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Agents causing occupational asthma

Published:October 28, 2008DOI:https://doi.org/10.1016/j.jaci.2008.09.010
      The workplace is a significant contributor to the burden of asthma. Although the majority of cases probably represent what is labeled work-exacerbated asthma, in a significant number of subjects, asthma is actually caused by 1 or more agents present in the workplace; this is occupational asthma. Two types of occupational asthma are distinguished, according to whether the asthma appears after a latency period. This article discusses (1) two types of agents causing asthma with a latency period and acting through an apparently immunologic mechanism (high-molecular-weight agents and low-molecular-weight agents) and (2) agents causing asthma without a latency period.

      Key words

      Abbreviation used:

      OA (Occupational asthma)
      The workplace is a significant contributor to the burden of asthma, with approximately 1 in every 10 patients with asthma in population-based studies reporting that their symptoms are worse at work.
      • Blanc P.D.
      • Toren K.
      How much asthma can be attributed to occupational factors?.
      • Kogevinas M.
      • Zock J.P.
      • Jarvis D.
      • Kromhout H.
      • Lillienberg L.
      • Plana E.
      • et al.
      Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II).
      Although the majority of cases probably represent what is labeled work-exacerbated asthma,
      • Henneberger P.K.
      Work-exacerbated asthma.
      in a significant number of subjects, asthma is actually caused by the workplace—that is, occupational asthma (OA; Fig 1). OA has been defined as follows:[A] disease characterized by variable airflow limitation and/or hyperresponsiveness and/or inflammation due to causes and conditions attributable to a particular occupational environment and not to stimuli encountered outside the workplace. Two types of occupational asthma are distinguished by whether they appear after a latency period:1. After a latency period (allergic): this category is characterized by work-related asthma appearing after a latency period and encompasses: (a) occupational asthma caused by most high- and certain low-molecular-weight agents for which an allergic (IgE mediated) mechanism has been proven; and (b) occupational asthma induced by specific occupational agents (e.g. Western red cedar) but the allergic mechanisms responsible have not yet been fully characterized. 2. Without a latency period (non-allergic).This category includes irritant-induced asthma or reactive airways dysfunction syndrome (RADS), which may occur after a single or multiple exposures to non-specific irritants at high concentrations.
      • Bernstein I.L.
      • Bernstein D.I.
      • Chan-Yeung M.
      • Malo J.L.
      Definition and classification of asthma in the workplace.

      Agents causing asthma with a latency period and acting through an apparently immunologic mechanism

      Agents that cause OA can be divided into 2 groups according to their molecular weight: agents of high-molecular and low-molecular weights. Some characteristics of these 2 types of agents are shown in Table I.
      Table ICharacteristics of high-molecular-weight and low-molecular-weight agents as causes of occupational asthma
      High-molecular-weight agentsLow-molecular-weight agents
      StructureProteins, polysaccharidesChemicals, metals
      Duration of the latency period before getting “sensitization”Generally longer (ex: flour)Generally shorter (ex: isocyanates)
      Oculonasal symptoms++++
      Accompanying dermatitisRarePossible
      Immunologic mechanismIgE-dependentGenerally not IgE-dependent IgG, MCP-1 (isocyanates)
      Cellular componentEosinophilsEosinophils and neutrophils
      Feasibility of skin testing to elicit immediate reactionsYesNo
      Type of asthmatic reaction after challengeImmediate, dualIsolated late or atypical
      Frequency of referralOne thirdTwo thirds
      Diagnostic meansNumerousMore limited

       High-molecular-weight agents

      Virtually all proteins of animal or plant origin are capable of causing IgE-dependent sensitization, rhinoconjunctivitis, and asthma. There is a huge list of agents, and many new agents are reported each year (see www.asthme.csst.qc.ca). In this summary article, only the most frequent causes are covered.

