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Saturday, August 16, 2008

CFRI eFlow info

I still haven't heard from the eFlow people, nor have I heard from my CF Center regarding any info they picked up at the Denver Conference.

However, CFRI apparently had a discussion about the device, and a DVD about the event can be ordered here.....


Offers DVD and Audio CD-Rom

of the eFlow® Presentation

October 25, 2006

(Please circle your choice of Audio CD or DVD)

Topics/Speakers Audio CD-Rom or DVD

It's All About Time- eFlow® Electronic Nebulizer
Terry Lyn Bishop, RCP & Bill Aikins of SourceCF

(62 minutes) Disc 1

Single DVD $3.00

Single CD $1.00

The speakers' presentations are reproduced in DVD-R (DVD minus R) and are compatible with most DVD players. The enclosed DVD can easily be played on PC computers and many newer DVD players. There are other DVD players that have been identified to playback only DVD+R (DVD plus R), DVD+RW or DVD-RW and may not play the DVD-R. Examining the specifications of the owner's manual will help identify these DVD players.

Depending on the number of orders and time needed to complete them, your patience is appreciated.

(Please circle your selections and send in your order with check or credit card information)


Address_____________________________City____________________State_____Zip Code __________ Telephone________________Email___________________________# of DVDs/CDs ordered ________

Card Account Number_______________________________________ Expiration Date _______________

Amount Submitted $_____________Signature________________________________________________

Please mail to:

Cystic Fibrosis Research, Inc.

2672 Bayshore Pkwy, Suite 520

Mountain View, CA 94043

or fax to 650-404-9981.

Questions? 650-404-9975 cfri@cfri.org

Please note that the pricing for the educational DVDs and CDs are for shipping and handling only.

eFlow Diary

You read it right - I just had a decrease in eFlow treatment time.

Colistin was taking me 8.5 minutes... this morning it was 7 minutes on the dot. (remember, colistin takes upwards of 20 minutes with traditional nebs)

Why? Foundation Care sent me a sonic jewelry cleaner from WalMart (free - aren't they great???). I stuck the head in the "La Sonic Supreme" over night and took it out before use this morning.

BAM! shaved 1.5 minutes off my treatment time. I think that's cool as heck. :) :) :) :)

I know more and more of you are jumping on the eFlow bandwagon and getting more of your life back. Thank you for all of your PM's. I love hearing from you all.


Well since I last posted about my eFlow times, things haven't changed. At all. Which I found strange.

I expected the times to increase gradually over time. But they haven't. I just had that spike at about 2 weeks when times increased by 2 minutes a treatment.

And I'm embarassed to say this, but I'm doing it for the sake of others reading it - I know now why the times increased.

I flew to New Jersey & back around the time the treatment times increased. And I didn't keep the head in alcohol for the plane ride because I figured I would spill it all over myself or have a hard time keeping it level.

I can't believe I didn't connect the two events. It seems so obvious now. But this is exactly why treatment times increased right at that time, and treatment times haven't increased since then.

Okie doke (I picked that phrase up from Minnesota when I went.... [I] everyone [/I] said it there) . So two things I've learned: one, as has been told to me, if you take care of the eFlow head, treatment times should remain short. And two, taking the head out of the alcohol, even for 6 hours, will affect treatment times.

So I'm going to have to figure out a strategy for TSA not to freak out at me when I go to paris in 2 weeks. And I'll have to figure out a way to keep the darn thing level while flying.

But it will be worth it! I don't have to bring a seperate PARI ProNeb Ultra (American ones don't work in Europe, in case you weren't aware.... even with the outlet converter. I had to buy a whole new compressor specifically for Europe when I was there a year ago) but instead I can bring my small, compact, battery operated eFlow!

I will continue to keep you all posted on my findings. And to those of you who have received push back from your physicians - stay tenacious! Studies are out there. More and more people are using the eFlow. There's no reason why your lungs should be left out.

Afterall, who has more of a interest in your health than you?


Well I started Colistin in the eFlow last night.

1st time I've ever used Colistin, eFLow or not, so I didn't know what to expect other than my doc told me my tongue might go numb (I think that's hysterical). But it didn't.

I'm not sure how long Colistin is supposed to take with a traditional neb since I've never do it that way, but it's taking me about 9.5 minutes.

That will be a nice time-saver since I'm leaving for Paris in 2 weeks and of course I will want to maximize my time NOT doing meds while on vacation.

Also I've heard that you need to mix the stuff - I get mine pre-mixed from Foundation Care in little ampules (just like Pulmozyme). It's nice not to have to mix.

I'll keep you all posted on my eFlow adventure....


I want to keep you guys in the loop of my eFlow experience.

It's been two weeks that i've had the thing and I've learned quite a bunch.

I was told (corrected) that I need to rinse the "head" in distilled water instead of tap water due to the mineral content of tap water.

Treatment time has increased from 2 minutes to 4.5 with my albuterol + cromolyn sodium. Pulmozyme has gone from 3 minutes to 5. And HTS has gone from 8 minutes to 9.5

So treatment time for all meds but HTS are about what they were with my traditional neb. HTS is still 17 minutes less than with my traditional neb, which is a huge time saver.

Additionally, all those plugs I've been coughing up I'm convinced is from the eFlow's high rate of respirable dose.

Foundation Care is sending me a jewelry cleaner from Walmart that people have had success with for cleanign the head.

The lady at Foundation Care did say that she sees less clogging with eFlows that are used for just colistamethate or tobramycin. Of course, that makes sense.

But I'll continue to report to you all my neb timing, cleaning procedures, etc.


Well I was feeling kind of tight days 2-4 using the eFlow. I was going to wait it out to see if it was the fires out here in LA, seasonal allergies, or some eFlow defect I was going to have to tell everyone about.

Then days 5-8, I've been coughing up mucus plugs. More so than I have the past few years of my life combined. That's why I was tight.... my plugs were working their way up through my larger airways.

I spoke to Mike Schulz over at Foundation Care and he says that more medicine is getting into newer parts of my lungs than with the traditional neb. Not all of his patients cough up plugs but he's heard it before.

He wants me to call him after my PFT's on Friday. He thinks my FEV1 could be higher as well as my 75-25 which has been decreasing quite a bit over the past few years.

I'll keep you guys posted.....


So the eFlow is working just great - 7 days after I got it.

I'm cleaning & disinfecting it just as I stated - except for the past 3 days I've been in NJ so instead of using the dishwasher I'm using the tupperwear that Foundation Care sent me to clean with soap & water & disinfect with 70% alcohol.

I've been closely monitoring neb times and they're identical to those that I was timing 7 days ago.

I'll keep you all posted on neb times as time goes on....

But the shortened time has been amazing. I'm able to socialize/network more on my biz trip, but still get decent amount of sleep.

The device is tiny so it takes up less space in my luggage which is always fabulous. I carry on all my meds so the smaller the devices the easier for me to lug around the airport.


Since 130 people read my eFlow II, I didn't want to go back and modify it for fear that those 130 people wouldn't return back & would thus miss the new pics.

Here is that eFlow head for any and all that are interested:



above is the "head"

Here is a pic of the bowl that Foundation Care gave me to soak the head in alcohol after rinsing it in distilled water. The head stays in the bowl until I'm ready to use it for my next treatment.

They don't want you to soak any other part of the whole head device than the metal head itself. I found out from Jem that those prongs don't need to stay out of the alcohol (as in the pic). Foundation Care just instructed me to do that so I could save alcohol. Weird.



Two above pics are the "head"

And finally here are the other parts of the eFlow that I toss into the dishwasher after every use.


Hopefully I'll have a video soon of the eFlow and my old compressor so you can compare the noise. You won't believe the difference!


Here is a pic of the device compared to the size of my PARI LC Plus and my PARI ProNeb Ultra compressor so you guys can get a feel for the size of the thing. Basically, it's smaller than the compressor & there's no neb so it saves space.


Here is a pic of me puting cromolyn sodium into the eFlow. You take off this dome thing, squeeze in the med, then put the dome part back on :) Also you can see the on/off button which is the black thing on the bottom of the picture.


Now he's a pic of what the "cup" looks like after meds have been put in. It holds 4mL and you can easily see how many mL's you have put in.


Finally, I wanted to show how you can modify the eFlow. You can hold the device all together if you wish. Or you can use this attachment to seperate the mouth piece & med cup from the power source (the saucer shaped blue thing). This is nice because it makes it easier to hold the mouth piece with your teeth & chat with you all!

You can see the blue & white dome better in this pic that you have to remove to put the meds in the device.


I am posting this right away because I owe so much to this site and I try to do anything I can to give back. Similarly to my trip to see Warwick, it never would have dawned on me to visit him if it weren't for some of you posting last summer about visiting him. So I posted his letter so that all may benefit from my visit.

I didn't even know that the eFlow existed until I came to this site. Fortunately some of you were generous enough to post about the fact that you had it, how you got it, etc. So I am eager to give back as much information to the site as possible so that all may benefit from this huge improvement in technology.

I'll say it until I can't speak anymore - information makes people with CF live longer. In this case, with the eFlow,

eFlow = time savings
time savings = greater compliance
greater compliance = longer life.


It's here. I have the eFlow. And it's fantastic

I did my first treatment in the middle of the day cuz I couldn't wait to use it. I did 2.5mg of cromolyn sodium combined with 0.5mg of albuterol.

I felt like I was doing my 1st dose of hypertonic saline all over again. That stuff was POTENT! wooooo!!!! For the 1st time in years, the albuterol made me jittery.

So, this combination of cromolyn sodium + albuterol used to take me 7 minutes. Now it takes 2 minutes.

Pulmozyme takes 3 minute with the eFlow instead of 5 minutes with my PARI LC Plus + PARI ProNeb Ultra

Hypertonic saline at 5mL, 7% took 27 minutes. Now I'm doing 4mL and it's probably working out to be able 6.5% of HTS which took about 10 minutes.

So what used to take me 39 minutes of nebs is now 15 minutes. That's 24 minutes of time savings, twice a day.

I just had 48 minutes added to my day. Unreal.

The cool thing is how quiet the thing is. You can barely hear it! And it shuts itself off one the medicine is done - so no more guessing if you're truely finished with the neb or not. I can't believe how quiet it is - I'm going to have to take a video so you all can hear.

I used it plugged in, but you can use it with batteries too. Which makes it great for overseas traveling (I had a seperate PARI ProNeb just for Euro travel). And I can use it on a palne too!!!!

The cleaning is not the nightmare people on this site have made it out to be. Probably, as I hypothesized a few months ago, because I do neb cleaning twice a day anyway, so this isn't anything different for me.

Foundation care provided two plastic bowls for me with lids. The "head" (which I'll take a pic of and post) you rinse in distilled water.. Then you put it in alcohol and you leave it there until you're ready to use it again.

The second bowl is for the rest of the parts which are more or less kind of sort of similar to the regular neb parts. They're plastic and some parts are blue soft things. So same difference. Foudnation care instructs us to put one dab of soap they provide in the bowl, shake it up with distilled water for 2 minutes and then let air dry.

I told the guy that I don't think this is sufficient sanitizing so he said I could leave the parts in alcohol after every treatment if i wanted to. Or i could boil. Or i could simply put them in the dishwasher as we've all discussed a million times and ensure that the water gets up above 158 degrees.

Guess what I chose? Dishwasher.

OK, that's all for now. I need to go eat. But I'll post more later and if you have questions, post on here and I'll answer in my next post.


Well, here are the studies. Cold, hard studies.

They were presented at the NACF. If your doc is telling you that the eFlow hasn't been studied, present these posters, and your physician's ignorance will be corrected.

Simple as that.


Low particle size variation is extremely important. There is an ideal particle size where the drug is most useable by the body. If the particle is too small or too large, the drug is unusable and basically it goes to waste. This is why the eFlow requires a smaller amount of drug - because its output of particles are more frequently of a useable size than any other nebulizer. And with a smaller amount of drug, neb time is shorter! It's an exciting technology.


I don't know about you guys, but with my PARI Pro Neb Ultra as my compressor and my PARI LC Plus nebulizers, I take Albuterol/Intal, Pulmozyme and then Hypertonic Saline 7% which takes me a total of 45 minutes. Then I do the Vest for 30 minutes.

So if I could cut that not even in half, but maybe from 45 minutes to 30, that would give me an extra 15 minutes in the morning and 15 minutes in the evening.

And when I do TOBI, I could do it in the car with my eFlow. My drive time to work varies, but gosh with the eFlow I'm sure it won't be more than 10 minutes.

My device is on order - and I would encourage ALL OF YOU regardless of insurance status to contact www.SourceCF.com. Even if you have Medicaid or crappy HMO/PPO insurance, chances are SourceCF can get one of these for you. I'm serious. You'll never know unless you call....


Hey guys,

I'm investigating purchasing an eFlow. It's been a long journey of information gathering over the past 24 hours.

At first I thought the eFlow wasn't available in the US. Then I found it is available, and has been since Nov 2004, but the FDA has given its approval only for use with CF patients. This is why you don't find the eFlow on the PARI US website.

So I contacted PARI, but they couldn't give me many specifics about the device's use with typical CF meds because they claim that the FDA doesn't allow device manufacturers to discuss the device's use with specific medications.

So I had talked to Foundation Care, one of the 3 pharmacies in the US that is approved to sell the eFlow.

I spoke to Mike Schultz, PharmD this morning.

