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.

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.

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.

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.

Weight status and nonadherence to asthma maintenance therapy among children enrolled in a public drug insurance plan.

Objective: The pediatric obese-asthma phenotype is associated with poor control, perhaps because of medication nonadherence. This study aimed to assess whether weight status is associated with nonadherence in children prescribed new asthma maintenance therapies.Methods: A historical cohort was constructed from a clinical database linking individual patient and prescription data to Quebec's prescription claims registry. Children aged 2-18 years with specialist-diagnosed asthma who were newly prescribed one of the following maintenance controllers: leukotriene receptor antagonists (LTRA); low-dose inhaled corticosteroids (ICS); medium/high-dose ICS; or combination therapy (ICS with long-acting beta-2 agonists and/or LTRA), at the Asthma Center of the Montreal Children's Hospital from 2000-2007 were included. Primary nonadherence was defined as not claiming any prescriptions, whereas secondary nonadherence was measured with the proportion of prescribed days covered (PPDC ≤ 50%) among primary adherers over a 6-month follow-up period. A modified Poisson regression model served to estimate the effect of excess weight (BMI > 85th percentile) on primary and secondary nonadherence.Results: Approximately one third of patients were primary nonadherers and 60% took less than 50% of prescribed therapy. Excess weight was associated with a trend toward increased risk of primary nonadherence in children newly prescribed low-dose ICS (RR 1.53, 95%CI 0.94-2.49), and of secondary nonadherence in children initiating medium/high-dose ICS (RR 1.24; 95%CI 0.98-1.59).Conclusions: Excess weight status is a possible determinant of primary nonadherence in children initiating low-dose ICS and secondary nonadherence to higher-dose ICS regimens. This hypothesis-generating study suggests that nonadherence may be a potential contributor to higher morbidity in children with obese-asthma.

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.

Evaluating the effectiveness of systemic corticosteroids to mitigate relapse in children assessed and treated for acute asthma: A network meta-analysis.

OBJECTIVE: The objective of this systematic review was to explore the effectiveness of various systemic corticosteroid (SCS) regimens to mitigate relapse in children with asthma discharged from an acute care setting. DATA SOURCES: Medline, EMBASE, Global Health, International Pharmaceutical Abstracts, EMB ALL, CINAHL, SCOPUS, Proquest Dissertations and Theses Global, and LILACS were searched using controlled vocabulary and key words. Additional citations were searched via clinical trial registries, Google Scholar, bibliographies, a SCOPUS forward search of a sentinel paper, and hand searching conference abstracts. STUDY SELECTION: No limitations based on language, publication status, or year of publication were applied. Two independent reviewers searched to identify randomized controlled trials comparing the effectiveness of SCS regimens to prevent relapse in children following treatment for acute asthma. RESULTS: Fifteen studies were included. In 3 studies comparing SCS to placebo, asthma relapse was significantly reduced (RR = 0.10; 95% CI: 0.01, 0.77; I2 = 0%). A network analysis identified a significant reduction in relapse in children treated with intramuscular corticosteroids (OR = 0.038; 95% CrI: 0.001, 0.397), short-course oral prednisone (OR = 0.054; 95% CrI: 0.002, 0.451), and oral dexamethasone (OR = 0.071; 95% CrI: 0.002, 0.733) compared to placebo. CONCLUSION: This review found evidence that SCS reduces relapse in children following treatment for acute asthma, albeit based on a limited number of studies. Additional studies are required to assess the differential effect of SCS doses and treatment duration to prevent relapse in children following discharge for acute asthma.

The obese-asthma phenotype in children: An exacerbating situation?

BACKGROUND: Current evidence regarding the relationship between childhood obesity, decreased response to inhaled corticosteroids (ICSs), and poor asthma control is conflicting. OBJECTIVES: We assessed whether obesity (1) is associated with time to first exacerbation among children with asthma initiating step 3 maintenance therapies and (2) modifies the effectiveness of step 3 therapies. METHODS: A retrospective cohort study was conducted from clinical data linked to health and drug administrative databases. The cohort consisted of children aged 2 to 18 years with specialist-confirmed asthma who initiated medium/high-dose ICS monotherapy or low/medium-dose ICS with leukotriene receptor antagonist/long-acting ß-agonist (combination therapy) at the Montreal Children's Hospital Asthma Center from 2000 to 2007. Children were classified as exposed to step 3 therapies when they were dispensed a corresponding drug claim during follow-up, whereas those without claims were classified as nonadherers. Marginal structural Cox models were used to estimate the effect of obesity (body mass index > 97th percentile) and treatment on time to exacerbation, which was defined as any emergency department visit, hospitalization, or use of oral corticosteroids for asthma. RESULTS: Of the 4621 cohort patients, 231 initiated ICS monotherapy, and 97 initiated combination therapy. The hazard ratio (HR) for obesity was 1.67 (95% CI, 1.41-1.98). Compared with nonobese nonadherers, the HR for obese nonadherers was 1.54 (95% CI, 0.97-2.45); the HR for ICS monotherapy in obese and nonobese children was 0.85 (95% CI, 0.47-1.52) and 0.58 (95% CI, 0.37-0.91), respectively; and the HR for combination therapy in obese and nonobese children was 0.50 (95% CI, 0.13-1.89) and 0.46 (95% CI, 0.23-0.92), respectively. CONCLUSION: Obesity might be a determinant of shorter exacerbation-free time in children with asthma; however, we could not rule out a differential response to step 3 therapies by obesity status, potentially because of a lack of precision.

Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice.

Although montelukast is generally well tolerated, postmarketing studies have reported serious neuropsychiatric adverse drug reactions (ADRs) leading to a United States Food and Drug Administration black box warning. The objective of this study was to determine the incidence of neuropsychiatric ADRs leading to discontinuation of montelukast in asthmatic children.We conducted a retrospective cohort study in children aged 1-17 years initiated on montelukast. In a nested cohort study, children initiated on montelukast as monotherapy or adjunct therapy to inhaled corticosteroids (ICS) were matched to those initiated on ICS monotherapy. A non-leading parental interview served to ascertain the occurrence of any ADRs with any asthma medication, and circumstances related to, and evolution of, the event.Out of the 106 participants who initiated montelukast, most were male (58%), Caucasian (62%) with a median (interquartile range) age of 5 (3-8) years. The incidence (95% CI) of drug cessation due to neuropsychiatric ADRs was 16 (10-26)%, mostly occurring within 2 weeks. Most frequent ADRs were irritability, aggressiveness and sleep disturbances. The relative risk of neuropsychiatric ADRs associated with montelukast versus ICS was 12 (2-90).In the real-life setting, asthmatic children initiated on montelukast experienced a notable risk of neuropsychiatric ADRs leading to drug cessation, that is significantly higher than that associated with ICS.

Assessing adherence to inhaled corticosteroids in asthma patients using an integrated measure based on primary and secondary adherence.

PURPOSE: There are very few studies on primary adherence (i.e., first filling of a prescription) to inhaled corticosteroids (ICS) in asthma patients; two have involved children. Moreover, adherence can be overestimated when considering only secondary adherence (i.e., following the medication recommendations for a defined period) and ignoring primary adherence. We aimed thus to evaluate the real-world primary and secondary adherence to ICS and to develop an integrated primary and secondary adherence (IPSA) measure. METHODS: From two clinical databases of pediatric and adult asthma patients, we included 198 children and 206 adults with one ICS prescription recorded in their medical chart between 2010 and 2012 and follow-up data for ≥12 months. Adherence was estimated from written prescriptions and prescription claims data. Primary adherence was defined as filling the ICS prescription at a pharmacy within 12 months. Secondary adherence was defined as the proportion of days covered (PDC) in subjects who filled their prescription at least once. The IPSA was based on the PDC with a correction factor for primary adherence. RESULTS: Primary adherence to ICS at 12 months was 89.4 % in children and 69.4 % in adults. Secondary adherence at 12 months in children was 33.9 %, and the IPSA was 30.3 %. These values were 52.8 and 36.6 %, respectively, in adults. CONCLUSIONS: Primary adherence to ICS is low in adults and secondary adherence is poor in children and adults. Using the PDC as a unique measure of adherence led to significant overestimation in adults; IPSA leads to more valid estimates of adherence to ICS.

Addition of anti-leukotriene agents to inhaled corticosteroids for adults and adolescents with persistent asthma.

