Anyone reading the books?
Monday, December 26, 2011
Saturday, December 10, 2011
Green Smoothie Time!
As many of you know, our fellow Cyster Mandy has infinite wisdom about SO MANY CF related topics.
One of these many is a CFer's diet: she correctly points out (this isn't a direct quote, but rather a summation of her opinion) that sugar, refined carbs, etc are not a great way for a CFer to put on weight as these foods create inflammation in the body. Who cares if you are a normal BMI if your lungs are inflamed and in bad shape?
I have tried drinking Mandy's green smoothie recommendation off and on over the past years, but a few weeks ago I finally made the plunge and purchased "Green Smoothie Revolution" by Victoria Boutenko as well as "Green For Life." I by far don't eat enough greens and smoothies are such an easy way for me to the nutrition I know I need.
So this book includes dozens upon dozens of smoothie recipes - great to find a version to your liking and also important for variety (greens contain alkaloids - and too many alkaloids from one type of green can cause some unwanted symptoms. so rotating greens daily or weekly is smart). One thing I just learned from the book is that banana masks the taste of chlorophyll, so I basically feel like I'm drinking a banana smoothie that just happens to look green (and have kind of a green texture).
Anyway, just wanted to share - I will keep you posted on how I feel. I'm sure I won't feel worse than I do without eating greens :) :) :)
The below smoothie contains: 1 Green Apple, 1 Banana, 1/2 inch ginger root, 4 leaves of kale and 2 cups of water (I kind of wish I would have put in some ice instead of just plain water - it would have made the smoothie a little bit colder and frothie sp?).
PS that tube thing in the back is the sink hook up for my neb dishwasher :)
One of these many is a CFer's diet: she correctly points out (this isn't a direct quote, but rather a summation of her opinion) that sugar, refined carbs, etc are not a great way for a CFer to put on weight as these foods create inflammation in the body. Who cares if you are a normal BMI if your lungs are inflamed and in bad shape?
I have tried drinking Mandy's green smoothie recommendation off and on over the past years, but a few weeks ago I finally made the plunge and purchased "Green Smoothie Revolution" by Victoria Boutenko as well as "Green For Life." I by far don't eat enough greens and smoothies are such an easy way for me to the nutrition I know I need.
So this book includes dozens upon dozens of smoothie recipes - great to find a version to your liking and also important for variety (greens contain alkaloids - and too many alkaloids from one type of green can cause some unwanted symptoms. so rotating greens daily or weekly is smart). One thing I just learned from the book is that banana masks the taste of chlorophyll, so I basically feel like I'm drinking a banana smoothie that just happens to look green (and have kind of a green texture).
Anyway, just wanted to share - I will keep you posted on how I feel. I'm sure I won't feel worse than I do without eating greens :) :) :)
The below smoothie contains: 1 Green Apple, 1 Banana, 1/2 inch ginger root, 4 leaves of kale and 2 cups of water (I kind of wish I would have put in some ice instead of just plain water - it would have made the smoothie a little bit colder and frothie sp?).
PS that tube thing in the back is the sink hook up for my neb dishwasher :)
Saturday, October 15, 2011
How to clean nebs
My first year out of college, living on my own for the 1st time, I got pretty overwhelmed with cleaning/sterilizing my nebs. I'm of the school of thought that bacteria (mainly, pseudamonas) will grow on nebs in between treatments if you don't clean and sterilize them (if you don't believe me, take your neb to a lab and have it swiped to see what bacteria are growing). Why put bacteria back in to your lungs while doing a breathing treatment?
So my solution when I first started living on my own to the cleaning/sterilizing neb thing? Simple. Stop doing pulmozyme regularly, and therefore have one less neb to clean.
Trust me, that didn't work out very well.
So the method I came up with was to get a little table top dishwasher that cleaned and sterilized nebs in one simple step!
I bought the dishwasher from Walmart online, and had it delivered. http://www.walmart.com/ip/Danby-Compact-Countertop-EnergyDishwasher/9854464
The CFF states that if your nebs are explosed to water that is at least "158° F for 30 minutes," this will kill PA. http://www.cff.org/UploadedFiles/LivingWithCF/StayingHealthy/Germs/StoppingTheSpread/Stopping-the-Spread-of-Germs.pdf (page 2, right column)
Bingo! the dishwasher sterilizes AND cleans all in one. I don't think any other method does this - if so, let me know so we can spread the word!
