Vol.2 No.1       An RRP Foundation Publication       1993 Spring

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From the Editor

This is the first issue since the support group has organized as a non-profit corporation called the Recurrent Respiratory Papillomatosis Foundation (RRPF) . Continued expansion of our RRP support group, networking of the RRP community, a national registry of RRP patients and increasing RRP awareness/understanding are major goals of the Foundation.

Some of the highlights of this issue include:

The RRP Newsletter is vital to our support services and networking efforts. We welcome your comments and suggestions with regard to the content of future issues. Your feedback will be very helpful in improving this publication.

We are asking for your help in supporting this newsletter and other RRP support services. Although all of our time is donated strictly on a volunteer basis, it costs money to publish and distribute this newsletter, to maintain a long distance telephone network, to run periodic Medline searches, and to carry out additional support and awareness activities . Any donations from individuals or from the business community will be very much appreciated. We are currently in the process of obtaining a 501(c)(3) tax exempt status. Contributions may be made to:

RRP Foundation

50 Wesleyan Drive

Hamilton, NJ 08690

Bill Stern

OPEN LETTER TO PHARMACEUTICAL COMPANIES

There is abundant clinical literature showing that alpha interferon can sometimes reduce the recurrence rate of RRP. While interferon is not a perfect drug and does not seem to cure the disease, it can help.

While pharmaceutical companies have sought and obtained approval of alpha interferon for many diseases, including condyloma acuminata (genital warts) and Kaposi’s sarcoma, they have yet to obtain FDA approval of this drug for treatment of RRP.

We have recently heard a rumor that there will be no further efforts to obtain FDA approval, because the approval process is costly and too much of a "hassle."

Children whose vocal cords are permanently scarred and who have to undergo surgery every other week because there are no other treatment options do not understand cost-benefit politics or "hassle." People whose insurance will not reimburse them for interferon treatment and who have to pay their costs out-of-pocket do not appreciate being written-off as "rare" by pharmaceutical companies.

Hopefully, this rumor is untrue, and pharmaceutical companies are aggressively pressing the FDA for approval to use their products for treatment of RRP. If there is an obstacle to the approval process within FDA, please let the RRPF know about it so we can contact the appropriate governmental agents.

Your support will be appreciated, in fact it is most welcome, and we urge you to stay in touch and be part of our growing RRP network.

RRP Practitioners: Please help us to convince the pharmaceutical companies that RRP is indeed life threatening in many cases, and should be taken seriously. Promising drug therapies should be pursued for RRP.

RRPF Officers, Directors & Advisors

Marlene Stern
President
50 Wesleyan Drive
Hamilton, NJ 08690
(609) 890-0502

Michael Green, MSW, ACSW
Vice-President and Director
12219 Phinney Ave. N.
Seattle, WA 98133
(206)361-8185

Bill Stern
Treasurer and Director
50 Wesleyan Drive
Hamilton, NJ 08690
(609) 890-0502

Henry Woo
Secretary
600 New Hampshire Ave., N.W.
Suite 720
Washington, D.C. 20037

Susan Woo
Director
7107 Georgia St.
Chevy Chase, MD 20815
(301)652-6826

Scientific Advisory Committee

Thomas Broker, PhD, U. of Al. at Birmingham
Haskins K. Kashima, MD, Johns Hopkins
Linda Miller, RN, MSN, Children’s Hospital of Philadelphia
Robert J. Ruben, MD, Albert Einstein College of Medicine
Bettie M. Steinberg, PhD, L.I.J. Med. Ctr.
Kathleen Sullivan, RN, Children’s Hospital of Boston

RRP Network News

Patient/Family Support Network:

Our national support network has grown to over 50 respiratory papilloma families with whom we have made contact plus a few more who we know of but have not been able to contact as yet. We are now an international organization, with patients from two Canadian provinces in addition to RRP families from 18 states. Current ages of patients range from 8 months to 70 years with about 75% under 16 and approximately an equal number of males and females.

