Pernille Milvang Grønager

The Danish urban–rural gradient of allergic sensitization and disease in adults

The reported prevalence of allergic sensitization among children is lower in rural areas than in urban areas of the world. The aim was to investigate the urban–rural differences of allergic sensitization to inhalant allergens in adults depending on childhood exposure living in an industrialized country as Denmark.

Become a farmer and avoid new allergic sensitization: Adult farming exposures protect against new-onset atopic sensitization

cutoffs. Furthermore, although blood eosinophil levels are suggested to be useful biomarkers contributing to the characterization of subphenotypes of asthma, they poorly predict sputum eosinophil levels. Similarly, the more sensitive but less specific cutoff of 0.35 kU/L for atopy may result in children without active allergic inflammation to be classified as atopic. In addition, atopy may not be causally related to wheeze even if temporality is established, which is reflected in population-attributable risk proportions around 60%. Moreover, there is evidence that suggests that different sensitization patterns drive different phenotypes of wheeze or asthma and differential effects of eosinophil levels on asthma over time during childhood have been described. However, atopy and eosinophil levels were assessed only once and for atopy a limited number of allergens were tested, both precluding the exploration of sophisticated patterns. Likewise, because of the exclusion of children who had wheeze or asthma at baseline, analyses were restricted to late-onset wheeze, which has a stronger association with atopy than does early-onset persistent wheeze. Nonetheless, increased wheeze incidence in both atopic groups—low and high eosinophil levels—would not explain the discrepancy in the interaction measures between asthma at baseline and during follow-up. In conclusion, the detected synergistic interaction provides evidence that atopy and eosinophils act through a common causal pathway in the pathogenesis of childhood wheeze. Both biomarkers may be useful for predicting and phenotyping childhood wheeze in clinical routine, but special care should be devoted to patterns and levels of atopic sensitization and blood eosinophils.

High exposure to endotoxin in farming is associated with less new-onset pollen sensitisation

Objectives Little is known about risk factors for new onset and loss of atopic sensitisation in adulthood. The aim is to examine the longitudinal effect of quantitatively assessed endotoxin exposures on changes in specific allergen sensitisation in young adults. Methods The cohort consisted of 1113 young Danish farmers and rural controls, with a mean age of 19 years at baseline. Sensitisation to birch pollen, grass pollen, cat dander and house dust mite was measured by specific IgE levels in serum samples from baseline and at 15 years’ follow-up. Changes in sensitisation were analysed in relation to cumulative endotoxin exposure during follow-up, considering early life farm exposure. Results Endotoxin exposure during follow-up was significantly associated with less new onset of specifically grass and birch pollen sensitisation. For the highest versus lowest quartile of cumulative endotoxin exposure, the OR for new-onset IgE sensitisation was 0.35 (0.13–0.91) for birch and 0.14 (0.05–0.50) for grass. On the other hand, loss of pollen sensitisation showed a positive, although mostly non-significant, association with increased levels of endotoxin exposure. Endotoxin exposure was not associated with significant changes in cat dander and house dust mite sensitisation. Conclusions High exposure to endotoxin during young adulthood appears to protect against new onset of pollen sensitisation, independent of childhood farm exposure.

Adult farming exposure does not protect against sensitization to the storage mite Lepidoglyphus destructor