Needless to say, nearly 10 years later, I of course do my pulmozyme 2x/day like I am supposed to, because it's easy to have clean and sterile nebs! :)
So my solution when I first started living on my own to the cleaning/sterilizing neb thing? Simple. Stop doing pulmozyme regularly, and therefore have one less neb to clean.
Trust me, that didn't work out very well.
So the method I came up with was to get a little table top dishwasher that cleaned and sterilized nebs in one simple step!
I bought the dishwasher from Walmart online, and had it delivered. http://www.walmart.com/ip/Danby-Compact-Countertop-EnergyDishwasher/9854464
The CFF states that if your nebs are explosed to water that is at least "158° F for 30 minutes," this will kill PA. http://www.cff.org/UploadedFiles/LivingWithCF/StayingHealthy/Germs/StoppingTheSpread/Stopping-the-Spread-of-Germs.pdf (page 2, right column)
Bingo! the dishwasher sterilizes AND cleans all in one. I don't think any other method does this - if so, let me know so we can spread the word!
Needless to say, nearly 10 years later, I of course do my pulmozyme 2x/day like I am supposed to, because it's easy to have clean and sterile nebs! :)
Sunday, August 28, 2011
Why Long-Term Azithromycin Use Increases Infection With a Mycobacterium
ScienceDaily (Aug. 1, 2011) — The clinical outcome is improved if patients with chronic lung diseases such as cystic fibrosis are treated long-term with the antibiotic azithromycin. However, azithromycin treatment in patients with cystic fibrosis as recently associated with increased infection with nontuberculous mycobacteria. Now, researchers have confirmed that long-term use of azithromycin by adults with cystic fibrosis is associated with infection with nontuberculous mycobacteria and identified an underlying mechanism.
Specifically, the team found that in mice, azithromycin treatment inhibited the intracellular killing of nontuberculous mycobacteria within immune cells known as macrophages by impairing the cellular process autophagy. As azithromycin was not known to block autophagy prior to this work, these data highlight a clinical danger associated with inadvertent pharmacological blockade of this important cellular process.
http://www.sciencedaily.com/releases/2011/08/110801122952.htm
Azithromycin is an antibiotic that also has antiinflammatory properties. It is these antiinflammatory properties that are thought to account for the improvement in clinical outcome observed when patients with chronic lung diseases such as cystic fibrosis are treated long-term with azithromycin.
However, a recent study indicated that azithromycin treatment in patients with cystic fibrosis is associated with increased infection with nontuberculous mycobacteria, a serious complication in such individuals. Now, a team of researchers -- led by Andres Floto and David Rubinsztein, at the University of Cambridge, United Kingdom; and Diane Ordway, at Colorado State University, Fort Collins -- has confirmed that long-term use of azithromycin by adults with cystic fibrosis is associated with infection with nontuberculous mycobacteria and identified an underlying mechanism.
Specifically, the team found that in mice, azithromycin treatment inhibited the intracellular killing of nontuberculous mycobacteria within immune cells known as macrophages by impairing the cellular process autophagy. As azithromycin was not known to block autophagy prior to this work, these data highlight a clinical danger associated with inadvertent pharmacological blockade of this important cellular process.
http://www.sciencedaily.com/releases/2011/08/110801122952.htm
Thursday, July 28, 2011
Pfizer’s Zyvox and Antidepressants May Be Fatal Combination
Pfizer’s Zyvox and Antidepressants May Be Fatal Combination
Pfizer Inc. (PFE)’s Zyvox antib
iotic can cause potentially fatal central nervous system reactions in patients who also take antidepressants that increase levels of the brain chemical serotonin, U.S. regulators said.
Pfizer’s Zoloft and Pristiq, Eli Lilly & Co. (LLY)’s Cymbalta andGlaxoSmithKline Plc (GSK)’s Paxil and Wellbutrin are among 29 psychiatric drugs that patients may need to stop taking temporarily when they require treatment with Zyvox, the Food and Drug Administration said today in a drug safety communication.
