Asthma is a common condition, affecting an estimated 5% to 10% of the general population.1 Approximately one out of every 10 adult asthmatics has a work-related connection, ie, asthma that was caused by their occupation or preexisting asthma aggravated by the job.2 The former is called occupational asthma (OA), and the latter is called work-aggravated asthma (WAA3-6). Whereas OA implies asthma first caused by something inhaled at the workplace, WAA implies a current or preexisting history of asthma. In WAA, symptoms are from exposure(s) that could have occurred anywhere, eg, from dusts, fumes, or cold air.
While there is a general consensus for dividing work-related asthma into OA and WAA, this classification may not be easily applied to an individual worker with asthma symptoms. A prior diagnosis of asthma may be unknown or hard to pin down. Conversely, patients with preexisting asthma can also develop OA if it can be proved they became sensitized to an agent unique to the workplace. Of course, patients do not present with a label but with symptoms—typically cough, dyspnea, and/or wheezing or chest tightness. It is up to the physician to determine if there is a job connection. Given a patient with asthma symptoms and a possible work relationship, there are four key questions:
1. Is it asthma?
2. If so, is it work-related?
3. If work-related, is it WAA or OA?
4. What is (are) the cause(s)?
For this article, I will define asthma as reversible airflow obstruction causing symptoms that include cough, dyspnea, and/or wheezing or chest tightness. Diagnosis usually requires spirometry to demonstrate airflow obstruction, and reversibility either with treatment or spontaneously. In addition, other conditions, such as pneumonia or COPD, should be ruled out.
If the diagnosis is asthma, the second question is usually answerable with a detailed history. Any temporal relationship to the job should suffice to call it work-related. In some situations, serial peak flow measurements have been used to demonstrate work-relatedness, but more often specific testing is not necessary if the history is clear and consistent.
The answer to the third question is also heavily dependent on medical history. A preexisting history of asthma will usually suffice to indicate the asthma is work-aggravated rather than OA. There are exceptions, as when patients with preexisting airflow obstruction become sensitized to something unique to the job, but this is difficult to demonstrate without specialized testing. Distinction between WAA and OA is more useful for epidemiologic and research purposes than for managing individual patients. As a clinical pulmonologist, I find it best to avoid rigid labeling and just describe the patient’s condition in as detailed fashion as possible. This means a) pointing out the temporal relationships and potential cause(s), and b) determining the degree of impairment with pulmonary function tests and a thorough history. If and when the issue of workers’ compensation arises (and it invariably does), such detailed description should help prevent misunderstanding and confusion.
The fourth question is usually the most difficult to answer. This is because many patients react to processes or conditions for which no single chemical or agent can be determined, only surmised. Moreover, for medical management, elucidating a definite causative agent is not necessary.
Prevalence of Work-Related Asthma
Asthma is the most prevalent occupational lung disease in developed countries,3-6 but just how common is it? A review of available literature in 1999 found 23 studies that estimated the attributable risk of asthma due to occupational exposures; this review included new onset disease and reactivation of preexisting asthma.2 These data were from 17 countries, and the estimated risk varied widely, from 2% to 33%. Based on these data, and additional studies that allowed estimation of the attributable risk, the authors concluded that “half of the attributable risk estimates were between 5% and 19%, with a median of 9% … occupational factors are associated with about 1 in 10 cases of adult asthma, including new onset disease and reactivation of preexisting asthma.”2
There are approximately 200 million people in the United States 18 years of age or older (www.census.gov). Given a 5% to 10% prevalence rate of asthma, an estimated 1 million to 2 million US adults have asthma in some way related to workplace exposures. (These are prevalence estimates only, and do not mean 1 million to 2 million new cases each year.)
Definition of OA
Occupational asthma is defined as a disease characterized by variable airflow limitation and/or bronchial hyperresponsiveness, due to cause(s) unique to a particular working environment. Two types of OA are generally recognized. 3-6
Immunologically mediated. An immunologic mechanism—inhaled antigen eliciting antibody reaction—has been identified or is thought to play a role. Characteristic of this type of OA is a latency period; symptoms do not occur immediately, but often days or longer after the initial sensitization.
