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Environmental
Health Perspectives Supplements Volume 110, Number 4, August 2002
Work-Related Asthma and Implications for the General Public
Edward L. Petsonk
Surveillance Branch, Division of Respiratory Disease Studies, National
Institute for Occupational Safety and Health, Morgantown, West Virginia,
USA
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Full Article in PDF
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Abstract
Asthma has been increasing over the last two decades in the United States.
The onset of asthma has also been increasingly reported as a result of
occupational exposures to over 350 different agents. Work-related asthma
(WRA) has become the most frequently diagnosed occupational respiratory
illness. Epidemiologic studies from the United States reported WRA incidence
rates of 29-710 cases per million workers per year and suggest that
10-25% of adult asthma is work related. Much can be learned about
asthma in the general population from investigations of asthma in the
workplace. Surveillance of WRA continues to highlight an important role
for low molecular weight chemical sensitizers, as well as high molecular
weight antigens. Additionally, recent reports implicate mixed exposures,
including commercial cleaning solutions, solvents, and other respiratory
irritants, as well as contamination in nonindustrial environments, including
schools and offices. Investigations of WRA have demonstrated a clear dose-related
increase in sensitization and symptoms for exposures to both chemical
and protein sensitizers. High proportions of exposed working groups can
be affected. Skin exposures may affect the likelihood of individuals developing
respiratory symptoms. Atopy increases the risk of sensitization and illness
from workplace exposure to antigens but not to chemical sensitizers. Irritant
exposures can act as adjuvants among individuals exposed to sensitizing
substances, increasing the proportion who become sensitized. Atopy might
also be a result of irritant exposures in some persons. Occupational asthma
often has important long-term adverse health and economic consequences
but can resolve completely with timely control of exposures. Detailed
study of such asthma "cures" may prove useful in understanding factors
that influence asthmatic airway inflammation in the general population.
Key words: asthma, occupational asthma, reactive airways dysfunction
syndrome. Environ Health Perspect 110(suppl 4):569-572 (2002).
http://ehpnet1.niehs.nih.gov/docs/2002/suppl-4/569-572petsonk/abstract.html
This article is part of the monograph Environmental
Air Toxics: Role in Asthma Occurrence?
Address correspondence to E.L. Petsonk, National Institute
for Occupational Safety and Health, Mail Stop HG 900.2, 1095 Willowdale
Rd., Morgantown, WV 26505-2888 USA. Telephone: (304) 285-6115. Fax:
(304) 285-6111. E-mail: elp2@cdc.gov
Received 30 November 2001; accepted 26 February 2002.
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Introduction
During the last decade, a remarkable increase has occurred in the prevalence
of asthma in the United States as well as in a number of other countries. This
increase has occurred among both children and adults (1). Studies have
associated asthma symptoms with a number of factors, including familial (2),
nutritional (3), socioeconomic and psychosocial (4), and environmental
(5) factors. Widely accepted definitions of asthma describe a chronic
inflammatory disorder of the airways with characteristic pathologic features
that can be attributed to a variety of recognized and undefined factors (6).
The specific cause or causes of the rise in asthma morbidity and mortality remain
incompletely understood. Although knowledge of the genetic determinants of asthma
is expanding, it is generally acknowledged that the explanations for the recent
increase in asthma must be found among the many changes in our living environments,
including lifestyles as well as exposures at work, school, and home (7-10).
Work-Related Asthma Is Increasingly Recognized
During the same period as the overall rise in asthma prevalence, work-related
asthma (WRA)--asthma caused or significantly exacerbated by work exposures (11)--has
emerged as the most commonly reported occupational lung condition (12,13).
Over 350 chemicals, mixtures, and processes found in the workplace have been
associated with the onset or exacerbation of asthma, with over 250 documented
as airway sensitizers (14,15). Recent studies implicate workplace exposures
in an important proportion of cases of new-onset asthma among adults, and exposures
to agents in the workplace that result in the onset of asthma continue to be
described (16,17). In addition to the new onset of asthma from occupational
exposures, individuals with preexisting asthma can experience work-aggravated
asthma caused by a variety of exposures during work. Work-aggravated asthma
results in increasing medication requirements and/or clinical deterioration
among affected persons and contributes to the importance of occupational factors
in asthma morbidity. Overall, the findings from research, surveillance, and
clinical experience among individuals with WRA have yielded a wealth of information
that can enlighten understanding of the initiation, exacerbation, management,
and even cure of asthma in the general population.
Work-Related Asthma Surveillance
Reports
from Canada and the United Kingdom as well as the United States indicate that
occupational asthma has surpassed the traditional occupational dust disorders
to become the most commonly reported occupational lung disease (18-20).
