NoExcuses

Aquagenic palmar wrinkling

2012-01-21T19:03:00.000-05:00

Again, I think we as a CF community are so fortunate to have Mandy and all of her amazing research around treatments for CF. I have learned so much from her and this post is another testament to her dedication to the lives of all CFers.

As many of you know, I have been drinking green smoothies in an attempt to get more greens in my diet - I truly eat like a crazy teenager, which I know is not good for my health. I really love the smoothies and they taste wonderful.

A benefit I didn't realize I could expect from these wonderful smoothies is my aquagenic palmar wrinkling has disappeared. It took about 4 weeks of drinking the smoothies everyday, but it worked!

Now what exactly the health consequences are of this, we aren't sure. But we do know that those with CF and those who are CFTR carriers wrinkle much faster when submerged in water.

I'll continue to keep you all posted on any other exciting changes!

MDRPA to MDSPA

2012-01-21T18:26:00.000-05:00

In July 2011, I was so bummed to be admitted to the hospital with very, very few antibiotic options to treat my PA. Basically I had colistin and sorta kinda beta-lactams (intermediate resistance). Not too fun.

Well, thanks to the amazing wisdom of Ms. Mandy - who is always giving me great ideas), I have been taking Chilated Magnesium every day since October.

And in clinic on Jan 12, for the first time in 3 years, my clinic took me off isolation because I no longer have multi-drug resistant PA. Meaning all 3 of my PA strains are susceptible to nearly all classes of antibiotics (one strain is resistant to one class).

Talk about amazing. Incredible. Truly, a God-send.

Here are some studies supporting this outcome (thank you to Mandy's blog for these references):

Proteomic analysis of Pseudomonas aeruginosa grown under magnesium limitation.

Guina T, Wu M, Miller SI, Purvine SO, Yi EC, Eng J, Goodlett DR, Aebersold R, Ernst RK, Lee KA.

Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, Washington 98195, USA. tguina@u.washington.edu

In this study, large-scale qualitative and quantitative proteomic technology was applied to the analysis of the opportunistic bacterial pathogen Pseudomonas aeruginosa grown under magnesium limitation, an environmental condition previously shown to induce expression of various virulence factors. For quantitative analysis, whole cell and membrane proteins were differentially labeled with isotope-coded affinity tag (ICAT) reagents and ICAT reagent-labeled peptides were separated by two-dimensional chromatography prior to analysis by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) in an ion trap mass spectrometer (ITMS). To increase the number of protein identifications, gas-phase fractionation (GPF) in the m/z dimension was employed for analysis of ICAT peptides derived from whole cell extracts. The experiments confirmed expression of 1331 P. aeruginosa proteins of which 145 were differentially expressed upon limitation of magnesium. A number of conserved Gram-negative magnesium stress-response proteins involved in bacterial virulence were among the most abundant proteins induced in low magnesium. Comparative ICAT analysis of membrane versus whole cell protein indicated that growth of P. aeruginosa in low magnesium resulted in altered subcellular compartmentalization of large enzyme complexes such as ribosomes. This result was confirmed by 2-D PAGE analysis of P. aeruginosa outer membrane proteins. This study shows that large-scale quantitative proteomic technology can be successfully applied to the analysis of whole bacteria and to the discovery of functionally relevant biologic phenotypes.

PMID: 12837596 [PubMed - indexed for MEDLINE]

Green Smoothie for Lunch

2011-12-26T14:09:00.002-05:00

Yummy green smoothie for lunch today! :)

Anyone reading the books?

Green Smoothie Time!

2011-12-10T15:05:00.000-05:00

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 :)

How to clean nebs

2011-10-15T22:18:00.000-04:00

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! :)

Why Long-Term Azithromycin Use Increases Infection With a Mycobacterium

2011-08-28T21:01:00.002-04:00

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.

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

Pfizer’s Zyvox and Antidepressants May Be Fatal Combination

2011-07-28T00:04:00.000-04:00

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

http://www.bloomberg.com/news/2011-07-26/pfizer-s-zyvox-can-cause-toxicity-with-antidepressants-fda-says.html?cmpid=yhoo

CF associated changes in lung stem cells may contribute to disease progression

2011-07-26T10:05:00.000-04:00

Cystic fibrosis-associated changes in lung stem cells may contribute to disease progression

26/07/2011 02:49:00

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

Treatment of Hemoptysis with Tranexamic Acid

2011-07-19T23:25:00.000-04:00

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

Severity of Cystic Fibrosis Linked to Genetics

2011-07-19T23:21:00.000-04:00

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.

http://www.healthtalkandyou.com/severity-of-cystic-fibrosis-linked-to-genetics/

Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation.

2011-07-10T12:30:00.000-04:00

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]

Replace Your Jacket!

2011-07-08T15:31:00.000-04:00

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.

The role of female hormones on lung function in chronic lung diseases

2011-06-27T11:06:00.000-04:00

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

Dr. Oz hearts GSH

2011-06-18T22:08:00.001-04:00

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.

Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study.

2011-04-16T10:01:00.000-04:00

Eur Respir J. 2011 Apr 8. [Epub ahead of print]

Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study.

Bilton D, Robinson P, Cooper P, Gallagher CG, Kolbe J, Fox H, Jaques A, Charlton B.

* 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

2011-04-16T09:59:00.000-04:00

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

2011-04-16T09:58:00.000-04:00

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.

Yang Y, Tsifansky MD, Shin S, Lin Q, Yeo Y.

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.

TOBI® Podhaler® approved in Canada

2011-04-06T23:00:00.002-04:00

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.

Inhaled PDE5's treat CF

2011-03-28T22:54:00.000-04:00

Never realized the plan was to nebulize cialis or levitra - always thought we would just take them as a pill. So interesting....

Expert Opin Investig Drugs. 2011 Mar 24. [Epub ahead of print]

Inhaled phosphodiesterase type 5 inhibitors for cystic fibrosis: a new therapy for systemic disease?

Antoniu SA.

University of Medicine and Pharmacy "Gr.T.Popa" Iasi, Department of Internal Medicine II-Pulmonary Disease, Pulmonary Disease University Hospital, 30 Dr I Cihac Str, 700115 Iasi, Romania +40 232

239408 ; +40 232 270918 ; sabina.antonela.antoniu@pneum.umfiasi.ro.

Abstract

Cystic fibrosis is a rare disease characterized by abnormalities in chloride and sodium transmembrane transportation due to various mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, F508del being the most commonly found. Corrective therapies for this defect are currently under investigation and PDE5 inhibitors such as sildenafil or vardenafil were found to improve CFTR activity in vitro as well as in vivo. This paper evaluates a study investigating the effects of inhaled PDE5 inhibitors in an animal model of F508del cystic fibrosis, demonstrating that in this new formulation, such compounds are also able to improve CFTR function. Such results support the further development of this therapy for a systemic disease such as cystic fibrosis, provided several issues are addressed.

PMID: 21434839 [PubMed - as supplied by publisher

Using Tobra in the eFlow

2011-03-28T22:53:00.000-04:00

Pediatr Pulmonol. 2011 Apr;46(4):401-8. doi: 10.1002/ppul.21376. Epub 2010 Dec 30.

Higher Tobramycin concentration and vibrating mesh technology can shorten antibiotic treatment time in cystic fibrosis.

Coates AL, Denk O, Leung K, Ribeiro N, Chan J, Green M, Martin S, Charron M, Edwardes M, Keller M.

Physiology and Experimental Medicine, Research Institute of Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. allan.coates@sickkids.ca.

Abstract

Poor adherence to recommended therapy in cystic fibrosis (CF) is often because of the time demands of therapy. Tobramycin (TOBI®, 300 mg at 60 mg/ml) inhaled from the PARI LC PLUS® nebulizer requires about 20 min.

This study determined if equivalent levels of pulmonary deposition could be achieved in shorter time using 1.5 ml of 100 mg/ml tobramycin solution delivered by an investigational eFlow® nebulizer.

Sixteen males with stable CF, 8 children and 8 adults, and an FEV(1) > 45% predicted inhaled both preparations on two occasions with (99m) Tc-DTPA added to the tobramycin. Blood samples were taken for quantification of tobramycin in the serum. The PARI LC PLUS® delivered 45.4 (39.3-51.6), mean and 95% CI, mg to the lungs in 17.0 ± 2.5 min (mean ± SD) with serum levels of 1,089 ± 388 µg/L.

The investigational eFlow® delivered 46.3(40.3-51.7) mg in 4.0 ± 1.0 min with blood levels of 909 ± 458 µg/L. Only the time of delivery was significantly different with P < 0.0001 (paired t-test). Tolerability of the treatment was comparable for both inhalation regimes, but the shorter treatment was preferred by all patients.

These results demonstrate the possibility of delivering equivalent levels of tobramycin much faster into the lungs of CF patients when using eFlow®, a very efficient electronic nebulizer. Pediatr Pulmonol. 2011; 46:401-408. © 2010 Wiley-Liss, Inc.

A Comparison of Amount and Speed of Deposition Between the PARI LC STAR(®) Jet Nebulizer and eFlow(®) Nebulizer

2011-03-06T01:51:00.000-05:00

J Aerosol Med Pulm Drug Deliv. 2011 Mar 1.

A Comparison of Amount and Speed of Deposition Between the PARI LC STAR(®) Jet Nebulizer and an Investigational eFlow(®) Nebulizer.

Coates AL, Green M, Leung K, Chan J, Ribeiro N, Ratjen F, Charron M.

Divisions of Nuclear Medicine and Respiratory Medicine, Hospital for Sick Children Research Institute, University of Toronto , Toronto, Canada .

Abstract

Abstract Background: The potency and physical properties of many of the drugs used in the treatment of cystic fibrosis necessitates the use of nebulization, a relatively time-consuming pulmonary delivery method. Newer, faster, and more efficient delivery systems are being proposed.

The purposes of this study was to compare the length of time it took to deliver the equivalent of normal saline nebulized for 10 min in a PARI LC STAR(®) nebulizer to that of an investigational PARI eFlow(®).

Methods: Six normal adults inhaled a 4-mL (36-mg) charge volume of saline from the LC STAR(®) or a 2.5-mL (22.5-mg) charge volume from the investigational eFlow(®). The saline was mixed with (99m)Tc-DTPA to allow two-dimensional imaging. The inhalation was preceded by a xenon equilibration scan to allow more accurate separation of deposition into central and peripheral lung regions.

Results: The investigational eFlow(®) delivered 8.6 ± 1.0 mg, approximately 90% of the lung dose compared to the LC STAR(®), 9.6 ± 1.0 mg, but did in less than half the time (p < 0.02 for both). There were no differences in central versus peripheral distribution for either device. Conclusions: In conclusion the investigational eFlow(®) was both faster and more efficient than the LC STAR(®).

The cystic fibrosis sufferer who took off around the world

2011-03-06T01:40:00.000-05:00

The cystic fibrosis sufferer who defied doctors and took off around the world... with a backpack full of life-saving drugs

By CAVAN ARROWSMITH
Last updated at 8:29 PM on 28th February 2011

For as long as I can remember, I have wanted to travel the world – and forget for a while that I have cystic fibrosis (CF).

