AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

Chemical worker's lung is an arbitrary, ill-defined, and confusing term because many chemicals are known to induce lung injury. For example, asbestosis could be considered a subclassification of chemical worker's lung, but in the real world, it is a separate disease entity and a subgroup of occupational lung disease and pneumoconiosis.

In general, chemical worker's lung is defined as lung disease in a person who is exposed to chemicals during work. Because many chemicals can cause such disease, the specific substance must be identified.

Patients may have lung disease and be exposed to numerous known and unknown substances.

The list of substances that can cause lung damage continues to expand. An increasing number of chemicals that have been used in the flavoring industries are now being recognized as potential causes of lung disease (eg, popcorn worker's lung) with an increase in litigation directed to these industries.

In one of several arbitrarily limited definitions, the terminology refers to isocyanates and trimellitic anhydride exposure (National Jewish Hospital, Denver, Colo). Chemicals are used in manufacturing of polyurethane foam, molding, insulation, synthetic rubber, and packaging materials and can induce lung cell injury when inhaled. Chemical toxins and chemical warfare agents, such as tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), VX nerve gas, sulfur mustard, chlorine, phosgene, and diphosgene, can cause life-threatening lung disease.

Recently, various chemical food-flavoring agents have been shown to cause bronchiolitis obliterans. Other known causes of bronchiolitis obliterans include occupational or environmental exposures to nitrogen oxides (eg, silo gas), sulfur dioxide, chlorine, ammonia, and phosgene.

Pathophysiology

The pathophysiology differs depending on the substance to which an individual is exposed and may be unique and specific with certain exposures. In the acute phase, an inflammatory reaction may be observed with a spectrum extending to fibrotic changes within the lung.

Frequency

United States

Determining the actual prevalence rate of chemical worker's lung is difficult because of low reporting, poor appreciation of symptoms and signs associated with substance exposure, and lack of proper understanding of and diagnostic guidelines for the disease.

International

The prevalence rate is unknown, but it is presumably higher than in the United States given the lack of reporting and regulatory bodies.

Mortality/Morbidity

Mortality and morbidity vary with the substance and the frequency, intensity, and duration of inhalational exposure. Host factors include underlying cardiopulmonary disease and immunopathogenesis.

Race

Data comparing the prevalence rates of chemical worker's lung among various races are not available; however, African Americans and Asians may have smaller lungs and, possibly, a higher risk of lung disease with the same exposure.

Sex

Prevalence varies in accord with the distribution of the sexes in industry. No specific predisposition is noted for either sex.

Age

The kind of substance, the duration of exposure, and the total cumulative dose are more important than the age of an exposed individual.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

Occupational exposure is the most important part of the history. Initially, a temporal relationship may exist between onset of symptoms and work. Subsequently, patients may have more prolonged symptoms, even in the absence of recent exposure. At times, the exposure is subtle and difficult to elicit, thus requiring particular alertness and environmental investigation on the part of the physician.

• The clinical presentation may be acute, subacute, or chronic, depending on the frequency, intensity, and duration of inhalational exposure, and perhaps on host and other factors determining immunopathogenesis. In the acute form, respiratory symptoms may include cough (with or without sputum), dyspnea, wheeze, chest pain, or chest tightness. Constitutional symptoms, such as myalgia, lassitude, and headaches, may also be present. Patients with underlying lung disease tend to present with the more severe symptoms.
• Depending on the exposure intensity and substance, chemical worker's lung may take subacute or chronic forms. The condition may appear over a period of several days to weeks and is marked by cough and dyspnea, which may progress to severe dyspnea with cyanosis. Fatigue and weight loss may be prominent complaints.
• The following is a partial list of diseases that do not fall under the definition of chemical worker's lung:
• • Asbestosis
  • Rubber worker's lung
  • Illness caused by wood dust and formaldehyde exposure
  • Berylliosis
  • Baker-associated occupational asthma
• Lung disease associated with chemical food-flavoring industry
• • Although not included in the definition of chemical worker's lung, an increasing number of chemicals used in the food-flavoring industry are being recognized as contributory to lung disease in employees working in these plants.
  • The safety of these chemicals has been established for humans consuming small amounts in food but not for industry workers inhaling the chemicals. Production workers employed by flavoring manufacturers often handle a large number of chemicals, many of which can be highly irritating to breathe in high concentrations.
  • Recently, diacetyl, the predominant ketone in artificial butter flavoring used in the microwave popcorn industry, was recognized as causing lung disease in employees working in these plants.
  • Occupational exposure guidelines have been developed for only a small number of the thousands of ingredients used in flavorings. The Occupational Safety and Health Administration (OSHA) permissible exposure limits (PELs) and the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limits (RELs) have only been established for fewer than 5% of the flavoring ingredients considered by the flavoring industry to represent potential respiratory hazards due to possible volatility and irritant properties.

