Recurrent Respiratory Papillomatosis

Contents

q Opening Comments – p1

q RRPF Organization Information – p2

q RRPF Publication and Subscription Policy – p2

q RRPF Support and Fundraising Activities – p3-4
RFP for treating pulmonary papillomatosis – p3
Cody Pate Fdn. to join RRPF – p3
3^rd Annual RRPF Hockey Night – p3
Running for RRP – p3-4

q RRP Remission – p5

q RRP Network/Internet News – p5

q RRP Listserve Highlights – p5-6
Cause of RRP – p6

q RRP Patient Statistics - p7

q RRP Meetings– p7

RRP Focus Session 2004 – p7

q Adjunct Therapy and Protocol Update – p7-9

I3C/DIM – p8-9

Phytosorb –DIM update – p9

q Science & Research Activities – p10-12
Reflux Diagnosis and Management – p10

Celebrex Trial for RRP – p10

Cidofovir Study – p11
HspE7 Phase II trial update – p11-12

q Support/Subcriber Info – p13-14

From the Newsletter Coordinator and Editor

The RRP Foundation has been supporting and networking the RRP community for more than a decade and wants to continue to be responsive to the needs of the RRP community. In this regard we would appreciate any comments or criticisms you may have regarding the RRPF. The best way to let us know what you are thinking is by email to one of the members of the RRPF Board, i.e., Chris Neuberger, Susan Woo or Bill Stern, (see addresses listed in the section on “Organizational Information”.)

We continue to seek additional help in preparing, editing and coordinating the publication of the RRP Newsletter. In particular, we are asking for a volunteer to take on the lead role of coordinating and publishing future issues. If you are interested in assisting in any way, please contact Bill Stern (bills@rrpf.org).

We hope you find this newsletter issue to be interesting and helpful.

We are most grateful to all those individuals, medical professionals and corporations who have supported the RRPF. Although it is impossible to publish the names of all who contribute, we extend our sincere thanks to everyone who has supported our efforts. Future donations from individuals, professionals or from the business community will be very much appreciated.
Tax-deductible contributions may be made to:

RRP Foundation
P.O. Box 6643
Lawrenceville, NJ 08648-0643

Do you donate to the United Way through your employer? You can select a "Donor Choice" option, which would allow you to direct a donation to the RRPF as the 501 (c) (3) of your choice. Since the RRP Foundation is a 501(c) (3) foundation, you may specify the RRP Foundation directly by writing in the name and address of the foundation as follows' RRP Foundation, P. O. Box 6643, Lawrenceville, NJ 08648. If you should need to add our Fed. ID number, it is 521798693. Thank you for your support.

Donations accepted online via Pay Pal

From the RRPF home page (www.rrpf.org) or go dirctly to http://www.rrpf.org/donate.htm

Special Acknowledgment

We once again want to acknowledge the generous efforts of Ed and Maura Weiner along with their friends for a very successful 3rd Annual RRP Hockey Night" fundraiser for the RRPF.
(see page 3 for more)

RRPF Officers, Directors & Advisors

Marlene Stern

President

P.O. Box 6643

Lawrenceville, NJ 08648-0643

(609) 530-1443

marlenelin@aol.com

Bill Stern

Treasurer and Director

P.O. Box 6643

Lawrenceville, NJ 08648-0643

(609) 530-1443

bills@rrpf.org

Henry Woo, Esq.

Secretary

Medtronic International Inc.

Suite 1602 16/F., Manulife Plaza

The Lee Gardens, 33 Hysan Ave.

