Respiratory diseases and allergy in farmers working with livestock: a EAACI position paper.

Farmers constitute a large professional group worldwide. In developed countries farms tend to become larger, with a concentration of farm operations. Animal farming has been associated with negative respiratory effects such as work-related asthma and rhinitis. However, being born and raised or working on a farm reduces the risk of atopic asthma and rhinitis later in life. A risk of chronic bronchitis and bronchial obstruction/COPD has been reported in confinement buildings and livestock farmers. This position paper reviews the literature linking exposure information to intensive animal farming and the risk of work-related respiratory diseases and focuses on prevention. Animal farming is associated with exposure to organic dust containing allergens and microbial matter including alive microorganisms and viruses, endotoxins and other factors like irritant gases such as ammonia and disinfectants. These exposures have been identified as specific agents/risk factors of asthma, rhinitis, chronic bronchitis, COPD and reduced FEV1. Published studies on dust and endotoxin exposure in livestock farmers do not show a downward trend in exposure over the last 30 years, suggesting that the workforce in these industries is still overexposed and at risk of developing respiratory disease. In cases of occupational asthma and rhinitis, avoidance of further exposure to causal agents is recommended, but it may not be obtainable in agriculture, mainly due to socio-economic considerations. Hence, there is an urgent need for focus on farming exposure in order to protect farmers and others at work in these and related industries from developing respiratory diseases and allergy.

Household dampness and microbial exposure related to allergy and respiratory health in Danish adults.

Background: Indoor dampness has consistently been associated with respiratory symptoms and exacerbations. The causal mechanisms may involve increased microbial exposures. However, the evidence regarding the influence of indoor microbial exposures under damp- and non-damp conditions on the risk of asthma and allergy has been inconclusive. Objective: The aim of this study was to investigate the association between dampness and microbial exposure with allergy and respiratory health in Danish adults using a cross-sectional design. Methods: From 1,866 participants of the Health2006 cohort, we selected three non-overlapping groups: 196 at random, 107 with confirmed atopy, and 99 without atopy. Bedroom dust was sampled using electrostatic dust fall collectors and analysed for endotoxin, ß-(1,3)-D-glucan, 19 microbial species or groups, and total fungal load. Household moisture-related problems and asthma were self-reported by questionnaire. Atopy was determined by skin-prick-testing and lung function was measured by spirometry. Results: Household moisture damage was positively associated with asthma outcomes, although this was statistically significant only in atopics for self-reported asthma (odds ratio (OR) 3.52; 95%CI 1.01-12.7). Mould odor was positively associated with wheezing (OR 6.05; 95%CI 1.19-30.7) in atopics. Inconsistent associations were found for individual microbial exposures and health outcomes. Inverse associations were observed between microbial diversity and rhinitis in the random sample and both doctor-diagnosed and self-reported asthma in non-atopics. Conclusions: In conclusion, our findings suggest that household moisture damage may increase the risk of asthma and wheeze with mould odor in atopics. In addition, asthma and allergy may be affected by the indoor microbial composition in urban domestic environments. Further studies are needed to identify and understand the causal agents and underlying mechanisms behind the potential effects of environmental microbial exposure on human health.

Workplace exposure to wood dust and the prevalence of wood-specific sensitization.

Wood is processed worldwide, and occupational exposure to wood dust is affecting millions of workers. Studies have identified wood dust as a risk factor for non-malignant respiratory diseases consistent with both an allergic and a non-allergic origin. This paper summarizes our current knowledge on the importance of specific sensitization among subjects occupationally exposed to wood dust. Specific sensitization to wood dust exists, but is probably of minor importance for most wood species. In order to move the research field forward increased focus on more standardized tools for specific IgE (sIgE) diagnostics is needed and more specific tools are necessary to identify clinical relevant cases of wood dust sensitization. Moreover epidemiological studies on the occurrence of sIgE-mediated sensitization in different populations of woodworkers are needed.

Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring.

BACKGROUND: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. OBJECTIVE: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. METHODS: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. RESULTS: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. CONCLUSION & CLINICAL RELEVANCE: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Allergen exposure chambers: harmonizing current concepts and projecting the needs for the future - an EAACI Position Paper.

BACKGROUND: Allergen exposure chambers (AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. METHODS: For this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. RESULTS: The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. CONCLUSION: This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.

Method for a homogeneous distribution of pollens in an environmental exposure chamber.

