Association of vitamin D with disease severity in infants with bronchiolitis.

Vitamin D's role in immune system regulation and its contribution to host defenses against respiratory infections may have implications for bronchiolitis pathophysiology. This cross-sectional study aimed to determine the association between the clinical severity of bronchiolitis and serum vitamin D levels in infants. Infants aged 1 month to 12 months, diagnosed with bronchiolitis, and healthy controls attending routine immunization were enrolled. Baseline characteristics were recorded, including clinical details, bronchiolitis severity, and course during hospital stay. Bronchiolitis severity score (BSS) was used to score the severity. A 1-2 ml serum sample was obtained for vitamin D levels estimation. The median age of cases (n = 64; 65.6% male) was 5 [3, 8] months, and that of the control group (n = 30) was 3 [2, 9] months. No statistically significant differences were observed between the two groups in age, gender, weight, mode of delivery, family history of atopy/asthma, feeding pattern, smoke exposure, and daily vitamin D supplementation. The median vitamin D levels were not significantly different between the groups (p = 0.68). Among infants with bronchiolitis, 62.5% had vitamin D insufficiency (≤ 20 ng/ml). A significantly higher median BSS indicates that infants with vitamin D insufficiency exhibited more severe disease (p = 0.019). Although a negative correlation between BSS and vitamin D levels was noted, it did not reach statistical significance [rs = (-)0.17; p = 0.16]. CONCLUSION:  Infants with Vitamin D insufficiency experienced more severe bronchiolitis with elevated BSS scores. It highlights the potential role of vitamin D deficiency in severe bronchiolitis. WHAT IS KNOWN: • Vitamin D level is low in infants with bronchiolitis. WHAT IS NEW: • Infant with low vitamin D level experienced more severe bronchiolitis.

Lactate Levels as a Predictor of Emergency Department Revisits in Infants With Acute Bronchiolitis.

OBJECTIVE: This study aimed to identify predictive biomarkers for unscheduled emergency department (ED) revisits within 24 hours of discharge in infants diagnosed with acute bronchiolitis (AB). METHODS: A retrospective observational study was conducted on infants diagnosed with AB who visited 3 emergency medical centers between January 2020 and December 2022. The study excluded infants with comorbidities, congenital diseases, and prematurity and infants who revisited the ED after 24 hours of discharge. Demographic data, vital signs, and laboratory results were collected from the medical records. Univariable and multivariable logistic regression analyses were performed on factors with P of less than 0.1 in univariable analysis. Receiver operator curve analysis was used to assess the accuracy of lactate measurements in predicting ED revisits within 24 hours of discharge. RESULTS: Out of 172 participants, 100 were in the revisit group and 72 in the discharge group. The revisit group was significantly younger and exhibited higher lactate levels, lower pH values, and higher pCO 2 levels compared to the discharge group. Univariable logistic regression identified several factors associated with revisits. Multivariable analysis found that only lactate was a variable correlated with predicting ED revisits (odds ratio, 18.020; 95% confidence interval [CI], 5.764-56.334). The receiver operator curve analysis showed an area under the curve of 0.856, with an optimal lactate cutoff value of 2.15. CONCLUSION: Lactate value in infants diagnosed with AB were identified as a potential indicator of predicting unscheduled ED revisits within 24 hours of discharge. The predictive potential of lactate levels holds promise for enhancing prognosis prediction, reducing health care costs, and alleviating ED overcrowding. However, given the study's limitations, a more comprehensive prospective investigation is recommended to validate these findings.

