Wijga, A.H.

Opposite effects of allergy prevention depending on CD14 rs2569190 genotype in 3 intervention studies (Article)

2012-01-01T00:00:00Z

Asthma symptoms and medication in the PIAMA birth cohort: Evidence for under and overtreatment (Article)

2011-11-01T00:00:00Z

Objective: Under and overtreatment of asthma may be a serious problem especially in young children, but the evidence is scarce and no longitudinal data are available. Our aim was to investigate whether inhaled medication use in young children was in agreement with asthma symptoms at the age of 2-8yr. Methods: Data were used from the 'Prevention and Incidence of Asthma and Mite Allergy' birth cohort, consisting of 3963 children born in the Netherlands. Between age 2 and 8yr, children were followed up using annual postal questionnaires. Age-specific prevalences of asthma symptoms were assessed and compared with reported use of inhaled bronchodilators and/or corticosteroids. Results: The proportion of current wheeze decreased with age. About a third of 'current wheezers' did not use any inhaled medication during the years in which symptoms were reported. At 8yr, 30% of children with reported 'severe current asthma symptoms' were not using inhaled corticosteroids. On the other hand, up to 50% of children with inhaled corticosteroids for at least 2yr did not report any wheezing during those 2yr. Conclusion: The proportion of symptomatic children without appropriate treatment was substantial throughout childhood, even when parents reported prolonged or severe symptoms. Treatment of asymptomatic children with inhaled corticosteroids increased with age and accounted for up to a third of all inhaled steroid use at 8yr. These findings suggest that under and overtreatment of asthma in children was common.

Reply (Article)

2011-08-01T00:00:00Z

Uncontrolled asthma at age 8: The importance of parental perception towards medication (Article)

2011-08-01T00:00:00Z

Background: Despite existing effective treatment options, asthma is uncontrolled in a considerable proportion of patients. The aim of this study was to identify determinants of uncontrolled asthma at age 8 in children participating in the PIAMA birth cohort study. Methods: One hundred seventy children using inhaled corticosteroids in the previous 12months at age 8 were included. Uncontrolled asthma was defined as: ≥3 items present in the past month: (1) day-time or (2) night-time asthma symptoms, (3) limitations in activities, (4) rescue medication use, (5) FEV1<80% predicted and (6) unscheduled physician visits because of asthma. Binomial regression was performed to study five groups of determinants representing asthma control: child and parental characteristics, environmental factors, therapy adherence and parental perception towards medication use (Beliefs about Medicines Questionnaire). Results: Seventy seven children (45%) had uncontrolled asthma. Low maternal education (RR 1.6, 95% CI: 1.0-2.4) was associated with uncontrolled asthma. Parental necessity beliefs about medication use to maintain present and future health and parental concerns about potential adverse consequences of medication were also associated with uncontrolled asthma (RR 1.6, 95% CI: 1.1-2.2; and 1.6, 95% CI: 1.0-2.5, respectively). Conclusions: Environmental factors and therapy adherence were not associated with asthma control. In our cohort, uncontrolled asthma is associated with low maternal education and with strong parental beliefs about medication necessity and higher concern about potential side effects of medication.

Predicting the risk of newborn children to become overweight later in childhood: The PIAMA birth cohort study (Article)

2011-06-01T00:00:00Z

Objective. To develop a decision rule by which children with a high risk to develop overweight can be distinguished at birth from children at low risk. Design, setting and participants. Data of 1 687 Dutch children born in 1996/1997 who participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) longitudinal birth cohort study were analysed. Perinatal candidate predictors of overweight at 8 years of age were selected and a prediction model was developed using stepwise model selection based on the Akaike Information Criterion (AIC). The prediction model was internally validated using resampling techniques. Outcome measure. Overweight at the age of 8 years. Results. A total of 13.9% (n = 253) of the children were overweight at 8 years of age. Independent positive predictors of overweight were paternal and maternal body mass index, female gender, smoking in the parental house, birth weight and hospital delivery. From the model, a decision rule was derived by which an overweight score could be calculated. Of the children with an overweight score below 89.45, only 2.7% were overweight at the age of 8, whereas in children with an overweight score above 105.02 the prevalence of overweight was 35.4%. Conclusion. The risk of overweight at the age of 8 years can be predicted with six characteristics that are available at birth. The decision rule developed in this study may help to target early preventive measures against overweight in high-risk children.