BACKGROUND: A variety of different environmental exposure chambers (EECs) have been used to evaluate treatments for allergic rhinitis. OBJECTIVE: To describe and test a system for a homogenous distribution of grass pollen, Phleum Pratense, in an EEC to be used for controlled pollen exposure studies in allergic participants. METHODS: A chamber made of stainless steel with completely rounded corners, seating four individuals at a time, was used. Room pressure, temperature, humidity and the air change rate were kept constant throughout the study period. A rotating pipette dispensed a uniform supply of pollen into a turntable's v-shaped grooves. A stainless steel capillary tube sucked the pollens into a venturi throat at which time the pollens were mixed with a high-pressure airstream of compressed high-efficiency particulate arrestance filtered air and then transported to a spreading plate inside the EEC. To achieve uniform concentrations in the EEC, the turntable's rotating speed was continuously adjusted using information from video-coupled feedback and feed forward mechanisms. Pollen levels were detected using standard volumetric air samplers and laser particle counters. The target pollen exposure level was 1000 pollens/m(3) . Twenty-one participants were exposed to pollens in the EEC twice for 210 min. Participants evaluated their symptoms every 30 min using a total nasal symptom score (TNSS) consisting of blocked nose, runny nose, nasal itching and sneezing. RESULTS: Across fifteen study days, the average pollen level was 982 pollens/m(3) (SD, 102 pollens/m(3) ). On average, participants experienced a 10% difference in overall pollen levels between their two visits to the EEC. The mean TNSSs rose throughout the exposure period, with a low at baseline of 0.43 (SD, 0.68) to a high of 4.71 (SD, 2.43) just before exiting the EEC. CONCLUSION AND CLINICAL RELEVANCE: This EEC provides a reproducible, precise and homogenous distribution of pollens making it suitable for single-centre allergy clinical trials.

The risk of respiratory symptoms on allergen exposure increases with increasing specific IgE levels.

BACKGROUND: The relation between IgE sensitization and allergic respiratory symptoms has usually been evaluated by dichotomizing specific IgE levels. The aim of this study was to evaluate the association between specific IgE levels and risk of symptoms on allergen-related exposure, with special reference to allergen-related asthma-rhinitis comorbidity. METHODS: We considered 6391 subjects enrolled within the European Community Respiratory Health Survey 2, having information on cat/grass/D. pteronyssinus IgE levels and symptoms on exposure to animals/pollen/dust. The risk of oculonasal/asthmalike/both symptoms was evaluated by a multinomial logistic model. RESULTS: A clear positive association was observed between specific IgE levels to cat/grass/mite and the risk of symptoms on each allergen-related exposure (test for trend with P < 0.001). This trend was particularly pronounced when considering the coexistence of asthmalike and oculonasal symptoms. Compared to non-sensitized subjects, subjects with specific IgE to cat >= 3.5 kU/l presented relative risk ratios of 11.4 (95% CI 6.7-19.2), 18.8 (8.2-42.8), and 55.3 (30.5-100.2) when considering, respectively, only oculonasal symptoms, only asthmalike symptoms, or both. A similar pattern was observed when considering specific IgE to grass/mite and symptoms on exposure to pollen/dust. Also the proportion of people using inhaled medicines or visiting a general practitioner for breathing problems in the previous year increased with increasing sum of specific IgE to cat/grass/mite. CONCLUSION: Specific IgE level is the most important predictor of allergen-related symptoms. The risk of both oculonasal/asthmalike symptoms increases with specific IgE levels, suggesting that specific IgE contributes to the 'united airways disease'.

Allergy and respiratory health effects of dampness and dampness-related agents in schools and homes: a cross-sectional study in Danish pupils.

Little is known about the health effects of school-related indoor dampness and microbial exposures. In this study, we investigated dampness and dampness-related agents in both homes and schools and their association with allergy and respiratory health effects in 330 Danish pupils. Classroom dampness was identified based on technical inspection and bedroom dampness on parents' self-report. Classroom and bedroom dust was analyzed for seven microbial components. Skin prick testing determined atopic sensitization. Lung function was expressed as z-scores for forced expiratory volume in one-second (zFEV1 ), forced vital capacity (zFVC) and the ratio zFEV1 /zFVC using GLI-2012 prediction equations. The parents reported children's allergies, airway symptoms, and doctor-diagnosed asthma. High classroom dampness, but not bedroom dampness, was negatively associated with zFEV1 (ß-coef. -0.71; 95% CI -1.17 to -0.23) and zFVC (ß-coef. -0.52; 95% CI -0.98 to -0.06) and positively with wheezing (OR 8.09; 95% CI 1.49 to 43.97). No consistent findings were found between any individual microbial components or combination of microbial components and health outcomes. Among other indoor risk factors, environmental tobacco smoke (ETS) decreased zFEV1 (ß-coef. -0.22; 95% CI -0.42 to -0.02) and zFEV1 /zFVCratio (ß-coef. -0.26; 95% CI -0.44 to -0.07) and increased upper airway symptoms (OR 1.66; 95% CI 1.03-2.66). In conclusion, dampness in classrooms may have adverse respiratory health effects in pupils, but microbial agents responsible for this effect remain unknown.

