How can we optimise inhaled beta2 agonist dose as ‘reliever’ medicine for wheezy pre-school children? Study protocol for a randomised controlled trial

Background: Asthma is a common problem in children and, if inadequately controlled, may seriously diminish their quality of life. Inhaled short-acting beta2 agonists such as salbutamol are usually prescribed as ‘reliever’ medication to help control day-to-day symptoms such as wheeze. As with many medications currently prescribed for younger children (defined as those aged 2 years 6 months to 6 years 11 months), there has been no pre-licensing age-specific pharmacological testing; consequently, the doses currently prescribed (200–1000 μg) may be ineffective or likely to induce unnecessary side effects. We plan to use the interrupter technique to measure airway resistance in this age group, allowing us for the first time to correlate inhaled salbutamol dose with changes in clinical response. We will measure urinary salbutamol levels 30 min after dosing as an estimate of salbutamol doses in the lungs, and also look for genetic polymorphisms linked to poor responses to inhaled salbutamol. Methods: This is a phase IV, randomised, controlled, observer-blinded, single-centre trial with four parallel groups (based on a sparse sampling approach) and a primary endpoint of the immediate bronchodilator response to salbutamol so that we can determine the most appropriate dose for an individual younger child. Simple randomisation will be used with a 1:1:1:1 allocation. Discussion: The proposed research will exploit simple, non-invasive and inexpensive tests that can mostly be performed in an outpatient setting in order to help develop the evidence for the correct dose of salbutamol in younger children with recurrent wheeze who have been prescribed salbutamol by their doctor. Trial registration: EudraCT2014-001978-33, ISRCTN15513131. Registered on 8 April 2015

Update of the European paediatric respiratory medicine syllabus

The 10-year-old European syllabus for paediatric respiratory medicine (PRM; also known as paediatric pulmonology) was updated by a consensus-based method using an expert task force for redrafting, and a subsequent Delphi process to achieve consensus. There was a high degree of consensus for the final syllabus, which has been streamlined and made more relevant to current practice. All modules are now mandatory apart from the undertaking of research projects, which is optional. Although there are still a number of countries in Europe which do not recognise PRM as a separate subspecialty, there are paediatric respiratory physicians practising in every country in Europe, and a current and harmonised European syllabus in the subspecialty remains important for defining the training and areas of practice of PRM practitioners

Investigating the association between obesity and asthma in 6- to 8-year-old Saudi children:a matched case-control study

Background: Previous studies have demonstrated an association between obesity and asthma, but there remains considerable uncertainty about whether this reflects an underlying causal relationship. Aims: To investigate the association between obesity and asthma in pre-pubertal children and to investigate the roles of airway obstruction and atopy as possible causal mechanisms. Methods: We conducted an age- and sex-matched case–control study of 1,264 6- to 8-year-old schoolchildren with and without asthma recruited from 37 randomly selected schools in Madinah, Saudi Arabia. The body mass index (BMI), waist circumference and skin fold thickness of the 632 children with asthma were compared with those of the 632 control children without asthma. Associations between obesity and asthma, adjusted for other potential risk factors, were assessed separately in boys and girls using conditional logistic regression analysis. The possible mediating roles of atopy and airway obstruction were studied by investigating the impact of incorporating data on sensitisation to common aeroallergens and measurements of lung function. Results: BMI was associated with asthma in boys (odds ratio (OR)=1.14, 95% confidence interval (CI), 1.08–1.20; adjusted OR=1.11, 95% CI, 1.03–1.19) and girls (OR=1.37, 95% CI, 1.26–1.50; adjusted OR=1.38, 95% CI, 1.23–1.56). Adjusting for forced expiratory volume in 1 s had a negligible impact on these associations, but these were attenuated following adjustment for allergic sensitisation, particularly in girls (girls: OR=1.25; 95% CI, 0.96–1.60; boys: OR=1.09, 95% CI, 0.99–1.19). Conclusions: BMI is associated with asthma in pre-pubertal Saudi boys and girls; this effect does not appear to be mediated through respiratory obstruction, but in girls this may at least partially be mediated through increased risk of allergic sensitisation

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Relationships between Specific Airway Resistance and Forced Expiratory Flows in Asthmatic Children

. The first aim was to assess the relationships between forced expiratory flows and sRaw in a large group of asthmatic children in a transversal study. We then performed a longitudinal study in order to determine whether sRaw of preschool children could predict subsequent impairment of forced expiratory flows at school age.Pulmonary function tests (sRaw and forced expiratory flows) of 2193 asthmatic children were selected for a transversal analysis, while 365 children were retrospectively selected for longitudinal assessment from preschool to school age. (% predicted) (−0.09, 95% CI, −0.20 to 0). and could be used in preschool children to predict subsequent mild airflow limitation

The multiple meanings of "wheezing": a questionnaire survey in Portuguese for parents and health professionals