It is a disease that I was born with and it affects the lungs and digestive system, causing them to become clogged with thick, sticky mucus. I will die from it, although I don’t know when. I am 24 – the average life expectancy is 35.

About 8,500 people in the UK have CF and, so far, there’s no cure. Five babies are born every week with the condition. But I live a pretty normal life. I work in IT, I’m an avid cricket fan and have played since my early teens.

Down Under: Cavan Arrowsmith with his girlfriend Claire in Sydney on his trip to remember

I spend time with my girlfriend, Claire. I also have to take medicine morning and night to manage my condition.

As a child, being told you aren’t going to live for many years is hard to understand. Now I have to be realistic, and know my limits, but I am also determined to live a fulfilled life.

More...

Victoria Beckham slammed for denying cystic fibrosis sufferer a parking space after stopping in disabled bay at toy shop

My aim was a ten-month trip to the US, Asia and Australia to prove I could do it, and to inspire others.

It took months to organise and there were a few medical dramas along the way, but in the end even they turned out to be part of the adventure . . .

Hot and dirty: Cavan struggled on the India leg of his trip because the country's environment was not good for his health

FEBRUARY 28, 2010

It’s a little after 5am when my dad, John, my 67-year-old nan, Irene, and Claire pile into Dad’s car for the short trip from his home in Stourbridge, West Midlands, to Birmingham Airport and the big send-off.

My 120-litre red-and-black backpack is stuffed to bursting, but not because I need lots of clothes. Half the pack contains a three-month supply of medicine. I have to take five tablets to help my digestion, and Creon capsules that contain a pig enzyme that helps break down food.

I also have two inhalers with drugs that help keep my airways open and free from inflammation, and a nebuliser (a machine that turns medicines into vapour that I can then inhale through a mask) to deliver a daily antibiotic that helps to tackle chest infections.

There is another nebuliser that helps break down the mucus in my lungs, reducing the amount I cough.

Majestic: Cavan and friends at the Grand Canyon

On top of these I need a daily calcium supplement and multivitamins as I can’t absorb nutrients properly.

Oh, and there are more tablets such as emergency antibiotics. The other half of my pack has all the usual stuff such as walking boots, my laptop and sleeping bag.

I told my doctor about my plans and he said as I was well, it was a good time for me to travel. Dad and Claire hug me goodbye, leaving me alone with Gordon Clarke, my best friend from primary school, who is joining me for the whole journey.

After a few final waves we’re through security and on our way. Next stop: San Francisco.

MARCH 1

Our flight goes via Frankfurt, where we join Robert Black and Matthew Smith, friends from Birmingham City University. Gordon and I will come back to the UK, briefly, after three months to replenish my medical supplies.

Rob and Matt will be with us for the America leg and then head home. We allow a week to see San Francisco but just two days in, my nebuliser breaks.

We have to order a spare part from my hospital consultant back home in Birmingham, who arranges for the manufacturers to send out the part. It takes a week to arrive.

But we make the most of the time to see all the city’s famous sights, such as the Golden Gate Bridge, cable cars, the ferry ride to Alcatraz, and Chinatown.

Eastern promise: Cavan and his friend Gordon conquer the Great Wall of China

MARCH 10

We’re finally on the move again and from San Francisco we head inland to Las Vegas in our rather cramped camper van. It’s the best our budget can manage. There’s one double bed at the back, which two of us share, and one single bed in the kitchen.

There’s also a double bed above the driver’s area. We call this the ‘penthouse’ and take turns to sleep there every fourth night. My friends have never treated me any differently because I have CF. But I can’t be as carefree as they are.

When Matt comes down with a chest infection, I have to make sure I sleep as far away from him as possible. Catching a cold can mean hospital for me. I am also supposed to eat 5,000 calories of food a day, which is double the normal recommendation for a man.

This is because my body is constantly fighting infection, which burns up huge amounts of energy. I can’t miss meals and I am always hungry. Luckily, there are no shortage of food stops on a US road trip.

MAY 3

After Vegas, and then the Grand Canyon, we head to Scottsdale, Arizona, and carry on across America, stopping in Texas, Tennessee and then New York, where we watch Ricky Gervais at Madison Square Garden.

It reminds me of home and how much I miss Claire. We have known each other since the age of five, growing up together as friends before becoming a couple in secondary school.

Meeting the locals: Cavan with members of the Black Hmong hill tribe in Vietnam

My CF is part of her life, too. I have been hospitalised five times, mainly for chest infections, for about two weeks each time. The last time, Claire came back to visit me from Portsmouth where she was studying law.

We plan to move in together when I get back, and settle down. I want children, although not right away. We have discussed the fact that I might not be around for ever, and when my children are teenagers I don’t want to be so unwell that I can’t be part of their lives.

But I’m hoping by then there will be a cure. And it is all the more reason to stay fit and active, as exercise really helps reduce infection.

With Central Park, the Statue of Liberty and Fifth Avenue behind us, we head north to Boston and our final stop on this particular leg.

MAY 20

We are back in Birmingham so I can restock with medicine. My consultant said I needed to come to see him only if I wasn’t well, and I feel fine. Better than that. It’s so fantastic to see Claire.

We have to wait for Gordon’s India visa to come through. In the meantime, I begin filling my bag with boxes of tablets, inhalers . . . My stepmum, Joanne, and sister, Lucy, 17, come to see me off.

Next time I see Dad, I’ll be 24, which is amazing really as when I was born the doctors told him I wouldn’t live beyond my teens.

One of the gang: Cavan on a group camping trip on Fraser Island in Australia

JUNE 5

Bombay is shocking. We stay in a cheap hotel 60 miles from the city centre with cockroaches on the floor and no proper loos. It’s hot and dirty and a constant challenge to find unopened, bottled water to clean the mouthpieces of my nebuliser.

The air is dusty and I cough a lot. Parts of India are really beautiful, particularly the Taj Mahal, and Goa is gorgeous but it’s always in the back of my mind that this place isn’t good for me.

Leaving at the end of June does not come soon enough.

JUNE 25

We’re in Beijing, struck by the vastness of Tiananmen Square and everything that’s in it, including Mao’s Mausoleum. We’ve heard the best place to access the Great Wall is from Mutianyu, about 90 minutes out of the city, and we’re not disappointed.

There’s a cable car to the top but Gordon and I walk up instead. It’s about 800 steps, which takes 40 minutes. I beat Gordon up there. With regular long walks and cricket, I’m actually pretty fit by any standards.

My lung function – a measure of how well the lungs are working – is average, not for CF patients but for anyone of my age, although when I have a chest infection this drops dramatically.

Our thighs burn from the effort but it really is worth it. The views from the top are stunning.

JULY 7

From Beijing we head to Shanghai. It’s humid, something I have to avoid. Damp, warm air in my lungs is a breeding ground for bacteria.

Gordon and I stay in an eight-bed dorm and there are a lot of sniffles going round. I start to feel unwell.

We press on to see the Terracotta Army at Xi’an. I’m feeling pretty terrible and I suspect I have picked up a cold as I am coughing a lot, but we continue to Hong Kong, by train, and then fly to Hanoi, Vietnam.

I know if I seek medical help it will be admitting defeat, so I take emergency antibiotics as a last resort.

Brave face: Cavan on a drip while being treated at Bangkok Hospital

AUGUST 10

By now we’re at Nha Trang, a beautiful city on Vietnam’s coast, but I’m feeling worse and the cold has become a full-on chest infection.

One of the biggest obstacles to this trip was finding insurance. I was turned down by 15 companies before the Cystic Fibrosis Trust put me in touch with Ageas, which covered me for £470. Gordon paid just £120.

I need treatment and though it takes them five days, the insurers find me a hospital in Bangkok, so we board a bus. I’m in hospital for two weeks while the insurance company organises accommodation for Gordon.

Finding high-calorie food isn’t that easy, and noodle soup just doesn’t cut it. So every day Gordon brings a McDonald’s milkshake, burgers and fries, and then spends the rest of the day with me as I slowly recover.

AUGUST 28

Rested and back to health, I am discharged and we fly to Perth. In hospital I was running on a treadmill with the physiotherapist every day, so I feel great. And now in Australia I’m out on the beach, swimming and attempting to surf. Being outdoors really agrees with me.

Within a few weeks Gordon and I are broke, so we both get jobs in call centres and work for the next two months.

NOVEMBER 4

It’s my 24th birthday and, like all my birthdays, it’s a real reason to celebrate. I’m planning to live a long time. But I am aware that 50 years ago babies born with CF often didn’t live beyond a year.

Claire and two friends, Laura and Karl, have flown out and I am over the moon. We hire a car and drive to Adelaide, Melbourne and then Sydney, where we climb the Harbour Bridge. I would move here in a heartbeat.

DECEMBER 23

Gordon and I arrive back to a freezing Birmingham. I’ll be for ever grateful to him for helping me achieve something I’ve held in my heart for so long and to the people who stepped in along the way to keep me on track. I’m home.

Job done. The sky really is the limit.

●Cavan is raising money for the Cystic Fibrosis Trust. www.justgiving.com/cavanarrowsmith

Association between genotype and pulmonary phenotype in CFers

2011-03-06T01:35:00.002-05:00

J Cyst Fibros. 2011 Feb 25. [Epub ahead of print]

Association between genotype and pulmonary phenotype in cystic fibrosis patients with severe mutations.

Geborek A, Hjelte L.

Abstract

BACKGROUND: Despite numerous studies a clear relationship between genotype and pulmonary phenotype has not been established within the group pancreatic insufficient cystic fibrosis (CF) patients. We studied the relationship between class I and class II mutations and pulmonary function in Swedish patients with known CFTR functional classification.

METHODS: 170 CF patients with two class II mutations, 18 with two class I mutations and 78 with a combination of class I and II mutations were included in the study. Spirometry was performed when patients were in an optimal clinical condition.

RESULTS: Patients with two class I mutations had lower lung function (FEV(1) and FVC) compared to the group with either a combination of class I and II mutations or two class II mutations.

CONCLUSION: CF patients carrying two class I mutations risk developing more severe lung disease compared to patients with at least one class II mutation.

Effects of Ginseng on PA motility and biofilm formation.

2011-02-10T11:07:00.000-05:00

FEMS Immunol Med Microbiol. 2011 Feb 8. doi: 10.1111/j.1574-695X.2011.00787.x. [Epub ahead of print]

Effects of Ginseng on Pseudomonas aeruginosa motility and biofilm formation.

Wu H, Lee B, Yang L, Wang H, Givskov M, Molin S, Høiby N, Song Z.

Department of Clinical Microbiology, Rigshospitalet, Copenhagen, DENMARK Department of Systems Biology, Technical University of Denmark, Lyngby, DENMARK Department of International health, Immunology and Microbiology, University of Copenhagen, Copenhagen, DENMARK ESCMID Study Group on Biofilms.

