G. de Meer

Early, current and past pet ownership: associations with sensitization, bronchial responsiveness and allergic symptoms in school children

Background Studies have suggested that early contact with pets may prevent the development of allergy and asthma.

Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children

Background: Exhaled nitric oxide (eNO) may serve as a non-invasive marker of airway inflammation but its relationship with other commonly used measures has not been evaluated. Methods: Levels of eNO in a sample of 450 children aged 7–12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV1 and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing. Results: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV1 and MMEF were not associated with eNO levels. Conclusions: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health.

Diet and asthma in Dutch school children (ISAAC‐2)

Background: The rise in the prevalence of asthma in western societies may be related to changed dietary habits. Epidemiological studies in children have shown inverse associations of asthma related outcomes with intake of fruits, vegetables, dairy and whole grain products, and fish. In contrast to most previous studies, we used both questionnaire and clinical data to define asthma. Methods: Intake of the abovementioned foods was studied in relation to asthma in 598 Dutch children aged 8–13 years. Dietary intake was estimated using a parent completed semi-quantitative food frequency questionnaire. Current wheeze and current asthma were defined based on questionnaire data. More complex end points were defined using information on bronchial hyperresponsiveness (BHR) and atopic sensitisation as well. Linear associations were studied using logistic regression analysis and odds ratios presented for the highest versus the lowest tertile of intake. In the final models, adjustments were made for maternal educational level, foreign descent, and total energy intake. Results: The intake of whole grain products and of fish was inversely associated with asthma. Adjusted odds ratios for the independent associations with whole grains and fish were 0.46 (95% CI 0.19 to 1.10) and 0.34 (95% CI 0.13 to 0.85) for current asthma and 0.28 (95% CI 0.08 to 0.99) and 0.12 (95% CI 0.02 to 0.66) for atopic asthma with BHR. Similar results were observed for current wheeze and atopic wheeze with BHR. Intake of (citrus) fruits, vegetables, and dairy products showed no clear associations with asthma end points. Conclusions: Our findings suggest that a high intake of whole grain products and fish may have a protective effect against asthma in children.

Early childhood environment related to microbial exposure and the occurrence of atopic disease at school age

Background:  There is a growing body of evidence that the early childhood environment with respect to day care attendance, older siblings, pet ownership, and early life airway infections may protect from developing atopic disease. Few studies have distinguished between atopic sensitization and symptoms, and none have evaluated independent contributions for all of these different environmental conditions.

The relationship between exhaled nitric oxide and allergic sensitization in a random sample of school children

Background Exhaled nitric oxide (NO) has been proposed as novel a non‐invasive marker of airway inflammation.

Der p I concentrations in mattress surface and floor dust collected from infants' bedrooms.

Background Allergen exposure in early childhood is thought to be important for sensitization and subsequent development of asthma. Not much is known, however, about exposure of young children to allergens in the home.

Immunoglobulin G4 antibodies to rat urinary allergens, sensitization and symptomatic allergy in laboratory animal workers

Background and objectives We have previously reported that high rat urinary allergen (RUA) exposure was not associated with increased risk of rat allergy in long‐term‐exposed laboratory animal (LA) workers. We aimed to assess whether strong allergen‐specific IgG4 responses could explain the absence of a dose response in these subjects. We investigated whether IgG4 was associated with allergen exposure and prevalence of sensitization or respiratory symptoms to rats. The longitudinal relation between IgG4 and rat allergy was studied using data obtained during 2 years of follow‐up.

Direct or indirect stimuli for bronchial challenge testing: what is the relevance for asthma epidemiology?

