Diagnostic and Prognostic Risk Assessment of Heat Shock Protein HSPA1B rs2763979 Gene Variant in Asthma.

Given the significant role the heat shock protein Hsp70 plays in modulating cellular homeostasis in several chronic inflammatory disorders, the genetic variation of the inducible HSP70 (HSPA1B) gene may impact protein expression and disease phenotype. The HSPA1B rs2763979 variant has been associated with multiple inflammatory scenarios, but no previous studies have explored its association with asthma. In this sense, this cross-sectional study enrolled 90 children with asthma and 218 age-/sex-matched healthy volunteers for rs2763979 variant genotyping by TaqMan allelic discrimination analysis. The results were investigated under several genetic models and associated with disease susceptibility and clinicolaboratory data. Overall analysis, including the 308 participants, revealed a higher C allele frequency among patients relative to controls (43.0% vs. 33%, p = 0.006). Furthermore, patients with the C variant initially had a higher risk of asthma under heterozygous (OR = 2.75, 95%CI = 1.46-5.18, p = 0.003), homozygous (OR = 3.35, 95%CI = 1.19-9.39, p = 0.008), dominant (OR = 2.83, 95%CI = 1.52-5.25, p < 0.001), and overdominant (OR = 2.12, 95%CI = 1.20-3.74, p = 0.008) models. However, after employing a 1:1 nearest propensity matching analysis, the studied variant showed only borderline significance with asthma under the dominant model in 71 matched cohorts. Interestingly, patients who carry the rs2763979 CC genotype showed favorable spirometric parameters in terms of better (mean ± SD) forced vital capacity (86.3 ± 7.4 vs. 77.7 ± 6.1 and 75.7 ± 7.2 for CT and TT, respectively, p = 0.021), forced expiratory volume in one second before bronchodilation (60.7 ± 12.9 vs. 54.9 ± 7.6 and 56.1 ± 7.5 for CT and TT, respectively, p = 0.021), and an improvement in peak expiratory flow rate after inhaled salbutamol bronchodilator (p = 0.044) relative to the counterpart genotypes. In conclusion, the HSPA1B rs2763979 variant might have prognostic utility as a genetic marker for asthma in our population. Further larger studies on different ethnicities are recommended to validate the results.

Monoclonal Antibody Treatment of RSV Bronchiolitis in Young Infants: A Randomized Trial.

BACKGROUND: Monoclonal antibody to respiratory syncytial virus (RSV; palivizumab) is recommend for prophylaxis of high-risk infants during bronchiolitis seasons but not for RSV bronchiolitis treatment. Our aim was to determine if palivizumab would be helpful in young infants with acute RSV bronchiolitis. METHODS: Eligible infants ≤3 months old presenting to the pediatric emergency service with RSV-positive bronchiolitis requiring inpatient admission underwent double-blind random assignment to single-dose intravenous palivizumab (15 mg/kg) or placebo. The primary efficacy outcome was the need for inpatient readmission in the 3 weeks after discharge. Secondary outcomes were time to readiness for hospital discharge, need for PICU on the initial admission, and need for revisit not requiring readmission for the same illness during 3-week follow-up. RESULTS: A total of 420 infants (median age 49 days) diagnosed with RSV bronchiolitis were randomly assigned; 417 received treatment, and 413 completed follow-up. Readmission during follow-up was needed for 23 (11%) patients on palivizumab and 19 (9.3%) patients in the placebo group (difference 1.8%; 95% confidence interval -4.4% to 7.7%; P = .51). Geometric mean time to readiness for discharge was 29.5 hours for the palivizumab group and 30.2 hours for the placebo group (ratio 0.98; 95% confidence interval 0.81 to 1.20). No safety issues were reported. CONCLUSIONS: Intravenous palivizumab did not appear to help or harm young infants with acute RSV-positive bronchiolitis.

Caffeine for the Treatment of Apnea in Bronchiolitis: A Randomized Trial.