Irritant-mediated. Irritants have a direct effect on bronchial mucosa and do not work through an immunologic mechanism. This type can occur immediately after an acute exposure such as the reactive airways dysfunction syndrome (RADS), or over a longer period of time, from low level exposure to one or more irritants.
Immunologically Mediated OA
Immunologic OA is reversible airway obstruction due to an allergic mechanism. There is a reaction between the offending substance (an antigen) and an antibody produced by the body’s immune system; the resultant antigen-antibody reaction triggers a release of chemicals that cause bronchial inflammation, airway narrowing, and asthma symptoms. This mechanism is far more common than irritant-induced, accounting for more than 85% of cases of OA.6
Characteristic of immunologic OA is a latency period (from days to years) between first contact with the allergen and development of asthma; this is because the worker must first become “sensitized” to the allergen and build up an immune response before there is clinical asthma.
Well over 400 substances have been identified in the workplace that can cause occupational asthma. The majority of these are antigens; a list with descriptions is maintained on the Internet.7 Antigens causing OA are typically categorized as high or low molecular weight (MW) compounds,3-6 although the two groups cannot be distinguished on clinical grounds. Generally, high molecular weight compounds are mostly proteins from animals and plants; low molecular weight compounds include numerous chemicals. A few examples of these compounds, and the occupations at risk, are listed in Table 1.
Note that OA can occur in “clean” environments, such as in the pharmaceutical industry, where workers may develop sensitization after repeated exposures to low molecular weight antibiotics. Another example of clean environment OA is latex allergy.8-11 Latex, or natural rubber, is found in many medical products, particularly gloves. Reactions range from contact hives (skin reaction only) to asthma and, in some extreme cases, shock (anaphylaxis). For this reason, many hospitals and dental offices have switched to nonlatex gloves and other products.
Irritant-Mediated Occupational Asthma
This type of OA was first brought to prominence in 1985 with the description of RADS.12,13 (The first epidemiologic identification of irritant-induced asthma occurred in follow-up studies of World War I gas victims.14)
Initially, RADS was applied to all irritant-mediated asthma, and the terms were used interchangeably, but that has changed in recent years. RADS now describes an acute irritant reaction with immediate or almost immediate asthma symptoms, in a worker with no preexisting asthma. There are also numerous cases of low-level irritation that—over time—can lead to asthma. Table 2 (see page 21) lists some agents responsible for irritant-induced asthma. Table 3 (page 21) compares RADS or acute irritant-induced asthma, with the condition that can occur from low-level, chronic exposures.
Distinguishing between immunologic and irritant OA usually requires identifying the offending agent(s). Clinically, this distinction is not nearly as important as is removing the patient from the source and providing proper treatment.
OA in Health Care Workers
Several studies indicate the increased risk of OA among health care workers, particularly nurses and respiratory therapists.15-18 From a 1989 survey of Rhode Island therapists, the authors concluded there is “a previously unrecognized excess of asthma in respiratory therapists. The excess develops after entry into the profession, and does not appear to be explained by confounding, information bias, or selection bias.”15
In a more recent survey, questionnaire results from 275 Canadian respiratory therapists and 628 physiotherapists were compared; the former had more than twice the risk of being awakened by dyspnea, or having wheeze, asthma attacks, and asthma diagnosed after entering the profession.17 Two work factors associated with asthma for RTs were sterilizing instruments with glutaraldehyde-based solutions and the use of aerosolized ribavirin.
