Purine degradation pathway metabolites at birth and the risk of lower respiratory tract infections in infancy.

Background: Lower respiratory tract infections (LRTIs) are the leading cause of infant morbidity and mortality worldwide, and altered metabolite production is recognised as a critical factor in LRTI pathogenesis. Methods: This study aimed to identify prenatal metabolic changes associated with LRTI risk in infancy, using liquid chromatography-mass spectrometry unbiased metabolomics analysis on cord blood from 810 full-term newborns. Results: We identified 22 compounds linked to LRTIs in infancy, enriched for purine degradation pathway (PDP) metabolites. High cord blood PDP metabolites, including xanthine, hypoxanthine, xanthosine and inosine, were linked to reduced LRTI risk during infancy. Notably, a low xanthine to uric acid ratio at birth predicted a four-fold increased LRTI risk. Conclusion: This study is the first to reveal that high cord blood PDP metabolites identify newborns at lower LRTI risk, stratifying disease risk at birth. Moreover, our results prompt further study on PDP enzymes as pharmacological targets to decrease LRTI morbidity and mortality for at-risk newborns.

Association of respiratory virus types with clinical features in bronchiolitis: Implications for virus testing strategies. A systematic review and meta-analysis.

BACKGROUND: Bronchiolitis is a leading cause of infant hospitalization, linked to respiratory syncytial virus (RSV) and rhinovirus (RV). Guidelines lack specific viral testing for bronchiolitis management. To establish effective management strategies, it is crucial to assess whether specific respiratory virus types are correlated with distinct examination features. METHODS: Through a systematic search of three databases, 21 studies were qualitatively analyzed, with 18 used for meta-analysis. Various outcomes like wheezing on auscultation, fever, atopic traits, and infection severity were evaluated. RESULTS: RSV-positive bronchiolitis was associated with a higher need for oxygen supplementation (OR 1.78, 95% CI 1.04-3.02) in 5 studies, while RV-positive bronchiolitis was more frequently linked to personal history of eczema (OR 0.60, 95% CI 0.41-0.88) in 6 studies. No significant differences were observed in the other outcomes examined. CONCLUSIONS: Bronchiolitis caused by RSV or RV presents with similar clinical features. Despite the associations between RSV-positive bronchiolitis and need for oxygen supplementation, and RV-positive bronchiolitis and a history of eczema, our study shows that viral etiology of bronchiolitis cannot be determined solely based on clinical presentation. Tailored management strategies, informed by accurate viral testing, seem crucial in clinical practice for enhancing patient outcomes in severe bronchiolitis.

Phenotypical Characterization of Obstructive Sleep Apnea in Premature Infants using Polysomnography.

OBJECTIVE: To use objective quantification of polysomnographic (PSG) parameters in premature infants to define the severity and nature of obstructions (partial hypopnea vs. total obstruction), along with the impact on sleep fragmentation and oxygenation patterns. METHODS: Retrospective comparison of PSG features in 207 infants (<12 months) referred for sleep disordered breathing. Our study groups included term (> = 37 weeks GA, n = 162) and premature (<37 weeks GA, n = 45) infants. Groups were compared for OSA sleep-stage-specific apnea hypopnea (AHI) indexes (REM and NREM), hypopnea indexes (HI), obstructive apnea indexes (OI) and arousal indexes. Oxygenation was assessed as % of time with SpO2 < 90%, nadir with apneic events and frequency of SpO2 desaturations (>3%) calculated as stage-specific O2 desaturation indexes. RESULTS: Overall, premature infants had greater apnea severity (AHI premature 13.9/h vs. Term 7.9/h, p = 0.018). Additional analyses showed that the primary difference between premature and term infants is seen in the group with partial obstructions (HI index) and severe OSA (OAHI> = 10/h). Premature infants also had greater arousal indexes (premature 13.8/h vs. term 10.5/h, p = 0.003). Although the percentage of time <90% at night and the median SpO2 nadir during apneic events was similar in premature vs. term, O2 desaturation indexes were greater in premature infants (10.3/h in term vs. 18.3/h in prematurity, p = 0.03). CONCLUSIONS: Children born premature have an OSA phenotype in infancy characterized by greater severity mostly due to frequent partial obstructions (hypopneas) rather than full obstructions (obstructive apnea). Prematurity is also associated with more intermittent hypoxemia and sleep fragmentation. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1933-1938, 2024.

Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea.

