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. Event history analysis was performed on annually registered data of 2951 children, participating in the PIAMA birth cohort study. 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. 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.
Summary
As an ‘inflammometer’, the fraction of nitric oxide in exhaled air (FeNO) is increasingly used in the management of paediatric asthma. FeNO provides us with valuable, additional information ...regarding the nature of underlying airway inflammation, and complements lung function testing and measurement of airway hyper‐reactivity. This review focuses on clinical applications of FeNO in paediatric asthma. First, FeNO provides us with a practical tool to aid in the diagnosis of asthma and distinguish patients who will benefit from inhaled corticosteroids from those who will not. Second, FeNO is helpful in predicting exacerbations, and predicting successful steroid reduction or withdrawal. In atopic asthmatic children FeNO is beneficial in adjusting steroid doses, discerning those patients who require additional therapy from those whose medication dose could feasibly be reduced. In pre‐school children FeNO may be of help in the differential diagnosis of respiratory symptoms, and may potentially allow for better targeting and monitoring of anti‐inflammatory treatment.
The aim of our study was to examine the associations of breastfeeding duration and exclusiveness with the risks of asthma-related symptoms in preschool children, and to explore whether these ...associations are explained by atopic or infectious mechanisms. This study was embedded in a population-based prospective cohort study of 5,368 children. Information on breastfeeding duration, exclusiveness and asthma-related symptoms, including wheezing, shortness of breath, dry cough and persistent phlegm, was obtained by questionnaires. Compared with children who were breastfed for 6 months, those who were never breastfed had overall increased risks of wheezing, shortness of breath, dry cough and persistent phlegm during the first 4 yrs (OR 1.44 (95% CI 1.24-1.66), 1.26 (1.07-1.48), 1.25 (1.08-1.44) and 1.57 (1.29-1.91), respectively). Similar associations were observed for exclusive breastfeeding. The strongest associations per symptom per year were observed for wheezing at 1 and 2 yrs. Additionally adjusted analyses showed that the associations of breastfeeding with asthma-related symptoms were not explained by eczema but partly by lower respiratory tract infections. Shorter duration and nonexclusivity of breastfeeding were associated with increased risks of asthma-related symptoms in preschool children. These associations seemed, at least partly, to be explained by infectious, but not by atopic, mechanisms.
Little is known about the etiology of childhood acute lymphoblastic leukemia (ALL). The presence of atopic disease has been shown to protect against developing childhood ALL. The aim of this study ...was to examine whether single nucleotide polymorphisms (SNPs) in innate immunity genes previously associated with atopic disease, can elucidate the inverse association between childhood ALL and atopic disease. We studied 525 children, including 192 with childhood ALL, 149 with atopic disease and 184 healthy control subjects. We compared genotype distributions of 29 SNPs in genes of TLR2, TLR4, TLR6, TLR9, TLR10 and CD14 between the three groups and corrected for multiple testing. The genotype distributions of two SNPs in the TLR6 gene, rs5743798 and rs6531666, differed significantly between children with ALL, children with atopic disease and control subjects. Particularly in children with atopic eczema, risk alleles for atopic disease were observed more often than in control subjects, and less often in children with ALL than in control subjects. These findings support the immune surveillance hypothesis as an explanation for the protective association of atopic disease on childhood ALL. Further investigation is warranted to examine in more detail the role of innate immunity in the development of childhood ALL.
ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and ...decline of forced expiratory volume in 1 s (FEV₁) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33. To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene-environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort. Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV₁ and BHR at age 8 years; asthma was based on questionnaire data at age 8. In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV₁% predicted. We confirm associations between ADAM33 and the development of asthma (+BHR). This is the first study suggesting that interaction of in utero CSE with ADAM33 results in reduced lung function and the development of BHR, which needs further confirmation.