Glutaraldehyde is used to disinfect and clean heat-sensitive equipment such as dialysis instruments, surgical instruments, bronchoscopes, and endoscopes. It is also used as a tissue fixative in histology and pathology laboratories. Glutaraldehyde, a colorless, oily liquid with a pungent odor, is sold under several different brand names. In hospitals it is used in a diluted form mixed with water. According to asmanet.com, “Atopy does not appear to play a role. No immunological mechanism has been demonstrated to date.”7
Evaluation of Work-Related Asthma
The standard paradigm for evaluating any new patient is: 1) detailed history of the present illness, 2) medical history, 3) physical examination, and 4) selected tests. Clearly, for any condition that might be work-related, a complete occupational and environmental history must be woven into 1 and 2. An outline of the evaluation process is provided in Table 4 (page 22).
As a rule, the most important aspect of diagnosing work-related asthma is establishing temporal relationships between exposure(s) and symptoms. A thorough history is essential. This means a detailed job description (initially from the worker) coupled with the nature and timing of all symptoms. Physical examination and spirometry can be normal when the patient first sees a physician and are not usually helpful for diagnosis of work-relatedness.
Much has been written about self-tested, serial peak flow measurements.19-22 The idea behind this strategy is to establish temporal relationships between peak flows and work exposures by having the worker measure their own peak flows. The peak flow test is technically simple to do, with each measurement taking only a few seconds.
Typically, the worker checks their peak flow every 2 hours, at work and at home, for a period of about 2 weeks. A symptom diary is also kept, and in this manner temporal relationships between exposure and airflow obstruction may be established. If the peak flow is seen to fall, say, 4 hours after entering the workplace every day and to improve on weekends away from work, then a clear temporal relationship is established. Although the idea is a good one, for various reasons self-tested peak flows are rarely used in practice. The test is entirely effort-dependent, record keeping can be onerous, and there is no way to assure that the results recorded are entirely valid.19-22
Given a patient with possible work-related asthma, there are three main scenarios:
1) Not work-related. Example: A 27-year-old man had childhood asthma, but no symptoms since age 15. He has worked in a factory for 5 years, with no job-related symptoms. He developed an upper respiratory infection (URI) at home, went to an urgent care facility, and was given medication for cough and wheezing. After returning to work the next day, he was sent home because of persistent coughing. Detailed history could not relate his symptoms to anything at work, but only to the URI.
2) Work-aggravated asthma. Example: A 35-year-old man has asthma well controlled with daily inhalations of a combination steroid and long-acting bronchodilator, plus occasional use of a short-term inhaled bronchodilator. He recently took a new job in the meat section of a supermarket, which required him to enter the freezer area several times a day. Within weeks of starting this job, his asthma became worse, requiring addition of oral steroids. Detailed history and temporal relationships suggested that cold air aggravated his preexisting asthma.
3) Occupational asthma. A 32-year-old nonsmoking nurse worked on a medical ward for 3 years. She changed position to work in the operating room, which required her to wear latex gloves daily. Within a few weeks, she began noticing a rash on her hands. She was prescribed a cream and advised not to use gloves for a few days. A week later, she returned to work and began wearing the gloves again; the first day back, she developed some wheezing and dyspnea. She was taken to the hospital’s emergency department where she was given inhalation bronchodilator therapy and sent home. She returned to work the next day and again developed some wheezing a few hours after putting on gloves for the first surgery. She was treated in the ED, then sent to a pulmonary specialist. Latex allergy was presumptively diagnosed. She left the operating room job, avoided all latex products, and had no further respiratory problems. (The hospital where she worked has since changed over entirely to nonlatex surgical gloves.)
Medical management of work-related asthma is no different from that of asthma unrelated to the job, with one important exception: advice about continued working. If workers have developed asthma from something in the work environment, they must leave that environment; avoidance of further exposure offers the best chance of recovery. Continued exposure to the offending agent is associated with further deterioration of lung function.23 Also, the longer the worker remains in the offending environment, the more likely their asthma will become persistent once all exposure has ceased. Masks and other devices to minimize the exposure are of no help, and should not be relied on. Even tiny amounts of allergen can trigger a reaction if the worker is sensitized to it.