Causeway Bay,

Hong Kong

henry.woo@medtronic.com

Chris Neuberger

Director

13001 Burlingame Ave.

Oklahoma City, OK 73120

(405) 749-8499

cneuberger@eti1.com

Susan Woo

Director
The Manhattan, Flat 33D

33 Tai Tam Road

Hong Kong
(852) 2812 7379

susanleewoo@hotmail.com

[Please see the support info. on page 13 for a complete list of the RRPF regional and state coordinators]

Scientific Advisory Committee

Thomas R. Broker, PhD, University of Alabama at Birmingham Schools of Medicine & Dentistry

Haskins K. Kashima, MD, Johns Hopkins University School of Medicine

Linda Miller, RN, MSN, Children’s Hospital of Philadelphia

Clark Rosen, MD, University of Pittsburgh Voice Center

Robert J. Ruben, MD, Albert Einstein College of Medicine

Keerti V. Shah, MD, DrPH, Johns Hopkins University School of Hygiene and Public Health

Bettie M. Steinberg, PhD, Long Island Jewish Medical Center

Kathleen Sullivan, RN, Children’s Hospital of Boston

Voice Specialist/Advisor

Julie Bowne, M.S., CCC-SLP

RRP Newsletter Editors

Chris Neuberger
Jennifer Woo

Other RRP Newsletter Contributors

Randy Sparkman

Marlene Stern

Bill Stern

RRP Reference Service Editor

David Wunrow

RRPF Fundraising Coordinator

Ed Weiner

(703) 691-1922

eweiner@weinerandassociates.com

RRPF Corresponding Secretaries

Jenny Shamblin

Christine-Hartman Davis

RRPF Publication and Subscription Policy

The RRPF produces two publications, the RRP Newsletter and the RRP medical reference service. The RRP Newsletter focuses mainly on the human and clinical aspects of recurrent respiratory papillomatosis and in this regard targets a broad readership, including patients/families, attending physicians/nurses, as well as researchers and the general public seeking to stay in touch with RRP from a clinical perspective. The RRP medical reference service serves those in the community seeking a more comprehensive understanding of this disease. Please help us by supporting these publications and other RRP services including patient outreach, support, advocacy and research

Subscription Policy and Suggested Minimum Annual Donations:

RRP Newsletter

Professional/Corporate - $25
Individual - $15

RRP Newsletter plus Medical Reference Service

Professional/Corporate - $40
Individual - $25

[Note: Issues of the RRP Newsletter and Medical Reference Service are available on the website, see RRP Web News.]

RRPF Support and Fundraising Activities

Past Research/Support activities:

Research collaboration with Dr. K. Shah et al., from Johns Hopkins using RRPF patient data to better determine risk factors for J-O RRP.

Provided support to Strang-Cornell center for testing urine of RRP Patients to determine the impact of I3C/DIM on estrogen metabolites.

Supported research by Dr. K. Auborn and associates from LIJ North Shore Research Inst., to study the impact of I3C/DIM on bone density in mice.

Funded a study by Lin Lewis, RN, et al. from Univ. of Alabama to study biases against children with RRP.

Funded research by Dr. Lindman, et al. from Univ. of Alabama to utilize the PedsQLTM 4.0 Generic questionnaire to evaluate the impact of RRP on the quality of life of children affected by this disease.

Current Research/Support activities:

Reseach collaboration with Thomas Mingot, Director, Clinical Research and Operations at Stressgen Biotechnologies Inc. This involves the development of a comprehensive web based RRP survey and database, which is also part of PhD. Research project. It is anticipated that the information gathered from this survey will: 1) Help to convince funding agencies of the public health importance of RRP and hopefully get more funds committed to RRP research. 2) Assist the RRP Task Force and other RRP practitioners in refining treatment and practice guidelines for RRP.

RRPF website redesign, ongoing development and maintenance.

RRPF patient and practitioner database management.

RRP Newsletter publication and dissemination.

RRP Reference Service publication and dissemination.

