to the morbidity and mortality of these infants (3). Yet, the underlying cellular and molecular mechanisms are poorly defined, and there is no effective therapy.Connective tissue growth factor (CTGF) is a matricellular protein that plays an important role in tissue development and remodeling (4). Recent studies have highlighted the potential role of CTGF in BPD development and progression. The clinical association of CTGF with BPD is best established by studies demonstrating increased CTGF concentrations in bronchoalveolar lavage fluid from preterm infants developing BPD (5) and increased CTGF expression in lung tissues of infants who died of BPD (6). Multiple studies have examined the potential role of CTGF in experimental BPD and demonstrated that increased CTG...

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“…Estudios recientes sugieren que la presencia de HP se asocia con mayor morbimortalidad en pacientes con DBP, evidenciándose una tasa de mortalidad de 33%-48% a los 2 años del diagnóstico de HP, y que esta es más frecuente mientras más severa sea la DBP 5 . Debido a esto, la realización de un tamizaje de rutina podría ser útil para identificar esta patología en aquella población de alto riesgo.…”

Section: Evaluaciónunclassified

“…En algunos estudios se ha demostrado que la presencia de HP conlleva un aumento de la mortalidad en los pacientes portadores de DBP, llegando ésta hasta un 48% a los 2 años en pacientes diagnosticados con esta asociación 5 .…”

Section: Introductionunclassified

El rol de la hipertensión pulmonar en la displasia broncopulmonar

Valenzuela

Moya

Luco

et al. 2017

Rev. chil. pediatr.

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Palabras clave: Displasia broncopulmonar, Hipertensión pulmonar, enfermedad pulmonar crónica, recién nacido prematuro ResumenHace 50 años Northway describió la Displasia Broncopulmonar (DBP), en nacidos de pretérmino expuestos a ventilación mecánica. Desde entonces, ha aumentado la sobrevida de ellos; sin embargo, ha aparecido una "nueva DBP" y la incidencia de esta no ha disminuido. Una de las características de esta patología es la remodelación vascular anómala, que en su expresión más severa se conoce como Hipertensión Pulmonar (HP); con una incidencia de 17%, que es proporcional a la severidad de la DBP (33% en DBP severa); y como un factor de mortalidad (hasta un 48% mortalidad a 2 años con HP por DBP). Debido a esto resulta importante conocer los métodos diagnósticos y alternativas terapéuticas, tema que se discute en esta revisión. Considerando la alta mortalidad de la asociación HP-DBP, adquiere importancia una estrategia de tamizaje en la población de riesgo. El gold standard para el diagnóstico de HP es el cateterismo cardíaco, sin embargo, el ecocardiograma transtorácico es una herramienta útil para el tamizaje y diagnóstico de HP en pacientes displásicos, con mediciones cuantitativas y cambios cualitativos en la evaluación diagnóstica. A nivel sanguíneo el péptido natriurético tipo B (BNP), ha mostrado ser útil en el seguimiento; en cuanto a imágenes, la tomografía computarizada se utiliza en casos severos. En cuanto a las terapias, se han propuesto el óxido nítrico inhalado como vasodilatador pulmonar, los inhibidores de la fosfodiesterasas -sildenafil-, los antagonistas de la endotelina -bosentán-y los análogos de prostaciclinas -iloprost-. Aún no se cuenta con evidencia de alta calidad para su uso, dosis y duración del tratamiento, pero hay variadas experiencias clínicas. Además, es relevante el cuidado interdisciplinario, destacando optimizar la nutrición. El desafío es lograr una prevención efectiva de la DBP y de sus complicaciones. Un protocolo de tamizaje de HP debe asociarse a una estratificación de riesgo y directrices de tratamiento.

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Pulmonary Artery Hypertension in Formerly Premature Infants With Bronchopulmonary Dysplasia: Clinical Features and Outcomes in the Surfactant Era

Abstract: Premature infants with bronchopulmonary dysplasia and severe pulmonary artery hypertension are at high risk of death, particularly during the first 6 months after diagnosis of pulmonary artery hypertension.

Cited by 490 publications

References 36 publications

Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits?

Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits?

Inhibition of β-catenin signaling protects against CTGF-induced alveolar and vascular pathology in neonatal mouse lung

El rol de la hipertensión pulmonar en la displasia broncopulmonar

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