RATIONALE: Lower respiratory tract infections (LRTI) during the first 2 years of life increase the risk of pediatric obstructive sleep apnea (OSA), but whether this risk varies by LRTI severity is unknown. METHODS: We analyzed data from 2962 children, aged 0-5 years, with early-life LRTI requiring hospitalization (severe LRTI, n = 235), treated as outpatients (mild LRTI, n = 394) and without LRTI (reference group, n = 2333) enrolled in the Boston Birth Cohort. Kaplan-Meier survival estimates and Cox proportional hazards models adjusted by pertinent covariables were used to evaluate the risk of pediatric OSA. RESULTS: Compared to children without LRTI, those with mild LRTI were at a higher risk of having OSA (hazard ratio [HR] 1.44, 95% confidence interval [CI]: 1.01-2.05), and those with severe LRTI were at the highest risk (HR 2.06, 95% CI: 1.41-3.02), independently of relevant covariables (including maternal age, race, gestational age, and type of delivery). Additional risk factors linked to a higher risk of OSA included prematurity (HR 1.34, 95% CI 1.01-1.77) and maternal obesity (HR 1.82, 95% CI 1.32-2.52). The time elapsed between LRTI and OSA diagnosis was similar in mild and severe LRTI cases, with medians of 23 and 25.5 months, respectively (p = .803). CONCLUSION: Infants with severe early-life LRTI have a higher risk of developing OSA, and surveillance strategies to identify OSA need to be particularly focused on this group. OSA monitoring should continue throughout the preschool years as it may develop months or years after the initial LRTI hospitalization.

High TSLP responses in the human infant airways are associated with pre-activated airway epithelial IFN antiviral immunity.

Thymic stromal lymphopoietin (TSLP) is a primarily epithelial-derived cytokine that drives type 2 allergic immune responses. Early life viral respiratory infections elicit high TSLP production, which leads to the development of type 2 inflammation and airway hyperreactivity. The goal of this study was to examine in vivo and in vitro the human airway epithelial responses leading to high TSLP production during viral respiratory infections in early infancy. A total of 129 infants (<1-24 m, median age 10 m) with severe viral respiratory infections were enrolled for in vivo (n = 113), and in vitro studies (n = 16). Infants were classified as 'high TSLP' or 'low TSLP' for values above or below the 50th percentile. High versus low TSLP groups were compared in terms of type I-III IFN responses and production of chemokines promoting antiviral (CXCL10), neutrophilic (CXCL1, CXCL5, CXCL8), and type 2 responses (CCL11, CCL17, CCL22). Human infant airway epithelial cell (AEC) cultures were used to define the transcriptomic (RNAseq) profile leading to high versus low TSLP responses in vitro in the absence (baseline) or presence (stimulated) of a viral mimic (poly I:C). Infants in the high TSLP group had greater in vivo type III IFN airway production (median type III IFN in high TSLP 183.2 pg/mL vs. 63.4 pg/mL in low TSLP group, p = 0.007) and increased in vitro type I-III IFN AEC responses after stimulation with a viral mimic (poly I:C). At baseline, our RNAseq data showed that infants in the high TSLP group had significant upregulation of IFN signature genes (e.g., IFIT2, IFI6, MX1) and pro-inflammatory chemokine genes before stimulation. Infants in the high TSLP group also showed a baseline AEC pro-inflammatory state characterized by increased production of all the chemokines assayed (e.g., CXCL10, CXCL8). High TSLP responses in the human infant airways are associated with pre-activated airway epithelial IFN antiviral immunity and increased baseline AEC production of pro-inflammatory chemokines. These findings present a new paradigm underlying the production of TSLP in the human infant airway epithelium following early life viral exposure and shed light on the long-term impact of viral respiratory illnesses during early infancy and beyond childhood.

Respiratory Comorbidities Associated with Bronchiectasis in Patients with Common Variable Immunodeficiency in the USIDNET Registry.