We have received questionnaires from about half of the families. An expanded questionnaire has been enclosed which includes some additional research questions suggested by a committee of otolaryngologists and gynecologists. Please take a few minutes to complete them to the extent needed to bring the information about yourselves up to date. Please return them to Marlene and Bill Stern.

As part of our efforts to network the RRP community, we are exploring ways to encourage communication among members of the support group. Telephone is still probably the best way to efficiently communicate, although relatively expensive. Let us know what long distance carrier you are using. In future RRP directories we will include this information so that sub-groups within the network could coordinate to take advantage of group discounts (i.e., MCIs Friends & Family). Alternative methods of communications are being explored, such as electronic mail, for those who have access to a computer and a modem or other networking capabilities. The RRPF now has accounts with two on-line services, Compuserve (Comp) and America On-Line (AOL) as well as access to internet (see page 7 for the specific address listings). Those support group members that have computer network capabilities - let us know about it. We also welcome suggestions on innovative ways to provide for cost effective communication among members of the RRP community.

RRP Practitioner/Researcher Network:

The RRP Foundation is currently collaborating on a proposal to develop a comprehensive national registry of RRP patients. The Centers for Disease Control (CDC) is exploring the possibility of coordinating this project in close collaboration with some of the major medical schools. Some of the potential goals (taken from a CDC draft proposal) of an RRP registry are:

Marlene, Bill and Lindsay Stern

Marlene and Bill Stern are RRPF President and Treasurer, respectively. Bill also serves as one of three members of the Board of Directors. Their daughter Lindsay is now approaching 3 1/2 and was diagnosed with RRP at just over the age of two. Marlene is an administrator at a University and Bill is a research meteorologist.

Michael Green

Michael Green serves both as Vice-President of the RRPF and also as one of the Board of Directors. He is an RRP patient diagnosed in 1978 (see the RRP patient update feature for more details). Michael is a clinical social worker.

Susan and Henry Woo and children (left to right) Alex, Stephanie and Jennifer.

Susan Woo serves as a member of the RRPF Board of Directors and Henry Woo serves as RRPF secretary. They have three children, Jennifer is 9 years old, Stephanie is 3 1/2 and Alex is a year old. Their oldest daughter Jennifer was diagnosed with RRP at the age of one. Henry is an attorney and Susan is currently devoting most of her time to raising her children.

Prof. Tom Broker, PhD and Prof. Louise Chow, PhD, husband- wife HPV/RRP research team

Dr. Thomas Broker and his wife Dr. Louise Chow are Professors of Biochemistry and Oncology, in the Biochemistry Department of the University of Alabama - Birmingham School of Medicine. They have been investigating the fundamental nature of human papillomaviruses since 1980, focusing both on genital and respiratory HPV. One of their recent accomplishments has been to reproduce virus particles of HPV type-11 (one of the primary RRP types) in the laboratory.

Prof. Haskins Kashima, MD

Dr. Haskins Kashima is a Professor at the Johns Hopkins University School of Medicine,with dual appointments in the Department of Otolaryngology and Oncology. He received his undergraduate degree at Stanford University and attended medical school at Yale University. He received his surgical and otolaryngologicaltraining at Barnes Hospital (Washington University) in St. louis and has been a staff member at the National Cancer Institute and at Georgetown Medical School. Since 1970, Dr. Kashima has been on the faculty at Johns Hopkins. Haskins Kashima’s comprehensive clinical and research experience with RRP patients spans many years, and he has written and spoken extensively on the subject

Linda Miller, RN, MSN

Linda Miller has been with Children’s Hospital of Philadelphia (CHOP) since 1979, first as a nurse in the surgical unit and since 1983 she has been with the Department of Otolaryngology. Linda received her BSN from the University of Delaware in 1979 and a Masters Degree and Nurse Practitioner Degree from the University of Pennsylvania in 1986. Recently she has been appointed to the National Board of Certification for Otorhinolaryngology Head-Nurses and have participated in developing the first certification exam for ORL nurses. CHOP Department of Otolaryngology has regularly been treating approximately 20 RRP patients. Linda has not only been involved with most of the surgical procedures that these patients have had, but also serves the families and patients as an RRP information resource and support person.