Comparison of childhood wheezing phenotypes in 2 birth cohorts: ALSPAC and PIAMA (Article)

2011-06-01T00:00:00Z

Background: Asthma has its origins in early childhood, but different patterns of childhood wheezing vary in their associations with subsequent asthma, atopy, and bronchial hyperresponsiveness (BHR). Novel wheezing phenotypes have been identified on the basis of analyses of longitudinal data from the Avon Longitudinal Study of Parents And Children (ALSPAC). It is unclear whether these phenotypes can be replicated in other birth cohorts. Objective: To compare wheezing phenotypes identified in the first 8 years of life in the ALSPAC study and the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study. Methods: We used longitudinal latent class analysis to identify phenotypes on the basis of repeated reports of wheezing from 0 to 8 years in 5760 children from the ALSPAC study and 2810 children from the PIAMA study. Phenotypes were compared between cohorts. Associations with asthma, atopy, BHR, and lung function were analyzed by using weighted regression analyses. Results: The model with the best fit to PIAMA data in the first 8 years of life was a 5-class model. Phenotypes identified in the PIAMA study had wheezing patterns that were similar to those previously reported in ALSPAC, adding further evidence to the existence of an intermediate-onset phenotype with onset of wheeze after 2 years of age. Associations with asthma, atopy, BHR, and lung function were remarkably similar in the 2 cohorts. Conclusion: Wheezing phenotypes identified by using longitudinal latent class analysis were comparable in 2 large birth cohorts. Study of genetic and environmental factors associated with different phenotypes may help elucidate the origins of asthma.

Quantification of the energy gap in young overweight children. the PIAMA birth cohort study (Article)

2011-05-19T00:00:00Z

Background: Overweight develops gradually as a result of a long term surplus on the balance between energy intake and energy expenditure. Aim of this study was to quantify the positive energy balance responsible for excess body weight gain (energy gap) in young overweight children. Methods. Reported data on weight and height were used of 2190 Dutch children participating in the PIAMA birth cohort study. Accumulated body energy was estimated from the weight gain observed between age 2 and age 5-7. Energy gap was calculated as the difference in positive energy balance between children with and without overweight assuming an energy efficiency of 50%. Results: Ten percent of the children were overweight at the age of 5-7 years. For these children, median weight gain during 4-years follow-up was 13.3 kg, as compared to 8.5 kg in the group of children who had a normal weight at the end of the study. A daily energy gap of 289-320 kJ (69-77 kcal) was responsible for the excess weight gain or weight maintenance in the majority of the children who were overweight at the age of 5-7 years. The increase in daily energy requirement to maintain the 4.8 kilograms excess weight gain among overweight children at the end of the study was approximately 1371 kJ. Conclusions: An energy gap of about 289-320 kJ per day over a number of years can make the difference between normal weight and overweight in young children. Closing the energy gap in overweight children can be achieved by relatively small behavior changes. However, much more effort is required to lose the excess weight gained.

Childhood diet and asthma and atopy at 8 years of age: The PIAMA birth cohort study (Article)

2011-05-01T00:00:00Z

Diet may affect the development of asthma. We investigated whether asthma or atopy outcomes at 8 yrs of age were associated with long-term dietary exposure, and whether associations were different for consumption at early or later age. The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort enrolled 4,146 participants at baseline, who were followed up to 8 yrs of age. Dietary intakes of interest were fruit, vegetables, brown/wholemeal bread, fish, milk, butter and margarine. Associations between food intake at early (2-3 yrs) and later (7-8 yrs) age, and long-term intake, asthma and atopy at 8 yrs of age were calculated by logistic regression. Complete longitudinal dietary data for at least one of the food groups were available for 2,870 children. Fruit consumption at early age was associated with reduced asthma symptoms (OR per 1 consumption day per week increase 0.93, 95% CI 0.85-1.00). Long-term fruit intake was inversely associated with asthma symptoms (OR 0.90, 95% CI 0.82-0.99) and sensitisation to inhaled allergens (OR 0.90, 95% CI 0.82-0.99). We found no consistent associations between diet and outcomes for other foods. This study indicates no consistent effects of increased early or late consumption, or long-term intake of certain foods on asthma and atopy in 8-yr-olds, with a possible exception for fruit. Copyright