These surveillance systems highlight the contemporary importance of WRA but
do not document trends over time. However, time trends have been documented
in Finland, where a 70% increase in confirmed cases of occupational asthma was
noted from 1986 to 1993, on the basis of data from the comprehensive Finnish
national registry of occupational illnesses (21). In the United States,
four states are currently submitting reports of WRA as part of the Sentinel
Event Notification System for Occupational Risks (SENSOR) surveillance system,
which is sponsored by the National Institute for Occupational Safety and Health
(NIOSH) (22). In this program a number of core variables are collected
from cases meeting defined criteria for WRA. The pattern of agents implicated
in these reports is of interest (Table 1) The diisocyanate group of chemicals,
which are used in the production of a wide variety of consumer and commercial
products, represented the largest single group of agents--a finding similar
to that reported from several other countries (18,19,23). Contamination
in nonindustrial workplaces such as offices and schools represented the second
largest group of agents reported in association with asthma onset. To better
understand the role in asthma of exposure to molds, bacteria, volatile organic
compounds, and other contaminants found in buildings, NIOSH has initiated a
major research effort. Surveillance reports have identified several additional
agents increasingly associated with asthma, including commercial and industrial
cleaning products, and metalworking fluids, which are used in foundries, mills,
and machine shops. Overall, surveillance of WRA underscores the importance of
exposures to highly reactive low molecular weight (<5 kDa) chemical sensitizers,
mixed contaminant exposures in nonindustrial settings, and respiratory tract
irritants such as cleaning solutions and solvents.
Work-Related Asthma: Population-Based Studies
Population-based epidemiologic research of asthma in the workplace has evaluated
the incidence of WRA and the proportion of asthma in adults that can be attributed
to occupation. Studies from Europe, Asia, and the United States have varied
widely in the proportion of asthma morbidity among adults that can be attributed
to workplace exposures (24). The variability in these estimates is likely
due to differences in study methodology as well as the differing profiles of
occupational exposures found in the study locations. Several recent studies
have suggested that between 10 and 25% of adult asthma is likely to be related
to occupational exposures (25,26). Estimates of the overall yearly incidence
of occupational asthma in the U.S. working population have ranged in different
studies from 29 to 710 cases per million workers. The corresponding rate was
reported to be 174 in Finland but varies greatly by industry and occupational
categories (27-29). The relatively broad range of estimates emphasizes
the importance of design factors in results of these studies. Additional studies
are under way to define further the overall impact of occupation on asthma,
including both the new onset of asthma and the exacerbation of existing asthma
due to job exposures.
Work-Related Asthma: Workforce-Based Studies
Workforce-based studies of asthma have demonstrated that people who work with
asthma-causing agents, such as bakers, animal handlers, and isocyanate workers,
often have an elevated prevalence of asthma symptoms (12,13). Recently,
several detailed studies, including those with quantitative measurements of
exposure to sensitizers, have been completed in various work environments. For
example, among bakers, the proportion of workers sensitized (as evidenced by
responses to skin prick tests) to alpha amylase, a flour additive, increased
with increasing measured airborne exposure to the amylase (30). Similarly,
exposure-related increases in sensitization have been observed among laboratory
animal workers (31,32). In these studies, tobacco smoking, which may
be a risk factor for development of asthma (33), was associated with
increased sensitization in the animal handlers; a smoking effect was not observed
among the bakery workers. Smoking has also been associated with increased rates
of sensitization among workers exposed to platinum salts and certain acid anhydrides
but not to diisocyanates or plicatic acid (34).
Study designs of WRA have important consequences for the results. Emphasis
on rigorous case finding or a more extensive case confirmation process may result
in greater or lesser numbers of individuals with asthma who are eventually available
for analysis in a study. Individuals who develop asthma symptoms from workplace
exposures may transfer out of the exposed job or leave the workplace altogether
(35). Workers with airway hyperresponsiveness, a cardinal finding in
asthma, appear to choose jobs that minimize dust exposures (36). Because
of these selection factors (manifestations of the healthy worker effect), cross-sectional
prevalence studies are likely to underestimate the risk of asthma related to
occupational exposures compared with more resource-intensive longitudinal study
designs. Similarly, when susceptible or symptomatic workers avoid or leave jobs
with potential exposures, the relationships among job exposures, work tenure,
and asthma-related outcomes can be obscured (32).
A number of studies have found that persons with atopy (IgE-mediated sensitization
to common environmental allergens) have an increased risk of sensitization in
relation to workplace exposures to a number of high molecular weight (generally
protein) antigens. In contrast, atopy does not consistently affect the risk
of sensitization among workers exposed to low molecular weight reactive chemicals
such as diisocyanates (12,13). An intriguing finding was reported from
a study of Dutch pig farmers (37). The authors found that atopy was significantly
more common among farmers who reported using certain disinfectants in their
work, particularly quaternary ammonium compounds. This finding, which calls
for further study and confirmation, suggests that an individual's tendency to
produce IgE antibody on exposure to an aeroallergen, in addition to reflecting
his or her genotype, is influenced by certain environmental chemical exposures.
Similar accentuated specific antibody responses in human volunteers have been
observed after nasal mucosal exposure to diesel exhaust particulate (10).