       Cereals and flours

      Cereals and flour are the oldest causes reported
      • Pepys J.
      • Bernstein I.L.
      Historical aspects of occupational asthma.
      and remain, with isocyanates, the most common causes (Table II). Dockworkers are exposed to various cereals that can cause, apart from OA, different syndromes as a result of exposure to organic dust, including allergen-induced airway obstruction and a febrile alveolitis-like condition.
      • Chan-Yeung M.
      • Bernstein I.L.
      • Essen S Von
      • Singh J.
      • Schwartz D.A.
      Acute airway diseases due to organic dust exposure.
      Wheat is the most commonly incriminated cereal, probably because it is the most frequently encountered, but soya is highly allergenic, responsible for cases of allergy and asthma in population living in the vicinity of harbors, as in the Barcelona epidemics.
      • Anto J.M.
      • Sunyer J.
      • Rodriguez-Roisin R.
      • Suarez-Cervera M.
      • Vazquez L.
      Community outbreaks of asthma associated with inhalation of soybean dust.
      Bakers are at risk of developing sensitization not only to various cereal flours they handle at work but also to storage mites, various other added protein products, and enzymes (α-amylase is the most common) that are added to offer better control of processing. During the 1990s, several immunoassays became available to determine the allergenic content of material obtained from personal sampling.
      • Heederik D.
      • Newman-Taylor A.J.
      Occupational asthma in the baking industry.
      Bakeries, along with small animal facilities, were the first workplace for which a dose-response curve between exposure and risk of sensitization was clearly established,
      • Houba R.
      • Heederik D.
      • Doekes G.
      Wheat sensitization and work-related symptoms in the baking industry are preventable.
      with atopic individuals at risk even at lower exposure, although nonatopic subjects can develop sensitization at higher concentrations. A relatively low exposure of 0.2 μg/m3 has been observed to reduce risk for sensitization significantly, leading to that threshold being specifically recommended in Europe. Diagnosis should not be based on symptomatology alone, however. Although 1 study showed an incidence of 16% of work-related rhinoconjunctivitis symptoms in apprentices in a bakery program, only a minority of the symptomatic subjects (10%) also developed IgE-mediated sensitization.
      • Gautrin D.
      • Ghezzo H.
      • Infante-Rivard C.
      • Malo J.L.
      Incidence and host determinants of work-related rhinoconjunctivitis in apprentice pastry-makers.
      Therefore, objective confirmation that combines assessment of IgE-mediated immunity and functional assessment (peak expiratory flow monitoring, specific inhalation challenges) is mandatory.
      Table IIAgents causing occupational asthma with a latency period
      ClassesAgentIndustry/exposure
      Low-molecular-weight agents
       AnhydridesPhthalate anhydride, trimellitic anhydride, maleic anhydride, tetrachlorophthalate anhydridePlastics, epoxy resin, dye
       MetalsFirst series of transitional metals: vanadium, chromium, cobalt, nickel, zincElectroplating, refineries, metal alloys for welding
      Second series of transitional metals: palladium, ruthenium, rhodium, and cadmiumRefineries
      Third series of transitional metals: iridium and platinumRefineries
      Group III metals: aluminumSmelters
      Indeterminate metals
       DiisocyanatesToluene diisocyanate, methylene diphenyl diisocyanate I, hexamethylene diisocyanate, prepolymers of TDI and hexamethylene di-isocyanatePolyurethanes, plastics, foundries, spray paints
       Cleaning agentsBiocides: hexachlorophene, chlorhexidine, glutaraldehyde, hypochlorite, quaternary ammonium compounds, chloramines THealth care professionals, professional or domestic cleaners
      Preservatives: benzalkonium chloride, isothiazolinones, formaldehyde
      Corrosion inhibitors: ethanolamines
      Surface care: acryl polymers, polyethylene
      Perfumes or scents: D-limonene, terpenes
       Wood dustsWestern red cedar, Thuja plicata; Eastern white cedar, Thuja occidentalis; California red wood, Sequoia sempervirens; iroko, Chlorophora excelsa; Cedar of Lebanon, Cedrus libani; oak, Quercus robur; Mahogony-Shereal sp; and othersSawmill workers, carpenters, woodcarvers, cabinet- or furniture-makers
       Soldering fluxesColophonyElectronics industry
       PesticidesOrganophosphatesFarming
       PharmaceuticalPsyllium, ipecacuanha, pancreatic, and glandular extractsHealth care professionals
      Antibiotics: penicillin, amoxicillin, ampicillin, penicillamine, cephalosporins, spiramycin
       Reactive dyesBlack henna, brilliant yellow E36, carmine, FD&C blue dye #2Hairdressers, textile workers, food industry workers
      High-molecular-weight agents
       EnzymesAlcalase, maxatase, amylase, variousSoaps, baking products, food industry workers
       Cereals and flourCereals, enzymesBaking and pastry-making, harbor workers
       AnimalsRat and mouse urine, various small animals, cows, shellfish (crab)Laboratory technicians, veterinarians, farmers, shellfish processors
       LatexLatexHealth care professionals