Zyvox, used to treat some types of drug-resistant bacteria including MSRA or methicillin-related Staphylococcus aureus, skin infections and nosocomial pneumonia, can interact with the antidepressants to cause a toxic reaction known as serotonin syndrome in which excess amounts of the chemical build up in the brain, according to the FDA.
Some deaths among patients who suffered such a reaction were reported to the FDA’s adverse-event database, the agency said. Pfizer, based in New York, reported $1.18 billion in revenue from Zyvox last year.
Excess Serotonin
Confusion, memory issues, hyperactivity, excessive sweating and muscle twitching are among the symptoms of excess serotonin levels. Patients taking psychiatric drugs shouldn’t stop using them without first consulting a health-care professional, the FDA said.
The current U.S. package insert for Zyvox “already includes prominent information regarding the potential for serotonergic interactions, the risk of serotonin syndrome and the need for careful observation of patients prescribed Zyvox who are on such agents,” Kristen Neese, a Pfizer spokeswoman, said today in an e-mail. The company hasn’t identified any new safety signals related to those drug interactions, she said.
“In an ongoing commitment to ensure patient safety, Pfizer continually monitors all relevant safety information including information pertaining to the concomitant use of Zyvox and serotonergic antidepressant medications,” Neese said.
To contact the reporter on this story: Molly Peterson in Washington atmpeterson9@bloomberg.net
To contact the editor responsible for this story: Adriel Bettelheim at abettelheim@bloomberg.net
Tuesday, July 26, 2011
CF associated changes in lung stem cells may contribute to disease progression
Cystic fibrosis-associated changes in lung stem cells may contribute to disease progression
Researchers at the University of Iowa's Roy J. and Lucille A. Carver College of Medicine have discovered that in cystic fibrosis (CF) patients, the airway glands are depleted of a specific population of airway stem cells that participate in airway repair following injury.
Their results are published in the July 18 issue of Journal of Clinical Investigation.
The research team was led by John F. Engelhardt, Ph.D., Roy J. Carver Chair in Molecular Medicineand professor and head of anatomy and cell biology, and graduate student Weiliang Xie, UI Molecular and Cellular Biology Program.
Extensive research carried out on cystic fibrosis over the past two decades has firmly established that loss of a functional chloride channel called CFTR leads to chronic bacterial lung infections associated with recurrent injury and repair of the airways. One feature of the lung that helps to fightinfection is the presence of airway glands, which secrete bacteria-killing factors into the airway.
These glands are also neighborhoods, or niches, for adult airway stem cells, sheltering them from toxic insults that bombard the airway surface. Without functional CFTR these glands fail to secrete these antibacterial factors, making the lung particularly susceptible to infection and to the tissue damage that accompanies it. A question about CF that remains to be resolved is whether the repair processes normally triggered by infection-associated damage remain intact in the CF lung.
The UI research team discovered that airway glands from CF humans and three CF animal models -- pig, ferret and mouse -- aberrantly express a "neuropeptide" that both activates CFTR and controlsstem-cell responses in airway glands following lung injury. Neuropeptides are small molecules that help the nervous system direct functions in tissues. This increase in neuropeptide causes stemcells to abandon their protected glandular niches, and the airway to adapt by establishing new niches for stem cells in the more dangerous setting of the airway surface.
"This is the first demonstration that lung stem cell niches may be altered in CF," Engelhardt said.
In their study, the researchers hypothesized that when it comes to CFTR dysfunction the nervous system may try to compensate by overproducing one of several neuropeptides. Their research shows that the neuropeptide called CGRP is excessively produced by glands in an attempt to activate CFTR, but because of the lack of CFTR activity in cystic fibrosis the CGRP signal remains on.
"Imagine the axle is broken on a car and because the driver senses he is not moving he pushes the accelerator more; when the car still doesn't move he pushes down even further," Engelhardt said. "Eventually the engine overheats and bursts into flames."
