Surfactant Protein A Inhibits Human Rhinovirus C Binding and Infection of Airway Epithelial Cells from Pediatric Asthma.

Rhinovirus C (RV-C) infection can trigger asthma exacerbations in children and adults, and RV-C-induced wheezing illnesses in preschool children correlate with the development of childhood asthma. Surfactant protein A (SP-A) plays a critical role in regulating pulmonary innate immunity by binding to numerous respiratory pathogens. Mature SP-A consists of multiple isoforms that form the hetero-oligomers of SP-A1 and SP-A2, organized in 18-mers.

Initiatives to improve lung and sleep health in children: Delphi consensus from the pediatrics, pulmonary, and sleep conference.

Background And Objectives: The lung and sleep health of adults is heavily influenced by early factors, both genetic and environmental; therefore, optimizing respiratory health begins in childhood. Multiple barriers impede improvements in lung and sleep health for children. First, the traditional siloing between general pediatric care in the community, pediatric pulmonary and sleep subspecialty care, and the research community limits the translation of knowledge into practice.

The Child Opportunity Index 2.0 and exacerbation-prone asthma in a cohort of urban children.

Rationale: Social determinants of health underlie disparities in asthma. However, the effects of individual determinants likely interact, so a summary metric may better capture their impact. The Child Opportunity Index 2.

Breathing zone pollutant levels are associated with asthma exacerbations in high-risk children.

Background: Indoor and outdoor air pollution levels are associated with poor asthma outcomes in children. However, few studies have evaluated whether breathing zone pollutant levels associate with asthma outcomes.

Objective: Determine breathing zone exposure levels of NO , O , total PM and PM constituents among children with exacerbation-prone asthma, and examine correspondence with in-home and community measurements and associations with outcomes.

Prediction of lung cancer risk based on age and smoking history.

Background And Objective: The CISNET models provide predictions for dying of lung cancer in any year of life as a function of age and smoking history, but their predictions are quite variable and the models themselves can be complex to implement. Our goal was to develop a simple empirical model of the risk of dying of lung cancer that is mathematically constrained to produce biologically appropriate probability predictions as a function of current age, smoking start age, quit age, and smoking intensity.

Methods: The six adjustable parameters of the model were evaluated by fitting its predictions of cancer death risk versus age to the mean of published predictions made by the CISNET models for the never smoker and for six different scenarios of lifetime smoking burden.

Airwave oscillometry to measure lung function in children with Down syndrome.

Background: Children with Down syndrome are at risk for significant pulmonary co-morbidities, including recurrent respiratory infections, dysphagia, obstructive sleep apnea, and pulmonary vascular disease. Because the gold standard metric of lung function, spirometry, may not be feasible in children with intellectual disabilities, we sought to assess the feasibility of both airwave oscillometry and spirometry in children with Down syndrome.

Methods: Thirty-four children with Down syndrome aged 5-17 years were recruited.

Three Alveolar Phenotypes Govern Lung Function in Murine Ventilator-Induced Lung Injury.

Mechanical ventilation is an essential lifesaving therapy in acute respiratory distress syndrome (ARDS) that may cause ventilator-induced lung injury (VILI) through a positive feedback between altered alveolar mechanics, edema, surfactant inactivation, and injury. Although the biophysical forces that cause VILI are well documented, a knowledge gap remains in the quantitative link between altered parenchymal structure (namely alveolar derecruitment and flooding), pulmonary function, and VILI. This information is essential to developing diagnostic criteria and ventilation strategies to reduce VILI and improve ARDS survival.

Using injury cost functions from a predictive single-compartment model to assess the severity of mechanical ventilator-induced lung injuries.

Identifying safe ventilation patterns for patients with acute respiratory distress syndrome remains challenging because of the delicate balance between gas exchange and selection of ventilator settings to prevent further ventilator-induced lung injury (VILI). Accordingly, this work seeks to link ventilator settings to graded levels of VILI to identify injury cost functions that predict injury by using a computational model to process pressures and flows measured at the airway opening. Pressure-volume loops were acquired over the course of ~2 h of mechanical ventilation in four different groups of BALB/c mice.

Linking lung function to structural damage of alveolar epithelium in ventilator-induced lung injury.

Understanding how the mechanisms of ventilator-induced lung injury (VILI), namely atelectrauma and volutrauma, contribute to the failure of the blood-gas barrier and subsequent intrusion of edematous fluid into the airspace is essential for the design of mechanical ventilation strategies that minimize VILI. We ventilated mice with different combinations of tidal volume and positive end-expiratory pressure (PEEP) and linked degradation in lung function measurements to injury of the alveolar epithelium observed via scanning electron microscopy. Ventilating with both high inspiratory plateau pressure and zero PEEP was necessary to cause derangements in lung function as well as visually apparent physical damage to the alveolar epithelium of initially healthy mice.

Alveolar leak develops by a rich-get-richer process in ventilator-induced lung injury.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition for which there are currently no medical therapies other than supportive care involving the application of mechanical ventilation. However, mechanical ventilation itself can worsen ARDS by damaging the alveolocapillary barrier in the lungs. This allows plasma-derived fluid and proteins to leak into the airspaces of the lung where they interfere with the functioning of pulmonary surfactant, which increases the stresses of mechanical ventilation and worsens lung injury.

Linking Ventilator Injury-Induced Leak across the Blood-Gas Barrier to Derangements in Murine Lung Function.

Mechanical ventilation is vital to the management of acute respiratory distress syndrome, but it frequently leads to ventilator-induced lung injury (VILI). Understanding the pathophysiological processes involved in the development of VILI is an essential prerequisite for improving lung-protective ventilation strategies. The goal of this study was to relate the amount and nature of material accumulated in the airspaces to biomarkers of injury and the derecruitment behavior of the lung in VILI.

Predicting the Mortality Benefit of CT Screening for Second Lung Cancer in a High-Risk Population.

Patients who survive an index lung cancer (ILC) after surgical resection continue to be at significant risk for a metachronous lung cancer (MLC). Indeed, this risk is much higher than the risk of developing an ILC in heavy smokers. There is currently little evidence upon which to base guidelines for screening at-risk patients for MLC, and the risk-reward tradeoffs for screening this patient population are unknown.

Predicting ventilator-induced lung injury using a lung injury cost function.

Managing patients with acute respiratory distress syndrome (ARDS) requires mechanical ventilation that balances the competing goals of sustaining life while avoiding ventilator-induced lung injury (VILI). In particular, it is reasonable to suppose that for any given ARDS patient, there must exist an optimum pair of values for tidal volume (VT) and positive end-expiratory pressure (PEEP) that together minimize the risk for VILI. To find these optimum values, and thus develop a personalized approach to mechanical ventilation in ARDS, we need to be able to predict how injurious a given ventilation regimen will be in any given patient so that the minimally injurious regimen for that patient can be determined.

Modeling the Progression of Epithelial Leak Caused by Overdistension.

Mechanical ventilation is necessary for treatment of the acute respiratory distress syndrome but leads to overdistension of the open regions of the lung and produces further damage. Although we know that the excessive stresses and strains disrupt the alveolar epithelium, we know little about the relationship between epithelial strain and epithelial leak. We have developed a computational model of an epithelial monolayer to simulate leak progression due to overdistension and to explain previous experimental findings in mice with ventilator-induced lung injury.