Abstract

BackgroundPrednisone has been shown to reverse lung function declines in hypersensitivity pneumonitis patients without established fibrosis. Second line immunosuppressants like azathioprine and mycophenolate mofetil have a steroid sparing effect and improve DLCO. There is no published literature on the use of leflunomide in such patients.MethodsWe reviewed our experience with leflunomide for treatment of chronic hypersensitivity pneumonitis in 40 patients. We stratified patients according to the presence or absence of significant (> 20%) fibrosis. We studied the effect of leflunomide on FVC and DLCO trajectory and reported the changes at 12 months.ResultsTreatment with leflunomide tended to improve the estimated FVC slope from 0.18 ± 1.90% (SEM) of predicted per year to 4.62 ± 1.65% of predicted (NS, p = 0.118). It significantly improved the FVC at 12 months of treatment by 4.4% of predicted (p = 0.02). DLCO continued to increase at 1.45 ± 1.44% (SEM) of predicted per year. Non-fibrotic cHP patients had the largest gain in pulmonary function. Their FVC increased by 8.3% (p = 0.001) and DLCO by 4.8% (p = 0.011). Patients with fibrotic cHP did not improve. Leflunomide treatment was associated with significant gastrointestinal and other adverse effects leading 40% of patients to discontinue therapy. It had a significant steroid sparing effect with half the patients weaned off prednisone entirely.ConclusionsLeflunomide appears to be a fairly well tolerated steroid sparing immunosuppressant that improves pulmonary function in cHP patients. It is most effective in patients without significant fibrosis.

Highlights

  • Prednisone has been shown to reverse lung function declines in hypersensitivity pneumonitis patients without established fibrosis

  • Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD), characterized by immune-mediated inflammation and fibrosis resulting from inhalational exposure to inciting antigens [1, 2]

  • HP is thought to be mediated by T lymphocytes via Th1/Th2 and Th17 immune response pathways which are associated with granulomatous inflammation and fibrosis [2]

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Summary

Introduction

Prednisone has been shown to reverse lung function declines in hypersensitivity pneumonitis patients without established fibrosis. Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD), characterized by immune-mediated inflammation and fibrosis resulting from inhalational exposure to inciting antigens [1, 2]. It can be classified into acute/inflammatory and chronic/fibrotic phenotypes based on clinical, radiological and pathologic features [3]. Corticosteroids are often used as first line treatment, they may confer no long term benefit [5] Immunosuppressive agents such as azathioprine (AZA) or mycophenolate mofetil (MMF) have been shown to favorably influence pulmonary function in patients with chronic HP [6, 7]

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