       Laboratory animals and shellfish allergy

      Small animals represent a frequent cause of OA in laboratory technicians and veterinarians. Of all proteins present in the workplace, whatever their nature, proteins excreted in urine are probably the most potent source of sensitization, especially proteins produced by male rats.
      • Gordon S.
      • Bush R.K.
      • Newman Taylor A.J.
      Laboratory animal, insect, fish and shellfish allergy.
      An incidence of 8.9 per 100 person-years has been found in approximately 400 apprentices examined before and after starting exposure,
      • Gautrin D.
      • Ghezzo H.
      • Infante-Rivard C.
      • Malo J.-L.
      Incidence and determinants of IgE-mediated sensitization in apprentices: a prospective study.
      with this figure dropping to 1.3 per 100 person-years once employed and seen on average 8 years afterward,
      • Gautrin D.
      • Ghezzo H.
      • Infante-Rivard C.
      • Magnan M.
      • L'Archevêque J.
      • Suarthana E.
      • et al.
      Long-term outcomes in a prospective cohort of apprentices exposed to high-molecular-weight agents.
      showing that onset of sensitization and symptoms is more common soon after exposure starts, with the latency period here relatively short. Atopy is a risk factor of relatively low impact, with the main personal risk factor baseline sensitization to the usual pets, dogs and cats.
      • Gautrin D.
      • Ghezzo H.
      • Infante-Rivard C.
      • Malo J.-L.
      Incidence and determinants of IgE-mediated sensitization in apprentices: a prospective study.
      As for antigens in bakeries, quantification of airborne antigens is feasible with reasonable precision. Animal facilities represent a workplace where control of exposure should represent a priority because this is feasible using individually ventilated cages.
      • Gordon S.
      • Bush R.K.
      • Newman Taylor A.J.
      Laboratory animal, insect, fish and shellfish allergy.
      Animal handlers are exposed not only to animal-derived allergens but also to endotoxin. Endotoxin exposure was found in 1 study to be responsible for the presence of symptoms in individuals who showed no evidence of IgE-mediated sensitization.
      Exposure to larger animals such as cows is also a common cause of OA. This is the leading cause of OA in Finland.
      • Piipari R.
      • Keskinen H.
      Agents causing occupational asthma in Finland in 1986-2002: cow epithelium bypassed by moulds from moisture-damaged buildings.
      Various fishes
      • Jeebhay M.F.
      • Robins T.G.
      • Lopata A.L.
      World at work: fish processing workers.
      and shellfishes can cause OA, especially crab, for unknown reasons, much more so than lobster. Both species are intensively harvested in waters off most parts of the northeastern coast of North America.
      • Cartier A.
      • Malo J.-L.
      • Forest F.
      • Lafrance M.
      • Pineau L.
      • St-Aubin J.-J.
      • et al.
      Occupational asthma in snow crab-processing workers.
      • Howse D.
      • Gautrin D.
      • Neis B.
      • Cartier A.
      • Horth-Susin L.
      • Jong M.
      • et al.
      Gender and snow crab occupational asthma in Newfoundland and Labrador, Canada.
      The responsible allergens are present in cooking water and meat.