Here is what I found out (in no specific order):

-The eFlow is $1680 for the unit, $2100 for a year due to cost of replacement parts
-Its covered by a good # of insurances
-What needs to be replaced? Its this metal disk that has 4000 microscopically drilled holes that allows medication to be aerosolized. It needs to be replaced every 90 days
-This metal disk needs to be cleaned after each use (ie if you do albuterol, pulmozyme, HTS in the AM, you need to clean it right after use and let it dry before you use it in the PM)
-The eFlow comes with a cleaning kit & instructions to faciliate cleaning
-Every drug for CF imaginable has been used in the eFlow, including Colistin, TOBI, Tobramycin, HTC, Albuterol, Pulmozyme, etc.
-How is the device tested? In vitro studies. They compare what the PARI LC Plus otuputs with a particular med and then they compare what the eFlow puts out. Turns out the eFlow puts out many more droplets than the PARI LC Plus, so usually less medication can be used with the eFlow.
-There are 650 patients in the US currently using the device
-eFlow will be at the North American CF Conference in Denver in 2 weeks. Call your doc up and tell him/her to attend the eFlow booth to get more information

If you want information mailed to you, email lindsay@foundcare.com

Say that you know someone who spoke with Mike Schulz this morning and you would like more information.

I'll let you guys know what else I find out. I'm going to talk to my boyfriend's dad who is a doc in Austria to see if PARI has any other studies/informatoin out in Europe.


eFLow learnings

I wanted to update you all on more information that I have learned regarding the eFlow.

1. The only medications that require dosage adjustment with the eFlow are antibiotics. This was a big concern for me because if I get my meds through my specific mail order pharmacy (or PBM), it's cheaper than if I go to another pharmacy. Like anyone, I want the cheapest option possible because med costs can add up. My albuterol, my cromolyn sodium, my pulmozyme and my HTS all require [U] no dosage adjustment [/U]. So I can continue to order nebs as usual.

2. Those who have negative side effects from pulmozyme or TOBI/tobramycin may see some of those side effects go away. Hoarse voice/sore throat and stomach aches from TOBI/tobra and/or pulmozyme will most likely go away because the eFlow produces particles that aren't large enough to hang out in the throat. The particles that hang out in the throat are larger than 5-7 microns - which the eFlow produces significantly low volumes of (lower than a traditional neb/compressor). The eFlow's particles are so small that they slip off of the throat and go right into the lungs.

So if you're thinking that your insurance might not cover the eFlow, this could be great prior authorization verbiage (although the specialty pharmacies that provide the eFlow are pratically masters at prior auth's).

3. The size of the particles that the eFlow doesn't just reduce side effects or increase the administration time - the eFlow actually helps the meds go down further in the lungs. And these depths of the lungs are where infection/inflammation typically occure. So, like the Vest, the eFlow isn't just a convenience item. [B] it's an improvement in care [/B]

Mike Schulz from Foundation Care has been incredible in answering all of my questions. He is very wise to realize that the more patients understand what they're doing with their meds & nebs, the more likely they will be compliant and will receive the immense benefits of the product. Wise man. Any of you on the West coast that are considering the eFlow, I would highly highly HIGHLY recommend giving Mike Schulz a call. You will learn so much more than you ever imaged.

eFlow studies

I realize that some of these studies are hard to read, and I'm sorry for that. I'm doing my best to find better pictures and/or links so you can read them better.

In the mean time, my reco is to right click on the pictures, save them to your desktop, and print them out. As ridiculous as it sounds, if you're passionate enough, use a magnifying glass to read. Yup, I said it. Magnifying glass :)

But you have my word that I'm doing my best to find you all better copies.

****if the pictures don't show up clearly, click on each picture. it will open up in a new window giving you the ability to zoom ***

These are from the German PARI site....







More studies....







Thursday, August 7, 2008

Description of Visit to see Warwick

September 21, 2006

Well, I'm exhausted. It's been a long day.

But my visit was Warwick was very informative. I learned about what he is currently researching (which I haven't heard anywhere else including this site) as well as his reasoning behind certain therapies that he uses.

He also showed me that my Vest jacket wasn't fitting me correctly. At all.

I'm too tired to detail it all right now, but I'll type up a long list of the details of what I learned tomorrow probably.

I think you all will be fascinated. I was.

September 22, 2006

So I'm finally sitting down to type about my visit with Warwick yesterday - where I learned a ton.

I've decided that I'm going to type on a topic one at a time... I got so overwhelmed thinking of typing all the info at once. And I do feel morally obligated to share all that I have learned to everyone in the CF Community. Information is so powerful with this disease - that there's no way I can just keep it to myself (which is the philosophy that I have when I post on the threads as well).

Before I type on my first topic, I want to put my visit in conext. And put Dr. Warwick in context. This will set the tone.

Dr. Warwick is 78 years old. He has been working with CF patients since the 1960s (maybe earlier but that's what he mentioned). This man invented the concept of high frequency chest compression (what many of us call "The Vest" even though there are many many versoins of it). He also has pioneered the use of many other therapies such as Mucomyst as well as the mist chamber (no longer used).

Dr. Warwick's patient population lives an average of 11 years more than the average of other centers around the United States. There are other centers in the US which have similar demographics to his (patient population size, race, income) but do not produce his results in terms of life expectancy.

Dr. Warwick has seen patients move from a life expectancy of 5 or 6 years old when he first worked with CFers to their 50s now.

And he is convinced that this success has nothing to do with him. His patients have taught him everything.

He has a passion for this disease that I haven't encountered with another practitioner in my lifetime. He is constantly reading what others have to say about CF and is always conducting experiments and studies on his own to confirm or deny his latest thoughts about CF.

So this is the context in which I wish to present what I have learned from Warwick.

No human on this earth is correct 100% of the time. And I suspect that some of his views on certain issues are going to provoke a great deal of discussion. So remember when I post, I am not saying that I agree with or disagree with what Dr. Warwick has said. I am simply posting what was discussed for the benefit of all CFers who come across this blog. Everyone will take what they will from it (as they do what on the threads).

And I wish I could post more now, but I'm off to my tour of the U of MN school of management. I'll post on my 1st topic tonight when I get back for evening meds.

September 22, 2006 Part II

So my mom and I had a blast at the Mall of America. We shopped for 6 hours. And covered every square inch of the place. TALK ABOUT EXERCISE!!!!!

And my apologies about my tease this morning. I really did think I would be able to talk about topic 1. But my new method of doing my Vest did allow me all that much type as I anticipated to type.

So Topic 1 from Warwick is going to be the Vest. Good topic in my opinion since the man came up with High Frequency Chest Compression.

First thing's 1st. Warwick had me bring my actual Vest (not the machine) to the visit. And what do you know - he said mine was the worst fitting jacket he had ever seen. Sweet. I wear an adult Small size jacket (not the Minnesota style...and I didn't even know there were different styles). Warwick said that the jacket didn't go up high enough (the middle part goes straight across the middle of my breasts) - it should be up to my collar bones. And the bottom is too low - shaking parts of me where I don't have lungs.

Oh yes and the straps were too lose. He says to messure the cicumference of your chest. Then at 10% to that. That should be the circumference of the Vest (how tight you should have it). Of course mine was wrong

His next question was what type of High Frequency Chest Compression device I had. I have the HillRom Vest 104. This lead into a discussion about types of frequency waves that these devices produce (and lead to my next question about his "new" device).

According to Dr. Warwick, the HillRom Vest 103 is superior in wave frequency shape than the HillRom Vest 104. But he submitted to me that the 104 is probably a better choice because I travel overseas so much (the 103 gave me an inguinal hernia from carrying it around Europe...along with a transformer for the darn thing).

So he moved over to the chalkboard in the room and drew the shape of waves that each device produces. But first, he stopped to inform me that he does receive royalties from the ICS system by Respirtech. He does not from HillRom. I replied that I hope that he makes some money for all the decades of research and contribution he has made for the improvement of CFer's lives. But he is all about full-disclosure.

The 103 HillRom Vest produces a sine shaped wave form. Which Warwick claims is superior for mucus clearance. I think, but cannot remember correctly, that my 104 produces a square wave form. Whichever shape it is, he says that his studies have proven this to be inferior.

Let me step back a bit. Warwick has many, many graduate and PhD students that work with him. They conduct vast amounts of research that Warwick claims he doesn't want to publish because there are too many hoops to jump through. He uses the results in his own patient population, however.

Warwick's newest High Frequency Chest Compressor produces waves in a triangle form. By measuring the amount of mucus that is produce and the amount of air that comes out of a patient's mouth during use, Warwick has concluded that the triangle wave form is the best form thus far.

You can read a peer-reviewed article at http://www.respirtech.com/images/whitepaperLO.pdf

While I was at the clinic, Warwick told me and the PFT nurse confirmed that a recent study involving his triangle waveform Vest was just conducted. He has no idea about the protocols nor the results. However the results will be presented next Thursday.

So, a mixed bag. We have one peer reviewed article on the Respirtech InCourage Vest and more studies to be revealed. Of course I'll email him on Thursday to check out the results. He said he'd let me know good or bad.

Our next discussion was about the frequencies and pressures with which I use my current HillRom Vest 104. I have been using the same frequencies since I started using a Vest 9 years ago. Someone long ago just told me what to do - and I haven't changed it. In terms of pressure - I just always used 5 because it seemed to be in the middle of the road. I did each of 3 frequencies (8, 14, 18) for 10 minutes for a total of 30 minutes.

No no no says Warwick. So he drew me a nifty chart. Which I wish I could put in excel format.

He has measured, definitively, the optimal frequencies for maximum sputum production. 6, 8, 9, 18, 19, 20. Each to be done for 5 minutes each.

In terms of pressure, there's a sliding scale. To find the pressure that's best for you, you start at frequency 6. And pressure 3. Then you take a few breaths. If that's easy for you to breath, then you move to pressure 4. If you're cool with that, then pressure 5. At some point, you'll reach a point where it's uncomfortable to breath. When you reach that point, chose the pressure below that and stick with that.

For me, at frequency 6, pressure 8 was too hard to breath. So pressure 7 is optimal for me. For frequency 6.

So the sliding scale is as follows - when I move to frequencies 8 and 9, I must move 1 pressure point down to pressure 6. And when I move to frequencies 18, 19, 20, I move to pressure 5.

So if you were good at pressure 10 for frequency 6, you would move to pressure 9 at frequencies 8,9 and then pressure 7 for frequencies 18,19,20 (I don't know why it's not 8....but he purposely did it that way). Hopefully I can find a way to post this chart.

Once we had that down, I wanted to know what his thoughts were on Europeans and Canadians not using the Vest. And studies that show manual CPT are just as good as HFCC.

His first comment was that he wishes the American healthcare system was more socialized like the Euros.

His second comment was that the studies that show euqality between manual CPT and HFCC must not have used optimal HFCC settings. LIke the ones I have been using the past 9 years. He says there is no question in his mind that his patients are so healthy because many of them have used HFCC for so many years (more so than the rest of patients in the US). It's better that manual CPT. And he believed that before he started to get royalties from Respirtech.

So that's it for today. There are many many more topics that I would like to write about in detail. But for today, this is enough. I hope you all find it useful.

September 24, 2006

Well, I am safely back in LA. I almost had a heart attack when i landed in Burbank and found that SC was only up 3-0 against Arizona at the 1/2.

So, since I have described my experience with HFCC, the next natural topic I feel is mucus. And sputum.

First I learned the difference between mucus and sputum. I thought they were synonymous. Nope.

Mucus is what everyone has in their lungs and sinus cavities. Everyone meaning even those without CF. It's meant to help lubricate the airways and nasal passages and assist in trapping foreign particles to be taken out of the lungs and sinuses.

Warwick believes that CFers have a normal amount of mucus. It just happens to be dehydrated.

Dehydrated mucus is a great living space for bacteria. Then inflammation occures. And white blood cells attack. And white blood cells die. And bacteria die. And they produce waste. Yadi Yadi.

This creates sputum. It's mucus plus everything else that occures in a CFers lungs due to the mucus' dehydrated state.

Warwick believes that as long as the sputum is kept mobile (through proper coughing techniques and HFCC), infection and other complications can often be avoided.

So along the lines of sputum, Warwick taught me a new way of coughing. He read a recent article discussing reptitive coughing causing damage to healthy airways of those with Chronic Obstructive Pulmonary Disease. He says that he would like the study to be duplicated to provide solid proof, but he has a feeling it will be.

So on that note, he taught me a new way of coughing (new to me anyway) to help my "lungs cough by themselves", as he put it.

This is how it's done. You take a normal breath. But you don't let the air out. Then you take another normal breath. And you don't let the air out. (not DEEP breaths...normal intake of breath). Then you repeat until you can't let any air in. Make sure not to take subsequent breaths in quick succession. Take the breaths as if you were breathing normally. A cough should come afterwards.

Let me warn you - i took me a solid 48 hours to the hang of this thing. And I tried probably once an hour to do it for 10 hours a day (plus after each 5 minute frequency session with my Vest).

And I still can't suck in enough air most of the time to cough reflexively. I usually have to let out a cough. So I'm going to have to email Warwick or ask those from his clinic that have been taught the cough to help me figure out what I'm doing wrong.

But I do have to say I was feeling really congested and short of breath while walking around the airport today. And I couldn't get whatever gunk out that was causing the problem. But I tried the new cough technique - and I got out a nice hung of junk. And not my normal thin, smooth stuff. This stuff was chunky and thick. That made me happy.

So, this cough, as I said, should be done after each 5 minutes of your total 6 frequency series on your Vest.

Warwick also mentioned several times during the consultation that I wasn't coughing enough. Like many CFers, my cough frequency varies from hour to hour. But when I'm at my baseline, I don't cough a whole lot.

Warwick wasn't happy with that. He said I need to purposely cough more often. Using the method he taught me. When I come to a stop sign, cough (I drive a lot at my job). When I change radio stations, cough. Yadi Yadi. Basically, get the gunk out that's causing the infection.

So I forgot to talk about the theory behind the cough. Warwick thinks that this technique can get air behind the sputum. And the air will force the sputum out.

So that's it for tonight. Next topics I'm thinking of talking about are antibiotic frequency (I know I've posted about the Denmark way of doing IV's), CF outlook, communication with phsycians, Mucomyst, CFers experimenting with treatments and having children.

Hope everyone is well. FIGHT ON.

September 24, 2006 PART II

Quoof was kind enough to send me the New Yorker article on Dr. Warwick.

