The benefits of drug therapy for asthma have been well established, but adherence to treatment is poor, and this might be associated with an increased risk of asthma exacerbations. The aim of this ...study was to review the literature on the association between adherence to asthma controller treatment and risk of severe asthma exacerbations in children and adults. A systematic literature search was performed in PubMed, Embase and Web of Science, from inception until January 2014. Studies were included if data on the association between medication adherence and severe asthma exacerbations were presented. Quality was assessed using a modified version of the Newcastle-Ottawa Scale. The search yielded 2319 unique publications, of which 23 met the inclusion criteria and underwent data extraction and quality scoring. High levels of heterogeneity across studies with regard to adherence and exacerbation measurements, designs and analysis precluded a formal meta-analysis. Although effect measures varied widely, good adherence was associated with fewer severe asthma exacerbations in high-quality studies. Good adherence tended to be associated with lower risk of severe asthma exacerbations. Future studies should use standardised methodology to assess adherence and exacerbations, and should consider inhaler competence.
Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined ...the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.
Summary
Background
Childhood eczema is variable in onset and persistence.
Objectives
To identify eczema phenotypes during childhood, and their associations with early‐life environmental and genetic ...factors.
Methods
In this study of 5297 children from a multiethnic population‐based prospective cohort study, phenotypes based on parent‐reported physician‐diagnosed eczema from age 6 months to 10 years were identified using latent class growth analysis. Information on environmental factors was obtained using postal questionnaires. Four filaggrin mutations were genotyped and a risk score was calculated based on 30 genetic variants. Weighted adjusted multinomial models were used for association analyses.
Results
We identified the following five eczema phenotypes: never (76%), early transient (8%), mid‐transient (6%) and late transient (8%) and persistent eczema (2%). Early transient and persistent eczema were most common in first‐born children, those with a parental history of eczema, allergy or asthma and those with persistent wheezing range of odds ratio (OR): 1.37, 95% confidence interval (CI) 1.07–1.74 and OR 3.38, 95%CI 1.95–5.85. Early transient eczema was most common in male children only (OR 1·49, 95% CI 1·18–1·89). Children with late transient or persistent eczema were more often of Asian ethnicity (OR 2·04, 95% CI 1·14–3·65 and OR 3·08, 95% CI 1·34–7·10, respectively). Children with early, late transient and persistent eczema more often had a filaggrin mutation or additional risk alleles (range OR: 1.07, 95%CI 1.02–1.12 and OR 2.21, 95%CI 1.39–3.50). Eczema phenotypes were not associated with maternal education, breastfeeding, day care attendance and pet exposure.
Conclusions
Five eczema phenotypes were identified in a multiethnic paediatric population with limited differences in risk profiles, except for sex and ethnicity.
What's already known about this topic?
Two previous studies in longitudinal birth cohorts identified four and six different eczema phenotypes, predominantly in children of European ethnicity.
What does this study add?
Five eczema phenotypes were identified in a multiethnic paediatric population using latent class growth analysis.
Children with early transient and persistent eczema were most often first‐born children and had persistent wheezing, filaggrin mutation or additional risk alleles.
Previously known eczema risk factors had limited differentiating capabilities for eczema phenotypes, except for the association of early transient eczema with male children, and late transient and persistent eczema with Asian ethnicity.
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Summary
Background
Eczema phenotypes and emotional and behavioural problems are highly prevalent in childhood, but their mutual relationship is not fully clear.
Objectives
To examine the associations ...of eczema phenotypes with school‐age emotional and behavioural problems, and the bidirectional associations of eczema and emotional and behavioural problems from birth until 10 years.
Methods
This study among 5265 individuals was embedded in a prospective population‐based cohort study. Never, early transient, mid‐transient, late transient and persistent eczema phenotypes were identified based on parent‐reported, physician‐diagnosed eczema from age 6 months until 10 years. Emotional (internalizing) and behavioural (externalizing) problems were measured repeatedly using the Child Behavior Checklist from age 1·5 to 10 years. Cross‐lagged models were applied for bidirectional analyses.
Results
All eczema phenotypes were associated with more internalizing problems and attention problems at age 10 years, compared with never having eczema: range of Z‐score differences 0·14 95% confidence interval (CI) 0·01–0·27 to 0·39 (95% CI 0·18–0·60). Children with early transient eczema had more aggressive behaviour symptoms at age 10 years (Z = 0·16, 95% CI 0·05–0·27). Bidirectional analysis showed that eczema at 0–2 years was associated with more internalizing and externalizing problems at ages 3–6 and 10 years, while, inversely, only internalizing problems at 0–2 years were associated with an increased risk of eczema at age 10 years.