Longitudinal plasma cytokine concentrations and recurrent wheezing after RSV bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis in young children has been associated with increased risk for developing recurrent wheezing, but the underlying mechanisms, are not completely defined. We hypothesized that RSV induces a disregulated immune response defined by a distinct cytokine profile in infants at increased risk for developing recurrent wheezing. METHODS: Previously healthy infants less than 12 months of age hospitalized with a first episode of RSV bronchiolitis were enrolled and blood samples and clinical and epidemiological data collected. A group of healthy non-infected controls were enrolled in parallel. Children were followed longitudinally and subsequent blood samples collected in RSV-infected infants at one month and at one year after hospital discharge to measure longitudinal plasma concentrations of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17 and IL1-ß. Risk of post-RSV wheezing was assessed by Poisson modelling. RESULTS: From October 2008 to March 2012 we enrolled 37 infants hospitalized with RSV bronchiolitis and 9 healthy age-matched controls. Within the RSV cohort, 17 (46%) children developed recurrent wheezing within the following 12 months. Plasma cytokine profiles measured during the acute infection were similar in children who developed recurrent wheezing versus those who did not, but lower in healthy controls vs RSV infants who subsequently developed wheezing. At one month and 12 months post-acute RSV infection, infants who developed recurrent wheezing had higher IFN-γ plasma concentrations versus those with no-wheezing (p < 0.05). Moreover, IFN-γ concentrations were identified as independent predictor of post-RSV wheezing. CONCLUSIONS: Children with RSV-associated recurrent wheezing had persistently elevated plasma concentrations of IFN-γ for a year after acute infection, suggesting that this cytokine could be used as a biomarker for risk of recurrent wheezing and possibly plays a role in the pathogenesis of this condition.

Transcriptome of airway neutrophils reveals an interferon response in life-threatening respiratory syncytial virus infection.

BACKGROUND: Neutrophils are the most abundant cell type infiltrating the airways during severe respiratory syncytial virus (RSV) infection. Their exact role in disease pathophysiology remains enigmatic. Therefore, we determined genome-wide RNA expression profiles of local and systemic neutrophils in RSV bronchiolitis to provide further insight into local neutrophil biology. METHODS: We performed a single-center analysis, in 16 infants, admitted to the pediatric intensive care unit with severe RSV bronchiolitis. Neutrophils were isolated from blood and tracheobronchial aspirates (sputum). After low input RNA sequencing, differential expression of genes was determined followed by gene set analysis. RESULTS: Paired transcriptomic analysis of airway versus blood neutrophils showed an inflammatory phenotype, characterized by NF-kB signaling and upregulated expression of IL-6 and interferon pathways. We observed distinct expression of neutrophil activation genes (TNFSF13B, FCER1G). DISCUSSION: Our data indicate that airway neutrophils regulate their function at the transcriptional level in response to viral infection. It also suggests that local interferon drives the neutrophil response of severe RSV bronchiolitis.

Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study.

BACKGROUND: Bronchiolitis is the leading cause of infant hospitalizations in the United States. Growing evidence supports the heterogeneity of bronchiolitis. However, little is known about the interrelationships between major respiratory viruses (and their species), host systemic metabolism, and disease pathobiology. METHODS: In an ongoing multicenter prospective cohort study, we profiled the serum metabolome in 113 infants (63 RSV-only, 21 RV-A, and 29 RV-C) hospitalized with bronchiolitis. We identified serum metabolites that are most discriminatory in the RSV-RV-A and RSV-RV-C comparisons using sparse partial least squares discriminant analysis. We then investigated the association between discriminatory metabolites with acute and chronic outcomes. RESULTS: In 113 infants with bronchiolitis, we measured 639 metabolites. Serum metabolomic profiles differed in both comparisons (Ppermutation  < 0.05). In the RSV-RV-A comparison, we identified 30 discriminatory metabolites, predominantly in lipid metabolism pathways (eg, sphingolipids and carnitines). In multivariable models, these metabolites were significantly associated with the risk of clinical outcomes (eg, tricosanoyl sphingomyelin, OR for recurrent wheezing at age of 3 years = 1.50; 95% CI: 1.05-2.15). In the RSV-RV-C comparison, the discriminatory metabolites were also primarily involved in lipid metabolism (eg, glycerophosphocholines [GPCs], 12,13-diHome). These metabolites were also significantly associated with the risk of outcomes (eg, 1-stearoyl-2-linoleoyl-GPC, OR for positive pressure ventilation use during hospitalization = 0.47; 95% CI: 0.28-0.78). CONCLUSION: Respiratory viruses and their species had distinct serum metabolomic signatures that are associated with differential risks of acute and chronic morbidities of bronchiolitis. Our findings advance research into the complex interrelations between viruses, host systemic response, and bronchiolitis pathobiology.