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

BACKGROUND: 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. METHODS: A total of 1236 male participants of 30-40 years of age recruited from two epidemiological studies were divided into four groups with regard to place of upbringing; city, town, rural area and farm. Allergic sensitization was assessed by skin prick tests (SPTs) to 10 inhalant allergens and measurements of serum specific IgE (sIgE) to four inhalant allergens (grass, birch, cat and house dust mite). RESULTS: The prevalence of allergic sensitization to inhalant allergens decreased with decreasing degree of urbanized childhood. The risk of being sensitized to one or more allergens also decreased with decreasing degree of urbanized upbringing measured by sIgE to 4 common allergens as odds ratio with 95% confidence intervals with city as reference; town 0.60 (0.39-0.92), rural area 0.34 (0.22-0.52) and farm 0.31 (0.21-0.46). Furthermore, it was measured by SPT to 10 common allergens; town 0.52 (0.33-0.84), rural area 0.34 (0.21-0.53) and farm 0.29 (0.19-0.45). This urban-rural association was also seen for the risk of sensitization to specific allergens, rhinitis and allergic asthma. CONCLUSION: This is the first study to show an urban-rural gradient of overall allergic sensitization and specific allergen sensitization in adults depending on their childhood exposure. In this highly homogenous western population, exposure to a less urbanized childhood was associated with lower risk of allergic sensitization and disease as an adult.

Nocturnal GERD - a risk factor for rhinitis/rhinosinusitis: the RHINE study.

BACKGROUND: It has been suggested that gastroesophageal reflux disease (GERD) is a risk factor for developing rhinitis/rhinosinusitis, but data are lacking. This is a prospective 10-year follow-up study of a large multicenter cohort from Northern Europe, evaluating the relationship between nocturnal GERD and noninfectious rhinitis (NIR). METHODS: The study comprised 5417 subjects born between 1945 and 1973, who answered a questionnaire in 1999-2001 and again in 2010-2012. Noninfectious rhinitis was defined as having nasal obstruction, secretion, and/or sneezing without having the common cold. Odds ratios for developing NIR in relation to age, gender, BMI, smoking, asthma, and nocturnal GERD were calculated. RESULTS: During the 10-year observation period, 1034 subjects (19.1%) developed NIR. Subjects reporting nocturnal gastroesophageal reflux in both 1999 and 2010 had more NIR in 2010 (2.8% vs 1.2%, P < 0.001). There was a significant dose-response relationship between the number of reflux episodes/week in 1999 and the risk of having NIR in 2010, P = 0.02. In the multiple regression adjusted for age, gender, BMI, tobacco smoke, and asthma, those with nocturnal GERD in 1999 (≥3 episodes of nocturnal gastroesophageal reflux symptoms per week) had an OR of 1.6 (95% CI 1.0-2.5, P = 0.03) to develop NIR in 2010. Smoking was associated both with an increased risk of developing NIR (30.7% vs 24.0%, P < 0.001) and with the development of nocturnal GERD. CONCLUSION: This large, population-based, 10-year study indicates that nocturnal GERD was a risk factor for noninfectious rhinitis/rhinosinusitis. GERD should therefore be considered in patients with rhinitis of known and unknown origin.

Determinants of house dust, endotoxin, and ß-(1→3)-D-glucan in homes of Danish children.

