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Background: We aimed to determine vaccine hesitancy and the main barriers associated with the 2019 novel coronavirus, SARS-CoV-2 (COVID-19) vaccination among families of children diagnosed with food/drug/environmental allergies. Methods: Between May and June 2021, we approached 146 families seen at the outpatient allergy clinic at the Montreal Children's Hospital and a community allergy practice were invited to complete an anonymous online survey on COVID-19 and vaccination attitudes and behaviour. Uni and multivariable logistic regressions were compared to estimate factors associated with vaccine hesitancy. Results: Among all patients, 24.1% reported vaccine hesitancy. The large majority of parents (95.2%) believed that vaccines work. The most common barrier to vaccination was fear of adverse side effects (57.0%). One-third of participants (31.5%) reported that a history of food, venom and drug allergy was a contraindication for COVID-19 vaccination. Fifty-nine (60.8%) participants stated that the dissemination of additional information would increase their willingness to be vaccinated. Most (96.9%) parents reported that their children's vaccinations were up to date. Hesitant families were more likely to be parents of children aged 6-10 years, be of Asian descent, report that mRNA vaccines are riskier than traditional vaccines, and report that the vaccine should not be given if the child has a history of allergic reaction to vaccines. Conclusion: Vaccine hesitancy exists mainly among certain ethnic groups and families with young children. Allergies to food, venom and drug allergy are commonly perceived as contraindications for COVID-19 vaccination. Knowledge translation activities addressing parental concerns will help increase vaccination rates.

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PURPOSE: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and clinical manifestations such as infections, autoimmunity, and malignancy. We sought to determine if responsiveness to interleukin-21 (IL-21), a key cytokine for B cell differentiation, correlates with distinct clinical phenotypes in CVID. METHODS: CVID subjects were recruited through the Canadian Primary Immunodeficiency Evaluative Survey registry. Peripheral blood mononuclear cells were cultured with anti-CD40 ± interferon-gamma, interleukin-4 (IL-4), IL-21, and/or IL-4+IL-21. B cell subpopulations and IgG production were determined at baseline and day 7 by flow cytometry and ELISA. Clinical complications were compared using contingency tables. RESULTS: CVID subjects exhibited decreased CD27+ B cells and IgG production after 7 days of stimulation with anti-CD40+IL-21 (p < 0.05). In a subset of subjects [CVID responders (R)], the addition of IL-4 led to significant increases in CD27+ B cells and IgG (p < 0.05). In CVID non-responders (NR), CD27+ B cells and IgG remained lower despite the addition of IL-4. CVID NR experienced significantly more non-infectious clinical complications of CVID than R [OR 8.8, 95% confidence interval (CI) 1.6 to 48.13]. Previous studies reported that CVID subjects with ≤ 2% class-switched memory B cells were more at risk of these complications, but no significant association was found among this cohort of subjects [OR 3.5, CI 0.9 to 13.3]. In fact, 34.6% of CVID NR had > 2% class-switched memory B cells at baseline. CONCLUSIONS: The IL-4 and IL-21 in vitro assays distinguish two groups of CVID subjects and can be used with baseline B cell subpopulation phenotyping to better identify patients experiencing more vs. fewer clinical non-infectious complications and potentially to modulate therapy.

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BACKGROUND: The implementation of international pediatric asthma guidelines hinges on the distinction between intermittent and persistent phenotypes and the prescription of recommended phenotype-specific pharmacotherapy. OBJECTIVES: To ascertain key factors associated with specialist-confirmed phenotype and document physicians' adherence to practice recommendations in an academic pediatric asthma center. DESIGN/METHODS: Using electronic health records, we identified a cohort of children aged 1-17 years who presented to a tertiary-care asthma center between 2002 and 2007 and received a diagnosis of asthma from a pediatric specialist. Outcomes included: determinants of phenotypes and conformity with phenotype-specific treatment recommendations. RESULTS: Of the 3490 eligible children (11,119 visits), most (47%) were preschoolers, 35% were 6-11 years and 18%, 13-17 years. Of children with confirmed asthma, 59% were classified on presentation as having intermittent, 41% as persistent, asthma. The within-patient phenotype varied over time with a consistency index of 0.76 (best=1); the latter was significantly lower in preschoolers than older children (p<0.0001). The persistent phenotype was highly physician-dependent; it was also positively associated with child's age, asthma severity, multiple triggers, calendar year, and duration of follow-up. Compared to 33% of children with intermittent asthma, 82% of those with persistent asthma were prescribed a maintenance controller, most as monotherapy; combination therapy was usually prescribed after a trial of monotherapy. CONCLUSION: Pediatric asthma specialists were highly adherent to phenotype-specific pharmacotherapy. However, even in an academic center, the notable degree of intra-patient and between-physician variation in phenotype, particularly in preschoolers, was an important impediment to prescribing a maintenance controller. The findings underline the importance of developing validated and standardized means of assessing phenotypes, applicable to the whole pediatric age spectrum.

