A. Introduction

1. Most prevalent occupational lung disease
2. Over 250 agents cause occupational asthma (and other lung diseases)
3. Types
   1. Occupational asthma - airflow limitation, bronchial hyperresponsiveness
   2. Work-aggravated asthma - preexisting or concurrent asthma aggravated in workplace
   3. Occupational asthma with latency - develops over time, often after exposure is gone
   4. Occupational asthma without latency - direct irritation, bronchial hyperresponsiveness
4. Most persons with occupational asthma (especially with latency) do not recover fully
5. Approximately 5% of population is affected by asthma
6. About 10-20% of this is occupational [5]

B. Agents Implicated in Occupational Asthma

1. High Molecular Weight (>5000 dlatons)
   1. Cereals
   2. Animal Danders
   3. Latex
   4. Seafoods
   5. Gums
2. Low Molecular Weight
   1. Isocyanates
   2. Wood Dusts
   3. Anhydrides / Amines / Aldehydes / Acrylate
   4. Persulfates / Metals / Dyes
   5. Fluxes (electronics)
3. Mineral and Organic Dusts (see below)

C. Presenting Symptoms

1. Recurrent upper respiratory irritations
2. Bronchitis (mucus production)
3. Adult onset asthma
4. Interstitial Lung Disease (see below)

D. Pathophysiology

1. IgE production to specific agents
   1. Usually high molecular weight products (>5K MW)
   2. Includes rat urine proteins, platinum salts, acid anhydrides
   3. Some of these reactions have an HLA association
   4. Smokers at at particularly increased risk for IgE mediated allergies
2. Some low molecular weight compounds induce IgE antibodies
   1. These compounds act as haptens that chemically react with body proteins
   2. These hapten-protein conjugates stimulate B and T lymphocytes
3. Most low molecular weight compounds do not induce antibodies
   1. Induction of inflammation by these agents is poorly understood
   2. Direct stimulation of T lymphocytes may be responsible
   3. Isocyanates fall into this class
4. Agents which induce asthma via non-immulogical mechanisms
   1. Cause apparent "direct" bronchoconstriction
   2. Include irritant gases, fumes, or chemicals

E. Diagnosis

1. Requires diagnosis of asthma and relationship to work exposure
2. Occupational cause for all new onset asthma should be considered
   1. History of improvement on weekends and holidays
   2. Concurrence of rhinorrhea, sneezing, during asthmatic symptoms
3. Allergen skin testing may be available for some agents
4. Measure bronchial hyperresponsiveness to specific agents (peak expiratory flow)

F. Treatment

1. Remove person from exposure (IgE levels should fall within 1-2 years)
2. Treatment similar to other forms of asthma
3. ß2-agonists should be used in addition to inhaled glucocorticoid therapy
4. Cromylin compounds may help prevent attacks

G. Other Occupational Respiratory Diseases [1]

1. Rhinitis and Laryngitis
   1. Large particles (>10µm) are deposited in nose, pharynx and larynx
   2. Soluble gases such as sulfur dioxide are absorbed in upper respiratory tract
   3. These gases and particles cause mucosal edema and mucus hypersecretion
2. Tracheitis and Bronchitis
   1. Large particles (>10µm) are deposited and then cleared by cilia
   2. Small particles and fine fibers deposited in bronchioles and alveolar ducts
   3. Less soluble gases penetrate deeper into small airways
   4. Bronchitis reversed by reduced exposure with physical barriers or removal
   5. Chronic bronchitis is treated with ipratropium bromide (Atrovent®) inhalers
   6. Additional ß-adrenergic agonist inhalers may be required if wheezing develops
   7. As noted above, inhaled glucocorticoids may be beneficial
3. Bronchiolitis
   1. Mainly due to inhalation of noxious gases and other compounds
   2. Narrowing and filling of bronchioles
   3. Now seen with exposure to nitrogen dioxide ("silo filler's disease)
   4. Dyspnea, chest tightness, and irreversible airflow obstruction occur
   5. Diagnosis by high resolution computerized tomography
   6. Early oral or intravenous glucocorticoids recommended
4. Interstitial Lung Diseases
   1. Includes alveolar and fibrotic diseases
   2. Mineral and organic dusts usually cause alveolar disease
   3. Small particles (<10µm) and fibers deposited in terminal bronchioles, alveolar areas
   4. Penetration into interstitium results in fibrosis and granuloma formation
5. Neoplasia
   1. Lung cancer usually associated with polycyclic hydrocarbon exposure
   2. Lung cancer and mesothelioma associated with asbestosis
   3. Concurrent smoking greatly increases risk of developing neoplasm

References

1. Beckett WS. 2000. NEJM. 342(6):406
2. Chan-Yeung M and Malo JL. 1995. NEJM. 333(2):107
3. Newman LS. 1995. NEJM. 333(17):1128
4. Venables KM and Chan-Yeung M. 1997. Lancet. 349:1465
5. Kogevinas M, Anto JM, Sunyer J, et al. 1999. Lancet. 353(9166):1750