The prevalence of asthma has increased substantially over the last several decades. In the industrialized world, it is now the most common chronic disease in childhood and early adolescence [1–3]. Asthma is characterized by reversible airway obstruction and bronchial hyperresponsiveness (BHR), defined as excessive airway narrowing, with symptoms of wheeze, shortness of breath, or cough in response to nonspecific stimuli such as cold air, exercise, and tobacco smoke. Epidemiological studies of asthma aim to estimate the burden of this disease and risk factors for its development. These studies may provide targets for prevention either in the general population, or in subgroups. Furthermore, they may provide tools to identify subjects in an early phase of the disease, preferably prior to the development of symptoms. In recent years, the assessment of BHR has become common practice in epidemiological studies. Steering committees of the European Community Respiratory Health Survey and the International Study on Allergy and Asthma in Childhood (ISAAC) have approved standardization of bronchial challenge tests for methacholine and hypertonic saline (HS). The worldwide use of these protocols allows international comparison of results. This may provide new insights into genetic and ecological risk factors, as well as the significance of BHR in the pathogenesis and diagnosis of asthma in the community. The pathological features that underlie BHR are presumably bronchial inflammation and airway remodelling. The assessment of BHR in the laboratory entails inhalation of a stimulus that causes bronchoconstriction in people with asthma, but causes little or no response in people without asthma. Different stimuli are being used to test for BHR, and each may constitute a piece of the jigsaw puzzle on the pathophysiology of BHR and asthma. In general terms, stimuli are categorized as either ‘directly’ or ‘indirectly’ acting. Histamine and methacholine are commonly used directacting stimuli that cause bronchoconstriction by directly stimulating the contraction of airway smooth muscle cells [4]. In contrast, indirect stimuli cause bronchoconstriction by mediators released from intermediary cells, like inflammatory cells, epithelial cells, or nerves [5, 6]. Common examples of indirect stimuli are exercise, hyperand hypotonic solutions, cold or dry air, and adenosine. The aim of this paper is to review BHR to the indirect stimuli adenosine and HS with respect to their mechanism of action, and their relationship to eosinophilic bronchial inflammation. Subsequently, we will discuss their value in epidemiological studies. We have chosen to focus on adenosine and HS as bronchoconstrictive stimuli because adenosine has been studied extensively in adults in recent years, and HS has been adopted as the stimulus for measuring BHR by the steering committee of the ISAAC and is currently widely used in clinical and epidemiological studies [7].

Poor perception of dyspnoea in children with undiagnosed asthma

The aim of the present study was to establish the differences in dyspnoea perception between children with undiagnosed and diagnosed asthma. A cross-sectional community-based study was performed, which included a parental questionnaire on the childs respiratory health and testing of airway reversibility and bronchial hyperresponsiveness (BHR). “Diagnosed asthma” was defined by a physicians diagnosis of asthma. “Undiagnosed asthma” was defined by the presence of asthma symptoms combined with either airway reversibility or BHR without a physicians diagnosis of asthma. Only children with a positive BHR test were selected for further analysis. Perception of dyspnoea was assessed using the Borg scale and the visual analogue scale (VAS), plotted against the percentage fall in forced expiratory volume in one second and expressed as the slope of the regression line. Of the initial 1,758 participating children, 70 had undiagnosed asthma and 38 had diagnosed asthma. The Borg and VAS slopes in children with undiagnosed asthma were less steep than those of children with diagnosed asthma (Borg: 0.07 and 0.14, respectively; VAS: 0.06 and 0.11, respectively). Among children with bronchial hyperresponsiveness, those without a parents report of physicians diagnosis of asthma had a worse perception of dyspnoea than children with diagnosed asthma.

Airway responsiveness to hypertonic saline: dose-response slope or PD15?

The result of airway challenge test with hypertonic saline (HS) is expressed as the dose causing a 15% fall in forced expiratory volume in one second (FEV1; PD15). A noncensored measure, such as the dose-response slope (DRS), allows the evaluation of the risk of asthma for subjects with a fall in FEV1 <15%. The aim of this study was to assess the relationship between airway responsiveness to HS by PD15 or DRS, asthma symptoms and markers of eosinophilic inflammation. Data on current wheeze and airway responsiveness were obtained for 1,107 children (aged 8–13 yrs). Blood eosinophils and serum eosinophil cationic protein (ECP) were assessed in subsets (n = 683 and 485). PD15 was assessed if FEV1 fell ≥15%, and the DRS was calculated for all tests. Graphs were constructed to visualise relationships with current wheeze, blood eosinophils and serum ECP. Odds ratios and Spearmans correlation coefficients were calculated to quantify these relationships. Children with features of asthma had lower PD15 and higher DRS, and separation was most pronounced for DRS. Prevalence of current wheeze increased continuously over the entire range of DRS values. Blood eosinophils were significantly higher only for the highest values of DRS. In conclusion, the continuous relationship between airway responsiveness and asthma symptoms is in favour of a noncensored measure of airway responsiveness, such as the dose-response slope.