Daycare Attendance is Linked to Increased Risk of Respiratory Morbidities in Children Born Preterm with Bronchopulmonary Dysplasia.

OBJECTIVES: To test the hypothesis that daycare attendance among children with bronchopulmonary dysplasia (BPD) is associated with increased chronic respiratory symptoms and/or greater health care use for respiratory illnesses during the first 3 years of life. STUDY DESIGN: Daycare attendance and clinical outcomes were obtained via standardized instruments for 341 subjects recruited from 9 BPD specialty clinics in the US. All subjects were former infants born preterm (<34 weeks) with BPD (71% severe) requiring outpatient follow-up between 0 and 3 years of age. Mixed logistic regression models were used to test for associations. RESULTS: Children with BPD attending daycare were more likely to have emergency department visits and systemic steroid usage. Children in daycare up to 3 years of age also were more likely to report trouble breathing, having activity limitations, and using rescue medications when compared with children not in daycare. More severe manifestations were found in children attending daycare between 6 and 12 months of chronological age. CONCLUSIONS: In this study, children born preterm with BPD who attend daycare were more likely to visit the emergency department, use systemic steroids, and have chronic respiratory symptoms compared with children not in daycare, indicating that daycare may be a potential modifiable risk factor to minimize respiratory morbidities in children with BPD during the preschool years.

Outpatient Respiratory Management of Infants, Children, and Adolescents with Post-Prematurity Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD. Methods: A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD. Conclusions: The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.

Lung function trajectories in children with post-prematurity respiratory disease: identifying risk factors for abnormal growth.

BACKGROUND: Survivors of prematurity are at risk for abnormal childhood lung function. Few studies have addressed trajectories of lung function and risk factors for abnormal growth in childhood. This study aims to describe changes in lung function in a contemporary cohort of children born preterm followed longitudinally in pulmonary clinic for post-prematurity respiratory disease and to assess maternal and neonatal risk factors associated with decreased lung function trajectories. METHODS: Observational cohort of 164 children born preterm ≤ 32 weeks gestation followed in pulmonary clinic at Boston Children's Hospital with pulmonary function testing. We collected demographics and neonatal history. We used multivariable linear regression to identify the impact of neonatal and maternal risk factors on lung function trajectories in childhood. RESULTS: We identified 264 studies from 82 subjects with acceptable longitudinal FEV1 data and 138 studies from 47 subjects with acceptable longitudinal FVC and FEV1/FVC data. FEV1% predicted and FEV1/FVC were reduced compared to childhood norms. Growth in FVC outpaced FEV1, resulting in an FEV1/FVC that declined over time. In multivariable analyses, longer duration of mechanical ventilation was associated with a lower rate of rise in FEV1% predicted and greater decline in FEV1/FVC, and postnatal steroid exposure in the NICU was associated with a lower rate of rise in FEV1 and FVC % predicted. Maternal atopy and asthma were associated with a lower rate of rise in FEV1% predicted. CONCLUSIONS: Children with post-prematurity respiratory disease demonstrate worsening obstruction in lung function throughout childhood. Neonatal risk factors including exposure to mechanical ventilation and postnatal steroids, as well as maternal atopy and asthma, were associated with diminished rate of rise in lung function. These results may have implications for lung function trajectories into adulthood.

Transcutaneous carbon dioxide pattern and trend over time in preterm infants.

BACKGROUND: Chronic lung disease remains a burden for extremely preterm infants. The changes in ventilation over time and optimal ventilatory management remains unknown. Newer, non-invasive technologies provide insight into these patterns. METHODS: This single-center prospective cohort study enrolled infants ≤32 0/7 weeks. We obtained epochs of transcutaneous carbon dioxide (TcCO2) measurements twice each week to describe the pattern of hypercarbia throughout their hospitalization. RESULTS: Patterns of hypercarbia varied based on birth gestational age and post-menstrual age (PMA) (p = 0.03), regardless of respiratory support. Infants receiving the most respiratory support had values 16-21 mmHg higher than those on room air (p < 0.001). Infants born at the youngest gestational ages had the greatest total change but the rate of change was slower (p = 0.049) compared to infants born at later gestational ages. All infants had TcCO2 values stabilize by 31-33 weeks PMA, when values were not significantly different compared to discharge. No rebound was observed when infants weaned off invasive support. CONCLUSIONS: Hypercarbia improves as infants approached 31-33 weeks PMA. Hypercarbia was the highest in the most immature infants and improved with age and growth despite weaning respiratory support. IMPACT: This study describes the evolution of hypercarbia as very preterm infants grow and develop. The pattern of ventilation is significantly different depending on the gestational age at birth and post-menstrual age. Average transcutaneous carbon dioxide (TCO2) decreased over time as infants became more mature despite weaning respiratory support. This improvement was most significant in infants born at the lowest gestational ages.