BACKGROUND: Asthma management guidelines recommend low-dose inhaled corticosteroids (ICS) as first-line therapy for adults and adolescents with persistent asthma. The addition of anti-leukotriene agents to ICS offers a therapeutic option in cases of suboptimal control with daily ICS. OBJECTIVES: To assess the efficacy and safety of anti-leukotriene agents added to ICS compared with the same dose, an increased dose or a tapering dose of ICS (in both arms) for adults and adolescents 12 years of age and older with persistent asthma. Also, to determine whether any characteristics of participants or treatments might affect the magnitude of response. SEARCH METHODS: We identified relevant studies from the Cochrane Airways Group Specialised Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, the Allied and Complementary Medicine Database (AMED), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the trial registries clinicaltrials.gov and ICTRP from inception to August 2016. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of adults and adolescents 12 years of age and older on a maintenance dose of ICS for whom investigators added anti-leukotrienes to the ICS and compared treatment with the same dose, an increased dose or a tapering dose of ICS for at least four weeks. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. The primary outcome was the number of participants with exacerbations requiring oral corticosteroids (except when both groups tapered the dose of ICS, in which case the primary outcome was the % reduction in ICS dose from baseline with maintained asthma control). Secondary outcomes included markers of exacerbation, lung function, asthma control, quality of life, withdrawals and adverse events. MAIN RESULTS: We included in the review 37 studies representing 6128 adult and adolescent participants (most with mild to moderate asthma). Investigators in these studies used three leukotriene receptor antagonists (LTRAs): montelukast (n = 24), zafirlukast (n = 11) and pranlukast (n = 2); studies lasted from four weeks to five years. Anti-leukotrienes and ICS versus same dose of ICSOf 16 eligible studies, 10 studies, representing 2364 adults and adolescents, contributed data. Anti-leukotriene agents given as adjunct therapy to ICS reduced by half the number of participants with exacerbations requiring oral corticosteroids (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.29 to 0.86; 815 participants; four studies; moderate quality); this is equivalent to a number needed to treat for additional beneficial outcome (NNTB) over six to 16 weeks of 22 (95% CI 16 to 75). Only one trial including 368 participants reported mortality and serious adverse events, but events were too infrequent for researchers to draw a conclusion. Four trials reported all adverse events, and the pooled result suggested little difference between groups (RR 1.06, 95% CI 0.92 to 1.22; 1024 participants; three studies; moderate quality). Investigators noted between-group differences favouring the addition of anti-leukotrienes for morning peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), asthma symptoms and night-time awakenings, but not for reduction in ß2-agonist use or evening PEFR. Anti-leukotrienes and ICS versus higher dose of ICSOf 15 eligible studies, eight studies, representing 2008 adults and adolescents, contributed data. Results showed no statistically significant difference in the number of participants with exacerbations requiring oral corticosteroids (RR 0.90, 95% CI 0.58 to 1.39; 1779 participants; four studies; moderate quality) nor in all adverse events between groups (RR 0.96, 95% CI 0.89 to 1.03; 1899 participants; six studies; low quality). Three trials reported no deaths among 834 participants. Results showed no statistically significant differences in lung function tests including morning PEFR and FEV1 nor in asthma control measures including use of rescue ß2-agonists or asthma symptom scores. Anti-leukotrienes and ICS versus tapering dose of ICSSeven studies, representing 1150 adults and adolescents, evaluated the combination of anti-leukotrienes and tapering-dose of ICS compared with tapering-dose of ICS alone and contributed data. Investigators observed no statistically significant difference in % change from baseline ICS dose (mean difference (MD) -3.05, 95% CI -8.13 to 2.03; 930 participants; four studies; moderate quality), number of participants with exacerbations requiring oral corticosteroids (RR 0.46, 95% CI 0.20 to 1.04; 542 participants; five studies; low quality) or all adverse events (RR 0.95, 95% CI 0.83 to 1.08; 1100 participants; six studies; moderate quality). Serious adverse events occurred more frequently among those taking anti-leukotrienes plus tapering ICS than in those taking tapering doses of ICS alone (RR 2.44, 95% CI 1.52 to 3.92; 621 participants; two studies; moderate quality), but deaths were too infrequent for researchers to draw any conclusions about mortality. Data showed no improvement in lung function nor in asthma control measures. AUTHORS' CONCLUSIONS: For adolescents and adults with persistent asthma, with suboptimal asthma control with daily use of ICS, the addition of anti-leukotrienes is beneficial for reducing moderate and severe asthma exacerbations and for improving lung function and asthma control compared with the same dose of ICS. We cannot be certain that the addition of anti-leukotrienes is superior, inferior or equivalent to a higher dose of ICS. Scarce available evidence does not support anti-leukotrienes as an ICS sparing agent, and use of LTRAs was not associated with increased risk of withdrawals or adverse effects, with the exception of an increase in serious adverse events when the ICS dose was tapered. Information was insufficient for assessment of mortality.

Caregiver's functional status during a young child's asthma exacerbation: A validated instrument.

