Matches in SemOpenAlex for { <https://semopenalex.org/work/W2185097851> ?p ?o ?g. }
- W2185097851 endingPage "126" @default.
- W2185097851 startingPage "1" @default.
- W2185097851 abstract "Background The clinical effectiveness of intermittent montelukast for wheeze in young children is unclear. Previous work has been equivocal. Variation in copy numbers of the specificity protein 1-binding motif in the arachidonate 5-lipoxygenase ( ALOX5 ) gene promoter; where the wild type has five copies per allele, denoted here as 5/5, but variant genotypes may have 1–8 copies on each allele, denoted as x/x or 5/x, influences montelukast efficacy in asthmatic adults. This polymorphism may identify a responsive subgroup within this population. Objectives To assess the clinical effectiveness of montelukast in preschool wheezing children. To explore the effect of the ALOX5 promoter genotype on this effect. Design A multicentre, parallel-group, double-blind, randomised, placebo-controlled trial. Setting Twenty-one primary care sites and 41 secondary care sites in England and Scotland. Participants Children aged 10 months to 5 years with two or more wheeze episodes, one within the last 3 months, stratified by ALOX5 promoter genotype, either 5/5 or [5/x + x/x]. Children with other respiratory vulnerabilities were excluded. Intervention Parent-initiated 4 mg oral granules of montelukast or identical placebo administered once daily for 10 days from the onset of every cold or wheeze episode over 12 months. Main outcome measure Need for unscheduled medical attendance for wheezing. Randomisation Children were stratified by ALOX5 promoter genotype, either 5/5 or [5/x + x/x], where x ≠ 5. Children in each stratum were independently randomised to receive montelukast or placebo in a 1 : 1 ratio via a permuted block schedule (size 10). Clinical investigators and parents were blinded to treatment group and genotype stratum. Methods Genotype was identified by analysis of salivary deoxyribonucleic acid. Analysis was by intention to treat. Primary outcome data came from treatment diaries, scheduled telephone calls and caregiver records. Results A total of 1358 children were randomised to receive montelukast ( n = 669) or placebo ( n = 677). Consent was withdrawn for 12 (1%) children. Primary outcome data were available for 1308 (96%) children. There was no difference in unscheduled medical attendances for wheezing episodes between children in the montelukast and placebo groups {mean 2.0 [standard deviation (SD) 2.6] vs. mean 2.3 (SD 2.7) unscheduled medical attendances; incidence rate ratio (IRR) 0.88, 95% confidence interval (CI) 0.77 to 1.01; p = 0.06}. Compared with placebo, unscheduled medical attendances for wheezing episodes were reduced in children given montelukast in the 5/5 stratum [mean 2.0 (SD 2.7) vs. mean 2.4 (SD 3.0) unscheduled medical attendances; IRR 0.80, 95% CI 0.68 to 0.95; p = 0.01], but not in those in the [5/x + x/x] stratum [mean 2.0 (SD 2.5) vs. mean 2.0 (SD 2.3) unscheduled medical attendances; IRR 1.03, 95% CI 0.83 to 1.29; p = 0.79, p -interaction = 0.08]. We recorded one serious adverse event: a skin reaction in a child allocated to placebo. Interpretation There is no clear benefit of intermittent montelukast in young children with wheeze. However, the 5/5 ALOX5 promoter genotype might identify a montelukast-responsive subgroup. Limitations The study lacks power to confirm the validity of the suggested genotype stratum effect. Additionally, the effect is contrary to that hypothesised and is not supported by urinary data. We could not robustly measure treatment compliance. Future work Future work should test the stratum effect with a repeat trial in the apparently more responsive (5/5) stratum only. Study registration ClinicalTrials.gov NCT01142505. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership." @default.
- W2185097851 created "2016-06-24" @default.
- W2185097851 creator A5007536017 @default.
- W2185097851 creator A5014464894 @default.
- W2185097851 creator A5017177848 @default.
- W2185097851 creator A5021159673 @default.
- W2185097851 creator A5023586294 @default.
- W2185097851 creator A5029547847 @default.
- W2185097851 creator A5046242737 @default.
- W2185097851 creator A5052175038 @default.
- W2185097851 creator A5056150470 @default.
- W2185097851 creator A5059761761 @default.
- W2185097851 creator A5073087024 @default.
- W2185097851 creator A5088572047 @default.
- W2185097851 creator A5090757754 @default.
- W2185097851 creator A5091351677 @default.
- W2185097851 date "2015-11-01" @default.
- W2185097851 modified "2023-10-11" @default.
- W2185097851 title "Parent-determined oral montelukast therapy for preschool wheeze with stratification for arachidonate 5-lipoxygenase (ALOX5) promoter genotype: a multicentre, randomised, placebo-controlled trial" @default.