Assistance to the Cody Pate Foundation (more info below)

Proposed Research/Support activities:

The RRP Foundation is asking the RRP research community to apply for funding a pilot study dedicated to finding a new treatment for pulmonary RRP, which is perhaps one the greatest challenges in dealing with this disease. Interested researchers should address inquiries to:

Bill Stern, Director

P.O. Box 6643

Lawrenceville, NJ 08648-0643

Email: bills@rrpf.org

Fundraising:

Cody Pate Foundation to Become Part of the RRP Foundation

The RRP Foundation is pleased to announce that we will be directly supporting the efforts of the Cody Pate Foundation to raise funds to help defray travel and some other expenses related to obtaining treatments for RRP. The Cody Pate Foundation will become a division of the RRP Foundation, but Lynette Pate will continue to spearhead activities with the goal of raising and disseminating funds for RRP families in need and also help create greater RRP awareness. For more information contact Lynette Pate at: Buddie4breathing@aol.com

3^rd Annual RRPF Hockey Night a Great Success

On January 31, 2004 the 3rd annual RRPF Hockey Night took place at the MCI Center in Washington, DC. The hard work of Ed and Maura Weiner (and their friends) netted the RRP Foundation over $15,000. It is largely due to their efforts that we now feel that we can afford to fund a pilot study for research into treating pulmonary RRP.

Running For RRP

On April 19, 2004, RRP patient and newsletter editor Jennifer Woo will be running the 2004 Boston Marathon to raise awareness and funds to support RRP research and networking between patients, physicians and scientists. Since her diagnosis at infancy, Jennifer has undergone over a dozen surgical procedures at the Children's Hospital of Philadelphia to remove papilloma growths. Her experiences as a patient in the operating room have motivated her involvement in the RRP Foundation as well as her dreams of someday becoming a pediatrician. A native of Washington DC and Hong Kong, Jennifer is currently a sophomore at Harvard University. She has grown accustomed to running in hot, tropical Asian climates as well as the frigid ice and slush of New England, and looks forward to running her first full marathon from Hopkinton, MA, to the center of Boston.

She encourages all Boston-area affiliates of the RRPF to contact her at jwoo@fas.harvard.edu if they would be interested in coming out to celebrate this fundraising effort for the RRP Foundation. (More on the next page)

RRP Remission News

!!! A new addition to our growing list of remissions!!!

by Bill Stern

Heather who lives in Oregon and is now 18, has now been in remission about 14 years. However, she had a very aggressive first 4 years with RRP. During that time Heather was trached and endured over 100 surgeries. She was treated with interferon for a while, but is not really sure that it was the interferon that put her in remission. Her voice today is remarkably good.

RRP Network News

Our international support network has grown to approximately 670 respiratory papilloma families. Patients range in age from about 2 to 88 years. Domestically, patients are located in 48 states plus the District of Columbia. Outside the U.S. there are currently 33 patients from 14 countries.

Our thanks to all who have taken the time to fill out the RRPF Patient/Therapy Survey. Please make sure to alert us of changed addresses by checking the “new address” box. There is also a box below the name and address section, which we ask you to check if you do not want your name and address information to be included in the RRPF Patient Directory. We are requesting the information contained in this survey be made available for RRP research. In this regard there is a place in the survey to grant permission.

As our support network has grown, we have become more dependent on the patient questionnaires to maintain our mailing list and keep our database of RRP patient information up to date. So if you haven't completed a questionnaire in the past, please take a few minutes to complete the patient survey. If you have previously filled out a questionnaire, you need only identify yourself, and answer only those questions where you have new or updated information to provide.

Doctors and nurses treating RRP patients take a few minutes to fill out the practitioner survey form.

You can find the online “patient survey” and “practitioner survey” respectively on the “patient” and “practitioner” page links from the RRPF home page (www.rrpf.org).

……………………………………………………………………

RRP Web/Internet News

by Bill Stern

The Internet is now the most often used information exchange for the RRPF. Our website (www.rrpf.org ) has recently been redone with a totally new look, which we hope will make finding information easier. It contains a wealth of information relevant to patients, families, doctors, nurses and researchers. It includes an online database of RRP practitioners. The website has a new Interactive Discussion Forum which allows for the posting of questions, comments and replies to previous postings relevant to RRP. We also have the RRPF Email Listserve.(see below), linked to the home page. As noted above, you can find the RRPF Patient/Therapy Survey and RRPF Practitioner Survey forms on line, which allow RRP patients and caregivers to easily submit their survey to the foundation. This is a very important aspect of the Foundation in that this information is used in analyzing RRP treatment therapies, experiences, etc. We ask that patients and practitioners update their survey at least once a year.

