Jorrit Gerritsen

Air pollution and development of asthma, allergy and infections in a birth cohort

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 = ∼4,000). Outdoor concentrations of traffic-related air pollutants (nitrogen dioxide PM2.5, particles with a 50% cut-off aerodynamic diameter of 2.5 μm 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.

The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study: Design and first results

The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study was initiated in 1996. Children born to allergic mothers were enrolled in a double‐blind placebo‐controlled trial for evaluating the use of mite‐impermeable mattress and pillow covers. Children born to allergic and non‐allergic mothers were enrolled in a ‘natural history’ study to assess the role of environmental and dietary risk factors for the development of allergic disease in childhood. Recruitment started by distributing a validated screening questionnaire among >10,000 pregnant women during their first visit to a prenatal health clinic. Allergic mothers‐to‐be were invited to participate in the intervention study. Allergic, and a random sample of non‐allergic, mothers‐to‐be were invited to participate in the ‘natural history’ arm of the study. In the intervention study, homes were visited before birth, 3 months after birth, and 12 months after birth for the collection of dust samples from floors and mattresses. In addition, the homes of about one‐third of the children in the ‘natural history’ part of the study were visited for dust collection when the children were 3 months of age. The intervention study started with 855 participants and the ‘natural history’ study with 3,291 participants. Follow‐up at 3 years of age has now been completed with satisfactory compliance (>90%). A medical investigation and home visit at 4 years of age are nearing completion. Preliminary results show that mite‐allergen levels were lower than found in previous Dutch studies, and that the intervention measure had a significant effect on mite‐allergen levels, without important clinical benefits up to age 2 years old. The allergic families lived in homes with fewer ‘triggers’ such as pets, smoking and carpets than the non‐allergic families, regardless of the intervention. The ongoing PIAMA cohort study will probably reveal useful information concerning effects of allergen load and reduction in the setting of a relatively low mite‐allergen exposure, as well as other variables on the development of allergic manifestions and asthma.

Early identification of atopy in the prediction of persistent asthma in children

The long-term solution to the asthma epidemic is thought to be prevention, and not treatment of established disease. Atopic asthma arises from gene-environment interactions, which mainly take place during a short period in prenatal and postnatal development. These interactions are not completely understood, and hence primary prevention remains an elusive goal. We argue that primary-care physicians, paediatricians, and specialists lack knowledge of the role of atopy in early life in the development of persistent asthma in children. In this review, we discuss how early identification of children at high risk is feasible on the basis of available technology and important for potential benefits to the children. Identification of an asthmatic childs atopic status in early life has practical clinical and prognostic implications, and sets the basis for future preventative strategies.

Effects of ambient air pollution on upper and lower respiratory symptoms and peak expiratory flow in children

BACKGROUND Previous epidemiological studies have shown acute effects of increased amounts of ambient air pollution on the prevalence of respiratory symptoms in children with respiratory disorders. We investigated whether children with bronchial hyperresponsiveness (BHR) and relatively high serum concentrations of total IgE (>60 kU/L, the median value) are susceptible to air pollution. METHODS We collected data from children during three winters (1992-95) in rural and urban areas of the Netherlands. Lower respiratory symptoms (wheeze, attacks of wheezing, shortness of breath), upper respiratory symptoms (sore throat, runny or blocked nose), and peak expiratory flow were recorded daily for 3 months. The acute effects of airborne particulate matter with a diameter of less than 10 microm, black smoke, sulphur dioxide, and nitrogen dioxide were estimated by logistic regression. FINDINGS 459 (73%) of 632 children had complete data. Of these, 26% had BHR and relatively high (above median) serum total IgE, 36% had no BHR and total IgE of 60 kU/L or less, 15% had BHR and total IgE of 60 kU/L or less, and 23% had a total IgE of more than 60 kU/L but no BHR. In children with BHR and relatively high serum total IgE the prevalence of lower respiratory symptoms increased significantly by between 32% and 139% for each 100 microm/m3 increase in particulate matter, and between 16% and 131% for each 40 microm/m3 increase in black smoke, SO2, or NO2. Decrease in peak expiratory flow of more than 10% in that group was more common with increased airborne particulate matter and black smoke. There were no consistent positive or negative associations between increased air pollution and prevalence of respiratory symptoms or decrease in peak expiratory flow in the other three groups of children. INTERPRETATION Children with BHR and relatively high concentrations of serum total IgE are susceptible to air pollution. Although our odds ratios were rather low (range 1.16-2.39) the overall effect of air pollution on public health is likely to be substantial since these odds ratios refer to large numbers of people.