- W2185097851 cites W1963981548 @default.
- W2185097851 cites W1966714873 @default.
- W2185097851 cites W1972893526 @default.
- W2185097851 cites W1986265591 @default.
- W2185097851 cites W1992110991 @default.
- W2185097851 cites W2038935515 @default.
- W2185097851 cites W2058065620 @default.
- W2185097851 cites W2108533816 @default.
- W2185097851 cites W2121964819 @default.
- W2185097851 cites W2128630233 @default.
- W2185097851 cites W2137612322 @default.
- W2185097851 cites W2137746159 @default.
- W2185097851 cites W2140553643 @default.
- W2185097851 cites W2150557343 @default.
- W2185097851 cites W2151527679 @default.
- W2185097851 cites W2151589341 @default.
- W2185097851 cites W2172149963 @default.
- W2185097851 cites W53646502 @default.
- W2185097851 doi "https://doi.org/10.3310/eme02060" @default.
- W2185097851 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26632627" @default.
- W2185097851 hasPublicationYear "2015" @default.
- W2185097851 type Work @default.
- W2185097851 sameAs 2185097851 @default.
- W2185097851 citedByCount "0" @default.
- W2185097851 crossrefType "journal-article" @default.
- W2185097851 hasAuthorship W2185097851A5007536017 @default.
- W2185097851 hasAuthorship W2185097851A5014464894 @default.
- W2185097851 hasAuthorship W2185097851A5017177848 @default.
- W2185097851 hasAuthorship W2185097851A5021159673 @default.
- W2185097851 hasAuthorship W2185097851A5023586294 @default.
- W2185097851 hasAuthorship W2185097851A5029547847 @default.
- W2185097851 hasAuthorship W2185097851A5046242737 @default.
- W2185097851 hasAuthorship W2185097851A5052175038 @default.
- W2185097851 hasAuthorship W2185097851A5056150470 @default.
- W2185097851 hasAuthorship W2185097851A5059761761 @default.
- W2185097851 hasAuthorship W2185097851A5073087024 @default.
- W2185097851 hasAuthorship W2185097851A5088572047 @default.
- W2185097851 hasAuthorship W2185097851A5090757754 @default.
- W2185097851 hasAuthorship W2185097851A5091351677 @default.
- W2185097851 hasBestOaLocation W21850978511 @default.
- W2185097851 hasConcept C104317684 @default.
- W2185097851 hasConcept C126322002 @default.
- W2185097851 hasConcept C135763542 @default.
- W2185097851 hasConcept C142724271 @default.
- W2185097851 hasConcept C168563851 @default.
- W2185097851 hasConcept C187212893 @default.
- W2185097851 hasConcept C204787440 @default.
- W2185097851 hasConcept C27081682 @default.
- W2185097851 hasConcept C2776042228 @default.
- W2185097851 hasConcept C2776322731 @default.
- W2185097851 hasConcept C2778338976 @default.
- W2185097851 hasConcept C2908647359 @default.
- W2185097851 hasConcept C54355233 @default.
- W2185097851 hasConcept C71924100 @default.
- W2185097851 hasConcept C86803240 @default.
- W2185097851 hasConcept C90924648 @default.
- W2185097851 hasConcept C99454951 @default.
- W2185097851 hasConceptScore W2185097851C104317684 @default.
- W2185097851 hasConceptScore W2185097851C126322002 @default.
- W2185097851 hasConceptScore W2185097851C135763542 @default.
- W2185097851 hasConceptScore W2185097851C142724271 @default.
- W2185097851 hasConceptScore W2185097851C168563851 @default.
- W2185097851 hasConceptScore W2185097851C187212893 @default.
- W2185097851 hasConceptScore W2185097851C204787440 @default.
- W2185097851 hasConceptScore W2185097851C27081682 @default.
- W2185097851 hasConceptScore W2185097851C2776042228 @default.
- W2185097851 hasConceptScore W2185097851C2776322731 @default.
- W2185097851 hasConceptScore W2185097851C2778338976 @default.
- W2185097851 hasConceptScore W2185097851C2908647359 @default.
- W2185097851 hasConceptScore W2185097851C54355233 @default.
- W2185097851 hasConceptScore W2185097851C71924100 @default.
- W2185097851 hasConceptScore W2185097851C86803240 @default.
- W2185097851 hasConceptScore W2185097851C90924648 @default.
- W2185097851 hasConceptScore W2185097851C99454951 @default.
- W2185097851 hasFunder F4320334626 @default.
- W2185097851 hasFunder F4320334783 @default.
- W2185097851 hasIssue "6" @default.
- W2185097851 hasLocation W21850978511 @default.
- W2185097851 hasLocation W21850978512 @default.