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.
GOOD THINGS ABOUT CF
"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
IF CF IS NOT A DISEASE, WHAT IS CF?
"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."
SOME BACKGROUND INFORMATION
"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
"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 :)
AEROSOLS TO TREAT CF
"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.
AN ALTERNATIVE WAY TO USE n-ACETYLECYSTEINE (MUCOMYST)
"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 AND HYPERTONIC SALINE AEROSOLS
"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.
STEROIDS AND STEROIDS INHALATIONS
"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 ARE PARTNERS WITH THE CF CENTER TEAM IN THE FIGHT AGAINST CF
"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."
OF COURSE YOU ARE PART OF THE CF TEAM
"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