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OBJECTIVES: To examine the real-life effectiveness of inhaled corticosteroids (ICS) versus leukotriene receptor antagonists (LTRA) monotherapy in children with mild or moderate asthma. METHODS: Using medical and drug records, we accrued a cohort of 227 children aged 2-17 years, prescribed daily LTRA or ICS monotherapy. LTRA-treated children were matched on age, gender, and previous acute-care visits in a 1:3 ratio to ICS-treated children. Outcomes included rescue oral corticosteroids, prescription duration and dispensing, acute-care visits, hospital admissions, and ß(2)-agonist use. RESULTS: More ICS- than montelukast-treated children had persistent asthma (73 vs. 50%) and fewer had good asthma control (35 vs. 61%) at baseline, suggesting residual confounding by indication. Physician prescriptions covered 62% of the follow-up period for ICS compared to 97% for montelukast (mean group difference [MGD]: -17%, 95% CI: -28%, -7%). In pharmacies, patients claimed 51 vs. 74% of prescribed ICS and montelukast, respectively (MGD = -12% [-20%, -4%]). Consequently, dispensed ICS and montelukast covered 24% and 38% of follow-up period, respectively (MGD = -14% [-22%, -6%]). No group differences in oral corticosteroids (RR = 1.10 [0.66, 1.84]) and acute-care visits (RR = 1.79 [0.96, 3.34]) were observed. ICS-treated children experienced more hospital admissions (RR = 3.63 [1.20, 11.03]) and needed more frequently rescue ß(2)-agonist use of ≥4 doses per week (RR = 2.54 [1.23, 5.23]). CONCLUSIONS: When compared to LTRA, the prescription of ICS monotherapy did not significantly reduce rescue oral corticosteroids or acute care visits and was associated with a higher rate of hospital admission for asthma and rescue ß(2)-agonist use. The findings may be due to paradoxical shorter ICS prescription duration and lower patient adherence, despite more persistent asthma and poorer control than in LTRA-treated children.

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RATIONALE: An acute-care visit for asthma often signals a management failure. Although a written action plan is effective when combined with self-management education and regular medical review, its independent value remains controversial. OBJECTIVES: We examined the efficacy of providing a written action plan coupled with a prescription (WAP-P) to improve adherence to medications and other recommendations in a busy emergency department. METHODS: We randomized 219 children aged 1-17 years to receive WAP-P (n = 109) or unformatted prescription (UP) (n = 110). All received fluticasone and albuterol inhalers, fitted with dose counters, to use at the discretion of the emergency physician. The main outcome was adherence to fluticasone (use/prescribed × 100%) over 28 days. Secondary outcomes included pharmacy dispensation of oral corticosteroids, ß(2)-agonist use, medical follow-up, asthma education, acute-care visits, and control. MEASUREMENTS AND MAIN RESULTS: Although both groups showed a similar drop in adherence in the initial 14 days, adherence to fluticasone was significantly higher over Days 15-28 in children receiving WAP-P (mean group difference, 16.13% [2.09, 29.91]). More WAP-P than UP patients filled their oral corticosteroid prescription (relative risk, 1.31 [1.07, 1.60]) and were well-controlled at 28 days (1.39 [1.04, 1.86]). Compared with UP, use of WAP-P increased physicians' prescription of maintenance fluticasone (2.47 [1.53, 3.99]) and recommendation for medical follow-up (1.87 [1.48, 2.35]), without group differences in other outcomes. CONCLUSIONS: Provision of a written action plan significantly increased patient adherence to inhaled and oral corticosteroids and asthma control and physicians' recommendation for maintenance fluticasone and medical follow-up, supporting its independent value in the acute-care setting. Clinical trial registered with www.clinicaltrials.gov (NCT 00381355).

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BACKGROUND: Although virus-induced wheezing is common in preschool-age children, optimal management remains elusive. We examined the efficacy and safety of preemptive treatment with high-dose fluticasone in reducing the severity of recurrent virus-induced wheezing in children. METHODS: We randomly assigned 129 children who were 1 to 6 years of age to receive 750 microg of fluticasone propionate (ex-valve [manufacturer-measured] dose) or placebo twice daily, beginning at the onset of an upper respiratory tract infection and continuing for a maximum of 10 days, over a period of 6 to 12 months. The primary outcome was rescue oral corticosteroid use. Secondary outcomes included symptoms, use of beta(2)-agonists, acute care visits, hospitalizations, discontinuation of the study drug, change in growth and bone mineral density, basal cortisol level, and adverse events. RESULTS: Over a median period of 40 weeks, 8% of upper respiratory tract infections in the fluticasone group led to treatment with rescue systemic corticosteroids, as compared with 18% in the placebo group (odds ratio, 0.49; 95% confidence interval [CI], 0.30 to 0.83). Children who were treated with fluticasone, as compared with those who were given placebo, had smaller mean (+/-SD) gains from baseline in height (6.23+/-2.62 cm [unadjusted value]; z score, -0.19 +/-0.42 vs. 6.56+/-2.90 cm [unadjusted value]; z score, 0.00+/-0.48; difference between groups in z score from baseline to end point, -0.24 [95% CI, -0.40 to -0.08]) and in weight (1.53+/-1.17 kg [unadjusted value]; z score, -0.15+/-0.48 vs. 2.17+/-1.79 kg [unadjusted value]; z score, 0.11+/-0.43; difference between groups in z score from baseline to end point, -0.26 [95% CI, -0.41 to -0.09]). There were no significant differences between the groups in basal cortisol level, bone mineral density, or adverse events. CONCLUSIONS: In preschool-age children with moderate-to-severe virus-induced wheezing, preemptive treatment with high-dose fluticasone as compared with placebo reduced the use of rescue oral corticosteroids. Treatment with fluticasone was associated with a smaller gain in height and weight. Given the potential for overuse, this preventive approach should not be adopted in clinical practice until long-term adverse effects are clarified. (ClinicalTrials.gov number, NCT00238927.)

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