I read it myself a week after it was published almost 2 years ago....and I haven't read it since until today.

It's incredible how similar Warwick is in the article and in person.

He spoke to me about experimenting and how to interpret my results. He used the stereo stethascope. He grilled me about why my PFT's were at 95% instead of 105%. And he challenged me to figure out new ways to make my lungs better than the average person's without CF.

So here's the article for any of you who haven't read it. It's quite fascinating how closely my clinic visit mirrors what is captured in the article.

And thanks Quoof for sending this to me.


September 25, 2006

So we've gone from HFCC, to sputum, and now I want to talk about IV antibiotics and hospitalization.

This topic came up when I visited Warwick because of the recent article I posted on this site about th Danish way of doing IV therapy - every 3 months regardless of health.

Warwick considers hospitalization a failure. But not a failure of the patient. A 100% failure on the shoulders of the physician. He feels that it is his job and the job of every CF doc to ensure that sputum clearance and medication adherence is such that patients don't deteriorate to a point where they need hospitalization. With proper clearance (HFCC) and adherence, patients should remain stable.

He submitted that many physicians don't like the perspective that responsability lies solely on their shoulders. But he says that its up to us as patients to teach this perspective to our docs. And its up to the docs to dig, and dig, to figure out why a patient slips into a need for hospitalization.

Warwick was looking at my records and saw that I was in the hospital last Sept 2005. He asked me why I was in the hospital? Told him I flew to the USC home opener against Hawaii in Hawaii and stood in the blazing hot sun without properly hydrating. Then I flew back to LA the next day and flew out to DC for an NIH study. Long story short, I exhausted myself with too much travel.

He looked at me, puzzled. "What else did you learn?" I didn't have much else than that. "Drink more water????" I replied. He told me that I need to have a heart to heart with my doc every time I'm in the hospital to figure out how the situation can be avoided. Hospitalization shouldn't become standard in CF therapy... it's a big red flag of failure.

So I asked him about the Danish way. He said that the every 3 month thing is probably because of lack of HFCC. He says patients wouldn't need all the hospitalizations if they kept their sputum coming up properly. He also added that there's probably a $ component to the hospitalizations as well.

I think it's pretty phenominal to have two drastically different views on hospitalization, yet two similarly unusual life expectancies (living into 40s and 50s).

So there's the Warwick view on IV antibiotics. Next topic will be Pulmozyme, Hypertonic Salene and Mucomyst.

September 26, 2006

My apologies for not posting last night. I was at the Stanford Women's Information Session. It seems like an incredible MBA school.... anyone have any connections to help me get in?????

So next topic is Pulmozyme, Hypertonic Salene and Mucomyst.

I asked Warwick what his thoughts were on the incredible new development of Hypertonic Salene. It had helped me cough up a bunch of plugs as well as help induce more coughing all together (he said I didn't cough enough, remember?).

He replied that he wasn't all that thrilled. he agrees that Hypertonic Salene is better than placebo or better than doing nothing, but he's not a fan.

Nor is he a fan of Pulmozyme. He claims that his patients do better when they dont' take it. Remember that he is big into his patients experimenting and teaching them how to experiment. He in fact went on to say that he thinks that for his patients the drug does do more harm than good.

He is a fan, as you all have heard, of Mucomyst. And this was one of the biggest a-ha moments for me during the visit. Mucomyst, for those who don't know (and I had no clue what the drug was made of) is N-Acetyl Cysteine. Sound familiar? It did to me once he said it. There has been a HUGE amount of research on this anti-oxident as it relates to CFpateints.

It is thought that CF patients are so suseptable to virulent bacteria because of a lack of Glutathione in the body. And it is thought that N-Acetyle Cysteine is the best building block to put into the body to induce Glutathione production. In fact, in pill form, the body gets more glutathione well all is said and done if N-Acetyle Cysteine is ingested as opposed to pure Glutathione. You can read more about the anti-oxidents on the internet.... Warwick didn't go into it in depth with me.

But as soon as Warwick said N-Acetyle Cysteine I perked up and blurted out "Glutathione!!!!" And he replied "You have just revealed of yourself how much research you are doing." DAMN STRAIGHT.

So Mucomyst goes directly into the airways, right where glutathione is missing in the lungs. And the theory goes that it produces glutathione, thins sputum and helps the body help itself in defending infections.

Warwick mentioned that some of his patients take an oral N-Acetyle Cysteine, mostly when they're on vacation or short on time and don't have time to take their Mucomyst. He says he hasn't seen benefits of doing the Mucomyst and taking the oral NAC.

So that was our conversation about Mucomyst, NAC, Pulmozyme and Hypertonic Salene. Not sure what my next topic will be but I'll try to post it tomorrow night

Well, I know we've all wondered this. And we've all probably gotten different answers from each of our physicians.

Can we do nebs while using the Vest????

I asked Dr. Warwick this in an email. And as I've said in everything else I've posted about Dr. Warwick, i post his reply in the spirit of information. Information can help CF patients live better, longer lives. And I know Warwick strongly believes this so I post his reply publically in the hopes that it will help other CFers out there.

Warwick lets his patients do nebs, as long as they aren't antibiotics, while doing the Vest.

No kidding. The inventor of the Vest, the man whose patients live in average 10 years longer than the US average, has his patients do this.

So for me, I'm doing it. It will save me so much time! Yey!!!!

Hopefully it will save you all time as well. Or at the very least, assure you that what you've been doing is correct. :)

I'll be back on later with eFlow news.... I have 3 more hours to work :)

Warwick's Vest Letter from 2007

I post this in the spirit of information sharing to my fellow CFers. Warwick is so dedicated to CF care that it is my assumption that he would be ok with me posting this to help and prolong the lives of my fellow CFers.

Everything that follows are his words:


Warren J. Warwick,
March 27, 2007


The four High Frequency Chest Compression (HFCC) systems in use today are the asymmetric sine waveform machines (the ElectroMed SmartVest and the Hill/Rom Model 104tm and Model 105tm, the symmetrical sine waveform Hill/Rom Model 103tm and the triangle waveform Respirtech InCourage Systemtm. All but the Hill/Rom Model 103tm, the most widely used HFCC system, are commercially available. The symmetrical sine waveform Hill/Rom Model 103tm is, in my opinion, better than the asymmetric sine waveform machines I expect it to be in use for many years,

The positive aspects of using HFCC therapy include; the simplicity of the HFCC technology, the ease of its use, and that it always works with 100% of the settings on the dials over the whole time of therapy. I believe that HFCC will always provide better treatment than other effective techniques including manual chest clearance, Autogenic Breathing and Active Cycle Breathing as well as the Flutter and Acapella.


HFCC works most effectively when patients breathe with their normal pattern of short inspiration and longer passive expiration. When the patient breaths at the prescribed highest pressures that are tolerated for each frequency the chest compressions, push micro-coughs of air flow through the airways and at the same time oscillating the air in the airway passages. There is a separate simultaneously beneficial effect, for patients with cystic fibrosis, for whom the triangle waveform pressure pulsations will increase the amount of water secreted by the respiratory mucous secreting cells and glands.

I recommend two HFCC therapy sessions of 30 minutes every day for routine preventive therapy (with a pause to cough about every five minutes of HFCC therapy). When the patient has a worsening lung problem, I recommend doing three HFCC therapy sessions a day with up to 60 minutes for therapy each session.


The sine waveform vests must be inflated before HFCC can start. That inflating compression pressure on the chest reduces the patient's lung volume making breathing difficult. Before HFCC therapy starts, every patient must use extra energy and more muscles to breathe. In addition, the Hill-Rom machines must have a tube disconnected from the vest or the machine after each 5 minutes so that the patient will be able to take the deep breath require for coughing.

With the InCourage Systemtm and The SmartVesttm the vest pressure drops to atmospheric pressure when compression pulses stop so a tube does not need to be detached.

Our prescription for HFCC frequencies was developed over 16 years ago measuring the airflow and velocity on 100 patients with CF who used the same vest with each machine. We found a wide scatter of 'best' velocities and volumes; sometimes with several frequencies having almost identical 'best' values. Milla CE, Hansen LG, Warwick WJ. Different Frequencies Should Be Prescribed For Different High Frequency Chest Compression Machines. Biomed Instrum Technol. 2006 Jul-Aug;40(4):319-24. Every frequency was a best frequency for at least one patient. For the sine waveform machine 103tm machine, and by analogy interpreting that data for all triangle waveform machines the best frequencies for large volumes are 6, 8 and 9 Hz and the best frequencies for highest velocities are 18, 19 and 20 Hz. The least effective frequencies are 10 to 17 Hz. Each of these frequencies is used for five minutes in any order followed with a pause for the patient to cough to clear the moved sputum.

With the original square waveform (101TM and 102tm) machines and the triangle waveform inCourage machine both the best flows and volumes are 6, 7, 8, 10, 11 and 14 Hz. The "triangle waveform" frequencies are the same as the square waveform machines.
For the inCourage System I recommend frequencies 6, 7, 8, 10, 11 and 14 for individual frequencies but I prefer the "Quick Start" that continuously, pulse by pulse, increases from 6 to 14 and then from 14 to 6 Hz over a five minute cycle followed with a pause for the patient to cough to clear the moved sputum.


The sine waveform interaction between frequencies and pressures was recognized immediately after the Model 103TM became available for which we developed a clinical adjustment and a teaching table that has now been improved by laboratory research. The guideline for the use of the table remained unchanged. The pressure change is in the 18, 19, and 20 table line for two "4's" for the 103TM and for two "5's" for the 1004TM.

For the "sine waveform" machines, the pressure column is determined by starting with frequency 6 and pressure 3. Then after a few breaths increasing the pressure to 4. If the patient notices no difference to increase the pressure 5 dial setting...and so forth... until the parent notices that the new pressure changes the breathing pattern or the patient complains that the new pressure makes breathing harder. That frequency is TOO high.

The previous lower pressure column is then selected to use to reduce the vest pressure at higher frequencies. For example if the patient notices a difference in breathing with pressure 7 then the patient should use pressure column 6 for all the frequencies. This will need to be checked each year for a growing child in good health and more frequently if changes in height or growth or health are significant.

Patients using Model 103tm or any "symmetric sine waveform" system should adjust frequencies and pressures using the Table for the Model 103tm with frequencies 6, 8, 9, 18, 19 and 20 in sequence, for 5 minutes each frequency followed by a cough. The frequencies 10 to 17 have been shown in our Minnesota Research to be the least likely to be a useful for airway clearance.

Table for the Model 103tm

Frequencies to be used in sequence Pressure Columns
6 3 4 5 6 7 8 9 10
8 and 9 2 3 4 5 6 7 8 9
18, 19 and 20 1 2 3 4 4 5 6 7

Patients using the Model 104tm should use the Model 104tm table with frequencies 6, 8, 9, 18, 19 and 20 in sequence, for 5 minutes each frequency followed by a cough.

Table for the Model 104tm

Frequencies to be used in sequence Pressure Columns
6 5 6 7 8 9 10
8 and 9 4 5 6 7 8 9
18, 19 and 20 3 4 5 5 6 7

*This graphic is simply to help understand the information posted above. I realize that the numbers aren't the same as what Warwick says, so please follow Warwick's instruction rather than what appears on the table. The graphic is simply to help you better visualize what Warwick is talking about

Neither the SmartVest nor the ICS can have dial frequency and dial pressures settings with too great a variation for the preparation of a table for adjusting dial pressure with the dial frequency. The SmartVest System has such a high increase in vest pressure as frequencies are raised that the pressure to use for each frequency will have to be individually determined for each patient.

The ICS system jacket pressure has a large drop in vest pressure as frequencies are increased so the RespirTech Inc's guidance should be used. Using the QuickStart ramp with frequencies going up and down, 6 to 14 Hz and back to 6 Hz, wit the highest pressure that can be tolerated over the five-minute cycle is proving to be very effective. The goal is to have the patient use 100% of power.

When the patient first starts HFCC therapy I recommend rechecking the pressure columns after several weeks because strengthening of the chest muscle may make a higher pressure column a better choice. I will be very pleased to hear from patients about their experience.


The InCourage Systemtm and the Model102TM use valve systems rather than a piston equivalent pressure system to generate the HFCC compressions. Therefore we used the Model 102TM best frequencies we compared this triangle waveform versus the Model 103tm symmetric sine waveform ( Milla CE, Hansen LG, Weber A, Warwick WJ. High-frequency Chest Compression: Effect of the Third Generation Compression Waveform. Biomed Instrum Technol. 2004 Jul-Aug; 38(4):322-8). With the triangle waveform was used with frequencies 6, 7, 8, 10, 11 and 14 Hz frequencies with the highest tolerated pressure. With the symmetric sine waveform using the Model 103tm these patients used the 103 table to adjust the pressures with the frequencies 6, 8, 9, 18, 19 and 20. [U]The patients using the triangle waveform system produced an average of 22% more sputum than with the sine waveform. [/U]

I recommend that the InCourage Systemtm Quick Start program start at frequency 6 Hz and go up to 14 Hz and then back to 6 Hz over five minutes:... then to stop the pulsations for a brief time to cough. After coughing, the patient will repeat these steps five more times. Each ramp provides a virtual 3000+ frequency, in sequence, pulses from low to high and high to low during each 5-minute cycle. All the airways, regardless of dimensions, will have optimum frequencies plus harmonics and hypo-harmonics many times throughout each cycle.

The InCourage Systemtm has a unique range of pressures. Pressures 10% to 50% have been designed for babies and very small children. The use of these pressures should be considered experimental because we have not yet studied this use. At this time, I recommend that these low pressures should be used only under close medical supervision since accidental use of these pressures by toddlers and older patients show that, for users after infancy, these pressures are too low for effective airway clearance of sputum.

