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.
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
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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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.
Patients with chest pain and no obstructive coronary artery disease have shown a high incidence of major adverse cardiovascular events (MACE). We evaluated the role of absolute myocardial perfusion ...quantification in predicting all-cause mortality and MACE during long-term follow-up in this group of patients.
We studied 79 patients who underwent Nitrogen-13 ammonia PET for quantification of global myocardial blood flow (MBF) and myocardial flow reserve (MFR) due to suspected impaired myocardial perfusion. Patients with coronary artery disease (i.e., > 30% stenosis in one or more coronary arteries) were excluded. We assessed all-cause mortality and MACE. MACE was defined as the composite incidence of death, myocardial infarction (MI), or hospitalization due to heart failure.
Median follow-up was 8 (IQR: 3-14) years. Univariate Cox regression showed that only MFR (P = 0.01) was a predictor of all-cause mortality. Univariate Cox regression analysis showed that both MFR and Stress MBF were predictors of the composite endpoint of MACE (P < 0.001 and P = 0.01, respectively).
Quantitative assessment of myocardial perfusion may predict all-cause mortality and MACE in patients with chest pain and normal coronary arteries in the long-term follow-up.
Los pacientes con dolor torácico y sin enfermedad arterial coronaria obstructiva tienen una alta incidencia de eventos cardiovasculares adversos mayores (ECAM). Evaluamos el papel de cuantificación absoluta de perfusión miocárdica para predecir la mortalidad por cualquier causa y por ECAM en el seguimiento a largo plazo en este grupo de pacientes.
Estudiamos 79 pacientes a quienes se les realizó PET con 13-Nitrógeno Amonia para la cuantificación absoluta del flujo sanguíneo miocárdico global (FSM) y la reserva de flujo miocárdica (RFM) por sospecha de alteraciones en la perfusión miocárdica. Se excluyeron a los pacientes con enfermedad arterial coronaria (estenosis > 30% en una o más arterias). Evaluamos las causas de mortalidad y de ECAM. ECAM fue definida como la incidencia combinada de muerte, infarto al miocardio (IM) u hospitalización por falla cardíaca.
La media de seguimiento fue de 8 años (IQR: 3-14). La regresión univariada COX mostró que solo la RFM, es un predictor de mortalidad por cualquier causa. El análisis de regresión univariada Cox mostró que tanto la RFM como la FSM en estrés, fueron predictores para el desenlace de ECAM (P < 0.001 y P = 0.01, respectivamente).
La evaluación cuantitativa de la perfusión miocárdica, puede predecir la mortalidad por cualquier causa y por ECAM en pacientes con dolor torácico y arterias coronarias normales en el seguimiento a largo plazo.
患有胸痛但无阻塞性冠状动脉疾病的患者仍存在较高的主要不良心血管事件 (MACE) 发生率。 本研究评估了心肌灌注绝对定量对该组患者长期随访期间全因死亡率和 MACE的预测价值。
共纳入79例疑似心肌缺血患者, 行13N-氨水 PET 心肌灌注显像获得定量的心肌血流值 (MBF) 和心肌血流储备 (MFR)。 排除冠状动脉疾病 (即一支或多支冠状动脉狭窄 > 30%) 的患者。 分析全因死亡率和 MACE。 MACE 定义为死亡,心肌梗死 (MI) 或因心力衰竭住院的复合事件。
随访中位时间为8年 (IQR:3-14)。 单变量Cox回归分析显示只有 MFR (P = 0.01) 是全因死亡率的预测因子。而 MFR 和负荷MBF是 MACE 复合终点事件的预测因子 (分别为 P < 0.001和 P = 0.01)。
在有胸痛但冠状动脉正常患者的长期随访中, 心肌灌注血流定量分析可预测全因死亡率和 MACE。
A certain nombre de patients présentant des douleurs thoraciques sans évidence de coronaropathie obstructive ont une incidence élevée d’événements cardiovasculaires indésirables majeurs. Nous avons étudié le rôle de la quantification absolue de la perfusion myocardique en tant que valeur prédictive de mortalité et d’événements cardiovasculaires majeurs indésirables chez ces patients.
