Farmer's Lung

Farmer's lung is a type of hypersensitivity pneumonitis. Hypersensitivity pneumonitis, also known as extrinsic allergic alveolitis, is an immunologically mediated inflammatory disease of the lung involving the terminal airways. The condition is associated with intense or repeated exposure to inhaled biologic dusts. The classic presentation of farmer's lung results from inhalation exposure to thermophilic Actinomyces species and occasionally from exposure to various Aspergillus species.[1]

The thermophilic actinomycetes are ubiquitous organisms usually found in contaminated ventilation systems and in decaying compost, hay, and sugar cane (bagasse). Exposure to large quantities of contaminated hay is the most common source of inhalation exposure in farmers who develop farmer's lung[2] ; therefore, grain farmers are not at risk for the development of the disease.

Farming practices change over time and antigens may be introduced to or disappear from a region (eg, the disappearance of bagassosis in Louisiana sugar cane workers,[3] the appearance of Pseudomonas fluorescens in machine operator's lung). Exposure to the causative antigens depends on the type of farming, industry, and climate in the area; the changing environment may lead to new challenges for the clinician.

In addition to the inhalation exposure to the organic dusts responsible for the hypersensitivity reaction in farmer's lung disease, allergens, chemicals, toxic gases, and infectious agents must also be considered as potential triggers of airway symptoms in symptomatic farmers. Farming is among the most hazardous occupations, along with construction and mining.[4, 5]

No single diagnostic or clinical laboratory study is specific to the diagnosis of farmer's lung. The most important diagnostic tool is a detailed environmental history. Systemic corticosteroid administration and avoidance measures constitute the primary treatment for farmer's lung. Farmer's lung is prevented by complete avoidance of antigens. Protective devices (eg, masks) help reduce the amount of exposure. Maintaining humidity at less than 60% and keeping hay on farms dry and well protected discourages microbial growth.

The pathogenesis of farmer's lung depends on the intensity, frequency, and duration of exposure and on host response to the causative antigen. Both humoral and cell-mediated immune responses seem to play a role in the pathogenesis of farmer's lung. During acute episodes, acute neutrophilic infiltration is followed by lymphocytic infiltration of the airways. Levels of interleukins 1 and 8 and tumor necrosis factor-alpha are increased.[6] These cytokines have proinflammatory and chemotactic properties. They cause the recruitment of additional inflammatory mediators, resulting in direct cellular damage and changes in the complement pathway, which provide the necessary stimuli to increase vascular permeability and migration of leukocytes to the lung.[7, 8]

If the acute exposure is large, a dramatic increase in inflammation leads to increased vascular permeability, which can alter the alveolar capillary units, thus promoting hypoxemia and decreased lung compliance. If the exposure is prolonged and continuous, collagen deposition and destruction of the lung parenchyma occur with resultant decreased lung volumes.

Strong evidence suggests the involvement of immune complex–induced tissue injury (type III hypersensitivity). The timing of the development of symptoms after exposure supports this conclusion. The presence of antigen-specific immunoglobulin and complement activation and deposition in the lung also supports immune-complex or type III hypersensitivity in the pathogenesis of farmer's lung.

Cell-mediated, delayed-type hypersensitivity (type IV hypersensitivity) also plays a major role in the pathophysiology of this syndrome. The presence of lymphocytes, macrophages, and granulomas in the alveolar spaces and the interstitium supports this conclusion.

Farmer's lung results from inhalation exposure to thermophilic Actinomyces species and occasionally from exposure to various Aspergillus species. Thermophilic actinomycetes species include Saccharopolyspora rectivirgula (formerly Micropolyspora faeni), Thermoactinomyces vulgaris, Thermoactinomyces viridis, and Thermoactinomyces sacchari, among others.[9] In Japan, Aspergillus niger has been reported as a causative agent.[10]

These organisms flourish in areas of high humidity and prefer temperatures of 40-60°C. Exposure to the causative antigens depends on the type of farming, industry, and climate in the area.

The prevalence of hypersensitivity pneumonitis ranges from 5-15% in individuals exposed to one allergen, and the frequency of the disease is related to several factors (the amount of allergen inhaled, the duration of exposure, the nature of the antigen, and the host immune response). Heredity may play an important role, with families positive for HLA-DR7, HLA-B8, and HLA-DQw3 showing a stronger predisposition.[11]

United States data

Farmer's lung is one of the most frequent types of hypersensitivity pneumonitis. Note the following:

• Incidence is highly variable and depends on multiple factors, such as intensity, frequency, and duration of exposure, type of farming, and climate.

