PCD Foundation Blog

Many of you may not know that Dr. Ken Olivier at NIH got involved in the PCD study due to his interest in NTM infections. He was seeing patients with NTM disease with no underlying disorder identified to explain their infections. He hypothesized (having been trained at Chapel Hill) that undiagnosed CF, PCD or Alpha-1 might be involved and worked with UNC to get his site added to the GDMCC study to look for PCD and atypical CF in adult patients with NTM.

I had the chance to speak with Dr. Olivier briefly at dinner tonight and asked him what he was finding at his site. He said that, based on nasal NO levels, they have been “surprised” at the number of people coming in with NTM infections who appear to actually have PCD. The connection has not been as strong with CF or Alpha-1, probably because the diagnosis of those disorders is a little easier and patients have probably had those diagnoses ruled out prior to coming to see him. We didn’t have time for details, but it is a tantalizing tidbit of info. I’m sure it he will get more into detail about this tomorrow…

One of the best things about this meeting has been the really practical information presented. Keeping neb equipment clean was an interesting topic covered by Dr. Gwen Huitt. For inhaled antibiotics (TOBI, colistin, etc.) National Jewish recommends using only a Pari (http://www.pari.com/) neb cup with filter (which is pretty standard, I believe) and the DeVilbiss Pulmo-Aide nebulizer machine, available online at http://www.devilbisshealthcare.com/index.jsp.

Pari neb cups can be boiled for sterilization, but the tubing is another matter. Since people with bronchiectasis are prone to “water” bugs like Pseudomonas and NTMs, it it important that the tubing be kept dry. Dr. Huitt recommends having seven sets of tubing, one for each day of the week. After use, she has her patients jerry-rig a blow drying system for the tubing by taking a standard rubber glove, cutting a slit in one fingertip and inserting one end of the tubing in the slit. A standard hair dryer is then attached to the wrist end of the glove and hot, dry air blown through the glove and into the tubing for one minute. Then leave the tubing in the open air until the next use. Both Dr. Huit and the RT strongly suggested NOT bagging up tubing for storage, but leaving it out in the air.

Some patients have also pulled their neb cup off the tubing at the end of a treatment and allowed the compressor to keep running for several minutes to dry the tubing. This also seems to work, but the hot, dry air of the blow dryer appears to be the most effective at curtailing bug growth.

*Please note–the following is not intended as an endorsement of any particular form of airway clearance, but is provided for informational purposes only.

At the NTM conference, a respiratory therapist (RT) from National Jewish talked about their preferences for airway clearance and highlighted the need for diligent, daily therapy. This talk was given in the context of patients with bronchiectasis and NTM infections, but much of what she presented would apply equally well to PCD patients.

First off, they really like the Vest (any brand) and the blue (for pediatric or low lung volume patients) or the green (adults) original versions of the Acapella. They are not so keen on the Acapella Choice (the cleanable one) at this point because it tends to break easily. Apparently, the manufacturer is working on this and hopefully will be able to come up with a solution to the breaking issue. The treatment regimen they like is Vesting for 10 minutes, followed by five blows (exhaling only) on the Acapella, followed by huff coughing, then repeat x 1 (for a total of 20 minutes Vest time).

The speaker was very clear about the fact that any form of airway clearance is better than nothing and they don’t want to discourage people from doing whatever therapy they find most effective. However, National Jewish does not generally prescribe IPV devices for patients with bronchiectasis because the “jack hammer” effect can lead to hemoptysis in these patients. Also, cough alone is not as effective in bronchiectatic airways because they become “floppy” and can collapse from the pressure of coughing, trapping mucus. PEP devices like the Acapella essentially use positive pressure to stent the airway open, so mixed with with cough or Vest to loosen secretions you may get good results. The speaKer also made a strong point about not confusing lack of productive cough with failure of treatment and suggested that airway clearance is happening with therapy regardless of whether you notice a demonstrable result.

The blue and green Acapella devices cannot be boiled or sanitized, so it is crucial that you only exhale into them and don’t breath in. For those of us (like me) who have difficulty walking and chewing gum at the same time, remembering not to inhale could present a challenge! Acapella is a vibratory PEP (positive expiratory pressure) device. Other devices in this category include the Flutter valve and the Quake. The Flutter is the old standard, but it is positioning-dependent, meaning that it’s effectiveness is strongly impacted by user ability. The Quake is a newer PEP device that allows the user to control the amount of vibration using a hand-turned crank that looks a bit like a fishing reel. The Quake also requires a certain amount of coordination–must exhale and turn the crank simultaneously–so it is not appropriate for everyone.

Postural drainage (tipping upside down) works great for some people and they do it a lot at National Jewish to help people get sputum samples up. However, you need to be sure you don’t have any reflux issues before embarking on a postural drainage regimen and it is always a good idea to do it on an empty stomach to prevent aspiration!

