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.