Recommendations for asthma monitoring in children: A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

The effects of vitamin D supplementation on inflammatory biomarkers in patients with asthma: a systematic review and meta-analysis of randomized controlled trials.

Background: While the association between vitamin D and several inflammatory biomarkers in asthma patients has been extensively reported, it remains unclear whether supplementation modifies these biomarkers. This review aims to evaluate the impact of vitamin D supplementation on inflammatory biomarkers measured in vivo in individuals with asthma. Methods: We conducted a systematic review of randomized controlled trials (RCTs) published until November 2022 in six electronic databases evaluating the impact of vitamin D supplementation (any dose, form, administration route, frequency, or duration) compared to placebo in children or adults. The two co-primary outcomes were serum IgE and blood eosinophils reported at the endpoint. Secondary outcomes included other markers of type 2 inflammation (e.g., sputum eosinophils, fractional exhaled nitric oxide, etc.), anti-inflammatory biomarkers (e.g., interleukin (IL)-10, etc.), markers of non-type 2 inflammation (e.g., high-sensitivity C-reactive protein, etc.), and non-specific biomarkers (e.g., macrophages, etc.). Data were aggregated using fixed or random effect models. Results: Thirteen RCTs (5 in adults, 5 in pediatric patients, and 3 in mixed age groups) testing doses of vitamin D supplementation ranging from 800 to 400,000 IU over periods of 6 weeks to 12 months were included. Eight studies provided data on serum IgE and four on blood eosinophils. As secondary outcomes, three studies reported on sputum eosinophils, four on FeNO, five on serum IL-10, and two on airway IL-10. Compared to placebo, vitamin D supplementation had no significant effect on serum IgE (Mean difference [MD] [95% CI]: 0.06 [-0.13, 0.26] IU/mL), blood eosinophils (MD [95% CI]: - 0.02 [-0.11, 0.07] 103/µL), or FeNO (MD [95% CI]: -4.10 [-10.95, 2.75] ppb) at the endpoint. However, the vitamin D supplementation group showed higher serum IL-10 levels compared to placebo (MD [95% CI]: 18.85 [1.11, 36.59] pg/ml) at the endpoint. Although data could not be aggregated, narrative synthesis suggested no significant effect of supplementation on sputum eosinophils and IL-10 in both sputum and exhaled breath condensate, at the endpoint. Conclusion: Vitamin D supplementation in individuals with asthma was not associated with lower inflammatory biomarkers related to type 2 inflammation. However, it was significantly associated with higher serum IL-10 compared to placebo. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022365666.

Asthma and Rhinitis Through the Lifespan of Nonpregnant Women.

Increasingly, clinical practice guidelines advocate a precision medicine-based approach to care for asthma. This focus requires knowledge of not only different asthma phenotypes and their associated biomarkers but also sex and gender differences through the lifespan. Evidence continues to build in favor of different lifetime prevalence, clinical presentations, responses to management, and long-term prognosis of asthma. Women transition through many biological and psychosocial phases in their lives, all of which may interact with, and influence, their health and well-being. Historically, explanations have focused on hormonal effects on asthma in reproductive life, but a greater understanding of mechanisms starting before birth and changing over a lifetime is now possible, with immunologic, inflammatory, and hormonal factors playing a role. This article describes the evidence for the differences in asthma and rhinitis between men and women at different stages of life, the potential underlying mechanisms that contribute to this, and the implications for management and research. Future research studies should systematically report sex differences in asthma so that this knowledge can be used to develop a personalized approach to care, to achieve best possible outcomes for all.

Perinatal and early life factors and asthma control among preschoolers: a population-based retrospective cohort study.