In this analogy, CFTR is the broken axle, CGRP is the fuel that feeds the engine, and the centralnervous system is the driver who senses that thing are not functioning properly. CF airways thus produce more CGRP in an attempt to reactive the broken CFTR channel—the untoward side effectbeing that this pathway also stimulates stem cells in the gland to divide.
It remains unclear why the CGRP pathway is selectively hyperactivated in the CF lung, since other neuropeptides can also stimulate CFTR. Engelhardt and Xie hypothesize that this may be due to airway-gland injury caused by the lack of CFTR, since CGRP is transiently induced even in healthy glands following injury, to spur stem cells into action.
"The future excitement of these findings relates to the potential of manipulating lung stem cellsthrough neuropeptides or their inhibitors," Engelhardt said. He cautioned that "the identity of lungstem cell is a matter of hot debate, and it remains unclear how the majority of functional studies we conduct in mice will translate to humans. However, given the similar findings of CGRP dysregyulation in four CF species, this pathway appears to be important in CF."
The research team included UI researchers from the UI Carver College of Medicine and UCSF.
The study was funded in part by grants from the National Institutes of Health, and the UI Center for Gene Therapy.
STORY SOURCE: UI Health Care Marketing and Communications, University of Iowa Health Care, 200 Hawkins Dr., W319 GH, Iowa City, Iowa 52242-1178
MEDIA CONTACT: Molly Rossiter, 319-356-7127, molly-rossiter@uiowa.edu
http://www.healthcanal.com/disorders-conditions/19130-Cystic-fibrosis-associated-changes-lung-stem-cells-may-contribute-disease-progression.html
Their results are published in the July 18 issue of Journal of Clinical Investigation.
The research team was led by John F. Engelhardt, Ph.D., Roy J. Carver Chair in Molecular Medicineand professor and head of anatomy and cell biology, and graduate student Weiliang Xie, UI Molecular and Cellular Biology Program.
Extensive research carried out on cystic fibrosis over the past two decades has firmly established that loss of a functional chloride channel called CFTR leads to chronic bacterial lung infections associated with recurrent injury and repair of the airways. One feature of the lung that helps to fightinfection is the presence of airway glands, which secrete bacteria-killing factors into the airway.
These glands are also neighborhoods, or niches, for adult airway stem cells, sheltering them from toxic insults that bombard the airway surface. Without functional CFTR these glands fail to secrete these antibacterial factors, making the lung particularly susceptible to infection and to the tissue damage that accompanies it. A question about CF that remains to be resolved is whether the repair processes normally triggered by infection-associated damage remain intact in the CF lung.
The UI research team discovered that airway glands from CF humans and three CF animal models -- pig, ferret and mouse -- aberrantly express a "neuropeptide" that both activates CFTR and controlsstem-cell responses in airway glands following lung injury. Neuropeptides are small molecules that help the nervous system direct functions in tissues. This increase in neuropeptide causes stemcells to abandon their protected glandular niches, and the airway to adapt by establishing new niches for stem cells in the more dangerous setting of the airway surface.
"This is the first demonstration that lung stem cell niches may be altered in CF," Engelhardt said.
In their study, the researchers hypothesized that when it comes to CFTR dysfunction the nervous system may try to compensate by overproducing one of several neuropeptides. Their research shows that the neuropeptide called CGRP is excessively produced by glands in an attempt to activate CFTR, but because of the lack of CFTR activity in cystic fibrosis the CGRP signal remains on.
"Imagine the axle is broken on a car and because the driver senses he is not moving he pushes the accelerator more; when the car still doesn't move he pushes down even further," Engelhardt said. "Eventually the engine overheats and bursts into flames."
In this analogy, CFTR is the broken axle, CGRP is the fuel that feeds the engine, and the centralnervous system is the driver who senses that thing are not functioning properly. CF airways thus produce more CGRP in an attempt to reactive the broken CFTR channel—the untoward side effectbeing that this pathway also stimulates stem cells in the gland to divide.
It remains unclear why the CGRP pathway is selectively hyperactivated in the CF lung, since other neuropeptides can also stimulate CFTR. Engelhardt and Xie hypothesize that this may be due to airway-gland injury caused by the lack of CFTR, since CGRP is transiently induced even in healthy glands following injury, to spur stem cells into action.