Conclusions
Eczema phenotypes are very modestly associated with more somatic symptoms and attention problems at school age. Early transient eczema is associated with more aggressive behaviour symptoms. Directional effects seem to occur from early‐life eczema to later‐life internalizing and externalizing problems, rather than the reverse.
What's already known about this topic?
Previous cohort studies using non‐data‐driven methods to define eczema phenotypes observed that children with early‐onset and persistent eczema had a higher risk of emotional and behavioural problems in preadolescence.
Alternatively, previous cohort studies showed that children with emotional and behavioural problems had more severe eczema and eczema exacerbations in childhood.
The direction of effects between eczema and emotional and behavioural problems is not fully clear.
What does this study add?
Taking the variability of eczema onset and persistence within and between children over time into account, all identified eczema phenotypes were very modestly associated with more somatic symptoms and attention problems at school age.
Directional effects seem to occur from eczema leading to emotional and behavioural problems, rather than the reverse.
Future research should focus on the effect of early optimal eczema management on mental health disorders in children later in life.
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Objectives
To assess the associations of folate, homocysteine and vitamin B12 levels of children at birth and their methylenetetrahydrofolate reductase (MTHFR) variants with asthma and eczema in ...childhood.
Methods
This study was embedded in a population‐based prospective cohort study (n = 2,001). Neonatal cord blood folate, homocysteine and vitamin B12 levels were measured, and MTHFR C677T and A1298C genotyped. Wheezing and physician‐diagnosed eczema were annually obtained by questionnaire until 4 years. At 6 years, we collected information on physician‐diagnosed asthma ever and self‐reported eczema ever, measured fractional exhaled nitric oxide (FeNO), and interrupter resistance (Rint). Data were analysed with generalized estimating equations or logistic regression: continuous outcomes with linear regression models.
Results
Folate, homocysteine and vitamin B12 levels of children at birth were not associated with wheezing or eczema until 4 years, asthma and eczema ever, or FeNO or Rint at 6 years. In children carrying C677T mutations in MTHFR, higher folate levels were associated with an increased risk of eczema (repeated eczema until 4 years: OR 1.40 (95% CI 1.09–1.80) (SD change) P‐interaction = 0.003, eczema ever at 6 years: OR 1.41 (0.97–2.03) P‐interaction = 0.011). No interactions between MTHFR and child folate and homocysteine levels were observed for wheezing and asthma.
Conclusions
Folate, homocysteine and vitamin B12 levels of children at birth did not affect asthma‐ and eczema‐related outcomes up to the age of 6 years. Further studies are warranted to establish the role of MTHFR variants in these associations.
Summary
Background
A novel data‐driven approach was used to identify wheezing phenotypes in pre‐schoolchildren aged 0–8 years, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth ...cohort. Five phenotypes were identified: never/infrequent wheeze, transient early wheeze, intermediate onset wheeze, persistent wheeze and late onset wheeze. It is unknown which perinatal risk factors drive development of these phenotypes.
Objective
The objective of the study was to assess associations of perinatal factors with wheezing phenotypes and to identify possible targets for prevention.
Methods
In the PIAMA study (n = 3963), perinatal factors were collected at 3 months, and wheezing was assessed annually until the age of 8 years. Associations between perinatal risk factors and the five wheezing phenotypes were assessed using weighted multinomial logistic regression models. Odds ratios were adjusted for confounding variables and calculated with ‘never/infrequent wheeze’ as reference category.
Results
Complete data were available for 2728 children. Risk factors for transient early wheeze (n = 455) were male gender, maternal and paternal allergy, low maternal age, high maternal body mass index, short pregnancy duration, smoking during pregnancy, presence of older siblings and day‐care attendance. Risk factors for persistent wheeze (n = 83) were male gender, maternal and paternal allergy, and not receiving breastfeeding for at least 12 weeks. Intermediate onset wheeze (n = 98) was associated with a lower birth weight and late onset wheeze (n = 45) with maternal allergy.
Conclusion and Clinical Relevance
We identified different risk factors for specific childhood wheezing phenotypes. Some of these are modifiable, such as maternal age and body mass index, smoking, day‐care attendance and breastfeeding, and may be important targets for prevention programmes.