Animal studies have also indicated that respiratory mucosal exposures to chemical
agents can result in augmentation of immunologic responses to airway antigen
exposure (38). This augmentation effect can depend on the timing and
site of the chemical exposure: for example, rats showed a 6-fold increase in
peak specific IgE levels after ovalbumin aerosol when exposed to lower airway
irritant (1 hr of NO2 at 100 ppm) 24 hr before antigen but not when
the irritant exposure occurred 7 days before antigen. Upper airway irritation
(NH3) did not augment levels of ovalbumin specific IgE.
Another interesting observation was reported from a study of workers in a
wood products plant that uses methylene diphenyl diisocyanate (MDI), a low molecular
weight sensitizer (39). Workers in this study were at increased risk
of developing asthmalike symptoms if they had noted skin stains due to the MDI.
This association was significant even after accounting for potential exposure
to airborne MDI. This finding suggests that immunologic sensitization from diisocyanates
may initially result from skin exposure and subsequently be manifest by respiratory
symptoms, consistent with reports of some previous human and animal studies
(40,41).
In light of the recognized familial aggregation of asthma, several studies
have investigated genetic markers among individuals with WRA. Although results
are still preliminary, several human leukocyte antigen (HLA) markers have been
identified that appear to be protective, whereas other markers appear to confer
increased risk of WRA (42,43).
Work-Related Asthma: Preventive Interventions
For certain agents associated with occupational asthma, the ability of investigators
to identify and quantify allergen exposures has facilitated the assessment of
interventions designed to prevent or reduce asthma symptoms among workers. For
example, a number of interventions have been recommended to reduce asthma symptoms
caused by exposure to protein allergens found in natural latex gloves (44).
Use of reduced-protein gloves during surgery has been documented to reduce airborne
allergen levels (45). Latex-specific IgE levels in the serum of sensitized
healthcare workers decline with time after the adoption of a policy regarding
low-allergen gloves (46). Levy et al. (47) reported that among
dental students, the adoption of a policy of using only reduced-allergen powder-free
gloves diminished the onset of sensitization during training from 11 to 0%.
Thus, occupational intervention studies have indicated that control of antigen
exposure can both reduce symptoms and specific IgE among sensitized individuals
as well as prevent the onset of sensitization among newly exposed individuals.
Clinical follow-up among persons with occupational asthma caused by a variety
of agents has indicated that prompt control of exposures is associated with
a better chance of improvement or resolution of symptoms and findings, whereas
workers who have continued exposures have a poorer prognosis (23,48).
Irritant-Induced Asthma
Occupational exposures to irritants can result in airway hyperresponsiveness,
bronchospasm, and persistent respiratory symptoms. This represents a third mechanism
for WRA onset, in addition to exposures to high molecular weight allergens and
low molecular weight chemical sensitizers. Symptoms and hyperresponsiveness,
often called the reactive airways dysfunction syndrome (RADS), may develop after
a single intense inhalational exposure to a respiratory irritant such as an
acid or alkali (49). Although the clinical symptoms mimic asthma, the
airway pathology associated with RADS may be distinguishable from the airway
inflammation typically associated with asthma (50). A similar syndrome
of persistent asthmalike symptoms has been observed among pulp mill workers
who experienced repeated but less intense exposures to chlorine gas (51,52).
Consistent with these workplace observations, a recent report has associated
incident asthma among children with exercise in environments with high ozone
exposure (53). Preexisting allergies may play a role in the development
of asthma symptoms after repeated inhalation exposures to irritants (54).
Summary: Lessons from the Study of Work-Related Asthma
Studies of asthma in the workplace have demonstrated that with increasing levels
of airborne exposure, an increasing proportion of the exposed population is
sensitized. These exposure-response relationships have been observed for high
molecular weight allergens as well as low molecular weight chemical sensitizers.
The susceptibility to sensitization varies among working populations (Figure
1). Workers who are susceptible may select out of exposed working populations,
particularly if sensitization and symptoms develop, whereas studies in some
settings find that a high proportion of workers are sensitized. Skin exposures
may play a role in initial immunologic sensitization. For a given measured airborne
exposure, atopic workers appear have an increased likelihood of becoming sensitized
to high molecular weight allergens but not to low molecular weight occupational
sensitizers such as diisocyanates. Concurrent exposure to airborne antigens
with nonsensitizing chemical irritants (such as diesel exhaust particulate,
nitrogen oxides, or tobacco smoke) may increase the likelihood of immunologic
sensitization. Thus, the expression of atopy may at least in part be a result
of nonsensitizing environmental irritant exposures. Even in the absence of specific
sensitizing exposures, inhalational exposure to irritants can at times result
in the development of persistent asthmalike symptoms (e.g., RADS). After sensitization
has occurred, continuing exposure to an occupational sensitizer is often associated
with persistent symptoms and airway hyperresponsiveness. Conversely, timely
control of workplace exposure to sensitizers may result in improvement in both
symptoms and immunologic sensitization, or even complete resolution of all symptoms
and signs of asthma. Detailed study of such asthma cures may prove useful in
understanding risk factors and mechanisms that control asthmatic airway inflammation
in the general population.
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| Figure 1. Factors
influencing population susceptibility to sensitizing exposures. |
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Last Updated: August 6, 2002