Little is known about the geographic variation and determinants of bacterial endotoxin and ß-(1,3)-D-glucan in Danish house dust. In a population of 317 children, we: (i) described loads and concentrations of floor dust, endotoxin, and ß-(1→3)-D-glucan and (ii) their correlations and (iii) assessed their determinants; (iv) Finally, we compared our findings with previous European studies. Bedroom floor dust was analyzed for endotoxin content by the kinetic limulus amoebocyte lysate assay and for ß-(1→3)-D-glucan by the inhibition enzyme immunoassay. The parents answered questions regarding potential determinants. We found: geometric means (geometric standard deviations) 186 mg/m(2) (4.3) for dust; 5.46 × 10(3) EU/m(2) (8.0) and 31.1 × 10(3) EU/g (2.6) for endotoxin; and 142 µg/m(2) (14.3) and 0.71 × 10(3) µg/g (7.3) for ß-(1→3)-D-glucan. High correlations (r > 0.75) were found between floor dust and endotoxin and ß-(1→3)-D-glucan loads, while endotoxin and ß-(1→3)-D-glucan concentrations were moderately correlated (r = 0.36-0.41) with the dust load. Having a carpet was positively associated with dust load and with endotoxin and ß-(1→3)-D-glucan concentrations. Pet keeping, dwelling type, and dwelling location were determinants of endotoxin concentrations. No other determinants were associated with ß-(1→3)-D-glucan concentrations. Compared with other European studies, we found lower ß-(1→3)-D-glucan loads and concentrations but higher endotoxin loads and concentrations suggesting a geographically determined different composition of Danish floor dust compared with other European regions.

Exposure levels, determinants and IgE mediated sensitization to bovine allergens among Danish farmers and non-farmers.

BACKGROUND: Bovine allergens can induce allergic airway diseases. High levels of allergens in dust from stables and homes of dairy farmers have been reported, but sparse knowledge about determinants for bovine allergen levels and associations between exposure level and sensitization is available. OBJECTIVE: To investigate levels and determinants of bovine allergen exposure among dairy, pig and mink farmers (bedroom and stable), and among former and never farmers (bedroom), and to assess the prevalence of bovine allergen sensitization in these groups. METHODS: In 2007-2008, 410 settled dust samples were collected in stables and in bedrooms using an electrostatic dust-fall collector over a 14 day period among 54 pig farmers, 27 dairy farmers, 3 mink farmers as well as 71 former and 48 never farmers in Denmark. For farmers sampling was carried out both during summer and winter. Bovine allergen levels (µg/m(2)) were measured using a sandwich ELISA. Determinants for bovine allergen exposure in stables and bedrooms were explored with mixed effect regression analyses. Skin prick test with bovine allergen was performed on 48 pig farmers, 20 dairy farmers, 54 former and 31 never farmers. RESULTS: Bovine allergen levels varied by five orders of magnitude, as expected with substantially higher levels in stables than bedrooms, especially for dairy farmers. Bovine allergen levels in bedrooms were more than one order of magnitude higher for dairy farmers compared to pig farmers. Former and never farmers had low levels of bovine allergens in their bedroom. Bovine allergen levels during summer appeared to be somewhat higher than during winter. Increased bovine allergen levels in the bedroom were associated with being a farmer or living on a farm. Mechanical ventilation in the bedroom decreased bovine allergen level, significant for dairy farmers ß=-1.4, p<0.04. No other significant effects of either sampling or residence characteristics were seen. Allergen levels in dairy stables were associated to type of dairy stable, but not to other stable or sampling characteristics. Sensitization to bovine allergens was only found in one pig farmer. CONCLUSION: This study confirms high bovine allergen levels in dairy farms, but also suggests sensitization to bovine allergens among Danish farmers to be uncommon. Furthermore the importance of a carrier home effect on allergen load is emphasized. Whether the risk for bovine sensitization is related to the allergen level in the stable or the dwelling remains to be determined.

Monitoring of occupational and environmental aeroallergens-- EAACI Position Paper. Concerted action of the EAACI IG Occupational Allergy and Aerobiology & Air Pollution.

Exposure to high molecular weight sensitizers of biological origin is an important risk factor for the development of asthma and rhinitis. Most of the causal allergens have been defined based on their reactivity with IgE antibodies, and in many cases, the molecular structure and function of the allergens have been established. Significant information on allergen levels that cause sensitization and allergic symptoms for several major environmental and occupational allergens has been reported. Monitoring of high molecular weight allergens and allergen carrier particles is an important part of the management of allergic respiratory diseases and requires standardized allergen assessment methods for occupational and environmental (indoor and outdoor) allergen exposure. The aim of this EAACI task force was to review the essential points for monitoring environmental and occupational allergen exposure including sampling strategies and methods, processing of dust samples, allergen analysis, and quantification. The paper includes a summary of different methods for sampling and allergen quantification, as well as their pros and cons for various exposure settings. Recommendations are being made for different exposure scenarios.

EAACI position paper: irritant-induced asthma.