BACKGROUND: Few instruments exist to measure caregivers' functional status during a young child's asthma exacerbation. OBJECTIVE: We sought to develop and validate a measure of caregivers' functional status during a preschooler's asthma exacerbation. METHODS: The psychometric properties of the 21-item questionnaire Effects of a Young Child's Asthma Flare-up on the Parents (ECAP) were tested in a randomized placebo-controlled trial of pre-emptive high-dose fluticasone in preschoolers with virus-induced asthma. Caregivers completed the ECAP questionnaire on the last day their child exhibited symptoms of an upper respiratory tract infection or asthma exacerbation (episode). The mean of each item, scored on a scale of 1 (best) to 7 (worst), provided the ECAP score. RESULTS: Ninety-three preschoolers (2.5 ± 1.0 years old; 62.4% male) experienced 878 episodes. Feasibility (80% questionnaire return rate; 90% completion) and internal consistency (Cronbach α = 0.97) were high. Of 628 episodes with a completed ECAP questionnaire, 621 (98.9%) had data on exacerbations, and 609 (97.0%) had data on health care use. The ECAP score was significantly higher for children experiencing an asthma exacerbation versus those who were not (mean difference, 0.8; 95% CI, 0.6-1.0) and for episodes resulting versus not resulting in an emergency visit (mean difference, 1.2; 95% CI, 1.0-1.4), systemic corticosteroid use (mean difference, 1.4; 95% CI, 1.1-1.7), or hospitalization (mean difference, 1.9; 95% CI, 1.4-2.5). The ECAP score was significantly lower in children treated with fluticasone versus those treated with placebo (mean difference, -0.7; 95% CI, -1.1 to -0.3). CONCLUSIONS: The 21-item ECAP questionnaire, showing high feasibility, internal consistency, discriminative validity, and responsiveness, has the psychometric properties to serve as a validated outcome to measure the burden of preschoolers' asthma exacerbations on their caregivers' functional status.

Asthma Flare-up Diary for Young Children to monitor the severity of exacerbations.

BACKGROUND: Few instruments exist to ascertain the severity of a preschool-aged child's asthma exacerbations managed at home. OBJECTIVE: We sought to develop and validate a functional status instrument to assess asthma exacerbation severity in preschoolers. METHODS: The parent-completed Asthma Flare-up Diary for Young Children (ADYC), which was developed systematically, comprises 17 items, each scored from 1 (best) to 7 (worst). The ADYC was completed daily from the onset of an upper respiratory tract infection (URTI) until asthma symptom resolution; the cumulative daily score was reported. The ADYC was examined for key psychometric properties in a randomized placebo-controlled trial of pre-emptive high-dose fluticasone in preschoolers with URTI-induced asthma. RESULTS: In 121 children aged 2.7 ± 1.1 years (59.5% male), the ADYC's internal consistency (Cronbach α = .97), feasibility (97% completion), and test-retest reliability (r = 0.71; 95% CI, 0.59-0.80) were demonstrated. The ADYC was responsive to change between 2 consecutive days (Guyatt statistic = 0.77) with a minimal important difference of 0.22 (0.17-0.27). Of 871 episodes, the cumulative ADYC score was significantly higher during exacerbations than during URTIs (mean difference [MD], 7.6; 95% CI, 6.4-8.9) and for exacerbations with an acute-care visit (MD, 9.1; 95% CI, 7.6-10.7), systemic corticosteroids (MD, 10.1; 95% CI, 8.3-12.0), and hospitalization (MD, 6.8; 95% CI, 2.9-10.7) versus those without. In children receiving fluticasone, the ADYC score was significantly lower versus that in the placebo group (MD, 5.1; 95% CI, 1.8-8.3). CONCLUSIONS: The 17-item ADYC proved feasible, responsive to day-to-day changes, and discriminative across exacerbations of different severities. In a trial testing effective therapy in preschoolers, it identified a significant reduction in asthma exacerbation severity.

Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children.