Home Oxygen Therapy for Children. An Official American Thoracic Society Clinical Practice Guideline.

BACKGROUND: Home oxygen therapy is often required in children with chronic respiratory conditions. This document provides an evidence-based clinical practice guideline on the implementation, monitoring, and discontinuation of home oxygen therapy for the pediatric population. METHODS: A multidisciplinary panel identified pertinent questions regarding home oxygen therapy in children, conducted systematic reviews of the relevant literature, and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the quality of evidence and strength of clinical recommendations. RESULTS: After considering the panel's confidence in the estimated effects, the balance of desirable (benefits) and undesirable (harms and burdens) consequences of treatment, patient values and preferences, cost, and feasibility, recommendations were developed for or against home oxygen therapy specific to pediatric lung and pulmonary vascular diseases. CONCLUSIONS: Although home oxygen therapy is commonly required in the care of children, there is a striking lack of empirical evidence regarding implementation, monitoring, and discontinuation of supplemental oxygen therapy. The panel formulated and provided the rationale for clinical recommendations for home oxygen therapy based on scant empirical evidence, expert opinion, and clinical experience to aid clinicians in the management of these complex pediatric patients and identified important areas for future research.

Apnea in the Otherwise Healthy, Term Newborn: National Prevalence and Utilization during the Birth Hospitalization.

OBJECTIVES: To describe the prevalence of apnea in otherwise healthy term newborns, identify attributable length of stay (LOS) and healthcare utilization (cost) of apnea, and measure hospital variation in attributable LOS and cost of apnea in this population. STUDY DESIGN: We conducted a secondary analysis of a national administrative dataset, the 2012 Kids' Inpatient Database, which included 3.4 million newborn discharges in the US. The birth hospitalizations of approximately 2.6 million otherwise healthy, full-term newborns were included for analysis. Attributable LOS and cost of apnea were calculated using multivariate analyses. RESULTS: Apnea was diagnosed in 1 in 1000 healthy full-term newborns. Multivariate analyses showed that newborns with apnea had 0.6 days longer LOS (P < .001) and $483 greater costs (P < .001) compared with healthy term newborns, per birth hospitalization. Newborns diagnosed with apnea plus hypoxia and/or bradycardia had 1.4 days longer LOS (P < .001) and $653 greater costs (P < .001). The attributable LOS and cost attributable to apnea varied between individual hospitals and differed by hospital region. CONCLUSIONS: Apnea is associated with higher LOS and cost in the newborn hospitalization, with variation in hospital practice. This suggests the need for better comprehension of the underlying physiology and standardization of practice in its management in the term newborn.

Predictors of Persistent Infant Car Seat Challenge Failure.

BACKGROUND: Premature and other at-risk infants can experience cardiorespiratory problems when positioned in their car seats. The American Academy of Pediatrics recommends that all premature and at-risk infants undergo a period of observation in their car seat to monitor for apnea, bradycardia, and oxygen desaturation before hospital discharge. This Infant Car Seat Challenge (ICSC) is used to determine readiness for infant travel in a car seat. Infants failing the ICSC are discharged home in car beds and referred for a follow-up screen in the outpatient clinic. PURPOSE: The purpose of this study was to identify predictors for infants failing the follow-up ICSC after hospital discharge. METHODS/SEARCH STRATEGY: A retrospective, cross-sectional study design was used to examine charts of 436 infants referred from across New England, to Boston Children's Hospital's, Center for Healthy Infant Lung Development clinic between August 2008 and May 2015 for a follow-up ICSC. FINDINGS/RESULTS: Infants who failed the follow-up ICSC had statistically significant lower weights (0.27 ± 0.14 kg, difference ± standard error, P = .03) and younger postmenstrual ages (0.9 ± 0.4 weeks, P = .03). History of a cardiac condition (odds ratio, 3.6; 95% confidence interval, 1.5-8.5; P = .005) and respiratory illness (odds ratio, 2.1; confidence interval, 1.1 to 4.2; P = .03) were significant predictors of ICSC failure. IMPLICATIONS FOR PRACTICE: A follow-up ICSC is recommended for the safe transition of infants from a car bed to a car seat. IMPLICATIONS FOR RESEARCH: Further research is needed to investigate the causes of ICSC failure among high-risk infant populations.