Coming up next…

“What’s Growing in Your Nebulizer?” or “How I Learned to Stop Worrying and Love My Tubing.”

So you may be wondering why non-tuberculous mycobacterial (NTM) infections (MAC, absessum, MAI, etc.) are of interest to people with PCD. NTMs are nasty and destructive bugs in the same family as Tuberculosis (TB) and there is increasing evidence that bronchiectasis-causing disorders contribute to acquisition of these bugs. At Family Day this summer, Dr. Knowles presented a slide indicating that 20% of PCD patients over the age of 29 in a small review had some form of NTM. Since that review, NTM has also been cultured from adolescent PCD patients. The current recommendation is that all PCD adults and adolescents, regardless of whether they are symptomatic or not, be cultured for NTMs annually. This requires a specialized culture called an AFB culture. There are several labs that do quality cultures. Contact the PCD Foundation for more information.

Denver, November 2007

Great information so far. Here are a few surprises:

1.) There does not appear to be a correlation between the severity of bronchiectasis and acquiring an NTM infection. In fact, it appears that, at least in CF and PCD, most people who acquire NTM (non-tuberculous mycobacterial) infections have mild clinical disease. This really surprised me and also adds to the suspicion that susceptibility to these organisms may be more a matter of genetic pre-disposition than of disease progression or exposure. The same is true of ABPA (allergic bronchopulmonary aspergillosis).

2.) The crucial factor in predicting how well you will respond to NTM treatment is whether or not you culture clarithromycin (Biaxin)-resistant organisms.

3.) The importance of not only getting very regular cultures, but cultures that are sent to appropriate labs was reiterated over and over again. This is not just true for NTM bugs. As patients we have to not accept lax culture practices from our personal pulmonary physicians.

Off to lunch–more this afternoon.

Michele

Saturday was a busy, jammed-packed day. Here are some brief highlights-

–Maimoona Zariwala gave a talk on PCD genetics. All of the mutations
found so far in PCD are considered “stop” mutations, meaning that they
may be amenable to genetic therapy with some of the new drugs
currently being tested to override stop mutations.

–Amelia Drake (ENT) indicated that nasal washing in the absence of
windows or some other access is probably of little value because the
natural hole or window in the sinuses is tiny. She is going to
publish their (UNC ENT group) findings and best practices for ear and
sinus issues in PCD to counteract the current published info (from the
UK only) that suggests tubes are a bad idea in PCD and recommends
substituting hearing aids. There are actual cases here where ENT docs
are suggesting removing tubes that are working wonderfully because of
the UK publications. The patient group in the US is collectively for
the use of tubes when appropriate in PCD and we were able to make a
strong point that we need something in writing from the experts to
support this experience.

–Johnny Carson talked about another tool in the diagnostic arsenal for
difficult cases. There is a new computer program that analyzes
ciliary beat frequency. In the past, the docs “eyeballed” the ciliary
movement and sometimes this can be very misleading. Johnny showed a
video comparison of three samples. Two appeared to be beating
normally and the other was clearly impaired. Turns out that actually
one of the “normal” appearing videos was from a PCD patient. To the
eye, the beat looked vigorous but on the computer program, it showed a
slow and erratic beat. The data has not been published yet, but
Johnny’s experience appears to show that any beat frequency less then
4 Hz on this computer program is indicative of PCD.

–Peadar Noone gave an excellent talk on end-stage lung disease and
transplant. He went through the decision-making process of when to
consider transplant and provided statistics for post-transplant
success. For now, PCD is lumped into all forms of bronchiectasis. It
is unlikely that the UNOS folks will be willing to separate it out for
us (like they do for CF and Alpha-1), but it might be worth
considering for us to do on our own (collect stats on PCD patients who
are on the list and on post-transplant outcomes). One surprising
thing that Dr Noone said is that in all bronchiectasis, including PCD,
the average age at transplant is in the 40s! Fortunately, that
doesn’t seem to be the case for most of the folks we know.

–In the panel discussion, we asked about evaluations for heterotaxy.
The recommendation for now was that if there are questionable
findings on chest CT (splenic abnormalities, liver position, etc), a
full abdominal CT be done. There is not a push to do full abdominal
CTs in asymptomatic people at this point because of the risk of
radiation exposure. However, there may be requests for research
purposes in the future. At least 6-18% of the PCD population has
heterotaxy–many of them undiagnosed. It’s important to know if you
fall into this category because there is a greatly increased risk
(200X) of heart defect/disease in the heterotaxy cohort.

–Dr Leigh provided copies of the UNC “PCD Action Plan,” a form they give
to their patients at every visit. We revised it for PCD Foundation
use and it will be made available on the website and we’ll email a copy to everyone on our database list. It is used in the pediatric clinic at UNC, so there may be items
missing for more mature patients. However, it is only intended as a
guide to remind physicians to do things like check sputum and PFTs
(you’d be surprised how many don’t). Feel free to add your own
questions to the form.