BACKGROUND: Preventing poor childhood asthma control is crucial for short-term and long-term respiratory health. This study evaluated associations between perinatal and early-life factors and early childhood asthma control. METHODS: This retrospective study used administrative health data from mothers and children born 2010-2012 with a diagnosis of asthma before age 5 years, in Alberta, Canada. The outcome was asthma control within 2 years after diagnosis. Associations between perinatal and early-life factors and risk of partly and uncontrolled asthma were evaluated by multinomial logistic regression. RESULTS: Of 7206 preschoolers with asthma, 52% had controlled, 37% partly controlled and 12% uncontrolled asthma 2 years after diagnosis. Compared with controlled asthma, prenatal antibiotics (adjusted risk ratio (aRR): 1.19; 95% CI 1.06 to 1.33) and smoking (aRR: 1.18; 95% CI 1.02 to 1.37), C-section delivery (aRR: 1.11; 95% CI 1.00 to 1.25), summer birth (aRR: 1.16; 95% CI 1.00 to 1.34) and early-life hospitalisation for respiratory illness (aRR: 2.24; 95% CI 1.81 to 2.76) increased the risk of partly controlled asthma. Gestational diabetes (aRR: 1.41; 95% CI 1.06 to 1.87), C-section delivery (aRR: 1.18; 95% CI 1.00 to 1.39), antibiotics (aRR: 1.32; 95% CI 1.08 to 1.61) and hospitalisation for early-life respiratory illness (aRR: 1.65; 95% CI 1.19 to 2.27) were associated with uncontrolled asthma. CONCLUSION: Maternal perinatal and early-life factors including antibiotics in pregnancy and childhood, gestational diabetes, prenatal smoking, C-section and summertime birth, and hospitalisations for respiratory illness are associated with partly or uncontrolled childhood asthma. These results underline the significance of perinatal health and the lasting effects of early-life experiences on lung development and disease programming.

Impact of Unmet Social Needs, Scarcity, and Future Discounting on Adherence to Treatment in Children With Asthma: Protocol for a Prospective Cohort Study.

BACKGROUND: Asthma is one of the most prevalent chronic diseases of childhood and disproportionately affects children with lower socioeconomic status. Controller medications such as inhaled corticosteroids significantly reduce asthma exacerbations and improve symptoms. However, a large proportion of children still have poor asthma control, in part owing to suboptimal adherence. Financial barriers contribute to hindering adherence, as do behavioral factors related to low income. For example, unmet social needs for food, lodging, and childcare may create stress and worry in parents, negatively influencing medication adherence. These needs are also cognitively taxing and force families to focus on immediate needs, leading to scarcity and heightening future discounting; thus, there is the tendency to attribute greater value to the present than to the future in making decisions. OBJECTIVE: In this project, we will investigate the relationship between unmet social needs, scarcity, and future discounting as well as their predictive power over time on medication adherence in children with asthma. METHODS: This 12-month prospective observational cohort study will recruit 200 families of children aged 2 to 17 years at the Asthma Clinic of the Centre Hospitalier Universitaire Sainte-Justine, a tertiary care pediatric hospital in Montreal, Canada. The primary outcome will be adherence to controller medication, measured using the proportion of prescribed days covered during follow-up. Exploratory outcomes will include health care use. The main independent variables will be unmet social needs, scarcity, and future discounting, measured using validated instruments. These variables will be measured at recruitment as well as at 6- and 12-month follow-ups. Covariates will include sociodemographics, disease and treatment characteristics, and parental stress. Primary analysis will compare adherence to controller medication, measured using the proportion of prescribed days covered, between families with versus those without unmet social needs during the study period using multivariate linear regression. RESULTS: The research activities of this study began in December 2021. Participant enrollment and data collection began in August 2022 and are expected to continue until September 2024. CONCLUSIONS: This project will allow the documentation of the impact of unmet social needs, scarcity, and future discounting on adherence in children with asthma using robust metrics of adherence and validated measures of scarcity and future discounting. If the relationship between unmet social needs, behavioral factors, and adherence is supported by our findings, this will suggest the potential for novel targets for integrated social care interventions to improve adherence to controller medication and reduce risk across the life course for vulnerable children with asthma. TRIAL REGISTRATION: ClinicalTrials.gov NCT05278000; https://clinicaltrials.gov/ct2/show/NCT05278000. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37318.

Concordance in COVID-19 serology, bone mineralization, and inflammatory analytes between venous and self-collected capillary blood samples exposed to various pre-analytical conditions.

