Definition

The definition of occupational asthma, much like the definition of asthma itself, has changed over the years; therefore, it is difficult to determine the prevalence of the disorder. According to the current consensus definition,¹ patients with occupational asthma have variable airflow limitation or airway hyperresponsiveness, or both. It occurs in response to a specific work environment and not to stimuli encountered elsewhere.

There are two types of occupational asthma. One is immunologic, occurs after a latency period, and is caused either by agents with a known immunoglobulin E (IgE) reaction or by agents with no known IgE reaction. The other is nonimmunologic and is also known as irritant-induced asthma (IrIA) or reactive airways dysfunction syndrome (RADS). The irritant type can occur after one or more exposures to high concentrations of irritants (no latency period). A related form of occupational asthma has been termed work-aggravated asthma. In this instance, preexisting asthma is aggravated by a workplace exposure. Although work-aggravated asthma is not specifically addressed in this chapter, evaluation of all cases of asthma should include a detailed environmental history regarding exposures in both the home and the workplace.

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Prevalence

Occupational asthma is a part of a larger category of diseases known as occupational respiratory diseases and includes occupation-induced rhinitis and laryngitis, tracheitis, bronchitis and bronchiolitis, chronic obstructive pulmonary disease, lung cancer, and interstitial diseases such as fibrosis and granuloma formation.² Physicians and the lay public are aware of other occupational lung disorders such as silicosis and asbestosis (see “ Occupational Lung Disease” in Section 12), but occupational asthma is the most prevalent occupational lung disease in industrialized countries.

Findings regarding the significance of occupation as a cause of asthma vary based on the definition used and the methods of patient selection. In addition, persons who develop occupational asthma often leave the industry in which the illness began (a bias known as the healthy worker effect), even when occupational asthma has not yet been diagnosed. In general, asthma affects 5% to 10% of people worldwide, and it is estimated that 2% to 15% of asthma is occupational in origin.

The incidence of occupational asthma also varies with specific exposures. Occupational asthma has been reported in 8% to 12% of laboratory animal workers, 7% to 9% of bakers, and 1.4% of health care workers exposed to natural rubber latex. Even these percentages vary significantly depending on the study cited. Farmers, painters, plastic and rubber workers, and cleaners (window cleaners, chimney sweepers, and road sweepers) are at greatest risk for developing asthma.³

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Pathophysiology

Like childhood asthma, occupational asthma is the result of interactions between multiple environmental and genetic factors. Some of the known environmental factors include the route, duration, and intensity of exposure and the substance (or agent) to which the person is exposed. Using the definition of Mapp and coworkers,¹ occupational asthma can be divided into immunologic causes (associated with a latency period) and nonimmunologic causes. Agents associated with an immunologic cause can be further divided into high-molecular-weight (HMW) agents, usually allergens such as proteins from laboratory animals, flour, or plants, and low-molecular-weight (LMW) agents, usually chemicals such as isocyanates, biocides, or drugs.

Occupational Asthma with a Latency Period

HMW agents can induce an IgE response in susceptible persons and can cause asthma by an IgE-mediated mechanism, similar to that seen in a patient with atopic asthma. The bridging of IgE molecules by antigen leads to mast-cell degranulation and the initiation of an inflammatory cascade that results in airway inflammation and airway hyperresponsiveness. It is therefore not surprising that patients with atopic asthma or patients with a family history of atopy are at increased risk for developing occupational asthma from exposure to HMW agents. Smoking is also a risk factor for sensitization.

The pathogenic mechanisms of LMW agents are less well understood; however, there appear to be several mechanisms, both immunologic and nonimmunologic, that can lead to occupational asthma. LMW agents probably act as haptens, combining with human proteins in the respiratory tract to become complete immunogens. Atopy and smoking are not risk factors for occupational asthma caused by LMW agents, as they are for occupational asthma caused by HMW agents. Some of the better-studied agents include isocyanates and plicatic acid. Isocyanates are found in paints and are involved in the manufacture of plastics, rubber, and foam, and plicatic acid is the causative agent in asthma caused by western red cedar. Specific IgE for isocyanates or plicatic acid is found in only a small percentage of patients with documented disease. However, the detection of specific IgE may be a marker of exposure and not of disease.⁴

Activated T cells also play an important role in the pathogenesis and in the inflammation of occupational asthma as they do in other forms of asthma. Bronchial biopsies of patients with occupational asthma induced by isocyanate or red cedar show many activated T cells.^5,6 Several recent studies have also shown associations between HLA class II antigens and various types of occupational asthma.⁷

LMW agents also cause occupational asthma by direct pharmacologic action. Isocyanates can block β₂-adrenergic receptors, and high concentrations of plicatic acid can activate complement. Isocyanates and other agents can stimulate sensory nerves, leading to the release of substance P and other neuropeptides. They can also inhibit the neutral endopeptidases that normally inactivate these substances. This affects a variety of cells in the airways, resulting in cough, smooth muscle contraction, and mucus production.