BACKGROUND: People with asthma may experience exacerbations or "attacks" during which their symptoms worsen and additional treatment is required. Written action plans may advocate doubling the dose of inhaled steroids in the early stages of an asthma exacerbation to reduce the severity of the attack and to prevent the need for oral steroids or hospital admission. OBJECTIVES: To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids (ICS) as part of a patient-initiated action plan for home management of exacerbations in children and adults with persistent asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, which is derived from searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to March 2016. We handsearched respiratory journals and meeting abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared increased versus stable doses of ICS for home management of asthma exacerbations. We included studies of children or adults with persistent asthma who were receiving daily maintenance ICS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality and extracted data. We contacted authors of RCTs for additional information. MAIN RESULTS: This review update added three new studies including 419 participants to the review. In total, we identified eight RCTs, most of which were at low risk of bias, involving 1669 participants with mild to moderate asthma. We included three paediatric (n = 422) and five adult (n = 1247) studies; six were parallel-group trials and two had a cross-over design. All but one study followed participants for six months to one year. Allowed maintenance doses of ICS varied in adult and paediatric studies, as did use of concomitant medications and doses of ICS initiated during exacerbations. Investigators gave participants a study inhaler containing additional ICS or placebo to be started as part of an action plan for treatment of exacerbations.The odds of treatment failure, defined as the need for oral corticosteroids, were not significantly reduced among those randomised to increased ICS compared with those taking their usual stable maintenance dose (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.68 to 1.18; participants = 1520; studies = 7). When we analysed only people who actually took their study inhaler for an exacerbation, we found much variation between study results but the evidence did not show a significant benefit of increasing ICS dose (OR 0.84, 95% CI 0.54 to 1.30; participants = 766; studies = 7). The odds of having an unscheduled physician visit (OR 0.96, 95% CI 0.66 to 1.41; participants = 931; studies = 3) or acute visit (Peto OR 0.98, 95% CI 0.24 to 3.98; participants = 450; studies = 3) were not significantly reduced by an increased versus stable dose of ICS, and evidence was insufficient to permit assessment of impact on the duration of exacerbation; our ability to draw conclusions from these outcomes was limited by the number of studies reporting these events and by the number of events included in the analyses. The odds of serious events (OR 1.69, 95% CI 0.77 to 3.71; participants = 394; studies = 2) and non-serious events, such as oral irritation, headaches and changes in appetite (OR 2.15, 95% CI 0.68 to 6.73; participants = 142; studies = 2), were neither increased nor decreased significantly by increased versus stable doses of ICS during an exacerbation. Too few studies are available to allow firm conclusions on the basis of subgroup analyses conducted to investigate the impact of age, time to treatment initiation, doses used, smoking history and the fold increase of ICS on the magnitude of effect; yet, effect size appears similar in children and adults. AUTHORS' CONCLUSIONS: Current evidence does not support increasing the dose of ICS as part of a self initiated action plan to treat exacerbations in adults and children with mild to moderate asthma. Increased ICS dose is not associated with a statistically significant reduction in the odds of requiring rescue oral corticosteroids for the exacerbation, or of having adverse events, compared with a stable ICS dose. Wide confidence intervals for several outcomes mean we cannot rule out possible benefits of this approach.

Diagnosis, management, and prognosis of preschool wheeze.

Preschool children (ie, those aged 5 years or younger) with wheeze consume a disproportionately high amount of health-care resources compared with older children and adults with wheeze or asthma, representing a diagnostic challenge. Although several phenotype classifications have been described, none have been validated to identify individuals responding to specific therapeutic approaches. Several risk factors related to genetic, prenatal, and postnatal environment are associated with preschool wheezing. Findings from several cohort studies have shown that preschool children with wheeze have deficits in lung function at 6 years of age that persisted until early and middle adulthood, suggesting increased susceptibility in the first years of life that might lead to persistent sequelae. Daily inhaled corticosteroids seem to be the most effective therapy for recurrent wheezing in trials of children with interim symptoms or atopy; intermittent high-dose inhaled corticosteroids are effective in moderate-to-severe viral-induced wheezing without interim symptoms. The role of leukotriene receptor antagonist is less clear. Interventions to modify the short-term and long-term outcomes of preschool wheeze should be a research priority.

Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children.

