Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis.

BackgroundIn extremely premature infants, postnatal growth restriction (PNGR) is common and increases the risk of developing bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). Mechanisms by which poor nutrition impacts lung development are unknown, but alterations in the gut microbiota appear to play a role. In a rodent model, PNGR plus hyperoxia causes BPD and PH and increases intestinal Enterobacteriaceae, Gram-negative organisms that stimulate Toll-like receptor 4 (TLR4). We hypothesized that intestinal dysbiosis activates intestinal TLR4 triggering systemic inflammation which impacts lung development.MethodsRat pups were assigned to litters of 17 (PNGR) or 10 (normal growth) at birth and exposed to room air or 75% oxygen for 14 days. Half of the pups were treated with the TLR4 inhibitor TAK-242 from birth or beginning at day 3. After 14 days, pulmonary arterial pressure was evaluated by echocardiography and hearts were examined for right ventricular hypertrophy (RVH). Lungs and serum samples were analyzed by western blotting and immunohistochemistry.ResultsPostnatal growth restriction + hyperoxia increased pulmonary arterial pressure and RVH with trends toward increased plasma IL1β and decreased IκBα, the inhibitor of NFκB, in lung tissue. Treatment with the TLR4 inhibitor attenuated PH and inflammation.ConclusionPostnatal growth restriction induces an increase in intestinal Enterobacteriaceae leading to PH. Activation of the TLR4 pathway is a promising mechanism by which intestinal dysbiosis impacts the developing lung

Surveillance sanitaire des cocoteraies adultes en Afrique de l'Ouest. I. Contrôles ordinaires

La plupart des ravageurs connus dans les cocoteraies d'Afrique de l'Ouest passent le plus souvent inaperçus, bien qu'ils soient toujours présents. Dans certaines conditions, difficiles à définir, il y a pullulation d'un ou de plusieurs d'entre eux et, en conséquence, des dégâts importants peuvent alors se produire. Des contrôles sanitaires fréquents sont nécessaires pour la conduite de la méthode de lutte intégrée, généralement adoptée à présent en défense des cultures, ce qui suppose une bonne connaissance des ravageurs, de leur biologie et de leurs ennemis naturels. Comme pour le palmier à huile, il y a deux types de contrôles phytosanitaires : - les contrôles ordinaires, décrits dans ces " Conseils ", qui permettent de suivre l'ensemble des populations de ravageurs, d'insectes auxiliaires, et de détecter toute anomalie susceptible de se traduire par des dégâts préjudiciables ; - les contrôles spéciaux, spécifiques d'un ravageur donné, qui feront l'objet d'une autre page de Pratique agricole (1 ), et sont réalisés sur un échantillon d'observation plus important. Ils permettent de suivre plus précisément l'évolution de ce ravageur, l'intensité et l'étendue des dégâts qu'il provoque. Toutefois, la décision d'intervention par traitement ne peut être prise à bon escient qu'après examen attentif des résultats d'un ou de plusieurs contrôles spéciaux réalisés après détection de l'attaque par un contrôle ordinaire. La présente " Page de pratique agricole " traite de la conduite des contrôles phytosanitaires en cocoteraie de plus de quatre ans, entrée en production. La surveillance des jeunes cocoteraies, beaucoup plus vulnérables, fera également l'objet d'autres " Conseils ". (Résumé d'auteur

Bronchopulmonary Dysplasia: Executive Summary of a Workshop

Comment in Bronchopulmonary Dysplasia: The Ongoing Search for One Definition to Rule Them All. [J Pediatr. 2018] Midlife crisis? In its 50th year, BPD redefines itself. [J Pediatr. 2018

Umbilical cord blood metabolomics reveal distinct signatures of dyslipidemia prior to bronchopulmonary dysplasia and pulmonary hypertension

Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia (BPD) and remains a primary contributor to increased morbidity and mortality among preterm infants. Unfortunately, at the present time, there are no reliable early predictive markers for BPD-associated PH. Considering its health consequences, understanding in utero perturbations that lead to the development of BPD and BPD-associated PH and identifying early predictive markers is of utmost importance. As part of the discovery phase, we applied a multiplatform metabolomics approach consisting of untargeted and targeted methodologies to screen for metabolic perturbations in umbilical cord blood (UCB) plasma from preterm infants that did ( n = 21; cases) or did not ( n = 21; controls) develop subsequent PH. A total of 1,656 features were detected, of which 407 were annotated by metabolite structures. PH-associated metabolic perturbations were characterized by reductions in major choline-containing phospholipids, such as phosphatidylcholines and sphingomyelins, indicating altered lipid metabolism. The reduction in UCB abundances of major choline-containing phospholipids was confirmed in an independent validation cohort consisting of UCB plasmas from 10 cases and 10 controls matched for gestational age and BPD status. Subanalyses in the discovery cohort indicated that elevations in the oxylipins PGE1, PGE2, PGF2a, 9- and 13-HOTE, 9- and 13-HODE, and 9- and 13-KODE were positively associated with BPD presence and severity. This expansive evaluation of cord blood plasma identifies compounds reflecting dyslipidemia and suggests altered metabolite provision associated with metabolic immaturity that differentiate subjects, both by BPD severity and PH development

Advances in Neonatal Pulmonary Hypertension.

Persistent pulmonary hypertension of the newborn (PPHN) is a surprisingly common event in the neonatal intensive care unit, and affects both term and preterm infants. Recent studies have begun to elucidate the maternal, fetal and genetic risk factors that trigger PPHN. There have been numerous therapeutic advances over the last decade. It is now appreciated that oxygen supplementation, particularly for the goal of pulmonary vasodilation, needs to be approached as a therapy that has risks and benefits. Administration of surfactant or inhaled nitric oxide (iNO) therapy at a lower acuity of illness can decrease the risk of extracorporeal membrane oxygenation/death, progression of disease and duration of hospital stay. Milrinone may have specific benefits as an ‘inodilator', as prolonged exposure to iNO plus oxygen may activate phosphodiesterase (PDE) 3A. Additionally, sildenafil and hydrocortisone may benefit infants exposed to hyperoxia and oxidative stress. Continued investigation is likely to reveal new therapies such as citrulline and cinaciguat that will enhance NO synthase and soluble guanylate cyclase function. Continued laboratory and clinical investigation will be needed to optimize treatment and improve outcomes.</jats:p