BACKGROUND: Bronchiectasis is a major respiratory complication in patients with common variable immunodeficiency (CVID) and is associated with recurrent pulmonary infections. However, it is unclear whether other infections or non-infectious respiratory conditions are related to its development. OBJECTIVE: To identify respiratory comorbidities associated with bronchiectasis in patients with CVID. METHODS: A total of 1470 CVID patients enrolled in the USIDNET registry were included in a cross-sectional analysis. The primary outcome of our study was to determine the clinical characteristics and other respiratory conditions associated with respiratory comorbidities and physician-reported bronchiectasis. RESULTS: One hundred ninety-seven CVID patients were noted to have bronchiectasis (13.4%). Affected patients were significantly older than patients without bronchiectasis (median age 54 years vs. 49 years, p = 0.0004). These patients also had lower serum IgA (13 mg/dL IQR 60 mg/dL vs. 28.4 mg/dL IQR 66 mg/dL, p = 0.000). Notably, chronic rhinosinusitis (OR = 1.69 95%CI 1.05-2.75), sinusitis (OR = 2.06 95%CI 1.38-3.09), pneumonia (OR = 2.70 95%CI 1.88-3.88), COPD (OR = 2.66 95%CI 1.51-4.67), and interstitial lung disease (OR = 2.34 95%CI 1.41-3.91) were independently associated with the development of bronchiectasis in this population. CONCLUSION: These data suggest that lower and upper respiratory infections, chronic lower airway disease, and interstitial lung diseases are independently associated with bronchiectasis in CVID patients. Further study into predisposing conditions related to the development of bronchiectasis in CVID patients may allow prediction and early intervention strategies to prevent the development of this complication.

Impact of bronchopulmonary dysplasia on brain GABA concentrations in preterm infants: Prospective cohort study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with cognitive-behavioral deficits in very preterm (VPT) infants, often in the absence of structural brain injury. Advanced GABA-editing techniques like Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) can quantify in-vivo gamma-aminobutyric acid (GABA+, with macromolecules) and glutamate (Glx, with glutamine) concentrations to investigate for neurophysiologic perturbations in the developing brain of VPT infants. OBJECTIVE: To investigate the relationship between the severity of BPD and basal-ganglia GABA+ and Glx concentrations in VPT infants. METHODS: MRI studies were performed on a 3 T scanner in a cohort of VPT infants [born ≤32 weeks gestational age (GA)] without major structural brain injury and healthy-term infants (>37 weeks GA) at term-equivalent age. MEGA-PRESS (TE68ms, TR2000ms, 256averages) sequence was acquired from the right basal-ganglia voxel (∼3cm3) and metabolite concentrations were quantified in institutional units (i.u.). We stratified VPT infants into no/mild (grade 0/1) and moderate-severe (grade 2/3) BPD. RESULTS: Reliable MEGA-PRESS data was available from 63 subjects: 29 healthy-term and 34 VPT infants without major structural brain injury. VPT infants with moderate-severe BPD (n = 20) had the lowest right basal-ganglia GABA+ (median 1.88 vs. 2.28 vs. 2.12 i.u., p = 0.025) and GABA+/choline (0.73 vs. 0.99 vs. 0.88, p = 0.004) in comparison to infants with no/mild BPD and healthy-term infants. The GABA+/Glx ratio was lower (0.34 vs. 0.44, p = 0.034) in VPT infants with moderate-severe BPD than in infants with no/mild BPD. CONCLUSIONS: Reduced GABA+ and GABA+/Glx in VPT infants with moderate-severe BPD indicate neurophysiologic perturbations which could serve as early biomarkers of future cognitive deficits.

Real-world data evaluation of PAP responsiveness in pediatric obstructive sleep apnea.

STUDY OBJECTIVES: The use of positive airway pressure (PAP) in children is a complex process determined by multiple factors. There are limited data on the response of the pediatric population to PAP therapy at home. The goal of the study was to examine real-world responses using PAP home monitoring in children with obstructive sleep apnea. METHODS: The study included PAP therapy data for 195 children aged between 1 month and 18 years with obstructive sleep apnea and polysomnogram baseline study. We collected demographics, clinical variables, and polysomnogram parameters in all study participants. The individual response to PAP therapy was calculated comparing the apnea-hypopnea index (AHI) in the initial polysomnogram with the mean AHI provided by the download of PAP devices. Multivariate models (logistic regression) were used to examine the predictors of positive PAP response defined as a reduction in AHI ≥ 75%. RESULTS: We found excellent responses to PAP therapy in children (median 85% AHI reduction). However, there was substantial heterogeneity in AHI reductions while on PAP therapy. The best PAP responses were linked to more severe obstructive sleep apnea and higher PAP levels. We also identified that the response to PAP was higher in obese children and lower in males. The best predictive model for individual PAP response was biological sex, obesity, and obstructive AHI ≥ 20 events/h (area under the receiver operating characteristic curve of 0.791). CONCLUSIONS: Real-world data show that PAP is overall an effective therapy in children but the response is heterogeneous. Obstructive sleep apnea parameters and individual factors can be used to predict individual AHI reductions while on PAP and optimize PAP responses at home. CITATION: Aguilar H, Kahanowitch R, Weiss M, et al. Real-world data evaluation of PAP responsiveness in pediatric obstructive sleep apnea. J Clin Sleep Med. 2023;19(7):1313-1319.