Abstract

Biofilm associated chronic Pseudomonas aeruginosa lung infections in patients with Cystic Fibrosis (CF) are virtually impossible to eradicate with antibiotics because biofilm growing bacteria are highly tolerant to antibiotics and host defence mechanisms. Previously we found that Ginseng treatments protected animal models from development of chronic lung infection by P. aeruginosa. In the present study, the effects of Ginseng on the formation of P. aeruginosa biofilms were further investigated in vitro and in vivo. Ginseng aqueous-extract at concentrations of 0.5-2.0% did not inhibit growth of P. aeruginosa, but significantly prevented P. aeruginosa from forming biofilm. Exposure to 0.5% Ginseng aqueous-extract for 24 h destroyed most of 7-day-old mature biofilms formed by both mucoid and non-mucoid P. aeruginosa strains. Ginseng treatment enhanced swimming and twitching motility, but reduced swarming of P. aeruginosa at concentrations as low as 0.25%. Oral administration of ginseng extracts in mice promoted phagocytosis of P. aeruginosa PAO1 by airway phagocytes, but did not affect phagocytosis of a PAO1-filM mutant. Our study suggests that Ginseng treatment may help to eradicate the biofilm associated chronic infections caused by P. aeruginosa.

PMID: 21303421 [PubMed - as supplied by publisher]

Australian Approval for Pharmaxis

2011-02-09T22:14:00.002-05:00

08 February 2011

PHARMAXIS' BRONCHITOL RECEIVES TGA APPROVAL FOR AUSTRALIANS WITH CYSTIC FIBROSIS

Pharmaceutical company Pharmaxis (ASX: PXS) today announced that the Australian Therapeutic Goods Administration (TGA) has approved Bronchitol (inhaled dry powder mannitol) for marketing in Australia for the treatment of cystic fibrosis and it is now to be included in the Australian Register of Therapeutic Goods (ARTG).

Bronchitol has been approved for the treatment of cystic fibrosis (CF) in both adult and paediatric patients aged over six years as either an add-on therapy to dornase alfa or in patients intolerant of, or inadequately responsive to, dornase alfa.

Mr Terry Stewart, CEO of CF Australia, said: "We welcome the approval of Bronchitol and congratulate Pharmaxis on its commitment to helping patients and in getting a long awaited new treatment to this point. There is a great need for new medicines for people with CF. We must not forget that this is a genetic condition; people have cystic fibrosis from their first breath, so anything new that can improve patients' way of living, their quality of life and potentially their length of life is a wonderful step forward."

Dr Alan Robertson, Pharmaxis Chief Executive Officer, said: "The TGA's decision is the first approval for Bronchitol anywhere in the world and is an historic milestone for the company. It is fitting for a product that has been discovered and developed in Australia to be made available first to Australian patients. We are extremely pleased to have concluded the regulatory review process for Bronchitol with the TGA, one of the world's leading regulatory bodies. This approval is a testament to the hard work of many people in Pharmaxis and those in the CF community worldwide who have assisted in the clinical development of Bronchitol."

Bronchitol has been the subject of two pivotal clinical trials in cystic fibrosis in over 600 people involving 93 hospitals around the world. In April 2009 Bronchitol was awarded Orphan Drug designation in Australia for the treatment of patients with cystic fibrosis to improve lung function and reduce exacerbations.

Bronchitol has received Orphan Drug Designation and fast track status from the US Food and Drug Administration and Orphan Drug Designation from the European Medicines Agency.

#ENDS#

SOURCE: Pharmaxis Ltd, Sydney, Australia
CONTACT: Alan Robertson - Chief Executive Officer
Ph: +61 2 9454 7200 or email alan.robertson@pharmaxis.com.au

RELEASED THROUGH:
Australia:
Felicity Moffatt, phone +61 418 677 701 or email felicity.moffatt@pharmaxis.com.au

Cystic Fibrosis Gene Mutation Tied to Pancreatitis Risk

2011-02-04T11:21:00.000-05:00

Cystic Fibrosis Gene Mutation Tied to Pancreatitis Risk

Last Updated: February 03, 2011.

Patients with pancreatic-sufficient cystic fibrosis carrying genotypes associated with mild phenotypes appear to be at an increased risk of developing pancreatitis as compared to patients with the disease carrying genotypes associated with moderate-severe phenotypes, according to a study published in the January issue of Gastroenterology.

Patients with pancreatic-sufficient cystic fibrosis (CF) carrying genotypes associated with mild phenotypes appear to be at an increased risk of developing pancreatitis as compared to patients with the disease carrying genotypes associated with moderate-severe phenotypes, according to a study published in the January issue ofGastroenterology.

Chee Y. Ooi, of The Hospital for Sick Children in Toronto, and colleagues identified 277 patients with pancreatic-sufficient CF from two CF population-based databases to assess whether genotypes of the CF gene (CFTR) determined the risk of pancreatitis.

The investigators found that patients with pancreatitis were more likely to have genotypes associated with mild (70 percent) as compared with moderate-severe (30 percent) pancreatic insufficiency prevalence (PIP) scores. The investigators also found that the cumulative proportion of patients who developed pancreatitis through age 50 years was significantly greater for genotypes associated with mild (50 percent) than moderate-severe (27 percent) PIP scores. Compared to patients without pancreatitis, patients with pancreatitis were diagnosed with CF at an older median age and had lower mean levels of sweat chloride.

"Specific CFTR genotypes are significantly associated with pancreatitis. Patients with genotypes associated with mild phenotypic effects have a greater risk of developing pancreatitis than patients with genotypes associated with moderate-severe phenotypes," the authors write

http://www.doctorslounge.com/index.php/news/pb/17582

Breakthrough On Cystic Fibrosis One Step Closer As New Research Alliance Formed

2011-01-30T10:33:00.000-05:00

Breakthrough On Cystic Fibrosis One Step Closer As New Research Alliance Formed

Article Date: 27 Jan 2011 - 3:00 PST

McGill University and GlaxoSmithKline plc (GSK) have signed a collaboration agreement to develop a potential breakthrough approach to treat cystic fibrosis, a fatal genetic disease. The trans-Atlantic effort between researchers from McGill's Faculty of Medicine and their GSK collaborators in the UK, will focus on developing molecules that could treat the disease by correcting the dysfunction caused by the mutated gene. This revolutionary approach will be a departure from current treatments, which only manage the symptoms or complications of the disorder. The collaborative research is co-sponsored by the Canadian Institutes of Health Research (CIHR).

Cystic fibrosis (CF) is one of the most common fatal genetic diseases. It is a multi-organ disease but primarily affects the lungs and digestive system, causing mucous to thicken and leaving patients at higher risk of infections. CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR). About 90 per cent of those living with cystic fibrosis have a particular mutant form of this gene, which makes a protein that could still work but has a defect that prevents it getting to the right place in the cell to function correctly.

Dr. David Thomas, Chair of McGill's Department of Biochemistry and Canada Research Chair in Molecular Genetics, is an expert in protein quality control. Dr. John Hanrahan is Professor in McGill's Department of Physiology and an expert in chloride transport and epithelial biology. They are uniquely qualified as lead investigators on McGill's side, having conducted extensive research on the CFTR protein and have identified a number of molecules that look to restore normal CFTR function.

"If we can restore normal function to the mutant cystic fibrosis protein, we can radically transform the lives of millions of children. It will move us from treatment of symptoms to prevention of the disease and would ultimately save lives," said Dr. Thomas. "We will now be looking at enhancing these small molecules to improve their ability to "rescue" or "correct" the mutant protein, allowing it to reach its proper location and be more active," added Dr. Hanrahan.

"GSK is excited to be applying our expertise in areas including medicinal chemistry to this innovative area of research," said Dr. Roberto Solari, head of respiratory biology at GSK. "We hope at the end of this two year collaboration we will have a compound that is be ready to be investigated as a potential new medicine. Collaborations such as these - where we share knowledge, expertise and resource - provide a highly effective way of progressing cutting edge research."

"This strong collaboration between an industry partner, government granting agencies and the University is a superb example of partners building on mutual strengths and collaborating where our research interests converge," said Dr. Rose Goldstein, Vice-Principal (Research and International Relations). "We are grateful for the support provided by GSK and CIHR, facilitating our work together to give people with cystic fibrosis a healthy and full life expectancy."

"Health research successes in the 21st century will be very much dependent on the ability of organizations from the public, academic and private sector to combine efforts and pool resources," said Dr. Marc Ouellette, Scientific Director for The Canadian Institutes of Health Research's Institute of Infection and Immunity. "In particular, this grant will increase our understanding of the cellular mechanisms causing cystic fibrosis and provide novel ways of targeting genetic based diseases. Research done through the support of this partnership will add to groundbreaking work done by Canada's strong Cystic Fibrosis research community, including those funded under the Canadian led Human Microbiome Initiative."

This research program has funding from both GSK and from an R&D operating grant from CIHR. It builds on previous work carried out with support from the Canadian and US CF Foundations, Génome Québec, CIHR and the Canadian Foundation for Innovation (CFI). It is the flagship project of a new cystic fibrosis translational research CFTR centre at McGill that has been established with support from the CFI.

About the Cystic Fibrosis

Cystic Fibrosis is caused by a single faulty gene that controls the movement of salt in the body. In people with Cystic Fibrosis, the internal organs become clogged with thick, sticky mucus resulting in infections and inflammation making it hard to breathe and digest food. There is no cure for the disease. About one in every 3,600 children born in Canada has CF. Treatment is aimed at controlling symptoms and infections. All disease-causing mutations in the gene for CFTR prevent the chloride channel from functioning properly, blocking movement of salt and water into and out of cells. As a result, cells that line the passageways of the lungs, pancreas, and other organs produce abnormally thick, sticky mucus. This viscous mucus cannot be easily cleared by the body, leading to obstruction of airways and glands and trapping bacteria that give rise to chronic infections.

Source:
McGill University
GlaxoSmithKline
Canadian Institutes of Health Research

http://www.medicalnewstoday.com/articles/214887.php

New Method Attacks PA

2011-01-30T10:31:00.000-05:00

New Method Attacks Bacterial Infections on Contact Lenses

ScienceDaily (Jan. 25, 2011) — Researchers at National Jewish Health and the University of Texas Southwestern Medical Center have discovered a new method to fight bacterial infections associated with contact lenses. The method may also have applications for bacterial infections associated with severe burns and cystic fibrosis. The results were published online January 18 in the journalInvestigative Ophthalmology and Visual Science.

"Infections by the bacteriaPseudomonas aeruginosa can cause severe scarring and vision loss when they spread to the cornea," said senior author Jerry Nick, MD, Associate Professor of Medicine at National Jewish Health. "By breaking apart a molecular scaffolding that encases the organisms and makes them more difficult to eradicate, we were able to significantly reduce bacterial infection of the cornea."

The eye normally fights infections through a variety of defense mechanisms including blinking of the eyes, which helps remove bacterial organisms from the surface of the eye. Contact lenses, however, inhibit the effectiveness of blinking eyelids.

