Occupational asthma: Current concepts in pathogenesis, diagnosis, and management

doi:10.1016/j.jaci.2009.01.061

Journal of Allergy and Clinical Immunology

Volume 123, Issue 3, March 2009, Pages 519-528

https://doi.org/10.1016/j.jaci.2009.01.061 Get rights and content

Occupational asthma (OA) may account for 25% or more of de novo adult asthma. The nomenclature has now better defined categories of OA caused by sensitizing agents and irritants, the latter best typified by the reactive airways dysfunction syndrome. Selecting the most appropriate diagnostic testing and management is driven by assessing whether a sensitizer is involved, and if so, identifying whether the sensitizing agent is a high-molecular-weight agent such as a protein or a low-molecular-weight reactive chemical such as an isocyanate. Increased understanding of the pathogenesis of OA from reactive chemical sensitizers is leading to development of better diagnostic testing and also an understanding of why testing for sensitization to such agents can be problematic. Risk factors for OA including possible genetic factors are being delineated better. Recently published guidelines for the diagnosis and management of occupational asthma are summarized; these reflect an increasingly robust evidence basis for recommendations. The utility of diagnostic tests for OA is being better defined by evidence, including sputum analysis performed in relation to work exposure with suspected sensitizers. Preventive and management approaches are reviewed. Longitudinal studies of patients with OA continue to show that timely removal from exposure leads to the best prognosis.

Section snippets

Sensitizer-induced OA

Occupational asthma from sensitizers typically presents with a latent period of exposure, followed by the onset of clinical disease. After sensitization, airway reactions develop from levels of exposure to the sensitizing agent that were tolerated before sensitization. Although the mechanism causing OA from some sensitizers has been demonstrated to have an immunologic basis (IgE antibody–mediated or otherwise), no immunologic mechanism has been demonstrated for some suspected sensitizers (eg,

OA from HMW sensitizers

High-molecular-weight agents such as proteins and glycoproteins (Table I) characteristically act as complete antigens that cause sensitizer OA through a classic IgE antibody–mediated mechanism. The allergens responsible for OA from some HMW agents have been well characterized—for example, in detergent workers who develop asthma from exposure to Bacillus subtilis enzymes, or in egg processing workers. However, identifying the actual protein sensitizers in complex plant or animal materials can be

Epidemiology and risk factors

Other than the intrinsic physicochemical and immunogenic properties of agents, the most important risk for developing OA is the level and duration of exposure to agents capable of causing OA.³² Although tobacco smoking not been found to be consistently associated with increased risk for OA,³³ reports of an association between smoking and OA from certain agents suggest that the absence or presence of such an association may vary depending on the agent. Atopy is a risk factor for OA from HMW

Diagnosis

Although the diagnosis and management of OA can be complex, published guidelines provide a logical, structured approach (Fig 2). In summary, it is first necessary to establish that a patient has asthma, then that OA is present. A combined approach of using history and objective testing is important for increasing the reliability of the assessment of possible OA.

Differential diagnosis

There are a number of diagnoses that may mimic OA, including vocal cord dysfunction, upper respiratory tract irritation, hypersensitivity pneumonitis, rhinosinusitis, and psychogenic factors. Byssinosis, popcorn workers' disease, and flock workers' disease are examples of other occupational lung diseases that may also mimic OA, with the last 2 capable of causing bronchiolitis obliterans. In addition, eosinophilic bronchitis may present with a nonproductive cough, associated with increased

Management

In OA from sensitizers, complete avoidance of the sensitizer is best from a medical perspective, because better outcomes occur in patients who leave work early in the course of OA versus those who remain at work⁴⁹ (Fig 2). Even when additional medications including anti-inflammatory agents are used, continued exposure after diagnosis is associated with worsening symptoms, lung function, and overall outcomes.2, 64 When patients are unable or unwilling to change jobs, an alternative approach is

Prevention and surveillance

A diagnosis of OA in an individual worker showed always be viewed as a potential sentinel health event that may merit workplace evaluation to identify and prevent OA in other workers.²

Prevention of OA is considered to have 3 components2, 3:

1.
Primary prevention of new OA is directed at reducing workplace exposure to potential causal agents. This may involve reduction of exposure by complete elimination of a causal agent (eg, through substitution), process modification, respirator use, or

Prognosis and outcomes

The prognosis of occupational asthma depends primarily on cessation of exposure to the offending agent, the duration of exposure to sensitizers, and the severity of asthma when diagnosed.2, 7 Timely removal of workers from exposure to a sensitizer causing OA is generally associated with favorable outcomes. Prolonged follow-up may be required to ascertain outcomes in any individual, particularly in OA from sensitizers in which there may be continued improvement of lung function for 2 years or