       Latex

      Latex allergy became a real epidemic of allergies and OA in the 1980s. Allergic sensitization causing life-threatening anaphylactic reactions has been documented in patients as well. Health professionals are affected by skin and anaphylactoid reactions as well as asthma. The prevalence of OA was 2.5% in 1 meticulous study.
      • Vandenplas O.
      • Delwich J.P.
      • Evrard G.
      • Aimont P.
      • van der Brempt X.
      • Jamart J.
      • et al.
      Prevalence of occupational asthma due to latex among hospital personnel.
      Diagnosis was initially hampered by the lack of satisfactory and safe extracts for skin testing. Adequate reduction of this allergen in workplaces, along with the case of enzymes (see “Enzymes” below), provided proof that environmental control (for example, use of low-latex content gloves, low-powdered gloves, or no latex gloves) can considerably reduce the number of cases. This has been the case in health care workers who are nowadays much less frequently affected. Subjects who are allergic to latex often experience cross-allergic reactions to foods such as banana, kiwi, avocado, and chestnut.

       Enzymes

      If latex allergy was a major cause of OA in the 1980s, enzymes presented a major threat of allergic sensitization, especially in the soap industry, in the 1970s.
      • Juniper C.P.
      • How M.J.
      • Goodwin B.F.J.
      Bacillus subtilis enzymes: a 7-year clinical, epidemiological and immunological study of an industrial allergen.
      The prevalence of sensitization to enzymes derived from Bacillus subtilis, alcalase and maxatase, reached levels of 20% to 60% at the time. Although adequate control of the environment through encapsulation has greatly reduced the risk of sensitization, cases continue to be reported. Enzymes were the first occupational agent for which control of the environment was convincingly shown to reduce the risk greatly. A multitude of plant-derived and microbe-derived enzymes are used in the workplace, and many have been reported to cause sensitization and asthma.
      Various occupational allergens of plant and flower origins, beans and gums, can cause OA. Greenhouse workers, who represent a high-risk group, have been the focus of epidemiologic surveys because they represent a large population and the environment can well be characterized.
      • Monso E.
      Occupational asthma in greenhouse workers.
      Many ubiquitous allergens can, at times, be considered as occupational allergens. This is the case of grass pollens for municipal workers cutting lawns or mites for hotel employees making beds. These workers are exposed to higher doses of antigens, which can cause asthmatic reactions that would not occur in the context of ubiquitous exposure. For some jurisdictions, a diagnosis of occupational asthma can be accepted in these instances.

       Low-molecular-weight agents

      There are at present approximately 100,000 individual chemical entities on the European Inventory of Existing Commercial Substances, and new low-molecular-weight chemicals are frequently introduced into the market. It is possible to predict potential sensitizing properties of these agents.
      • Jarvis J.
      • Seed M.J.
      • Elton R.
      • Sawyer L.
      • Agius R.
      Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds.
      Many low-molecular weight agents are capable of inducing OA. Some of these agents, such as acid anhydrides, and some metals, such as platinum salts, induce asthma through an IgE mechanism, but for a large number of agents of this class, the mechanisms of induction of asthma remain unknown. Inhalation challenge testing with the responsible agent can induce different types of asthmatic reactions, most often isolated late and atypical reactions. The following discussion is confined to the more common causes of occupational asthma caused by low-molecular-weight agents.