So far we have found that with every constant pressure setting the InCourage Systemtm jacket pressures decrease as the frequencies are increased. Each patient should test a pressure setting over a "Quick Start" ramp cycle to determine the highest pressure that the patient can tolerate over the cycle. The cycle is hardest to breath at the start and end of the cycle and easier during the middle of the cycle. My goal is to have all patients using 100% of the machine pressure. I recommend that patients 4 years and older start at 80%. For younger patients I recommend starting at 70%. No patient should use pressure below 70% for therapy although 60% may be used to accommodate small children to the feel of HFCC. I recommend working with the patient to adapting the 100% pressure..

The InCourage Systemtm and Models 103tm and 104tm and the SmartVest have collectively and successfully been used by over sixty thousands of patients for over 28 years with success, mostly without my guidelines. Never the less when one of these patients tries these recommendations I frequently hear that their system works better. These guidelines are the best guidelines I have developed.


At this time, only RespirTech has specific directions for the measurement of the patient and the adjustment of their jackets to fit with the vest circumference/chest circumference ratio is about 110%. Regardless of the HFCC system every patient's vest/jacket should fix the 110% circumference ratio by means of safety-pins or re-adjust the circumference ratio fitting to about 110% with every use. The safety pin fixation should be checked when the patient has grown, gained weight or changes the clothes that are worn during HFCC therapy. For all machines, the vest/jacket should cover all of the rib cage, from the collar bones down to the lowest ribs, with the un-inflated circumference of the vest/ chest circumference being about 110%.

If an increase of pressure alters breathing or breathing becomes uncomfortable, assume that that pressure is, at least for a while, too high for daily use. This may require daily testing of pressure, see above. Keep in mind that, as the airways become cleaner, higher-pressure pulses the patient's breathing may become less comfortable and effective.

Our basic science research has developed much of the information discussed above and confirmed earlier work. We are studying the Minnesota HFCC technology that has built or inspired the development of the Models 101tm, 102tm, 103tm, 104tm, 104tm, the SmartVest and the ICS systems. Graduate students working in the Minnesota Defense of The Lungs Project have earned three MS degrees and one PhD degree with two more PhD's expected later in 2007.

Our laboratory research ranking of estimated effectiveness, which will need to be confirmed by CF patient studies by other researchers and, is that the ICS > Model 103tm > Models 104tm and 105tmand the SmartVestTM which we assume to be equal because all three have almost identical asymmetric sine waveform output.

Your observations and questions will help us define tasks to solve and will help us improve all forms of HFCC.

My expiration date for these recommendations is March 27, 2008.


Phase II NAC Trial / Patent Application

Dr. Moss, the author of the Stanford NAC study, has filed for an NAC patent relating to an NAC kit.

This tells me that what he's seeing in his Phase II clnical trials with NAC are very promising. Take a read at what they've found regarding safety in Phase II trials....

If you haven't read Moss' NAC Phase I study, check it out on my blog.

You don't have to read the whole article but it is quite educational....

Methods for treating and monitoring inflammation and redox imbalance cystic fibrosis

The present invention relates to pharmaceutical kits and methods to treat lung inflammation and redox imbalance in human cystic fibrosis patients using pharmaceutical compositions containing N-acetylcysteine (NAC), pharmaceutically acceptable salts of N-acetylcysteine, or N-acetylcysteine derivatives.

In phase I studies, treatment with oral NAC at a dose of from about 1800 mg/day to about 3000 mg/day for a period of 4 weeks produced significant positive effects, namely, it decreased absolute numbers of white blood cells and neutrophils in the sputum and produced concomitant decreases in sputum neutrophil elastase specific activity and sputum interleukin-8 levels, suggesting an amelioration of lung inflammation in the patients.

These effects were associated with an increased total GSH level in whole blood as well increased staining for reduced GSH in blood neutrophils, both of which reflect an amelioration of the redox imbalance in the patients.

In ongoing phase II studies, oral NAC at a dose of about 2700 mg/day administered in double-blind manner for 12 weeks showed excellent safety and significantly decreased white blood cells in sputum as compared to placebo.

Patent Agent: Patent Docket Administrator Lowenstein Sandler PC - Roseland, NJ, US

Patent Inventors: Rabindra Tirouvanziam, Lenore A. Herzenberg, Leonard A. Herzenberg, Carol Conrad, Richard B. Moss

Applicaton #: 20070049641 Class: 514562000 (USPTO)

Related Patents:Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Radical -xh Acid, Or Anhydride, Acid Halide Or Salt Thereof (x Is Chalcogen) Doai, Carboxylic Acid, Percarboxylic Acid, Or Salt Thereof (e.g., Peracetic Acid, Etc.), Nitrogen Other Than As Nitro Or Nitroso Nonionically Bonded, Sulfur Nonionically Bonded
Brief Patent Description - Full Patent Description - Patent Application Claims


[0001] This application claims the benefit of priority to U.S. Provisional Application No. 60/710,807 (filed Aug. 24, 2005) entitled "Methods For Treating And Monitoring Inflammation And Redox Imbalance In Cystic Fibrosis," the entire contents of which are incorporated by reference.


[0002] The present invention relates to pharmaceutical kits and methods for treating lung inflammation and redox imbalance conditions in cystic fibrosis using pharmaceutical compositions comprising N-acetylcysteine, pharmaceutically acceptable salts of N-acetylcysteine, or pharmaceutically acceptable derivatives of N-acetylcysteine and a pharmaceutically acceptable carrier.



[0109] Based on the described phase I results, an Investigational New Drug application was submitted to the Food and Drug Administration (IND #73,410), detailing plans for a phase II trial. This application successfully passed the Food and Drug Administration review process. The phase II trial consists of a 12-wk placebo controlled portion, followed by a 12-wk open label portion, both featuring oral NAC treatment at about 2700 mg/day, administered t.i.d. As of June 2006, the 12-wk placebo-controlled portion of this phase II trial was brought to completion.

[0110] In compliance with guidelines defined in the Investigational New Drug application, safety data and efficacy data for the primary (sputum cellularity) and main secondary (functional expiratory volume in 1 second) outcome measurements were communicated to the Data and Safety Monitoring Board of the Cystic Fibrosis Foundation before unblinding the study.

[0111] 1--Enrollment and Compliance

[0112] Of the 24 CF study patients who underwent screening, 21 were found eligible for enrollment, based on evidence of ongoing lung inflammation (sputum cellularity >0.9, Log.sub.10 scale). Of these 21 patients who received NAC or placebo, 3 were withdrawn for poor compliance before the 12-wk time point. Hence, a total of 18 patients completed the 12-wk time point (% completion=85.7). Among these 18 patients, compliance at the 12-wk time point was excellent, reaching 93.0.+-.1.9% (mean.+-.SE). Compliance was not different between the NAC and placebo groups (93.3.+-.2.3 vs. 92.6=3.2, respectively, N=9 in each group, P=0.9).

[0113] 2--Safety

[0114] The first 12 weeks of this phase II trial (placebo-controlled phase) yielded excellent safety data. No NAC- or placebo-induced serious adverse events were reported. Only 1/18 patients reported adverse events that were likely to be related to treatment (patient in the NAC group), i.e., abdominal discomfort/indigestion which was treated by daily Pepcid AC.RTM.. There was no other GI complaint related to NAC (or placebo). Exacerbations of sinus and lung disease affected 5 and 4 out of 18 patients, respectively. The occurrence of exacerbations did not differ between NAC and placebo groups and was not considered to be linked to the trial. Complete blood count and blood chemistry (including liver enzymes) did not show any significant change for either NAC or placebo groups. Hence, safety of high-dose oral NAC administration over the course of 12 weeks showed even better safety results than the 4-week-treatment tested in phase I.

[0115] 3--Efficacy Data on Lung Inflammation

[0116] In this placebo-controlled phase II, results obtained in phase I were confirmed with regard to the ability of NAC to decrease sputum cellularity significantly (Table 3). There was no significant change in sputum cellularity in the placebo group. The significance of this positive effect of NAC on sputum cellularity was further increased when the 6 patients (3 in each group) with confounding treatments administered during the 12-week trial period (prednisone and tobramycin) were excluded from the analysis (Table 3). With these 6 patients excluded, the difference between NAC and placebo groups was statistically significant upon between-group analysis. Hence, the primary outcome measurement in this phase II trial yielded positive results.

[0117] 4--Efficacy Data on Lung Function

[0118] CF lung disease is characterized by the progressive decline in functional expiratory volume in 1 second (FEV1% predicted). The term "FEV1%" as used herein refers to Forced Expiratory Volume during the first second/FVC, where FVC refers to Forced (ExpiratoryVital Capacity (Liters), meaning the maximum volume of air exhaled as rapidly, forcefully and completely as possible from the point of maximum inhalation. Slowing down, stopping or reversing this decline reflect positive effects of a treatment, which generally requires long-term administration. When the 6 patients (3 in each group) with confounding treatments administered during the 12-week trial period (prednisone and tobramycin) were excluded, the NAC group, but not the placebo group, showed a significant increase in FEV.sub.1 % predicted (Table 3). This effect, however, did not reach significance in the between-group analysis, underlining the necessity for larger patient cohorts to ascertain the potential positive effect of oral NAC treatment on CF lung function. TABLE-US-00003 TABLE 3 Chosen drug effects (post-treatment vs. baseline) during the phase II trial Placebo: Between- Subjects Outcome NAC: Median Median group (N) measurement [interquartile] [interquartile] analysis All Sputum -0.22 -0.16 P = 0.825 cellularity [-0.34; +0.01] [-0.51; +0.35] (Log10) P = 0.030 P = 0.221 6 [Decrease is a -0.27 +0.06 P = 0.025 ex- positive effect] [-0.43; -0.19] [-0.19; +0.77] cluded P = 0.002 P = 0.218 All FEV1 +1.0 +2.0 P = 0.791 (% predicted) [-1.0; +6.0] [-12.0; +10.5] [Increase is a P = 0.150 P = 0.470 6 positive effect] +3.5 -3.0 P = 0.328 ex- [-0.3; +8.5] [-11.0; +7.0] cluded P = 0.037 P = 0.328

[0119] While the present invention has been described with reference to the specific embodiments thereof, it should be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the Invention. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, process step or steps, to the objective, spirit and scope of the present invention. All such modifications are intended to be within the scope of the claims appended hereto.

Phase I NAC Trial


High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis.

Tirouvanziam R, Conrad CK, Bottiglieri T, Herzenberg LA, Moss RB, Herzenberg LA.

Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. tirouvan@stanford.edu

Neutrophilic airway inflammation is a hallmark of cystic fibrosis (CF). As high oxidant producers, airway neutrophils contribute largely to the systemic redox imbalance seen in CF. In turn, this chronic and profound imbalance can impact circulating neutrophils before their migration into airways. Indeed, in 18 CF patients with stable disease, blood neutrophils were readily deficient in the pivotal antioxidant glutathione (P = 0.003, compared with 9 healthy controls). In a phase 1 study, this deficiency was improved (P = 0.025) by the glutathione prodrug N-acetylcysteine, given orally in high doses (0.6 to 1.0 g three times daily, for 4 weeks). This treatment was safe and markedly decreased sputum elastase activity (P = 0.006), the strongest predictor of CF pulmonary function. Consistently, neutrophil burden in CF airways was decreased upon treatment (P = 0.003), as was the number of airway neutrophils actively releasing elastase-rich granules (P = 0.005), as measured by flow cytometry. Pulmonary function measures were not improved, as expected with short-term treatment. After excluding data from subjects without baseline airway inflammation, positive treatment effects were more pronounced and included decreased sputum IL-8 levels (P = 0.032). Thus, high-dose oral N-acetylcysteine has the potential to counter the intertwined redox and inflammatory imbalances in CF.

PMID: 16537378 [PubMed - indexed for MEDLINE]

Anti-histamines even when you don't have allergies

February 20, 2007

White Blood Cells In Lung Produce Histamine Seen In Allergies

In a surprise finding, scientists have discovered that histamine, the inflammatory compound released during allergic reactions that causes runny nose, watery eyes, and wheezing, can be produced in large amounts in the lung by neutrophils, the white blood cells that are the major component of pus.

Pus, a fluid found in infected tissue, is produced as a result of inflammation.

The study in mice is the first to show that lung neutrophils can produce histamine in significant quantities, according to principal investigator George Caughey, MD, chief of pulmonary/critical care medicine at the San Francisco VA Medical Center.

"Previously it was thought that the primary sources of lung histamine, in health as well as disease, was mast cells, which are classically associated with allergy," notes Caughey, who is also a professor of medicine at the University of California, San Francisco.

Caughey says the result could mean that histamine acts as a link between airway infections and asthma and bronchitis, which are associated with allergy. "In both, we observe inflammation - swelling, blood vessel leak, and muscle contraction that narrows the airway."

The study appears in the January 2007 issue of the Journal of Experimental Medicine.

Caughey was investigating the well-known fact that upper respiratory infections often trigger acute asthma attacks. "We hypothesized that an infection in the airway would release histamine from mast cells, and that would be one of the reasons," he explains.

To test the hypothesis, Caughey and his team exposed two different populations of mice to mycoplasma, a common respiratory infection in rodents and humans. One population had a genetic abnormality that causes a total lack of mast cells; the other population was made up of normal, wild-type mice. Both populations of infected mice developed pneumonia.

"We thought the mice without mast cells would do better than the wild-type mice, because the infection wouldn't be provoking mast cells to release histamine," recalls Caughey. "In fact, they did much worse. Even though there were no mast cells, histamine levels rose up to 50 times normal."

The reason was straightforward, Caughey says. Neutrophil numbers increased in response to infection, and neutrophils in turn produced histamine. "It's a direct effect of the mycoplasma bacteria on neutrophils. They induce neutrophils to produce the enzyme that produces histamine."

Individual neutrophils produce much less histamine than individual mast cells, says Caughey, but "because pus contains millions if not billions of neutrophils, the overall amount they make is very considerable."