The term irritant-induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high-level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant-related asthma: (i) definite IIA, that is acute-onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA, that is asthma that develops in workers with multiple symptomatic high-level exposures to irritants; and (iii) possible IIA, that is asthma occurring with a delayed-onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA.

Residential culturable fungi, (1-3, 1-6)-ß-d-glucan, and ergosterol concentrations in dust are not associated with asthma, rhinitis, or eczema diagnoses in children.

Qualitative reporting of home indoor moisture problems predicts respiratory diseases. However, causal agents underlying such qualitative markers remain unknown. In the homes of 198 multiple allergic case children and 202 controls in Sweden, we cultivated culturable fungi by directly plating dust, and quantified (1-3, 1-6)-ß-D-glucan and ergosterol in dust samples from the child's bedroom. We examined the relationship between these fungal agents and degree of parent or inspector-reported home indoor dampness, and microbiological laboratory's mold index. We also compared the concentrations of these agents between multiple allergic cases and healthy controls, as well as IgE-sensitization among cases. The concentrations of culturable fungal agents were comparable between houses with parent and inspector-reported mold issues and those without. There were no differences in concentrations of the individual or the total summed culturable fungi, (1-3, 1-6)-ß-D-glucan, and ergosterol between the controls and the multiple allergic case children, or individual diagnosis of asthma, rhinitis, or eczema. Culturable fungi, (1-3, 1-6)-ß-D-glucan, and ergosterol in dust were not associated with qualitative markers of indoor dampness or mold or indoor humidity. Furthermore, these agents in dust samples were not associated with any health outcomes in the children.

Associations between selected allergens, phthalates, nicotine, polycyclic aromatic hydrocarbons, and bedroom ventilation and clinically confirmed asthma, rhinoconjunctivitis, and atopic dermatitis in preschool children.

Previous studies, often using data from questionnaires, have reported associations between various characteristics of indoor environments and allergic disease. The aim of this study has been to investigate possible associations between objectively assessed indoor environmental factors and clinically confirmed asthma, rhinoconjunctivitis, and atopic dermatitis. The study is a cross-sectional case-control study of 500 children aged 3-5 years from Odense, Denmark. The 200 cases had at least two parentally reported allergic diseases, while the 300 controls were randomly selected from 2835 participating families. A single physician conducted clinical examinations of all 500 children. Children from the initially random control group with clinically confirmed allergic disease were subsequently excluded from the control group and admitted in the case group, leaving 242 in the healthy control group. For most children, specific IgE's against various allergens were determined. In parallel, dust samples were collected and air change rates were measured in the children's bedrooms. The dust samples were analyzed for phthalate esters, polycyclic aromatic hydrocarbons (PAH), nicotine, and various allergens. Among children diagnosed with asthma, concentrations of nicotine were higher (P < 0.05) and cat allergens were lower (P < 0.05) compared with the healthy controls; air change rates were lower for those sensitized (specific IgE+) compared with those not sensitized (specific IgE-, P < 0.05); and dust mite allergens were higher for specific IgE+ cases compared with healthy controls (P < 0.05). When disease status was based solely on questionnaire responses (as opposed to physician diagnosis), significant associations were found between di(2-ethylhexyl) phthalate (DEHP) and dog allergens in dust and current wheeze.

Guidelines for the management of work-related asthma.

Work-related asthma, which includes occupational asthma and work-aggravated asthma, has become one of the most prevalent occupational lung diseases. These guidelines aim to upgrade occupational health standards, contribute importantly to transnational legal harmonisation and reduce the high socio-economic burden caused by this disorder. A systematic literature search related to five key questions was performed: diagnostics; risk factors; outcome of management options; medical screening and surveillance; controlling exposure for primary prevention. Each of the 1,329 retrieved papers was reviewed by two experts, followed by Scottish Intercollegiate Guidelines Network grading, and formulation of statements graded according to the Royal College of General Practitioners' three-star system. Recommendations were made on the basis of the evidence-based statements, which comprise the following major evidence-based strategic points. 1) A comprehensive diagnostic approach considering the individual specific aspects is recommended. 2) Early recognition and diagnosis is necessary for timely and appropriate preventative measures. 3) A stratified medical screening strategy and surveillance programme should be applied to at-risk workers. 4) Whenever possible, removing exposure to the causative agent should be achieved, as it leads to the best health outcome. If this is not possible, reduction is the second best option, whereas respirators are of limited value. 5) Exposure elimination should be the preferred primary prevention approach.