Association of consumption of products containing milk fat with reduced asthma risk in pre-school children: the PIAMA birth cohort study

Background: Environment and lifestyle contribute to the development of asthma in children. Understanding the relevant factors in this relationship may provide methods of prevention. The role of diet in the development of asthma in pre-school children was investigated. Methods: Data from 2978 children participating in a prospective birth cohort study were used. Food frequency data were collected at the age of 2 years and related to asthma symptoms reported at the age of 3 years. Results: The prevalence of recent asthma at age 3 was lower in children who consumed (at age 2) full cream milk daily (3.4%) than in those who did not (5.6%) and in those who consumed butter daily (1.5%) than in those who did not (5.1%). The prevalence of recent wheeze was lower in children who consumed milk products daily (13.7%) than in those who did not (18.4%) and in children who consumed butter daily (7.7%) than in those who did not (15.4%). These effects remained in a logistic regression model including different foods and confounders (adjusted odds ratio (CI) for recent asthma: full cream milk daily v rarely 0.59 (0.40 to 0.88), butter daily v rarely 0.28 (0.09 to 0.88)). Daily consumption of brown bread was also associated with lower rates of asthma and wheeze, whereas no associations were observed with the consumption of fruits, vegetables, margarine, and fish. Conclusions: In pre-school children, frequent consumption of products containing milk fat is associated with a reduced risk of asthma symptoms.

Follow−up of asthma from childhood to adulthood: Influence of potential childhood risk factors on the outcome of pulmonary function and bronchial responsiveness in adulthood

The outcome of asthma in 406 children, aged 8 to 12 years, was studied. Follow-up in adulthood was 86%, with a mean age of 24.7 years and a mean interval of follow-up of 14.8 years. The predictive value of gender and various childhood variables on the adult level of pulmonary function (forced expiratory volume in 1 second [FEV1]) and bronchial responsiveness in adulthood was assessed. An increase in mean percent predicted FEV1 from childhood to adulthood was found, both in subjects with (76%) and without (24%) current respiratory symptoms. The only childhood variable predictive of adult level of FEV1 was the level of percent predicted FEV1 (p < 0.01). The proportion of subjects with a histamine provocative concentration causing a 10% decrease in FEV1 less than or equal to 16 mg/ml decreased significantly in adulthood. The degree of bronchial responsiveness had increased slightly in adults with symptoms (p = 0.87), whereas it had decreased significantly in subjects without symptoms (p < 0.01). Female subjects were significantly more responsive in adulthood than male subjects (p = 0.047). The childhood degree of bronchial responsiveness significantly predicted the presence of bronchial responsiveness in adulthood (p = 0.02). We conclude that childhood percent predicted FEV1 is relevant to predict the outcome of the adult pulmonary function level, whereas female gender and the childhood degree of bronchial responsiveness are important for the prediction of adult degree of bronchial responsiveness among children with asthma.

Asthma at 8 years of age in children born by caesarean section

Background: Caesarean section might be a risk factor for asthma because of delayed microbial colonisation, but the association remains controversial. A study was undertaken to investigate prospectively whether children born by caesarean section are more at risk of having asthma in childhood and sensitisation at the age of 8 years, taking into account the allergic status of the parents. Methods: 2917 children who participated in a birth cohort study were followed for 8 years. The definition of asthma included wheeze, dyspnoea and prescription of inhaled steroids. In a subgroup (n = 1454), serum IgE antibodies for inhalant and food allergens were measured at 8 years. Results: In the total study population, 12.4% (n = 362) of the children had asthma at the age of 8 years. Caesarean section, with a total prevalence of 8.5%, was associated with an increased risk of asthma (OR 1.79; 95% CI 1.27 to 2.51). This association was stronger among predisposed children (with two allergic parents: OR 2.91; 95% CI 1.20 to 7.05; with only one: OR 1.86; 95% CI 1.12 to 3.09) than in children with non-allergic parents (OR 1.36; 95% CI 0.77 to 2.42). The association between caesarean section and sensitisation at the age of 8 years was significant only in children of non-allergic parents (OR 2.14; 95% CI 1.16 to 3.98). Conclusions: Children born by caesarean section have a higher risk of asthma than those born by vaginal delivery, particularly children of allergic parents. Caesarean section increases the risk for sensitisation to common allergens in children with non-allergic parents only.