The neutrophil-histamine effect was similar in the wild-type mice, reports Caughey: "Histamine levels from neutrophils blew right past the histamine levels contributed by mast cells."

The wild-type mice suffered less severe infections overall because "as a number of recent studies, including ours, have shown, mast cells actually play a role in protecting against bacteria," Caughey explains. "For example, a mouse without mast cells with the equivalent of a ruptured appendix will die of the resulting infection, while a mouse with mast cells can survive."

When the infected mice without mast cells were given antihistamines, the level of histamine, and therefore the severity of the pneumonia, dropped in proportion to the amount of antihistamine given.

"This is a study in mice, so we cannot freely extrapolate the results to human beings," cautions Caughey. "Nonetheless, antihistamines may deserve more of a look as therapeutic options in lung and airway infection."

He says the study also has implications for other types of airway infection "in which there are a lot of white blood cells -cystic fibrosis, for example, which can be associated with asthma-like airway contraction."

The next steps for Caughey and his research team are to investigate "how general this result might be. Does only one type of bacteria cause the effect, or do others, also? Is it limited to rodents, or does it carry forward to humans? And if it does, is the amount of histamine produced by neutrophils enough to make a clinical difference?"


Co-authors of the study were Xiang Xu, MD, PhD, Dongji Zhang, MD, PhD, Hong Zhang, PhD, Paul J. Wolters, MD, Nigel P. Killeen, PhD, Brandon M. Sullivan, Richard M. Locksley, MD, and Clifford A. Lowell, MD, PhD, of UCSF.

The study was supported by funds from the National Institutes of Health, the Diamond Family Foundation, and an Elizabeth Nash memorial fellowship from Cystic Fibrosis Research, Inc. A part of the NIH funds was administered by the Northern California Institute for Research and Education.

NCIRE is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.

SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.

Contact: Steve Tokar
University of California - San Francisco


Anti-histamines explained

So here's the low down with anti-histamines per my research. Keep in mind there are two items you must keep in mind in terms of drugs: efficacy & side effects. I'll examine both.

There are two generations: 1st and 2nd.

1st generation includes meds like diphenhydramine (Benadryl). This med, in terms of efficacy, is by far the best. Benadryl is an extremely powerful anti-histamine. Side effects, however, are just as strong. It has anti-cholinergic effects and can dry up sputum. Additionally, the med crosses the blood brain barrier and causes lots of drowsiness (a SUBJECTIVE measurement) and impairment (OBJECTIVE measurement). There is a difference between drowsiness and impairment.

2nd generation includes Claritin (loratadine), Clarinex (desloratadine), Zrtec (ceterizine) and Allegra (fexofenadine).

Claritin was 1st to market and was considered a miracle drug cuz it worked pretty well and didn't have those horrible side effects like drowsiness and impairment like Benadryl did. The makers dosed it at 1/2 the European dose, though, so that it wouldn't cause as much drowsiness. Many people don't feel the efficacy of Claritin unless they double the 10mg dose to 20mg. At 20mg, the Euro dose, it can cause drowsiness or impairment. But it does not have anti-cholinergic effects.

Claritin is metabolized by the liver into Clarinex (loradadine into desloradadine) so you can treat them as the same drug.

There are 2 head to head studies, 1 compariing Zyrtec to Claritin, 1 comparing Allegra to Claritin, showing that both Zyrtec and Allegra relieve allergy symptoms better than Claritin.

Zyrtec has more sedation & impairment side effects than Allegra & Claritin, as it readily crosses the blood brain barrier. It also has mild anti-cholinergic effects, but not as bad as Benadryl.

Allegra does not have anti-cholinergic affects nor does it cross the blood-brain barrier so sedation & impairment do not occure.

2 head to head studies, both studying patients with the most severe allergy symptoms, showed that Allegra & Zyrtec are equally as powerful.

So the winner in my mind, and what I take, is Allegra 180mg.

Hope this helps

Anti-histamines Benedryl (diphenhydramine), Claritin (loratadine), Clarinex (desloratadine), Allegra (fexofenadine), Zyrtec (ceterizine), Xyzal (levoceterizine)

Differences Between Nose Sprays per my Research

Differences Between Nose Sprays per my Research

There are 4 Rx nose sprays on the market. Flonase, Nasacort AQ, Nasonex and Rhinocort Aqua.

Rhinocort Aqua is by far the weakest. Unlike the others on the market, you need to titrate up for maximum efficacy. This can mean 4 sprays per nostril per day - and a prescription that only lasts about 2 weeks. But RA does lack alcohol, which is a good thing.

Head to head studies of Nasonex vs. Flonase demonstrate that Flonase has superior efficacy. But Nasonex does lack alcohol whereas Flonase contains alcohol (which causes nose bleeds and heads).

Head to head studies of Flonase vs. Nasacort AQ demonstrate equal efficacy (even in patients with severe symptoms). Nasacort AQ lacks alcohol as well.

Nasacort AQ is the winner.

Wednesday, August 6, 2008

How I treat Allergies

What I do to treat allergies

1. Allergy testing. Many people have house-hold allergies in addition to outdoor allergies. Controlling indoor allergies can greatly diminish symptoms of outdoor allergies. But first, you need to get skin tested (by an allergist, not a GP) - IgE blood levels are useless so don't go down that route.

2. Most of us have dust mite feces allergies. I have dust mite encasings on my pillows and mattress (purchased at www.allergyasthmatech.com)

3. I have no carpet in my place, but when I did in college I put dust mite powder on my carpet (simple to use - just put it on the carpet and then vacuum it up a few hours later. it lasts 6 months). Also can be found at www.allergyasthmatech.com

4. HEPA air purifier in the room that I do meds and my bedroom. Nothing else but HEPA will do. I bought mine at www.costco.com

5. I never open windows in my house. It's a pain, but it lets allergens in. Instead, I run my air conditioner

6. I take an anti-histamine. 70% of the allergic cascade is attributed to histamines. As Nicole said, check out my blog for an explanation of the differences between anti-histamines (school down to categories on the left, then click medications)

7. I take a leukotriene agonist. 30% of the allergic cascade is attributed to leukotrienes. Singulair is my med of choice there

8. I take an intranasal steroid. Flonase has alcohol in it (spraying alcohol up my nose hurts, burns, smells badly and causes nose bleeds). I use Nasacort AQ instead. It's just as powerful, but no alcohol.

9. Allergy shots.

10. One thing I forgot - getting rid of down comforters and pillows if you're allergic to down. What a difference that makes!

Treating allergies when you have CF can dramatically improve lung function. Allergies cause inflammation in the lungs - and as you know, as CFers, we already deal with so much inflammation to begin with. So heading allergies off at the pass is essential to good health.

My experience with NAC

Originally posted in Fall 2006

I figured there is no way I could see a difference in my lungs after two doses of Euro NAC.....

If someone else posted this, I would dismiss it immediately.....

But I have never had an easier time exercising on my elliptical as I did this morning. Granted, I have been exercising consistently for 2.5 weeks now. So I guess all of a sudden my endurance could have gone up.

But man did I feel different exercising this morning. Really different.

At worst, this is a huge endorsement for exercising and lung function. At best, this NAC stuff works quickly.

I'm still skeptical of the NAC stuff working quickly.

So, as many of you Americans know, vitamins, minerals and supplements in the US aren't regulated.

So if you go to the drug store, buy NAC, there's no guarantee that what you're buying is really NAC. Or the quantity of NAC that the bottle claims. And powder NAC (in capsules) can be OXIDIZED, rendering it useless.

This is why Dr. Moss up at Stanford didn't use NAC from the US because you can't do a study where the quality could be highly variable. Plus the NAC he uses is in the fizzy form - tablets that can be plopped in water. These fizzy tabs are NOT oxidized and therefore you are guarenteed their integirty.

So my boyfriend went home to Europe over New Year's and bought me some NAC. In Europe, vitamins, minerals and supplements are regulated. They're prescription! So you know what you're getting is exactly what's on the bottle.

Some don't like that it's Rx, but that's the trade off i suppose.

You can also get fizzy NAC from Canada from the company that Moss uses: www.bioadvantex.com

So today was my 1st day with NAC the Euro way. It's a 600mg tablet that dissolves in water. Body absorbs liquid NAC better than tablets, apparently.

It tastes gross. My BF tells me that that's how I know it's working. Hhahaha. I know I'll get used to it becuase I'll be drinking this stuff 2-3 times a day.

As the Moss study says, it can take a few months to see clinical benefits from the NAC, but I'll keep you guys posted. Hopefully I'll get used to the taste :-P

2.5 years later I'm still taking NAC and I'm convinced it's played a big role in keeping my lung function up and helping me recover from colds / PA flare-ups.

But remember: no capsule form of NAC!!! It can be oxidized. Fizzy NAC only

Tuesday, August 5, 2008

Warwick's Letter after my visit in 2006

This is a re-posting of Warwick's Letter to me after visiting him in September 2006. I wanted to have his whole letter in one place instead of multiple blog entries.

Even if you've read the Letter before, it's wise to read it again. You'll be surprised about how much you've forgotten.....

Just to re-iterate .... the words that follow come from a letter that Warwick sent me in the mail after my consultation with him. To my knowledge none of this has been published (unless he refers to a specific publication in the letter). I am posting this in the spirit of information for my fellow CFers from a man who has been instrumental in extending all of our lives. I am posting it for everyone because I believe that Dr. Warwick believes as I do that information can help CF patients improve the quality of their lives as well as longevity. All words that follow are Dr. Warwick's words and his words only. Even the grammar and spelling errors :-P


So I received a 39 page letter from Warwick yesterday.

The first few pages detailed our visit...and then rest covered his theories on all aspects of CF.

So I'm going to re-type some of his points on here so you guys can hear his words instead of mine. Of course the overall theme is the same, but stil highly educational.

He starts the general discussion portion of the letter by saying:

"These thoughts are based on over 45 years of caring for patients, parents and families with CF and by the wonderful questions that have been asked during these consultations. But be careful, do not consider what I believe and say about the treatment of CF is the "right" or "only" way CF care should be given. There are many very good opinions of very good CF doctors that are diferent from my opinions.

"When you share these pages with your CF doctors I hope that they will not be offended by a different opinion I have discussed with you or have wirtten in this letter if what they do differs from what I do. If all doctors were to think the same then only onew ould be needed and we would never improve treatments or the future for patients with CF.

"Remember the old English saying: 'Opinions between good men is knowledge in the making.' So as your physicians disagree with some of the things I have written; knowledge is in the making.


"I have my own answers, based on observations I have made while caring for over 1000 patients.

-Children with CF are on the average smarter than other children
-They have better lungs before they acquire the CF associated with airway disease
-CF is not a disease


"The facts are that the clinical diseases associated with CF have the common origin in the inheritance of a mutation in two CFTR genes, one each from father and mother, that these two inherited genes produce an increased risk for the person to acquire a large number of diseases. These diseases are common in the general population and include: bronchitis, pneumonia, sinusitis, nasal polyps, pancreatic insufficiency, diabetes, male infertility, and less frequently cirrhosis, symptomatic gallstones, and even kidney stones.

"The assumption that comes next is that acquired diseases can be pevented or controlled with currently available treatments. While the inheritence of CF brings such a large risk to develop the large number of unwanted problems, there is a good side to this information. Both the person who has the genetic CF and the CF doctor know, once the diagnosis of CF is made, which specific illlnesses are at risk for and so can take preventative precautions.

" CF patients are not alone. Everyone has at least a few unknown genetic risk factors for other diseases but, not knowing the diseases at risk, do not know what the risks are. All of us have no idea of what actions might be taken to prevent such potential problems."


"The name of this genetic problem should return to the orginal name [B] Cystic Fibrosis of the Pancreas [/B] The generic use of preventative pulmonary treatments has demonstrated that CFP patients can grow old with pulmonary function tets are in or above normal range. But these patients are similar to the rest of the CF patients: about 97% have pancreatic insufficiency, over 20% have diabetes and another 20% have two hour glucose levels characteristic of pre-diabetes. They and their CFP doctors have ben diligent in prophylactic pulmonary treatment and perhaps a bit lucky.

"When I started working with CF the life table survival age was two years and now, at the Minnesota CF Center, the life table survival age is over 48 years. I believe the philosophy of prescribing the known preventative treatments to try to prevent as many of these problems as possible, the Minnesota CF Center's practice, is the reason for our Minnesota success. I am certain that the most effective approach is vigorous airway clearance started at the time of diagnosis and continued twice daily. This is now built around our prescription of high frequency chest compression therapy starting as low as 12 months of age. "

OK there are a million more topics such as HFCC, Mucomyst, Steroids, Inhaled Antibiotics, Coughing Technique, Weight, Exercise, Enzymes, etc that I promise I will type about in the coming days. Some of it will repeat what I have already typed, but it will be Warwick's words instead of my memory of them :)

High Frequency Chest Compression

"The three HFCC systems manufactured today are the sine waveform HillRom Moden 104 and the ElectroMed SmartVest and triangle waveform RespirTech inCourage System. The Advanced Respiratory Model 103 is as of 2006 still used by over half of the patients using HFC. The following recommendations for the Hill/Rom Model 104 and the ElectroMed SmartVest are based on the similarity of the mechanical systems and the sine waveforms generated by their pulse generator machines.

"The positive aspects of using HFCC therapy include: the simplicity of the HFCC technology, the ease of use, and that is always works 100% of the settings on the dials over the whole time of therapy and for the older patient is always available. HFCC will forever provide better treatment than other effective techniques including manual chest clearance, Autogenic Breathing and Active Cycle Breathing because, until it wears out, will always deliver 100% what each system can deliver. My experience with the Flutter and Acapella is the technique is critical, that they are seldom used well and that they waste time, money and the opportunity for doing better HFCC airway clearance.