BACKGROUND: The COVID-19 has led to a significant increase in demand for remote blood sampling in clinical trials. This study aims to ascertain the concordance between venous versus capillary samples, processed immediately or exposed to various pre-analytical conditions. METHODS: Participants (≥12 years old) provided a venous blood sample (processed immediately) and capillary samples allocated to one of the following conditions: processed immediately or exposed to 12-, 24-, or 36-h delays at room temperature or 36-h delays with a freeze-thaw cycle. The analytes of interest included SARS-CoV-2 IgG, 25-hydroxy vitamin D (25(OH)D), alkaline phosphate (ALP), calcium (Ca), phosphate (Ph), and c-reactive protein (CRP). Paired samples were considered interchangeable if they met three criteria: minimal within-subject mean difference, 95% of values within desirable total errors, and inter-class correlation (ICC) > 0.90. RESULTS: 90 participants (44.1% male) were enrolled. When comparing rapidly processed venous with capillary samples, 25(OH)D, ALP, and CRP met all three criteria; SARS-CoV-2 IgG met two criteria (mean difference and ICC); and Ca and Ph met one criterion (mean difference). When considering all three criteria, concentrations of 25(OH)D, CRP, and ALP remained unchanged after delays of up to 36 h; SARS-CoV-2 IgG met two criteria (mean difference and ICC); Ca and Ph met one criterion (mean difference). CONCLUSION: These findings suggest that remote blood collection devices can be used to measure anti-SARS-CoV-2 IgG, 25(OH)D, CRP, and ALP. Further analysis is required to evaluate the interchangeability between venous and capillary testing in Ca and Ph levels, which are more sensitive to pre-analytical conditions.

Oral vitamin D supplemental therapy to attain a desired serum 25-hydroxyvitamin D concentration in essential healthcare teams.

BACKGROUND: The study objectives were to ascertain the efficacy of vitamin D supplementation in rapidly increasing serum vitamin D and of implementation of a hybrid (virtual and in-person) trial. METHODS: In a randomized triple-blind controlled trial, healthcare workers were allocated to receive an oral bolus of 100,000 IU with 10,000 IU/week of vitamin D3 or placebo. The co-primary outcomes were the change from baseline in serum 25-hydroxyvitamin D [(Δ) 25(OH)D] and proportion with vitamin D sufficiency (25(OH)D ≥ 75 nmol/L), at endpoint. Adherence to supplements and procedures as well as adverse event rates were documented. RESULTS: Thirty-four (19 intervention, 15 control) subjects were randomized, with 28 (41%) virtual visits. After 44.78 ± 11.00 days from baseline, a significant adjusted group difference of 44.2 (34.7, 53.8) nmol/L was observed in the Δ 25(OH)D (95% CI) in favor of supplementation; 77.8% of intervention, and 13.3% of control, patients were vitamin D sufficient (OR:6.11, 95% CI:1.6, 22.9). The adherence to intervention was 94.7% in the intervention and 100% in the control groups. Irrespective of visit type, high adherence was observed in sampling procedures and completion of fortnightly online questionnaire. No adverse events attributable to vitamin D were reported. CONCLUSION: The vitamin D supplementation rapidly and safely raised 25(OH)D levels to sufficient levels for a biological effect. Similarly high adherence to study procedures was observed with virtual and in-person participation. TRIAL REGISTRATION: This trial was registered at https://clinicaltrials.gov on July 23, 2020 (# NCT04483635 ).

Reference values for respiratory sinusoidal oscillometry in children aged 3 to 17 years.

BACKGROUND: New oscillometry devices allowing quantification of respiratory function using tidal breathing are commercially available, but reference equations are lacking for the multiethnic Canadian pediatric population. METHODS: We conducted a prospective cross-sectional study of healthy children carefully selected for absence of asthma, atopy, tobacco smoke, obesity, prematurity, and recent respiratory infection. Triplicate measures were obtained of respiratory system resistance (Rrs) and reactance (Xrs), area under the reactance curve (AX) and resonant frequency (Fres) on four signals, whose testing order was randomized: two signals on the Resmon Pro Full (8 Hz and 5-11-19 Hz) and two signals on the tremoflo C-100 (5-37 Hz and 7-41 Hz). Feasibility was defined as the ability to obtain valid reproducible results. Prediction equations and 95% confidence intervals were derived for whole- and within-breath Rrs and Xrs and for AX and Fres, using linear regression or Generalized Additive Models for Location, Scale and Shape. RESULTS: Of 306 children randomized, valid and reproducible results on ≥1 signal were obtained in 299 (98%) multiethnic (69% Caucasians: 8% Black: 23% Others) children aged 3-17 years, 91-189 cm tall. Standing height was the strongest predictor with no significant effect of sex, age, body mass index or ethnicity. Significant within-patient differences were observed between Resmon Pro and tremoflo C-100 measurements, justifying the derivation of device-specific reference equations. CONCLUSION: Valid reproducible oscillometry measurements are highly feasible in children aged 3 years and older. Device-specific reference equations, valid for our multiethnic population, are derived.

Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis.

The COVID-19 outbreak has rapidly expanded to a global pandemic; however, our knowledge is limited with regards to the protective factors against this infection. The aim of this systematic literature review and meta-analysis was to evaluate the impact of vitamin D supplementation on COVID-19 related outcomes. A systematic search of relevant papers published until January 2022 was conducted to identify randomized controlled trials (RCTs) and non-randomized studies of intervention (NRISs). The primary outcomes included the risk of COVID-19 infection (primary prevention studies on uninfected individuals), hospital admission (secondary prevention studies on mild COVID-19 cases), and ICU admission and mortality rate (tertiary prevention studies on hospitalized COVID-19 patients). We identified five studies (one RCT, four NRISs) on primary prevention, with five (two RCTs, three NRISs) on secondary prevention, and 13 (six RCTs, seven NRISs) on tertiary prevention. Pooled analysis showed no significant effect on the risk of COVID-19 infection. No meta-analysis was possible on hospitalization risk due to paucity of data. Vitamin D supplementation was significantly associated with a reduced risk of ICU admission (RR = 0.35, 95% CI: 0.20, 0.62) and mortality (RR = 0.46, 95% CI: 0.30, 0.70). Vitamin D supplementation had no significant impact on the risk of COVID-19 infection, whereas it showed protective effects against mortality and ICU admission in COVID-19 patients.

Association Between Asthma Control Trajectories in Preschoolers and Long-Term Asthma Control.

BACKGROUND: The potential influence of asthma control in early life on long-term outcomes in childhood remains largely unknown. OBJECTIVE: To examine whether asthma control trajectories in the 2 years after diagnosis in preschoolers are associated with long-term unsatisfactory asthma control. METHODS: We conducted a multicenter population-based retrospective cohort study, including four Canadian provincial birth cohorts derived from administrative databases. We included preschoolers (aged <5 years) with a diagnosis of asthma, defined as having one hospitalization or two physician visits for asthma within 2 years. Asthma control trajectories, ascertained over four 6-month periods after diagnosis using a validated index, were classified as controlled throughout, improving control, fluctuating control, worsening control, and out of control throughout. Long-term unsatisfactory control was defined as four or more short-acting ß2-agonist average doses per week or an exacerbation, measured within 6 months before index ages 6, 8, 10, 12, 14, and 16 years. Average risk ratios for long-term unsatisfactory control across all index ages were estimated using a robust Poisson model by province and meta-analyzed with a random effects model. RESULTS: In 50,188 preschoolers with asthma, the pooled average risk of having unsatisfactory control at any index age was 42% (95% confidence interval, 34.6-49.4). Compared with children who were controlled throughout, incrementally higher average risk ratios (95% confidence interval) of long-term unsatisfactory control were observed in each trajectory: improving control, 1.38 (1.28-1.49); fluctuating control, 1.54 (1.40-1.68); worsening control, 1.70 (1.55-1.86) and out of control throughout, 2.00 (1.80-2.21). CONCLUSIONS: Suboptimal asthma control trajectories shortly after a preschool diagnosis were associated with long-term unsatisfactory asthma control. Early control trajectories appear to be promising for predicting the risk for long-term adverse outcomes.

Adherence to inhaled corticosteroids prescribed once vs twice daily in children with asthma.

BACKGROUND: Suboptimal adherence to inhaled corticosteroids (ICS) is associated with poor asthma control. Adult studies suggest that simplification of ICS regimen leads to better adherence. OBJECTIVE: We aimed to determine whether once-daily, compared with twice-daily, ICS dosing was associated with better adherence among children with asthma. METHODS: We conducted a retrospective observational study of children with asthma prescribed with either once-daily or twice-daily ICS monotherapy between 2011 and 2019. Our primary adherence outcome was the proportion of prescribed days covered (PPDC)-that is, the number of days for which the drug was dispensed by the pharmacy divided by the number of days for which it was prescribed. The impact of once-daily vs twice-daily ICS regimen on adherence was evaluated using linear multivariable regression analysis adjusting for covariates. Secondary outcomes included the proportion of patients with greater than or equal to 75% adherence analyzed using logistic regression models. RESULTS: A total of 232 children (61% boys; mean age of 5.8 [3.6] years) were included; 120 children were prescribed once-daily, and 112 twice-daily, ICS. The median PPDC was 66.8% for the once-daily and 57.9% for the twice-daily group (P = .03). Children prescribed once-daily ICS had a 7.2% (95% confidence interval, 1.3-13.1) greater mean PPDC compared with the twice-daily group and greater odds of having PPDC greater than or equal to 75% (71.4% vs 45.5%; odds ratio, 1.80; 95% confidence interval, 1.01-3.26). CONCLUSION: Our findings suggest that once-daily dosing of ICS is associated with better medication adherence than twice-daily dosing. Whether the gain in adherence leads to better asthma control and health outcomes remains to be evaluated.

