Transgenerational occurrence of allergic disease and autoimmunity: general practice-based epidemiological research.

BACKGROUND: Corresponding with the T helper cell type 1/T helper cell type 2 hypothesis, autoimmune and allergic diseases are considered pathologically distinct and mutually exclusive conditions. Co-occurrence of autoimmune disorders and allergy within patients, however, has been reported. Transgenerational co-occurrence of autoimmune and allergic disease has been less often described and may differ from the intra-patient results. AIMS: To test the hypothesis that autoimmune disorders in parents are a risk factor for the development of an allergic disease in their offspring. METHODS: Prospectively registered (by academic general practitioners) International Classifications of Primary Care (ICPC) for diagnoses of autoimmune disorders and allergy within families were evaluated (n=5,604 families) by performing multiple logistic regression analyses. RESULTS: The presence of any ICPC-encoded autoimmune disorder in fathers appeared to be associated with an increased risk in their eldest children of developing an allergy (odds ratio (OR) 1.4, 95% CI 1.042 to 1.794). Psoriasis in fathers was particularly shown to be of influence (OR 1.5, 95% CI 1.061 to 2.117) and, although any ICPC-encoded autoimmune disease in mothers was found not to be of significance, the combined international code for registering rheumatoid arthritis/ankylosing spondylitis in mothers was OR 1.7 (95% CI 1.031 to 2.852). CONCLUSIONS: The occurrence of ICPC-encoded autoimmune disorders in parents, especially psoriasis and rheumatoid arthritis/ankylosing spondylitis, significantly increases the occurrence of allergic disease in their children. After validation in follow-up research in a larger sample, these results may lead to the inclusion of 'parental autoimmune condition' as a risk factor in the general practitioner's diagnostics of allergic disease.

Cost-effectiveness of primary prevention of paediatric asthma: a decision-analytic model.

BACKGROUND: Many children stand to benefit from being asthma-free for life with primary (i.e., prenatally started) prevention addressing one environmental exposure in a unifaceted (UF) approach or at least two in a multifaceted (MF) approach. We assessed the cost-effectiveness of primary prevention programmes for Dutch children in a decision-analytic framework. METHODS: A decision-analytic tree model analysing healthcare costs and asthma cases prevented was developed to compare usual care (UC) with two UF and three MF programmes on the primary prevention of asthma amongst children. Programmes were evaluated through incremental cost-effectiveness ratios and net monetary benefits. Decision and parameter uncertainty were subjected to value-of-information analyses. RESULTS: The current UC and one of three MF programmes dominated the other alternatives. The MF programme was more costly but also more effective than UC at an incremental cost-effectiveness ratio of 8,209.20/additional asthma case prevented. The value of perfect information to reduce uncertainty was 291.6M at its lowest. Most of the uncertainty in the cost-effectiveness threshold was attributable to the probability and cost estimates for low-risk children. CONCLUSION: This study supports the feasibility of a structured programme that simultaneously addresses exposure to house dust mites, pet dander, environmental tobacco, and breast-feeding as a cost-effective alternative to UC in the primary prevention of asthma amongst children.

Prevention of asthma in genetically susceptible children: a multifaceted intervention trial focussed on feasibility in general practice.

BACKGROUND: Although the effectiveness of the multifaceted allergen-reducing interventions for the prevention of asthma in susceptible children was showed to be proven, the feasibility was not clear. METHODS: The research question of the PREVention of asthma in susceptible children (PREVASC) trial was focused on the assessment of the effectiveness and feasibility of a multifaceted intervention on the prevention of allergic asthma in general practice. The effectiveness and feasibility of an intervention aimed at the simultaneous reduction in the environmental exposures to inhalant- and food allergens in susceptible children was investigated. A total of 476 children susceptible for developing asthma were initially included during pregnancy and were randomly divided over an intervention group of n = 222 children whose parents were offered a multifaceted environmental exposure-reducing intervention. Controls (n = 221) received usual care. The main outcome was 'diagnosis of allergic asthma at age 6'. RESULTS: A significant reduction in inhalant allergen exposure levels of house dust mite [(Der p1), p = 0.043], cat [(Fel d1), p = 0.037], and dog [(Can f1), p = 0.012] was reached. Significantly more intervention group children started using cow's milk and solids after the age of 6 months (p ≤ 0.001). No statistical difference, however, was reached between groups on the duration of breast-feeding (p = 0.635) and the reduction in smoke exposure (p = 0829). At age 6, the intervention had no influence on the development of main outcome allergic asthma (OR = 1.010 (CI 0.580-1.758). CONCLUSION: Other primary preventive asthma-reducing interventions were shown to be effective in reducing the occurrence of asthma for at least the first 7-8 yr of life. The multifaceted PREVASC allergic asthma primary preventive intervention was effective in reducing the exposure to inhalant and food allergens, but was not feasible for the parents. A lack of sufficient room for improvement focus on stimulating adherence seemed to be involved. It is suggested that a multifaceted environmental exposure-reducing intervention may have to be adapted to the personal circumstances of patients at baseline.