Prevalence of Continuous Pulse Oximetry Monitoring in Hospitalized Children With Bronchiolitis Not Requiring Supplemental Oxygen.

Importance: US national guidelines discourage the use of continuous pulse oximetry monitoring in hospitalized children with bronchiolitis who do not require supplemental oxygen. Objective: Measure continuous pulse oximetry use in children with bronchiolitis. Design, Setting, and Participants: A multicenter cross-sectional study was performed in pediatric wards in 56 US and Canadian hospitals in the Pediatric Research in Inpatient Settings Network from December 1, 2018, through March 31, 2019. Participants included a convenience sample of patients aged 8 weeks through 23 months with bronchiolitis who were not receiving active supplemental oxygen administration. Patients with extreme prematurity, cyanotic congenital heart disease, pulmonary hypertension, home respiratory support, neuromuscular disease, immunodeficiency, or cancer were excluded. Exposures: Hospitalization with bronchiolitis without active supplemental oxygen administration. Main Outcomes and Measures: The primary outcome, receipt of continuous pulse oximetry, was measured using direct observation. Continuous pulse oximetry use percentages were risk standardized using the following variables: nighttime (11 pm to 7 am), age combined with preterm birth, time after weaning from supplemental oxygen or flow, apnea or cyanosis during the present illness, neurologic impairment, and presence of an enteral feeding tube. Results: The sample included 3612 patient observations in 33 freestanding children's hospitals, 14 children's hospitals within hospitals, and 9 community hospitals. In the sample, 59% were male, 56% were white, and 15% were black; 48% were aged 8 weeks through 5 months, 28% were aged 6 through 11 months, 16% were aged 12 through 17 months, and 9% were aged 18 through 23 months. The overall continuous pulse oximetry monitoring use percentage in these patients, none of whom were receiving any supplemental oxygen or nasal cannula flow, was 46% (95% CI, 40%-53%). Hospital-level unadjusted continuous pulse oximetry use ranged from 2% to 92%. After risk standardization, use ranged from 6% to 82%. Intraclass correlation coefficient suggested that 27% (95% CI, 19%-36%) of observed variation was attributable to unmeasured hospital-level factors. Conclusions and Relevance: In a convenience sample of children hospitalized with bronchiolitis who were not receiving active supplemental oxygen administration, monitoring with continuous pulse oximetry was frequent and varied widely among hospitals. Because of the apparent absence of a guideline- or evidence-based indication for continuous monitoring in this population, this practice may represent overuse.

Serum Metabolome Is Associated With the Nasopharyngeal Microbiota and Disease Severity Among Infants With Bronchiolitis.

BACKGROUND: Emerging evidence suggests relationships between the nasopharyngeal metabolome and both the microbiota and severity of bronchiolitis. However, the influence of host systemic metabolism on disease pathobiology remains unclear. We aimed to examine metabolome profiles and their association with more-severe disease, defined by use of positive pressure ventilation (PPV), in infants hospitalized for bronchiolitis. METHODS: In 140 infants with bronchiolitis, metabolomic profiling was performed on serum; samples from 70 were in a training data set, and samples from 70 were in an independent test data set. We also profiled the nasopharyngeal airway microbiota and examined its association with the serum metabolites. RESULTS: Serum metabolome profiles differed by bronchiolitis severity (P < .001). In total, 20 metabolites in the training data set were significantly associated with the risk of PPV, of which 18 remained significant following adjustment for confounders (false-discovery rate [FDR], < 0.10). Phosphatidylcholine metabolites were associated with higher risks of PPV use, while metabolites from the plasmalogen subpathway were associated with lower risks. The test data set validated these findings (FDR < 0.05). Streptococcus abundance was positively associated with metabolites that are associated with higher risks of PPV. CONCLUSIONS: Serum metabolomic signatures were associated with both the nasopharyngeal microbiota and the severity of bronchiolitis. Our findings advance research into the complex interrelations between the airway microbiome, host systemic response, and pathobiology of bronchiolitis.

Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.

BACKGROUND: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in children. There is no specific treatment for bronchiolitis except for supportive treatment, which includes ensuring adequate hydration and oxygen supplementation. Continuous positive airway pressure (CPAP) aims to widen the lungs' peripheral airways, enabling deflation of overdistended lungs in bronchiolitis. Increased airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. Observational studies report that CPAP is beneficial for children with acute bronchiolitis. This is an update of a review first published in 2015. OBJECTIVES: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis. SEARCH METHODS: We conducted searches of CENTRAL (2017, Issue 12), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to December, 2017), Embase (1974 to December 2017), CINAHL (1981 to December 2017), and LILACS (1982 to December 2017) in January 2018. SELECTION CRITERIA: We considered randomised controlled trials (RCTs), quasi-RCTs, cross-over RCTs, and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data using a structured pro forma, analysed data, and performed meta-analyses. MAIN RESULTS: We included three studies with a total of 122 children (62/60 in intervention/control arms) aged up to 12 months that investigated nasal CPAP compared with supportive (or "standard") therapy. We included one new trial (72 children) that contributed data to the assessment of respiratory rate and need for mechanical ventilation for this update. The included studies were single-centre trials conducted in France, the UK, and India. Two studies were parallel-group RCTs and one was a cross-over RCT. The evidence provided by the included studies was low quality; we assessed high risk of bias for blinding, incomplete outcome data, and selective reporting, and confidence intervals were wide.The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (3 RCTs, 122 children; risk ratio (RR) 0.69, 95% confidence interval (CI) 0.14 to 3.36; low-quality evidence). None of the trials measured time to recovery. Limited, low-quality evidence indicated that CPAP decreased respiratory rate (2 RCTs, 91 children; mean difference (MD) -3.81, 95% CI -5.78 to -1.84). Only one trial measured change in arterial oxygen saturation, and the results were imprecise (19 children; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on change in arterial partial carbon dioxide pressure (pCO2) was imprecise (2 RCTs, 50 children; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low-quality evidence). Duration of hospital stay was similar in both CPAP and supportive care groups (2 RCTs, 50 children; MD 0.07 days, 95% CI -0.36 to 0.50; low-quality evidence). Two studies did not report about pneumothorax, but pneumothorax did not occur in one study. No studies reported occurrences of deaths. Several outcomes (change in partial oxygen pressure, hospital admission rate (from emergency department to hospital), duration of emergency department stay, and need for intensive care unit admission) were not reported in the included studies. AUTHORS' CONCLUSIONS: Limited, low-quality evidence suggests that breathing improved (a decreased respiratory rate) in children with bronchiolitis who received CPAP; this finding is unchanged from the 2015 review. Further evidence for this outcome was provided by the inclusion of a low-quality study for the 2018 update. Due to the limited available evidence, the effect of CPAP in children with acute bronchiolitis is uncertain for other outcomes. Larger, adequately powered trials are needed to evaluate the effect of CPAP for children with acute bronchiolitis.

Association Between Maternal 2nd Trimester Plasma Folate Levels and Infant Bronchiolitis.

Objectives Viral bronchiolitis is the most common cause of infant hospitalization. Folic acid supplementation is important during the periconceptional period to prevent neural tube defects. An area of investigation is whether higher prenatal folate is a risk factor for childhood respiratory illnesses. We investigated the association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Methods We conducted a retrospective cohort analysis in a subset of mother-infant dyads (n = 676) enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study and Tennessee Medicaid. Maternal folate status was determined using 2nd trimester (16-28 weeks) plasma samples. Bronchiolitis diagnosis in the first year of life was ascertained using International Classification of Diagnosis-9 codes from Medicaid administrative data. We used multivariable logistic regression to assess the adjusted association of prenatal folate levels and infant bronchiolitis outcome. Results Half of the women in this lower-income and predominately African-American (84%) study population had high levels of folate (median 2nd trimester level 19.2 ng/mL) and 21% of infants had at least one bronchiolitis healthcare visit. A relationship initially positive then reversing between maternal plasma folate and infant bronchiolitis was observed that did not reach statistical significance (poverall = .112, pnonlinear effect = .088). Additional adjustment for dietary methyl donor intake did not significantly alter the association. Conclusions for Practice Results did not confirm a statistically significant association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Further work is needed to investigate the role of folate, particularly higher levels, in association with early childhood respiratory illnesses.

