Aerosolized Pentamidine

Last week physicians at San Francisco General Hospital and the University of California San Francisco Medical Center published the first article on aerosolized pentamidine inhalation therapy to appear in a medical journal (The Lancet August 29, 1987). We interviewed A. Bruce Montgomery, M.D., a principal investigator in this study, in order to answer some widespread questions about this anti-pneumocystis treatment which is already well known in the community.
Pneumocystis usually infects only the air sacs of the lungs. Physicians have long injected pentamidine as a standard
pneumocystis treatment, but when given this way the drug causes severe side effects and often must be discontinued. Scientists found that very little of the injected pentamidine went to the lungs, where it was useful; most went elsewhere in the body where it did no good and could be harmful. But when made into a fine mist and inhaled, almost all of the medicine went to the lungs and stayed there, greatly reducing the side effects.
The Lancet article reports the results of treating 15 patients who had already developed mild to moderate pneumocystis. Aerosolized pentamidine in large doses was the sole treatment for 21 days. In 13 of the 15 patients the
treatment was successful; of the other two, one died and one was switched to other pneumocystis treatments and recovered. Except for coughing, no one had any side effects attributed to the treatment.
In addition to the 15 patients in the study, three others were also given the aerosol because they could not tolerate
other pneumocystis treatments. All three recovered.
Aerosolized pentamidine also reduced the average length of hospital stay to eight days, from two to three weeks for
comparable patients treated with standard therapies.


Use for Prevention

The Lancet article does not discuss preventive use of aerosolized pentamidine -- which uses much smaller doses, given every two to four weeks. Another team at San Francisco General is conducting a separate preventive study, expected to enroll up to 400 patients. Meanwhile physicians especially in New York and San Francisco are already prescribing the preventive treatment for their patients.
For preventive use, many different doses are being tried - - 30 mg, 45, 60, 90, even 150, at different schedules varying
from once a week to once every four weeks. We asked Dr. Montgomery, an expert in inhalation therapy, to help resolve
the confusion about doses common among patients and physicians. He made the following points:
* Most importantly, doses cannot be compared across different nebulizers (the machines which make the aerosol
mist). The size of the droplets produced is more important in determining the effective dose than the amount of pentamidine in the nebulizer.
* Most nebulizers in common use do not make a fine enough spray. Most make droplets about five microns in diameter. However, animal studies in San Francisco have shown that pentamidine is three times as effective if the droplets are reduced to less than two microns. Most of the large droplets are deposited in the airways of the lung rather than the air sacs, where the pneumocystis organism lives. And large doses with the wrong droplet size could cause severe coughing or possibly asthma-type reactions, because the form of pentamidine currently available was not prepared for inhalation use.
* The most convenient nebulizers are ultrasonic, often hand held and battery powered. But the ones in use today do
not produce small enough droplets. Ultrasonic nebulizers use a piezoelectric crystal -- a crystal which vibrates at the frequency of an electric current which is applied. The droplet size depends on the electrical frequency. Unfortunately the ultrasonic nebulizers available today were designed to produce larger droplets for delivering asthma medicines to the air passages of the lung, not to the air sacs. Presumably it would be easy to use a higher frequency to make smaller droplets, but no one is manufacturing such a machine at this time.
So the San Francisco team designed its own nebulizer, which uses a gas jet to produce the droplets and a baffle to
filter out most of the larger ones. This nebulizer is less convenient than the ultrasonic machines because it needs a
source of compressed air or oxygen.
* The Lancet article tells physicians everything they need to know to use aerosolized pentamidine with the correct droplet size--including where to get the nebulizer.
* In San Francisco a large community-based study of preventive use of aerosolized pentamidine is testing three
different doses. If physicians find any dose to be less effective than the others, they will stop using that dose immediately. But it will take much longer to prove efficacy for the preventive treatment than for therapy given to persons
who are already ill.