Interleukin-1 receptor-like 1 polymorphisms are associated with serum IL1RL1-a, eosinophils, and asthma in childhood (Article)

2011-03-01T00:00:00Z

Background: IL-1 receptor-like 1 (IL1RL1) is a membrane receptor involved in TH2 inflammatory responses and eosinophilia. Single nucleotide polymorphisms (SNPs) in IL1RL1 have been associated with blood eosinophil counts in a genome-wide association study and with asthma in family-based and case-control studies. Objective: We assessed in the prospective birth cohort Prevention and Incidence of Asthma and Mite Allergy (PIAMA) whether IL1RL1 SNPs associate with levels of its soluble transcript IL1RL1 (IL1RL1-a) in serum, blood eosinophil counts, and asthma prevalence from birth to age 8 years, and whether IL1RL1-a serum levels associate with blood eosinophil counts. Methods: Fifteen IL1RL1 SNPs were genotyped. Serum IL1RL1-a levels were measured in 2 independent subsets within PIAMA, at 4 and 8 years. Blood eosinophil counts were measured in 4-year-old children. Results: In 2 independent subsets of children, 13 of 15 SNPs were associated with serum IL1RL1-a levels at ages 4 and 8 years with a consistent direction of effect for each allele. Rs11685480 allele A and rs1420102 allele A were significantly associated with lower numbers of blood eosinophils. In the total cohort, rs1041973 allele A was associated with a decreased risk of developing asthma (odds ratio, 0.70; 95% CI, 0.54-0.90). Rs1420101, recently identified in a genome-wide association study in the Icelandic population, was not associated with asthma in this study. IL1RL1-a levels were not associated with eosinophil counts. Conclusion: We demonstrate that IL1RL1 polymorphisms are associated with serum IL1RL1-a, blood eosinophils, and asthma in childhood.

Traffic-related air pollution and dry night cough during the first 8years of life (Article)

2011-02-01T00:00:00Z

High agreement between parental reported inhaled corticosteroid use and pharmacy prescription data (Article)

2010-11-01T00:00:00Z

Purpose: This study was conducted to assess the validity of parental reported use of inhaled corticosteroids (ICS) in children. Methods: ICS users were identified within the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study and the PIAMA pharmacy sub-cohort which is nested within the PIAMA study. Complete medication histories were available for the first 8 years of life for children within the PIAMA pharmacy sub-cohort. Parental reported ICS use was measured by using data from questionnaires. ICS use in the pharmacy records was determined by using the Anatomical Therapeutic Chemical (ATC) codes. The proportion of overall agreement and kappa statistics with their corresponding 95% confidence intervals were calculated to quantify agreement between self-reported medication use and pharmacy prescription data. Results: At all ages overall agreement was very high (>97%) and Cohen's kappa's ranged from 0.80 to 0.88 which also reflects excellent agreement between parental reported use of ICS and pharmacy prescription data. Conclusions: Our finding suggests that parental report of medication use is a reliable source of data to asses ICS use in children. The questionnaire-based medication data collected within the PIAMA study can be used to study asthma medication use in a large group of children.

Patterns of asthma medication use: Early asthma therapy initiation and asthma outcomes at age 8 (Article)

