The Journal of Allergy and Clinical Immunology
Volume 123, Issue 3 , Pages 567-568, March 2009

Current perspectives in occupational asthma

  • Robert K. Bush, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Robert K. Bush, MD, Section of Allergy and Immunology, Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Wisconsin, K4/910 CSC Box 9988, 600 Highland Ave, Madison, WI 53792.

Section of Allergy and Immunology, Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Wisconsin, Madison, Wis

Received 2 December 2008; accepted 4 December 2008.

Article Outline

Key words: Asthma, occupational asthma, work-related asthma, workplace exposure

 

This issue of the Journal focuses on occupational asthma (OA). Up to 10% to 15% of adult asthmatic patients report that their symptoms worsen at work. The term work-related asthma would apply to most of these patients, whereas true OA is asthma caused by exposure encountered in the workplace. Work-exacerbated asthma is a preexisting condition that is worsened by exposure in the workplace to aeroallergens, irritants, or as a consequence of physical activity. Work-exacerbated asthma affects more individuals than true OA.

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Historical perspective 

Dr Jack Pepys is regarded by many allergists, immunologists, and pulmonologists as one of the fathers of OA. Dr Pepys was well known for his work on allergic bronchopulmonary aspergillosis, but clearly OA was another major focus of his clinical activity and research. The article by Nelson1 includes an illustration of Pepys' challenge methods for OA, which mimic exposures occurring in the workplace. In addition, Pepys described a variety of pulmonary responses that can occur from exposures in patients with OA. These include immediate, late-phase, dual, and repetitive late-phase reactions. Pepys' description of these responses and his challenge methods are still important today. Dr Pepys not only mentored but also inspired many of the contributors to this issue of the Journal and countless other physicians as well. His son, Dr Mark Pepys,2 provides us with additional insights into the humanistic qualities of this remarkable man.

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Agents causing OA 

Malo and Chan-Yeung3 describe a variety of agents that have been implicated in causing OA. OA can result from sensitizing agents that lead to IgE or other immunologic responses (usually referred to as OA with a latency period). Non–latent-onset asthma most often involves reactive airway dysfunction syndrome, which can result from a single exposure to a high concentration of an airway irritant, such as chlorine gas or anhydrous ammonia, or irritant-induced asthma as a result of repeated exposures to these agents. Higher-molecular-weight agents (usually proteins, such as organic dusts like animal urinary proteins and wheat flour) typically elicit IgE-mediated responses. Low-molecular-weight agents can elicit IgE responses (examples are acid anhydrides and isocyanates), but often the mechanisms have not been fully elucidated.

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Mechanisms of OA 

Maestrelli et al4 provide a comprehensive review of the currently known mechanisms involved in OA. OA results from the interactions of host factors, genetic factors, and levels and routes of exposure to an inciting agent. In many instances, a TH2-mediated mechanism generates specific IgE antibodies to a high-molecular-weight agent that results in classical “allergic asthma.” The mechanisms involved with low-molecular-weight agents are steadily being elucidated. Organic chemicals, particularly those that are able to cross-link with human proteins, can elicit TH2 responses. The picture is more complex in responses to irritant chemicals, which can damage airway epithelium and generate innate immune processes. Understanding novel immune responses, such as the generation of CD3+CD4−CD8+ lymphocytes that can produce IL-5 by diisocyanates, are advancing our knowledge of the mechanisms involved in OA, yet much needs to be learned.

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Diagnosis of OA 

Dykewicz5 describes the importance of the occupational history, as well as occupational environmental assessment, in the diagnosis of OA. Materials Safety Data Sheets, which list potential sensitizers encountered in the workplaces of patients, are of valuable assistance to the clinician. Serial pulmonary function tests, which use data loggers at least 4 times a day over a 4-week period with at least 2 weeks away from the workplace and 2 weeks at the workplace, are helpful in establishing decreases in lung function associated with work exposure. Methacholine testing performed within proximity to workplace exposure, when the results are negative, is useful in ruling out OA. A specific inhalant challenge, as demonstrated by Pepys, is the gold standard for the diagnosis of OA, but inhalation challenges are often limited to specialized centers, and there might be risks, particularly from exposure to low-molecular-weight agents. More recently, induced sputum analyses performed before and after work exposure can demonstrate increased inflammatory cells, often eosinophils, in response to high-molecular-weight substances and neutrophilic responses to irritants and low-molecular-weight agents. Immunologic testing, either by using skin prick testing or in vitro assays, can be useful in certain instances, as pointed out Bernstein.6 High-molecular-weight agents, in particular, might elicit IgE responses that can be demonstrated by appropriately conducted prick skin tests. In some cases, immunoassays can supplement the skin testing. Some low-molecular-weight agents, such as isocyanates, might bind to human proteins and elicit IgE responses that can be detected by immunoassays. Clearly, there is a need for standardized reagents for testing and validated in vitro assays.

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Management of OA 

Bernstein6 stresses the need for early diagnosis of OA to prevent the long-term impairment that often occurs with ongoing exposure. The diagnosis rests on appropriate testing procedures. The most effective management approach to OA is exposure avoidance or reduction by appropriate methods. For patients with work-exacerbated asthma, pharmacologic therapy based on asthma treatment guidelines can be extremely useful. In addition to reducing the effects of exposure on established OA, attention to primary prevention by minimizing exposure to hazardous agents within an industry should also be considered.

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Conclusions 

In conclusion, many advances have been made in the diagnosis and treatment of OA. Further elucidating mechanisms, particularly those that do not involve IgE responses, are crucial. Standardization and better diagnostic reagents are called for as well. Exposure avoidance is a key component in the management of OA. For patients with work-exacerbated asthma, pharmacologic management can reduce economic effects on the individual and improve workers' productivity. Ultimately, effective measures for primary prevention will improve the health of our patients and reduce the economic effect of work-related asthma.

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References 

  1. Nelson HS. The allergy archives. Pioneers and milestones. Jack Pepys' contribution to the medical literature. J Allergy Clin Immunol. 2009;123:720–723
  2. Pepys MB. The allergy archives. Pioneers and milestones. Jack Pepys (May 15, 1914–September 9, 1996): a personal recollection. J Allergy Clin Immunol. 2009;123:718–720
  3. Malo J-L, Chan-Yeung M. Agents causing occupational asthma. J Allergy Clin Immunol. 2009;123:545–550
  4. Maestrelli P, Boschetto P, Fabri LM, Mapp C. Mechanisms of occupational asthma. J Allergy Clin Immunol. 2009;123:531–542
  5. Dykewicz MS. Occupational asthma: current concepts in pathogenesis, diagnosis and management. J Allergy Clin Immunol. 2009;123:519–528
  6. Bernstein DI. Management of work-related asthma. J Allergy Clin Immunol. 2009;123:551–557

 Disclosure of potential conflict of interest: R. K. Bush receives speakers' honoraria from Gundersen-Lutheran Health and the University of Wisconsin Pharmacy Extension and receives grant support from the National Institutes of Health and Greer Laboratories.

PII: S0091-6749(08)03477-5

doi:10.1016/j.jaci.2008.12.1109

The Journal of Allergy and Clinical Immunology
Volume 123, Issue 3 , Pages 567-568, March 2009

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