       Anhydrides

      Acid anhydrides are used in making alkyd and epoxy resins. Epoxy resins are widely used in adhesives, casting, coating, and sealants, whereas alkyd resins form the base for paints, varnishes, and plastics.
      Phthalate anhydride has long been known to cause OA and rhinitis. Trimellitic anhydride exposure is associated with a spectrum of lung diseases: asthma, rhinitis, late respiratory systemic syndrome, and pulmonary disease–anemia syndrome.
      • Patterson R.
      • Zeiss C.R.
      • Pruzansky J.J.
      Immunology and immunopathology of trimellitic anhydride pulmonary reactions.
      As many as 2.5% of workers exposed to trimellitic anhydride and 8.8% of workers exposed to various anhydrides may show work-related respiratory symptoms. A significant association has been found between HLA antigens DR3 and specific IgE antibodies to trimellitic anhydride.
      Exposure to tetrachlorophthalate anhydride has been associated with asthma. Specific IgE antibodies have been reported in 12% of atopic subjects and 6% of nonatopic subjects exposed to tetrachlorophthalate anhydride.
      • Venables K.M.
      • Topping M.D.
      • Howe W.
      • Luczynska C.M.
      • Hawkins R.
      • Newman Taylor A.J.
      Interaction of smoking and atopy in producing specific IgE antibody against a hapten protein conjugate.
      Smokers who are atopic have the highest prevalence of increased specific IgE antibodies.

       Metals

      Metals in the first series of the periodic table are more potent sensitizers compared with the rest, but cases of OA caused by metals mostly come from platinum and aluminum exposure.
      Platinum salts, particularly the halides, are more potent in inducing sensitization and asthma than any other metallic salts.
      • Pepys J.
      Occupational allergy due to platinum complex salts.
      In some chemical plants, the cumulative risks for sensitization can be as high as 51% within 5 years. Smoking is a strong risk factor for a positive skin prick test, but not atopy or bronchial hyperresponsiveness. The HLA-DR3 phenotype has been associated with a significant increased risk of skin sensitization to platinum salts.
      The prevalence of sensitization correlates closely with OA. Skin prick testing has a high sensitivity and specificity for detecting patients with platinum salt–induced OA. A maximum concentration of 1 g/L sodium hexachloroplatinate has been recommended for skin testing and for bronchial challenge testing, because this concentration does not induce false-positive reactions.
      The threshold limit value for exposure platinum salts is 2 ug/m3, but it is not known whether this level prevents sensitization. Secondary prevention by medical surveillance programs using skin prick testing with platinum salt and a questionnaire has been recommended.
      • Merget R.
      • Caspari C.
      • Kulzer S.A.
      • Dierkes-Globisch R.
      • Breitsadt R.
      • Kniffka A.
      • et al.
      Effectiveness of a medical surveillance program for the prevention of occupational asthma caused by platinum salts: a nested case-control study.
      A variant of OA has been reported among potroom workers in aluminum smelters who report respiratory symptoms, including wheezing, during a shift at work. The cause of potroom asthma is not known. There is a large variation in the prevalence/incidence of potroom asthma in the aluminum industry, from 0.06% to 4% of exposed workers, with a low prevalence in North American studies compared with Scandinavian studies.
      • Kongerud J.
      • Boe J.
      • Soyseth V.
      • Naalsund A.
      • Magnus P.
      Aluminum potroom asthma: the Norwegian experience.
      A typical asthmatic reaction with changes in FEV1 beyond 20% on a work shift has rarely been demonstrated.