Thus, bacteria can adhere to the surface of the contact lens that sits against the eye. If those bacteria infect the corneal surface they can destroy the delicate corneal cells, which can lead to scarring and vision loss. The condition is known as microbial keratitis, and affects about two to four lens wearers per 10,000 each year.

Eye infections can be treated with antibiotics. However, it can be difficult to eliminate the bacteria on the contact lenses, especially when they form a biofilm. A biofilm is a matrix that harbors and encases communities of the organisms, making them harder to eradicate.

The researchers confirmed earlier findings that cellular debris from immune cells fighting the infection actually provide the raw materials for the biofilm -- DNA, actin and histones. So, they used the enzyme DNAase together with negatively charged poly aspartic acid to break down the chemical bonds of these elements that support the biofilm.

This treatment reduced biofilms on the contact lenses by 79.2 percent. The same treatment reduced infection of the cornea in an animal model by 41 percent. There was no evidence of any harm caused by the treatments. (Abstract)

"These are very promising early results that point to potentially new methods for removing bacterial biofilms from contact lens surfaces, thereby reducing the risk of microbial keratitis, as well as the for the treatment of infections by Pseudomonas that are associated with cystic fibrosis and severe burns,' said Danielle Robertson, OD, PhD, first author and Assistant Professor of Ophthalmology at UT Southwestern, and first author on the study.

Mpex Initiates Phase 3 Clinical Trial Program with Aeroquin

2011-01-10T22:11:00.000-05:00

Mpex Initiates Phase 3 Clinical Trial Program with Aeroquin™ for the Treatment of Chronic Bacterial Infections in Cystic Fibrosis Patients

SAN FRANCISCO, Jan. 10, 2011 /PRNewswire/ -- Mpex Pharmaceuticals, Inc. today during the JP Morgan 29th Annual Healthcare Conference, announced that it has initiated its Phase 3 clinical trial program with Aeroquin™ (MP-376) for the treatment of pulmonary infections in patients with cystic fibrosis (CF). Aeroquin is Mpex's proprietary aerosol formulation of levofloxacin, an antibiotic that has potent activity against key bacterial pathogens in CF including Pseudomonas aeruginosa.

The first study in this program is a multi-center, international, randomized, double-blind, placebo-controlled trial (Mpex 207) that is expected to enroll approximately 300 stable CF patients to evaluate the safety, tolerability and efficacy of 240 mg of Aeroquin administered twice daily using an optimized, Investigational eFlow Nebulizer System for 28 days. To ensure that results from this trial are predictive of efficacy in heavily treated cystic fibrosis patient and consistent with current clinical practice, the study will enroll patients that have recently received multiple courses of inhaled antibiotics and in most cases are receiving concomitant medication such as dornase alpha, azithromycin and hypertonic saline. Patient enrollment in this study has already begun.

The primary efficacy endpoint to be assessed in the trial will be time to exacerbation. Additional endpoints include time to need for anti-pseudomonal antimicrobials, as well as change from baseline to Day 28 in lung function, the respiratory domain score of the CFQ-R and sputum Pseudomonas aeruginosa density.

An additional Phase 3 trial comparing Aeroquin to TOBI® (tobramycin inhalation solution) over three 28-day cycles (Mpex 209) is expected to begin enrolling patients in the next several weeks.

A previous Phase 2b study in 151 CF patients (Mpex 204) demonstrated that Aeroquin had a significant impact on bacterial load, respiratory function and time to need for anti-pseudomonal antibiotics (a measure of exacerbations) versus placebo in a heavily treated patient population. The primary endpoint, a reduction in sputum Pseudomonas aeruginosa density at Day 28 (end of treatment) was achieved, with a twice daily 240mg dose showing the greatest effect. Statistically significant improvements in respiratory function including percent predicted FEV1, FEF25-75 and percent predicted FVC at Day 28 versus placebo were also observed with the 240mg twice-daily dose. Consistent with these results, a statistically significant reduction in the need for other inhaled and/or systemic anti-pseudomonal antimicrobials was also observed. There were no safety concerns identified in Mpex 204 and there was no evidence for emergence of bacterial resistance during the study.

"The Phase 2b study with Aeroquin showed strong, consistent results in a very heavily treated patient population which bodes well for Phase 3," stated Jeff Loutit, Chief Medical Officer of Mpex Pharmaceuticals, Inc. "A new inhaled antimicrobial with potent activity against a broad spectrum of pathogens, good tolerability, and with a low treatment burden would be a significant advance for CF patients. We are very excited to be starting this Phase 3 program and look forward to working with patients and clinical investigators to extend the results we observed in our Phase 2b trial."

Results from the Aeroquin Phase 3 program are expected in mid-2012.

About Cystic Fibrosis

Patients with CF suffer from chronic infections of the lower respiratory tract that can be caused by multiple bacteria, includingPseudomonas aeruginosa. Chronic pulmonary infection is associated with a decrease in lung function over time caused by inflammation arising from bacteria and their toxins. Periodic exacerbations in the lung result from bacterial overgrowth (requiring antibacterial intervention), and these exacerbations are implicated as a major cause of morbidity and mortality in CF patients.

About Aeroquin (MP-376)

Aeroquin is a proprietary formulation of levofloxacin that has been optimized for aerosol delivery using an optimized Investigational eFlow Nebulizer System (PARI Pharma GmbH). Levofloxacin is a fluoroquinolone antibiotic that has been widely used in a variety of indications for over a decade and has established safety and efficacy when administered orally or intravenously against many bacterial pathogens, including Pseudomonas aeruginosa. Administration of Aeroquin with a high efficiency nebulizer to the lungs allows for the delivery of high concentrations of active drug directly to the site of infection in approximately 5 minutes, while minimizing systemic exposure.

About Mpex Pharmaceuticals

Mpex Pharmaceuticals is a clinical stage biopharmaceutical company whose mission is to develop important new therapies to combat the growing issue of antibiotic resistance. Mpex's most advanced product candidate, Aeroquin™ (MP-376), is a proprietary aerosol formulation of levofloxacin that is being developed clinically as a therapy for patients with cystic fibrosis. The Company has a number of additional antibiotic programs designed to address antibiotic resistance in gram negative organisms, including a collaboration with GlaxoSmithKline focused on developing multiple drug candidates utilizing Mpex's efflux pump inhibitor (EPI) technology. Company website: www.mpexpharma.com.

About the Investigational eFlow Nebulizer System and PARI Pharma

Aeroquin (MP-376) is delivered via an Investigational eFlow Nebulizer System, an inhalation delivery device optimized specifically for Aeroquin. The Investigational eFlow Nebulizer System uses eFlow® Technology to enable highly efficient aerosolization of medication via a vibrating, perforated membrane that includes thousands of small holes to produce the aerosol mist. Compared to other nebulization technologies, eFlow Technology produces aerosols with a very high density of active drug, a precisely defined droplet size, and a high proportion of respirable droplets delivered in the shortest possible period of time. Combined with its quiet mode of operation, small size (it fits in the palm of the patient's hand), light weight and battery use, eFlow Technology reduces the burden of taking daily, inhaled treatments. PARI Pharma focuses on the development of aerosol delivery devices and comprehensive inhalation drug development to advance aerosol therapies where drug and device can be optimized together.

SOURCE Mpex Pharmaceuticals, Inc.

Denufosol TIGER II - Fail

2011-01-03T10:31:00.000-05:00

RALEIGH, N.C. (AP) — Inspire Pharmaceuticals Inc. said Monday that its potential cystic fibrosis drug failed to meet key treatment goals in a late-stage study. Its shares tumbled more than 54 percent in pre-market trading.

The company is studying denufosol tetrasodium as a treatment for the genetic condition, which results in thick mucus buildup in the lungs. The results from the latest Tiger-2 test mark a reversal from the prior successful Tiger-1 study of the drug candidate.

"These Tiger-2 results were disappointing and unexpected given the treatment effect observed in the Tiger-1 trial," President and CEO Adrian Adams said in a statement. "We will conduct a thorough analysis of the data to fully understand the results from this trial and the impact on any future development of denufosol and on the company going forward."

The latest study involved 466 patients taking either denufosol or placebo.

Adams said the company will continue to focus on its drug candidates aimed at treating glaucoma.
Shares of Inspire fell $4.58, or 54.5 percent, to $3.82 in pre-market trading on Monday. The stock closed at $8.40 on Friday.

http://www.bloomberg.com/news/2011-01-03/inspire-cystic-fibrosis-drug-fails-in-study.html

EXTENDED BENEFIT WITH BRONCHITOL IN SECOND PHASE III CYSTIC FIBROSIS TRIAL

2010-12-18T21:16:00.000-05:00

16 December 2010

EXTENDED BENEFIT WITH BRONCHITOL IN SECOND PHASE III CYSTIC FIBROSIS TRIAL

Pharmaceutical company Pharmaxis (ASX:PXS) today announced positive first results for the open label component of its second international Phase III trial of Bronchitol in people with cystic fibrosis. In this part of the trial, all participants were treated with Bronchitol, including those that were in the control arm for the first six months. The key findings were:

Lung function change (FEV1) for those participants treated with Bronchitol for 6 months was 8.2% (p=0.001 versus baseline) and this was maintained out to 12 months (FEV1 improvement of 8.2%). The withdrawal rate in the open label phase was 7%.

Subjects who were switched from control to Bronchitol at the end of the first 6 months had a 6.3% improvement in lung function relative to baseline at the end of 12 months (p=0.031).

Dr Alan Robertson, Pharmaxis Chief Executive Officer said: "We are very pleased with this result which confirms the robust clinical response and good safety profile we have demonstrated with Bronchitol over a number of clinical trials. Cystic fibrosis is a disease that leads to slow decline in lung performance over time and, in this trial, Bronchitol was again able to improve lung function at commencement of treatment, at week 26, and maintain that improvement over 52 weeks for patients who were already receiving best standard of care. The repeated demonstration of sustained benefit in this second trial with Bronchitol holds out the promise that long term use of Bronchitol can change the course of the disease."

The trial objective was to determine the safety of Bronchitol in patients with cystic fibrosis following twelve months treatment and to assess the long term effects on lung function. This clinical trial of Bronchitol was conducted in two phases. The first six months was controlled and blinded and designed to assess efficacy and safety. The second six months was open label, unblinded and not controlled. Patients initially randomized to the control group were switched to receive Bronchitol during the subsequent six month open phase.

A total of 260 subjects (Bronchitol=153, placebo=107) participated in the open label phase and of these, 242 subjects (93%) completed this six month phase. For the subjects that entered the open label phase, the average age was 19.6 years and the mean lung function on entry was 64.6% of the predicted normal FEV1. The ages ranged from 6 years to 53 years and the lung function ranges were from 34% to 96% of the predicted FEV1.

In all subjects in the open label phase, the most commonly reported adverse events were haemoptysis (5.7%), headache (4.2%) and cough (8.8%). Haemoptysis and cough are common clinical features of cystic fibrosis.

The trial was conducted in 53 centres in the United States, Argentina, Canada, Belgium, France and Germany. Additional data from the trial including other lung function parameters and effects on exacerbation will be presented at a forthcoming scientific meeting.