Influence of neonatal screening and centralized treatment on long-term clinical outcome and survival of CF patients

After an experimental neonatal screening program for cystic fibrosis (CF) from 1973-1979, a follow-up study took place from 1980-1997. Patients were treated at specialized centres (C) or at local hospitals (non-C). Aims of the study were: 1) to determine whether the previously reported benefits from screening persisted with time and after adjustment for confounding variables; and 2) to investigate whether centre treatment was associated with improved prognosis of CF patients. Prognosis of patients detected by screening (S; n=24) was compared with patients detected clinically, born during (non-S; n=29) and after the screening programme (post-S; n=39). In addition, prognosis was compared between 45 C and 47 non-C patients. Multivariable regression analysis was used to compare survival and mixed-effects model regression analysis was used to compare clinical outcome between patients. The analyses included the variables screening, centre treatment, sex, meconium ileus and genotype. S patients had a significantly smaller decline in forced expiratory volume in one second (FEVI) (difference +2.74% predicted) and significantly lower immunoglobulin-G (IgG) levels (difference -473.69 mg x dL(-1)) than non-S patients until 12 yrs of age. At 12 yrs of age, vital capacity was significantly higher in S patients than in non-S patients (difference +362.79 mL). Survival seemed to be best for S patients compared to both non-S and post-S patients. Post-S patients were significantly heavier (difference in SD weight +0.77), had a significantly smaller decline in FEV1 (difference +2.80% pred) and lower IgG levels (difference -453.04 mg x dL(-1)) than non-S patients until 12 yrs of age. C patients had a significantly improved survival (relative risk (RR) 0.18, 95% confidence interval 0.05-0.57) than non-C patients. Early diagnosis through neonatal screening leads to better preservation of lung function in the long term in cystic fibrosis patients. Management of cystic fibrosis patients in specialized centres improves survival.

Maternal Food Consumption during Pregnancy and the Longitudinal Development of Childhood Asthma

RATIONALE Maternal diet during pregnancy has the potential to affect airway development and to promote T-helper-2-cell responses during fetal life. This might increase the risk of developing childhood asthma or allergy. OBJECTIVES We investigated the influence of maternal food consumption during pregnancy on childhood asthma outcomes from 1 to 8 years of age. METHODS A birth cohort study consisting of a baseline of 4,146 pregnant women (1,327 atopic and 2,819 nonatopic). These women were asked about their frequency of consumption of fruit, vegetables, fish, egg, milk, milk products, nuts, and nut products during the last month. Their children were followed until 8 years of age. Longitudinal analyses were conducted to assess associations between maternal diet during pregnancy and childhood asthma outcomes over 8 years. MEASUREMENTS AND MAIN RESULTS Complete data were obtained for 2,832 children. There were no associations between maternal vegetable, fish, egg, milk or milk products, and nut consumption and longitudinal childhood outcomes. Daily consumption of nut products increased the risk of childhood wheeze (odds ratio [OR] daily versus rare consumption, 1.42; 95% confidence interval [95% CI], 1.06-1.89), dyspnea (OR, 1.58; 95% CI, 1.16-2.15), steroid use (OR, 1.62; 95% CI, 1.06-2.46), and asthma symptoms (OR, 1.47; 95% CI, 1.08-1.99). CONCLUSIONS Results of this study indicate an increased risk of daily versus rare consumption of nut products during pregnancy on childhood asthma outcomes. These findings need to be replicated by other studies before dietary advice can be given to pregnant women.

House dust mite allergen reduction and allergy at 4 yr: Follow up of the PIAMA-study

Exposure to high allergen levels in early life is a risk factor for the development of allergy. We previously reported limited effects of mite allergen impermeable mattress covers in the prevention and incidence of asthma and mite allergy (PIAMA) cohort at the age of 1 and 2 yr. We now present the results of follow‐up at 4 yr objectives. To examine the effects of early reduction of house dust mite (HDM) allergen exposure by means of mattress covers on the incidence of allergy and asthma symptoms in the PIAMA birth cohort at the age of 4 yr. High‐risk children (allergic mother) were prenatally recruited and randomly allocated to three groups; receiving mite allergen impermeable mattress covers (n = 416), placebo covers (n = 394) or no intervention (n = 472). At 4 yr of age, atopy was assessed by questionnaire; specific Immunoglobulin E (IgE) to inhalant and food allergens was measured in serum. Dust samples collected from the childrens mattresses were analysed for mite allergens. Dermatophagoides farinae1 allergen (Der f 1) levels in dust were reduced in the active group. However, Dermatophagoides pteronissinus 1 (Der p 1) levels, sensitization and atopic symptoms were similar in all groups. We found no effect of mite allergen impermeable mattress covers on sensitization and atopy at 4 yr. Moreover, the allergen reducing effects of the covers had disappeared for one of the two mite allergens that were measured.