Prof. Robert Ruben, MD, FAAP, FACS

Dr. Robert J. Ruben is Chairman of the department of Otolaryngology and Professor of Pediatrics at the Albert Einstein College of Medicine of Yeshiva University and the Montefiore Medical Center. Additionally, Dr. Ruben serves as director of the Institute of Human Communication Disorders at the Albert Einstein College of Medicine and the Montefiore Medical Center. Among other activities, Robert Ruben has been intensely concerned with pediatric otolaryngology. He has been instrumental in the founding and the establishment of several pediatric otolaryngic societies and is Editor-in-Chief of the International Journal of Pediatric Otorhinolaryngology, which is the only medical journal devoted to the problems of pediatric otolaryngology.

Robert Ruben has been an active researcher. He has conducted studies in the trials of drug efficacy for the treatment of papillomatosis in children, continues to care for children with these disorders and carry out research within this area. Dr. Ruben has also participated on the review commissions and advisory councils of the National Institutes of Health and private foundations.

Prof. Bettie Steinberg, PhD

Dr. Bettie M. Steinberg is Chief of the Division of Otolaryngology Research at Long Island Jewish Medical Center in New York. She is also an Associate Professor of Otolaryngology at the Albert Einstein College of Medicine in New York. Dr. Steinberg has studied the interactions between papillomaviruses and the tissues they infect for many years, with a primary focus on laryngeal tissues and recurrent respiratory papillomatosis. She has authored numerous articles and several book chapters on this subject.

Kathy Sullivan, R.N.

Kathy Sullivan has been a member of the Department of Otolaryngology at Children's Hospital of Boston (CHOB) for six years. Children's Hospital of Boston is the largest pediatric facility in the United States.

Her involvement includes that of Clinical Trial Nurse for research as well as Nurse Associate for five ORL physicians. Her ORL research interests include management of chronic otitis media and alpha-interferon for RRP. Kathy has previously served as a staff member in the Neonatal Intensive Care Unit at CHOB, working both in clinical research, direct patient care as well as being involved with high risk transports.

Kathy will admit (much to her chagrin) to being in the nursing field for twenty years. She has published in areas of neonatolgy and otolaryngology. She lives in Westwood, Mass with her 9 year old daughter, Elizabeth.

RRP Patient Update

Introduction and Clinical History

by Michael Green, MSW, ACSW

I am 48 years old and was first diagnosed with laryngeal papillomatosis in 1978. Since then, I've had around thirty surgeries.

When I first understood the recurrent nature of this disease, I researched the literature in hopes of finding treatment outside of repeated laser surgeries. (RRPF will have abstracts of current literature on file for distribution.)

Although I was recently diagnosed with severe dysplasia, I seem to have had a relatively indolent form of RRP so far. The trachea and lungs have not been involved.

I have had periods where my speech was not much better than Marlon Brando's Godfather. It needs to be noted, however, that RRP is not just a debilitating disease in which patients are verbally isolated from the outside world. In the midst of their pain, patients and families are usually isolated from one another. It was almost fifteen years before I talked to another adult patient with RRP. As a clinical social worker by profession, networking patients and their significant others is a major goal of mine with the RRP Foundation.

RRP has affected all aspects of my life, including my job. Long ago, I found that things like new paint, new carpets, or even the electrical burn-off coming from a new TV or VCR invariably caused vocal cord irritation, which physicians agreed was exacerbating the papillomatosis. I have to work in an accommodated space, with access to fresh air, and I use an air cleaner in my home.