Mono and multifaceted inhalant and/or food allergen reduction interventions for preventing asthma in children at high risk of developing asthma.

BACKGROUND: Allergen exposure is one of the environmental factors seemingly associated with the development of asthma. If asthma is a multi-factorial disease, it is hypothesised that prevention might only prove effective if most or all relevant environmental factors are simultaneously avoided. OBJECTIVES: To assess effect(s) of monofaceted and multifaceted interventions compared with control interventions in preventing asthma and asthma symptoms in high risk children. SEARCH STRATEGY: We searched the Cochrane Airways Trials Register (December 2008). SELECTION CRITERIA: Randomised controlled trials of allergen exposure reduction for the primary prevention of asthma in children. Interventions were multifaceted (reducing exposure to both inhalant and food allergens) or monofaceted (reducing exposure to either inhalant or food allergens) Follow up had to be from birth (or during pregnancy) up to a minimum of two years of age. DATA COLLECTION AND ANALYSIS: We included in the analysis studies assessing the primary outcome (current diagnosis: asthma) and/or one of the secondary outcomes (current respiratory symptoms: wheezing, nocturnal coughing and dyspnoea). We pooled multifaceted and monofaceted intervention trials separately. We made an indirect comparison of their effects using tests for interaction to calculate relative odds ratios. MAIN RESULTS: We included three multifaceted and six monofaceted intervention studies (3271 children). Physician diagnosed asthma in children less than five years, and asthma as defined by respiratory symptoms and lung function criteria in children aged five years and older, both favoured treatment with a multifaceted intervention compared to usual care (< 5 years: odds ratio (OR) 0.72, 95% confidence interval (CI) 0.54 to 0.96, and > 5 years: OR 0.52, 95% CI 0.32 to 0.85). However, there was no significant difference in outcome between monofaceted intervention and control interventions (< 5 years: OR 1.12, 95% CI 0.76 to 1.64, and > 5 years: OR 0.83, 95% CI 0.59 to 1.16). Indirect comparison between these treatments did not demonstrate a significant difference between multiple interventions and mono-interventions in reducing the frequency of asthma diagnosis in children under five years (relative OR 0.64 (95% CI 0.40 to 1.04, P = 0.07) or five years and older (relative OR 0.63, 95% CI 0.35 to 1.13, P = 0.12). There was also no significant difference between either mono- and multifaceted intervention and control in reducing the likelihood of symptoms of nocturnal coughing at follow up. Wheezing, however, showed a significant difference between multifaceted and mono-interventions (relative OR 0.59, 95% CI 0.35 to 0.99, P = 0.04), but the significance was lost when data on treatment only was analysed. AUTHORS' CONCLUSIONS: The available evidence suggests that the reduction of exposure to multiple allergens compared to usual care reduces the likelihood of a current diagnosis of asthma in children (at ages < 5 years and 5 years and older). Mono-intervention studies have not produced effects which are statistically significant compared with control. In children who are at risk of developing childhood asthma, multifaceted interventions, characterised by dietary allergen reduction and environmental remediation, reduce the odds of a physician diagnosis of asthma later in childhood by half. This translates to a number needed to treat (NNT) of 17. The effect of multi-faceted interventions on parent reported wheeze was inconsistent and had no significant impact on nocturnal coughing or dyspnoea. Data from monofaceted intervention exposed children studies were not significantly different from those of control groups for all outcomes. There remains uncertainty as to whether multiple interventions are more effective than mono-component interventions. The comparisons made were indirect, making the conclusions drawn uncertain. To our knowledge there are no ongoing studies in which both intervention strategies are randomly compared. The findings, however, warrant further direct comparison between multiple- and monofaceted interventions aimed at reducing the prevalence of asthma in children.

Is there any role for allergen avoidance in the primary prevention of childhood asthma?

In this article we discuss 3 hypotheses to attempt to understand why preventive measures thus far studied with the aim of preventing (or delaying) the development of asthma have shown such disappointing results. The most likely explanation is that the development of a multifactorial disease, such as asthma, is extremely difficult, if not impossible, to prevent by eliminating only one risk factor. In a meta-analysis we investigated the effect of a multifaceted and monofaceted intervention in 10 prospective birth cohorts of a total of 3473 children on a diagnosis of asthma. Multifaceted intervention studies had an odds ratio (OR) of 0.73 (95% CI, 0.55-0.97), whereas the monointervention studies had an OR of 1.22 (95% CI, 0.83-1.78) in patients younger than 5 years and an OR of 0.52 (95% CI, 0.32-0.84) versus 0.93 (95% CI, 0.66-1.31) in patients older than 5 years. We therefore hypothesize that studies with a multifaceted approach will have a much greater chance of being successful than studies using a monofaceted approach, with the latter being unlikely to yield a clinically relevant reduction of asthma.