More detail to follow in the upcoming newsletter

Patients wanting to participate in NIH-sponsored research now have a resource to help with travel costs.  Angel Flights/Mercy Medical Airlift has established an office at the Office of Rare Diseases in Bethesda, MD to better serve patients participating in research studies (like the PCD study [GDMCC]).

Here are the guidelines:

*Flights must be for research, evaluation or treatment.
*The appointment must already be set prior to calling Angel Flights.
*Flights are primarily for people who are 300-1,000 miles from the
target medical site, but there are occasionally resources for people
traveling longer distances.
*Financial need is considered, but the terms can be flexible.

The contact person at Angel Flights/Mercy Medical Airlift for GDMCC study participants is Marita Eddy.  Here is her phone number: 301-451-9646

Angel Flights/Mercy Medical Airlift also wants us to let our group members know that they accept and greatly appreciate donations of frequent flyer miles for United Airlines.  If you have miles you would like to donate on a different carrier, there are airline miles exchange sites on the Internet.

I received a letter from Genentech/Novartis outlining a new warning about Xolair.  This is an update from the Feb. 2007 FDA alert, which merely encouraged people to fully read the package insert that comes with Xolair.  Here is Genentech’s warning:

“Anaphylaxis, presenting as bronchospasm, hypotension, snycope, urticaria, and/or angioedema of the throat or tongue, has been reported to occur after administration of Xolair.  Anaphylaxis occurred as early as after the first dose of Xolair, but also has occurred beyond 1 year after beginning regularly administered treatment.* Because of the risk of anaphylaxis, patients should be closely observed for an appropriate period of time after Xolar administration, and health care providers administering Xolair should be prepared to manage anaphylaxis that can be life-threatening.**Patients should also be informed of the signs and symptoms of anaphylaxis and instructed to seek immediate medical care should symptoms occur.”

Anaphylactic reactions can be deadly within minutes.  Neither the FDA nor Genentech is providing guidelines for who is at risk, so we have to assume that any user could potentially have an anaphylactic response to Xolair.  If you or your child is currently using this medication, please discuss this warning with your physician.  If you would like copies of the actual letter from Genentech, let me know and I can get them to you.

*This means that because even if you have used Xolair with no problems in the past, you still may experience anaphylaxis at some point.
**This means careful observation after each dose of Xolair

Since 2005, the Genetic Alliance and other patient advocacy groups have been working to get legislation passed that would protect individuals with genetic disorders (and their blood relatives) from discrimination in insurance coverage and in the workplace.  The resulting bill called “GINA” has received broad support from both parties.  The bill (details at link below) has been passed in the House of Representatives.  It looked to be a slam-dunk in the Senate, as well, but Oklahoma Senator Tom Coburn (a physician) has put a hold on the bill meaning that it won’t even be considered for an up or down vote.  Senator Coburn’s office has not provided an explanation for this action yet.  President Bush has already indicated that he will sign this bill into law if it is passed in the Senate.  The only hold-up now is Senator Coburn’s hold.

According to Senator John Kyl (R-AZ), enacting GINA requirements will result in little to no direct cost to taxpayers.  The biggest opponents of this legislation have been the health insurance industry and employer groups who would like to reserve the right to deny costly services to persons with genetic disorders.

Genetic Alliance is requesting that patients impacted by this legislation contact Senator Coburn (if they are from Oklahoma) or contact the Republican leadership in the Senate to request that they persuade Senator Coburn to release the hold.

Here is the bill:
http://rpc.senate.gov/_files/L2GeneticNondisDBJS021605.pdf

Here is Senator Coburn’s legislative aide email (if you live in OK):
courtney_cox at coburn.senate.gov

Senate leadership contacts for non-OK residents:
Trent Lott (R-MS)                  Phone 202.224.6253
Mitch McConnell (R-KY)           Phone 202.224.2541

It seems a bit ridiculous that we have to fight to prevent discrimination due to our genes.  However, the threat of discrimination in the U.S. is real.  Here is an example, the International Classification of Disease (ICD) now in its 10th revision, is used by the majority of the world to categorize disease and to keep medical statistics.  It does this by assigning numerical codes (PCD has not be given a specific code yet, that is a different problem).  In the 10th edition, the ICD distinguished the numerical codes for genetic diseases by putting a letter “V” in front of them.   These so-called “V” codes were great for countries with national health plans where all patients are covered regardless of their condition.  However, in the U.S. where ICD-10 codes are used for private insurance reimbursement, it is feared that V codes will prove to be “handy guide to discrimination” by insurance providers, allowing them to easily deny claims submitted using a  V code.  Please note–this has not happened yet–this is merely an example of why Genetic Alliance, the AMA, and other professional groups have been fighting for GINA for nearly 3 years now.

If you have the ability to make a call or send an email, please consider it.

Michele