• An incidence of 8-540 cases per 100,000 persons per year for farmers has been reported.

• Hypersensitivity pneumonitis affects 0.4-7% of the farming population.

• In a 2007 study in the United States, farmer's lung accounted for 11% of cases of hypersensitivity pneumonitis.[12]

International data

As reported in 2006, farmer's lung appears to be on the decline, at least in some parts of the world. Effective changes in farming practice and an increase in awareness of the disease has contributed to this decline. Note the following:

• Between 1996-2015, the annual incidence of hypersensitivity pneumonitis in the United Kingdom was 1.4 per million workers but the proportion of cases due to agricultural exposures fell from 44% to 12%.[13]

• A prevalence of 5.7% was reported in greenhouse farmers in rural regions of Northeastern China.[14]

• In Japan, the prevalence of farmer's lung is 5.8% and hypersensitivity pneumonitis among pigeon breeders is 10.4%.[10]

The long-term prognosis of farmer's lung varies and depends on the extent of fibrosis and the amount of irreversible damage to the lung parenchyma.[15] In some patients, the disease may progress even after the antigen exposure has been eliminated.

If the diagnosis of farmer's lung is confirmed before irreversible changes have developed, most patients recover with minimal functional abnormalities and few become disabled. In the acute stages, restriction with decreased static compliance and diffusing capacity that reverses over several weeks (with antigen avoidance) may occur. In subacute disease, bronchiolitis and granuloma formation might be slower to resolve even with corticosteroid therapy.

Individuals with a ground-glass appearance on high-resolution CT scans of the chest have higher response rates to systemic corticosteroids. Patients with honeycombing or pulmonary fibrosis may have less than a 20% response to corticosteroids and a mortality rate greater than 90% at 5 years after diagnosis.

Predictors of long-term decline in farmer's lung include recurrent acute episodes, allergy to mites, organic dust, and fungal elements, and smoking, which promotes deterioration of lung function in patients diagnosed with farmer's lung.[16]

The mortality rate from farmer's lung is reportedly 0-20% and death usually occurs 5 years after diagnosis. Several factors have been shown to increase mortality rates including clinical symptoms occurring more than 1 year before diagnosis, symptomatic recurrence, and pulmonary fibrosis at the time of diagnosis.

Although a history of smoking appears to decrease the overall risk for the development of hypersensitivity pneumonitis, a smoking history is the strongest predictor of increased respiratory symptoms once the diagnosis is made. Preexisting bronchial hyperreactivity with airway obstruction is also a factor.

Complications

Complications of farmer's lung include the following:

• Cor pulmonale

• Hypoxemic respiratory failure

• Pulmonary fibrosis

• Emphysema[17]

Environmental control and complete avoidance of the antigen should be the goal. Complete avoidance of the environment or farm may be required to ensure prevention of chronic disease and survival.

Many farmers have thought that salting the hay can prevent the growth of molds in the hay. However, salting does not significantly decrease the amount of Saccharopolyspora rectivirgula (the actinomycetes most commonly involved in farmer's lung disease). Therefore, palatable hay is not safe hay. Salting of hay may provide a false sense of security that the farmer is protected from developing farmer's lung; this false notion should be dispelled.[18]

For patient education information, see Bronchoscopy.

The clinical syndrome of farmer's lung, as with other types of hypersensitivity pneumonitis, is categorized as acute, subacute, or chronic.

Acute farmer's lung develops after large exposure to moldy hay or contaminated compost. Symptoms often spontaneously resolve within 12 hours to days if antigen exposure is eliminated or avoided. Acute farmer's lung manifests as new onset of fever, chills, nonproductive cough, chest tightness, dyspnea, headache, and malaise. If the inhalational exposure is large, patients may develop acute respiratory failure.

Subacute farmer's lung manifests as chronic cough, dyspnea, anorexia, and weight loss. Subacute disease is insidious in onset and may occur over weeks to months.

Chronic farmer's lung results from prolonged and continuous exposure to the antigen. Patients may have irreversible lung damage. Patients may experience severe dyspnea at rest or with exertion.

In acute farmer's lung, physical findings are as follows:

• Fever

• Tachycardia

• Nonproductive cough

• Rales

• Rales that persist after fever subsides

• Wheezing (rare)

In subacute farmer's lung, physical findings are as follows:

• Normal examination findings between presentations

• Anorexia

• Weight loss

• Chronic nonproductive cough

• Generalized fatigue

In chronic farmer's lung, physical findings are as follows:

• Bibasilar rales

• Clubbing - More often observed in patients with chronic farmer's lung with long-standing hypoxemia and parenchymal damage

• Anorexia

• More severe dyspnea

• Weight loss

• Impaired exercise tolerance

No single diagnostic or clinical laboratory study is specific to the diagnosis of farmer's lung. The most important diagnostic tool is a detailed environmental history.