       Di-isocyanates

      In many parts of the world, di-isocyanates are the most common cause of OA. The commonly used di-isocyanates in industries are shown in Table II. All these chemicals have N=C=O groups that are highly reactive and explain their sensitizing properties. The prevalence of di-isocyanate–induced OA is from 5% to 10%. In recent years, lowering the permissible concentration from 20 ppb to 5 ppb may have reduced cases.
      • Tarlo S.M.
      • Liss G.M.
      Prevention of occupational asthma: practical implications for occupational physicians.
      Dermal exposure is postulated as a reason for sensitization.
      As for most low-molecular-weight agents, atopy is not a predisposing factor. However, predisposition conferred by certain HLA class II antigens has been reported in some studies, whereas the presence of GSTP1 Val/Val genotype was found to confer protection.
      • Mapp C.E.
      • Fryer A.A.
      • DeMarzo N.
      • Pozzato V.
      • Padoan M.
      • Boschetto P.
      • et al.
      Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates.
      Although the mechanism of OA caused by di-isocyanates has been explored in a vast number of studies, there is still considerable controversy regarding its pathogenesis, more specifically whether the disease is a result of a non–IgE-dependent mechanism. Specific IgE antibodies to toluene di-isocyanate (TDI) have been reported in only a minority of workers with (TDI-induced OA (0% to 50%, depending on the study). Bronchial biopsies of patients with di-isocyanate–induced OA show the absence of bronchial IL-4 RNA message, irrespective of response to inhalation challenge, suggesting that this is a non–IgE-mediated disease. Specific IgG and monocyte chemoattractant protein 1 have also been incriminated. The characteristics of the inflammatory process in di-isocyanates–induced OA are similar to those of common asthma. Both neutrophils and eosinophils are found in induced sputum and lavage.

       Cleaning agents

      In many population-based studies, exposure to cleaning agents at work has steadily been shown to be associated with increased risks of asthma after adjusting for confounders.
      • Medina-Ramon M.
      • Zock J.P.
      • Kogevinas M.
      • Sunyer J.
      • Torralba Y.
      • Borrell A.
      • et al.
      Asthma, chronic bronchitis, and exposure to irritant agents in occupational domestic cleaning: a nested case-control study.
      Many cleaning and sterilizing agents can cause OA (Table II). The most notable example is glutaraldehyde, which is used extensively for disinfecting heat-sensitive equipment such as fiber-optic endoscopes and also for developing radiographs. Health care workers are known to be at risk for exposure to a number of sensitizers other than cleaning agents at work (Table II).
      Much less is known about the risk factors, exposure levels, clinical features, and pathogenetic mechanisms of asthma related to cleaning agents. Professional cleaners are exposed not to 1 agent but to many such as bleach, ammonia, and hydrochloric acid. Most of these agents are low-molecular-weight compounds, and it is not clear whether they induce the production of specific IgE antibodies. Many are irritants and may interact with sensitizers to induce asthma.

       Wood dusts

      Many different species of wood have been identified as being associated with OA; some are listed in Table II. Most cases of OA caused by wood dusts were published as case reports, with the exception of OA caused by Western red cedar (Thuja plicata), which has been studied extensively.
      • Chan-Yeung M.
      • Malo J.L.
      Western red cedar (Thuja plicata) and other wood dusts.
      The prevalence of work-related asthma in Western red cedar sawmills ranges from 1.6% to 13.5% and is directly related to the level of exposure. The permissible concentration of Western red cedar dust has currently been reduced from 10 mg/m3 to 1 mg/m3. The agent responsible for asthma has been identified as plicatic acid, which is a low-molecular-weight compound of 440 d. The clinical picture and outcome have been well described, and the pathology is similar to di-isocyanate–induced OA. As for OA caused by di-isocyanates, the mechanisms responsible for red cedar asthma are still unclear but are likely a combination of immunologic and nonimmunologic factors. Atopy is not a predisposing factor, but certain HLA class II antigens are associated with predisposition and others with protection.
      Much less is known about OA caused by other wood dusts shown in Table II because epidemiologic studies have not been as systematically carried out as for Western red cedar. Specific IgE antibodies have been found in some workers, but in most instances, this is not the case.

       Colophony and fluxes

      Colophony is widely used as a flux in electronic industry. In the United Kingdom, colophony-induced asthma was responsible for 9% of all cases of OA in 1998. Colophony is obtained from pine trees containing abietic acid. The prevalence of work-related respiratory symptoms among electronic workers was 22%. The prevalence of symptoms was related to the degree of exposure. Half of the workers with colophony-induced asthma continued to have symptoms 4 years after cessation of exposure.
      • Burge P.S.
      • Edge G.
      • Hawkins R.
      • White V.
      • Taylor A.N.
      Occupational asthma in a factory making flux-cored solder containing colophony.

