Occupational lung diseases refers to the development of lung diseases from inhalational exposure that occurs at the work place. However, these lung diseases may also occur in environments other than work, even home. Occupational lung disease can result from inhalational exposure to minerals and dusts, microbes, animal and insect proteins, and chemicals and can have long-lasting effects even after the exposure ceases.
Chemical worker's lung refer to the development of lung disease in the work environment from inhalational exposure to chemicals. The U.S. Occupational Safety and Health Administration (OSHA) has established 8-hour time-weighted averages (TWA) on the airborne concentrations of hazardous chemicals. These permissible exposure limits (PELs) have been established for approximately 500 chemicals; however, many of the limits are outdated and there are many chemicals for which OSHA had not yet set a workplace exposure limit.[1]
Additionally, nanoparticles are engineered particles less than 100 nm.[2, 3] Commercially, nanoparticles are used in various industries. Nanoparticles like zinc oxide are widely used in sunscreens, paints, textiles, and other products and can lead to accidental occupational inhalational exposure. Few occupational exposure limits exist specifically for nanomaterials and certain nanoparticles may be more hazardous than larger particles of the same substance. Therefore, existing occupational exposure limits for a substance may not provide adequate protection from nanoparticles of that substance. For example, OSHA has issued a PEL nanoscale particles of titanium dioxide (TiO2) that exposure should not exceed 0.3 milligrams per cubic meter (mg/m3). By contrast, the recommended exposure limit for fine-sized TiO2 (particle size greater than 100 nm) is 2.4 mg/m3. Because exposure limits for most nanomaterials do not exist yet, OSHA recommends that worker exposure should be minimized by using the hazard control measures and best practices that include engineering controls, administrative controls, personal protective equipment and regular medical screening and surveillance.[2, 3]
Workplace exposure to inhaled chemicals can lead to changes in the airway, lung parenchyma, blood vessels, and pleura or a combination of these structures in the lung. Systemic manifestations may also be present, depending on the chemical exposure.
The nasal mucosa and airway are the first areas of contact with inhalational exposures to chemicals. Larger particles are trapped and deposited within the nares, whereas the smaller particles are deposited in the trachea, bronchi, and bronchioles; only particles smaller than 5 micrometers may reach the alveoli. More soluble gases may be directly absorbed from the nasal mucosa while lesser soluble gases may be absorbed further down the respiratory mucosa. This can lead to vascular dilatation, mucosal edema, and rhinorrhea resulting in sneezing, nasal stuffiness, drainage, epistaxis, and even septal perforation (eg, with arsenic, chromic acid).
Occupational rhinitis usually results in worsening of symptoms at the workplace and tends not to have seasonal variation in symptoms.
Tracheitis, acute and chronic bronchitis, and bronchiolitis can result from the airway inflammation. Bronchiolitis obliterans has also been reported with certain chemicals (eg, chlorine, phosgene, nitrogen dioxide). Manifestations include cough with and without sputum production, shortness of breath, and even hemoptysis.
Chemical irritation of the airway can result in the development of new onset asthma or worsening of prior symptoms of asthma. Higher molecular weight antigens stimulate the release of IgE. Patients with a history of atopy and smokers are at a higher risk for developing asthma. Lower molecular weight antigens can induce airway sensititzation without the mediation of IgE. Examples of substances that can result in asthma include acid anhydrides used in epoxy adhesives and paints. Isocyanates used in polyurethane paints and foam are commonly associated with asthma.[4]
A commonly asked employer question is why other coworkers do not have similar complaints of occupational asthma (OA). Development of OA is also genetically mediated with several different associated HLAs being implicated.
Chronic obstructive pulmonary disease (COPD) can develop following exposure to chemicals.[5]
Chemicals like anhydrides, diisocyanates including trimellitic anhydrides, and other chemicals can result in hypersensitvity pneumonitis (HP). The onset may be acute, subacute, or chronic, depending on the intensity, duration, and susceptibility of the patient.
