Tobacco Workers Lung Disease

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Practice Essentials

Tobacco worker's lung (TWL) is one disease in the group of parenchymal lung diseases categorized as hypersensitivity pneumonitis or extrinsic allergic alveolitis. This disease entity is caused by inhalation of tobacco molds and is encountered in persons who work in tobacco fields and in cigarette manufacturing plants. Increased humidity plays a major role in favoring mold growth.[1, 2, 3] The clinical features and natural history are akin to hypersensitivity pneumonitis of other causes.[4, 5, 6, 7]

Tobacco worker's lung can affect workers exposed to tobacco leaves and molds in the humidified environment of the tobacco production industry. Limited epidemiologic data point to a prevalence of TWL that is not negligible and probably is underestimated. As with other types of hypersensitivity pneumonitis, an acute versus a chronic presentation depends on the pattern of exposure. Therefore, the clinical presentation can vary from an acute influenza-like syndrome, most often self-limiting with removal of exposure, to an insidious onset of cough, exertional dyspnea, fatigue, and weight loss in chronic presentations, where fibrotic changes may be observed.

Causes

Tobacco worker's lung usually involves inhalation of an antigen, particularly organic ones. This leads to an exaggerated immune response, which produces a complex clinical presentation within the pulmonary parenchyma. Immune mediation plays a major pathogenetic role in TWL. Serum antibodies are present in most patients with TWL, but lack of correlation between presence of serum antibodies and occurrence of pulmonary symptoms has been noted.

Major causative antigens include the following:

In TWL, the primary culprit antigen is the Aspergillus species, with the source in tobacco molds. These antigens induce injury by causing macrophages and polymorphonuclear leukocytes to produce substances such as proteolytic enzymes and reactive oxygen compounds, further leading to synthesis and release of interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and IL-6 from macrophages and lymphokines from lymphocytes, all of which result in pulmonary inflammation. Lung biopsies in patients with long-term exposure usually reveal chronic interstitial inflammation and poorly formed nonnecrotizing granulomas.[9]

In addition, smoking can potentiate the effects of tobacco dust.[10]

Studies have shown that there may be a genetic predisposition to hypersensitivity pneumonitis, which is postulated to play a major role in an individual's risk of disease. It is likely that immunologic abnormalities that underlie hypersensitivity pneumonitis reflect the interplay of multiple genes involved in the immune response. Genetic involvement can be extrapolated to apply to risk for TWL.[11]

Diagnosis

Lung biopsy is rarely required to confirm the diagnosis because diagnosis is primarily derived from a thorough occupational history, assessment of clinical features, and review of radiography results. Both transbronchial and video-assisted thoracoscopic lung biopsies are done to obtain adequate specimens for histopathologic examination.[12]

Treatment and prevention

The main treatment strategy consists of removal of exposure to tobacco dust and molds, and the main aim of corticosteroid therapy is to reduce morbidity and prevent complications—namely, the development of pulmonary fibrosis and permanent lung dysfunction. Preventing further exposure to offending agents usually leads to symptom resolution.

Avoidance of exposure to tobacco leaves is the best prevention. Curwin and associates reported that washing hands in the field while harvesting significantly reduces the amount of nicotine absorbed through the skin.[13]

Devices that limit inhalation of inciting antigens are recommended for those who must continue to work on tobacco farms. Installing controls that reduce moisture and humidity in occupied buildings helps to prevent excessively moldy tobacco leaves.

History

A comprehensive history of exposure to tobacco mold and leaves should be obtained. Workers who do not use masks during their working period are 5 times more likely to develop this disease,[14] and longer duration of work is associated with increased risk of disease. In one study, those working with tobacco for longer than 10 years were twice as likely to develop the disease than those who worked in the field for less than 5 years.[14]

Tobacco worker’s lung, as with most hypersensitivity pneumonitis syndromes, has acute, subacute, and chronic presentations. In acute presentations, patients develop abrupt onset of fever, cough, chills, myalgias, headache, and malaise about 4 to 6 hours after exposure to tobacco plants and molds. These symptoms are self-limited, resolving in 12 hours to several days once the patient avoids the inciting agent. Symptoms may recur with reexposure.

Patients who have had long-term exposure to tobacco plantations usually have insidious onset of cough, exertional dyspnea, fatigue, and weight loss. Disabling and irreversible respiratory findings due to pulmonary fibrosis may occur late in the course of the disease. Removing patients from tobacco exposure results in only partial improvement.

Physical

Physical examination reveals the following:

Laboratory Studies

There are no specific tests for tobacco worker's lung (TWL); the diagnosis is established with a history of exposure and possibly with the support of the following tests:

Nonspecific markers of inflammation such as the following are elevated:

Pulmonary function testing shows mostly restrictive patterns with occasionally mixed restrictive and obstructive patterns, impaired diffusion capacity, and lung volume loss. Peak expiratory flow rates are reduced.[19]

Arterial hypoxemia with hypocapnia reflecting an increased A-a oxygen gradient commonly occurs at rest, with further worsening on exercise.