Reply to Leong et al. Comment on "Hosseini et al. Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis. Nutrients 2022, 14, 2134".

We thank Drs. Leong et al. for their comments [...].

Physician's perspective regarding asthma guided self-management: directives or guidance?

INTRODUCTION: Asthma guided self-management enhances patients' control of their condition under the guidance of the treating physician. The aim of the present study was to understand how physicians perceive, endorse, uptake, and support asthma guided self-management. METHODS: We conducted a secondary supplementary analysis of data originally collected as part of a multicenter collective case study in which physicians treating patients with asthma were interviewed. Using reflective thematic analysis, we aimed to explore physicians' understanding of guided asthma self-management as related to four ideas, namely: (a) understanding of the disease management and treatment goals; (b) defining medical frame and guidance; (c) describing the importance of patient-physician relationship; and (d) implementing asthma guided self-management. RESULTS: Evidence indicates that physicians perceived optimal guided self-management as related to patients' adherence to physician's instructions and recommendations, supported by the adjustment of prescribed pharmaceutical therapy contingent upon patient's symptoms. Some physicians also perceived behavior change and environmental control along with the medical recommendations. While physicians' perception of asthma and its treatment were aligned with the recommended guidelines-i.e., patient-centered care approach based on guided self-management, the actual guidance offered to patients remained primarily directive and paternalistic. Non-pharmacological approaches, such as exercise, smoking cessation, patient self-monitoring, and self-management supported by education and written self-management plans, were given little consideration in the context of the recommended treatment plan.

Tiotropium bromide as adjunct therapy in children with asthma: a clinical experience.

BACKGROUND: The Global Initiative for Asthma has only recently added tiotropium bromide as adjunct controller therapy in severe asthma (Step 4 or 5) in adults (2015) and children (2019). Although not yet approved for pediatric use by Health Canada, it has been occasionally offered by asthma specialists as a therapeutic trial in children with troublesome asthma or treatment for adverse effects. The objective of this study was to describe the indications and real-life clinical experience in initiating tiotropium in children with asthma. METHODS: We designed a retrospective mixed-method case series study of children aged 1-17 years who initiated tiotropium in our tertiary-care centre between 2013 and 2020. Clinical information was extracted from electronic medical records and tiotropium dispensing, from drug claims. Parents/children and physicians independently completed a questionnaire about treatment goals, perceived efficacy, safety, satisfaction, and lessons learned. RESULTS: The 34 (11 females; 23 males) children had a median (range) age of 9.1 (1.4-17.8) years. Children were primarily on Step 4 (85%) or 5 (6%) prior to tiotropium initiation, yet most (84%) did not increase their treatment step after tiotropium initiation. The physicians' treatment goals were to improve asthma control, alleviate adverse effects of current therapy, and/or improve lung function. The most improved symptoms were coughing/moist cough, difficulty breathing, whistling breath, and bronchial secretions/mucus. Although most parents and physicians reported a significant benefit with tiotropium bromide, physicians particularly remarked, as their "lesson learned', on the improvement in chronic symptoms in asthmatic children, particularly those with prominent moist cough and in lung function, in those with seemingly none (or incompletely) reversible obstruction as well as the ability to decrease the ICS and/or LABA dose to lessen adverse effects. A few physicians raised caution on the risk of lower adherence with an additional inhaler. CONCLUSION: In children with severe asthma on Step 4 or 5, tiotropium bromide was primarily used as substitute, rather than additional, adjunct therapy to improve asthma control, alleviate adverse effects, and/or to improve lung function. The latter two indications, combined with its perceived effectiveness in children with prominent moist cough, also suggest additional indications of tiotropium to be formally explored.

Comparing lung oscillometry with a novel, portable flow interrupter device to measure lung mechanics.