Developmental changes in obstructive sleep apnea and sleep architecture in Down syndrome.

BACKGROUND: Down syndrome (DS, also known as Trisomy 21) is a condition associated with abnormal neurodevelopment and a higher risk for sleep apnea. Our study sought to better understand and characterize the age-related developmental differences in sleep architecture and obstructive sleep apnea (OSA) severity in children with DS compared to euploid individuals. METHODS: Retrospective review of polysomnograms in over 4151 infants, children, and adolescents in the pediatric sleep center at Children's National Hospital in Washington D.C. (0-18 years) including 218 individuals with DS. RESULTS: The primary findings of our study are that: (1) severe OSA (obstructive apnea-hypopnea index ≥ 10/h) was more prevalent in the DS group (euploid 18% vs. DS 34%, p < 0.001) with the highest OSA severity being present in young children (<3 years old) and adolescents (>10 years old), (2) abnormalities in sleep architecture in children with DS were characterized by a prolonged rapid-eye movement (REM) sleep onset latency (SOL) (euploid 119 min vs. DS 144 min, p < 0.001) and greater arousal indexes (euploid 10.7/h vs. DS 12.2/h, p < 0.001), (3) developmental changes in the amount of REM sleep or slow wave sleep were not different in DS individuals relative to euploid children, (4) multivariate analyses showed that OSA and REM sleep latency differences between DS and euploid individuals were still present after adjusting by age, biological sex, and body mass index. CONCLUSION: Severe OSA is highly prevalent in children with DS and follows an age-dependent "U" distribution with peaks in newborns/infants and children >10 years of age. Children with DS also have disturbances in sleep architecture characterized by a longer REM SOL and elevated arousal indexes. As sleep cycle generation and continuity play crucial roles in neuroplasticity and cognitive development, these findings offer clinically relevant insights to guide anticipatory guidance for infants, children, and adolescents with DS.

Oxygen saturation thresholds for bronchiolitis at high altitudes: a cost-effectiveness analysis.

BACKGROUND: There is evidence suggesting that exaggerated reliance on pulse oximetry (SpO2) and the use of arbitrary/inadequate thresholds of SpO2 might drive unnecessary hospitalizations for viral bronchiolitis, especially among high-altitude residents. The aim of the present study was to compare the cost-effectiveness of two oxygen SpO2 thresholds for deciding whether infants with viral bronchiolitis living at high altitudes need hospital admission or can be discharged home. METHODS: A cost-effectiveness study was performed to compare the cost and clinical outcomes of two oxygen SpO2 thresholds, adjusted or not, to an altitude above the sea level of Bogota, Colombia (2640 m), for deciding whether infants with viral bronchiolitis need hospitalization or can be discharged home. The principal outcome was avoidance of hospital admission. RESULTS: Compared to the use of an SpO2 threshold of 90%, using an SpO2 threshold of 85% in infants with viral bronchiolitis was associated with lower overall costs (US$130.4 vs. US$194.0 average cost per patient) and a higher probability of hospitalization avoided (0.7500 vs. 0.5900), thus leading to dominance. CONCLUSIONS: The use of an SpO2 threshold below 90% for deciding on hospitalization in infants with viral bronchiolitis living at high altitudes appears to be logical, secure, and cost-effective.

Defining Age-related OSA Features in Robin Sequence Using Polysomnographic-based Analyses of Respiratory Arousal Responses and Gas-exchange Parameters.