BACKGROUND: Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed for children with asthma. OBJECTIVES: To assess the safety and efficacy of adding a LABA to an ICS in children and adolescents with asthma. To determine whether the benefit of LABA was influenced by baseline severity of airway obstruction, the dose of ICS to which it was added or with which it was compared, the type of LABA used, the number of devices used to deliver combination therapy and trial duration. SEARCH METHODS: We searched the Cochrane Airways Group Asthma Trials Register until January 2015. SELECTION CRITERIA: We included randomised controlled trials testing the combination of LABA and ICS versus the same, or an increased, dose of ICS for at least four weeks in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included markers of exacerbation, pulmonary function, symptoms, quality of life, adverse events and withdrawals. DATA COLLECTION AND ANALYSIS: Two review authors assessed studies independently for methodological quality and extracted data. We obtained confirmation from trialists when possible. MAIN RESULTS: We included in this review a total of 33 trials representing 39 control-intervention comparisons and randomly assigning 6381 children. Most participants were inadequately controlled on their current ICS dose. We assessed the addition of LABA to ICS (1) versus the same dose of ICS, and (2) versus an increased dose of ICS.LABA added to ICS was compared with the same dose of ICS in 28 studies. Mean age of participants was 11 years, and males accounted for 59% of the study population. Mean forced expiratory volume in one second (FEV1) at baseline was ≥ 80% of predicted in 18 studies, 61% to 79% of predicted in six studies and unreported in the remaining studies. Participants were inadequately controlled before randomisation in all but four studies.There was no significant group difference in exacerbations requiring oral steroids (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.28, 12 studies, 1669 children; moderate-quality evidence) with addition of LABA to ICS compared with ICS alone. There was no statistically significant group difference in hospital admissions (RR 1.74, 95% CI 0.90 to 3.36, seven studies, 1292 children; moderate-quality evidence)nor in serious adverse events (RR 1.17, 95% CI 0.75 to 1.85, 17 studies, N = 4021; moderate-quality evidence). Withdrawals occurred significantly less frequently with the addition of LABA (23 studies, 471 children, RR 0.80, 95% CI 0.67 to 0.94; low-quality evidence). Compared with ICS alone, addition of LABA led to significantly greater improvement in FEV1 (nine studies, 1942 children, inverse variance (IV) 0.08 L, 95% CI 0.06 to 0.10; mean difference (MD) 2.99%, 95% CI 0.86 to 5.11, seven studies, 534 children; low-quality evidence), morning peak expiratory flow (PEF) (16 studies, 3934 children, IV 10.20 L/min, 95% CI 8.14 to 12.26), reduction in use of daytime rescue inhalations (MD -0.07 puffs/d, 95% CI -0.11 to -0.02, seven studies; 1798 children) and reduction in use of nighttime rescue inhalations (MD -0.08 puffs/d, 95% CI -0.13 to -0.03, three studies, 672 children). No significant group difference was noted in exercise-induced % fall in FEV1, symptom-free days, asthma symptom score, quality of life, use of reliever medication and adverse events.A total of 11 studies assessed the addition of LABA to ICS therapy versus an increased dose of ICS with random assignment of 1628 children. Mean age of participants was 10 years, and 64% were male. Baseline mean FEV1 was ≥ 80% of predicted. All trials enrolled participants who were inadequately controlled on a baseline inhaled steroid dose equivalent to 400 µg/d of beclomethasone equivalent or less.There was no significant group differences in risk of exacerbation requiring oral steroids with the combination of LABA and ICS versus a double dose of ICS (RR 1.69, 95% CI 0.85 to 3.32, three studies, 581 children; moderate-quality evidence) nor in risk of hospital admission (RR 1.90, 95% CI 0.65 to 5.54, four studies, 1008 children; moderate-quality evidence).No statistical significant group difference was noted in serious adverse events (RR 1.54, 95% CI 0.81 to 2.94, seven studies, N = 1343; moderate-quality evidence) and no statistically significant differences in overall risk of all-cause withdrawals (RR 0.96, 95% CI 0.67 to 1.37, eight studies, 1491 children; moderate-quality evidence). Compared with double the dose of ICS, use of LABA was associated with significantly greater improvement in morning PEF (MD 8.73 L/min, 95% CI 5.15 to 12.31, five studies, 1283 children; moderate-quality evidence), but data were insufficient to aggregate on other markers of asthma symptoms, rescue medication use and nighttime awakening. There was no group difference in risk of overall adverse effects, A significant group difference was observed in linear growth over 12 months, clearly indicating lower growth velocity in the higher ICS dose group (two studies: MD 1.21 cm/y, 95% CI 0.72 to 1.70). AUTHORS' CONCLUSIONS: In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but it was superior for improving lung function compared with the same or higher doses of ICS. No differences in adverse effects were apparent, with the exception of greater growth with the use of ICS and LABA compared with a higher ICS dose. The trend towards increased risk of hospital admission with LABA, irrespective of the dose of ICS, is a matter of concern and requires further monitoring.

Leukotriene receptor antagonists as maintenance and intermittent therapy for episodic viral wheeze in children.