OBJECTIVE: To evaluate the efficacy and safety of caffeine citrate in the treatment of apnea in bronchiolitis. STUDY DESIGN: Eligible infants aged ≤4 months presenting to the main pediatric emergency service with apnea associated bronchiolitis were stratified by gestational age (<34 weeks or longer) and randomized to receive a single dose of intravenous 25 mg/kg caffeine citrate or saline placebo. The primary efficacy outcome was a 24-hour apnea-free period beginning after completion of the blinded study drug infusion. Secondary outcomes were frequency of apnea by 24, 48, and 72 hours after study medication, need for noninvasive/invasive ventilation, and length of stay in the hospital's pediatric intensive care/step-down unit. RESULTS: A total of 90 infants diagnosed with viral bronchiolitis associated with apnea (median age, 38 days) were enrolled. The rate of respiratory virus panel positivity was similar in the 2 groups (78% for the placebo group vs 84% for the caffeine group). The geometric mean duration to a 24-hour apnea-free period was 28.1 hours (95% CI, 25.6-32.3 hours) for the caffeine group and 29.1 hours (95% CI, 25.7-32.9 hours) for the placebo group (P = .88; OR, 0.99; 95% CI, 0.83-1.17). The frequency of apnea at 24 hours, 24-48 hours, and 48-72 hours after enrollment and the need for noninvasive and invasive ventilation were similar in the 2 groups. No safety issues were reported. CONCLUSIONS: A single dose of caffeine citrate did not significantly reduce apnea episodes associated with bronchiolitis. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01435486.

Rapid Intravenous Rehydration Therapy in Children With Acute Gastroenteritis: A Systematic Review.

BACKGROUND: Rapid intravenous (IV) rehydration is commonly used for the management of pediatric gastroenteritis in the emergency department. The current practice shows wide variation in the volume and rate of rapid IV hydration. The aim of this review was to assess the efficacy of rapid IV rehydration compared with standard method in children with gastroenteritis. METHOD: MEDLINE (1946-2014), EMBASE (1974-2014), and CENTRAL via the Cochrane Library (Issue 8, 2014) were systematically searched to identify eligible studies. Inclusion criteria were randomized controlled trials of rapid IV rehydration in children with gastroenteritis. RESULTS: A total of 1513 articles were retrieved, and our inclusion criteria were met by 3 studies, with a total of 464 participants. The percentage of children who were successfully rehydrated and tolerated oral fluids at 2 to 4 hours after starting IV fluid therapy ranged from 69% to 100% in both rapid IV rehydration and standard method. Time to discharge ranged from 2 to 6 hours (rapid rehydration) versus 2 to 5 hours (standard rehydration). Emergency department revisits ranged from 3% to 16% (rapid rehydration) versus 5% to 14% (standard). Summarized results suggested that rapid IV rehydration may be associated with longer time-to-discharge and higher readmission rates. The new evidence fails to demonstrate superiority of large-volume (60 mL/kg/h) over standard (20 mL/kg/h) IV rehydration. CONCLUSIONS: Standard volume IV rehydration for 1 to 4 hours followed by oral hydration or maintenance IV fluids seems sufficient for most children with gastroenteritis requiring IV fluid administration. However, more evidence is needed to establish an optimal IV rehydration regimen.

Life-threatening cardiac arrhythmia after a single dose of nebulized epinephrine in pediatric emergency department.

Cardiac adverse effects are not commonly reported complications of nebulized epinephrine therapy. We present a case of critical cardiac arrhythmia developed at the Pediatric Emergency Department in an otherwise healthy infant after receiving 3 mg of L-epinephrine (1:1000) nebulization over a 90 min period for a diagnosis of bronchiolitis. Unstable ventricular tachycardia was found after the nebulization therapy that required chemical cardioversion. Frequent premature ventricular contractions (PVCs) were found initially following the cardiac insult that was controlled with oral amiodarone, and disappeared during follow-up. Although epinephrine inhalation is generally safe, adverse life-threatening events could be unpredictable and may evolve even after a single dose of nebulized epinephrine.