"The future excitement of these findings relates to the potential of manipulating lung stem cellsthrough neuropeptides or their inhibitors," Engelhardt said. He cautioned that "the identity of lungstem cell is a matter of hot debate, and it remains unclear how the majority of functional studies we conduct in mice will translate to humans. However, given the similar findings of CGRP dysregyulation in four CF species, this pathway appears to be important in CF."
The research team included UI researchers from the UI Carver College of Medicine and UCSF.
The study was funded in part by grants from the National Institutes of Health, and the UI Center for Gene Therapy.
STORY SOURCE: UI Health Care Marketing and Communications, University of Iowa Health Care, 200 Hawkins Dr., W319 GH, Iowa City, Iowa 52242-1178
MEDIA CONTACT: Molly Rossiter, 319-356-7127, molly-rossiter@uiowa.edu
http://www.healthcanal.com/disorders-conditions/19130-Cystic-fibrosis-associated-changes-lung-stem-cells-may-contribute-disease-progression.html
Tuesday, July 19, 2011
Treatment of Hemoptysis with Tranexamic Acid
Treatment of Recurrent Severe Hemoptysis in Cystic Fibrosis with Tranexamic Acid
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=50470&Ausgabe=227718&ProduktNr=224278&filename=50470.pdf
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=50470&Ausgabe=227718&ProduktNr=224278&filename=50470.pdf
Severity of Cystic Fibrosis Linked to Genetics
Such a fascinating debate in the CF community over to what extent CF genes influence clinical outcomes. This is such an amazingly cool study!
Dr. Garry Cutting, from the Institute for Genetic Medicine at Johns Hopkins, explains, “We already know which gene causes cystic fibrosis, but to a large extent that gene does not by itself explain how severe the condition will be.”Severity of Cystic Fibrosis Linked to Genetics
by Rudolph Yap in Health News on Jul 13, 2011
Researchers have found that the severity of cystic fibrosis, which is a life-threatening hereditary condition that affects the lungs and digestive system, is seemed to be influenced by genetic variations.
According to Dr. Garry Cutting, a professor of pediatrics and a member of the McKusick-Nathans Institute for Genetic Medicine at Johns Hopkins, most cystic fibrosis patients born today live to their mid-30’s but that’s an average. Some succumb to the disease before their 10th birthday, while others live into their 50s and we wanted to know why.
For the study, the researchers used and analyzed a data from 3,467 patients, which included unrelated patients from the Genetic Modifier Study out of the University of North Carolina at Chapel Hill, the Canadian Consortium for Genetic Studies out of the University of Toronto, and related patients and their parents from the CF Twin and Sibling Study at Johns Hopkins. With this study, the team aims to achieve help extend the life expectancy of the people having this kind of disease.
The team of the three studies collaborated and analyzed 600,000 sites of variation that is found within the genome, hoping to search common variations which are more frequently associated with severe cases of the disease.
After this, the researchers were “able to identify a region encompassed by two genes on chromosome 11 linked to severe cases of the disease.” Chromosome 20 on the second region was also identified.
Cutting explained, “We already know which gene causes cystic fibrosis, but to a large extent that gene does not by itself explain how severe the condition will be.” He further added that they’ve already discovered new genes that influence the course of disease and may enable prediction of the disease’s severity and, most importantly, the customization of treatments for patients with unfavorable genetic modifiers — this is the realization of individualized medicine.
Moreover, Cutting concluded that this study might be the first step in developing therapies for the patients with cystic fibrosis.
Sunday, July 10, 2011
Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation.
Anyone know what a "Smart Nebulizer" is? I have never heard of it and I'm trying to google but not really finding much....
Eur Respir J. 2011 Jul 7. [Epub ahead of print]
Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation.
Bakker EM, Volpi S, Salonini E, van der Wiel-Kooij EC, Sintnicolaas CJ, Hop WC, Assael BM, Merkus PJ, Tiddens HA.
Source
Erasmus MC - Sophia Children's Hospital Rotterdam The Netherlands.
