The Science Journal of the American Association for Respiratory Care

2006 OPEN FORUM Abstracts

AEROSOLIZED CIDOFOVIR IN RECURRENT RESPIRATORY PAPILLOMATOSIS: A CASE REPORT

Grey Benton, MA, RCP, RRT-NPS, RPFT; Yvonne Fanous, MD; John Pfeifle, BS, RCP, RRT; Michael H. Terry, RCP, RRT; Leo Langga, BS, RCP, RRT-NPS.

Loma Linda University Children's Hospital, Loma Linda, California.

Introduction: We are presenting a pediatric patient who received aerosolized cidofovir in an effort to slow the progression of Recurrent Respiratory Papillomatosis (RRP) in the lungs. This was caused by the Human Papilloma Virus (HPV). Cidofovir has been given intravenously (IV), has been injected into, and applied as a topical treatment onto lesions. We believe this is the first report of aerosolized cidofovir therapy in humans for the treatment of RRP.

Case Summary: The patient, a Hispanic male, contracted HPV in the birth canal (maternal genital warts). He required his first laser excision of laryngeal papillomas at 16 months of age for airway patency. Over the next 11 years the patient required many lesion excisions. The period between excisions varied (on average) between 51.4 and 22.6 days, with an overall average of 39.6 days. The patient had multiple infections, including yeast strains and pseudomonas aeruginosa. He contracted a mucoid strain of pseudomonas aeruginosa about 16 months before he died (at 13 years and 10 months). The patient was started on IV cidofovir at age 11. The patient experienced nausea, loss of appetite and fatigue with this antiviral agent. At age 12 it was noted that the papillomas had progressed beyond the right and left main stem bronchi. We began aerosolized cidofovir (300mg/treatment) at age 13 utilizing a Respirgard IIT nebulizer in which we replaced the regular nebulizer with an AeroEclipseT nebulizer. Using a lung scan we demonstrated effective peripheral deposition for our nebulizer setup (using a radio labeled substance). Aerosolized cidofovir therapy was well tolerated with less severe side effects than IV therapy (which he still received on alternate weeks). The patient received 16 treatments over a 167-day period. During this time there were 5 surgical excisions. The days between laser excisions with the aerosolized cidofovir increased on average to 45.8 days; increased from the previous period in which he received only IV therapy, which averaged 33.6 days between excisions.

Discussion: The progression of RRP in this patient could neither be halted, nor reversed. The time between excisions was decreasing, so the physician decided to try aerosolized cidofovir. Surgery and cidofovir (by IV or by injection into lesions) are among the current therapies for RRP in humans (1). In mice, the aerosol route can prevent viral infections and provides higher tissue drug levels in the lungs compared to the IV route (2). Since the drug is expensive, we assembled a nebulizer system (described above) to increase the efficiency of delivery and reduce exposure to caregivers (we used the same precautions as pentamidine during nebulization). The data from our experience suggests that adding aerosolized cidofovir increases the time between surgical excisions, however, this was a retrospective case study, and variables were not controlled. In keeping with the usual practice when delivering IV cidofovir, the patient was prehydrated with a liter of saline and given probenecid before aerosol therapy.

Conclusion: Our experience suggests that aerosolized cidofovir can be delivered to the periphery of the lungs, that side effects may be decreased by using the aerosol route, and that the time between RRP lesion excisions might be lengthened. Further study of aerosolized cidofovir is warranted.

References: (1) Silverman DA, Pitman MJ. Current diagnostic and management trends for recurrent respiratory papillomatosis. Current Opinion in Otolaryngology & Head and Neck Surgery. 2004 Dec;12(6):532-7. (2) Roy CJ, Baker R, Washburn K, Bray M. Aerosolized cidofovir is retained in the respiratory tract and protects mice against intranasal cowpox virus challenge. Antimicrobial Agents And Chemotherapy, Sept. 2003, p.2933-37.

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