Also, we maintain an online library of RRP Newsletter and RRP Reference Service issues plus links with many other sites relating to RRP and much more.

If you have some experience/expertise with the WWW and would like to help us improve our website, please contact Bill Stern.

……………………………………………………………………

RRPF Listserve Highlights

by Randy Sparkman

The RRPF-sponsored e-mail distribution list, or “Listserve” continues to be very active. With 200+ subscribers made up of RRP patients, health care providers, and caregivers, this low volume list is a valuable resource for the whole RRP community.

Recent significant discussion topics included: dealing with insurance companies for RRP treatment, availability and dosing of adjunct therapies like DIM and Cidofovir, information about emerging adjunct therapies like Celebrex, assistance in locating experienced RRP physicians, HPV/RRP transmission issues and, most important, discussions among RRP patients and caregivers about the daily experience of dealing with RRP.

Listserve users should be aware that the RRPF Listserve is vulnerable to the same issues as all on-line services. Concerns among Listserve users about patient privacy led the RRPF leadership to restrict access to the Listserve to only users who have registered with the Listserve hosting service, YahooGroups. Even though anyone may register with YahooGroups, limiting access to registered users prevents Listserve access from open Internet services like search engines, etc. In any case, Listserve users with privacy concerns should not post full names, postal addresses, e-mail addresses, etc.

There have also been recent posts about computer viruses. Users should not forward e-mail attachments to the Listserve and should not open any attachments within messages received from the Listserve. This does not mean that the Listserve increases the risk of receiving a computer virus, it is simply good practice to delete e-mail messages with attachments unless you are absolutely certain of the sender and the content.

Basic subscription information and complete list archives are available on the Internet/World WideWeb at: http://groups.yahoo.com/group/rrpf. The messages may be generated and received from within your e-mail computer client or can be completely generated and received from the yahoogroups rrpf list web pages. Messages may be received one at a time or in a "daily digest". Anyone within the RRPF community that needs technical assistance with any aspect of the mailing list can send an e-mail to: rsparkman@bellsouth.net

[Ed. Note: The following article was posted on the RRPF listserve by RRPF scientific advisor, Dr. Bettie Steinberg, in an attempt to address many concerns expressed about HPV/RRP transmission, infection and disease expression. Because of the importance of this topic to many RRP patients and families we have published it in this newsletter issue with Dr. Steinberg’s permission]

Cause of RRP

I would like to try to clear up some of the confusion that has been expressed on the RRPF egroup site in the last few days, and hopefully answer some of your questions (although I assure you that researchers who spend all their time studying this disease have many of the same questions you do).

First, RRP is definitely caused by Human Papillomaviruses (HPVs). There is no question about that. However, infection does not always, or even usually, cause disease. Most of the time, HPVs cause silent or "latent” infection with no evidence of any problem. The virus just sits in the tissue, where it probably stays for life. Many, many people carry HPV in their throats without having RRP In a few people, the virus becomes active and then you get RRP. Why this happens to one person and not another is only starting to be understood - one of the questions scientists and physicians have. Clearly, it has something to do with the way the immune system sees (or doesn't see) the virus in this tissue. This appears to be at least partly genetic. It does not mean that people with RRP have a "bad" or "weak" immune system, just that their immune system does not respond to HPVs in an effective way. The genetics is complicated, and involves many genes. Recent studies suggest that you need just the right combination to be susceptible. Since people in the same family are not genetically identical (except for identical twins), even two children from the same parents would not have equal susceptibility.