<p>Abstract</p> <p>Background</p> <p>Most epidemiological studies on pediatric asthma rely on the report of "wheezing" in questionnaires. Our aim was to investigate the understanding of this term by parents and health professionals.</p> <p>Methods</p> <p>A cross-sectional survey was carried out in hospital and community settings within the south of Portugal. Parents or caregivers self-completed a written questionnaire with information on social characteristics and respiratory history. Multiple choice questions assessed their understanding of "wheezing". Health professionals (physicians, nurses and physiotherapists) were given an adapted version. We used bivariate analysis and multivariate models to study associations between definitions of "wheezing" and participants' characteristics.</p> <p>Results</p> <p>Questionnaires from 425 parents and 299 health professionals were included. The term "wheezing" was not recognized by 34% of parents, more frequently those who were younger (OR 0.4 per 10-year increment, 95% CI 0.3-0.7), had lower education (OR 3.3, 95% CI 1.5-7.4), and whose children had no history of respiratory disease (OR 4.6, 95% CI 2.5-8.7) (all ORs adjusted). 31% of parents familiar with "wheezing" either did not identify it as a sound, or did not locate it to the chest, while tactile (40%) and visual (34%) cues to identify "wheezing" were frequently used. Nurses reported using visual stimuli and overall assessments more often than physicians (p < 0.01). The geographical location was independently associated with how parents recognized and described "wheezing".</p> <p>Conclusions</p> <p>Different meanings for "wheezing" are recognized in Portuguese language and may be influenced by education, respiratory history and regional terminology. These findings are likely applicable to other non-English languages, and suggest the need for more accurate questionnaires and additional objective measurement instruments to study the epidemiology of wheezing disorders.</p

In vivo and ex vivo percutaneous absorption of [14C]-bisphenol A in rats: a possible extrapolation to human absorption?

Bisphenol A (BPA) is a monomer used mainly in the synthesis of polycarbonates and epoxy resins. Percutaneous absorption is the second source of exposure, after inhalation, in the work environment. However, studies on this route of absorption are lacking or incomplete. In this study, percutaneous BPA absorption was measured in vivo and ex vivo in the rat, and ex vivo in humans. An approximately 12-fold difference in permeability between rat skin and human skin was found, with permeability being higher in the rat. In addition, inter- and intra-individual variability of up to tenfold was observed in humans. No accumulation of BPA in the skin was found during exposure. The skin clearance rate following exposure was estimated at 0.4 μg/cm²/h. Ex vivo and in vivo percutaneous absorption fluxes of BPA in the rat were in the same range (about 2.0 μg/cm²/h), suggesting that extrapolation to the in vivo situation in humans may be possible. The European tolerable daily intake (TDI) of BPA is 50 μg/kg body weight. However, many research projects have highlighted the significant effects of BPA in rodents at doses lower than 10 μg/kg/day. A 1-h occupational exposure over 2,000 cm² (forearms and hands) may lead to a BPA absorption of 4 μg/kg/day. This is 8% of the European TDI and is very close to the value at which effects have been observed in animals. This absorption must therefore be taken into account when evaluating risks of BPA exposure, at least until more relevant results on the toxicity of BPA in humans are available

Use of interrupter technique in assessment of bronchial responsiveness in normal subjects

BACKGROUND: A number of subjects, especially the very young and the elderly, are unable to cooperate and to perform forced expiratory manoeuvres in the evaluation of bronchial hyperresponsiveness (BHR). The objective of our study was to investigate the use of the interrupter technique as a method to measure the response to provocation and to compare it with the conventional PD(20 )FEV(1). METHODS: We studied 170 normal subjects, 100 male and 70 female (mean ± SD age, 38 ± 8.5 and 35 ± 7.5 years, respectively), non-smoking from healthy families. These subjects had no respiratory symptoms, rhinitis or atopic history. A dosimetric cumulative inhalation of methacholine was used and the response was measured by the dose which increases baseline end interruption resistance by 100% (PD(100)Rint, EI) as well as by percent dose response ratio (DRR). RESULTS: BHR at a cut-off level of 0.8 mg methacholine exhibited 31 (18%) of the subjects (specificity 81.2%), 21 male and 10 female, while 3% showed a response in the asthmatic range. The method was reproducible and showed good correlation with PD(20)FEV(1 )(r = 0.76, p < 0.005), with relatively narrow limits of agreement at -1.39 μmol and 1.27 μmol methacholine, respectively, but the interrupter methodology proved more sensitive than FEV(1 )in terms of reactivity (DRR). CONCLUSIONS: Interrupter methodology is clinically useful and may be used to evaluate bronchial responsiveness in normal subjects and in situations when forced expirations cannot be performed

A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample

BACKGROUND: In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. METHODS/DESIGN: A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in The Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. DISCUSSION: Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardized. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population