Imaging Studies

No distinctive changes are noted on chest radiography, but progressive fibrotic changes associated with upper lobe volume loss or diffuse reticulonodular infiltrates may be evident in chronic exposure. In acute exposure, the infiltrates usually are more prevalent in the lower lobes.

High-resolution computed tomography (HRCT) scan may show a ground-glass appearance, prominent medium-sized bronchial walls, parenchymal micronodules, and absence of hilar adenopathy.

(See the images below.)



View Image

High-resolution CT scan of lungs shows ground-glass opacification seen in an acute phase of tobacco worker's lung.



View Image

High-resolution CT (HRCT) scan shows a ground-glass appearance and reticulonodular opacities in subacute phase of hypersensitivity pneumonitis (HP) se....

Histologic Findings

Samples from lung biopsies show chronic interstitial inflammation with infiltration of plasma cells, mast cells, macrophages, and lymphocytes, usually with poorly formed nonnecrotizing granulomas. The granulomas are loosely formed and tend to occur close to the bronchioles. Cholesterol clefts and giant cells, as shown in the image below, are observed within and outside the granulomas.



View Image

Giant cells are a characteristic feature of acute tobacco worker's lung, which is a form of hypersensitivity pneumonitis.

Medical Care

The major treatment strategy is elimination of exposure to tobacco molds or leaves. Preventing further exposure to offending agents usually leads to symptom resolution.

Most available studies have focused on farmer's lung. Because farmer's lung has strong similarities to tobacco worker's lung, treatment strategies for TWL are generally extrapolated from those for farmer's lung. Antigen avoidance usually results in disease regression, but corticosteroid treatment may be required in more severe cases.

Corticosteroids are effective for initial recovery in severely ill patients; however, the long-term outcome appears unchanged by corticosteroid treatment.[20] Treatment is recommended for patients with subacute or chronic disease presentations and for patients with persistent symptoms, abnormal pulmonary function tests, hypoxemia, and radiographic evidence of extensive lung involvement.

Therapy is usually initiated with prednisone, 0.5 to 1 mg/kg of ideal body weight daily (maximum daily dose, 60 mg/day), given as a single dose each morning. This dose is maintained for about 2 weeks and is tapered over the next 2 to 4 weeks.

Maintenance doses are not necessary, assuming patients have implemented good measures to avoid the culprit antigen. Inhaled corticosteroids might be an option, but no strong supporting data are available at the present time.

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications. Avoiding exposure to antigen usually results in regression of disease, but corticosteroid treatment may be required in more severe cases. However, long-term outcomes appear unchanged by treatment.

Prednisone

Clinical Context:  May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

Prednisolone (Millipred, Orapred, Prelone)

Clinical Context:  Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Methylprednisolone (A-Methapred, Medrol, Solu-Medrol)

Clinical Context:  Decreases inflammation by suppressing migration of PMNs and reversing increased capillary permeability.

Class Summary

Corticosteroids are recommended for patients with subacute or chronic disease presentations and for patients with persistent symptoms, abnormal pulmonary function tests, hypoxemia, and radiographic evidence of extensive lung involvement.

Author

Roger B Olade, MD, MPH, Medical Director, Genesis Health Group

Disclosure: Nothing to disclose.

Coauthor(s)

Jazeela Fayyaz, DO, Attending Physician, Department of Pulmonary and Sleep Medicine, Medical Director of Sleep Lab, Unity Hospital

Disclosure: Nothing to disclose.

Klaus-Dieter Lessnau, MD, FCCP, Former Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP, Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba Faculty of Medicine; Site Director, Respiratory Medicine, St Boniface General Hospital, Canada

Disclosure: Nothing to disclose.

Acknowledgements

Gregg T Anders, DO Medical Director, Great Plains Regional Medical Command , Brooke Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio

Disclosure: Nothing to disclose.

References

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High-resolution CT scan of lungs shows ground-glass opacification seen in an acute phase of tobacco worker's lung.

High-resolution CT (HRCT) scan shows a ground-glass appearance and reticulonodular opacities in subacute phase of hypersensitivity pneumonitis (HP) secondary to moldy hay.

Giant cells are a characteristic feature of acute tobacco worker's lung, which is a form of hypersensitivity pneumonitis.

High-resolution CT scan of lungs shows ground-glass opacification seen in an acute phase of tobacco worker's lung.

Giant cells are a characteristic feature of acute tobacco worker's lung, which is a form of hypersensitivity pneumonitis.

High-resolution CT (HRCT) scan shows a ground-glass appearance and reticulonodular opacities in subacute phase of hypersensitivity pneumonitis (HP) secondary to moldy hay.