Physical

Physical examination findings are usually normal. Other findings may include wheezing and bilateral, generalized, crepitant inspiratory rales. Fever may be present in acute exposure. Cyanosis may be noted in severe disease. Clubbing is not generally expected.

Causes

The list of substances that can be inhaled by a chemical worker and cause lung disease is long. However, by arbitrary definition, the implicated chemicals are restricted to the manufacture of polyurethane foam, molding, insulation, synthetic rubber, and packaging materials and include toluene diisocyanate (TDI) and trimellitic anhydride.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Occupational lung disease
Pneumoconiosis
Reactive airway disease syndrome (RADS)
Bioterrorism and lung disease

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Imaging Studies

• Chest radiography (posteroanterior and lateral) is the first-line imaging modality to help diagnose chemical worker's lung.
• A regular helical chest CT scan is not helpful if results of the chest radiograph are normal. Contrast-enhanced chest CT scans may help to better delineate the various hilar/mediastinal lymph nodes.
• High-resolution CT scan may show ground-glass infiltrates or other abnormalities that are not visualized on chest radiography.

Other Tests

• Pulmonary function testing should include spirometry, lung volumes, and diffusing capacity of the lungs for carbon monoxide (DLCO). Findings may include obstructive and restrictive lung indices. With disease progression, DLCO values will decline.
• Pulmonary physiological testing may be included in the monitoring of disease progression. These tests may include the 6-minute walk test and cardiopulmonary exercise testing.

Procedures

• Flexible bronchoscopy with or without bronchoalveolar lavage (BAL), endobronchial biopsies, endobronchial brushing, transbronchial biopsies, and transbronchial needle aspiration and histology can be helpful.
• Video-assisted thoracoscopy (VATS) is rarely used for larger lung tissue sampling.
• Open lung biopsies are rarely necessary, although they may be useful if the aforementioned tests do not help confirm a diagnosis.

Histologic Findings

Data are few. Expected findings are nonspecific and are probably related to the length of exposure and the specific substance involved.

Staging

A published staging system is not available. Differentiating between nodular and infiltrative lung disease may be useful.

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

Providing health education, reducing exposures, and changing occupation are commonly used strategies. Avoidance of further exposure is critical.

• Advise patients with underlying cardiopulmonary disease to avoid working in occupations that could expose them to hazardous chemicals.
• Baseline pulmonary function studies are useful to help monitor workers in industries that expose them to potentially harmful chemicals.
• Administration of pneumococcal vaccine (q3-5y) and influenzal vaccines (annually) are indicated in persons with lung disease.
• Pulmonary rehabilitation programs should be encouraged

Drug therapies mainly address symptoms and include the following:

• Oxygen supplementation
• Bronchodilators
• Inhaled or systemic steroids (not much evidence supports routine use)
• Treatment of pulmonary hypertension

Surgical Care

With severe parenchymal lung disease, single- or double-lung transplantation should be considered in suitable candidates.

Consultations

Referral to a pulmonologist is recommended for patients with progressive disease.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admitted patients may have acute exacerbation of asthmalike symptoms, fever with bilateral infiltrates, or end-stage lung disease.
• Inpatient management is similar to that of other patients with lung disease.

In/Out Patient Meds

• Steroids, either inhaled or systemic, may be helpful.
• Supplemental oxygen for 18-24 hours per day increases survival rates in patients with advanced lung disease and a PO₂ of less than 60 mm Hg.
• Bronchodilators are used for patients with respiratory symptoms and airway obstruction.

Complications

• Pulmonary fibrosis
• Lung nodules (benign or malignant)
• Bronchial hyperreactivity
• Right heart disease (eg, pulmonary hypertension, cor pulmonale)

Prognosis

• Avoiding exposure to the offending toxin or toxins is essential.
• A change of occupation may be necessary.
• The ultimate prognosis is related to the specific exposure.

Patient Education

• Advise patients that administration of pneumococcal vaccine (q3-5y) and influenzal vaccines (annually) are indicated with lung disease.
• For additional information on flavoring substances, see the NIOSH Pocket Guide to Chemical Hazards.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The differential diagnosis includes many diseases. The length of exposure, the type of chemical, and the temporal relationship with symptoms must all be included in the occupational history.
• Financial compensation is an important issue in occupational disease.