HPVs are a very large family of related viruses (more than 100 types) that cause warts or papillomas in many parts of the body. Some types cause skin warts. In fact, everyone carries latent or silent HPVs in their skin, and recent studies have shown that every square inch of skin has these silent HPVs. We now know that these viruses are really just part of us. As far as we know, when these infections are latent they are not contagious, because there is no production of new virus. However, it is possible that small amounts of virus might be made from time to time. When the virus is active, and a wart is present, virus is produced and released from the surface of the wart, and it can then infect another site on the same person or infect other people. Skin warts, especially those plantar warts on the bottom of your foot, tend to make a lot of virus, and are therefore quite contagious.

Different HPV types cause warts or papillomas on mucous membranes, like those of the respiratory tract and the genital tract. There are at least 15-20 different types that can cause mucous membrane papillomas. Most of the time, they also cause silent infections. When the virus is active, andcausing RRP, it can make new virus. However, most papillomas in the throat make very little or no new virus. "Why" is another question where we don't have answers, but it means that those papillomas are not very contagious if they are contagious at all.

Of all of the HPV types that exist, just two are most commonly found in RRP, type 6 and type 11. These same two types are also present in many genital warts, although the most common HPV infection of the cervix in women is type 16. (Yes, HPV 16 is considered more likely to cause cancer, but it is also the most common HPV in the genital tract and usually does not cause cancer). Another question we cannot answer: if HPV 16 is most common in the genital tract, how come it is rare in the throat? Only explanation we have right now is that subtle differences in the mucous membrane tissues that we don't understand affect susceptibility to different HPV types. We know that skin HPV types don't normally cause mucous membrane papillomas, and vice versa. People are studying this question, but no answers yet. See - I told you scientists have lots of questions too.

Now to the whole STD question. Yes, genital warts are an STD. That just means that the HPV virus that causes genital warts can be transferred by sexual contact. Does not say what type of contact - between a husband and wife is still sexual contact and clearly appropriate behavior. Also does not say that is the only way to transfer it. Many, many people (probably at least half) have had a genital HPV infection. Some know they do, many do not even know it. Again, the virus can cause a silent or latent infection.

Physicians and researchers do believe that most babies with RRP get the virus from their mothers - usually while being born. If the mother has large genital warts that are making lots of virus the baby is more likely to get infected than if only a small amount of virus is being made from a wart you don't know is there. Young mothers are more likely to have an active infection, because the immune system seems to get better at handling genital tract HPV infections with time and keeping the virus latent. Therefore young mothers would generally make more virus - this could explain why a disproportionate share of babies with RRP are first born and had young mothers. Also, first babies usually take longer to be born, and therefore are exposed longer. A few babies with RRP were born by C-section. We think, but have not proven, that the virus occasionally gets up into the uterus during pregnancy and infects the baby before it is born - one more of our unanswered questions.

Finally, HPVs are completely unrelated to the viruses which cause herpes, which are Herpes Simplex Viruses (HSVs). Confusing because the abbreviations both start with H and end with V but completely different viruses.

Hope this answers some of your questions, and doesn't confuse you more. Bottom line - we should all support each other, not try to blame anyone for the wrong combination of genes and exposure to a virus that is very widespread. I like the idea of sending people with questions to the RRPF URL. The more we can educate people, the better.

Bettie M. Steinberg, Ph.D.

Chief, Otolaryngology Research

Associate Director and

Chief Scientific Officer

North Shore - LIJ Research Institute

Long Island Jewish Medical Center

RRP Patient Stats

The statistics that follow are based on RRPF patient questionnaire responses. Although suggestive trends are apparent, there has been no attempt to determine statistical significance, so caution is urged in drawing conclusions from the numbers below. (Also, see adjuvant therapy stat on page 7)

Table 1. Total number of patients in support group reporting.

	Females	Male
All Ages	281	350

Distribution of patients based on current and diagnosis age brackets and sex (sample sizes range from 563 to 591)

Table 2. Distribution of patients based on current age brackets and sex.

Age Groups	Females	Male	Total
Under 10	29	41	70
10-20

On April 19, 2004,

On April 25, 2004,

An(old)RRP parent

Your support for this cause is very much appreciated!

Pledge per mile or a flat amount to: marathon@rrpf.org