We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

Exposure to endotoxin in home environments has become a key issue in asthma and allergy research. Most studies have analyzed floor or mattress dust endotoxin, but its validity as a proxy for airborne exposure is unknown, while active airborne dust sampling is not feasible in large-scale population studies because of logistic and financial limitations. We therefore developed and evaluated a simple passive airborne dust collection method for airborne endotoxin exposure assessment. We explored an electrostatic dust fall collector (EDC), consisting of a 42- by 29.6-cm-sized folder with four electrostatic cloths exposed to the air. The EDC was tested during two 14-day periods in seven nonfarm and nine farm homes and in farm stables. In parallel, active airborne dust sampling was performed with Harvard impactors and floor dust collected by vacuuming, using nylon sampling socks. The endotoxin levels could be measured in all EDC cloth extracts. The levels (in EU/m²) between EDCs used simultaneously or in different sampling periods in the same home correlated strongly (r> 0.8). EDC endotoxin also correlated moderately to strongly (r= 0.6 to 0.8) with the endotoxin measured by active airborne dust sampling and living room floor dust sampling and—in farm homes—with the endotoxin captured by the EDC in stables. In contrast, endotoxin levels measured by floor dust sampling showed only a poor correlation with the levels measured by active airborne dust sampling. We therefore conclude that measuring endotoxin levels with the EDC is a valid measure of average airborne endotoxin exposure, while reproducibility over time is at least equivalent to that of reservoir dust analyses.

House dust-associated bacterial endotoxins have been shown to be associated with asthma severity, and a similar role has been suggested for fungal (1 → 3)- β -d-glucans. In this study the relation between these agents and peak expiratory flow (PEF) variability was investigated in 148 children 7 to 11 yr of age of whom 50% had self- or parent-reported chronic respiratory symptoms. All children self-monitored twice daily their PEF for a period of 16 wk. Dust samples were collected from mattresses and from living room and bedroom floors, and endotoxin and (1 → 3)- β -d-glucan were measured in dust extracts. The relations with mean daily PEF variability (Ampl%mean) were investigated by linear regression analysis, adjusting for dust mite allergen levels, presence of pets, and type of floor cover. In unadjusted analyses the levels of both endotoxin and (1 → 3)- β -d-glucan per square meter of living room floor were significantly associated with PEF-variability (but not when expressed per gram of sampled dust), particularly in atopic children with asthma symptoms. Adjusted analyses showed the same association for (1 → 3)- β -d-glucan but not for endotoxin. Although no associations were found with microbial agent levels in bedroom floor or mattress dust, high levels of (1 → 3)- β -d-glucan in living room floor dust apparently increase PEF variability in asthmatic children.

Chronic exposure to farm environments is a risk factor for nonallergic lung disease. In contrast to allergic asthma, in which type 2 helper T cell (Th2) activation is dominant, exposure to farm dust extracts (FDE) induces Th1/Th17 lung inflammation, associated with neutrophil infiltration. Macrophage influx is a common feature of both types of lung inflammation, allergic and nonallergic. However, macrophage functions and phenotypes may vary according to their polarized state, which is dependent on the cytokine environment. In this study, we aimed to characterize and quantify the lung macrophage populations in two established murine models of allergic and nonallergic lung inflammation by means of fluorescence-activated cell sorting and immunohistochemistry. We demonstrated that, whereas in allergic asthma M2-dominant macrophages predominated in the lungs, in nonallergic inflammation M1-dominant macrophages were more prevalent. This was confirmed in vitro using a macrophage cell line, where FDE exerted a direct effect on macrophages, inducing M1-dominant polarization. The polarization of macrophages diverged depending on the exposure and inflammatory status of the tissue. Interfering with this polarization could be a target for treatment of different types of lung inflammation.

Endotoxin is a well-known bacterial toxin that causes several health effects. Animal faeces and plant materials contaminated with bacteria have been identified as important determinants of organic dust related endotoxin exposure. Although high exposure to organic dust and endotoxins has been described regularly in agricultural industries, a detailed overview of levels of airborne exposure to endotoxins in the agricultural industry, as well as a systematic comparison between several specific branches using the same exposure assessment protocols are lacking. In this study, personal endotoxin exposure in a broad spectrum of agricultural industries was investigated and possible determinants of exposure were explored. 601 personal inhalable dust samples were taken in 46 companies of three agricultural industrial sectors: grains, seeds and legumes sector (GSL), horticulture sector (HC) and animal production sector (AP), with 350 participating employees. Dust and endotoxin levels were determined gravimetrically and by using the Limulus Amoebocyte Lysate (LAL) assay, respectively. Basic descriptive analysis and elaborate analysis of variance were performed. Mean exposure levels were high, with large differences between sectors and between companies within the sectors. Highest dust and endotoxin exposures were found in companies of the GSL sector. In all three sectors exposure was higher in the primary production part compared to the (industrial) products processing part of the sector. The Dutch proposed health based occupational exposure limit (50 EU m⁻³) and temporary legal limit (200 EU m⁻³) for endotoxin were often exceeded. Differences in exposure between workers were larger than the day-to-day variability. Identified determinants increasing exposure levels were company, dustiness of the product and contact with animals/faeces. ‘Wet’ processes resulted in less dusty working environments and thus lowered endotoxin exposure. Overall, exposure to endotoxins over the whole range of agricultural industries is high. A 10–1000 fold reduction in exposure is needed to reduce endotoxin related health risks.