Vitamin D Status at the Time of Hospitalization for Bronchiolitis and Its Association with Disease Severity.

OBJECTIVE: To investigate the association between circulating 25-hydroxyvitamin D [25(OH)D] status at admission and disease severity among infants hospitalized for bronchiolitis and to determine whether the association differs by the form of 25(OH)D-total, bioavailable or free 25(OH)D. STUDY DESIGN: We conducted a 17-center prospective cohort study of 1016 US infants <12 months old hospitalized with bronchiolitis. Vitamin D status was defined by total 25(OH)D levels, and by calculated levels of bioavailable and free 25(OH)D. Bronchiolitis severity was defined by requirement for intensive care and hospital length-of-stay (LOS). Logistic and Poisson regression were used for unadjusted and multivariable analyses. RESULTS: The median age of hospitalized infants was 3.2 months (IQR 1.6-6.0). The median total 25(OH)D was 26.5 ng/mL (IQR 18.0-33.1); 298 (29%) infants had total 25(OH)D <20 ng/mL. In multivariable models, infants with total 25(OH)D <20 ng/mL had higher risk of requiring intensive care (aOR 1.72, 95% CI 1.12-2.64) and longer LOS (adjusted rate ratio 1.39, 95% CI 1.17-1.65) compared with infants with total 25(OH)D ≥30 ng/mL. Infants with the lowest tertile of bioavailable 25(OH)D, compared with those with the highest tertile, had longer LOS (adjusted rate ratio 1.32, 95% CI 1.07-1.62); admission to the intensive care unit was not statistically significant in the adjusted model (aOR 1.39, 95% CI 0.96-2.64). Free 25(OH)D level was not associated with severity of bronchiolitis in either unadjusted or adjusted models. CONCLUSION: In a large, multicenter cohort of US infants hospitalized for bronchiolitis, infants with total 25(OH)D <20 ng/mL had increased risk of intensive care and longer hospital LOS.

Serum LL-37 Levels Associated With Severity of Bronchiolitis and Viral Etiology.

BACKGROUND: LL-37 is a host defense peptide with antimicrobial and immunomodulatory properties. We examined the relation of serum LL-37 levels to the severity of bronchiolitis and viral etiology. METHODS: We performed a 17-center prospective cohort study in infants hospitalized with bronchiolitis over 3 winters (2011-2014). Site teams collected clinical data, nasopharyngeal aspirates and serum. We used real-time polymerase chain reaction to test nasopharyngeal aspirates for 16 viruses. We tested serum for LL-37. Severity of bronchiolitis was defined by intensive care use and hospital length of stay. Viral etiology was defined as respiratory syncytial virus (RSV) or rhinovirus (RV), including coinfections with other viruses. RESULTS: The median age of the 1005 enrolled infants was 3 months (interquartile range, 2-6 months). After adjustment for 12 variables, LL-37 levels in the lowest quartile, compared with the highest, were associated both with intensive care use (adjusted odds ratio [aOR], 1.97; P = .01) and longer hospital stay (1.34; P < .001). In separate multivariable models, infants with LL-37 levels in the lowest 3 quartiles, compared with the highest, were more likely to have RSV (eg, aOR, 2.6 [lowest quartile]; P < .001 [all quartiles]). By contrast, infants with the lowest 3 LL-37 quartiles were less likely to have RV (eg, aOR, 0.5 [lowest quartile]; Pall quartiles ≤ .03 [all quartiles]). CONCLUSIONS: In a large multicenter study of infants hospitalized with bronchiolitis, lower levels of serum LL-37 were associated with increased severity of illness. There was also an inverse relationship between LL-37 levels and the most common virus causing bronchiolitis, RSV. These findings highlight the role of LL-37 in the pathogenesis of bronchiolitis.