INTRODUCTION: Robin sequence (RS) is a leading cause of obstructive sleep apnea (OSA) in newborns. Most studies have focused on understanding anatomic factors leading to OSA and changes in apnea-hypopnea index (AHI) on polysomnography (PSG) beyond the neonatal period. This study aims to define age-related OSA features between patients with RS, without RS and healthy controls using PSG-based analyses of respiratory arousal responses and gas-exchange parameters. DESIGN: Retrospective comparison of PSG features in a total of 48 children encompassing three groups: (a) infants with RS (n = 24, <1-year old), (b) non-RS older children (1-2 years old) with severe OSA (obstructive AHI (OAHI) of ≥10 events; n = 12), and (c) control infants and children (0-2 years old) without sleep apnea (OAHI ≤1.5/h, n = 12). We examined OSA sleep-stage specific and position-specific indexes, and the relationship between OSA severity and respiratory arousal indexes (OAHI/respiratory arousal indexes). RESULTS: OSA sleep-stage specific indexes (rapid eye movement [REM] vs non-REM[NREM]) as well as position-specific indexes (supine vs nonsupine) were similar in individuals with and without RS. Relative to the non-RS groups, infants with RS have more sustained hypoxemia (time with SpO2 < 90%) and reduced arousal responses to OSA demonstrated by higher OAHI/respiratory arousal indexes. OAHI/respiratory arousal indexes significantly correlated with the severity of hypoxemia in infants with RS. CONCLUSION: Infants with RS and OSA show reduced arousal responses to apneic events, which correlates with higher hypoxemia severity. OAHI/respiratory arousal indexes in RS may identify high-risk individuals with upper airway obstruction and reduced arousal protective responses.

The lung in inborn errors of immunity: From clinical disease patterns to molecular pathogenesis.

In addition to being a vital organ for gas exchange, the lung is a crucial immune organ continuously exposed to the external environment. Genetic defects that impair immune function, called inborn errors of immunity (IEI), often have lung disease as the initial and/or primary manifestation. Common types of lung disease seen in IEI include infectious complications and a diverse group of diffuse interstitial lung diseases. Although lung damage in IEI has been historically ascribed to recurrent infections, contributions from potentially targetable autoimmune and inflammatory pathways are now increasingly recognized. This article provides a practical guide to identifying the diverse pulmonary disease patterns in IEI based on lung imaging and respiratory manifestations, and integrates this clinical information with molecular mechanisms of disease and diagnostic assessments in IEI. We cover the entire IEI spectrum, including immunodeficiencies and immune dysregulation with monogenic autoimmunity and autoinflammation, as well as recently described IEI with pulmonary manifestations. Although the pulmonary manifestations of IEI are highly relevant for all age groups, special emphasis is placed on the pediatric population, because initial presentations often occur during childhood. We also highlight the pivotal role of genetic testing in the diagnosis of IEI involving the lungs and the critical need to develop multidisciplinary teams for the challenging evaluation of these rare but potentially life-threatening disorders.

TSLP bronchoalveolar lavage levels at baseline are linked to clinical disease severity and reduced lung function in children with asthma.

Rationale: Thymic stromal lymphopoietin (TSLP) is increasingly recognized as a key molecule in asthma pathogenesis and as a promising therapeutic target in adults. In contrast, in asthmatic children the clinical relevance of TSLP secretion in the lower airways has been remarkably understudied. We tested the hypothesis that pulmonary TSLP levels in asthmatic children correlate with clinical severity, airway inflammation and lower airway obstruction. Methods: Bronchoalveolar lavage (BAL) samples and relevant clinical data were collected from asthmatic children undergoing clinically indicated bronchoscopy at Children's National Hospital in Washington D.C. Protein levels of TSLP, IL-5, IL-1ß, and IL-33 were quantified in BAL at baseline and correlated with individual severity and clinical features including spirometry, serum IgE and eosinophils, BAL neutrophil and eosinophil counts. Results: We enrolled a total of 35 asthmatic children (median age: 9 years). Pediatric subjects with severe asthma had greater TSLP BAL levels at baseline relative to mild or moderate asthmatic subjects (p = 0.016). Asthmatic children with the highest TSLP levels (>75th percentile) had higher IL-5 and IL-1ß BAL levels and greater lower airway obstruction (lower FEV1/FVC ratios). Conclusion: Our study demonstrates for the first time that higher pulmonary TSLP levels obtained at baseline are linked to asthma disease severity in a subset of children. These data indicate that TSLP may play a key role in the pathogenesis of pediatric asthma and thus provide initial support to investigate the potential use of anti-TSLP biologics to treat severe uncontrolled asthmatic children.

The Next Frontier of Prematurity: Predicting Respiratory Morbidity During the First Two Years of Life in Extremely Premature Babies.