In 1981, I was given autogenous vaccine, made by a leading specialist in New Jersey. In 1982, I entered a University of Arizona protocol for treatment with isotretinoin (13-cis retinoic acid). In 1985, I entered a treatment protocol in Seattle using alpha interferon, and I have used that drug off-and-on for over three years. In late 1988, I entered LIJ's protocol using Photo-Dynamic Therapy (PDT). In the interim, I've also used NAC, isoprinosine, and drugs such as hypericin, which have been distilled from herbs.

Anecdotally, I might also note that I've tried just about every alternative therapy available--without much success. This included meditation, acupuncture, herbs, vitamin and mineral supplements, etc.

Of all the medical treatments available, Schering's interferon (Intron 2b) has helped me most. I found I could keep the disease under control with as little as 1-1.5 million units three times a week ( approximately half the dosage suggested by some clinical trials).

While I am not currently using interferon, I am following LIJ's indole-3 carbinol cruciferous vegetable protocol. My initial response appears to be quite positive.

In closing, I'd like to warmly welcome the medical community's interest in the RRPF. Patients and their significant others should not be left to fend for themselves. Your support is needed.

The disease may not be as rare or obscure as some people think. A CDC epidemiological register of RRP is also needed.

There is also need for continued research on RRP. There are many unanswered questions. Why do only certain persons get it? What are the possible co-factors that may predispose to the disease? Is the disease sexual transmissible (oral/genital) in adults? Why is RRP not an opportunistic infection in people with AIDS?

I'd like to hear from anyone who may wish to discuss any aspects of this disease. I can be reached at the following address: 12219 Phinney Ave. N., Seattle, WA. 98133. My phone is (206) 361-8185.

RRP Research News

In this issue we are featuring two current clinical studies involving RRP patients.

The Effect of Acyclovir on Recurrent Respiratory Papillomatosis

This article describes early results from an on going clinical trial using Acyclovir, it is primarily based on an abstract written by Dr. Amelia F. Drake, MD, Division of Otolaryngology, University of North Carolina, Chapel Hill, NC.

Acyclovir has been shown to be beneficial as an anti viral agent, at least with regard to Herpes. In a report of an earlier study using Acyclovir ( Aguado, et al., 1991, International Journal of Pediatric Otolaryngology), an apparent positive impact on three laryngeal papillomatosis patients was seen (although two of the three had no prior history of recurrence).

This pilot study involves ten patients at three different institutions. All ten patients were started on Acyclovir (in a 20 mg per kilogram qid dose). In seven of the ten cases, the patients improved. Improvement was based on decreased severity of the disease and increased time between surgeries. It usually took three months for improvement to be noted and in some patients the maximal effect of the medication appeared to be temporary.

Currently, a prospective randomized study of these effects is being initiated. Dr. Drake notes that the apparent positive impact of Acyclovir in this pilot study should be viewed with caution at least until it is supported by a broader based randomized experiment.

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Clinical Study involving cruciferous vegetables

The Department of Otolaryngology at Long Island Jewish (LIJ) Medical Center is currently organizing a program to study the impact of cruciferous vegetables on recurrent respiratory papillomatosis(RRP) in humans.

Early results of experiments being conducted by researcher Dr. K. Auborn and her colleagues at LIJ, have indicated that a chemical which naturally occurs in cruciferous vegetables may help to suppress the growth of respiratory papillomas in mice. Their findings indicate at least some positive response (i.e., preventing growth of papillomas) in approximately 75% of the mice in the group receiving cruciferous vegetables.

LIJ is seeking patients with moderate to severe RRP (i.e., requiring surgeries at least as frequently as every four to six months) who are interested in participating, either as recipients of the experimental therapy or as part of a control group.

For more details please contact:

Dr. Allan Abramson
Dept. of Otolaryngology
Long Island Jewish Medical Center
270-05 76th Ave.
New Hyde Park, NY 11402
(718) 470-7555

Currently there are approximately six patients in the support network following this therapy, which involves high levels of dietary indole-3-carbinol. In at least three cases there appears to be some positive response.