Salivary caffeine concentrations are comparable to plasma concentrations in preterm infants receiving extended caffeine therapy.

AIMS: Caffeine concentrations in preterm infants are usually measured in the blood. However, salivary assays may provide a valid and practical alternative. The present study explored the validity and clinical utility of salivary caffeine concentrations as an alternative to blood concentrations and developed a novel plasma/salivary caffeine distribution model. METHODS: Paired salivary and plasma samples were obtained in 29 infants. Salivary samples were obtained using a commercially available salivary collection system. Caffeine concentrations in the saliva and plasma were determined using high-performance liquid chromatography. A population pharmacokinetic (PK) model was developed using NONMEM 7.3. RESULTS: The mean (± standard deviation) gestational age (GA) at birth and birth weight were 27.9 ± 2.1 weeks and 1171.6 ± 384.9 g, respectively. Paired samples were obtained at a mean postmenstrual age (PMA) of 35.5 ± 1.1 weeks. The range of plasma caffeine concentrations was 9.5-54.1 µg ml(-1) , with a mean difference (95% confidence interval) between plasma and salivary concentrations of -0.18 µg ml(-1) (-1.90, 1.54). Salivary and plasma caffeine concentrations were strongly correlated (Pearson's correlation coefficient = 0.87, P < 0.001). Caffeine PK in plasma and saliva was simultaneously described by a three-compartment recirculation model. Current body weight, birth weight, GA, PMA and postnatal age were not significantly correlated with any PK parameter. CONCLUSIONS: Salivary sampling provides an easy, non-invasive method for measuring caffeine concentrations. Salivary concentrations correlate highly with plasma concentrations. Caffeine PK in saliva and plasma are well described by a three-compartment recirculation model.

Number of children in the household influences respiratory morbidities in children with bronchopulmonary dysplasia in the outpatient setting.

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD. METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations. RESULTS: The mean gestational age of the study population was 26.5 ± 2.2 weeks and most subjects (69.1%) had severe BPD. The mean number of children in households (including the subject) was 2.1 ± 1.3 children. Each additional child in the household was associated with a 13% increased risk for hospital admission, 13% increased risk for antibiotic use for respiratory illnesses, 10% increased risk for coughing/wheezing/shortness of breath, 14% increased risk for nighttime symptoms, and 18% increased risk for rescue medication use. Additional analyses found that the increased risks were most prominent when there were three or more other children in the household. CONCLUSIONS: We observed that additional children in the household were a risk factor for adverse respiratory outcomes. We speculate that secondary person-to-person transmission of respiratory viral infections drives this finding. While this risk factor is not easily modified, measures do exist to mitigate this disease burden. Further studies are needed to define best practices for mitigating this risk associated with household viral transmission.

Th17 cytokines are critical for respiratory syncytial virus-associated airway hyperreponsiveness through regulation by complement C3a and tachykinins.

Respiratory syncytial virus (RSV) infection is associated with serious lung disease in infants and immunocompromised individuals and is linked to development of asthma. In mice, acute RSV infection causes airway hyperresponsiveness (AHR), inflammation, and mucus hypersecretion. Infected cells induce complement activation, producing the anaphylatoxin C3a. In this paper, we show RSV-infected wild-type mice produce Th17 cytokines, a response not previously associated with viral infections. Mice deficient in the C3aR fail to develop AHR following acute RSV infection, and production of Th17 cytokines was significantly attenuated. Tachykinin production also has been implicated in RSV pathophysiology, and tachykinin receptor-null mice were similarly protected from developing AHR. These animals were also deficient in production of Th17 cytokines. Tachykinin release was absent in mice deficient in C3aR, whereas C3a levels were unchanged in tachykinin receptor-null animals. Thus, our data reveal a crucial sequence following acute RSV infection where initial C3a production causes tachykinin release, followed by activation of the IL-17A pathway. Deficiency of either receptor affords protection from AHR, identifying two potential therapeutic targets.

Validation of an outpatient questionnaire for bronchopulmonary dysplasia control.