"HFCC works most effectively when a patient inhales slowly and deeply (this also lowers the blood pressure). Exhalation should be passive. The patients should breath through the nose so that the chest compression oscillations in the airways will also oscillate air in the nasal passages. Patients should pause to cough (see the section later in the these pages) after every five or six minutes of HFCC therapy. I recommend 2 daily HFCC therapies in sessions of 30 to 36 minutes each for routine preventative therapy with an increase to 3 times a day during times when the patient has a worsening lun problem.

"All sine waveform vests must be inflated before HFCC can state. Becuase the inflation compression reduces the patient's lung volume breathing becomes difficult. Thus every breath requires extra energy and use of more muscles. As inspired air increases the volume of chest, the volume of the vest decreases; the result is increased pressure in the vest making it heard to finish that breath. The less air in the lungs the less effective is the HFCC oscillation of the air in the airways.

"Patients hsould puase to cough every 5 to 6 minutes of HFCC therapy. With the HillRom Models 103 and 104 and the SmartVest "sine waveform" machines the patient must remove a connection tubing from the vest, or the machine, in order ot remove the chest restriction and so to be able to take the full breath required for best coughing. The SmartVest is the only sine waveform machine that reduces the vest pressure to atmospheric when compression pulses stop (claim of ElectroMed which we have not confirmed). With Model 101 and Model 102 "square waveform" machines and inCourage System "triangle waveform" macine the vest pressure drops to atmospheric when the vibrations stop so a tube does not need to be detached.

"The Minnesota clinical prescription for frequencies to be used with the 103 sine waveform the HFCC machine was developed over 16 years ago and remains our prescription for all sine waveform HFCC machines. We tuned 100 patients to find out the best frequencies for the compression induce volume and air velocity with each compression for each frequency. We found a wide scatter of 'best' velocities and volumes; sometimes with several frequencies having almost equal 'best' values. Every frequency was a best frequency for some patients. For the 103 machine the largest volumes were under 10 Hertz (Hz) [times per second ] and the highest velocities were 15 to 20 Hz. With the 102 machines both the best flows and volumes were 6 to 15 Hz (different frequencies should be prescribed for different high frequency chest compression macines. Biomed Instrum Technol. 2006 July-Aug; 40(4):319-24.) The triangle wave form produced by the inCourage System frequenices have not been tuned by laboratory studies predict that the range of frequencies will be the same as for the 102 machine.

"When we started prescribing HFCC wih the Model 1 and then the Model 2 we shortened the therapy time from 60 for the manual percussion treatment to 30 minutes using the three highest velocities and the three largest volume frequencies (frequencies 6, 7, 8, 11 and 140 for 5 minutes each followied by three coughs; and to save more time we prescibed Mucomyst aerosols to be used during the 30 minutes of HFCC).

Pressure and Frequency Interactions

"Model 101 had only one pressure so no interaction should occur.

"Model 102 had five pressures over a small range and most patients used only the highest pressure for all frequencies. No interaction was reported by patients or parents.

"For the inCourage System I recommend ramping frequencies from 6 to 15 and back (15 to 5) under computer control over six minute periods. This covered completely the range of best frequencies from teh Model 102 machine. With the inCourage System we have observed a mirror imagine of the jacket pressure than that we observed with the Model 103, i.e., a decrease in the MOdel 103 with the increasing frequencies. Our adjustment is to recommend the use of the histest pressure that can be used without difficulty breathing at frequency 6. This varies a lot for one four year old using pressure 80, the third highest pressure, without difficulty.

"For the Model 103 the interaction was first recognized by patients who reduced the dial pressure when they used the high frequencies. After years of patients' complaints Lee Hansen and I measured the relationship between frequencies and pressures and the percent of pressure transfer of vest pressure that was measurable at the mouth. We found that the pressure we mesured in the mouth/vest ratio was reduced by about 30% the percent of the highest measurement. using that information I developed THE MINNESOTA TABLE FOR FREQUENCIES AND PRESSURES for reducing the pressure when higher frequencies are used. My advice for pateints using Model 103 (or any sine waveform syste) is to adjust frequencies and pressure using the Minnesota table using preferred frequencies 6, 8, 9, 18, 19, 20. " (Note that the table below is a visual representation of the Minnesota Table. Frequencies and pressures shown in the graphic aren't the same as what Warwick recommends.... the table is just to help you better understand the information that follows below. Also, please see Warwick's 2007 letter posted on this blog for further clarification about the Minnesota Table)

"For the sine waveform machines the pressure column is determined by starting therapy with frequency 6 and pressure 3. Then after several breaths increase the pressure to 4 and if the patient ontices no difference go to pressure 5 continuingly testing higher pressures until the patient notices that with the new pressure it is harder to breath. That lat pressure is too high for frequency 6

"The pressure lower determines the column to be used to reduce the vest pressure at higher frequencies. For example, if the patient notices a difference in breathing with pressure 7 then use pressure column D for all frequencies. This should be checked twice a year for a growing child in good health and more frequently if changes in height or growth or health are significant.

"The inCourage System uses a new valve that interrupts a constant flow of air from the machine into triangle wave forms of energy.We did one clinical study with an early very large prototype machine comparing the effectiveness of new trangle waveform versus the sine waveform. The triangle waveform, using the frequency recommened for the square waveform machines and a pressure that did not make breathing difficult, produced an average of 20% more sputum than the sine waveform delivered using the table to adjust pressures to avoid difficulty breathing. We know now that the assumptioms for choosing presures used for the triangle waveform were wrong. This produced lower pulse pressures, the pressures that move air through the airways, instead of staying constant when that formula is used for the sine waveform system.

"I recommend that the inCourage System have a default program to start at frequency 6Hz and go up to the 15Hz and then back to 6Hz over fie minutes. This would eliminate the need to get another 100 CF patients to have the best air flow rate and velocities and so to prescribe specific frequencies. By using 3000+ frequencies in sequence from low to high and back treatments would covera ll of the frequencies in range best frequencies for the other valve machines making treatment very simple. So that all the patients would have to remember would be to cough after each cycle and to repeat these steps five more times. Another advantage is that regardless of the dimensions of any airway it wil ahve treatment with optimum frequencies plus harmonics many times throughout each cycle.

"The inCourage System has a unique range of pressures which, as of Sept 2006, have only been partly evaluated. The pressures 10% (of the max pressure in the machine) to 40% were designed for babies and msall children and should not be used by a child over 12 months of age without a doctor's or therapist's presciption and close monitoring. Probably no patient over one year of age should use a pressure under 50. These directions still require study before I can make a validated recommendation.

"Knowing that we had to evaluate the relationship of frequencies and pressures with the new ICS we found in less than 6 months, that with a constant machine pressure the ICS Jacket pressure decreases as frequencies are increased. This is the reverse of the sine waveform machines were the pressure in teh vest increases through the machine pressure setting is constant and which it took over * years to discover the relationship.

"The following adjustment is effective but, I expect, will be changed during the next year. The inCourage System's wider range of pressures has four settings (10%, 20%, 30% and 40%) that are lower than the lowest pressures of all other HFCC machines in anticipation of th eneed for preventitive HFCC starting in infancy. The pressure range 50% to 100% covers the dial number range 1 to 10 inall other HFCC machines.

"I recommend that patients start with pressure 50% and after each 6 minutes ramp cycle pause to cough. then after this first pressure cycle increase the pressure to 60% for the next cycle repeating this until a pressure is found that was hard to tolerate. That pressure may be too high so the patient should use the last pressure the patient tolerated and used for every treatment. If the pressure 100% is tolerated that is the pressure to use. Occasionally, perhaps every 1-3 months, check that the next higher pressure is still not tolerated.

"The inCourage System jacket is designed to fit effectively when applied as directed with a jacket/chest circumference ratio of 110% to 120%.

"I have not seen satisfactory recommendation for prescribing the vest size or tightness for Models 103 and 104 or the Smart Vest. For these machines I recommend that you measure the greatest circumference of the chest (just under the arms or at the lowerest part of the ribs above the abdomen). Adjust the standard vest to circumference, that, when deflated, is 110% or 120% of that the torso circumference and then put safety pins in the straps so that they will not loosen. use that fitting of the vest until he grows taller or heavier.

"These guidelines for the sine waveform machiens are a good way for respiratory therapists to help patients with thes emachines to find the pressures and to use the frequency in the Minnesota Table. An unsolved problem is that larger pateints, who need larger jackets, will require higher dial pressures. Another problem is that some of the new HillRom vests have several large metal holes that leak so much air that patients using these vests may be able to use the highest pressure and frequencies without effort or discomfort. I believe that ehse vests will give inadequate HFCC treatments. This assumption is an assumption that we will study when a supply of these leaky vests becomes available to our study.

"Our basic science research is done by the Electrical Engineering Graduate Students who, working on the Defense of the Lungs Project (DLP), have developed much of the information discussed above and also confirmed earlier work. In the DLP, we are studying the Minnesota HFCC technology that has been built into the Models 101, 102, 103, 104 and the ICS systems. So far ElectroMed has declined to donate one of their SmartVest machines with the vest for our study.

"The DLP so far has produced three MS and one PhD degrees. Their labroatory research ranking of theoretical effectiveness (this will need to be confirmed by patients and patient studies) is that the ICS>Model 1 and 2> Model 103 > Model 4. The first independent clinical study under way to compare the ICS and the Model 104 was designed before we learned of the relationship of machine pressures and frequencies with the ICS is the reverse of the Model 103. With the Model 103 breathing becomes harder as pressure is held constant and the frequency is increaed. With the inCourage System breathing becomes easier as pressure is held constant and the frequency is increased. With the Model 103 the dial pressure must be decreased to keep the pressure in the vest close to constant whereas with the inCourage System the dial pressure must be increased to keep the pressure in the vest close to constant.

"All of the HFCC machines work. They have been effective in almost every way they have been used despite that most of these ways have been less than optimal. We are aware of no adequate studies comparing any HFCC machines because no adequate research has been performed to find the optimum way to use each machine.

"My directions are based on clincal observations plus parents and patients' experiments. These directions are effective but they may not be optimal. Such studies are needed because of the high cost of thes emachines and their durability and the essentiality of optimum airway clearance to growing old with healthy lungs.

"Clinical studies should have been done to compare the effectiveness of Model 103 and Model 104 before the change was made. This may have been because our unpublished laboratory studies may be interpereted as suggesting that the old Model 103 may be more effective than the old Model 104. So no dustides have been possible to demonstrate the best way to use eithe rModel 103 or Model for pateints.

"All bench and laboratory studies for HFCC equipment need to be studied in either clinical studies as critially planned as the labroatory studies. When the lab studies have been translated to the best way to use each machine on patients then studies can be done to compare teh different machines used by patients.

"Meanwhile I want to hear of your observations or questions concerning your HFCC system, regardless of the kind, because the DLP Lab continues to study all available machines regardless of waveform. We are comprehensively studying Model 101, Model 102, Model 103, Model 104 and the inCourage System (we are not studying the MedPulse or the SmartPulse machines because, so far, the company that makes them will not give us machines or jackets for our research). Your observations and questions will help us defnie tasks to solve. Our sultions to your observations or problems will improve all forms of HFCC.

"I will reply to your observations or problems with whatever HFCC system you are using; if possible provide a suggestion or suggestions concerning your use of your HFCC which you should discuss with your CF Doctor before trying them. You know yourself best, your CF doctor knows best the medical and scientific problems that you have, so even if I know HFCC best, the best application of any suggestions I make should be worked out by you with your CF doctor.

"There are times HFCC needs to be increased to three or more times:

" 1. The start of a cold. My recommendation is to start an extra HFCC therapy a day at the start of a viral respiratory illness and to continue the extra therapy for two weeks. About 10 to 12 days after the start of a typical viral illness the boyd's immune system takes a day or two of rest after fighting tihe virus. During that couple of days a bacteria infection can get a head start and can cause a much more serious infection. The increased HFCC for two weeks will keep the airways less colonized by bacteria and clear out excessive bacterial growth until the immune system returns from the brief rest.

"2. When a new lung infection or worsening of a chronic infection occurs. I presscribe HFCC treatments three times a day with each treatment for 45 to 60 minutes until recovery. i favor three times a day because there is less iterruption of daily life than with four a day.


"It is important to do twice daily HFCC treatment every day because risks are day-by-day events and prevention is a day-by-day process. The risk of a person without CF of developing a serious lung infection any day, based on published data, is about 0.01%. So the chance of staying well of not catching serious lung infection today requiring antibiotic treatment must be about 99.99%.

"I estimate the daily risk of a person with CF, who does not do HFCC treatment twice a day, of developing a serious lung infection every day requiring antibiotics treatment, is about 0.5%. So the chance of not doing HFCC treatments and staying well and not catching serious lung infection today is about 99.5%.

"I estimate the risk of a person with CF, who does HFCC twice every day, of developing a serious lung infection today requiring antibiotic treatment, is about 0.034%. the chance of staying well and not catching serious lung infection today is about 99.965%. "

He then lists a table which I can't quite duplicate here but I'll show the bottom line of table:

"Chance of being sick at least once this year if you have no CF: 4%. Chance of being sick at least once this year if you have CF plus HFCC Rx: 12%. Chance of being sick at least once this year if you have CF no HCFF Rx: 84%"

"Doing HFCC twice daily as prescribed can reduce the risk of a pulmonary infection 7.3 times as compared with not doing daily HFCC. A pay off of staying well, statistically, occurs about every seven weeks when you do HFCC daily."

I'll post more of the letter later :)


"Aerosol therapy has a long way to go before there is a general agreement for when to use, the time for each treatment, the medicines to be used and the equipment for delivering the aerosol. I try to avoid all aerosols that provoke coughing by irritation. Although many patients and physicians use hypertonic saline, I am only partly convinced because I suspent that the irritation induced coughing will occur mainly in the least affected airways andthat such coughing may injure the mucus membrane of the healthiest airways and eventually increase the severity of the CF associated chronic pulmonary disease (COPD). [See : Interpreting the Hisopathology of Chronic Cough: A Prospective, Controlled, Comparative Study; CHEST;, 2006; 130; 362-370]

"Keep in mind that almost all CF patients have a super strong ability to suppress coughing which they learned at home, at school, at concerts, at movies, in crowds and at curches and other places. The balance between structured coughing, irritation induced coughing, and spontaneous coughing and the subconcious learned suprsession of oughing is an area in need of more research. It is one area where patients and families with CF can do their own experimentation.

