624 SECTION V Pediatric Critical Care Pulmonary PVD and (2) sensitive, objective, and adaptive outcome measures to evaluate long term outcomes, particularly as they relate to pul monary and physical f[.]
624 S E C T I O N V Pediatric Critical Care: Pulmonary PVD and (2) sensitive, objective, and adaptive outcome measures to evaluate long-term outcomes, particularly as they relate to pulmonary and physical functioning Currently, echocardiography is the sole noninvasive technique to screen for and follow PVD Despite being readily available, current echocardiographic measures are not adequately sensitive, particularly in the setting of abnormal volume status and changing systemic vascular resistances often seen in our critically ill population Additionally, outcomes after PVD and severe lung injury are studied using subjective surveys, pulmonary function tests, and crude objective counts of illness episodes (e.g., emergency department visits and hospitalizations) To more fully understand the long-term effects of congenital or acquired PVD, we need to increase the sensitivity, objectivity, and adaptability of our assessments to identify and measure functional pulmonary deficits that may affect a child’s physical capacity as manifested in everyday life Novel methods to study physical activity, exercise tolerance, and subtle pulmonary deficits in an objective manner will allow for a complete understanding of the long-term effects of PVD on the vulnerable, immature pulmonary system As hospitalizations of children with PH secondary to CHD have decreased, it is important to note that, despite decreased mortality, hospitalization rates and costs have increased for children with PH that is unrelated to CHD.147 This trend is partially due to improved recognition and, hence, more aggressive treatment of pediatric PH (e.g., PH associated with BPD) but also due to the fact that therapies currently available to children with severe PH often require continuous infusion of medication, which carries inherent risks Therefore, the development of alternative therapies that can be given intermittently and enterally is critical Future Directions and Perspectives Survival and quality of life of pediatric PH patients have improved considerably over the past decade due to advances in clinical care and development of new treatment strategies based on molecular pathways discovered in bench and translational research However, therapy of PH remains challenging, and gaps in the current clinical and lab-based research need to be addressed to not only manage the symptoms but someday cure at least some forms of PH Clinical challenges in the therapy of PH that will need to be addressed in conjunction with basic and translational research are as follows Currently, pharmacotherapy for PH is mostly focused primarily on vasodilation Though vasoconstriction is critical for the development of PH, vasodilator therapy only partially addresses the pulmonary vascular changes in the chronically diseased lung Although the current treatments for PH contribute to improved patient well-being, they not halt or reverse PAH since these treatments not directly address the mechanisms contributing to the inflammatory, fibro proliferative changes characteristic of chronic PH.231,232 Identifying underlying mechanisms and then proving that they are pharmacologically targetable will be necessary first steps Improved assessment of the effects of new classes of therapeutic agents (targeting metabolism, epigenetics, inflammation, and angiogenesis) on lung vascular changes and RV function should include increased use of advanced imaging (MRI and PET) to allow evaluation of metabolism, blood flow, and function in the lung and RV in children receiving conventional and experimental PAH therapies Lack of RCTs in pediatric patients and the generally small number of patients enrolled in pediatric trials is another obstacle Limitations to establishing robust treatment guidelines for pediatric PH are due to the varied etiology of PH in children, small patient numbers in individual centers, lack of interdisciplinary PH centers, and lack of a national/ international PH registry Additionally, biomarkers that can predict susceptibility, severity, and progression of PH and PVD are lacking Therapeutic strategies adapted from adult PAH have not been sufficiently studied in children to allow the definition of potential toxicities or optimal dosing, a problem that we continue to need to address.232 Improved pediatric-specific models of pediatric pulmonary hypertensive vascular disease are needed, focusing on the developmental aspect of PH Identification must be made of perinatal risk factors of PH, as this might present a window of opportunity in the identification of susceptibility factors that could lead to earlier or improved interventions Key References Simonneau G, Montani D, Celermajer DS, et al Haemodynamic definitions and updated clinical classification of pulmonary hypertension Eur Respir J 2019;53(1):1801913 Cerro MJ, Abman S, Diaz G, et al A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric 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