INTRODUCTION: Despite bronchopulmonary dysplasia (BPD) being a common morbidity of preterm birth, there is no validated objective tool to assess outpatient respiratory symptom control for clinical and research purposes. METHODS: Data were obtained from 1049 preterm infants and children seen in outpatient BPD clinics of 13 US tertiary care centers from 2018 to 2022. A new standardized instrument was modified from an asthma control test questionnaire and administered at the time of clinic visits. External measures of acute care use were also collected. The questionnaire for BPD control was validated in the entire population and selected subgroups using standard methodology for internal reliability, construct validity, and discriminative properties. RESULTS: Based on the scores from BPD control questionnaire, the majority of caregivers (86.2%) felt their child's symptoms were under control, which did not differ by BPD severity (p = 0.30) or a history of pulmonary hypertension (p = 0.42). Across the entire population and selected subgroups, the BPD control questionnaire was internally reliable, suggestive of construct validity (albeit correlation coefficients were -0.2 to -0.4.), and discriminated control well. Control categories (controlled, partially controlled, and uncontrolled) were also predictive of sick visits, emergency department visits, and hospital readmissions. CONCLUSION: Our study provides a tool for assessing respiratory control in children with BPD for clinical care and research studies. Further work is needed to identify modifiable predictors of disease control and link scores from the BPD control questionnaire to other measures of respiratory health such as lung function testing.

Respiratory Outcomes for Ventilator-Dependent Children With Bronchopulmonary Dysplasia.

OBJECTIVES: To describe outpatient respiratory outcomes and center-level variability among children with severe bronchopulmonary dysplasia (BPD) who require tracheostomy and long-term mechanical ventilation. METHODS: Retrospective cohort of subjects with severe BPD, born between 2016 and 2021, who received tracheostomy and were discharged on home ventilator support from 12 tertiary care centers participating in the BPD Collaborative Outpatient Registry. Timing of key respiratory events including time to tracheostomy placement, initial hospital discharge, first outpatient clinic visit, liberation from the ventilator, and decannulation were assessed using Kaplan-Meier analysis. Differences between centers for the timing of events were assessed via log-rank tests. RESULTS: There were 155 patients who met inclusion criteria. Median age at the time of the study was 32 months. The median age of tracheostomy placement was 5 months (48 weeks' postmenstrual age). The median ages of hospital discharge and first respiratory clinic visit were 10 months and 11 months of age, respectively. During the study period, 64% of the subjects were liberated from the ventilator at a median age of 27 months and 32% were decannulated at a median age of 49 months. The median ages for all key events differed significantly by center (P ≤ .001 for all events). CONCLUSIONS: There is wide variability in the outpatient respiratory outcomes of ventilator-dependent infants and children with severe BPD. Further studies are needed to identify the factors that contribute to variability in practice among the different BPD outpatient centers, which may include inpatient practices.

Does recorded oximetry utilizing a consensus-based algorithm compare to polysomnography in discontinuing home oxygen therapy in premature infants?

BACKGROUND: Approximately a third of all extremely preterm infants diagnosed with bronchopulmonary dysplasia will require home oxygen therapy (HOT). Lack of consensus-based guidelines has led to significant variability in outpatient HOT management in the United States. A common assessment performed before discontinuing oxygen is a formal polysomnogram (PSG). PSGs are potentially undesirable due to cost, lack of convenient access, and parental stress, so alternative testing to determine the optimal timing of safe oxygen discontinuation are needed. METHODS: We compared nocturnal recorded home oximetry (RHO) with PSG data in a cohort of patients from the RHO trial for patients who had recordings performed simultaneously to or within 24 h of their PSG. The RHO trial was a randomized, unblinded, multi-center trial comparing two oxygen management strategies. Parameters of oxygenation were compared between PSG and RHO, and nonoximegtry findings from the PSG that changed clinical management were identified. RESULTS: A total of 53 infants randomized to obtain a PSG as part of the RHO trial (55%) completed a PSG, and of those, 32 (64%) completed both a PSG with comparison RHO. There were more white infants in both groups than other races and ethnicities. Bland-Altman analysis showed a strong agreement of oxygen saturation time below 90% SpO2 between PSG and RHO results (slope = 1.014, p = 0.24). Results agreed in 96% of cases. CONCLUSION: RHO is a safe and effective alternative to PSG to assist in determination of discontinuing HOT in infants with BPD without other risks for sleep-disordered breathing.

Impact of a targeted volume-increase nutrition guideline on growth and body mass index in premature infants: A retrospective review.

