Surfactant protein variants in pediatric lung injury

[unreadable] DESCRIPTION (provided by applicant): The care of critically ill children who require mechanical ventilation for respiratory failure has advanced in the past decades. The majority of these children will survive to hospital discharge, but some will progress to develop long-term pulmonary dysfunction. However, there is no present mechanism available to identify which of these children will develop chronic lung disease, or to identify both the environmental and genetic determinants of the chronic pulmonary dysfunction in these children. The proposed studies aim to gain insight into these questions by focusing on the following specific aims: 1) to determine early predictors of chronic lung disease in pediatric patients who require mechanical ventilation for respiratory failure; 2) to determine associations between physiologically relevant genetic variants of surfactant proteins A and B and children who develop early predictors; and 3) to determine associations between these same genetic variants and children who develop symptoms of pulmonary dysfunction at 6 and 12 months after hospital discharge. The methodology employed is outlined below. Two hundred and forty pediatric patients (ages 0-2 years) who are admitted to one of the ten participating pediatric intensive care units will be enrolled. A blood sample will be drawn for determination of the surfactant protein A and B genetic variants. During the hospital stay, a large amount of data will be collected that will include etiology of respiratory failure, ventilator parameters and strategies undertaken, severity of lung injury, therapies utilized, and outcome. Predictors of chronic lung disease will be assessed at hospital discharge or at 28 days after initiation of mechanical ventilation. In order to determine which children develop chronic lung disease, parents of the subjects will complete a telephone survey 6 and 12 months after hospital discharge with questions related to general pulmonary wellness. Data will then be analyzed to address the three specific aims. The rationale for pursuing this study with the proposed study design is that: a) if clinical or genetic markers can be recognized early in the course of treatment for respiratory failure, pediatric patients at high-risk may benefit from specific therapy aimed at decreasing the incidence of chronic respiratory dysfunction; and b) if children who will develop chronic lung disease can be identified prior to hospital discharge, early intervention and education can be instituted in an attempt to prevent multiple physician visits and hospitalizations in this high-risk subset of pediatric patients. [unreadable] [unreadable]