COVID vaccine evaluation of barriers and resources among families of children with diagnosed allergies.

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.

Modulation of the Interleukin-21 Pathway with Interleukin-4 Distinguishes Common Variable Immunodeficiency Patients with More Non-infectious Clinical Complications.

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.

High physician adherence to phenotype-specific asthma guidelines, but large variability in phenotype assessment in children.

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.

Clinical effectiveness of inhaled corticosteroids versus montelukast in children with asthma: prescription patterns and patient adherence as key factors.

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.

Written action plan in pediatric emergency room improves asthma prescribing, adherence, and control.

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).

Preemptive use of high-dose fluticasone for virus-induced wheezing in young children.

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.)