Dick Heederik

Exposure to Environmental Microorganisms and Childhood Asthma

BACKGROUND Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. In previous studies, markers of microbial exposure have been inversely related to these conditions. METHODS In two cross-sectional studies, we compared children living on farms with those in a reference group with respect to the prevalence of asthma and atopy and to the diversity of microbial exposure. In one study--PARSIFAL (Prevention of Allergy-Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle)--samples of mattress dust were screened for bacterial DNA with the use of single-strand conformation polymorphism (SSCP) analyses to detect environmental bacteria that cannot be measured by means of culture techniques. In the other study--GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study)--samples of settled dust from childrens rooms were evaluated for bacterial and fungal taxa with the use of culture techniques. RESULTS In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma (odds ratio for PARSIFAL, 0.62; 95% confidence interval [CI], 0.44 to 0.89; odds ratio for GABRIELA, 0.86; 95% CI, 0.75 to 0.99). In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma; this included exposure to species in the fungal taxon eurotium (adjusted odds ratio, 0.37; 95% CI, 0.18 to 0.76) and to a variety of bacterial species, including Listeria monocytogenes, bacillus species, corynebacterium species, and others (adjusted odds ratio, 0.57; 95% CI, 0.38 to 0.86). CONCLUSIONS Children living on farms were exposed to a wider range of microbes than were children in the reference group, and this exposure explains a substantial fraction of the inverse relation between asthma and growing up on a farm. (Funded by the Deutsche Forschungsgemeinschaft and the European Commission.).

Do farming exposures cause or prevent asthma? Results from a study of adult Norwegian farmers

Background: A protective effect of endotoxin exposure on atopy and asthma in farmers’ children has been postulated. Studies of adult farmers have shown conflicting results but often lack exposure data. The prevalence of asthma in farmers with different exposure levels to microbial agents and irritant gases was compared. Methods: Atopy was defined as a positive response to multiple radioallergosorbent tests (RAST) with a panel of 10 common respiratory allergens, and asthma was ascertained by a questionnaire using a stratified sample (n = 2169) of a farming population from south-eastern Norway. Exposure of farmers to total dust, fungal spores, bacteria, endotoxins, and ammonia was assessed by exposure measurements. Results: The prevalence of asthma was 3.7% for physician diagnosed asthma and 2.7% for current asthma. The prevalence of atopy was 14%, but most asthmatic subjects were non-atopic (80%). Compared with farmers without livestock, (1) asthma was significantly higher in cattle farmers (ORadj 1.8, 95% CI 1.1 to 2.8) and pig farmers (ORadj 1.6, 95% CI 1.0 to 2.5), (2) non-atopic asthma was significantly higher in pig farmers (ORadj 2.0, 95% CI 1.2 to 3.3) and in farmers with two or more types of livestock (ORadj 1.9, 95% CI 1.1 to 3.3), and (3) atopic asthma was less common in farmers with two or more types of livestock (ORadj 0.32, 95% CI 0.11 to 0.97). Exposure to endotoxins, fungal spores, and ammonia was positively associated with non-atopic asthma and negatively associated with atopic asthma. No associations were found with atopy. Conclusions: Exposure to endotoxins and fungal spores appears to have a protective effect on atopic asthma but may induce non-atopic asthma in farmers.

Methicillin Resistant Staphylococcus aureus ST398 in Veal Calf Farming : Human MRSA Carriage Related with Animal Antimicrobial Usage and Farm Hygiene

Introduction Recently a specific MRSA sequence type, ST398, emerged in food production animals and farmers. Risk factors for carrying MRSA ST398 in both animals and humans have not been fully evaluated. In this cross-sectional study, we investigated factors associated with MRSA colonization in veal calves and humans working and living on these farms. Methods A sample of 102 veal calf farms were randomly selected and visited from March 2007–February 2008. Participating farmers were asked to fill in a questionnaire (n = 390) to identify potential risk factors. A nasal swab was taken from each participant. Furthermore, nasal swabs were taken from calves (n = 2151). Swabs were analysed for MRSA by selective enrichment and suspected colonies were confirmed as MRSA by using slide coagulase test and PCR for presence of the mecA-gene. Spa types were identified and a random selection of each spa type was tested with ST398 specific PCR. The Sequence Type of non ST398 strains was determined. Data were analyzed using logistic regression analysis. Results Human MRSA carriage was strongly associated with intensity of animal contact and with the number of MRSA positive animals on the farm. Calves were more often carrier when treated with antibiotics, while farm hygiene was associated with a lower prevalence of MRSA. Conclusion This is the first study showing direct associations between animal and human carriage of ST398. The direct associations between animal and human MRSA carriage and the association between MRSA and antimicrobial use in calves implicate prudent use of antibiotics in farm animals.