The list of chemicals that can result in HP continues to increase. Symptoms include fever, chills, fatigue, cough, shortness of breath, and cough. Recurrent exposure can lead to interstitial lung disease and pulmonary vascular pathologies.
As the pulmonary parenchymal involvement progresses, it may lead to the development of pulmonary arterial hypertension.
Occupational lung cancer can result from exposure to a variety of chemicals used in the manufacturing of pesticides and water and flame repellents. These chemicals and be found in the National Toxicology Program Report on Carcinogens.
The list of chemicals asociated with lung disease continues to increase. Traditionally the implicated industries included the manufacture polyurethane foam, molding, insulation, synthetic rubber, and packaging materials and include toluene diisocyanate (TDI)[6, 7, 8, 9] and trimellitic anhydride. However, with the development of newer chemical agents and with the novel use of existing agents the industries being associated with lung disease continue to expand.
As discussed earlier, nanoparticles, particularly engineered nanoparticles, are a relatively new, emerging occupational and environment exposure that can lead to the development of lung disease.[10, 11, 12] A unique feature of nanoparticles is their very large surface area-to-mass ratio, indicating their toxic effects may be more related to surface area than mass.[12] An increasing area of concern is that engineered nanoparticles may exhibit new or increased reactivity and increased toxic effects following inhalation exposure.[12] The Occupational Safety and Health Administration (OSHA) has a site dedicated to working safely with nanotechnology at https://www.osha.gov/dsg/nanotechnology/index.html[3]
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. Prevalence varies in accord with the distribution of the sexes in industry. No specific predisposition is noted for either sex. The kind of substance, the duration of exposure, and the total cumulative dose are more important than the age of an exposed individual.
The ultimate prognosis is related to the specific exposure. Mortality and morbidity vary with the substance and the frequency, intensity, and duration of inhalational exposure. Host factors include underlying cardiopulmonary disease and immunopathogenesis.
A study by Hart et al assessed ambient air pollution exposures and mortality.[13] The study concluded that cause-specific mortality (ie, lung cancer, cardiovascular and respiratory disease) were observed with particulate matter less than 2.5 micrometers in diameter, sulfur dioxide, and nitrogen dioxide, but not with particulate matter less than 10 micrometers in diameter.
Complications may include the following:
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 medical history should include the onset and timing of the patient’s chest symptoms, past medical history, review of systems, current medications, family history, and personal habits, including use of tobacco, alcohol, and recreational drugs. The components of a detailed occupational history include current, past, and longest held jobs; job description(s); and symptoms during or after exposure to specific fumes, dusts, and chemicals. Information on nonoccupational exposures, particularly those associated with particular hobbies or recreational activities, should be elicited.[14]
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 earlier and with the more severe symptoms.
Findings at lung examination are generally nonspecific and often occur late in the course of chronic occupational pulmonary diseases. For interstitial diseases, inspiratory crackles on auscultation reflect later stages of fibrosis and may be accompanied by digital clubbing and findings of right heart failure. For occupational airways diseases, physical examination findings are often normal. Wheezing may be a sign of large airways obstruction, and end-inspiratory squeaks may be heard in patients with bronchiolitis. Signs of pulmonary arterial hypertension like an elevated jugular venous pressure (JVP), loud P2, pedal edema, and an enlarged liver maybe seen.
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. A careful exposure history in combination with imaging and pulmonary function testing is often enough to make the diagnosis of an occupational lung disease. For example occupational asthma and most other obstructive lung diseases are diagnosed without histologic findings and the pneumoconioses usually have distinct imaging abnormalities and common occupational histories. Depending on the occupational history and suspected, serologic and other laboratory studies may help distinguish exposure-related diseases from autoimmune and other conditions that may be included in the differential diagnosis.
Chest radiography (posteroanterior and lateral) is the first-line imaging modality to help diagnose chemical worker's lung.