BACKGROUND: Episodic viral wheeze (EVW) associated with viral respiratory tract infections is a common reason for pre-school children to utilise health care resources and for carers to take time away from employment. About a third of children experience a wheezing episode before the age of five years. EVW therefore represents a significant public health problem. Many pre-school children only wheeze in association with viral infections and in such cases EVW appears to be a separate entity from atopic asthma. Some trials have explored the effectiveness of leukotriene receptor antagonists (LTRAs) as regular (maintenance) or episodic (intermittent) treatment in this context. OBJECTIVES: To evaluate the evidence for the efficacy and safety of maintenance and intermittent LTRAs in the management of EVW in children aged one to six years. SEARCH METHODS: We searched the Cochrane Airways Group register of trials with pre-specified terms. We performed additional searches by consulting the authors of identified trials, online trial registries of manufacturers' web sites, and reference lists of identified primary papers and reviews. Search results are current to June 2015. SELECTION CRITERIA: We included randomised controlled trials with a parallel-group or cross-over (for intermittent LTRA only) design. Maintenance was considered as treatment for more than two months and intermittent as less than 14 days. EVW was defined as a history of at least one previous episode of wheezing in association with a viral respiratory tract infection in the absence of symptoms between episodes. As far as possible, relevant specific data were obtained from authors of studies that included children of a wider age group or phenotype.   DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion in the review and assessed risk of bias. The primary outcome was number of children with one or more viral-induced episodes requiring one or more treatments with rescue oral corticosteroids. We analysed combined continuous data outcomes with the mean difference and dichotomous data outcomes with an odds ratio (OR). MAIN RESULTS: We identified five studies eligible for inclusion in the review (one investigated maintenance treatment, three intermittent therapy and one had both maintenance and intermittent treatment arms) these included 3741 participants. Each study involved oral montelukast and was of good methodological quality, but differed in choice of outcome measures thus limiting our ability to aggregate data across studies. Only primary outcome and adverse event data are reported in this abstract.For maintenance treatment, specific data obtained from a single study, pertaining to children with only an EVW phenotype, showed no statistically significant group reduction in the number of episodes requiring rescue oral corticosteroids associated with daily montelukast versus placebo (OR 1.20, 95% CI 0.70 to 2.06, moderate quality evidence).For intermittent LTRA, pooled data showed no statistically significant reduction in the number of episodes requiring rescue oral steroids in children treated with LTRA versus placebo (OR 0.77, 95% CI 0.48 to 1.25, moderate quality evidence). Specific data for children with an EVW phenotype obtained from a single study of intermittent montelukast treatment showed a small, but statistically significant reduction in unscheduled medical attendances due to wheeze (RR 0.83, 95% CI 0.71 to 0.98).For maintenance compared to intermittent LTRA treatment no data relating to the primary outcome of the review were identified.There were no other significant group differences identified in other secondary efficacy outcomes for maintenance or intermittent LTRA treatment versus placebo, or maintenance versus intermittent LTRA treatment. We collected descriptive data on adverse events as reported by four of the five included studies, and rates were similar between treatment and placebo groups.Potential heterogeneity in the phenotype of participants within and across trials is a limitation of the evidence. AUTHORS' CONCLUSIONS: In pre-school children with EVW, there is no evidence of benefit associated with maintenance or intermittent LTRA treatment, compared to placebo, for reducing the number of children with one or more viral-induced episodes requiring rescue oral corticosteroids, and little evidence of significant clinical benefit for other secondary outcomes. Therefore until further data are available, LTRA should be used with caution in individual children. When used, we suggest a therapeutic trial is undertaken, during which efficacy should be carefully monitored. It is likely that children with an apparent EVW phenotype are not a homogeneous group and that subgroups may respond to LTRA treatment depending on the exact patho-physiological mechanisms involved.

Patients' perspective of barriers and facilitators to taking long-term controller medication for asthma: a novel taxonomy.

BACKGROUND: Although asthma morbidity can be prevented through long-term controller medication, most patients with persistent asthma do not take their daily inhaled corticosteroid. The objective of this study was to gather patients' insights into barriers and facilitators to taking long-term daily inhaled corticosteroids as basis for future knowledge translation interventions. METHODS: We conducted a collective qualitative case study. We interviewed 24 adults, adolescents, or parents of children, with asthma who had received a prescription of long-term inhaled corticosteroids in the previous year. The one-hour face-to-face interviews revolved around patients' perceptions of asthma, use of asthma medications, current self-management, prior changes in self-management, as well as patient-physician relationship. We sought barriers and facilitators to optimal asthma management. Interviews were transcribed verbatim and transcripts were analyzed using a thematic approach. RESULTS: Patients were aged 2-76 years old and 58% were female. Nine patients were followed by an asthma specialist (pulmonologist or allergist), 13 patients by family doctors or pediatricians, and two patients had no regular follow-up. Barriers and facilitators to long-term daily inhaled corticosteroids were classified into the following loci of responsibility and its corresponding domains: (1) patient (cognition; motivation, attitudes and preferences; practical implementation; and parental support); (2) patient-physician interaction (communication and patient-physician relationship); and (3) health care system (resources and services). Patients recognized that several barriers and facilitators fell within their own responsibility. They also underlined the crucial impact (positive or negative) on their adherence of the quality of patient-physician interaction and health care system accessibility. CONCLUSIONS: We identified a close relationship between reported barriers and facilitators to adherence to long-term daily controller medication for asthma within three loci of responsibility. As such, patients' adherence must be approached as a multi-level phenomenon; moreover, interventions targeting the patient, the patient-physician interaction, and the health care system are recommended. The present study offers a potential taxonomy of barriers and facilitators to adherence to long-term daily inhaled corticosteroids therapy that, once validated, may be used for planning a knowledge translation intervention and may be applicable to other chronic conditions.