2010-10-01T00:00:00Z

Wheeze has many underlying pathophysiologies in childhood, but is the main reason for anti-asthma drugs prescription. This study was conducted to describe asthma medication use patterns among children in their first eight years of life. Longitudinal medication use data from 777 children participating in the PIAMA study were used. Medication patterns were described for four groups that started therapy before the third birthday, when the peak in prescriptions occurred in our cohort; short-acting β-agonists (SABA), inhaled corticosteroids (ICS), SABA + ICS or none of these. One third (n = 255) of the children received a first SABA or ICS prescription before age 8. Only three children (1.2%) used medication continuously during follow-up. Of the children who started SABA, 53.8% discontinued within 1-2 years. Of the children who started ICS before age 3, 42.1% discontinued within 1-2 years and 31.6% received additional SABA. 41.5% of the children who started SABA + ICS used this short-term (≤1-2 years) and 21.5% long-term (≥3 years). Fifteen percent of children who did not start asthma therapy in their first 3 years of life did receive prescriptions between age 3 and 8. Children prescribed SABA + ICS before age 3 had the highest prevalence of hyper responsiveness at age 8, and similar prevalence of atopy as the other groups. Asthma medication is prescribed frequently in the first 8 years of life, particularly before age 3, and only few children use it continuously. ICS and SABA prescription occurs especially in those who were more likely to develop signs of asthma at age 8.

Prediction of asthma in symptomatic preschool children using exhaled nitric oxide, Rint and specific IgE (Article)

2010-09-01T00:00:00Z

Rationale: For clinicians it remains very difficult to predict whether preschool children with symptoms suggestive of asthma will develop asthma in later childhood. Objective: To investigate whether measurement of fraction of exhaled nitric oxide (FENO), interrupter resistance (Rint) or specific immunoglobulin E (IgE) in 4-year-old children with suggestive symptoms can predict asthma symptoms up to age 8 years. Methods: Children were recruited from the PIAMA birth cohort. All children with symptoms suggestive of asthma at age 3 or 4 years, who were invited for medical examination at age 4 (n=848), were eligible. Associations of FENO(n=308), Rint (n=482) and specific IgE (n=380) at 4 years with wheezing and asthma at the ages of 5-8 years were assessed using repeated measurement analyses. The added predictive value of these objective tests was then investigated by including parameters for clinical history in the model. Results: FENOand specific IgE measured at 4 years were associated with wheezing and asthma at 8 years. Both tests also remained significant predictors after mutual adjustment and adjustment for clinical history: OR on wheezing at 8 years for FENO(10log-scale, per IQR) 1.6 (95% CI 1.1 to 2.2) and for specific IgE 2.8 (95% CI 1.9 to 4.1). Rint was significantly associated with wheezing at age 6, but not at 7 and 8 years. Conclusions: In preschool children with symptoms suggestive of asthma, both FENOand specific IgE measured at age 4, but not Rint, improved the prediction of asthma symptoms until the age of 8 years, independent of clinical history.

Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure (Article)

2009-12-01T00:00:00Z

Background: Filaggrin gene (FLG) mutations contribute to the development of eczema and asthma, but their contribution to sensitization and hay fever remains unclear. Methods: FLG mutations R501X, 2282del4 and R2447X were genotyped in the Prevention and Incidence of Asthma and Mite Allergy birth cohort (n = 934) to evaluate longitudinally, for up to 8 years, their association with eczema, sensitization, asthma, hay fever and their interaction with cat exposure. Results: The combined FLG mutations were significantly associated with eczema at all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4-2.8). Combined FLG mutations were associated with both atopic and nonatopic eczema, as well as asthma (OR = 3.7; 95% CI: 1.8-7.5). When the FLG 2282del4 mutation was analysed separately, it was significantly associated with the development of eczema during the first year, having eczema up to 8 years and sensitization at the age of 8 years, which was enhanced by early-life cat exposure (ORs being 8.2; 95% CI: 2.6-25.9, 6.0; 95% CI: 3.2-11.3 and 5.4; 95% CI: 1.2-23.6 respectively). FLG 2282del4 was significantly associated with hay fever from the age 5 years onwards (OR = 3.9; 95% CI: 1.5-10.5). Conclusions: FLG mutations are associated both with atopic and nonatopic eczema starting in the first year of life. FLG mutations combined with eczema in the first year of life are associated with a later development of asthma and hay fever, a clear example of the atopic march. We confirm that cat exposure enhances the effect of a FLG mutation on the development of eczema and sensitization.