Box 1 shows some of the more common causes of occupational asthma associated with a latency period.

Occupational Asthma Without Latency

The mechanisms of IrIA or RADS are also poorly understood. IrIA is a nonimmunologically induced asthma that occurs without a latency period. It typically occurs after a brief, high-intensity inhalation exposure followed by the acute onset of persistent respiratory symptoms and ongoing airway hyperresponsiveness. It is postulated that extensive denudation of the airway epithelium occurs, resulting in airway inflammation due to the loss of epithelium-derived relaxing factors, exposure of nerve endings leading to neurogenic inflammation, and nonspecific activation of mast cells with release of inflammatory mediators and cytokines.⁸ Ammonia, chlorine, and sulfur dioxide are the most common causes of IrIA, although the list is extensive.

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Signs and symptoms

The signs and symptoms of occupational asthma may be identical to those of other forms of asthma. In patients whose occupational asthma is caused by HMW agents, rhinitis or rhinoconjunctivitis often precedes the onset of asthma symptoms by 1 year or more. In contrast, IrIA or RADS has a characteristically distinct presentation. The exposure is typically acute, singular, and extreme, often involving some type of accident or chemical spill. There is no latency period, and symptoms of airway obstruction are immediate or develop within a few hours of exposure.

In patients with occupational asthma with a latency period, symptom improvement has been noted over a weekend with 24 to 48 hours of work absence in about 70% of patients and in up to 90% of workers with vacation leaves of 7 to 10 days.⁹ Symptom patterns can also be very similar to those seen in nonoccupational asthma and include early, late, and dual responses. Early responses are seen within minutes of exposure, reach maximal severity within 30 minutes, and resolve within 1 to 2 hours. Late responses can occur after 4 to 6 hours, peak around 8 hours, and resolve after 24 hours. Dual responses involve both early response with complete or near-complete recovery followed by a late phase.

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Diagnosis

Occupational asthma should be considered in all working-age patients with new-onset asthma or worsening asthma. A detailed history of occupational and potential occupational exposures is just as important as identifying environmental triggers when evaluating an asthmatic patient. Although many patients themselves relate their symptoms to the workplace, many other cases of occupational asthma are recognized only because the physician performed a detailed environmental history. Common screening questions include the following: What are your workplace exposures? When during the work shift or work week do symptoms develop? Do symptoms improve during the weekend and over vacations? Do other workers have similar symptoms? The history can be supplemented with material safety data sheets from the workplace and can be compared with agents known to cause occupational asthma. A worksite visit by the physician or by an occupational hygienist might also provide helpful information.

A useful tool can be found at www.asmanet.com. This website provides a list of agents known to cause occupational asthma and the occupations in which they are encountered, and it can be searched by specific occupation.

Although taking a good occupational history is important in establishing a link between symptoms and potential workplace exposures, a history by itself is inadequate to make the diagnosis of occupational asthma. Algorithms and information on the diagnosis of occupational asthma can be found below and in Figure 1. More detailed information can be found elsewhere.^10-12 If possible, skin testing or specific IgE assessment should be performed. This is generally most useful for diagnosing occupational asthma caused by HMW agents.

A determination of nonspecific bronchial hyperresponsiveness (NSBH) with methacholine or histamine challenge should be performed in all patients with suspected occupational asthma. A negative challenge does not exclude occupational asthma if the patient left the workplace some time ago and is now free of symptoms. However, a negative challenge performed when the patient is working and symptomatic can reasonably exclude the diagnosis of occupational asthma.

Serial measurements of NSBH can also be useful. NSBH is typically worse after a period of exposure and can lessen after cessation of exposure. A minimum of 10 to 14 days after removal from the workplace is recommended before retesting. A minimum threefold improvement in PC₂₀ (dose of methacholine or histamine needed to cause a 20% decrease in the forced expiratory volume in 1 second [FEV₁]) while the patient is off work is significant; however, a lack of improvement in PC₂₀ does not exclude occupational asthma.¹³

Serial peak expiratory flow (PEF) self-monitoring with the subject at work and away from work for the same period is useful in obtaining objective information to confirm occupational asthma. Current recommendations are for four daily measurements; the subject should perform three forced-expiratory maneuvers, and at least two should be within 20 L/min of each other. All three readings should be recorded, but the best should be used for analysis. If a patient is taking inhaled corticosteroids, the dose should not be changed during the PEF monitoring period. All readings should be made before using bronchodilators. Readings should be performed for 2 weeks at work during exposure to the suspected agent and for 2 weeks away from the suspected agent.^13,14 A motivated and compliant patient is essential for PEF monitoring to be useful.