On the other hand, if the asthma was due to a one-time irritant exposure, and the irritant is removed completely, then there should be no contraindication to continued working in that environment. One caveat is that other pollutants in the environment may bother the worker more than before, even though the specific agent causing the asthma is removed.
Although stopping exposure generally results in clinical improvement, this is not invariable, particularly if the worker is a smoker or has coexisting sinusitis (which can also trigger asthma exacerbations). Even without other conditions, the patient might continue to manifest bronchial hyper-responsiveness and require medication for months or years after leaving the job.23
Implications of Diagnosing Work-Related Asthma
Anyone treating the patient—and this certainly includes respiratory therapists as well as physicians and nurses—should realize that diagnosis of “work-related” or “occupational” asthma means a claim of some sort will be filed. The claim may be for direct payment or for coverage of medical bills, and might end up in a workers’ compensation venue or in civil court. For several reasons, many claims for “occupational asthma” are disputed or challenged:
• Given the high prevalence of asthma in the general population, the multiple factors that can trigger an attack, the potential for variability of symptoms in a given patient, and the fact that most job descriptions do not identify a single asthma-causing agent, diagnosing asthma as work-related can be problematic without the added complexity of a compensation claim.
• Physicians’ opinions carry great weight in workers’ compensation claims, but physicians involved in the early stages of an asthma claim are often not knowledgeable about work-related asthma. A sloppy initial diagnosis is not uncommon, and it can embroil the patient in multiple evaluations before there is resolution of the claim.24
• The adversarial situation attendant to many claims often pits medical expert against medical expert. Perhaps more than any other area of occupational lung disease, the complexity of diagnosing work-related asthma allows latitude for experts to give selective history, ignore relevant facts, and display unwarranted bias.24
• Even when the diagnosis is undisputed, there is often dispute over the worker’s degree of impairment or disability, with many physicians confusing the two terms.24,25 Impairment is specific loss of function, such as a decline in peak flow or FEV1; it is a strictly medical determination. Disability is impairment plus all other factors that impact a person’s ability to work, such as skill level, education, job availability, etc; disability is based on medical and socioeconomic factors. Two workers with identical pulmonary impairment may have varying degrees of disability, by virtue of differences in age, education, skills, and job availability. Physicians are advised to adhere to the AMA Guides, 5th edition,26 which are largely based on the 1993 American Thoracic Society statement on impairment and disability.27 Even with adherence to published guidelines, the inherent variability of asthma can still lead to widely differing assessments of impairment and disability. Furthermore, private disability insurance policies, state workers’ compensation programs, the US Department of Labor, the Social Security Disability Program, and other state and federal programs may employ different criteria for determining eligibility.28 Once disputed, the diagnosis may involve the employer, administrators from workers’ compensation and social security agencies, lawyers, nontreating physicians hired as medical experts, and, if the case goes to trial, a judge and jury. As a result, the patient’s records are likely to be scrutinized closely, including any notes/comments by nurses and respiratory therapists (eg, patient’s effort during lung function testing). While professionalism in all aspects of patient care is assumed, adjudication is usually based on the written record (and experts’ reports). The best advice is to be legible, objective, thorough; assume that whatever you make part of the patient’s record will be reviewed at some point and, perhaps, influence a decision on the claim.
Lawrence Martin, MD, is chairman, Department of Medicine at UHHS-Richmond Heights Hospital, Richmond Heights, Ohio, and associate professor of medicine, Case Western Reserve University School of Medicine, Cleveland.
A Case of Occupational Asthma
A 33-year-old man has worked for 10 years in a machine shop, as a toolmaker and grinder. He has never smoked and has no history of asthma, allergies, or hay fever. In 2003 he began noting intermittent chest congestion and cough, worse at work and better on weekends. His symptoms gradually became more frequent, and when first evaluated in February 2005, he was wheezing and had mild airflow obstruction. Below are results from a spirometry test performed on February 15, 2005.