Abstract
Better treatment of obstructed small airways is needed in CF. This study investigated whether efficient deposition of dornase alfa in the small airways improves small airway obstruction. In a multi-centre, double-blind, randomized controlled clinical trial, CF patients on maintenance treatment with 2.5 mL dornase alfa once daily were switched to a smart nebulizer and randomized to small airways deposition (n=24) or large airways deposition (n=25) for 4 weeks.
The primary outcome parameter was Forced Expiratory Flow at 75% of Forced Vital Capacity (FEF75). FEF75 increased significantly by 0.7 SD (5.2% predicted) in the large airways group and 1.2 SD (8.8% predicted) in the small airways group. Intention to treat analysis did not show a significant difference in treatment effect between groups. Per protocol analysis, excluding patients not completing the trial or with adherence <70%, showed a trend (p=0.06) in FEF75 Z-score and a significant difference (p=0.04) between groups in absolute FEF75 (L·s(-1)) favouring small airways deposition.
Improved delivery of dornase alfa using a smart nebulizer that aids patients in correct inhalation technique resulted in significant improvement of FEF75 in children with stable CF. Adherent children showed a larger treatment response for small airways deposition.
- PMID:
- 21737560
- [PubMed - as supplied by publisher]
Friday, July 8, 2011
Replace Your Jacket!
Thanks to catboogie from www.cf2chat.com , I ordered a free replacement jacket from Respirtech. I have had my original jacket since 2006 so I figured it might be time for a replacement.
HUGS to catboogie for this tip because I had no idea what crappy shape my old jacket was in. WOW.
I would be able to do 100% pressure no problem with my old jacket - now I'm on 70% with this new jacket and it is MUCH more intense. wow wow wow! I'm guessing I had air leaking perhaps with my old jacket and just didn't notice it.
If you have a Respirtech vest, please make sure to replace it every so often to make sure you're getting the full effect (AND change the filter....something I also haven't done in a while). We use these devices way too often to not keep them in tip top shape.
HUGS to catboogie for this tip because I had no idea what crappy shape my old jacket was in. WOW.
I would be able to do 100% pressure no problem with my old jacket - now I'm on 70% with this new jacket and it is MUCH more intense. wow wow wow! I'm guessing I had air leaking perhaps with my old jacket and just didn't notice it.
If you have a Respirtech vest, please make sure to replace it every so often to make sure you're getting the full effect (AND change the filter....something I also haven't done in a while). We use these devices way too often to not keep them in tip top shape.
Monday, June 27, 2011
The role of female hormones on lung function in chronic lung diseases
The role of female hormones on lung function in chronic lung diseases
BMC Women's Health 2011, 11:24
".....it is known that sex hormones such as estrogen can also up-regulate MUC5B gene expression in normal
human airway epithelial cells [82]. MUC5B is one of the major mucins in the human airway
submucosal glands [83]. Estrogen is not the only regulator of MUC5B but also regulates a wide
diversity of genes involved in extracellular matrix, general cell growth, and differentiation processes
[24]. Taken together, estradiol may have the potential to augment mucin production resulting in
reduced clearance in CF. "
Read more here: http://www.biomedcentral.com/content/pdf/1472-6874-11-24.pdf
BMC Women's Health 2011, 11:24
".....it is known that sex hormones such as estrogen can also up-regulate MUC5B gene expression in normal
human airway epithelial cells [82]. MUC5B is one of the major mucins in the human airway
submucosal glands [83]. Estrogen is not the only regulator of MUC5B but also regulates a wide
diversity of genes involved in extracellular matrix, general cell growth, and differentiation processes
[24]. Taken together, estradiol may have the potential to augment mucin production resulting in
reduced clearance in CF. "
Read more here: http://www.biomedcentral.com/content/pdf/1472-6874-11-24.pdf
Saturday, June 18, 2011
Dr. Oz hearts GSH
Love me some Dr. Oz.
More support for our friend NAC, precursor to Glutathione (GSH).
CFers are known for lacking dearly in GSH.... The Superhero of Antioxidants, Pt 1.
I would love hear from anyone who has gotten IV GSH. Never heard of it before this segment.
More support for our friend NAC, precursor to Glutathione (GSH).
CFers are known for lacking dearly in GSH.... The Superhero of Antioxidants, Pt 1.