BACKGROUND: The negative impact of disproportionate growth in premature infants is well documented, but optimal nutrition practices needed to prevent an unhealthy body mass index (BMI) remain unclear. METHODS: An evidence-based, volume-increase guideline that advanced feeding volumes from 150-160 to 170-180 ml/kg/day between the postmenstrual age (PMA) of 31 0/7 and 34 0/7 weeks was implemented in October 2017 for infants born at ≤32 0/7 weeks' gestational age. Data were collected on 262 infants' weight and length at birth and at discharge for 20 months before and 21 months after guideline implementation, and retrospective analysis was conducted to determine disproportionate growth by comparing BMIs (in g/cm2 ) at birth and at discharge. Changes in infants' body habitus were determined through bivariate analysis of weight and length z-scores from the Fenton growth curve. RESULTS: Implementation of a targeted volume nutrition guideline resulted in fewer infants with growth failure, defined as weight <10th percentile (19.5% vs 11.2%; P = .06) at discharge. Infants who received treatment according to the targeted nutrition guideline had a statistically significant reduction in disproportionately low BMI (8.6% vs 2.5%; P = .0380) and an increase in disproportionately high BMIs (4.3% vs 12.3%; P = .025). There was minor change in the percentage of disproportionately large infants who received the guidelines from birth to discharge (11.5% vs 12.3%). CONCLUSIONS: A targeted volume-increase nutrition guideline may prevent growth failure, with some effects on disproportionate growth in preterm infants born at ≤32 0/7 weeks' gestational age.

Insurance coverage and respiratory morbidities in bronchopulmonary dysplasia.

INTRODUCTION: Preterm infants and young children with bronchopulmonary dysplasia (BPD) are at increased risk for acute care utilization and chronic respiratory symptoms during early life. Identifying risk factors for respiratory morbidities in the outpatient setting could decrease the burden of care. We hypothesized that public insurance coverage was associated with higher acute care usage and respiratory symptoms in preterm infants and children with BPD after initial neonatal intensive care unit (NICU) discharge. METHODS: Subjects were recruited from BPD clinics at 10 tertiary care centers in the United States between 2018 and 2021. Demographics and clinical characteristics were obtained through chart review. Surveys for clinical outcomes were administered to caregivers. RESULTS: Of the 470 subjects included in this study, 249 (53.0%) received employer-based insurance coverage and 221 (47.0%) received Medicaid as sole coverage at least once between 0 and 3 years of age. The Medicaid group was twice as likely to have sick visits (adjusted odd ratio [OR]: 2.06; p = 0.009) and emergency department visits (aOR: 2.09; p = 0.028), and three times more likely to be admitted for respiratory reasons (aOR: 3.04; p = 0.001) than those in the employer-based group. Additionally, those in the Medicaid group were more likely to have nighttime respiratory symptoms (aOR: 2.62; p = 0.004). CONCLUSIONS: Children with BPD who received Medicaid coverage were more likely to utilize acute care and have nighttime respiratory symptoms during the first 3 years of life. More comprehensive studies are needed to determine whether the use of Medicaid represents a barrier to accessing care, lower socioeconomic status, and/or a proxy for detrimental environmental exposures.

An Initiative to Reduce Preterm Infants Pre-discharge Growth Failure Through Time-specific Feeding Volume Increase.

Very low birth weight infants often demonstrate poor postnatal longitudinal growth, which negatively impacts survival rates and long-term health outcomes. Improving extrauterine growth restriction (EUGR) among extremely premature infants has become a significant focus of quality improvement initiatives. Prior efforts in the University of Massachusetts Memorial Medical Center neonatal intensive care unit were unsuccessful in improving the EUGR rate at discharge. METHODS: The primary aim of this initiative was to improve EUGR at discharge [defined as weight less than 10th percentile for postmenstrual age (PMA)] for infants born ≤32 0/7 weeks from a baseline of 25% to 20% by June 2019. We excluded all small for gestational age infants due to the limitation in the EUGR definition. A multidisciplinary team implemented evidence-based nutritional guideline changes using the Institute of Healthcare Improvement methods. The most notable change was the time-specific feeding volume advancement that increased the goal feeding volume between 31 0/7 and 34 0/7 weeks PMA from 150-160 to 170-180 milliliters per kilogram per day. The team monitored nutritional intake, weight, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), and length of stay (LOS). RESULTS: The EUGR rate improved from 25% to 12% after initiation of increased time-specific, enteral feeding guidelines at 31-34 weeks PMA. NEC rate, BPD rate, and LOS remained unchanged throughout the initiative. CONCLUSIONS: By implementing a time-specific volume increase guideline from 31 0/7 to 34 0/7 weeks PMA, the EUGR rate improved from baseline of 25% to 12% without increasing NEC rate, BPD rate, and LOS.