Spirometry FVC and FEV1 = forced vital capacity and forced expiratory volume in liters, respectively; % predicted values in parentheses. BD = bronchodilator (inhaled albuterol).
Generally, a BD response of 15% or greater is needed to diagnose hyperreactive airways and asthma. In February 2005, a diagnosis of “acute bronchitis” was made, and he was treated with prednisone and an inhaled bronchodilator. The patient improved for a while, but then relapsed. Chest x-ray was normal. Sinus CT scan revealed mucosal thickening in the left frontal and both maxillary sinuses, consistent with sinusitis.
He was seen several times over the following spring and summer, and each time reported symptoms that were worse after working. He was treated with steroids (inhaled and oral), antibiotics, and bronchodilator medication. At the same time, concern for possible occupational asthma prompted further investigation. He was asked to bring in the relevant material safety data sheets (MSDS), which are published for most industrial agents. One of the materials he was frequently exposed to goes by the name “cemented tungsten carbide with cobalt/nickel binder, tungsten carbide grade powder.”
Cobalt, nickel, and tungsten are just three of more than 400 agents that can lead to occupational asthma.7 About this particular product, the MSDS state: “Dust from grinding can cause irritation of the nose and throat. It also has the potential for causing transient or permanent respiratory disease, including occupational asthma and interstitial fibrosis, in a small percentage of exposed individuals. It is reported that cobalt dust is the most probable cause of such respiratory disease. Symptoms include productive cough, wheezing, shortness of breath, chest tightness and weight loss Interstitial fibrosis can lead to permanent disability or death. Certain pulmonary conditions may be aggravated by exposure. If symptoms of pulmonary involvement develop (coughing, wheezing, shortness of breath, etc.), remove from exposure and seek medical attention.”
The patient was advised to avoid all dust exposures, but economic circumstances required him to continue working in the same position (using whatever respiratory protection is available). To secure a more definitive OA diagnosis for workers’ compensation claim, he had a methacholine challenge test in July 2005. This is the standard test to show airway hyperreactivity when asthma is in question. Progressively higher doses of methacholine are inhaled, each followed by a measurement of spirometry 3 minutes later.
In the normal population (nonasthmatic, non-hyperreactive), there will be minimal, if any, decrement in airflow with methacholine. If at any point there is a decrease in FEV1by 20% or greater, the test is considered positive for bronchial hyperreactivity, a hallmark of asthma. This patient’s test became positive after the fifth inhaled dose of methacholine; FEV1 fell by 23% (see Table), and he complained of chest tightness and wheezing. At that point, he was given inhaled albuterol, which brought his FEV1 back up to normal.
Methacholine Challenge Test
Based on all of the following, then, this patient has occupationally induced asthma:
– No prior history of asthma or atopy
– No smoking history
– Symptoms temporally worse at work; improvement on weekends away from work
– Frequent exposure to substance known to cause airway irritation/asthma
– Positive methacholine challenge test
He applied for workers’ compensation, and his claim was allowed for occupational asthma. This means all medical care for asthma will be covered; it does not guarantee retraining or a new job. Nonetheless, medical coverage is especially important if he changes jobs and has difficulty getting health insurance for a preexisting condition.
Of course, claim allowance does not solve his health problem. He has been advised to retrain or find a new job, since over time repeated exposure to the carbide product (and possibly other materials inhaled at work) could lead to irreversible chronic lung disease. As of this writing, he is still working at the same job, but is considering alternatives.
1. American Academy of Allergy Asthma & Immunology. Allergy & Asthma disease Management Center. Asthma prevalence. Available at: [removed]www.aaaai.org/aadmc/ate/category.asp?cat=1005[/removed] Accessed April 3, 2006.
2. Blanc PD, Toren K. How much adult asthma can be attributed to occupational factors? Am J Med. 1999;107:580-7.
3. Venables KM, Chan-Yeung M. Occupational asthma. Lancet. 1997;349:1465-9.
4. Vandenplas O, Malo JL. Definitions and types of work-related asthma: a nosological approach. Eur Respir J. 2003;21:706-12.