Background Advances in perinatal and neonatal medicine have led to an increasing number of infants surviving extreme prematurity (≤27 weeks gestational age, GA). The goal of this study was to examine the respiratory outcomes after neonatal intensive care unit (NICU) discharge of this vulnerable population. We hypothesized that the rates of respiratory hospitalizations are disproportionally higher in the subset of infants born ≤27 weeks GA relative to premature infants born 28-32 weeks GA. Methodology A retrospective longitudinal study of severe premature children (≤32 weeks GA, n = 183) was conducted. We subdivided our sample into extremely preterm infants (≤27 weeks GA; n = 101) and those born very preterm (28-32 weeks GA; n = 82). Our main outcome was the presence of respiratory hospitalizations within 24 months of NICU discharge. Results Extremely premature infants had more than three times higher odds of respiratory hospitalization at 24 months relative to infants born 28-32 weeks GA (adjusted odds ratio = 3.4; 95% confidence interval = 1.8, 6.4; p < 0.01). The increased risk of respiratory hospitalization in extremely premature infants was independent of GA. Regression models identified that the duration of supplemental oxygen and Black/African American ethnicity were significant predictors of respiratory hospitalizations in both prematurity groups independent of gender and birth weight. Conclusions The results support that babies born ≤27 weeks GA represent a distinct high-risk group of severely premature infants that needs novel preventive strategies and targeted interventions to improve their respiratory outcomes after NICU discharge.

Emergency department-initiated home oxygen for viral bronchiolitis: A cost-effectiveness analysis.

OBJECTIVE: The use of emergency department (ED)-initiated outpatient oxygen therapy has been considered to be a possible alternative to hospitalization for otherwise healthy-appearing, well-hydrated infants with uncomplicated disease. However, a formal economic evaluation of this treatment strategy is lacking. The aim of the present study was to compare the cost-effectiveness of ED-initiated outpatient oxygen therapy versus conventional inpatient hospitalization in infants with uncomplicated hypoxic bronchiolitis living in Bogota, the high-altitude capital city of Colombia, a middle-income country (MIC). METHODS: A decision analysis model was developed to estimate the cost-effectiveness of ED-initiated outpatient oxygen therapy versus hospitalization. The main outcome of the model was avoidance of admission to a high-dependency unit. RESULTS: Compared to hospitalization, ED-initiated outpatient oxygen therapy was associated with lower total costs (US$306.7 vs. US$638.7 average cost per patient) and a higher probability of avoidance of admission to a high-dependency unit (0.9528 vs. 0.8960), thus leading to dominance. The results were robust to deterministic and probabilistic sensitivity analyses. CONCLUSIONS: Our study suggests that in infants attending the ED with an uncomplicated hypoxic bronchiolitis episode in the city of Bogota, a high-altitude city, ED-initiated outpatient oxygen therapy is a dominant strategy compared to conventional inpatient hospitalization, because it involves a higher probability of avoidance of admission to a high-dependency unit, at lower total treatment costs.

Predicting Failure of Non-Invasive Ventilation With RAM Cannula in Bronchiolitis.

INTRODUCTION: In infants hospitalized for bronchiolitis on non-invasive ventilation (NIV) via the RAM cannula nasal interface, variables predicting subsequent intubation, or NIV non-response, are understudied. We sought to identify predictors of NIV non-response. METHODS: We performed a retrospective cohort study in infants admitted for respiratory failure from bronchiolitis placed on NIV in a quaternary children's hospital. We excluded children with concurrent sepsis, critical congenital heart disease, or with preexisting tracheostomy. The primary outcome was NIV non-response defined as intubation after a trial of NIV. Secondary outcomes were vital sign values before and after NIV initiation, duration of NIV and intubation, and mortality. Primary analyses included Chi-square, Wilcoxon rank-sum, student's t test, paired analyses, and adjusted and unadjusted logistic regression assessing heart rate (HR) and respiratory rate (RR) before and after NIV initiation. RESULTS: Of 138 infants studied, 34% were non-responders. There were no differences in baseline characteristics of responders and non-responders. HR decreased after NIV initiation in responders (156 [143-156] to149 [141-158], p < 0.01) compared to non-responders (158 [149-166] to 158 [145-171], p = 0.73). RR decreased in responders (50 [43-58] vs 47 [41-54]) and non-responders (52 [48-58] vs 51 [40-55], both p < 0.01). Concurrent bacterial pneumonia (OR 6.06, 95% CI: 2.54-14.51) and persistently elevated HR (OR: 1.04, 95% CI: 1.01-1.07) were associated with NIV non-response. CONCLUSION: In children with acute bronchiolitis who fail to respond to NIV and require subsequent intubation, we noted associations with persistently elevated HR after NIV initiation and concurrent bacterial pneumonia.