Pulmonary alveolar proteinosis occurs as an idiopathic disease, or can be secondary to other conditions (HIV, silica exposure, infections, blood cancers). In the idiopathic form, autoantibodies to GM-CSF are thought to be responsible. Rituximab (a chimeric mouse-human monoclonal antibody binding CD-20) depletes human B-cells, reducing antibody production. Autoantibodies are particularly reduced after rituximab administration, leading to its successful use in many autoimmune conditions (lupus, rheumatoid arthritis, etc). Kavuru et al asked, why not try rituximab for idiopathic pulmonary alveolar proteinosis?
What They Did:
Kavuru, Malur, Thomassen et al gave two doses of rituximab to 10 adults with idiopathic pulmonary alveolar proteinosis (i-PAP) in an open-label prospective pilot study. All of the subjects were symptomatic, 8 of 10 were hypoxemic at baseline, and most had required whole lung lavage periodically. Follow-up was at six months:
What They Found:
- Oxygenation improved in most patients receiving rituximab for pulmonary alveolar proteinosis. PaO2 rose from 55 mm Hg pre-treatment to 74 mm Hg at 6 months in those receiving rituximab.
- Total lung capacity increased by ~500 mL; diffusion capacity and forced vital capacity were not significantly higher.
- High-resolution CT scans (blinded evaluations) showed improvement in ground glass opacities in several patients.
Investigators reported follow-up on 7 of the original 10 patients after a mean of 2.8 years:
- Four of the 7 had not needed whole lung lavage or home oxygen.
- One of the patients needed one lung lavage post-rituximab, but authors note that patient had needed monthly lavages for three years prior to rituximab.
- Eight of 10 had needed home oxygen before rituximab; at follow-up, only one still required home oxygen, and authors report that patient was living at high altitude.
There were no major adverse events, although one patient dropped out for unclear reasons.
Interestingly, measured anti-GM-CSF antibodies were no lower in serum after therapy (they were lower in bronchoalveolar lavage fluid, though).
Clinical Takeaway: Rituximab may be a useful treatment in idiopathic pulmonary alveolar proteinosis. A larger trial is justified and necessary to recommend rituximab as standard therapy for i-PAP, but barring contraindications and with appropriate risk counseling (including the risk of life-threatening anaphylaxis), it seems like a reasonable empiric therapy for patients with i-PAP who are dependent on and troubled by the cumbersome routine of regular whole lung lavage.
Kavuru MS et al. An open-label trial of rituximab therapy in pulmonary alveolar proteinosis. Eur Resp J 2011;38:1361-1367.