"I have prescribed the following aerosol during each vest therapy for over 30 years with such good success that it continues to be my choice as the most effective aerosol for CF:

"-Mix and nebulize for aerosol treatment:
-Mucomyst 20% 4mL
-Albuterol unti dose (2mL ampoule) 1 vial
-Intal unit dose aerosol (2mL ampoule) 1 vial

"This yields 8 ml of a 10% solution of the Mucomyst which can be nebulized in less than 30 minutes with a good nebulizer. I recommend stopping the aerosol when the nebulizer begins to sputter. The mixture provides anti-inflammatory, bronchial dilation, mast cell stabilization and reduces sputum.

"(The mucus in the airways is dehydrated and becomes functionally normal by the addition of water. There is no molecular abnormality of CF mucus. Since CF mucus is normal any treatment that will change it will most likely destroy the ability of mucus to protect the airways.)

"The 20% Mucomyst is concentrated enough to irritate airways in some patients so that I prescribe diluting it to 10% with albuterol and Intal. The albuterol main action is to assure dilated airways to improve the deep deposition of the mucomyst. The Intal's main action is to counteract the high probability (about 40%) that allergies and mast cells may interfer with treatment.


"The benefits of Mucomyst aerosols are sometimes offset by the odor of the aerosol which resembles rotten eggs, the stickiness of the not inhaled Mucomyst, which can interfere with function of table top computeres, television sets and other electronic equipment, and the risk of bacterial infection if the nebulizer is not carefully sterilized daily. Some of my patients have substituted three times a day of oral n-acetylcysteine as NAC capsules size 600 to 1000mg or, two or more teaspoons of 10% solution of Mucomyst or one or more teaspoons of 20% solution of Mucomyst.

"Some of these patients still benefit from the use of Intal and occasional bronchodilator inhalations by means of metered dose inhalers. Some of these patients do not use any; aerosols except antibiotics.


"Glutathione is a combination of three amino acids: glutamate, cysteine, and glycine. Cysteine is the active amino acid in this molecule. NAC is a more stable form of cysteine because it has only an acetic acid group attached. NAC is more water soluble and is the most cost effective way to increase glutathione levels in the body. N-acetylecysteine in solution is sourer than glutathione but NAC comes in capsules.

"I recommend oral or aerosol n-acetylecysteine over oral of aerosol glutathione. I have used Mucomyst for aerosols for many years. I have been encouraging patients to expiment with oral NAC capsules. The cysteine amino acid part to both molecules provides the antioxident, antiinflammatory and mucolytic actions of both molecules.

"Hypertonic saline increases the water in the periciliary fluid. It does this by attracting water to reduce the hypertonic saline to normal saline concentration. This extra water floats the mucus high enough that the cilia can beat and move the mucus out of the lungs. This activity lasts until the hypertonic saline is diluted to normal. I do not know how long it takes for this to happen.

"A balancing consideration is that our studies have showed that the regular twice a day use of HFCC with either the square or triangle waveform machines will increase the water content of water in the sputum for at least 12 hours after the last regular twice a day treatment. While the published studies show the immediate effectiveness of the hypertonic saline aerosols I prefer the HFCC method since it couples the increase of water on the mucus membranes with the removal of that mucus as well as round the clock effectiveness.

"I have been so very satisfied with our Mucomyst aerosols taht I have been slow to experiment with hypertonic saline. However I have one patient who had an unusual problems with airway clearance after a shelf full of supplies fell on her and broke her back. After 3 years of poor response to surgery and other treatments (her back was too painful that she could not tolerate even low pressure sine waveform HFCC therapy) show a very significant improvement of all her pulmonary function tests. Based on this observation and the good resports in the literature I regard hypertonic saline aersol as a therapy worth of physician and patient experiment as an addition to, but as a replacement for Mucomyst. My current appproach would be to recommend only 3% saline.


"Prednisone is often prescribed to reduce the inflammation in the airways and so reverse inflammation with the hope to restore and even preserve lung function. It works so well and so quickly that it is easy to have prednisone become a fixed medicine. When used for long times prednisone can cause unwelcome side effects; especially related to childhood growth, control of blood sugars and density of bones even with indefinite cycling between high and low doses. Rapid withdrawl can lead to recurrence of the symptoms treated. There is no perfect way to withdraw from prednisone dependence. I have had success allowing a child to outgrow the dosage over some years or more rapidly by decreasing the daily dose by 1 milligram per week or per month.

"Many pphysicians belive inhaled steroids are safter because their action is mostly in the airways where it is needed. Still the lowest effective dose is desired. Physicians usually start with the highest dose and somtimes forget to see if the benefits can be maintained witha lower dose...... Aerosol steroids also carry a steroid risk and so the lower the dose that works the better. Read the package insert about the risks, the side effects and the recommended doses and the duration of treatment....Discuss the inhaled steroids with your doctor, especially if you have another source of steroids such as by dermal, nasal or oral route.


"Antibiotics are prescibed to help treat a serious lung infection. Much has been and is being written concerning aerosolized antibiotics. If your doctor prescribes such treatment be sure you understand what the intention is, how to prepare and store each antibiotic, how to use it, how to clean and maintain the equipment, what to expect for a benefit, what adverse events to watch for, etc. [U] Always rinse your mouth with water after each antibiotic aerosol. [/U] "


"The Minnesota CF Center aggressive aerosol treatment component of preventive airway clearance protocol largely excludes Pulmozyme. My observations suggest that Pulmozyme benefits only 1 in 10 patients who also use Mucomyst aerosol.

-Milla's observations showed when pulmozyme was added to teh treatment of a hundred such Minnesota patients, that these patients had a more rapid drop of FEV1 than their matched patients who did not use Pulmozyme http://thorax.bmjjourn...om/...../12/10tm4).



-Suri, in The use of human deoxyribonuclease (rhDNase) in the measurement of cystic fibrosis.BioDrugs.2005; 19(3):135-44, reports that "the response to treatment is heterogeneous and only a proportion of patients with CF actually benefit from the treatment."

-Rochat et all. suggests a mechanism for rapid worsening when using Pulmozyme aerosols http://erj.ersjournals.cgi/reprint/9/11/220.

-Cobos, et all European Journal of Pediatrics, 159: 171-181, February 2000, found "benefits of DNase in daily practice are limited but apparently can be maintained in the medium term in some patients... the benefits are doubtful in around 50% of patients".

-Barker, et all, Pediatric Pulmonology 38: 70-74, May 2004 found "improvement of exercise performance with DNase is restricted to a subgroup of CF patients and may not be predicted or identified by spirometry and subject report alone."

"If your doctor prescribes Pulmozyme aerosol, discuss these papers with her. To be fair, on the positive side, Pulmozyme has a record of imporoving the lung function for many patients when these patients who have not had an effective aerosol treatment, such as Mucomyst, and when the Pulmozyme was compared to "normal saline" aerosols.

"I believe that Pulmozyme may have an adverse effective for some patients who are having rapid loss o flung function. I recall observing, during my early prescription of Pulmozyme, three patients who coincidently developed a rapid worsening of lung function when using Pulmozyme. I believe the rapid loss of pulmonary function might have been a possible adverse effect of Pulmozyme. If such a coincidence occurs I would investigate the possible association so to be able to confirm or rule out a provoking association of Pulmozyme with such a coincidental worsening of a present infection. My observation of only infrequent benefit and my concerns about the possibility of an uexplained rapid worsening of lung function in a rare patient using Pulmozyme have biased me to prescribing Pulmozyme to less than 1/10th of patients, for whom I have proven improved lung function with Mucomyst aerosols.

"On the positive side Pulmozyme is a wonderful enzyme designed to break the long molecules of DNA into very small pieces. A solution of DNA is very, very viscous. A solution of the Pulmozyme broken fragments of DNA is very thin and runny. The first solution is very hard to move with a cough; the second solution is so watery that almost any force, even gravity, will move it.

"Picture what might ahppen when a patient with CF coughs with or wihout Pulmozyme is airways when a coughing spasm occurs. Such a coughing spasm will lead to an emtpying of the air from the lungs that is so completely that the smaller airways are closed. Without Pulmozyme, the thick mucus will tend to adhere to the airway wall and the coughing may deform the cartilage and predispose to the development of bronchiectasis as the adjacent cartilage is injured. Such an event is good reason why control cough needs to be learned by patients and parents. Such a consequence of a coughing spams may be a common injury when patients not using Pulmozyme have a coughing spasm.

"Consider another possiblity that might appen when a CF patient using Pulmozyme the thin and running sputum develops a coughing spasm. Then instead of damaging the bronchi what happens may be like the changes in a tooth past tube that is squeezed in the middle. I see an event parrallel to the simultaneous application of toothpaste aplied to the tooth brush with some tooth paste going deeper into the tube. If that parallel event happens in the bronchi the thin and runny liquid of DNA fragments and bacteria might be forced deeper into the airway branches, spreading the bacteria and infection. While such an event may occur rarely and only in a patient taking Pulmozyme such an associated rapid progression of loss of lung function may be looked on as a new, unlucky and unexplainable event that has to be treated with more antibiotics. "


"That coughing is important and should be taught from diagnosis of CF. Even infants with no detectable lung idease need to be encouraged to cough frequently. how this can be done is ap roblem that parents of infants and preschools children will need to help us figure out because physicians and physical therapists do not know how to teach children how to cough and to cough regularly to keep their airways free of excess sputum. this will have to be your experiment since I have seen no such medical studies.

"Coughs compress the chest, narrow the airway diameters and force the expiratory air to flow through these airways at high frequencies. This moves sputum towards the mouth from which it can be spit out or swallowed. Every patient who has the CF genes needs to develop a style of life in which coughing many times a day can be done is such a way that their peers do not notice or ignore the coughing.

"All CF patients need to learn to [B] NEVER [/B] supress a cough. Cough supression is a dangerous accomplishment. Not to cough in order to be socially acceptable is not acceptable. The goal is to earn how to cough frequently so no one notices the coughing.

"The way to stop or prevent a coughing spasm is simple; just hold a breath for a few seconds.

"A patient can learn to prevent a coughing spasm. First to feel how much air is in the lungs at the end of a quiet breath, the functional residual capacity (FRC), when all airways are normally open. Second, learn to fill the lungs to total lung capacity (TLC) by actively increasing the volume of the thorax. This will insure that all the alveoli behind each partly blocked airway will be filled full of air to push the mucus out with a cough.

"The classic direction to fill the lungs is to tell the patient to take a deep, or big, breath. The quick breath that follows with linflate the alvoli distal to the open airways but not the alveoli that are distal to the partially obstructed airways. The following cough will clear the clean airways well but not the partially obstructed airways unless the patient holds his breath for several seconds before coughing to permit the air in the inflated alveoli be transferred to other alveoli that are behind the mucus in their airways. That extra air will make the cough more powerful and effective.

"The best cough to learn is my Improved Cough Technique.

"Normal coughs fill the alveoli least that are beyond sputum in the airways and most beyond the airways that have least sputum. The result is that the healthiest airways get the most power and cleanig. My improved Cough Technique gets an equal amount of air into the alveoli behind the most sputum in the airways. It uses regular normal inspirations but instead of exhalation the patient holds the inspired air in the lungs. When the inspiratory muscles relax the pressure in the alveoli becomes greatest in those that are beyond the least sputum causing some of the air to be transferred to the alveoli behind the most sputum. By continuing inspirations without expiration the lungs become inflated with equal amounts of air in all the alveoli. At this point the air behind the most sputum pushing the sputum which irritates the airway and causes a cough that clears the sputum that is least moved by usual coughs.

"Fill the lungs using a serious of regular breaths with a normal pause without expiration after each regular breath. The imprtant parts are the holding all the inhaled air in the breaths and then simulataneous pause so that the inhaled air can equalize throughout the lungs and air flow from te full alveoli to the less full alveoli and also enlarging the airways that are coated with non expectorated sputum. As the lungs fill closer to total lung capacity enough air will get behind the ucus in the airways and a cough will "happen." Practice filling the lungs may be the best way to clean the airways because a cough always happens even in "normal" lungs because all lungs have some sputum.

"Another point to consider in a recent paper, "Interpreting the Histopathology of Chronic Cough" (CHEST 2006; 130: 362-370) which demonstrates the association of airway inflammation associated with chronic cough. These author's observations do not cancel my suggestions that CF patients cough too little; they do cough too little. Their observations come fortuitously with my development of the Improved Cough and my arguments that CF patients need to cough more.

"Three of my Improved Coughs after each HFCC frequency or ramping cycle should always stop at FRC. My Improved Cough method preserves the magnificent power of the cough to clean the airways and never damages the airways or pushes mucus deeper in the airways.

"Patients using the Model 103, Model 104, the MedPulse and the SmartPulse machines must disconnect a tube at the end of each frequency when the vibrations are stopped to remove the constant compression of the chest. The Model 101, Model 102 and the InCourage System ahve no background pressure when the chest compressions stop since the pressure in their jackets become equal to room air pressure when the chest compressions stop. So their tubes do NOT need to be removed."

Happy breathing. FIGHT ON


"Parents and patients assume partnership in the CF Care Team when they experiment with prescribed treatments and other directions. if they don't talk with the CF Center Staff or learn their plans or discuss their variations of treatment a major breakdown develops in what must be a joint fight against cystic fibrosis.

"One of the problems with experiments if how to decide whether they succeed, fail, or are neither a success or failure. There is a whole scientific and scholarsly study of how to dtermine success or failure. Here are some possible ways of telling whether an experiment is a success or a failure.

