Dataset Information

Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations.

ABSTRACT: Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids.The design is a prospective cohort study of 1008 children aged 1-17 years meeting a strict definition of asthma and presenting with a clinical score of ?4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an ? of 0.05.Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host-environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide the needed reassurance regarding current treatment recommendations.Results will be disseminated at international conferences and manuscripts targeted at emergency physicians, paediatricians, geneticists and respirologists.This study is registered at Clinicaltrials.gov (NCT02013076).

SUBMITTER: Ducharme FM

PROVIDER: S-EPMC3987727 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations.

Ducharme F M FM Zemek R R Gravel J J Chalut D D Poonai N N Laberge S S Quach C C Krajinovic M M Guimont C C Lemière C C Guertin M C MC

BMJ open 20140407 4

<h4>Introduction</h4>Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corti ...[more]

PMID: 24710133

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Project description:BackgroundFractional exhaled nitric oxide (FeNO) is promising for diagnosing asthma and could replace bronchial provocation (BP). To date, cut-off values have been derived by post hoc analysis only. The aim was to validate the diagnostic accuracy for predefined FeNO cut-off values and the predictive value for responsiveness to inhaled corticosteroids (ICS).MethodsWe conducted a prospective, diagnostic, multicentre study with patients attending three private practices of pneumologists in Upper Bavaria, Germany, from July 3, 2020 to Jan 21, 2022. Index test was FENO measurement. Reference standard was Tiffeneau ratio (FEV1/VC) or airway resistance as assessed by whole body plethysmography, with additional BP or bronchodilation test. Follow-up was performed after 12 weeks. Analyses of Receiver Operating Characteristics curves were conducted to determine the diagnostic accuracy and predictive value of FeNO.Findings308 patients with complete follow-up were recruited, 186 (60·4%) were female, average age was 44·7 years, 161 (52·3%) had asthma. Regarding diagnostic accuracy, the area under the curve (AUC) was 0·718 (95% CI 0·661-0·775; p < 0·001). Sensitivity at FeNO >50 ppb was 0·24 (95% CI 0·18-0·32), specificity 0·99 (0·95-1·0), positive predictive value (PPV) 0·95 (0·84-0·99), negative predictive value (NPV) 0·54 (0·48-0·60). In 66 patients with ´wheezing´ and ´allergic rhinitis´, the sensitivity at FeNO >33 ppb was 0·49 (0·34-0·64), specificity 0·88 (0·64-0·99), PPV 0·92 (0·75-0·99), NPV 0·38 (0·23-0·54). In 68 patients with ICS medication, responsiveness was predicted at the cut-off >43 ppb, with a sensitivity of 0·55 (95%CI 0·36-0·74), specificity 0·82 (0·66-0·92), PPV 0·70 (0·47-0·87), NPV 0·71 (0·56-0·84).InterpretationFeNO measurement allows a valid ruling-in of an asthma diagnosis, whereas ruling-out of asthma is not possible. Enhanced probability of ICS responsiveness is also given with increased FeNO values.FundingCircassia Germany gave 25% discount on the purchase of three NIOX VERO devices.

Project description:BackgroundAsthma exacerbations reduce the patient's quality of life and are also responsible for significant disease burdens and economic costs. Machine learning (ML)-based prediction models have been increasingly developed to predict asthma exacerbations in recent years. This systematic review and meta-analysis aimed to identify the prediction performance of ML-based prediction models for asthma exacerbations and address the uncertainty of whether modern ML methods could become an alternative option to predict asthma exacerbations.MethodsPubMed, Cochrane Library, EMBASE, and Web of Science were searched for studies published up to December 15, 2022. Studies that applied ML methods to develop prediction models for asthma exacerbations among asthmatic patients older than five years and were published in English were eligible. The prediction model risk of bias assessment tool (PROBAST) was utilized to estimate the risk of bias and the applicability of included studies. Stata software (version 15.0) was used for the random effects meta-analysis of performance measures. Subgroup analyses stratified by ML methods, sample size, age groups, and outcome definitions were conducted.ResultsEleven studies, including 23 prediction models, were identified. Most of the studies were published in recent three years. Logistic regression, boosting, and random forest were the most used ML methods. The most common important predictors were systemic steroid use, short-acting beta2-agonists, emergency department visit, age, and exacerbation history. The overall pooled area under the curve of the receiver operating characteristics (AUROC) of 11 studies (23 prediction models) was 0.80 (95% CI 0.77-0.83). Subgroup analysis based on different ML models showed that boosting method achieved the best performance, with an overall pooled AUROC of 0.84 (95% CI 0.81-0.87).ConclusionThis study identified that ML was the potential tool to achieve great performance in predicting asthma exacerbations. However, the methodology within these models was heterogeneous. Future studies should focus on improving the generalization ability and practicability, thus driving the application of these models in clinical practice.

Dataset Information

Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations.

Publications

Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations.

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