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis.

Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p < 0.05). In the other illness groups, the serum S-ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

Relationships Between Adipokine Profiles, Physique Index, and Severity of Bronchiolitis in Infancy.

INTRODUCTION: Relationships between adipokines, adiposity and severity of acute viral bronchiolitis in infancy have not been elucidated. MATERIALS AND METHODS: We investigated the relationships between three serum adipokines (leptin, adiponectin and TNF-α), physique index (Kaup index) and clinical severity in 13 bronchiolitis infants. Seven healthy infants were enrolled as the control group. We used Modified Pulmonary Index Score (MPIS) to evaluate bronchiolitis severity. RESULTS: No significant differences in adipokine levels were found between groups. In bronchiolitis infants, Kaup index negatively correlated with MPIS (r = -0.614, p = 0.03). A positive correlation was observed between the serum leptin/adiponectin ratio and MPIS (r = 0.618, p = 0.03), although correlations were not observed between respective serum adipokines levels and MPIS. Serum leptin and adiponectin had significantly negative correlations with age (r = 0.815, p = 0.001 and r = 0.566, p = 0.04, respectively), but not Kaup index. CONCLUSION: The severity of viral bronchiolitis in infancy may be related to the adipokine profile, but not adiposity.

[Effect of atopy on serum glucocorticoid receptor levels in children with bronchiolitis].

OBJECTIVE: To investigate the effect of atopy on the expression of glucocorticoid receptors in children with bronchiolitis. METHODS: ELISA was used to measure the changes in the serum levels of glucocorticoid receptor α (GRα) and glucocorticoid receptor ß (GRß) in the bronchiolitis group (77 children, including 34 children with atopy) and pneumonia group (68 children). Thirty-eight children who were prepared to undergo surgeries for non-infectious diseases and had no atopy or family history of allergic diseases were enrolled as the control group. RESULTS: The bronchiolitis group and the pneumonia group had significant increases in the serum levels of GRα and GRß compared with the control group (P<0.01), and the bronchiolitis group had significant increases in these levels compared with the pneumonia group (P<0.01). Compared with the control group and the pneumonia group, the bronchiolitis group had a significant increase in the GRα/GRß ratio (P<0.01). Compared with the control group, the children with or without atopy in the bronchiolitis group had significant increases in the serum levels of GRα and GRß (P<0.01). The non-atopic children in the bronchiolitis group had a significant increase in the serum level of GRß compared with the atopic children (P<0.01). The atopic children in the bronchiolitis group had a significant increase in the GRα/GRß ratio compared with the control group and non-atopic children in the bronchiolitis group (P<0.01). CONCLUSIONS: Children with bronchiolitis have increased serum levels of GRα and GRß. The children with atopy have an increased GRα/GRß ratio, suggesting that the atopic children with bronchiolitis are highly sensitive to glucocorticoids.

Nasal irrigation with saline solution significantly improves oxygen saturation in infants with bronchiolitis.

AIM: Published guidelines do not recommend nasal irrigation in bronchiolitis, but it is common practice in Italy, despite a lack of data on its benefits or adverse effects. This single-blind, multicentre, randomised controlled trial compared nasal irrigation using either isotonic 0.9% sodium chloride or hypertonic 3% sodium chloride with simple supportive care in infants with bronchiolitis. METHODS: We randomly assigned 133 infants up one year of age, who were admitted to the emergency department with bronchiolitis and an oxygen saturation (SpO2) of between 88 and 94%, to the isotonic (n = 47), hypertonic (n = 44) or standard care (n = 42) groups. Variations in SpO2 and the wheeze, air exchange, respiratory rate, muscle use (WARM) respiratory distress score were recorded at zero, five, 15, 20 and 50 minutes. RESULTS: Five minutes after the intervention, the median SpO2 value (95%) in the isotonic group was higher than both the hypertonic (94%) and the standard care (93%) groups. The differences between the isotonic and standard treatment groups were statistically significant at each time point, while the hypertonic group only reached significantly higher values after 50 minutes. However, the WARM score did not improve. CONCLUSION: A single nasal irrigation with saline solution significantly improved oxygen saturation in infants with bronchiolitis.