"Take changing enzymes for example. If the number of bowel movements have decreased, the stomach pains have disappeared and there is no more unexpected weight gain, then there is really no need to repeat the experiment.

"On the other hand, say you are looking at something like Pulmozyme and are trying to tell wehther or not there's a difference with or without it. Since most of your observations will be subjective, you might try to see if you get the same subjective result for give trials in a row, or if you get 9 out of 10 trials giving the same result. The basis for this is flipping a coin if you get heads give times in a row the odds are about one in such events in 32 tries. Statistically the chance of something happening less than 5% is considered a significant result.

"The more precise the numbers of a result, the more confident you can be that you have significant results. Examples might be counting the sleeping respiratory rate for one minute while your child is sleeping. If the average rate per minute over a week would be, when lower the sign of a better response and when higher the sign of a poorer response.

"Work with your CF physicians on designing an experiment to be done at home. Try to find ways to obtain numerical and therefore analyzable results. For example there are small scales that you can carry in the pocket and will measure weight down ti milligrams. These scales run on batters and, while not cheap, are affordable. Your CF physician may actually have one that could be loaned to you. As you try to experiment in the use of different machines, different pressures and different frequencies you might use a paper cup and measure the weight of sputum produced during each high frequency chest compression treatment. Your CF physician could help you do the statistics to determine whehter a difference in the amount of sputum produce was significant.

"If your CF Center staff does not ask about your experimentation ,or they fail to listn about an experiment, it will be hard to improve treatment. If the CF Center statff does not listne or recognize the importance of patients' and parents' experiments, does not pay attention to the experiments, does not try to understand the experiments, or does not find out what can be learned from the experiments and discuss how to improve future experiments, then there is a major breakdown in the joint battle against CF.

"Doctors are slow to learn from patients. Be patient with them and with the other CF Center staff. It took me learns to learn to ask patients (parents) what kind of experiments they are doing: to interpret their failures to comply with my directions as experiemnts rather than seeing them as being non-compliant and non-adherent. I try to discuss the value of experiments and how to improve experiments. I ask them to figure out what is a positive and negative outcome and to discuss with me their ideas about an experiment before they do it, if they do the experiment on their own to share their plans and findings with me so we can plan future home experiments.

"Doctors are slow to apply what they learn from patients. I was taught; I was fortunate enough to have Annalisa Marzotto as my personal teacher during the years I served as her physician. Annalisa determined that she knew more about herself, how my prescriptions and directions worked (if and when she used them), what she thought of them and what she decided might be changed. My shceduled 40 minute clinic sessions never lasted less than 90 minutes and often went 2+ hours. My lessions occured every two weeks. Annalisa knew that doctors seldom listen so she came prepared to ask questions as well as answer questions. But more imporant she had answers to questions she wanted me to ask and she would use her answers as the starting place for her questions such as:

"Why didn't what you recommended work?

"Why did what you recommended work differently than you expected?

"Could it be because....?

"Could we try it this way?

"Could we try this instead?

"Was that idea based on the wrong assumptions?

"Would this be a better assumption?

"How about this idea?

"What do you expect your idea to do?

"How will I know if your idea doesn't work?

"What do I do if your idea works differently than you expect?

"Why did you not do?

"Analisa made these clinic visits very exciting and I looked forward to everyone. Annalisa changed me to be a collaborator with her with the goal to control the most serious complications of a CF patient that I have ever cared fro. We worked together for over 15 years.

"I've used many of the things she taught me with other patients in a hap-hazard way over the years since she died. I never tried to make Annalisa's teachings a principle for care of all my patients until I have had the honor to being the consultant to many patients and families to came to see me after reading "The Bell Curve" in the New Yorker. I have seen have needed to hear about Annalisa and her wisdom frot he treatment of CF. As I consider Annalisa's wisdom, I believe her system of a patient (or a family) and doctor working together to treat the illness acquired because of the inherited CF genes is essential to living healthy and growing old with CF.

"This must be learned by each patient and family xperimenting to learn how this approach can work with their doctor/patient assoiation. This could become a project for patients and families to add to the annual family education days. Doctors do not have the urgency to accomplish this because each probably has 70 or more patients. But each patient has just the one doctor and so a one to one relationship must start with the patient and the diagnosis of CF in order to be successful. "


"Read the fine print that comes with every prescription. you'll find much information about the many side effects that an occur with ever medicine.

"Afte ryou ahve questions about CF, treatment variations, medicine on the internet and in the literature including even non-prescription preparations you should meet with your (your child's) doctor and discuss your findings and your concerns. you and your (or your child's) doctor have to work together concerning each prescription, how to recognize if it is working and how to be aware of side effects.

"Every prescription is an experiment. Your doctor expects that the majority of times you (your child) will respond the way the majority of patients respond. The information on side effects and the interaction of the medicine with other medicines are also important for your benefit. Some of the side effects or interactions with other drugs are of little importance. Others might be significant. When you think a side effect or drug interaction could be significant you need to discuss that with your (your child's) doctor."


"You know your life style, your child's life style, successes and failures very well. You need to bring this knowledge to every clinic visit and develop partnership treatment plans with your CF Center doctor and staff that you agree are good and that you can do as your part of the battle against cystic fibrosis.

"This is the time for you to prtest if you cannot do what is recommended. If you don't do this, you will leave all the decisions and experiments to your doctor, who, as you know, does an experiment every time a prescription is written or a recommendation is made. Your doctor and your CF Center team will give you excellent care based on the published reports, all of which have been statistically vetted, and their personal observations when these have been tried on other patients. You need to speak up concerning any ways in which you (your child) differ from the patients in the reported studies.

"There is no greater problem in communication with your CF doctor than telling the doctor what you believe the doctor wants to know. Do not leave anything that might be important out of your replies to the doctor. Make sure that you tell al that has happened and tell the truth. Do not tell your interpretation of what has happened. If you leave something out or tell the story you believe the doctor would like to hear, your CF doctor will not be able to give you the recommendations, prescriptions and diretions that you or your child needs.

"Remember the published conclusions and recommendations have been formed using a Bell Curve like the one in the [U] New Yorker [/U] article. Every Bell Curve has a 5% high or low termination on each end. The middle 90% are considered to be [I] normal. [/I] Remember that 1/3rd of published papers will be improved upon or proven wrong in the next five years. Ine very study some patients will not have performed as well as the central "average" and some of the controls will have performed better than the central "average" that benefited. Be vigilant and talk with your CF Center and CF doctor."


"Your activities and participation are of equal importance with the activities, directions and prescriptions of the CF Center's staff and physicians. The success of the CF Center is equally shared by the CF patients and families and the CF Center staff. You will need to work very hard, to insist on the communication needed to make this collaboration be successful.

"One way to be ahead when your child with CF is young and is asleep in bed and before you go to bed is to count the number of breaths your child takes in one minute. Since every lung problem increases the respiration rate, this 60 second number of breaths can give you the earliest sign that your child is developing a lung infeciton .Exceptions are a dream or a full stomach. Count the 60 seconds sleeping respiratory rate daily and graph the numbers to discover the usual rate and the range of rates. Then when yourchild has an increased rate assume that there is a lung problem or a dream. Count the rate again after half an hour and if the rate is still high do an extra HFCC treatment and call his CF doctor. The increased respiratory rate is the most reliable and earliest sign of an infection or other significant change in lung funciton.

"Consider 'The Bell Curve' since that title has brought many to the Minnesota Cystic Fibrosis Center. That title was an over simplification since the studies considered only survival, height, weight and pulmonary function tests. However many other 'Bell Curves' come with each patient starting CF care at each CF Center. Some of these 'Bell Curves' are age at diagnosis, the already acquired CF related diseases, their severity at time of diagnosis, the kind of CFTR gene mutations, the number of children in the family including children with CF, sex, family income, existence and quality of the health insurance, one or two parents (each with no, one or two jobs), air pollution, distance from the CF Center, availability and kind of HFCC technology, knowledge of how to use the HFCC equipment, and so forth. Each such 'Bell Curve' affects each CF Center's multiple 'Bell Curves' and if their contribution to each patient's health is not considered that 'Bell Curve' is suspect.

"You need to develop the communication skills that will place your role, as a patient or a parent, equal with your doctor's role as a caregiver, with both of you fighting the clinical problem of cystic fibrosis. You need to explain the hanges in your child's body and teh response to the prescriptions that are given. You need to develop enough of a background so that you can, with intelligence, discuss the treatments your doctor is prescribing. You need to know the potential side effects from any presctipion and the potential interaction between the different medicines. For example: if multiple antibiotics are prescribed: Are they to treat different bacteria? Are all need to treat one bacterium? Should you be taking all of them continuously? If so, for how long? For example; if you are taking short and long acting bronchodilators, how can you determine if you need both kinds?

"The battle against CF that you (as parent or patient) and your CF doctor and CF Clinic work together to fight, is only part of the worlwide work, whcih in the United States is largely focused through the efforts of the Cystic Fibrosis Foundation (CFF). Help the local, regional and national efforts to raise funds to supporr the CFF's planned programs. Remember the CFF supports your CF Center.

"You and your CF Center's doctors and staff have good ideas that also need to be studied and you also have smart questions that need to be asked concerning how to treat and how to understand the ways the risk factors for the CF associated diseases operate in your child's and your CF Center's unique environment. Discuss such questions with your CF doctor and how you can help them to do such research.

"All CF parents and patients need to be good observers, note keepers and reporters as they know themselves and problems better than anyone else. They need to keep notes of their observations and of questions so that, having them writen down, when you see your CF doctor you will not forget problems that, because they are important to you, they are also ciritical for your doctor to help solve those problems and to resolve your questions.

"This may be difficult because doctors have been given a fixed amount of time for each clinic visit, to answer questions, to discover problems that need attention, to review your treatment and the results of your chronicle of changes in your treatment, to order new tests to improve his understandings, to make recommendations and to write prescriptions, and most important to answer your questions about what you have learned about CF between Center visits. You need to bring all of these to your clnic visit and work out plans with the CF Center physicians that you believe are good and that you can do."


"Since pancrease injury usually begins during pregnancy (severly enough ot produce meconium ileus in up to 10% of children with two CFTR mutations), causing pancreatic insufficiency after birth in about 95% of CF babies, nutrition problems are almost always a problem starting with their first feeding. So far that problem remains lifelong. For most patients everything that follows is colored by the problems of digesting and absorbing the digested food and of a diversity of potential malnutrition problems which range from night blindness (vitamin A deficiency), bleeding (vitamin K deficiency), osteoperosis (Vitamin D deficiency), failure to thrive and others well described in the CF literature. Pancreatic enzymes, extra fat solubl vitamins and essential fatty acid suppplementations are needed. Still there are controversies concerning their necessities and amounts. As excesses do not solve the problem of health, future studies will be needed to determine the optimum amount for health of each patient. For now the subject of indiviual optimum amounts is one for patients, parents and physicians to discuss.

"Later digestive problems seen in some patients include cirrhosis of the liver, gall stones, bowel obstruction, diarrhea, constipation, inussusception and gastro-esophageal reflux. These CF associated digestive problems respond to the treatments in patients who do not have CF.

"I worry about using supplements when patients are underweight because in almost all usage the supplement becomes replacement. Tube feeding is an occasional necesity which should be avoided if possible. Both gastro-esophageal reflux and inadequate or poorly used pancreatic enzymes can be causes of poor appetite and malnutrition.

"Perhaps the most common explanation of correction for malnutrition is the decision of the patient to eat more. The power of a decision, even though we don't know how to create the change in the patient's brain, has been the msot successful observation.

"There is a relationship between diabetes, a constant worry before and after diagnosis, and nutrition. I advise all patients to avoid all foods and liquids with sugar or high fructose corn syrup and to be wary of foods that have a high glycemic index. Fruit juice with meals may be reasonable exception to liquids with sugar, but eathing the whole fruit will be better. Restriction of high glycemic foods may be difficult when a patient with CF needs to gain weight. A concerned endocrinologist, preferably one who has or would like to develop expertise in CF related diabetes, may be needed in planning the diet for gaining weight. My concern about diabetes is real for already 1/5th of our patients have CF associated diabetes and almost another 1/5th have abnormal glucose tolerance tests. Another reason to avoid all soft drinks is the phosphate in these drinks can bind to calcium and so increase the risk of osteoporosis.

"I avoid fixed vitamin preparations for patients with CF unless they have B-xomplex and trace elements. I believe that CF pateints need larger amounts of beta carotene, vitamin E, Vitamin D, vitamin K, essential fatty acids, omega-3, vitamin B-12, folic acid, slenium, with perhaps more supplements to be discovered. I recommend the serum levels of vitamins A, E, and D be checked at least once a year. Beta caotene, the precursor of vitamin A, is my preferable source of vitamin A since the body produces the optimum concentration of vitamin A it needs any excess is a useful antioxidant. Your CF nutritionist dietician can help you study these needs.

"You may find Roger J. Williams' book, [I] Biochemical Individuality [/I], intersting. I have adopted his philosophical approach to optimum dose and nutritional side as the way to consider the nutritional approach for CF. "


"I recommend that CF patients try to maintain a weight 10% above average for age and height using per hight at age 18 as the index for older patients. The extra 10% should provide the muscles for good activity, for metabolizing glucose and body mass reserve in case of a serious infection.

"Now after years of constant efforts to gain weight some older patients (and some very young Patients) are having problems with obesity. Gaining too much weight in childhood needs to be recognized before adolescence so that obesity does not become another CF associated disease. This is a special problem because both CF and obesity predispose to diabetes."


"Exercise, especially aerobic exercise, is strongly advised throughout all of the European CF Centers. In Minnesota I have observed that CF patients can do very well in all forms of exercise and that their health improves in proportion to their enthusias for both aerobic and strength building exercises. I recommend such exercises with supervision. Several of Minnesota CF patients have received college scholarships because of their athletic successes in high school