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RRP Network News, continued from p. 2

Dr. Tom Broker, one of our scientific advisors, has been instrumental in this effort. If an RRP national registry becomes a reality, it will be in large part due to the efforts and devotion of Tom Broker.

The RRPF has started a preliminary study toward initiating a national registry. It involves locating centers and practices that are treating RRP patients and surveying them with regard to the total number and simple categorization of patients. If you have not received this one page RRP practitioner questionnaire please let us know. Please take a few minutes to fill out this form and return it to the RRPF c/o Bill Stern. Thus far we have received responses from ten medical centers treating a total of from approximately 350 to 400 RRP patients.

The prospect of a CDC coordinated national registry of RRP patients actually developing is starting to look promising. However, we can further enhance the possibility by making more people aware of RRP and the need for more serious attention. In particular, let your congressional representatives know about RRP and how a national registry could significantly help research and more clearly document the extent to which this disease represents a public health threat. Ask them to contact CDC regarding a national registry of RRP patients.

RRPF Information and Support Centers:

Main Info. Center and Northeast

50 Wesleyan Drive
Hamilton Square, NJ. 08690
(609)890-0502609-452-6545
e-mail (AOL): BillsLinsÝ
(bitnet): mstern@lindsay.princeton.edu

West Coast

12219 Phinney Ave. North
Seattle, WA 98133
(206)361-8185
e-mail (Comp): 75450,2252* (Michael Green)

Mid-Atlantic

7107 Georgia St.
Chevy Chase, MD 20815
(301)652-6826

Southeast

4800 S.W. 64th Ave., Suite 110
Davie, FL 33314-4449
(305)581-3400

Georgia Region

186 Pine Knoll Lane
Eatonton, GA 31204

Mid-West

1820 Brookview
Arlington, TX 76010
(817)261-1023

Ý for access from outside of AOL use billslins@AOL.com

* for access from outside of Compuserve use

75450.2252@compuserve.com

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The Recurrent Respiratory Papillomatosis Foundation is pleased to publish this issue of the RRP Newsletter. We hope that this and future issues will serve to enhance the support network among laryngeal papilloma families and also help to provide accurate medical and scientific information about this disease.

Please help us with our RRP work, including this newsletter and other publications, networking RRP patients families and physicians, and creating greater public awareness of RRP. In order to succeed we need your support. Contributions may be made to:

RRP Foundation
50 Wesleyan Drive
Hamilton, NJ 08690.

We are most grateful to those who have contributed to this cause, either financially or by volunteering their time.

Recurrent respiratory papillomatosis(RRP) is a disease in which tumors grow inside the larynx, vocal cords and trachea. It affects both children and adults. Research has determined that the Human Papilloma Virus (HPV), is present in these respiratory tumors. These growths are often associated with two specific types of the virus (HPV6 and HPV11) which are also found in genital and cervical warts.

There is no known cure for RRP, with CO2 laser surgery under general anesthesia being the accepted method of controlling theses growths. If left untreated these respiratory tumors will continue to grow, blocking the patient’s airway with suffocation being the likely result.

The Recurrent Respiratory Papillomatosis Foundation was created to provide family support, promote public awareness, and aid in the prevention , cure and treatment of RRP.

Our organization is primarily focusing on the networking of the RRP community, including patients (both juvenile and adult), families, medical practitioners and researchers. The nucleus of the network is the RRP Newsletter . The newsletter includes support group information and activities, individual RRP patient case histories, developments with regard to RRP (i.e., treatments and research), plus any additional information that might help further understanding and/or awareness with regard to this disease.

The concerns and objectives of the RRP Foundation are as follows:

The RRP Foundation is a completely volunteer organization, comprised of RRP families and friends. We very much appreciate your help and support in creating greater awareness so that RRP gets the attention it deserves.