Low eosinophils during bronchiolitis in infancy are associated with lower risk of adulthood asthma.

BACKGROUND: Infant bronchiolitis may be the first manifestation of asthma. AIM: To evaluate the association of early-childhood risk or protective factors for asthma and lung function reduction in adults 30 years after bronchiolitis in infancy. METHODS: Forty-seven former bronchiolitis patients attended the clinical study at the median age of 29.5 years, including doctoral examination and measurement of post-bronchodilator lung function with flow-volume spirometry. Data on early-life risk factors including blood eosinophil counts on admission for bronchiolitis and on convalescence 4-6 weeks after bronchiolitis were available. RESULTS: Low blood eosinophil count <0.25 × 10E9/l on admission for bronchiolitis was a significant protective factor and high blood eosinophil count >0.45 × 10E9/l on convalescence was a significant risk factor for asthma in adulthood independently from atopic status in infancy. Parental asthma and high blood eosinophil count >0.45 × 10E9/l during bronchiolitis were significant risk factors for irreversible airway obstruction (FEV1/FVC ratio below the 5th percentile lower limit of normality after bronchodilation). CONCLUSION: Our adjusted analyses confirmed that eosinopenia during infant bronchiolitis predicted low asthma risk and eosinophilia outside infection predicted high asthma risk up to the age of 28-31 years. Parental asthma and eosinophilia during bronchiolitis were recognized as risk factors for irreversible airway obstruction.

Low serum 25-hydroxyvitamin D levels and bronchiolitis severity in Spanish infants.

UNLABELLED: This cross-sectional study was performed to examine the prevalence of hypovitaminosis D in infants with acute bronchiolitis compared with control subjects and to evaluate the relationship between serum 25-hydroxyvitamin D (25(OH) D) and the severity of bronchiolitis. Serum 25(OH) D levels were measured by radioimmunoassay in 48 infants with acute bronchiolitis (2.5 ± 2.0 months) and in 30 healthy infants (3.2 ± 2.3 months). 25(OH) D levels (ng/ml) in children with acute bronchiolitis were significantly lower than in the control group (median 29.9 ng/ml (interquartile range (IQR) 21.4-37.5) versus median 38.2 ng/ml ((IQR 26.1-48.1), p = 0.022), mainly in infants with moderate-severe bronchiolitis (median 29.8 ng/ml, IQR 19.2-35.9). The prevalence of hypovitaminosis D was remarkably greater among infants with bronchiolitis than in control subjects (52.1 versus 26.6%). A significant inverse correlation was found between serum 25-hydroxyvitamin D levels and disease severity (rho = -0.457, p < 0.001). CONCLUSION: The prevalence of hypovitaminosis D is high in Spanish infants with bronchiolitis. The severity of acute bronchiolitis increases with a decline in serum 25 (OH) D level.

Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.