Few studies have addressed associations between traffic-related air pollution and respiratory disease in young children. The present authors assessed the development of asthmatic/allergic symptoms ...and respiratory infections during the first 4 yrs of life in a birth cohort study (n = approximately 4,000). Outdoor concentrations of traffic-related air pollutants (nitrogen dioxide PM(2.5), particles with a 50% cut-off aerodynamic diameter of 2.5 mum and soot) were assigned to birthplace home addresses with a land-use regression model. They were linked by logistic regression to questionnaire data on doctor-diagnosed asthma, bronchitis, influenza and eczema and to self-reported wheeze, dry night-time cough, ear/nose/throat infections and skin rash. Total and specific immunoglobulin (Ig)E to common allergens were measured in a subgroup (n = 713). Adjusted odds ratios (95% confidence intervals) per interquartile pollution range were elevated for wheeze (1.2 (1.0-1.4) for soot), doctor-diagnosed asthma (1.3 (1.0-1.7)), ear/nose/throat infections (1.2 (1.0-1.3)) and flu/serious colds (1.2 (1.0-1.4)). No consistent associations were observed for other end-points. Positive associations between air pollution and specific sensitisation to common food allergens (1.6 (1.2-2.2) for soot), but not total IgE, were found in the subgroup with IgE measurements. Traffic-related pollution was associated with respiratory infections and some measures of asthma and allergy during the first 4 yrs of life.
As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all ...patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the Netherlands, between 1975 and 2012, excluding those with the classic-infantile form. None were treated with enzyme replacement therapy at the time of evaluation. We collected information on first symptoms, diagnosis, use of a wheelchair and/or respirator, and enzyme and mutation analysis and assessed muscle strength, pulmonary function, and cardiac parameters.
Thirty-one patients participated. Median age at symptom onset was 2.6 years (range 0.5-13y) and at diagnosis 4.0 years. Most first problems were delayed motor development and problems related to limb-girdle weakness. Fatigue, persistent diarrhea and problems in raising the head in supine position were other first complaints. Ten patients were asymptomatic at time of diagnosis. Five of them developed symptoms before inclusion in this study. Over 50 % of all patients had low or absent reflexes, a myopathic face, and scoliosis; 29 % were underweight. Muscle strength of the neck flexors, hip extensors, hip flexors, and shoulder abductors were most frequently reduced. Pulmonary function was decreased in over 48 % of the patients; 2 patients had cardiac hypertrophy. Patients with mutations other than the c.-32-13T > G were overall more severely affected, while 18 out of the 21 patients (86 %) with the c.-32-13T > G/'null' genotype were male.
Our study shows that Pompe disease can present with severe mobility and respiratory problems during childhood. Pompe disease should be considered in the differential diagnosis of children with less familiar signs such as disproportional weakness of the neck flexors, unexplained fatigue, persistent diarrhea and unexplained high CK/ASAT/ALAT. Disease presentation appears to be different from adult patients. The majority of affected children with GAA genotype c.-32-13T > G/'null' appeared to be male.
Despite the critical role of soluble IgE in the pathology of IgE‐mediated allergic disease, little is known about abnormalities in the memory B cells and plasma cells that produce IgE in allergic ...patients. We here applied a flow cytometric approach to cross‐sectionally study blood IgE+ memory B cells and plasmablasts in 149 children with atopic dermatitis, food allergy, and/or asthma and correlated these to helper T(h)2 cells and eosinophils. Children with allergic disease had increased numbers of IgE+CD27‐ and IgE+CD27+ memory B cells and IgE+ plasmablasts, as well as increased numbers of eosinophils and Th2 cells. IgE+ plasmablast numbers correlated positively with Th2 cell numbers. These findings open new possibilities for diagnosis and monitoring of treatment in patients with allergic diseases.
The use of exhaled nitric oxide measurements (FEno) in clinical practice is now coming of age. There are a number of theoretical and practical factors which have brought this about. Firstly, FEno is ...a good surrogate marker for eosinophilic airway inflammation. High FEno levels may be used to distinguish eosinophilic from non-eosinophilic pathologies. This information complements conventional pulmonary function testing in the assessment of patients with non-specific respiratory symptoms. Secondly, eosinophilic airway inflammation is steroid responsive. There are now sufficient data to justify the claim that FEno measurements may be used successfully to identify and monitor steroid response as well as steroid requirements in the diagnosis and management of airways disease. FEno measurements are also helpful in identifying patients who do/do not require ongoing treatment with inhaled steroids. Thirdly, portable nitric oxide analysers are now available, making routine testing a practical possibility. However, a number of issues still need to be resolved, including the diagnostic role of FEno in preschool children and the use of reference values versus individual FEno profiles in managing patients with difficult or severe asthma.
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