This is a randomized, multi-center, open-label Phase II clinical trial to determine the efficacy of combined plasma exchange (PEX), rituximab, and conventional corticosteroid administration, in comparison to corticosteroids alone, among patients with acute Idiopathic Pulmonary Fibrosis (IPF) exacerbations.

The investigators central hypothesis is that antibody-mediated autoimmunity can play an important role in IPF exacerbations. The investigators propose to test our central hypothesis by establishing the efficacy of autoantibody removal by plasma exchange (PEX), in conjunction with B-cell depletion by rituximab to deplete immunoglobulins and minimize their further production, among patients with acute IPF exacerbations.

The primary goal of this randomized, multi-center, open-label Phase II clinical trial is to determine effects of combined plasma exchange (PEX), rituximab, and conventional corticosteroid administration on selected, relevant immunological parameters, in comparison to effects of steroids alone, among AE-IPF patients. The investigators anticipate the findings of this will lead to larger incremental trial(s) to determine actual clinical efficacy of this treatment.

A total of 40 subjects will be enrolled in this multi-center trial from 5 participating medical centers.

This is a randomized, multi-center, open-label Phase II clinical trial to determine the efficacy of combined plasma exchange (PEX), rituximab, and conventional corticosteroid administration, in comparison to corticosteroids alone, among patients with acute IPF exacerbations.

INCLUSION CRITERIA:

1. A diagnosis of idiopathic pulmonary fibrosis that fulfills American Thoracic Society Consensus Criteria.1
2. Unexplained worsening or development of dyspnea or hypoxemia within the preceding 30 days.
3. Radiographic imaging showing ground-glass abnormality and/or consolidation superimposed on a reticular or honeycomb pattern consistent with UIP.

EXCLUSION CRITERIA

1. Diagnosis of documented infection, thromboembolic disease, an additional etiology for acute lung injury/adult respiratory distress syndrome, congestive heart failure.
2. Presence of active hepatitis B infection.
3. Coagulopathy defined as an INR > 1.8, PTT > 2 x control, and platelet count < 50K.
4. Hyperosmolar state or diabetic ketoacidosis to suggest uncontrolled diabetes mellitus or uncontrolled hypertension.
5. Hemodynamic instability.
6. History of reaction to blood products, murine-derived products, or prior exposures to human-murine chimeric antibodies,
7. History of malignancy.
8. Unwillingness to accept a blood transfusion.
9. Unwillingness to agree to full supportive medical care (e.g., intubation) for up to 2 weeks after enrollment.
10. Inability or unwillingness to complete post-treatment surveillance for 60 days.
11. Diagnosis of major comorbidities expected to interfere with subjects study participation for 28 days.
12. Treatment for >5 days within the preceding month with >20 mg prednisone (or equivalent dose corticosteroid) or any treatment during the preceding month with a potent cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, mycophenolate, azathiaprine, calcineurin inhibitors, etc.) unless the patient has a BAL negative for opportunistic pathogens (e.g, Pneumocystis, viruses, intracellular organisms, mycobacteria, etc.).
13. Current treatment with an angiotensin converting enzyme inhibitor that cannot be discontinued and/or substituted with another antihypertensive agent (to minimize potential hemodynamic complications during PEX).