Gender-specific differences in the prevention of asthma-like symptoms in high-risk infants.

The prevalence of asthma in children has increased in the last decades, and gender-specific differences in asthma development have recently been suggested. The present study investigates whether gender differences are present in a population of young children (0-2 yr) with a high risk for the development of asthma on the basis of the presence of asthma in first-degree relative(s). The study was performed on 222 children (118 boys, 104 girls) with a familial predisposition of asthma, which received standardized recommendations to reduce exposure to allergens (dust mite, pets and food allergens) and to passive smoking. Health outcome (wheezing episodes and shortness of breath) and compliance with allergen-reducing measures were studied by means of multiple regression analyses. Boys suffered more from asthma-like complaints than girls, as diagnosed by the general practitioner (32% vs. 18%, respectively, p = 0.023). Compliance with intervention measures was similar for boys and girls for most allergens, but food allergen reduction was better applied for girls: duration of exclusive breastfeeding was longer in girls (median 9 wk vs. 4 wk, p = 0.009). Further analysis showed that 4 wk of longer breastfeeding reduced the number of wheezing episodes and shortness of breath in boys by 19% and 15%, respectively, but not in girls, suggesting sex as an effect modifier in the relationship between breastfeeding and asthma-like symptoms. The present findings indicate that application and effects of prevention strategies for children with a high risk for developing asthma might be gender-specific and suggest a special importance of breastfeeding boys.

The primary prevention of asthma in children study: design of a multifaceted prevention program.

The PREVASC study addresses the primary prevention of asthma in infants and small children. The objective of this study is to investigate whether a multifaceted prenatally started intervention strategy in high-risk infants leads to a decrease in the occurrence of (severe) asthma and whether a refinement of the prevention strategy leads to an increase in the adherence to the prevention program. The primary prevention program includes house dust mite impermeable bed coverings, education on breast feeding, hypoallergenic feeding, timing of introduction of solid food and smoking cessation. A total of 888 infants were prenatally included. By the time of inclusion the mothers were 3-7 months pregnant. About 27 infants were excluded from the study and 18 dropped out. Of the remaining 843 infants 535 had a first-degree familial predisposition of asthma (high-risk group), whereas a reference group of 308 (162 boys) infants was not predisposed for asthma in the first-degree (low-risk group). To evaluate the (cost-)effectiveness of the preventive intervention, 222 (118 boys) infants of the high-risk group allocated to the intervention group and 221 (112 boys) allocated to a control group are followed up. The low-risk infants served as controls to evaluate the predictive value of high risk (first-degree familial predisposition of asthma). The infants are followed from the prenatal stage until they reach the age of 6 yr. The remaining 92 high-risk infants were included in an optimized randomized-clinical adherence trial (RCAT). Of these 92 infants, 45 (20 boys) were allocated to an intervention group and 47 (24 boys) to a control group. Until now all infants have been followed for at least 1 yr.

Environmental exposure reduction in high-risk newborns: where do we start?

BACKGROUND: When analyzing the effect of environmental exposure reduction measures on asthma in high-risk children, one must know how far asthmatic families already have applied such measures, because this would affect the effectiveness and efficiency of interventions aimed at reducing environmental exposure. OBJECTIVE: To describe the room for improvement by asthmatic families in mite, pet, and food allergen reducing measures and in parental passive smoking and to determine the resulting levels of mite and pet allergens by the applied sanitation measures. METHODS: Data were sampled by observation, weekly diary entries, and questionnaire when the infant was 6 months old and 1 year old. Dust samples were collected by vacuuming the living room floor and the parental and infant mattresses. Multiple logistic regression analyses were applied with the use of mattress encasing, having a smooth floor covering, having pets, exclusive breast-feeding and/or hypoallergenic formula during the infant's first 6 months, and passive smoking as the dependent variables. RESULTS: Frequencies of applied measures were as follows: having a smooth floor covering, 36%; daily house cleaning, 27%; use of parental and infant antimite mattress encasings, 13% and 9%, respectively; keeping no pets, 66%; no cow's milk-based regular formula, 13%; no solid foods in the first 6 months of life, 28%; and abstinence of smoking by the mother prenatally, 89%; by the mother postnatally, 85%; and by her partner, 76%. Having a smooth floor covering and daily cleaning but not use of antimite mattress encasings resulted in significantly lower mite and pet allergen levels. CONCLUSIONS: There is (still) enough room for improvement to reduce exposure to inhalant and food allergens, especially by application of mattress encasings, exclusive breast-feeding and/or hypoallergenic formula feeding, and postponing the time until first solids are given.