What's in the pool? A comprehensive identification of disinfection by-products and assessment of mutagenicity of chlorinated and brominated swimming pool water

Background Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in the water and related that to mutagenicity. Objectives We performed a comprehensive identification of DBPs and disinfectant species in waters from public swimming pools in Barcelona, Catalonia, Spain, that disinfect with either chlorine or bromine and we determined the mutagenicity of the waters to compare with the analytical results. Methods We used gas chromatography/mass spectrometry (GC/MS) to measure trihalomethanes in water, GC with electron capture detection for air, low- and high-resolution GC/MS to comprehensively identify DBPs, photometry to measure disinfectant species (free chlorine, monochloroamine, dichloramine, and trichloramine) in the waters, and an ion chromatography method to measure trichloramine in air. We assessed mutagenicity with the Salmonella mutagenicity assay. Results We identified > 100 DBPs, including many nitrogen-containing DBPs that were likely formed from nitrogen-containing precursors from human inputs, such as urine, sweat, and skin cells. Many DBPs were new and have not been reported previously in either swimming pool or drinking waters. Bromoform levels were greater in brominated than in chlorinated pool waters, but we also identified many brominated DBPs in the chlorinated waters. The pool waters were mutagenic at levels similar to that of drinking water (~ 1,200 revertants/L-equivalents in strain TA100–S9 mix). Conclusions This study identified many new DBPs not identified previously in swimming pool or drinking water and found that swimming pool waters are as mutagenic as typical drinking waters.

Livestock-associated methicillin-resistant Staphylococcus aureus in animals and humans

Since 2004 MRSA emerged in animals, particularly in pigs and veal calves. This new MRSA variant was since its first appearance referred to as Livestock Associated-MRSA (LA-MRSA). In Europe and Northern America, LA-MRSA belongs predominantly to clonal complex (CC) 398 whereas in Asia ST9 seems to be dominant in pigs. Persons in direct contact with LA-MRSA-positive animals have an increased risk of becoming MRSA positive. The risk of carriage is mainly related with the intensity of animal contact and with MRSA prevalence among animals on the farm. In contrast with its success in animals, it seemed that MRSA CC398 is a poor persistent colonizer in humans. MRSA ST398 can, however, cause serious (invasive) infections and outbreaks, although, only incidentally reported so far. Farm hygiene and antimicrobial use contributed to MRSA occurrence in animals. Therefore these two determinants should in principle be incorporated into MRSA-control programmes in animal production. Like any other microorganism, LA-MRSA is expected to be able to adapt to new hosts and may change over time in the potential to colonize and to produce toxins. Also, the current circulating clone CC398 may be replaced by another clone in Western countries or emerge in countries where this clone is currently low-prevalent. Ongoing MRSA surveillance in humans and animals is needed to detect changes in epidemiology and to implement effective control measures.

Relationship of airborne endotoxin and bacteria levels in pig farms with the lung function and respiratory symptoms of farmers

SummaryPrevious studies have demonstrated a high prevalence of respiratory and other symptoms and a decrement in lung function among pig farm workers, although the relationships with specific agents present in the work environment remain obscure. This study was therefore undertaken to investigate the relationship between symptoms, lung function and airborne endotoxin, ammonia and dust levels in piggeries. Information on symptoms, lung function, endotoxin, ammonia and dust levels was available for 183 pig farmers who worked in 136 farms. For 62 farms information was present on the levels of bacteria and gram-negative bacteria. For these 62 farms, endotoxin exposure measurements were taken in more than one stable. In general, no significant correlations were found between lung function and chronic respiratory symptoms, or dust and ammonia levels. The endotoxin concentration in stables was negatively related to most lung function variables, but only for the subgroup of 62 farmers was a statistically significant relationship found between endoxtoxin exposure and FEV1. A borderline statistically significant and negative relationship was found between the endotoxin concentration and the FVC. Symptoms experienced during or shortly after work showed odds ratios larger than one with the levels of bacteria, gram-negative bacteria and endotoxin, indicating a positive relationship. No consistency in the relationship between symptoms and dust levels was found. The results suggest that endotoxins and (gram-negative) bacteria probably play an important role in the development of symptoms and lung function changes among pig farmers.

Low prevalence of atopy in young Danish farmers and farming students born and raised on a farm

Background Recent studies have shown that in several countries atopic sensitization to common allergens (common atopy) and atopic symptoms are markedly less prevalent in children living on a farm, compared with non‐farm children living in the same rural areas. Living conditions on farms may, however, vary largely between different countries. It is also not yet known whether the ‘protective’ effect of a farm environment can also be found in adults.