CT is commonly used as a secondary screening modality in symptomatic or physiologically impaired workers when the chest radiograph is normal or equivocal. CT is particularly useful in identifying and characterizing atypical presentations of occupational lung disease.
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.
The National Comprehensive Cancer Network (NCCN) recommends low dose CT (LDCT) lung cancer screening for people aged 50 and older with smoking histories of 20 or greater pack-years and one additional risk factor other than second-hand smoke. These other risk factors include occupational exposure to agents identified as carcinogens targeting the lungs. The NCCN guidelines do not specify a threshold for level of exposure to an occupational agent that is necessary to trigger surveillance. [18]
Low dose CT (LDCT) may also be used to screen for pneumoconiosis.
Pulmonary function tests are essential to determining lung disease pathophysiology, severity and management. Pulmonary function testing should include spirometry, lung volumes, and diffusing capacity of the lungs for carbon monoxide (DLCO). Occupational lung diseases are often characterized as obstructive, restrictive, or a combination of both. 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. Cardiopulmonary exercise testing can be helpful in determining the presence and degree of ventilatory and gas exchange abnormalities, in clarifying the presence of cardiac disease as a source of chest symptoms, and in determining lung disease severity and impairment.[14]
Interpretation of pulmonary function test results may be further enhanced when considered in relation to CT data. For example, subjects with normal spirometry findings but low lung diffusion capacity may have mixed emphysema and lung fibrosis evident on CT scans.[14]
Other testing may include echocardiogram, right heart catheterization, and sampling of pleural effusion.
Lung biopsy may be considered when diagnostic uncertainty exists. Fiberoptic bronchoscopy, with bronchoaveolar lavage and transbronchial biopsies, are useful in the evaluation of exposure-related granulomatous lung disease such as hypersensitivity pneumonitis. Surgical lung biopsy may be required to confirm a diagnosis of bronchiolitis or diffuse interstitial lung disease.
Video-assisted thoracoscopy (VATS) is rarely used for larger lung tissue sampling.
A published staging system is not available. Differentiating between nodular and infiltrative lung disease may be useful.
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. As the management approach is largely supportive, the opportunity to use the hospital admission to educate the patient of the avoidance of future exposure cannot be overemphasized.
Treatment generally involves the following:
Acute respiratory failure may require non- invasive BiPAP or even invasive mechanical ventilation. On rare occasions depending on the chemical inhaled and the dose intensity transient ECMO support maybe needed. In the presence of chemical induced malignancy, therapy directed to to treat this complication is indicated.
Referral to a pulmonologist is recommended for patients with progressive disease.
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.
In patients with hypersensitivity pneumonitis (HP) who develop progressive fibrosis, lung transplantation should be considered. [19]
Avoiding exposure to the offending toxin or toxins is essential. A change of occupation may be necessary. Industries known to be associated with lung disease should have routine screening of all workers who may become exposed to the offending agent. This should include repeated questionaires, spirometry, complete pulmonary function tests (PFTs), and, if needed, appropriate imaging studies. If concerning symptoms or findings are found, referral to a pulmonologist or occupational health physician is recommended.
Complete PFTs should be done at the time of employment, spirometry and complete PFTs during employment, and after termination of employment. This becomes extremely important in patients with pre-existing lung disease.
Longitundinal trending changes in FEV1 may also be used for monitoring. If a decline in FEV1 greater than 15% is noted from the workers pervious best, this indicates the need for a complete PFT (even if within the normal limits), and a repeat complete PFT be performed in 4-6 weeks. If the results are persistent, then specialist consultation is recommended as objective testing such as high-resolution CT chest may be indicated.
If a workplace lung disease is suggested, the physician should strongly recommend avoidance of further exposure. Use of protective gear may not always prevent exposure; thus, total avoidance of further exposure by alternative employment or change of work responsibilities is recommended.