Special Concerns

• Serial medical examinations, pulmonary function tests (including DLCO), and imaging (chest radiography) may be useful to diagnose chemical worker's lung early in its course.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

• Akpinar-Elci M, Kanwal R, Kreiss K. Bronchiolitis obliterans syndrome in popcorn plant workers. Am J Respir Crit Care Med. 2002;165:A526.
• Ali BA, Ahmed HO, Ballal SG, Albar AA. Pulmonary function of workers exposed to ammonia: a study in the Eastern Province of Saudi Arabia. Int J Occup Environ Health. Jan-Mar 2001;7(1):19-22. [Medline].
• American Lung Association. Fact Sheet: Occupational Lung Disease. September 2000. American Lung Association. Available at http://www.lungusa.org/diseases/occupational_factsheet.html.
• Atis S, Tutluoglu B, Levent E, Ozturk C, Tunaci A, Sahin K, et al. The respiratory effects of occupational polypropylene flock exposure. Eur Respir J. Jan 2005;25(1):110-7. [Medline].
• Barhad B, Pilat L, Teculescu D. Recent progress in the study of occupational lung diseases in Romania. Br J Ind Med. May 1975;32(2):164-8. [Medline].
• Berkow R, Beers MH, Fletcher AJ. Lung and airway disorders. In: The Merck Manual of Medical Information, Home Edition, Section 4, Chapter 39. Merck. Available at http://www.merck.com/mmhe/sec04.html.
• Bodner KM, Burns CJ, Randolph NM, Salazar EJ. A longitudinal study of respiratory health of toluene diisocyanate production workers. J Occup Environ Med. Oct 2001;43(10):890-7. [Medline].
• Brooks SM, Lockey JE, Harber P. Occupational Lung Diseases 1. Clin Chest Med. 1981;2:171-300.
• Clark RL, Bugler J, McDermott M, Hill ID, Allport DC, Chamberlain JD. An epidemiology study of lung function changes of toluene diisocyanate foam workers in the United Kingdom. Int Arch Occup Environ Health. May 1998;71(3):169-79. [Medline].
• Craighead JE. Enviromental and occupational aspects of pulmonary disease. In: Saldana MJ, ed. Pathology of Pulmonary Disease. Philadelphia, Pa: Lippincott-Raven; 1994:883-8.
• Hashimoto M, Sato K, Heianna J, Hirano Y, Omachi K, Izumi J. Pulmonary CT findings in acute mercury vapour exposure. Clin Radiol. Jan 2001;56(1):17-21. [Medline].
• Kay S. Toluene diisocyanate and lung function. Food Chem Toxicol. Mar 1985;23(3):411-3. [Medline].
• Kreiss K, Gomaa A, Kullman G, Fedan K, Simoes EJ, Enright PL. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N Engl J Med. Aug 1 2002;347(5):330-8. [Medline].
• Lees PS. Chromium and disease: review of epidemiologic studies with particular reference to etiologic information provided by measures of exposure. Environ Health Perspect. May 1991;92:93-104. [Medline].
• Lockey J, McKay R, Barth E. Bronchiolitis obliterans in the food flavoring manufacturing industry. Am J Respir Crit Care Med. 2002;165:A461.
• McKerrow CB, Davies HJ, Parry Jones A. Symptoms and lung function following acute and chronic exposure to tolylene diisocyanate. Proc R Soc Med. Apr 1970;63(4):376-8. [Medline].
• Mikoczy Z, Welinder H, Tinnerberg H, Hagmar L. Cancer incidence and mortality of isocyanate exposed workers from the Swedish polyurethane foam industry: updated findings 1959-98. Occup Environ Med. May 2004;61(5):432-7. [Medline].
• Olin AC, Alving K, Torén K. Exhaled nitric oxide: relation to sensitization and respiratory symptoms. Clin Exp Allergy. Feb 2004;34(2):221-6. [Medline].
• Osinubi OY, Gochfeld M, Kipen HM. Health effects of asbestos and nonasbestos fibers. Environ Health Perspect. Aug 2000;108 Suppl 4:665-74. [Medline].
• Parmet AJ, Von Essen S. Rapidly progressive, fixed airway obstructive disease in popcorn workers: a new occupational pulmonary illness?. J Occup Environ Med. Mar 2002;44(3):216-8. [Medline].
• Peters JM. Studies of isocyanate toxicity. Proc R Soc Med. Apr 1970;63(4):372-5. [Medline].
• Weill H. Disaster at Bhopal: the accident, early findings and respiratory health outlook in those injured. Bull Eur Physiopathol Respir. Nov-Dec 1987;23(6):587-90. [Medline].
• Zock JP, Sunyer J, Kogevinas M, Kromhout H, Burney P, Antó JM. Occupation, chronic bronchitis, and lung function in young adults. An international study. Am J Respir Crit Care Med. Jun 2001;163(7):1572-7. [Medline].

Article Last Updated: Oct 19, 2007