Diagnosis and management of asthma in preschoolers: A Canadian Thoracic Society and Canadian Paediatric Society position paper.

Asthma often starts before six years of age. However, there remains uncertainty as to when and how a preschool-age child with symptoms suggestive of asthma can be diagnosed with this condition. This delays treatment and contributes to both short- and long-term morbidity. Members of the Canadian Thoracic Society Asthma Clinical Assembly partnered with the Canadian Paediatric Society to develop a joint working group with the mandate to develop a position paper on the diagnosis and management of asthma in preschoolers. In the absence of lung function tests, the diagnosis of asthma should be considered in children one to five years of age with frequent (≥8 days/month) asthma-like symptoms or recurrent (≥2) exacerbations (episodes with asthma-like signs). The diagnosis requires the objective document of signs or convincing parent-reported symptoms of airflow obstruction (improvement in these signs or symptoms with asthma therapy), and no clinical suspicion of an alternative diagnosis. The characteristic feature of airflow obstruction is wheezing, commonly accompanied by difficulty breathing and cough. Reversibility with asthma medications is defined as direct observation of improvement with short-acting ß2-agonists (SABA) (with or without oral corticosteroids) by a trained health care practitioner during an acute exacerbation (preferred method). However, in children with no wheezing (or other signs of airflow obstruction) on presentation, reversibility may be determined by convincing parental report of a symptomatic response to a three-month therapeutic trial of a medium dose of inhaled corticosteroids with as-needed SABA (alternative method), or as-needed SABA alone (weaker alternative method). The authors provide key messages regarding in whom to consider the diagnosis, terms to be abandoned, when to refer to an asthma specialist and the initial management strategy. Finally, dissemination plans and priority areas for research are identified.

L'asthme fait souvent son apparition avant l'âge de six ans. Cependant, il subsiste des incertitudes relativement à quand et comment un enfant d'âge préscolaire ayant des symptômes de type asthmatique peut être diagnostiqué avec cette condition. Ceci retarde le traitement et contribue à la morbidité à court et à long terme. L'Assemblée clinique sur l'asthme de la Société canadienne de thoracologie s'est associée à la Société canadienne de pédiatrie pour créer un groupe de travail conjoint afin de préparer un document de principes sur le diagnostic et la prise en charge de l'asthme chez les enfants d'âge préscolaire. En l'absence de mesures de la fonction pulmonaire, le diagnostic d'asthme devrait être envisagé chez les enfants de un à cinq ans ayant des symptômes de type asthmatique fréquents (≥8 jours/mois) ou des exacerbations récurrentes (≥2) (épisodes accompagnés de signes compatibles). Le diagnostic nécessite une documentation objective des signes cliniques ou un compte rendu parental convaincant de symptômes d'obstruction des voies respiratoires et de réversibilité de l' obstruction (amélioration suite à un traitement pour l'asthme), ainsi que l'absence de suspicion clinique de tout autre diagnostic. La respiration sifflante, souvent accompagnée de difficultés respiratoires et de toux, est le signe cardinal de l'obstruction des voies respiratoires. La réversibilité à la suite de la prise de médicaments pour l'asthme se définie par l'observation directe par un professionnel de la santé compétent, d'une amélioration après l'administration de ß2-agonistes à courte durée d'action (BACA) (accompagnés ou non de corticostéroïdes par voie orale) pendant une exacerbation aigue (méthode diagnostique privilégiée). Cependant, chez les enfants qui n'ont pas à l'examen une respiration sifflante (ni d'autres signes d'obstruction des voies respiratoires), la réversibilité peut être déterminée par un compte rendu parental convaincant d'une réponse symptomatique à un essai thérapeutique de trois mois de corticostéroïdes inhalés, à dose moyenne, avec un BACA au besoin (méthode diagnostique alternative), ou avec seulement un BACA au besoin (méthode diagnostique alternative moins certaine) est recommandé. Les auteurs présentent des messages clés quant aux enfants chez lesquels on doit envisager le diagnostic, quant aux termes désuets à abandonner, quant aux situations pour lesquelles on doit orienter l'enfant vers un spécialiste de l'asthme et quant à la stratégie de prise en charge initiale. Enfin, ils décrivent la stratégie de diffusion de ces messages et identifient les domaines de recherche prioritaires.