I would love hear from anyone who has gotten IV GSH. Never heard of it before this segment.
Saturday, April 16, 2011
Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study.
Eur Respir J. 2011 Apr 8. [Epub ahead of print]
Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study.
* Royal Brompton Hospital London United Kingdom.
Abstract
This international phase III study of inhaled dry powder mannitol was a randomised double blind 26 week study, followed by a further 26 week open-label extension. 324 subjects were randomised 3:2 to mannitol (400 mg bid) or control. The primary efficacy endpoint was to determine the change in FEV1 over the double-blind phase. Secondary endpoints included changes in FVC and pulmonary exacerbations.
A significant improvement in FEV1 was seen over 26 weeks (p<0.001) and was apparent by 6 weeks irrespective of concomitant rhDNase use. At 26 weeks, there was a significant improvement of 92.9 mL in FEV1 for subjects receiving mannitol compared with control (change from baseline 118.9 mL [6.5%] vs. 26.0 mL [2.4%]; p<0.001). Improvements in FEV1 were maintained up to 52 weeks in the open-label part of the study. There was a 35.4% reduction in the incidence of having an exacerbation on mannitol (p=0.045).
The incidence of adverse events (AE) was similar in both groups, though treatment related AEs were higher in the mannitol compared to the control group. The most common mannitol related AEs were cough, haemoptysis and pharyngolaryngeal pain. Mannitol shows sustained, clinically meaningful benefit in airway function in CF, irrespective of concomitant rhDNase use. Mannitol appears to have an acceptable safety profile for patients with CF.
Insulin Production and Resistance in CF: Effect of Age, Disease Activity and Genotype
J Endocrinol Invest. 2011 Apr 6. [Epub ahead of print]
INSULIN PRODUCTION AND RESISTANCE IN CYSTIC FIBROSIS: EFFECT OF AGE, DISEASE ACTIVITY, AND GENOTYPE.
Street ME, Spaggiari C, Ziveri MA, Rossi M, Volta C, Viani I, Grzincich GL, Sartori C, Zanzucchi M, Raia V, Terzi C, Pisi G, Zanetti E, Boguszewski MC, Kamoi TO, Bernasconi S.
Department of Paediatrics, University Hospital of Parma, Via Gramsci, 14, 43126 Parma, Italy.
Abstract
Aim: To assess the major determinants of glucose tolerance between age, genotype and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF related diabetes (CFRD). Subjects and Methods: 119 patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age also were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. HOMA-IR, fasting glucose/insulin ratio(FGIR) were calculated as indices of insulin resistance and insulinogenic index as a marker of pancreatic β cell function. All patients underwent an OGTT, and 57 underwent an IVGTT for the calculation of first phase(FPIR) and acute insulin responses(AIR).
Results:The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMA-IR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses glucose tolerance was related to the age-group, and to the HOMA-IR ans insulinogenic indexes. Conclusions: IGT and CFRD were related mainly to genotype, although as expected the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, β-cell function and reduced insulin sensitivity to the onset of CFRD, however further studies are warranted to better elucidate this aspect.
Mannitol-Guided delivery of ciprofloxacin
Biotechnol Bioeng. 2011 Jun;108(6):1441-9. doi: 10.1002/bit.23046. Epub 2011 Jan 15.
Mannitol-Guided delivery of ciprofloxacin in artificial cystic fibrosis mucus model.
College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907; telephone: +1-765-496-9608; fax: +1-765-494-6545; Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun, PR China.
Abstract
Abnormal airway mucus presents a significant challenge for inhalational drug delivery. Recognizing the thick and tenacious airway mucus seen in the cystic fibrosis (CF) patients as a critical barrier to effective drug delivery, both into the mucus layer itself as well as across that layer to the underlying airway epithelium, we hypothesize that mannitol or NaCl can form inhalable drug carriers, improve drug penetration into the mucus, and ultimately enhance the drug's therapeutic effect. The objective of this study is to test whether mannitol and NaCl particles, as inhalable drug carriers, improve drug delivery into and enhance a drug's activity within a mucus-like material.