Clinical implications and future directions

Although great strides have been made in understanding OA, there remain many unanswered questions. There are important needs to understand better the pathogenesis of OA from LMW sensitizers, determine circumstances under which irritant asthma might occur when criteria are not met for the long-recognized condition of RADS, and develop improved diagnostic tests to assess sensitization to LMW agents. With the introduction of sputum analysis as a diagnostic tool for OA from suspected sensitizers,

References (73)

S.M. Tarlo et al.
Diagnosis and management of work-related asthma: American College of Chest Physicians consensus statement
Chest
(2008)
E.J. Bardana
Occupational asthma
J Allergy Clin Immunol
(2008)
S.M. Brooks et al.
Reactive airways dysfunction syndrome (RADS): persistent asthma syndrome after high level irritant exposures
Chest
(1985)
M. Weichel et al.
Wheat and maize thioredoxins: a novel cross-reactive cereal allergen family related to baker's asthma
J Allergy Clin Immunol
(2006)
A. Palacin et al.
Wheat lipid transfer protein is a major allergen associated with baker's asthma
J Allergy Clin Immunol
(2007)
C. Lemiere et al.
Changes in sputum cell counts after exposure to occupational agents: what do they mean?
J Allergy Clin Immunol
(2001)
R. Patterson et al.
Immunology and immunopathology of trimellitic anhydride pulmonary reactions
J Allergy Clin Immunol
(1982)
J.L. Malo et al.
Changes in specific IgE and IgG and monocyte chemoattractant protein-1 in workers with occupational asthma caused by diisocyanates and removed from exposure
J Allergy Clin Immunol
(2006)
Y.M. Ye et al.
Biophysical determinants of toluene diisocyanate antigenicity associated with exposure and asthma
J Allergy Clin Immunol
(2006)
M.G. Jones et al.
Is occupational asthma to diisocyanates a non-IgE-mediated disease?
J Allergy Clin Immunol
(2006)

C.A. Herrick et al.

A novel mouse model of diisocyanate induced asthma showing allergic-type inflammation in the lung after inhaled antigen challenge

J Allergy Clin Immunol

(2002)

C. Lemière et al.

Airway inflammation and functional changes after exposure to different concentrations of isocyanates

J Allergy Clin Immunol

(2002)

W.C. Moore et al.

Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program

J Allergy Clin Immunol

(2007)

A. Karjalainen et al.

Risk of asthma among Finnish patients with occupational rhinitis

Chest

(2003)

H. Jeal et al.

HLA associations with occupational sensitization to rat lipocalin allergens: a model for other animal allergies?

J Allergy Clin Immunol

(2003)

J.A. Bernstein et al.

T-cell receptor V beta gene segment expression in diisocyanate-induced occupational asthma

J Allergy Clin Immunol

(1997)

J.L. Malo et al.

From asthma in the workplace to occupational asthma

Lancet

(2007)

M. Kogevinas et al.

Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II)

Lancet

(2007)

J.L. Malo et al.

Natural history of occupational asthma: relevance of type of agent and other factors in the rate of development of symptoms in affected subjects

J Allergy Clin Immunol

(1992)

J.A. Bernstein

Material safety data sheets: are they reliable in identifying human. hazards?

J Allergy Clin Immunol

(2002)

D.E. Banks et al.

Absence of hyperresponsiveness to methacholine in a worker with methylene diphenyl diisocyanate (MDI)-induced asthma

Chest

(1986)

O. Vandenplas et al.

Occupational asthma in symptomatic workers exposed to natural rubber latex: evaluation of diagnostic procedures

J Allergy Clin Immunol

(2001)

A. Marabini et al.

Clinical and socioeconomic features of subjects with red cedar asthma: a follow-up study

Chest

(1993)

L.C. Grammer et al.

Effect of respiratory protective devices on development of antibody and occupational asthma to an acid anhydride

Chest

(2002)

D.E. Banks et al.

Persistence of toluene diisocyanate-induced asthma despite negligible workplace exposures

Chest

(1990)

H. Allmers et al.

Primary prevention of natural rubber latex allergy in the German health care system through education and intervention

J Allergy Clin Immunol

(2002)

J. Balmes et al.

Environmental and Occupational Health Assembly, American Thoracic Society. American Thoracic Society Statement: occupational contribution to the burden of airway disease

Am J Respir Crit Care Med

(2003)

J.L. Malo et al.