Effects of pets on asthma development up to 8 years of age: The PIAMA study (Article)

2009-08-01T00:00:00Z

Background: Recall bias may provide discrepant relationships of pet exposure with sensitization and asthma development. We studied prospectively effects of pets at home on development of sensitization, asthma and respiratory symptoms from birth up to age 8 years. Methods: Event history analysis was performed on annually registered data of 2951 children, participating in the PIAMA birth cohort study. Results: Children with a cat or dog at home at 3 months of age had a significantly lower prevalence of sensitization to inhalant allergens at age 8, but not of asthma. A cat decreased the risk of house dust mite sensitization at age 8 [odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.49-0.95], a dog of pollen sensitization (OR = 0.49, 95% CI: 0.29-0.83). A cat or dog at home did not significantly affect asthma incidence in each subsequent year. From 2 years of age onwards, the incidence of wheeze (OR = 1.52, 95% CI: 1.12-2.05) and a dry cough at night (OR = 1.28, 95% CI: 1.05-1.57) was higher in children with a dog, whereas removal of a dog increased the risk of developing asthma symptoms. Comparing analyses using prospectively and retrospectively collected data on diagnosed asthma showed important recall bias. Conclusions: Our prospective study shows a protective effect of early presence of pets at home on sensitization to inhalant allergens, but no prevention of asthma development. Furthermore, children with pets had more frequent transient or intermittent asthma symptoms. Parental report of asthma by recall may provide spurious results of these associations.

Overweight and changes in weight status during childhood in relation to asthma symptoms at 8 years of age (Article)

2009-06-01T00:00:00Z

Background: Asthma may be more prevalent in overweight children. However, how early overweight and changes in weight status during childhood affect the asthma risk is unclear. Objectives: To investigate overweight and changes in overweight status in children age 1 to 8 years in relation to asthma symptoms in childhood. Methods: We studied 3756 children who participated in a large birth cohort study. The parents reported their children's weight and height, and wheeze, dyspnea, and prescription of inhaled corticosteroids in yearly questionnaires. Sensitization to inhalant allergens and bronchial hyperresponsiveness (BHR) were determined at 8 years. Results: At 8 years, 275 children (7.3%) wheezed, 361 (9.6%) had dyspnea, and 268 (7.1%) had a prescription of inhaled corticosteroids in the preceding year. Children who had a persistent high body mass index (BMI, weight/height2) during childhood or a high BMI at 6 to 7 years had a significantly increased risk of dyspnea (adjusted odds ratio, 1.68; 95% CI, 1.18-2.39, for a high BMI at 6-7 years) and measured BHR (adjusted odds ratio, 1.66; 95% CI, 1.10-2.52) at 8 years. Children with a high BMI at a young age, but who developed a normal BMI at 6 to 7 years, did not have an increased risk of dyspnea or BHR at 8 years. BMI was not associated with sensitization. Conclusion: Children with a current high BMI are at increased risk to have dyspnea and BHR at 8 years. A high BMI at an earlier age is not related to an increased risk if the child has become normal weight at 6 to 7 years.

Long-chain polyunsaturated fatty acids in breast milk and early weight gain in breast-fed infants (Article)

2009-01-01T00:00:00Z

The long-chain PUFA (LCPUFA) content of an infant's diet might affect early weight gain. In early trials on supplementation of formula feeding n-3 LCPUFA affected weight gain adversely. n-6 LCPUFA are thought to promote adipose tissue development and might be associated with higher weight gain. We studied the association between the natural n-3 and n-6 LCPUFA content of breast milk of Dutch women and weight and BMI gain of their breast-fed infants in the first year of life. The children in this study were enrolled in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study and were born in 1996-1997 in the Netherlands. Parents reported their child's weight and length in a questionnaire. Of a subgroup of the total population breast-milk samples were collected (n 244). The fatty acid composition of breast milk was determined by GLC and expressed as weight percentages. Linear regression was used for data analysis. Mean gain in weight, length and BMI per week from birth to 1 year of age was 119.5 (sd 16.1) g, 0.48 (sd 0.05) cm and 0.06 (sd 0.03) kg/m2, respectively. The associations between n-6 and n-3 LCPUFA in breast milk, and infant weight, length and BMI gain were weak and inconsistent. The n-3 and n-6 LCPUFA content in breast milk did not affect weight or BMI gain in the first year of life in breast-fed term infants.