The gold standard for the diagnosis and confirmation of occupational asthma is a specific inhalational challenge with the suspected agent. However, this requires specialized facilities and is available at only a few centers. In general, specific challenge tests are useful when the diagnosis of occupational asthma remains in doubt after serial monitoring of PEF or NSBH, when a patient clearly has occupational asthma but it is necessary to confirm the causative agent for correct management, and when a new agent is suspected of causing occupational asthma.

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Treatment

The most important aspect in the treatment of occupational asthma is environmental control. Continued exposure can lead to persistent and irreversible airway obstruction, whereas early removal offers the best chance at complete recovery. Other than environmental control, the management of occupational asthma is no different than that for nonoccupational asthma. However, pharmacologic treatment is not effective in preventing deterioration of lung function in sensitizer-induced occupational asthma when subjects remain exposed to the causing agent. (For additional information on the management of asthma, see “ Asthma” elsewhere in this section).

In contrast, patients with RADS or IrIA without concurrent sensitization can usually return to the workplace if they have adequate pharmacologic control of their asthma and if there are appropriate occupational hygiene controls in place to prevent the likelihood of a repeat high-level respiratory irritant exposure.

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Outcomes

The outcome in occupational asthma depends on many of the same elements that are involved with initial sensitization and include the nature of the agent, the concentration of exposure, the duration of exposure, and the smoking history as well as host-dependent factors. Factors predicting a worse outcome are lower PC₂₀ at baseline, longer duration of exposure, and the interval since removal of the patient from exposure. Early removal offers the best chance at recovery. However, most patients with occupational asthma with latency do not recover, even after several years away from exposure. In addition, subjects with occupational asthma due to HMW agents seem to have a less favorable outcome. The typical plateau for improvement in spirometry is around 1 year, whereas the plateau for improvement in NSBH occurs around 2 years.

The socioeconomic outcomes of occupational asthma also vary significantly. For example, a patient in Quebec with occupational asthma is provided with a full salary for up to 2 years, which is the estimated time required for retraining for a new occupation. A survey of 134 workers with occupational asthma examined 2 years after diagnosis found that 41 (31%) had found jobs with the same employer in which they were no longer exposed to the causal agent, and only 11 (8%) of workers were still unemployed.¹⁵ In contrast, a survey of 55 patients in the United States with occupational asthma who were assessed an average of 31 months after removal from exposure found that 69% were still unemployed.¹⁶

Once the diagnosis of occupational asthma is made, that worker is 100% impaired for the job that caused the problem or for jobs with exposure to the same causative agent. It is recommended that long-term assessment of impairment should be performed 2 years after removal from exposure, when improvement tends to plateau. Guidelines for the assessment of permanent impairment due to asthma have been proposed by the American Thoracic Society.¹⁷

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Summary

• Occupational asthma should be considered in any new or worsening case of asthma in working-age persons.
• There are still many controversies regarding the diagnosis, pathophysiology, prognosis, and appropriate compensation for patients with occupational asthma.
• Prompt recognition, diagnosis, and removal from the work environment are necessary to ensure the best possible outcome.
• Additional information on occupational asthma can also be found at www.osha-slc.gov/sltc/occupationalastham/.

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Further Readings

• American Thoracic Society. Guidelines for the evaluation of impairment/disability in patients with asthma. Am Rev Respir Dis. 1993, 147: 1056-1061.
• Banks DE, Jalloul A. Occupational asthma, work-related asthma and reactive airways dysfunction syndrome. Curr Opin Pulm Med. 2007, 13: (2): 131-136.
• Beckett WS. Occupational respiratory diseases. N Engl J Med. 2000, 342: 406-413.
• Boulet LP, Lemiere C, Gautrin D, Cartier A. New insights into occupational asthma. Curr Opin Allergy Clin Immunol. 2007, 7: (1): 96-101.
• Chan-Yeung M, Malo JL. Occupational asthma. N Engl J Med. 1995, 333: 107-112.
• Chan-Yeung M, Malo JL, Tarlo SM, et al: Proceedings of the first Jack Pepys Occupational Asthma Symposium. Am J Respir Crit Care Med. 2003, 167: 450-471.
• Henneberger PK. Work-exacerbated asthma. Curr Opin Allergy Clin Immunol. 2007, 7: (2): 146-151.
• Holness DL, Tabassum S, Tarlo SM, et al: Practice patterns of pulmonologists and family physicians for occupational asthma. Chest. 2007, 132: (5): 1526-1531.
• Mapp CE, Boschetto P, Maestrelli P, Fabbri LM. Occupational asthma. Am J Respir Crit Care Med. 2005, 172: (3): 280-305.
• Nicholson PJ, Cullinan P, Taylor AJ, et al: Evidence based guidelines for the prevention, identification, and management of occupational asthma. Occup Environ Med. 2005, 62: (5): 290-299.