Bronchitol is designed to hydrate the airway surface of the lungs, and promote normal lung mucus clearance. It has received Orphan Drug Designation and fast track status from the U.S. Food and Drug Administration and Orphan Drug Designation from the European Medicines Agency. A marketing application is under review by the European Medicines Agency and it has been recommended for marketing approval by the Advisory Committee on Prescription Medicines in Australia.

SOURCE: Pharmaxis Ltd, Sydney, Australia

CONTACT: Alan Robertson - Chief Executive Officer

Ph: +61 2 9454 7200 or email alan.robertson@pharmaxis.com.au

RELEASED THROUGH:

Australia:

Felicity Moffatt, phone +61 418 677 701 or email felicity.moffatt@pharmaxis.com.au

About Pharmaxis

Pharmaxis (ACN 082 811 630) is a specialist pharmaceutical company involved in the research, development and commercialization of therapeutic products for chronic respiratory disorders. Its development pipeline of products includes Aridol for the assessment of asthma, Bronchitol for cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease (COPD), PXS25 for the treatment of lung fibrosis and ASM8 and PXS4159 for asthma. Pharmaxis is listed on the Australian Securities Exchange (symbol PXS). The company is headquartered in Sydney at its TGA-approved manufacturing facilities. For more information about Pharmaxis, go to www.pharmaxis.com.au or contact Investor Relations on phone +61 2 9454 7200.

About Bronchitol

Pharmaxis Ltd is developing Bronchitol for the management of chronic obstructive lung diseases including cystic fibrosis, and bronchiectasis. Bronchitol is a proprietary dry-powder mannitol, precision formulated for delivery to the lungs through an easy-to-use, pocket-size, portable inhaler. Once inhaled its five-way action on mucus helps restore normal lung clearance mechanisms. Bronchitol has received Orphan Drug Designation and fast track status from the US Food and Drug Administration and Orphan Drug Designation from the European Medicines Agency.

Denufosol Offers Hope for Early Intervention in Cystic Fibrosis Patients

2010-12-18T21:13:00.000-05:00

Novel Drug Offers Hope for Early Intervention in Cystic Fibrosis Patients

ScienceDaily (Dec. 17, 2010) — Cystic fibrosis (CF) patients with normal to mildly impaired lung function may benefit from a new investigational drug designed to help prevent formation of the sticky mucus that is a hallmark of the disease, according to researchers involved in a phase 3 clinical trial of the drug. Called denufosol, the investigational medication can be given early in the CF disease process, and may help delay the progression of lung disease in these patients, the researchers found.

The findings were published online ahead of the print edition of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

"Although the lungs of children with CF are thought to be normal at birth, studies have demonstrated significant lung damage that occurs early in life in children suffering from cystic fibrosis," said lead investigator Frank Accurso, MD, professor of pediatrics, University of Colorado School of Medicine, Denver. "Many patients continue to suffer progressive loss of lung function despite treatment of complications. Because denufosol can be used early in life, it offers hope for delaying or preventing the progressive changes that lead to irreversible airflow obstruction in CF patients."

Denufosol belongs to a class of drugs known as ion channel regulators. These drugs help balance the flow of ions through cell membranes, helping normalize the airway surface hydration and mucus clearance impairment present in patients who suffer from the disease. In cystic fibrosis, the ion sodium chloride does not flow normally through cell membranes, resulting in thick, sticky mucus which is difficult to cough out of the airways. In addition to causing breathing problems, the mucus becomes a breeding ground for bacteria and can cause serious respiratory infections.

Denufosol works by increasing chloride secretion, inhibiting sodium absorption and increasing the beat frequency of the tiny hairs, or "cilia," lining the airways move to clear mucus. Combined, these effects enhance airway hydration and aid in clearing mucus. The drug is different from other CF medications, which primarily treat the symptoms rather than the underlying causes, said Dr. Accurso, who is also the director of University of Colorado's cystic fibrosis center.

This study is the first large, phase 3 trial of an ion channel regulator in cystic fibrosis patients with little or no baseline pulmonary function impairment.

"Abnormal ion transport and defective mucociliary clearance are fundamental defects that contribute to complications of CF lung disease, including mucus plugging, chronic bacterial infection, inflammation and progressive airway damage," Dr. Accurso noted. "Although currently available drugs target these complications, denufosol was designed to treat the underlying defects that cause the complications, and could potentially modify the course of the disease, particularly when administered early in the disease process."

Researchers enrolled 352 cystic fibrosis patients 5 years of age or older, and enrolled them to receive either inhaled denufosol or placebo three times daily for 24 weeks, followed by a 24-week open-label period when all patients received denufosol. At baseline, most patients enrolled had mild impairment of lung function and were taking multiple medications to control their symptoms. Because the study outcomes were measured using spirometry, a lung function test that can be difficult to accurately use in young children, patients under five years of age were excluded.

Patients' exhalation rates and lung volume were measured throughout the study, and also were monitored for adverse events, such as cough, congestion, fever or sinusitis. At the end of the 24-week period, researchers determined patients who received denufosol had better lung exhalation rates than those in the placebo group, whose exhalation volumes remained relatively unchanged from the start of the study. Both groups had similar numbers and types of adverse events, with the denufosol patients experiencing significantly fewer headaches and lower rates of sinusitis and runny nose.

Although children under five years of age were excluded from this study, Dr. Accurso said future studies likely would address the use of denufosol in this younger population.

"Considering the evidence that early inflammation and infection results in impaired lung function and structural damage in early childhood, future studies of the effects of denufosol during the first 5 years of life is warranted," he said.

A second, similar phase 3 trial incorporating a longer placebo-controlled treatment phase is ongoing to further investigate the effectiveness of denufosol in patients with CF, Dr. Accurso added.

http://www.sciencedaily.com/releases/2010/12/101217145643.htm

Estrogen aggravates inflammation in PA pneumonia in CF mice

2010-12-03T22:11:00.001-05:00

Estrogen aggravates inflammation in PA pneumonia in CF mice

Among patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with Pseudomonas aeruginosa (P. aeruginosa).

A role for gender hormones in the causation of the CF "gender gap"has been proposed. The female gender hormone 17beta-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others.

Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules.

Recent evidence suggests a central role for the IL-23/ IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with P.aeruginosa by a Th17-mediated mechanism.

Results: Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the P. aeruginosa strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils).

Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid.

The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against P. aeruginosa in vitro.

Conclusions: Our data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences.

Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with P. aeruginosa in the CF lung.

Author: Yufa WangElvis CelaStephane GagnonNeil Sweezey

Credits/Source: Respiratory Research 2010, 11:166

Please Vote!

2010-11-28T09:44:00.000-05:00

The Cystic Fibrosis Foundation is eligable to win $250,000 from the Pepsi Refresh Challenge.

But we need your vote!

Top 2 charities will win $250,000 - so please vote DAILY here: http://pep.si/c8syLT

Pass on to your friends as well please.

Improving Clinical Trials Act passes!

2010-09-25T09:47:00.000-04:00

I know many of you wrote to your Congress people over the past year and I want to THANK YOU for your efforts.

WE HAVE BEEN SUCCESSFUL! This new bill will translate into more CFers participating in clinical trials for life-changing drugs for CF.

-----------------------------------------------------------

"Improving Clinical Trials Act" Passes House and Senate, Heads to President for Signature

Sept 23, 2010

Today the U.S. House of Representatives passed the “Improving Access to Clinical Trials Act” (I-ACT), in a victory for the Cystic Fibrosis Foundation, its advocates and 120 other health advocacy organizations.

The bill, which passed the Senate Aug. 5, now goes to President Obama’s desk for his signature. He is expected to sign it.

This legislation enables patients with rare diseases to participate in clinical trials without losing eligibility for public healthcare benefits. Passage of this legislation is particularly important for people with CF, a rare genetic disease.

A limited patient population makes it challenging to find enough people to participate in research studies evaluating the effectiveness of promising new drugs.

“Because of this groundbreaking legislation, people with CF and other rare diseases will no longer be forced to choose between critical health care coverage and participation in research that could lead to the development of a cure for our most serious illnesses,” said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation.

“We are grateful to our champions in Congress for approving this bill, which will help move new treatments more swiftly from the lab to the patients who need them most.”

Cystic Fibrosis Caucus Co-Chairs, Reps. Edward Markey, D-Mass., and Cliff Stearns, R-Fla., led the effort to pass the bill in the House. The House version of this legislation, HR 2866, has 141 co-sponsors.

"No one should have to choose between participating in a clinical trial and accessing the essential benefits they need. Today's bill will open doors of hope and offer the possibility of better health to those with rare diseases like cystic fibrosis. I am proud to partner with my friend and co-chairman of the Congressional Cystic Fibrosis Caucus, Congressman Cliff Stearns, in the passage of this bi-partisan bill, which now will be signed into law by President Obama. I also want to commend the Cystic Fibrosis Foundation for its incredible work on this vital issue. Today represents an important and hopeful milestone in the battle to beat devastating rare diseases that afflict millions of Americans around the country," Markey said.

Added Stearns: "As co-chair and co-founder of the Congressional Cystic Fibrosis Caucus, I commend my colleagues for approving this legislation allowing people with rare diseases such as cystic fibrosis to participate in life-saving clinical trials that provide nominal compensation without the risk of losing their health care coverage. I also deeply appreciate the work of the Cystic Fibrosis Foundation in supporting my legislation."

The Senate version of the legislation, S. 1674, was introduced by Sen. Ron Wyden, D-Ore., with Sens. Chris Dodd, D-Conn., James Inhofe, R-Okla., Richard Shelby, R-Ala., and Dick Durbin, D-Ill., as original co-sponsors. An additional 17 co-sponsors signed on.

Current law prevents many people who receive Supplemental Security Income (SSI) from accepting research compensation because it makes them ineligible to receive government medical benefits. This penalty has stopped significant numbers of people with rare diseases from participating in clinical studies.

EU approval rec for TIP

2010-09-25T09:17:00.000-04:00

Novartis International AG: Novartis receives EU approval recommendation for TOBI® Podhaler®, a fast and simple therapy that helps reduce treatment burden for cystic fibrosis patients

Fri Sep 24, 2010 9:17am EDT

Novartis International AG / Novartis receives EU approval recommendation for TOBI

Podhaler, a fast and simple therapy that helps reduce treatment burden for cystic fibrosis patients processed and transmitted by Hugin AS. The issuer is solely responsible for the content of this announcement.

CHMP supports approval of TOBI Podhaler, a new dry powder form of tobramycin for treating chronic P. aeruginosa lung infection in cystic fibrosis patients over six

Data show new formulation reduces administration time by 72% compared to TOBI, with same

efficacy[1] and using more convenient, patient-friendly device

*

Cystic fibrosis is a life-threatening genetic disease primarily affecting children and young adults - complex daily treatment reduces their ability to lead normal lives

Basel, September 24, 2010 - TOBI® Podhaler® (tobramycin inhalation powder), a fast and

convenient inhaled therapy[1] for use by patients with cystic fibrosis (CF), has been

recommended for approval in the European Union. The Committee for Medicinal Products for

Human Use (CHMP), which reviews medicines for the European Commission, issued a positive

opinion for TOBI Podhaler as a suppressive therapy for chronic Pseudomonas aeruginosa

(Pa) infections in CF patients aged six years and older.