In the community setting, assessing spirometry in school-aged children is often limited by the unavailability of respirology technicians at the point-of-care. We developed a new technique called the Rapid Expiratory Occlusion Method (REOM) that measures respiratory resistance during normal breathing, without specialized training. The aim was to examine the concordance between respiratory resistance measured with the REOM and respiratory resistance measured by oscillometry on the tremoflo. Children aged 6-17 yr, with or without asthma, received respiratory resistance testing on the tremoflo, then on the REOM. Three to five replicates with a coefficient of variation ≤15% were obtained on each instrument; the primary outcome was the concordance between the average respiratory resistance on the REOM and that measured at 5 Hz (R5) on the tremoflo. Thirty-two children (11 girls; 21 boys) were enrolled with a mean age of 11.2 (range 6-17) yr; after excluding two children not meeting reproducibility criteria, 9 healthy controls, 15 controlled asthmatics, and 6 poorly controlled asthmatics were included. Resistance measured on the REOM showed a strong correlation with R5 measured on the tremoflo (P < 0.0001) with no significant differences on the Bland-Altman analyses. Children and their parents found the REOM easy to use and would consider for home use if recommended by their doctor. With the high concordance between resistance values measured on the REOM and that on the tremoflo combined with perceived ease of use, the REOM appears as a promising means for measuring lung function, thus supporting further testing of other psychometric properties.NEW & NOTEWORTHY We have developed a novel version of the interrupter technique to measure respiratory resistance. The Rapid Expiratory Occlusion Method (REOM) is a small handheld device that measures respiratory resistance and demonstrates excellent correlation with airway oscillometry. With its ease of use, REOM may be promising for use in community practice, patient's homes, and, if paired with a telemedicine application, could enable the healthcare provider to monitor patients in their homes.

Association between asthma control trajectories in preschoolers and disease remission.

INTRODUCTION: Early disease morbidity has been associated with asthma persistence in wheezing preschoolers; however, whether asthma control trajectories shortly after diagnosis could influence remission is unknown. We examined the association between asthma control trajectories 2 years post-diagnosis in preschoolers and subsequent disease remission. METHODS: We conducted a multicentre population-based retrospective cohort study consisting of 48 687 children with asthma diagnosed before 5 years old and born between 1990 and 2013 in four Canadian provinces who had prolonged disease activity post-diagnosis. Prolonged disease activity was defined as one or more medical visits or medications for asthma every 6-month period for at least four of the six periods post-diagnosis. Follow-up began at 3 years post-diagnosis (at cohort entry). Remission was defined as 2 consecutive years without drug claims or medical visits for asthma or asthma-like conditions following cohort entry. Asthma control trajectories, ascertained over four 6-month periods following diagnosis using a validated index, were classified as: "controlled throughout", "improving control", "worsening control", "out of control throughout" and "fluctuating control". Adjusted Cox models estimated associations between asthma control trajectories and time to remission. A random effects meta-analysis summarised province-specific hazard ratios (HRs). RESULTS: The pooled remission rate was 8.91 (95% CI 8.80-9.02) per 100 person-years. Compared with children controlled throughout, poorer asthma control was associated with incrementally lower hazard ratios of remission in four other trajectories: improving control (HR 0.89, 95% CI 0.82-0.96), fluctuating control (HR 0.78, 95% CI 0.71-0.85), worsening control (HR 0.68, 95% CI 0.62-0.75) and out of control throughout (HR 0.52, 95% CI 0.45-0.59). CONCLUSIONS: Asthma control trajectories 2 years following a diagnosis in preschoolers were associated with remission, highlighting the clinical relevance of documenting control trajectories in early life.

Effect of Nebulized Magnesium vs Placebo Added to Albuterol on Hospitalization Among Children With Refractory Acute Asthma Treated in the Emergency Department: A Randomized Clinical Trial.

Importance: While intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown. Objective: To evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy. Design, Setting, and Participants: A randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed. Interventions: Participants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408). Main Outcomes and Measures: The primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes. Results: Among 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, -4.2%; absolute risk difference 95% [exact] CI, -11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, -0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, -1.32 to 1.67]; P = .82); oxygen saturation (-0.04% [95% CI, -0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, -1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%). Conclusions and Relevance: Among children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT01429415.

Impact of COVID-19 on Pediatric Asthma: Practice Adjustments and Disease Burden.

BACKGROUND: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. OBJECTIVE: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. METHODS: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma. RESULTS: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. CONCLUSIONS: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.