Tobacco Worker's Lung

Updated: Apr 17, 2018
Author: Roger B Olade, MD, MPH; Chief Editor: Zab Mosenifar, MD, FACP, FCCP 


Practice Essentials

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

TWL 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 tobacco worker’s lung. Serum antibodies are present in most patients with tobacco worker’s lung, but a lack of correlation between the presence of serum antibodies and pulmonary symptoms has been noted.

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

In addition, smoking can potentiate the effects of tobacco dust.[7]

Studies have shown that there may be a genetic predisposition to hypersensitivity pneumonitis, postulated to play a major role in determining an individual's risk of disease. It is likely that the 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 tobacco worker's lung.[8]

Major causative antigens include the following:

  • Aspergillus species

  • Scopulariopsis brevicaulis

  • Rhizopus nigricans[9]

Lung biopsies are rarely required to confirm diagnosis, because diagnosis is primarily derived from a thorough occupational history, clinical features, and radiography. Both transbronchial and video-assisted thoracoscopic lung biopsy are used to provide adequate specimens for histopathological examination.[10]

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

Avoidance of exposure to tobacco leaves is the best prevention. Curwin et al report that washing hands in the field while harvesting significantly reduces the amount of nicotine absorbed through the skin.[11]

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




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,[12] and longer duration of work is associated with an increased risk of disease. In one study, those working with tobacco for more than 10 years were twice as likely to develop the disease than those who worked in the field for less than 5 years.[12]

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 4-6 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. The 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 examination reveals the following:

  • Tachypnea

  • Diffuse fine rales

  • Wheezing

  • Weight loss

  • Digital clubbing

  • Fever

  • Evidence of cor pulmonale





Laboratory Studies

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

  • Elevated serum levels of angiotensin-converting enzyme (ACE), N-acetyl-beta-glucosaminidase (NAG), and beta-glucuronidase (beta-GLU) may be present. Elevation of these enzymes does not have a high sensitivity or specificity.[13]

  • Bronchoalveolar lavage (BAL) may show lymphocytosis, neutrophilia or eosinophilia, and reversal of CD4/CD8 ratio.[14]

  • Immunoglobulin G, immunoglobulin M, and immunoglobulin A serum antibodies to causative antigens may be present.

  • Nonsmoking tobacco harvesters may have cotinine and nicotine levels as high as active smokers in the general populations.[15]

  • ImmunoCAP technology can detect IgG antibodies against Aspergillus fumigatus.[16]

Nonspecific markers of inflammation, such as the following, are elevated:

  • Elevated erythrocyte sedimentation rate

  • Elevated C-reactive protein

  • Positive rheumatoid factor

  • Elevated serum lactate dehydrogenase (LDH)

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 also are reduced.[17]

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 it might show progressive fibrotic changes associated with upper lobe volume loss or diffuse reticulonodular infiltrates in chronic exposure. In acute exposure, the infiltrates are usually 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.)

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

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 in proximity to the bronchioles. Cholesterol clefts and giant cells, as shown in the image below, also are observed within and outside the granulomas.

Giant cells are a characteristic feature of acute 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 the offending agents usually leads to symptom resolution.

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

Corticosteroids are effective in the initial recovery in severely ill patients; however, the long-term outcome appears unchanged by corticosteroid treatment.[18] Treatment is recommended in patients with subacute or chronic disease presentations, 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 (up to a maximum daily dose of 60 mg per day), given as a single dose each morning. This dose is maintained for about 2 weeks and then tapered over the next 2-4 weeks.

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



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 outcome appears unchanged by the treatment.


Class Summary

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


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)

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

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

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