Guidelines for diagnosis of farmer's lung include the following:

Major criteria

• Symptoms compatible with hypersensitivity pneumonitis

• Evidence of exposure to appropriate antigen by history or detection of antigen-specific antibody in serum and/or BAL fluid

• Characteristic radiographic changes on plain radiographs or high-resolution CT scans

• Bronchoalveolar lymphocytes (if BAL was performed)

• Pulmonary histological changes compatible with hypersensitivity pneumonitis (if lung biopsy was performed)

• Positive natural challenge findings (reproduction of symptoms and laboratory abnormalities after exposure to the probable environment)

Minor criteria

• Presence of bibasilar rales

• Decreased diffusion capacity

• Arterial hypoxemia either at rest or during exercise

Leukocytosis with neutrophilia (but not eosinophilia) and elevated erythrocyte sedimentation rate (ESR), C-reactive protein level, and quantitative immunoglobulin level are noted. Precipitating immunoglobulin G (IgG) antibodies confirms past exposure but does not indicate active disease.

Precipitating antibodies are present in up to 50% of asymptomatic farmers exposed to the antigen.[19]

In farmer's lung, negative precipitin results have been reported because of a lack of appropriate antigen selection in serologic commercial testing.

Laboratories must select antigens based on knowledge of local climate and agricultural practices rather than reliance on commercially available antigen panels.

Chest radiography

Findings are normal between acute attacks. Findings are abnormal during acute and subacute stages of disease.

Diffuse air-space consolidation is typical of acute farmer's lung (with acute antigen exposure). Nodular or reticulonodular pattern is characteristic of the subacute phase. Linear radiodensities may be discovered and indicate areas of fibrosis from previous attacks.

Pulmonary apices are often spared on plain chest radiography.

High-resolution computed tomography

High resolution CT scanning is a superior diagnostic modality compared with plain radiography. A normal finding on high-resolution CT scans eliminates the possibility of active acute or chronic farmer's lung.

Pulmonary fibrosis with honeycombing is observed in chronic disease. Peri-bronchovascular distribution of nodules with ground-glass attenuation may be observed.

Pulmonary function tests

Spirometry findings may be normal between attacks and before the development of chronic disease. Acute, subacute, and chronic forms of farmer's lung have a restrictive ventilatory pattern with reduced forced vital capacity (FVC), reduced total lung capacity (TLC), and preserved airflow.

Mild-to-severe hypoxemia at rest or during minimal exercise may be present with active disease. Decreased diffusion capacity is present with active disease.

Bronchoscopy

Bronchoscopy is useful to exclude other disease processes in the acute setting and to obtain bronchoalveolar lavage (BAL) fluid samples for cell counts. Transbronchial biopsy may show evidence of peri-bronchovascular granuloma formation supporting the diagnosis, but its yield is limited because of sampling size.

Open lung biopsy

Open lung biopsy is considered if noninvasive tests are equivocal or inconclusive or if the patient's presentation is atypical in the presence of significant clinical evidence for the disease.

Chronic interstitial inflammation is present with infiltration of plasma cells, mast cells, histiocytes, and lymphocytes. Small and poorly organized nonnecrotizing granulomas are present, usually adjacent to bronchioles. Interstitial fibrosis is often present in chronic disease. Changes consistent with bronchiolitis obliterans may be evident.

Systemic corticosteroid administration and avoidance measures constitute the primary treatment for farmer's lung. Patients may decrease activity because of cough and dyspnea on exertion. In a patient with acute farmer's lung, pulmonary function improves once antigen exposure is eliminated. Between episodes of acute disease, activity may be unlimited.

In patients who develop progressive fibrosis, lung transplantation should be considered.[20]

Follow-up care should include routine spirometry with lung volumes and diffusion capacity, arterial PO2 and arterial-alveolar gradient assessment, and chest radiographs. Consider high-resolution CT scans of the chest to seek resolution of infiltrates or presence of ground-glass opacities that may indicate a need for further treatment with corticosteroids and/or continued insult to the lungs by antigen exposure.

Systemic corticosteroids (combined with avoidance measures) are the primary agents used to treat farmer's lung.

Nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, cromolyn, nedocromil) or systemic immune modulators are not indicated for treatment at this time.

Class Summary

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Orasone, Meticorten)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prescribed for severe symptoms or significant lung dysfunction despite antigen avoidance.