5. Chan-Yeung M, Malo JL, Tarlo SM, et al. American Thoracic Society. Proceedings of the first Jack Pepys Occupational Asthma Symposium. Am Rev Resp Crit Care Med. 2003;167:450-71.
6. Mapp CE, Boschetto P, Maestrelli P, Fabbri L. State of the art: occupational asthma. Am J Resp Crit Care Med. 2005;172: 280-305.
7. Table of agents which can cause asthma. Available at: www.asmanet.com/asmapro/agents.htm Accessed March 31, 2006.
8. Kelly KJ, Walsh-Kelly CM. Latex allergy: a patient and health care system emergency. Ann Emerg Med. 1998;32:723-9.
9. Avila PC, Shusterman DJ. Work-related asthma and latex allergy. Sorting out the types, causes, and consequences. Postgrad Med. 1999;105:39-46.
10. Cheng L, Lee D. Review of latex allergy. J Am Board Fam Pract. 1999;12:285-92.
11. Tilles SA. Occupational latex allergy: controversies in diagnosis and prognosis. Ann Allergy Asthma Immunol. 1999;83:640-4.
12. Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome (RADS); persistent asthma syndrome after high level irritant exposure. Chest. 1985;88:376-84.
13. Alberts WM, Do Pico GA. Reactive airways dysfunction syndrome. Chest. 1996;109:1618-26.
14. Blanc PD. Occupational and environmental “orphan” respiratory diseases. Am J Respir Crit Care Med. 2006;173(3):253-4. 15. Kern DG, Frumkin H. Asthma in respiratory therapists. Ann Intern Med. 1989;110:767-73.
16. Christiani DC, Kern DG. Asthma risk and occupation as a respiratory therapist. Am Rev Respir Dis. 1993;148:671-4.
17. Dimich-Ward H, Wymer ML, Chan-Yeung M. Respiratory health survey of respiratory therapists. Chest. 2004;126:1048-5.
18. Pechter E, Davis LK, Tumpowsky C, et al. Work-related asthma among health care workers: surveillance data from California, Massachusetts, Michigan, and New Jersey, 1993-1997. Am J Ind Med. 2005;47:265-75.
19. Henneberger PK, Stanbury MJ, Trimbath LS, et al. The use of portable peak flowmeters in the surveillance of occupational asthma. Chest. 1991;100:1515-21.
20. Quirce S, Contreras G, Dybuncio A, et al. Peak expiratory flow monitoring is not a reliable method for establishing the diagnosis of occupational asthma. Am J Respir Crit Care Med. 1995;152: 1100-2.
21 Malo JL. Assessment of peak expiratory flow in asthma. Curr Opin Pulm Med. 1996;2:75-80.
22. Huggins V, Anees W, Pantin C, Burge S. Improving the quality of peak flow measurements for the diagnosis of occupational asthma. Occup Med (Lond). 2005;55:385-8.
23. Nicholson PJ, Cullinan P, Taylor AJ, Burge PS, Boyle C. Evidence based guidelines for the prevention, identification, and management of occupational asthma. Occup Environ Med. 2005;62:288-9.
24. Martin L. Pitfalls in diagnosis of occupational lung disease for purposes of compensation: One physician’s perspective. Cleveland State Marshall Law School Journal of Law and Health. 1999;13( 1): 49-68.
25. Richman SI. Meanings of impairment and disability. The conflicting social objectives underlying the confusion. Chest. 1980;78(suppl):367-71.
26. American Medical Association. Guides to the Evaluation of Permanent Impairment. 5th ed. Chicago: American Medical Association; 2000.
27. American Thoracic Society. Guidelines for the evaluation of impairment/disability in patients with asthma. Am Rev Resp Dis. 1993;147:1056-61.
28. American Thoracic Society: Guidelines for assessing and managing asthma risk at work, school and recreation. Am J Resp Crit Care Med. 2004;169:873-88.