Microparticles containing Ciprofloxacin (Cipro), an active ingredient, and either mannitol or NaCl were produced by spray-drying. Cipro encapsulated in mannitol particles (Cipro-mannitol) was significantly more effective at killing Pseudomonas aeruginosa (P. aeruginosa) grown in artificial mucus (AM) than Cipro encapsulated in either NaCl particles (Cipro-NaCl) or in hydrophobic particles consisting of dipalmitoylphosphatidylcholine (DPPC), albumin, and lactose (Cipro-DAL). The relatively high antibacterial effectiveness of Cipro-mannitol was not due to the effect of mannitol on bacteria or on Cipro. Rather, the unique performance of the mannitol-based particles in AM is attributable to its ability to increase local water content in the AM and enhance drug penetration into it. Mannitol is a promising excipient for inhalable microparticles that facilitate the drug delivery into the CF mucus.
Wednesday, April 6, 2011
TOBI® Podhaler® approved in Canada
Canadian cystic fibrosis patients can now lead more independent lives
New dry powder tobramycin formulation and the easy-to-use, pocket-sized, portable device will treat lung infections due to Pseudomonas aeruginosa (Pa) and reduce treatment burden
MONTRÉAL, April 5 /CNW/ - Novartis Canada announced today that it has received Health Canada Notice of Compliance (NOC) for TOBI® Podhaler®, a fast and convenient inhaled therapy1 for cystic fibrosis (CF) patients aged six and over. Canadian CF patients will be the first in the world to have access to TOBI® Podhaler®. The TOBI® Podhaler® offers a new dry-powder formulation of tobramycin delivered in a convenient and portable breath-activated inhaler for treating Pseudomonas aeruginosa (Pa) infections in CF patients.
"It is anticipated that the introduction of portable therapy for Pa infections will be a tremendous advance for CF patients, and may have a significant, positive impact on quality of life and treatment success," says Dr. Felix Ratjen, Paediatric Respirologist. "By eliminating the need for a nebulizer and regular disinfection of the equipment, it is anticipated that the risk of bacterial contamination will be greatly reduced while patient compliance will likely improve. Ultimately, this will lead to more effective treatment and help CF patients live more active, normal lives."
Pseudomonas aeruginosa infection is one of the most common pulmonary pathogens for Canadians with CF.2 As a CF patient ages, they are more likely to develop a Painfection.3 By the age of 25 years, more than 70 per cent of CF patients will develop a lung infection due to Pa.4 This common respiratory pathogen is one of the main drivers of morbidity and mortality in CF.5
Due to the complexity of current anti-Pa treatment, most patients do not fully adhere to their therapy.6,7,8 Although disinfection and cleaning are suggested every time a nebulizer is used, it is estimated that only 30 per cent of patients comply, and some never clean their nebulizer.9 TOBI® Podhaler® is a dry formulation with a disposable inhaler device which can be replaced weekly and potentially reduce the risk of bacterial contamination.10
In addition, data shows that patients using TOBI® Podhaler® completed their tobramycin treatment in five to six minutes, a reduction of 72 per cent11 in the time traditionally required to administer nebulized tobramycin. By improving the delivery of tobramycin and reducing treatment administration times, the TOBI® Podhaler® has the potential to help patients lead more independent lives.
Unique formulation and delivery system
TOBI® Podhaler® has a unique dry powder formulation, developed using novel PulmoSphere® technology to produce particles that are light and porous for deep delivery into the lung. This means treatment can be given with a portable, patient-friendly device, in contrast to current treatment options which are administered with a nebulizer.
By eliminating the use of a nebulizer, TOBI® Podhaler® does not require additional time for assembly and disinfection of the delivery device. In addition, TOBI® Podhaler® removes the need for refrigeration and a power source for the delivery device. A study found that patients treated with TOBI® Podhaler® had significantly higher treatment satisfaction than those treated with TOBI®.12
In addition, TOBI® Podhaler® was generally well tolerated during clinical trials. The most frequent reactions associated with TOBI® Podhaler® during the first treatment cycle were: cough, dysphonia, productive cough and oropharyngeal pain. The frequency of these adverse reactions decreased over the study duration.
Subscribe to:
Posts (Atom)