Persistence of Livestock Associated MRSA CC398 in Humans Is Dependent on Intensity of Animal Contact

Introduction The presence of Livestock Associated MRSA (LA-MRSA) in humans is associated with intensity of animal contact. It is unknown whether the presence of LA-MRSA is a result of carriage or retention of MRSA-contaminated dust. We conducted a longitudinal study among 155 veal farmers in which repeated nasal and throat swabs were taken for MRSA detection. Periods with and without animal exposure were covered. Methods Randomly, 51 veal calf farms were visited from June - December 2008. Participants were asked to fill in questionnaires (n = 155) to identify potential risk factors for MRSA colonisation. Nasal and throat swabs were repeatedly taken from each participant for approximately 2 months. Swabs were analysed for MRSA and MSSA by selective bacteriological culturing. Spa-types of the isolates were identified and a ST398 specific PCR was performed. Data were analyzed using generalized estimation equations (GEE) to allow for correlated observations within individuals. Results Mean MRSA prevalence was 38% in farmers and 16% in family members. Presence of MRSA in farmers was strongly related to duration of animal contact and was strongly reduced in periods with absence of animal contact (−58%). Family members, especially children, were more often carriers when the farmer was a carrier (OR = 2, P<0.05). Only 7% (n = 11) of the participants appeared to be persistent carriers. A large heterogeneity in spa-types was detected, however 92.7% belonged to LA-MRSA CC398. A surprisingly high fraction of the spa-types (7.3%) did not belong to CC398. Conclusion The presence of LA-MRSA in farmers is strongly animal-exposure related. The rapidly decreasing MRSA prevalence during absence of animal contact suggests that LA-MRSA is a poor persistent colonizer in most humans. These results are of relevance for MRSA control strategies.

Assessment of occupational exposures in a general population: comparison of different methods

OBJECTIVES: To evaluate the relative merits of job specific questionnaires and various alternative assessment methods of occupational exposures often used in general population studies. METHODS: Subjects were participants in a hospital based case-control study of risk factors for male infertility. Estimates of exposure to organic solvents and chromium, based on job specific questionnaires, generic questionnaires, self reports of exposure, an external job exposure matrix (JEM), and a population specific JEM were compared with passive diffuse dosimeter results and measurements in urine. Urine samples from the end of the shift were analysed for metabolites of toluene, xylene, several glycol ethers, trichloroethylene, and chromium. Passive dosimeter date, metabolites of specific solvents, and urinary chromium concentrations were available for 89, 267, and 156 subjects, respectively. The alternative methods and measurements in urine were compared by means of the Cohens kappa statistic and by computing the positive predictive value, sensitivity, and specificity of the alternative methods against measurements in urine. RESULTS: Passive dosimeter results indicated that exposure classifications with job specific questionnaire information could discriminate between high and low exposures. The kappa coefficients were < 0.4, so agreement between the various methods and measurements in urine was poor. Sensitivity of the methods ranged from 0.21 to 0.85, whereas specificity ranged from 0.34 to 0.94. Positive predictive values ranged from 0.19 to 0.58, with the highest values for job specific questionnaires. CONCLUSIONS: The results indicate that the implementation of job specific questionnaires in a general population study might be worth the extra expense it entails, bearing in mind the paramount importance of avoiding false positive exposure estimates when exposure prevalence is low.

Exposure-response relationships for work-related sensitization in workers exposed to rat urinary allergens : results from a pooled study

BACKGROUND Recent studies in a few industries have shown that the likelihood of IgE-mediated sensitization increases with increasing exposure. The shape of the exposure-response relationships and modification by age, sex, and smoking habit has hardly been studied. OBJECTIVE The purpose of this study was to determine exposure sensitization relationships for rat sensitization and to evaluate the influence of atopy, smoking habits, and sex. METHODS Data from 3 cross-sectional studies in The Netherlands, the United Kingdom, and Sweden were used and involved 1062 animal laboratory workers. Selection criteria were harmonized, and this resulted in a study population of 650 animal laboratory workers (60.6% female) with less than 4 years of exposure. Air allergen levels were assessed previously and converted on the basis of an interlaboratory allergen analysis comparison. Available sera were analyzed for the presence of specific antibodies against common allergens (house dust mite, cat, dog, and grass and birch pollen) and work-related allergens (rat and mouse urinary proteins). Questionnaire items on work-related respiratory symptoms, hours worked with rats per week, job performed, smoking habits, and sex were used in this analysis RESULTS The prevalence of work-related sensitization to rat urinary allergens (IgE >0.7 KU/L) was 9.7 % (n = 63). Thirty-six of the sensitized workers had work-related symptoms (asthma or rhinitis). Two hundred forty-eight workers (38.2%) were atopic (defined as specific IgE to 1 of the common allergens). The sensitization rate increased with increasing air allergen exposure. Atopic workers exposed to low levels of allergen had a more than 3-fold increased sensitization risk compared with nonexposed atopic workers. For atopic subjects, the risk increased little with increasing exposure, whereas for nonatopic subjects, a steadily increasing risk was observed. Smoking and sex did not modify the sensitization risk. CONCLUSION Rat urinary allergen-sensitization risk increased with increasing exposure intensity. Workers who were atopic had a clearly elevated sensitization risk at low allergen exposure levels.