"TOBI Podhaler combines a number of innovations that significantly improve the delivery

of tobramycin, which is an established effective treatment for Pa lung infection in

patients with cystic fibrosis," said Professor Stuart Elborn, Professor of Respiratory

Medicine at Queens' University, Belfast, and President of the European Cystic Fibrosis

Society. "This therapy should help patients to lead more independent lives - an

important factor considering the relatively young age of many people with this disease."

The CHMP based its positive opinion on data showing that TOBI Podhaler provides the same

efficacy[2] as TOBI® (tobramycin solution) with a comparable safety profile[2]. TOBI is

the most widely used inhaled antibiotic for chronic Pa infections in CF[3]. 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 TOBI which is administered with a nebulizer.

Data show that patients using TOBI Podhaler completed their tobramycin treatment in five

to six minutes instead of 20 minutes with TOBI, a reduction of 72%[1]. Nebulized

treatments require additional time for assembly and disinfection, unlike TOBI Podhaler,

which also does away with the need for refrigeration of the active compound 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[1].

Due to the complexity of existing anti-Pa treatment, most patients do not fully adhere

to their therapy[4],[5],[6]. In addition, many patients do not clean their nebulizers

properly and these are often contaminated[7],[8],[9],[10]. With TOBI Podhaler, the

inhaler device is disposable and the dry formulation potentially reduces the risk of

bacterial contamination.

"TOBI Podhaler shows how we are applying innovative technologies to better meet the

needs of patients and their families," said David Epstein, Division Head of Novartis

Pharmaceuticals. "TOBI Podhaler also underscores our long-term commitment to improving

the quality of care for patients with diseases such as cystic fibrosis and helping them

to lead longer and more active lives."

Cystic fibrosis (CF) is a life-threatening genetic disease that affects the internal

organs, especially the lungs and digestive system, by clogging them with thick mucus

making it hard to breathe and digest food. A total of 70,000 patients have been

diagnosed with CF worldwide[11]. Symptoms usually develop within the first year of life

and only half of CF patients live to over 35 years of age[12]. In 90% of cases, death is

due to a progressive decline in lung function often made worse by chronic Pseudomonas

aeruginosa infection[13].

The first launch of TOBI came in 1997 and it is now approved in 46 countries including

the US and EU for the treatment of Pseudomonas aeruginosa in CF patients aged six years

old and above.

TOBI Podhaler was submitted for EU approval in December 2009 and is not yet approved in

any country. The European Commission generally follows the recommendations of the CHMP

and is expected to make a decision within three months.

$25 for a quick survey

2010-09-22T22:42:00.000-04:00

If you're a CF adult, you may qualify for $25 to participate in a quick online survey.

Please mention you heard about this from the NoExcuses blog.

please contact us at CF_Panel@WWMR.com call 888-947-2339, choosing option 3 at the main menu

Effects of exercise on respiratory flow and sputum properties in cystic fibrosis.

2010-09-12T22:33:00.000-04:00

Chest. 2010 Sep 9.

Effects of exercise on respiratory flow and sputum properties in cystic fibrosis.

Dwyer TJ, Alison JA, McKeough ZJ, Daviskas E, Bye PT.
1Discipline of Physiotherapy, Faculty of Health Sciences, University of Sydney, Sydney, Australia.

BACKGROUND: The physiological mechanisms by which exercise may clear secretions in subjects with cystic fibrosis (CF) are unknown. The purpose of this study was to compare ventilation, respiratory flow and sputum properties following treadmill and cycle exercise to resting breathing (control).

METHODS: In 14 adult subjects with CF, ventilation and respiratory flow were measured during 20 minutes of resting breathing, treadmill and cycle exercise in a three-day, cross-over study. Treadmill and cycle exercise were performed at the workrate equivalent to 60% of the subject's peak VO(2). Ease of expectoration and sputum properties (solids content and mechanical impedance) were measured before and immediately after the interventions and after 20 minutes recovery.
RESULTS: Ease of expectoration improved following exercise. Ventilation and respiratory flow were significantly higher during treadmill and cycle exercise, compared to control. Sputum solids content did not change following treadmill or cycle exercise. There was a significantly greater decrease in sputum mechanical impedance following treadmill exercise compared to control, but no significant decrease in sputum mechanical impedance following cycle exercise compared to control.
CONCLUSIONS: The improvement in ease of expectoration following exercise may have been due to the higher ventilation and respiratory flow. The reductions in sputum mechanical impedance with treadmill exercise may have been due to the trunk oscillations associated with walking.

Mutational spectrum of cystic fibrosis in the Lebanese population

2010-09-03T23:19:00.002-04:00

J Cyst Fibros. 2010 Aug 25. [Epub ahead of print]

Mutational spectrum of cystic fibrosis in the Lebanese population.

Farra C, Menassa R, Awwad J, Morel Y, Salameh P, Yazbeck N, Majdalani M, Wakim R, Yunis K, Mroueh S, Cabet F.

Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Department of Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Genetics Laboratory, Chronic Care Center, Hazmieh, Lebanon.

Abstract

BACKGROUND: Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians; it is however, considered to be rare in the Arab populations. Reports of the cystic fibrosis transmembrane regulator (CFTR) mutations from Arabs, especially from the Lebanese population, are limited.

METHODS: Twenty-two unrelated Lebanese families, with at least one child with CF, were studied. DNA extracts from blood samples of patients and parents were screened for CFTR gene mutations.
RESULTS: Eleven different mutations were identified. Of the 44 alleles studied, the most common mutations were: F508del (34%), N1303K (27%), W1282X (7%), and S4X (7%). Five mutations - not previously reported in the Lebanese population - were identified; these are: S549N, G542X, 2043delG, 4016insG, and R117H-7T.

CONCLUSIONS: The most common CFTR mutations in addition to five mutations not previously described in the Lebanese population were identified. Identification of CFTR mutations in the Lebanese population is important for molecular investigations and genetic counseling.

NIH Awards $1.2 Million To Study Protein Misfolding Diseases

2010-09-03T23:16:00.000-04:00

NIH Awards $1.2 Million To Study Protein Misfolding Diseases

Three University of Massachusetts Amherst scientists have received a four-year, $1.2 million EUREKA grant from the U.S. National Institutes of Health (NIH) to study folding and misfolding of secretory proteins in the cell's protein factory, the endoplasmic reticulum, where misfolding can lead to diseases such as cystic fibrosis and liver cirrhosis.

EUREKA stands for Exceptional, Unconventional Research Enabling Knowledge Acceleration. The program was created by NIH's National Institute for General Medical Sciences to support scientists who are testing new ideas in unusual ways or tackling major methodological or technical challenges. Janna Wehrle, who manages this and other protein folding grants at NIH, says, "This project represents an exceptionally bold effort to determine how proteins fold not in a test tube but in real cells. By examining how proteins take shape in the crowded and dynamic environment where it actually occurs, this work may lead to a better understanding of how the folding process goes awry in diseases like cystic fibrosis and some forms of liver cirrhosis."

Anne Gershenson and her biochemistry and molecular biology colleagues Daniel Hebert and Lila Gierasch begin pilot studies this month using new techniques they adapted to observe how individual secretory proteins fold, not only in real cells but in real time. For this work, they will also use a powerful new super-resolution fluorescence microscope built by UMass Amherst physicist Jennifer Ross and her students. It provides a clear view of individual molecules with far more precision than was possible using traditional light microscopy.

Members of this UMass Amherst research group have been pioneers in studying proteins in situ, or in place, rather than in test tubes. Up to now, much valuable protein-folding research has used whole purified proteins that are forced by heating or other treatment to unfold in a test tube. Scientists then study their refolding into the three-dimensional shapes necessary to carry out the cell's tasks. But as Gershenson and Gierasch pointed out in an influential 2009 article in Nature Chemical Biology, "we have arrived at the post-reductionist era of biochemistry" when it is no longer enough to study isolated parts of complex networks. Rather, they say scientists must now examine proteins in their native, complicated and highly concentrated environments to truly understand the way they work.

The cell's endoplasmic reticulum is a protein-folding factory, churning out hundreds of secretory proteins to be exported from cells, as well as membrane proteins that reside on the cell surface, Gershenson explains. This factory comes complete with a large number of proteins responsible for quality control. They assist in folding and determine whether and when a protein should be exported to take up its required position. How proteins fold as they are synthesized and how quality control mechanisms affect protein folding are the focus of Gershenson and colleagues' investigation.

The UMass Amherst researchers use a technique called fluorescence resonance energy transfer, or FRET, for light-marking proteins and monitoring their folding. In it, two differently-colored fluorescent dyes that are sensitive to each other, a donor and an acceptor, are introduced into the protein chain as it is made. When these are farther apart in a not-yet-folded protein, the donor emits greener fluorescence. As the protein folds and the two dyes get closer together on the three-dimensional structure, their proximity results in emission of a redder fluorescence. Spectroscopically analyzing the fluorescence allows investigators to precisely track donor-to-acceptor distance changes.

Further, by introducing the FRET donor and acceptor molecules at slightly different parts of the protein chains in each of hundreds of experiments, Gershenson and colleagues will be able to map protein changes associated with folding in situ, in real time.

"Once we get the system operating with good fluorescence and we become adept at incorporating the FRET dyes, our method should prove useful to other researchers for studying a wide variety of other proteins which are involved in many other disease processes," she says. "That's the big promise of this approach, and the challenge."

Over the three years of the program, NIH has awarded 56 grants totaling $67.4 million to support these highly innovative research projects which promise big scientific payoffs. Awards announced today total $25.2 million to 21 institutions.

Source: University of Massachusetts Amherst

Viagra Trial in Children and Young Adults With CF

2010-09-03T23:04:00.000-04:00

Sildenafil Trial in Children and Young Adults With CF

This study is not yet open for participant recruitment.

Verified by Children's Hospital Medical Center, Cincinnati, September 2010

First Received: September 1, 2010 No Changes Posted

Sponsor:	Children's Hospital Medical Center, Cincinnati
Information provided by:	Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:	NCT01194232

Purpose

Cystic Fibrosis (CF), the most common inherited disease in Caucasians, is characterized by chronic pulmonary inflammation and progressive loss of gas exchange units that eventually results in respiratory failure. There is strong evidence that, in CF, abnormally low perfusion carries a high risk of death independent from the presence of pulmonary hypertension. However, the evolution of pulmonary vascular disease in CF and how it might contribute to the rate of decline in lung function is not known. Our knowledge remains limited to the results of old observational studies which concluded that the major causes of pulmonary vascular remodeling and hypertension in CF are hypoxic respiratory failure and destruction of lung tissue. Our recent data obtained by state-of-the-art Magnetic Resonance Imaging (MRI) of the pulmonary circulation, challenges the existing paradigm. We demonstrate that in the absence of hypoxia, significant changes in pulmonary perfusion and in surrogate measures of vascular resistance as well as in collateral blood flow begin early in the course of CF. Newly developed therapeutics have altered dramatically the course of patients suffering from pulmonary vascular disease. Through this 8 week trial, we will examine by Magnetic Resonance Imaging the effect of Sildenafil on pulmonary perfusion and systemic vascularization of the lungs in subjects with mild to moderate disease.

