Pulmonary hypertension in bronchopulmonary dysplasia: Clinical findings, cardiovascular anomalies and outcomes

Cerro, María Jesús del; Sabaté-Rotés, Anna; Cartón, Antonio J.; Deiros, Lucía; Bret, M; Cordeiro, Malaika; Verdú, Cristina; Barrios, Maria Isabel; Albajara, Luis; Gutiérrez-Larraya, Federico

doi:10.1002/ppul.22797

Cited by 160 publications

(130 citation statements)

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“…Currently, premature birth is the leading cause of death in children under the age of 5 years, affecting 1 in 10 births and representing z15 million births per year worldwide (1)(2)(3)(4). In its most severe form, BPD can result in secondary cardiovascular sequelae such as pulmonary hypertension (PH) that persist into adulthood and abnormal ventilatory response (5)(6)(7)(8)(9)(10). Despite advances in clinical ventilator management, the introduction of surfactant, and antenatal glucocorticoids, there is a marked lack of adjunctive therapies.…”

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confidence: 99%

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

Lee

Lal

Persad

et al. 2016

Am J Respir Cell Mol Biol

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Myeloid cells are key factors in the progression of bronchopulmonary dysplasia (BPD) pathogenesis. Endothelial monocyte-activating polypeptide II (EMAP II) mediates myeloid cell trafficking. The origin and physiological mechanism by which EMAP II affects pathogenesis in BPD is unknown. The objective was to determine the functional consequences of elevated EMAP II levels in the pathogenesis of murine BPD and to investigate EMAP II neutralization as a therapeutic strategy. Three neonatal mouse models were used: (1) BPD (hyperoxia), (2) EMAP II delivery, and (3) BPD with neutralizing EMAP II antibody treatments. Chemokinic function of EMAP II and its neutralization were assessed by migration in vitro and in vivo. We determined the location of EMAP II by immunohistochemistry, pulmonary proinflammatory and chemotactic gene expression by quantitative polymerase chain reaction and immunoblotting, lung outcome by pulmonary function testing and histological analysis, and right ventricular hypertrophy by Fulton's Index. In BPD, EMAP II initially is a bronchial clubcell-specific protein-derived factor that later is expressed in galectin-3 1 macrophages as BPD progresses. Continuous elevated expression corroborates with baboon and human BPD. Prolonged elevation of EMAP II levels recruits galectin-3 1 macrophages, which is followed by an inflammatory state that resembles a severe BPD phenotype characterized by decreased pulmonary compliance, arrested alveolar development, and signs of pulmonary hypertension. In vivo pharmacological EMAP II inhibition suppressed proinflammatory genes Tnfa, Il6, and Il1b and chemotactic genes Ccl2 and Ccl9 and reversed the severe BPD phenotype. EMAP II is sufficient to induce macrophage recruitment, worsens BPD progression, and represents a targetable mechanism of BPD development.

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confidence: 99%

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

Lee

Lal

Persad

et al. 2016

Am J Respir Cell Mol Biol

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“…Del Cerro el al evaluó 29 pacientes con DBP, en los cuales se le realizó TC a 21 pacientes y cateterización cardiaca a 14, evidenciándose anomalías cardiovasculares en 2/3 de los pacientes, incluyendo colaterales aortopulmonares, estenosis de vena pulmonar, ductus arterioso persistente y defecto de septum atrial, algunas de estas difíciles de evaluar o pesquisar por medio de la ecocardiografía. Estos autores recomiendan su uso en todo RN que persista con HP moderada o severa a los 2 meses de vida 10 .…”

Section: Tomografía Computada (Tc)unclassified

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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“…This occurs in several settings: idiopathic, in prematurely born infants with bronchopulmonary dysplasia, after surgical repair of anomalously connected pulmonary veins (including those not obstructed at time of repair), in patients with congenital heart defects without anomalous pulmonary vein connection, and under other circumstances. 19,20,[23][24][25] It seems unlikely that a single stenotic pulmonary vein can cause significant PH, 26 although manifest obstruction of one or more pulmonary veins in one lung can exist with occult obstruction of small veins in the contralateral lung, and additional obstructed veins can develop over time. 27 ii) Pulmonary veno-occlusive disease.…”

Section: Causes Of Pvhmentioning

confidence: 99%

Pulmonary Hypertension Caused by Pulmonary Venous Hypertension

Kulik

2014

Pulm. circ.

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The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is extraordinarily variable, ranging from no impact on pulmonary vascular resistance (PVR) to a marked increase. The reasons for this are unknown. Both acutely reversible pulmonary vasoconstriction and pathological remodeling (especially medial hypertrophy and intimal hyperplasia) account for increased PVR when present. The mechanisms involved in vasoconstriction and remodeling are not clearly defined, but increased wall stress, especially in small pulmonary arteries, presumably plays an important role. Myogenic contraction may account for increased vascular tone and also indirectly stimulate remodeling of the vessel wall. Increased wall stress may also directly cause smooth muscle growth, migration, and intimal hyperplasia. Even long-standing and severe pulmonary hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an important clinical problem, especially because PVH due to left ventricular noncompliance lacks definitive therapy. The role of targeted PH therapy in patients with PVH-PH is unclear at this time. Most prospective studies indicate that these medications are not helpful or worse, but there is ample reason to think that a subset of patients with PVH-PH may benefit from phosphodiesterase inhibitors or other agents. A different approach to evaluating possible pharmacologic therapy for PVH-PH may be required to better define its possible utility.Keywords: pulmonary hypertension, pulmonary venous hypertension. As a perfect example of how clinical imperative can drive basic physiological investigation, studies of the effect of pulmonary venous hypertension (PVH) on the lung's circulation were in full swing by the very early 1950s, 1 close on the heels of the development of surgical relief of mitral valve stenosis. Cardiac catheterization of patients with mitral valve disease has characterized the physiology of PVH, and histological investigations demonstrated the microvascular changes provoked by PVH. Just as important, the effect of relief of left atrial (LA) hypertension on the circulation has been extensively reported, usually for patients who have had mitral valve intervention. We have learned that the circulatory alterations provoked by PVH share some characteristics with other forms of pulmonary hypertension (PH), such as the idiopathic variety, PH due to chronic alveolar hypoxia, and PH secondary to congenital cardiac shunting lesions. For example, acute "reactivity" to vasodilators may be observed, and there is overlap in the microarchitectural abnormalities seen. On the other hand, the "natural history" of PVH-PH is very different than that of the idiopathic variety or that seen with shunting defects: in the former (as demonstrated with mitral valve disease), PH is likely to largely or completely resolve if PVH is relieved, even with long-standing and severely increased pulmonary vascular resistance (PVR), 2,3 while in the latter two, PH is more likely to inexorably increase. PVH-PH is ther...

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Pulmonary hypertension in bronchopulmonary dysplasia: Clinical findings, cardiovascular anomalies and outcomes

Cited by 160 publications

References 37 publications

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

El rol de la hipertensión pulmonar en la displasia broncopulmonar

Pulmonary Hypertension Caused by Pulmonary Venous Hypertension

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