To the Editor, Storage mite infestations are common in grain, straw, and hay storages. Sensitization and allergy to storage mites have been found primarily in occupationally exposed individuals such as farmers, millers, and grain and also meat production workers where storage mite exposure is high. Growing up in a farm environment, however, is a well‐established protective factor against atopic sensitization to common allergens. Working as a farmer in young adulthood may also provide protection against incident sensitization and persistence of existing sensitization, especially to pollen allergens. As storage mites are most abundant in barns and stables, we assume that adults working in farming are exposed to much higher levels of storage mite allergens than children growing up in farm homes, with an at highest intermittent presence in barns and stables. However, it is so far unknown whether and how early‐life and adult farming exposures affect specific storage mite sensitization over time. As far as we are aware, we here present the first longitudinal data on new‐onset and loss of sensitization to the storage mite Lepidoglyphus destructor (Lep d). The change in Lep d sensitization in relation to farming exposure and elevated Lep d concentrations was examined in a cohort of 1166 young Danish farmers and controls, with a mean age of 19 years at baseline. Baseline data were collected between 1992 and 1994 and at follow‐up approximately 14 years later. Sensitization to Lep d was measured by specific IgE (sIgE) levels and skin prick test (SPT) at both baseline and follow‐up. Serum was stored at −80°C, and baseline and follow‐up sera were tested simultaneously in IgE duplex analyses (carried out at ALK Abello), to minimize interassay and day‐to‐day variation. A positive specific IgE response was defined as ≥0.35 kU/L, and a positive SPT response was defined as a mean wheal reaction ≥3 mm in the presence of a negative control. Changes in sensitization (new‐onset and loss) were analyzed in relation to farm exposure using self‐reported information on exposures, as well as quantitative estimates of dust and endotoxin exposures based on actual personal exposure measurements. The thus modeled dust and endotoxin exposure levels were in this study also used as surrogates for the lifetime levels of exposure to barns and animal stables where levels of Lep d and other storage mites are known to be high. New‐onset sensitization was defined as negative at baseline and positive at follow‐up, and loss of sensitization was defined as positive at baseline and negative at follow‐up. Childhood exposure was categorized as having grown up in an urban environment, in the countryside but not on a farm, or on a farm with animals. Farmwork during the follow‐up period was categorized as “never,” “ex‐,” or “current farmer” with participants leaving farming during the follow‐ up period categorized as ex‐farmers, and those still working as farmers at follow‐up as “current farmers.” Animal husbandry was subdivided into four exposure groups of “no animals,” “swine,” “cattle,” and “mixed swine and cattle.” Dust and endotoxin exposure was measured in a subpopulation, and the results were used in combination with detailed work diaries to estimate the cumulative exposure for all study participants. Analyses were based on exposure quartiles, the 4th quartile representing the highest exposure. Changes in sensitization in relation to farm exposures during follow‐up were analyzed by logistic regression to compare the participants with new‐onset sensitization with those never sensitized, and those who lost sensitization with the participants with persistent Lep d sensitization. Changes in sensitization in relation to endotoxin exposures were also analyzed by logistic regression models adjusted for farm childhood, pet‐keeping during childhood and smoking status. At baseline, the Lep d sensitization prevalence was 4.9% measured by SPT and 6.1% measured by sIgE. At follow‐up, the Lep d sensitization prevalence was 13.5% measured by SPT and 5.9% measured by sIgE. The unadjusted odds ratios in Table 1 show less new‐ onset sensitization to Lep d among participants with a rural or farm childhood and a greater loss of sensitization consistent with findings for other aeroallergens. In contrary, farming exposure during adulthood appeared to be consistently associated with increased new‐ onset Lep d sensitization and with less loss of sensitization, although rarely significant due to low numbers. Significantly less loss of sensitization was observed particularly for work with swine and for high dust and endotoxin exposure. Adjusted analyses of endotoxin exposure confirmed that an exposure environment with moderate and high endotoxin exposure, and presumably paralleled by an elevated Lep d exposure, was associated with increased new‐onset sensitization to Lep d and significantly less loss of Lep d IgE sensitization independent of childhood exposure (Figure 1 for IgE test results; Figure S1 shows the results of the adjusted SPT analyses). We previously showed that current farming exposure was protective against new pollen sensitization. This protective effect was, however, not seen for HDM, but neither was an increased risk of new HDM sensitization among current farmers, as now suggested for Lep d sensitization. General storage mite sensitization levels may Abbreviations: CI, confidence interval; HDM, house dust mite; IgE, immunoglobulin E; kU/ L, kilo units per liter; OR, odds ratio; SPT, skin prick test. DOI: 10.1111/all.13533