Approaches to addressing social determinants of health in the NICU: a mixed methods study.

OBJECTIVE: Examine current approaches to addressing social determinants of health (SDOH) in the NICU and perceived appropriateness of a standardized screening and referral process. STUDY DESIGN: We performed a mixed methods study in two Massachusetts safety-net NICUs. We examined rates that unmet basic needs were assessed and identified among 601 families. We conducted focus groups with NICU staff to understand current methods to assess unmet basic needs and perceived appropriateness of a standardized SDOH screening and referral process. RESULT: Except employment (89%), other unmet basic needs were infrequently assessed (housing 38%, food/hunger 7%, childcare 3%, transportation 3%, utilities 0.2%). Staff believed: (1) processes to assess SDOH were not standardized and inconsistently performed/documented; (2) addressing SDOH was important; and (3) using a standardized screening and referral process would be feasible. CONCLUSIONS: Current NICU assessment of SDOH is limited and use of a standardized screening and referral process could be useful.

Characteristics of infants or children presenting to outpatient bronchopulmonary dysplasia clinics in the United States.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is a common respiratory sequelae of preterm birth, for which longitudinal outpatient data are limited. Our objective was to describe a geographically diverse outpatient cohort of former preterm infants followed in BPD-disease specific clinics. METHODS: Seven BPD specialty clinics contributed data using standardized instruments to this retrospective cohort study. Inclusion criteria included preterm birth (<37 weeks) and respiratory symptoms or needs requiring outpatient follow-up. RESULTS: A total of 413 preterm infants and children were recruited (mean age: 2.4 ± 2.7 years) with a mean gestational age of 27.0 ± 2.8 weeks and a mean birthweight of 951 ± 429 grams of whom 63.7% had severe BPD. Total, 51.1% of subjects were nonwhite. Severe BPD was not associated with greater utilization of acute care/therapies compared to non-severe counterparts. Of children with severe BPD, differences in percentage of those on any home respiratory support (p = .001), home positive pressure ventilation (p = .003), diuretics (p < .001), inhaled corticosteroids (p < .001), and pulmonary vasodilators (p < .001) were found between centers, however no differences in acute care use were observed. DISCUSSION: This examination of a multicenter collaborative registry of children born prematurely with respiratory disease demonstrates a diversity of management strategies among geographically distinct tertiary care BPD centers in the United States. This study reveals that the majority of children followed in these clinics were nonwhite and that neither variation in management nor severity of BPD at 36 weeks influenced outpatient acute care utilization. These findings suggest that post-neonatal intensive care unit factors and follow-up may modify respiratory outcomes in BPD, possibly independently of severity.

FcgammaRIII is protective against Pseudomonas aeruginosa pneumonia.

Defenses against bacterial infections involve activation of multiple systems of innate immunity, including complement, Toll-like receptors, and defensins. Reactions to chronic infections bring adaptive immune mechanisms into play as well, with the introduction of modulatory interactions between the two. In humans with chronic lung infections, the severity of inflammation and disease correlate with elevated levels of pathogen-specific immune complexes and complement activation. In mice with genetic deficiency in C5, or targeted deletion of the C5a receptor, Pseudomonas lung infections reveal a role for the C5a anaphylatoxin in disease severity. Deficient animals exhibit significantly reduced survival and clearance of infecting bacteria, simultaneous with greatly increased pulmonary influx of inflammatory cells. Among the actions of C5a on inflammatory cells mediated through the C5a receptor is a shift in the relative expression of Fcgamma receptors to increase FcgammaRIII relative to FcgammaRII. This shift may significantly impact defenses against chronic infection, reflecting the cellular activation profiles of these IgG receptors. We addressed the role of FcgammaRIII in defense against Pseudomonas lung infection, and found that, like C5aR-deficient mice, animals with targeted deletion of FcgammaRIII are more susceptible to mortality upon infection and exhibit reduced clearance of the pathogen. Pseudomonas infection was associated with an increase in the FcgammaRIII/FcgammaRII ratio in wild-type mice, and the data support its role as an additional mechanism of host defense against bacterial infection.