Modelling studies suggest that urban cycling is associated with an increased inhaled dose of fossil fuel-derived black carbon (BC). Using the amount of black material in airway macrophages as a marker of long-term inhaled BC, we sought to compare inhaled BC dose in London (UK) cyclists and non-cyclists.Airway macrophage carbon was assessed in 28 (58%) out of 48 healthy adults (14 cyclists and 14 non-cyclists) who attended for induced sputum. Short-term (24 h) exposure to BC was assessed on a representative working day in 27 out of 28 subjects. Serum interleukin (IL)-1b, IL-2, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor and tumour necrosis factor (TNF)-a were assessed in 26 out of the 28 subjects.Cyclists were found to have increased airway macrophage carbon when compared with noncyclists (mean¡SE 1.81¡0.21 versus 1.11¡0.07 mm 2 ; p,0.01). Short-term monitoring showed no difference in 24 h BC exposure between the two groups. However, cyclists were exposed to higher concentrations of BC during commuting (p,0.01). Airway macrophage carbon was associated with monitored commute BC (n528; r50.47, p,0.05). TNF-a was found to be increased in cyclists (p,0.05), but no other cytokines were increased. Commuting to work by bicycle in London is associated with increased long-term inhaled dose of BC. Whether cycling per se increases inhaled BC dose remains unclear.

SummaryBackgroundThe effectiveness of intermittent montelukast for wheeze in young children is unclear. We aimed to assess whether intermittent montelukast is better than placebo for treatment of wheeze in this age group. Because copy numbers of the Sp1-binding motif in the arachidonate 5-lipoxygenase (ALOX5) gene promoter (either 5/5, 5/x, or x/x, where x does not equal 5) modifies response to montelukast in adults, we stratified by this genotype.MethodsWe did this multicentre, parallel-group, randomised, placebo-controlled trial between Oct 1, 2010, and Dec 20, 2013, at 21 primary care sites and 41 secondary care sites in England and Scotland. Children aged 10 months to 5 years with two or more wheeze episodes were allocated to either a 5/5 or 5/x+x/x ALOX5 promoter genotype stratum, then randomly assigned (1:1) via a permuted block schedule (size ten), to receive intermittent montelukast or placebo given by parents at each wheeze episode over a 12 month period. Clinical investigators and parents were masked to treatment group and genotype strata. The primary outcome was number of unscheduled medical attendances for wheezing episodes. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01142505.FindingsWe randomly assigned 1358 children 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 [SD 2·6] vs 2·3 [2·7]; incidence rate ratio [IRR] 0·88, 95% CI: 0·77–1·01; p=0·06). Compared with placebo, unscheduled medical attendances for wheezing episodes were reduced in children given montelukast in the 5/5 stratum (2·0 [2·7] vs 2·4 [3·0]; IRR 0·80, 95% CI 0·68–0·95; p=0·01), but not in those in the 5/x+x/x stratum (2·0 [2·5] vs 2·0 [2·3]; 1·03, 0·83–1·29; p=0·79, pinteraction=0·08). We recorded one serious adverse event, which was a skin reaction in a child allocated to placebo.InterpretationOur findings show no clear benefit of intermittent montelukast in young children with wheeze. However, the 5/5 ALOX5 promoter genotype might identify a montelukast-responsive subgroup.FundingMedical Research Council (UK) and National Institute for Health Research.

IntroductionVitamin D is best known for its role in bone health; however, the discovery of the vitamin D receptor and the expression of the gene encoding the vitamin D 1α-hydroxylase (CYP27B1) enzyme in a wide variety of tissues including immune cells and respiratory epithelium has led to the discovery of potential roles for vitamin D in the prevention of acute wheeze.MethodsWe review here the literature concerning the relationships between circulating 25-hydroxyvitamin D (25(OH)D) concentration and secondary prevention of acute wheeze attacks in preschool and school-age children.ResultsEpidemiological data suggest that vitamin D insufficiency (25(OH)D <75 nmol/L) is highly prevalent in preschool and school-age children with wheeze. Preschool age children with a history of wheeze attacks and circulating 25(OH)D <75 nmol/L are at increased risk and frequency of future acute wheeze. However, no consistent association between low vitamin D status and risk of acute wheeze is reported in school-age children. Seven randomised controlled trials (RCTs) with relatively small sample sizes (30–430) and variable quality showed inconsistent results regarding the effect of oral vitamin D supplementation during childhood on the risk of asthma attacks, asthma symptom control, inhaled corticosteroid requirements, spirometry and unscheduled healthcare attendances for wheeze. A RCT showed that vitamin D supplementation had no effect on the frequency of unplanned healthcare attendances due to acute wheeze in 22 preschool children.DiscussionAn evidence-based recommendation for the use of vitamin D as a preventive therapy for wheeze attacks cannot be made until results of further trials are available. The assessment of circulating 25(OH)D concentration and the optimisation of vitamin D status to prevent acute respiratory tract infections, and to maintain skeletal and general health in preschool and school-age children with acute wheeze is worthwhile in its own right, but whether this will reduce the risk of acute wheeze attacks is unclear.

ObjectivesTo compare the motives and experiences of different ethnic groups participating in a randomised double blind placebo-controlled trial of montelukast in preschool wheeze, and to assess parents’ or guardians’ understanding of trial procedures and their implications, including the collection of genetic material.DesignQualitative interviews with parents or guardians.SettingInterviews occurred in the homes of London children recruited to a national multicentre clinical trial following primary and secondary care attendance with wheeze.Participants42 parents (20 of Bangladeshi origin, 10 white UK, 12 other ethnicities) of preschool children enrolled in a clinical trial.ResultsBangladeshi families were relatively reluctant to participate in the qualitative study, despite strong engagement with the parent study. Anxiety related to wheezing was a common primary motive for trial enrolment. Parents viewed the trial as a route to improved treatment. Verbal delivery of trial information appeared more effective than study literature, especially for Bangladeshi families, with low parental literacy and high levels of trust in medical professionals potential contributors to this effect. All ethnic groups expressed a low understanding and/or retention of essential study concepts such as randomisation and genetic testing.ConclusionsBangladeshi families are particularly motivated to participate in clinical trials despite variable comprehension of study concepts. This motivation is more strongly contingent on strong researcher-subject rapport than on the quality of study literature. Trial teams seeking to recruit from South Asian populations should emphasise face-to-face verbal explanation of trial concepts and procedures and consider modified trial literature.