       Exposure to multiple agents

      In many industries or occupations, workers are exposed to a number of high-molecular-weight agents, low-molecular-weight sensitizers, and irritants, some of which are listed in Table III. Health care workers are the most obvious group, accounting for 16% of work-related asthma in the United States. Health professionals involved with instrument cleaning, exposed to powdered latex gloves, and administering aerosolized medications are at increased risk of asthma.
      Table IIIWorkplaces associated with exposure to more than 1 agent
      IndustryAgents
      Health careCleaning agents
      Sterilizing agents
      Pharmaceuticals: psyllium, antibiotics,
      Metals in dental alloys
      Methacrylates
      Aerosolized medications: ribavirin, pentamidine
      Spills of chemicals, such as acetic acid
      Latex
      HairdressingPersulfate salts, reactive dyes, henna
      Bleaching agents
      Secondary, tertiary and quarternary amines, either aliphatic, heterocyclic or aromatic
      Latex
      FarmingHerbicides, insecticides, fungicides
      Endotoxin
      Animal derived allergens, arthropods, plants, molds
      BakingCereals
      Enzymes
      Auto body repairIsocyanates
      Acrylates
      Amines
      Hairdressers are also exposed to multiple respiratory sensitizers. The prevalence/incidence of OA in hairdressers ranges from 0.20 to 0.26 per 1000 in Norway to 3.9 per 1000 in Sweden. In France, from 1996 to 1999, 6.8% of all reported cases of OA were hairdressers. Although persulfate salts are the most likely cause of asthma in most hairdressers, the mechanism is unknown.
      Farmers and other agricultural workers are exposed to a large variety of protein-derived and animal-derived allergen products as well as to chemicals and endotoxins at work (Table III). Exposure to organophosphate pesticides is known to be associated with airway hyperresponsiveness and asthma. Pesticides may also modulate inflammatory responses to endotoxin and allergens, because they are associated with atopic but not nonatopic asthma.

      Agents causing asthma without a latency period

      Irritant gases used in World War I, accidental spills from trains in residential urban areas, and events of immense public concern such as the Bhopal and World Trade Center catastrophes are examples of what is referred to as irritant-induced asthma or reactive airways dysfunction syndrome, a label given to this condition by Brooks et al in 1985.
      • Brooks S.M.
      • Weiss M.A.
      • Bernstein I.L.
      Reactive airways dysfunction syndrome (RADS): persistent asthma syndrome after high level irritant exposures.
      After an accidental inhalation event, exposed individuals start in the next few minutes and hours to present a sensation of burning in the nose and throat, followed by symptoms that mimic asthma. Coughing is more of a concern than wheezing.
      • Gautrin D.
      • Bernstein I.L.
      • Brooks S.M.
      • Henneberger P.K.
      Reactive airways dysfunction syndrome and irritant-induced asthma.
      Many agents have been incriminated, with vapors and aerosols more harmful than dry particles. Chlorine and ammonia are the most frequently reported agents. Workers often visit first-aid and emergency units, at which time they are mainly administered bronchodilators and oxygen, whereas they should instead be treated rapidly with oral and inhaled steroids that have a beneficial effect in irritant-induced asthma. Moreover, rather than discharging these patients, follow-up should be organized to ensure that workers are not left with permanent airway obstruction and hyperresponsiveness.
      In conclusion, although some agents are less often reported as causing OA with a latency period (such as detergent enzymes and latex), others (such as flour and isocyanates) still represent a significant threat. Many chemicals are introduced in the occupational environment without sufficient information on their potential sensitizing properties. Finally, all agents that exist as vapors or aerosols can cause irritant-induced asthma if generated at high concentrations. All workers are at risk of such inhalational accidents.

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