Condition	Intervention	Phase
Cystic Fibrosis With Mild to Moderate Lung Disease CMRI of Lung Perfusion Lung Perfusion Lung Vascularization	Drug: Sildenafil	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Control: Uncontrolled Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Controlled Study of Sildenafil in Children and Young Adults With Mild to Moderate Cystic Fibrosis Lung Disease

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Sildenafil Sildenafil citrate

U.S. FDA Resources

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:

Increase pulmonary perfusion [ Time Frame: 8 week visit ] [ Designated as safety issue: No ]
• Increase of pulmonary perfusion by a minimum of 15% as measured by gadolinium contrast MRI with segmental perfusion and scored on a continuous scale;

Secondary Outcome Measures:

Improved lung function [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Improved exercise performance as measured by the following variables:
- Ventilatory equivalent of O2 and CO2 (VEO2 and VECO2)
- Maximum oxygen consumption (VO2 max)

Estimated Enrollment:	36
Study Start Date:	October 2010
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Sildenafil: Experimental 24 subjects will receeive 8 week course of Sildenafil administered at a dose of 1 mg / Kg three times a day with a maximum dose of 20 mg per dose.	Drug: Sildenafil 8 week course of Sildenafil administered at a dose of 1 mg / Kg three times a day with a maximum dose of 20 mg per dose.

Eligibility

Ages Eligible for Study:	8 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Age 8 years to age 21 years
Diagnosis of cystic fibrosis confirmed by a prior sweat chloride evaluation of > 60 mmol/liter or by two identified CFTR mutations on genetic analysis
Able to perform acceptable and repeatable spirometry per American Thoracic Society/European Respiratory Society (ATS/ERS) joint consensus criteria.
Have valid spirometry data for at least 3 years
Must have mild to moderate lung disease (Mild lung disease will be defined as an FEV1%p of 80-99% predicted. Moderate lung disease will be defined as an FEV1%p of 60-79% predicted.)
If under the age of 18, the subject must assent to participation in the study, and the subject's parent or guardian must be able to give written informed consent and comply with the requirements of the study protocol
If 18 years of age or older, the subject must be able to give written parental permission and comply with the requirements of the study protocol
For female subjects: negative serum pregnancy test and must be willing to use contraception during study participation
Able to tolerate MRI without sedation
Subjects who are on alternating monthly on/off cycles of inhaled antibiotics must be willing to be off of inhaled antibiotic therapy for one "on" cycle.
Must be currently enrolled in CCHMC IRB#: 2008-0926 5.2 Exclusion Criteria

Research subjects will be excluded from the study based on:

History of CF-related liver disease with portal hypertension
Currently smoking cigarettes or other tobacco products
Use of daytime oxygen supplementation
Previous organ transplantation
Unstable or uncontrolled hypertension
Ongoing use of oral corticosteroids
For female subjects: pregnancy or lactation and unwillingness to use contraception during study participation
Any hemodynamically significant congenital or acquired cardiac disease or significant cardiomyopathy, hematologic disease (i.e. hemoglobinopathies), or pulmonary disease associated with an increased risk of pulmonary perfusion defects or pulmonary hypertension other than as an outcome of CF
History of renal and/or hepatic insufficiency, defined as cystatin-C level that exceeds normal range and a previous diagnosis of liver cirrhosis.
History of uncontrolled asthma defined as oral steroid dependent
History of hypersensitivity to gadolinium (Magnevist)
Contraindications specific to MRI including a history of claustrophobia, cardiac pacemaker, or other non-MRI compatible surgical implants (This includes neuro-stimulators containing electrical circuitry, or which generate electrical signals and/or have moving metal parts, and metal orthopedic pins or plates. The research coordinator and/or the MRI technologist will screen all subjects using the standard checklist of medical history and safety questions used by the Radiology Department in routine clinical scans.)
Daily use of montelukast and ibuprofen
Use of nitrate medicines or other drugs known to have unsafe interactions with Sildenafil
Known allergy to Sildenafil
Inability to comply with study procedures

Laboratory Exclusion Criteria for research subjects (based on history or bloodwork before first MRI):

Positive sputum, epiglottic, or brochoalveolar lavage culture for Mycobacterium abscessus during the 2 years prior to enrollment
A positive serum pregnancy test
Serum creatinine > two times the upper limit of normal for age
A serum Cystatin C outside of normal range for age

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194232

Contacts

Contact: Lorrie Duan, RN	513-636-7089	lorrie.duan@cchmc.org
Contact: Margo Moore, RN	60394	margo.moore@cchmc.org

Locations

United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229

Please vote for CF Pepsi Refresh Project

2010-09-02T10:33:00.002-04:00

We are currently #2!

Let's vote once per day to help win $250,000 to fight CF.

Please share with friends and family.

Pharmaxis in deal to support launch of cystic fibrosis drug

2010-08-31T23:10:00.000-04:00

Pharmaxis in deal to support launch of cystic fibrosis drug

Eli Greenblat

August 31, 2010 - 4:07PM

Biotech company Pharmaxis says it has finalised a strategic marketing and sales service agreement for the commercialisation of its cystic fibrosis drug, Bronchitol, for use in Europe.

The company said this morning that ahead of anticipated regulatory approval for Bronchitol, it had signed a six-year agreement with the highly respected Quintiles organisation to support the launch and commercialisation of the product in Western Europe.

Pharmaxis acting chief executive Gary Phillips said: “This important development means that Pharmaxis will move into the key European markets with a clear commercialisation plan. We will be bringing on board the European expertise and capabilities of a well recognised team of leaders in the field.

“Bronchitol is a new advance in the treatment of cystic fibrosis and it’s vital that we engage fully with the CF communities, healthcare professionals, funding bodies and governments across Europe as efficiently as possible.’’

Quintiles is a global biopharmaceutical services company offering clinical, commercial, consulting and capital solutions. The Quintiles network employs 20,000 people across 60 countries.

Two completed Phase 3 clinical trials of Bronchitol have demonstrated early and sustained improvement in lung function in people with cystic fibrosis. The product has been granted orphan drug designation by the European Medicines Agency, which helps accelerates its development and path to commercialisation.

Pharmaxis plans to launch Bronchitol across Western Europe, initially in Germany and the UK in the first quarter of 2011.

The Pharmaxis contract sales representatives will be supported and managed by the Quintiles organisation throughout Western Europe while marketing and market support will be managed by the Pharmaxis office in the UK.

egreenblat@theage.com.au

http://www.theage.com.au/business/pharmaxis-in-deal-to-support-launch-of-cystic-fibrosis-drug-20100831-14f6j.html

Luminex Announces Commercial Launch of New Cystic Fibrosis Test

2010-08-28T08:01:00.000-04:00

Luminex Announces Commercial Launch of New Cystic Fibrosis Test

Download image AUSTIN, Texas, Aug. 26 /PRNewswire-FirstCall/ -- Luminex Corporation (Nasdaq: LMNX), the worldwide leader in multiplexed solutions, today announced the full commercial launch of its xTAG® Cystic Fibrosis 60 Kit v2, a new diagnostic test that can simultaneously screen a single blood sample for up to 60 cystic fibrosis-causing genetic mutations in a matter of hours.

The test is the most comprehensive and flexible FDA-cleared cystic fibrosis (CF) test available, featuring an unsurpassed level of gene mutation coverage. It will be used to screen potential parents to determine if they are carriers of CF-causing gene mutations, and as an aid in newborn screening and in confirmatory diagnostic testing in newborns and children. The test recently received 510(k) clearance from the U.S. Food and Drug Administration (FDA).
"The launch of our new xTAG Cystic Fibrosis 60 Kit v2 is a great achievement in cystic fibrosis testing," said Patrick J. Balthrop, president and chief executive officer of Luminex. "This cleared test has the most comprehensive genetic mutation coverage available today, featuring mutations found among Caucasians as well as those that are more commonly found in other ethnic populations. It will give doctors the ability to screen children and potential parents of many ethnicities for CF."

Cystic fibrosis is a common genetic disorder that causes the body to produce thick mucus that can clog the lungs and affect the digestive system. Approximately 30,000 Americans have cystic fibrosis. Although CF is most common in those of Caucasian descent, it can affect people of any race or ethnicity.
CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. To date, more than 1,500 of these mutations have been discovered(i). CF can only be passed onto a child when both parents carry a gene that causes the disease. According to the Cystic Fibrosis Foundation, more than 10 million Americans are symptomless carriers of CF-causing gene mutations.
Early diagnosis of CF is important and studies have demonstrated that early treatment and intervention can reduce a child's therapeutic needs, lower rates of medical complications, increase life expectancy and improve overall quality of life. Late diagnosis of cystic fibrosis can lead to health complications, chronic lung infections and compromised growth.
The xTAG Cystic Fibrosis 60 Kit v2 can detect up to 60 CFTR gene mutations from a single patient blood sample. These mutations include the 23 CFTR gene mutations and four variants (polymorphisms) recommended by the American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG), as well as 37 additional common North American mutations, including 20 mutations that are found within Hispanic and African-American populations.
The xTAG Cystic Fibrosis 60 Kit v2 is flexible. It gives physicians the ability to select the mutations for which they want to test, allowing them to choose to test a patient for the ACMG/ACOG-recommended gene mutations or the entire panel of 60 CFTR gene mutations.
The test also is easy to use and requires only about one hour of hands-on time to process 48 purified samples. Additionally, the xTAG Cystic Fibrosis 60 Kit v2 does not require reflex testing. All test results are revealed and available for analysis at each run.
The xTAG Cystic Fibrosis 60 Kit v2 is one of a suite of CF tests developed by Luminex. The xTAG Cystic Fibrosis 39 Kit v2, which can simultaneously screen a single blood sample for up to 39 cystic fibrosis-causing gene mutations, is available throughout the U.S., Europe and Canada. The test is also cleared by FDA and was launched as a CE marked IVD product under the European Directive on In Vitro Diagnostic Medical Devices in 2009. It received clearance from Health Canada in 2010.
The xTAG Cystic Fibrosis 71 Kit v2, which can simultaneously screen a single blood sample for up to 71 cystic fibrosis-causing gene mutations, is available in Europe and Canada. The test became a CE marked IVD product in 2009 and was cleared by Health Canada in 2010.
The xTAG Cystic Fibrosis 60 Kit v2 will be available throughout the United States through Luminex Molecular Diagnostics or Fisher HealthCare, part of Thermo Fisher Scientific, Inc. For more information, please visit http://www.luminexcorp.com/cf.