BACKGROUND: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in infants. There is no specific treatment for bronchiolitis except for supportive therapy. Continuous positive airway pressure (CPAP) is supposed to widen the peripheral airways of the lung, allowing deflation of over-distended lungs in bronchiolitis. The increase in airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. In observational studies, CPAP is found to be beneficial in acute bronchiolitis. OBJECTIVES: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis. SEARCH METHODS: We searched CENTRAL (2014, Issue 3), MEDLINE (1946 to April week 2, 2014), EMBASE (1974 to April 2014), CINAHL (1981 to April 2014) and LILACS (1982 to April 2014). SELECTION CRITERIA: We considered randomised controlled trials (RCTs), quasi-RCTS, cross-over RCTs and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data using a structured proforma, analysed the data and performed meta-analyses. MAIN RESULTS: We included two studies with a total of 50 participants under 12 months of age. In one study there was a high risk of bias for incomplete outcome data and selective reporting, and both studies had an unclear risk of bias for several domains including random sequence generation. The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (two RCTs, 50 participants; risk ratio (RR) 0.19, 95% CI 0.01 to 3.63; low quality evidence). Neither trial measured our other primary outcome of time to recovery. One trial found that CPAP significantly improved respiratory rate compared with no CPAP (one RCT, 19 participants; mean difference (MD) -5.70 breaths per minute, 95% CI -9.30 to -2.10), although the other study reported no difference between groups with no numerical data to pool. Change in arterial oxygen saturation was measured in only one trial and the results were imprecise (one RCT, 19 participants; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on the change in partial pressure of carbon dioxide (pCO2) was also imprecise (two RCTs, 50 participants; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low quality evidence). Duration of hospital stay was similar in both of the groups (two RCTs, 50 participants; MD 0.07 days, 95% CI -0.36 to 0.50; low quality evidence). Both trials reported no cases of pneumothorax and there were no deaths in either study. Change in partial pressure of oxygen (pO2), hospital admission rate (from emergency department to hospital), duration of emergency department stay, need for intensive care unit admission, local nasal effects and shock were not measured in either study. AUTHORS' CONCLUSIONS: The effect of CPAP in children with acute bronchiolitis is uncertain due to the limited evidence available. Larger trials with adequate power are needed to evaluate the effect of CPAP in children with acute bronchiolitis.

Serum sRAGE as a potential biomarker for pediatric bronchiolitis: a pilot study.

PURPOSE: Traditional inflammatory biomarkers are insufficient for the evaluation of bronchiolitis severity. Recent investigations have shown that the receptor for advanced glycation end product (RAGE) and its soluble isoforms (sRAGE) play a critical role in the pathogenesis of lung injury. Main objective was to assess the serum levels of sRAGE of children with severe bronchiolitis admitted to the pediatric intensive care unit (PICU). Secondary objective was to study sRAGE correlation with the evolution and traditional biomarkers. METHODS: Prospective, observational and descriptive study, 43 healthy controls and 37 patients (December 2011-February 2012) were enrolled. sRAGE levels were assessed and compared. In patients, the relation between sRAGE levels and clinical evolution, respiratory assistance, white blood cell count, absolute neutrophils count, serum C-reactive protein, and serum procalcitonin was analyzed. RESULTS: A statistical difference was found in the mean value of sRAGE at PICU admission between patients and controls (1,215.7 ± 535 vs 849 ± 579 pg/ml). Also a significant inverse correlation was found between sRAGE and the Wood-Downes Score at admission (p = 0.02). CONCLUSIONS: Serum sRAGE could be elevated in children with bronchiolitis. Larger clinical studies are necessary to elucidate its role as a bronchiolitis inflammatory and/or lung injury biomarker.

Brain natriuretic peptide: the reason of respiratory distress is heart disease or lung disease?

OBJECTIVES: The aim of this study was to determine whether plasma levels of amino-terminal brain natriuretic peptide (BNP) could differentiate between heart failure and lung disease among infants with acute bronchiolitis. METHODS: Sixty-eight infants (age range, 1-26 months; median age, 5.9 ± 5.0 months) who presented with respiratory distress underwent physical examination, plasma BNP measurement, and echocardiography within 24 hours after admission. Nineteen (28%) patients had congenital heart disease. The control group was consisted of 30 healthy infants. RESULTS: Although mean plasma BNP levels were 118.9 ± 219.5 pg/mL in patients with isolated bronchiolitis (n = 49), it was 841.2 ± 1475.8 pg/mL in patients with congenital heart disease (n = 19). Plasma BNP levels were significantly higher in infants with congenital heart disease (P = .001). CONCLUSION: It was shown that plasma BNP levels were affected much more in cardiac disease rather than lung disease. Among infants with respiratory distress, plasma BNP measurements can differentiate congenital heart disease and lung disease and can be used to monitor the effects of treatment for infants with heart failure. RESPONSE TO REVIEWERS: The comments were taken for consideration. The patient groups control BNP levels were attached to the results. As it was a clinical study and multiple factors (respiratory score, respiratory rate, treatment, etc) may effect on BNP levels, the tables could not be decreased to 1 table.