Little is known about long‐term effects of neonatal intensive care on exercise capacity, physical activity, and fatigue in term borns. We determined these outcomes in 57 young adults, treated for ...neonatal respiratory failure; 27 of them had congenital diaphragmatic hernia with lung hypoplasia (group 1) and 30 had normal lung development (group 2). Patients in group 2 were age‐matched, with similar gestational age and birth weight, and similar neonatal intensive care treatment as patients in group 1. All patients were born before the era of extracorporeal membrane oxygenation, nitric oxide administration, and high frequency ventilation. Exercise capacity was measured by cycle ergometry, daily physical activity with an accelerometry‐based activity monitor, and fatigue by the fatigue severity scale. Median (range) VO
2peak in mL/kg/min was 35.4 (19.6–55.0) in group 1 and 37.6 (15.7–52.7) in group 2. There was a between‐group P‐value of 0.65 for exercise capacity. Daily activity and fatigue were also similar in both groups. So, residual lung hypoplasia did not play an important role in this cohort. There were no significant associations between exercise capacity and perinatal characteristics. Future studies need to elucidate whether exercise capacity is impaired in patients with more severe lung hypoplasia who nowadays survive.
Extracorporeal membrane oxygenation (ECMO) provides life support in acute reversible cardiorespiratory failure. Assessment of long-term morbidity is essential to confirm survival advantage. This ...study aimed to assess exercise capacity in the first 12 yrs of life after neonatal ECMO, and to evaluate the effect of primary diagnosis, lung function or perinatal characteristics on exercise capacity. 120 children who, as neonates, underwent ECMO performed 191 reliable exercise tests according to the Bruce treadmill protocol at ages 5, 8 and/or 12 yrs between 2001 and 2010. Primary diagnoses were meconium aspiration syndrome (n=66), congenital diaphragmatic hernia (n=18) and other diagnoses (n=36). At ages 5, 8 and 12 yrs, ANOVA resulted in mean ± se standard deviation score endurance time on the treadmill of -0.5 ± 0.1, -1.1 ± 0.1, and -1.5 ± 0.2, respectively, all significantly less than zero (p<0.001). Exercise capacity declined significantly over time irrespective of the primary diagnosis. Neonates treated with ECMO are at risk of decreased exercise capacity at school age. We therefore propose prolonged follow-up. Proactive advice on sports participation or referral to a physical therapist is recommended, especially when either the parents or the children themselves report impaired exercise capacity.
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.
Background
Current knowledge on the prevalence of asthma is mainly based on cross‐sectional questionnaire data. Current population‐based data on the incidence of asthma in children are scarce.
...Objective
To study the incidence, prevalence, and age at diagnosis of asthma in children in the Netherlands over the study period 2000–2012.
Methods
A population‐based cohort study was conducted in the Integrated Primary Care Information database. The cohort consisted of 176,516 children (379,536 personyears (PY) of follow‐up), aged 5–18 years between 2000 and 2012. All medical records of children with physician diagnosed asthma were validated. Incidence rates, annual percent change (APC), and prevalence for asthma were calculated. Influence of age and gender on incidence rates and change in age at diagnosis were studied.
Results
We identified an asthma cohort of 14,303 children with 35,118 PY. The overall incidence rate was 6.7/1000 PY (95% CI, 6.45–6.97). Until 2008, the incidence rate was significantly increasing (APC 5.79 (95% CI 1.43–10.34); from 2008 onwards, a non‐significant decrease was observed (APC −12.16 (95% CI −23.07 to 0.28). Incidence for girls was lower than for boys, this difference decreased with increasing age. (p < 0.001) Overall, the age at diagnosis increased over calendar time and was lower for boys. (linear trend p < 0.001).
Conclusion
Our population‐based cohort study observed an incidence rate of 6.7 per 1000 PY of physician‐diagnosed asthma in children in the Netherlands over 2000–2012. The asthma incidence rate was increasing until 2008. Further studies are needed to confirm the decrease in asthma incidence rate from 2008 onwards.
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