Prolonged livestock exposure and elevated serum IgE associated with pulmonary fibrosis.

To the Editor: A 48-year-old man presented to the pulmonary clinic with a 2-year history of a persistent dry cough, dyspnea, and an abnormal chest x-ray. The patient smoked 20 cigarettes daily for 20 years. He worked in an animal research laboratory for 12 years. He was exposed to primates, mice, dogs, pigs, rats and sheep. Physical examination on presentation showed a temperature of 98.6[degrees]F, blood pressure of 142/82 mm Hg, heart rate of 76/min and a respiratory rate of 16/min. Chest auscultation revealed bilateral diffuse crackles. Cardiac, abdominal, and neurologic examinations were unremarkable. Bilateral clubbing of both hands was noted. Pulmonary function testing revealed a total lung capacity (TLC) of 4.77 L (69%), a forced expiratory volume (FEV1) of 1.77 L (69%) and a diffusion capacity (DLCO) of 10.8 mL/mm Hg/min (38%). A computed tomography (CT) scan of the chest showed diffuse bilateral inter-stitial fibrosis with honeycombing, especially in the right upper lobe and small mediastinal lymph nodes (Fig.). A complete blood count, serum chemistry, liver function tests, serum angiotensin converting enzyme (ACE) level, anti-Scl-70 antibody, serum complement levels, rheumatoid factor, and erythrocyte sedimentation rate were normal. The antinuclear antibody (ANA), anticentromere antibody, and antineutrophil cytoplasm antibodies were negative. An interesting finding was an elevated serum IgE of 6501 mg/dL (1-180 mg/dL) with normal serum IgG, IgA, and IgM levels. The serum antibody precipitants to Aspergillus niger, A fumigatus, and A flavus were negative.

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A transbronchial biopsy was not diagnostic. Bronchoalveolar lavage (BAL) cultures were negative for bacterial, fungal, and mycobacterial pathogens. BAL differential cell count showed 66% macrophages, 25% neutrophils, 4% lymphocytes, and 5% eosinophils. Flow cytometry of BAL revealed that T-cells accounted for 86% of lymphocytes with a CD4:CD8 ratio of 1.47. Open lung biopsy was performed. Histologic examination of the lung parenchyma showed characteristic findings of usual intestinal pneumonitis (UIP): interstitial pneumonitis with spatial and temporal heterogeneity, frequent fibroblastic foci, no patchy areas of nonspecific pneumonitis, and no evidence of granuloma formation. Elevated serum IgE levels were an unusual finding in our patient. Past medical history was negative for asthma or atopy. Several stool samples and a BAL sample were negative for ova and parasites. We believe that this case represents UIP secondary to occupational exposure to livestock. The elevated IgE level can be explained by the history of exposure.

Several observational and case-controlled studies have suggested that environmental agents and occupational exposure may have an etiologic role in idiopathic pulmonary fibrosis (IPF). (1) A meta-analysis of six case-controlled studies showed that smoking, agriculture, livestock, wood dust, metal dust, and sand exposures are significantly associated with IPF. Iwai et al conducted an autopsy case-controlled study of 1,311 subjects with IPF. The IPF rate was more than two times higher among subjects with occupational exposure to dust or organic solvents compared with those in other jobs. (2)

Elevated serum IgE levels have been reported in patients with pulmonary fibrosis from a variety of conditions. Elevated serum IgE levels have been described in interstitial lung disease caused by asbestos exposure. (3) In one study of patients with pulmonary fibrosis secondary to silicosis, 20.7% of patients had serum IgE levels higher than 400 IU/mL and 9.7% patients had serum IgE levels higher than 1000 IU/mL. (4) Active eosinophilic airway inflammation, increased skin sensitivity to common allergens, increased serum IgE and eosinophilia in peripheral blood have been demonstrated in idiopathic UIP and atopy has been suggested to be an important determinant of susceptibility to cryptogenic fibrosing alveolitis. (5)

In conclusion, we believe this case of UIP may be secondary to prolonged occupational exposure to livestock. High serum IgE levels in patients with UIP may warrant more detailed investigation regarding exposure history.

Bobbak Vahid, MD

Keith Dombrowski, MD

Bharat Awsare, MD

Departments of Pulmonary and Critical Care and Medicine

Thomas Jefferson University Hospital

Philadelphia, PA

References

1. Hubbard R, Lewis S, Richards K, et al. Occupational exposure to metal or wood dust and aetiology of cryptogenic fibrosing alveolitis. Lancet 1996;347:284-289.

2. Iwai K, Mori T, Yamada N, et al. Idiopathic pulmonary fibrosis. Epidemiologic approaches to occupational exposure. Am J Respir Crit Care Med 1994;150:670-675.

3. Ilavska S, Jahnova E, Tulinska J, et al. Immunological monitoring in workers occupationally exposed to asbestos. Toxicology 2005;206:299-308.

4. Watanabe S, Shirakami A, Takeichi T, et al. Alterations in lymphocyte subsets and serum immunoglobulin levels in patients with silicosis. J Clin Lab Immunol 1987;23:45-51.

5. Marsh P, Johnston I, Britton J. Atopy as a risk factor for cryptogenic fibrosing alveolitis. Respir Med 1994;88:369-371.

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