Reviews and feature article
Mechanisms of occupational asthma

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Inhalation of agents in the workplace can induce asthma in a relatively small proportion of exposed workers. Like nonoccupational asthma, occupational asthma is probably the result of multiple genetic, environmental, and behavioral influences. It is important that occupational asthma be recognized clinically because it has serious medical and socioeconomic consequences. Environmental factors that can affect the initiation of occupational asthma include the intrinsic characteristics of causative agents as well as the influence of the level and route of exposure at the workplace. The identification of host factors, polymorphisms, and candidate genes associated with occupational asthma may improve our understanding of mechanisms involved in asthma. High-molecular-weight compounds from biological sources and low-molecular-weight chemicals cause occupational asthma after a latent period of exposure. Although the clinical, functional, and pathologic features of occupational asthma caused by low-molecular-weight agents resemble those of allergic asthma, the failure to detect specific IgE antibodies against most low-molecular-weight agents has resulted in a search for alternative or complementary physiopathologic mechanisms leading to airway sensitization. Recent advances have been made in the characterization of the immune response to low-molecular-weight agents. In contrast, the mechanism of the type of occupational asthma that occurs without latency after high-level exposure to irritants remains undetermined.

Section snippets

Characteristics of the allergen

More than 350 agents have been reported to cause OA. Although there are fewer LMW chemicals than HMW agents in the lists of occupational respiratory sensitizers, LMW chemicals still represent an important subset of etiologic agents, including approximately 100 separate chemical entities.7 The most important chemicals that cause OA include acid anhydrides, polyisocyanates and their prepolymers, plicatic acid (from Western red cedar), colophony fume, and metals such as chlorinated platinum salts,

Genetic aspects

Occupational asthma, a phenotype of adult-onset asthma, might provide a means to understand better the interaction between a susceptible genotype and multiple environmental factors. The expanding evidence for gene-environmental interactions in asthma highlights the importance of measuring environmental exposure in genetic studies of occupational and nonoccupational asthma.33 It is often hard to define environmental exposures, but among subjects with OA there is the advantage that exposure,

Specific IgE antibodies

The pathophysiology of immunologic OA usually involves an IgE-dependent mechanism. OA induced by IgE-dependent agents is similar to allergic asthma that is unrelated to work.2, 3, 4, 5, 73, 74, 75, 76 Many occupational sensitizers, particularly HMW agents (eg, flour and animal proteins), induce asthma by producing specific IgE antibodies. For some LMW agents (eg, chlorinated platinum salts, sulfonechloramide, trimellitic anhydride, and other acid anhydrides), the development of OA is

Nonimmunologic OA

Establishing mechanisms of irritant-induced asthma is challenging. One reason is that unintentional exposure to high concentrations of respiratory irritants, whether particulates or chemicals, at or outside the workplace can induce the new onset of asthma.134 Respiratory health consequences of these exposures can occur from both occupational exposure and environmental disasters.135 For example, irritant-induced asthma is one of the respiratory consequences observed in workers in the New York

Conclusion

Understanding the pathogenesis of OA is a crucial step toward optimal prevention and management of the disease. Identification of structure-activity relationships for causal agents of OA shows great promise for understanding induction of airway sensitization. A dose-response relationship between the level of exposure and the development of OA is well established for several sensitizing agents. Recent evidence indicates that chemical respiratory allergens may induce respiratory tract

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    (Supported by an educational grant from Merck & Co., Inc.)

    Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD

    Supported by the Ministry of University and Scientific Research; University of Padova; University of Ferrara; Consorzio Ferrara Ricerche; the Associazione per la Ricerca e Cura dell' Asma, Padova; and the Associazione per lo Studio dei Tumori e delle Malattie Polmonari, Padova.

    Terms in boldface and italics are defined in the glossary on page 532.

    These authors contributed equally to this work.

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