Nous avons étudié 79 patients suspect de maladie coronarienne. Nous avons évalué de manière quantitative leur perfusion myocardique globale et leur réserve de débit myocardique (MFR) par tomographique à positrons à l’ammoniac marqué à l’azote 13. Les patients atteints de maladie coronarienne définie par une sténose de plus de 30% d’une ou de plusieurs artères coronaires ont été exclus. Nous ont évalué la mortalité globale (quelqu’en soient les causes) et les événements cardiovasculaires majeurs indésirables
Le suivi moyen fut de 8 ans (3-14 ans). L’analyse des données au moyen de la régression univariée de Cox a montré que seul le flux de réserve myocardique (P = 0.01) est un facteur prédictif de mortalité, toutes causes confondues. La même régression statistique a également permis de démontrer que la perfusion myocardique globale et la réserve de débit coronaire sont des paramètres prédictifs déterminant pour la survenue événements cardiovasculaires majeurs indésirables majeurs (P < 0.001 et P = 0.01 respectivement).
L’évaluation quantitative de la perfusion myocardique des patients présentant des douleurs thoraciques et chez qui les artères coronaires s’avèrent normales permet de prédire le risque de mortalité et la survenue d’événements cardiovasculaires majeurs indésirables dans le suivi à long terme.
Background
Breastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of ...breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease‐related modification of the exposure or modified by maternal history of allergy, eczema, or asthma.
Methods
This study among 5828 children was performed in a population‐based prospective cohort from fetal life onwards. We collected information on duration (<2 months, 2‐4 months, 4‐6 months, and ≥6 months) and exclusiveness (nonexclusive vs exclusive for 4 months) of breastfeeding in infancy by postal questionnaires. At age 10 years, inhalant allergic sensitization and food‐allergic sensitization were measured by skin prick tests, and physician‐diagnosed inhalant and food allergy by a postal questionnaire. Data on parental‐reported eczema were available from birth until age 10 years.
Results
We observed no association of breastfeeding with any allergic sensitization, physician‐diagnosed allergy, or combination of these outcomes. Shorter breastfeeding duration was associated with an overall increased risk of eczema (P‐value for trend <.05). Nonexclusively breastfed children had an overall increased risk of eczema (adjusted odds ratio 95% confidence interval: 1.11 1.01, 1.23), compared with children exclusively breastfed for 4 months. Risk period‐specific sensitivity analyses, additional adjustment for ointment use for eczema at age 2 months, and cross‐lagged modeling showed no consistent results for disease‐related modification of the exposure. Results were not modified by maternal history of allergy, eczema, or asthma (lowest P‐value for interaction=.13).
Conclusion
Shorter duration or nonexclusiveness of breastfeeding is associated with a weak overall increased risk of eczema but not allergic sensitization or physician‐diagnosed allergy at age 10 years.
To cite this article: van der Valk RJP, Baraldi E, Stern G, Frey U, de Jongste JC. Daily exhaled nitric oxide measurements and asthma exacerbations in children. Allergy 2012; 67: 265–271.
Background: ... Fractional exhaled Nitric Oxide (FeNO) is a biomarker for eosinophilic airway inflammation and can be measured at home on a daily basis. A short‐term increase in FeNO may indicate a higher risk of future asthma exacerbations.
Objective: To assess changes in FeNO before and after asthma exacerbations compared to a stable control period.
Methods: A post hoc analysis was performed on daily FeNO measurements over 30 weeks in children with asthma (n = 77). Moderate exacerbations were defined by an increase in symptom scores and severe exacerbations by prescription of prednisone. Individual mean and maximum FeNO, the variability of FeNO assessed by the coefficient of variation (CV), and slopes of FeNO in time were all quantified in 3‐week blocks. Cross‐correlation of FeNO with symptoms and autocorrelation of FeNO were assessed in relation to exacerbations and examined as predictors for exacerbations compared to reference periods using logistic regression.
Results: Fractional exhaled nitric oxide could be assessed in relation to 25 moderate and 12 severe exacerbations. The CV, slope, cross‐correlation, and autocorrelation of daily FeNO increased before moderate exacerbations. Increases in slope were also randomly seen in 19% of 2‐week blocks of children without exacerbations. At least 3–5 FeNO measurements in the 3 weeks before an exacerbation were needed to calculate a slope that could predict moderate exacerbations. No specific pattern of FeNO was seen before severe exacerbations.
Conclusion: Fractional exhaled nitric oxide monitoring revealed changes in FeNO prior to moderate exacerbations. Whether this can be used to prevent loss of asthma control should be further explored.
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.
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