(i) Cystic Fibrosis Genetic Analysis Consortium. Cystic fibrosis mutation database. http://www.genet.sickkids.on.ca. Updated March 2, 2007.

Impact of cystic fibrosis on bone health

2010-08-28T07:58:00.000-04:00

Curr Opin Pulm Med. 2010 Aug 25.

Impact of cystic fibrosis on bone health.

Haworth CS.
Adult Cystic Fibrosis Centre, Papworth Hospital, Cambridge, UK.

Abstract

PURPOSE OF REVIEW: This review summarizes recently published data on the epidemiology, pathophysiology and treatment of cystic fibrosis (CF)-related low bone mineral density (BMD).

RECENT FINDINGS: A systematic literature review reports that the pooled prevalence of osteoporosis in adults with CF is 23.5% [95% confidence interval (CI) 16.6-31.0] and the pooled prevalences of radiologically confirmed vertebral and nonvertebral fractures are 14% (95% CI 7.8-21.7) and 19.7% (95% CI 6.0-38.8), respectively. Recent data suggest that the cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in bone cells and that CFTR dysfunction affects bone cell activity. The secondary effects of CFTR dysfunction also influence bone metabolism. For example, bone resorption increases during CF pulmonary exacerbations due to the stimulatory effects of proinflammatory cytokines on osteoclast activity. Bisphosphonates inhibit osteoclastic bone resorption and recent data show that both oral and intravenous bisphosphonates improve BMD in patients with CF.

SUMMARY: CF-related low BMD is a common but treatable complication of CF.

Prostaglandin-endoperoxide synthase genes COX1 and COX2 - novel modifiers of disease severity in cystic fibrosis patients

2010-08-21T09:34:00.000-04:00

J Appl Genet. 2010;51(3):323-30.

Prostaglandin-endoperoxide synthase genes COX1 and COX2 - novel modifiers of disease severity in cystic fibrosis patients.

Czerska K, Sobczynska-Tomaszewska A, Sands D, Nowakowska A, Bak D, Wertheim K, Poznanski J, Zielenski J, Norek A, Bal J.

Institute of Mother and Child, Department of Medical Genetics, Kasprzaka 17a, 01-211 Warsaw, Poland

Cystic fibrosis (CF) is one of the most common autosomal recessive diseases among Caucasians caused by a mutation in the CFTR gene. However, the clinical outcome of CF pulmonary disease varies remarkably even in patients with the same CFTR genotype. This has led to a search for genetic modifiers located outside the CFTR gene.

The aim of this study was to evaluate the effect of functional variants in prostaglandin-endoperoxide synthase genes (COX1 and COX2) on the severity of lung disease in CF patients. To the best of our knowledge, it is the first time when analysis of COX1 and COX2 as potential CF modifiers is provided. The study included 94 CF patients homozygous for F508del mutation of CFTR.

To compare their clinical condition, several parameters were recorded, e.g. a unique clinical score: disease severity status (DSS). To analyse the effect of non-CFTR genetic polymorphisms on the clinical course of CF patients, the whole coding region of COX1 and selected COX2 polymorphisms were analysed. Statistical analysis of genotype-phenotype associations revealed a relationship between the heterozygosity status of identified polymorphisms and better lung function.

These results mainly concern COX2 polymorphisms: -765G>C and 8473T>C. The COX1 and COX2 polymorphisms reducing COX protein levels had a positive effect on all analysed clinical parameters. This suggests an important role of these genes as protective modifiers of pulmonary disease in CF patients, due to inhibition of arachidonic acid conversion into prostaglandins, which probably reduces the inflammatory process.

vitamin D may treat or prevent allergy to common mold

2010-08-17T09:09:00.000-04:00

Contact: Leslie Capolcapo@lsuhsc.edu504-568-4806Louisiana State University Health Sciences Center

Research concludes vitamin D may treat or prevent allergy to common mold

New Orleans, LA – Research conducted by Dr. Jay Kolls, Professor and Chair of Genetics at LSU Health Sciences Center New Orleans, and colleagues, has found that vitamin D may be an effective therapeutic agent to treat or prevent allergy to a common mold that can complicate asthma and frequently affects patients with Cystic Fibrosis. The work is scheduled to be published online August 16, 2010, ahead of the print edition of the September 2010 issue of the Journal of Clinical Investigation.

The environmental mold, Aspergillus fumigatus, is one of the most prevalent fungal organisms inhaled by people. In the vast majority, it is not associated with disease. However, in asthmatics and in patients with Cystic Fibrosis (CF), it can cause significant allergic symptoms. Up to 15% of CF patients develop a severe allergic response called Allergic Bronchopulmonary Aspergillosis (ABPA). Since the mold is so common, the researchers wanted to identify the factors that determine why only a subset of patients develop the allergy and what factors regulate tolerance or sensitization to the mold resulting in the development of ABPA. To gain insights, the group studied two groups of patients with CF. Both groups were colonized with A. Fumigatus, but only one had ABPA.

The researchers focused on Th2 cells–the hormonal messengers of T-helper cells that produce an allergic response. They found that a protein called OX40L was critical in driving Th2 responses to A. fumigatus in the CD4+T cells isolated from patients with ABPA and that this group had a much greater Th2 responses to A. Fumigatus. The CD4+T cells from the group of patients that did not have ABPA had higher levels of the proteins, FoxP3 and TGF-ß, critical to the development of allergen tolerance. The researchers discovered that heightened Th2 reactivity in the ABPA group correlated with a lower average blood level of vitamin D.
"We found that adding vitamin D not only substantially reduced the production of the protein driving an allergic response, but it also increased production of the proteins that promote tolerance," notes Dr. Jay Kolls, Professor and Chair of Genetics at LSU Health Sciences Center New Orleans.

According to the National Institutes of Health, Cystic fibrosis (CF) is the most common, fatal genetic disease in the United States. About 30,000 people in the United States have the disease. CF causes the body to produce thick, sticky mucus that clogs the lungs, leads to infection, and blocks the pancreas, which stops digestive enzymes from reaching the intestine where they are required in order to digest food. It is estimated that about 70,000 people worldwide have the disease.

Recent research has suggested that low levels of vitamin D may contribute to heart disease, a higher risk of diabetes, certain cancers, and depression as well as asthma, colds, and other respiratory disorders.

"Our study provides further evidence that vitamin D appears to be broadly associated with human health," notes Dr. Jay Kolls, Professor and Chair of Genetics at LSU Health Sciences Center New Orleans. "The next step in our research is to conduct a clinical trial to see if vitamin D can be used to treat or prevent this complication of asthma and Cystic Fibrosis."

http://www.eurekalert.org/pub_releases/2010-08/lsuh-rcv080610.php

Estrogen and CF women

2010-08-11T10:36:00.001-04:00

Independent.ie

Contraceptive pill offers hope for cystic fibrosis sufferers
By Grainne Cunningham

Tuesday August 10 2010

DOCTORS are to consider treating female cystic fibrosis (CF) sufferers with the contraceptive pill in order to radically improve their health.

Newly published groundbreaking research found a clear link between an increase in levels of the female hormone oestrogen and the body's ability to fight the disease.

The Pill would allow levels of the hormone to be better regulated, thus giving the body a better chance to fight the disease.

Female sufferers of CF typically have much poorer survival rates than males with the potentially deadly condition.

Yesterday, the mother of a seven-year-old girl with CF welcomed the news as "optimistic" and said it offered reassurance to the families of sufferers that new methods of treatment would be available in the future.

Researchers at the Royal College of Surgeons in Ireland (RCSI) and Beaumont Hospital found a clear link between higher levels of oestrogen and the ability of the body to fight the disease.

Cystic fibrosis is an inherited disease that affects the lungs and the digestive system.

A build-up of mucus can make it difficult to clear bacteria and leads to cycles of lung infections, causing long-term damage and sometimes death.

The new study found that oestrogen hampers the creation of infection-fighting white blood cells in the lungs.

Ireland has the highest incidence of CF in the world, with almost four times the rate of other EU countries and the US.

During the menstrual cycle, higher levels of oestrogen increase women's risk of acquiring an infection and reduce the body's ability to fight bacteria, according to the study, which was published in the 'American Journal of Respiratory and Critical Care Medicine'.

The joint lead author, Dr Sanjay Chotirmall, said he hoped the findings would help narrow the gender gap in CF by "identifying new potential targets for treatment, such as stabilisation of oestrogen levels, or more aggressively employing preventative strategies against infection during the one week of the cycle when oestrogen levels are at their highest".

Insight

Dr Chotirmall, a specialist registrar in respiratory medicine, said the research was praised by the distinguished 'Faculty of 1000 Biology' guide for offering insight into the best way forward for treating CF.

The common Pill could prove to be a more valuable option than anti-inflammatory medicines, he suggested.

Deborah Kett, whose seven-year-old daughter Hannah has CF, said: "It's nice to get good news for a change."

She said the development would be particularly welcomed by families with girls in their teens, as they would have a new option to turn to immediately.

"When you hear something like this, it does give you hope, and that is particularly important for grandparents, siblings and others who may not be involved in the day-to-day care but are offering emotional support," Mrs Kett said.

Responding to the new research, the Cystic Fibrosis Association of Ireland welcomed the findings and commended the RCSI for its pioneering work.

"Cystic fibrosis continuous to be the most common life-threatening inherited disease in the country.

"Indeed, Ireland has the highest prevalence, and most severe types, of cystic fibrosis in the world, so we look forward to any possible future medical advances," she said.

Meanwhile, a new €1m outpatient unit for CF patients will open at Beaumont Hospital in the coming weeks.

The 580sq.m unit will consist of consultation and treatment rooms as well as a physiotherapy area and will be in addition to the six-bed in-patient centre already open at the hospital.

A spokesman for St Vincent's Hospital said discussions were still taking place with the contractor for the building of a 100-bed block which would include a CF unit comprising single-room beds.

- Grainne Cunningham

http://www.independent.ie/health/latest-news/contraceptive-pill-offers-hope-for-cystic-fibrosis-sufferers-2290598.html

Supplementation With Fatty Acids Influences the Airway Nitric Oxide and Inflammatory Markers in Patients With Cystic Fibrosis.

2010-07-20T23:38:00.001-04:00

J Pediatr Gastroenterol Nutr. 2010 May;50(5):537-544.

Supplementation With Fatty Acids Influences the Airway Nitric Oxide and Inflammatory Markers in Patients With Cystic Fibrosis.

Keen C, Olin AC, Eriksson S, Ekman A, Lindblad A, Basu S, Beermann C, Strandvik B.

*Departments of Pediatrics, Sweden daggerOccupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden double daggerDepartment of Public Health and Caring Sciences, Faculty of Medicine, Uppsala University, Uppsala, Sweden section signDanone Research, Centre for Specialized Nutrition, Friedrichsdorf, Germany.

Abstract

OBJECTIVES:: To obtain a balance in the fatty acid (FA) metabolism is important for the inflammatory response and of special importance in cystic fibrosis (CF), which is characterized by impaired FA metabolism, chronic inflammation, and infection in the airways. Nitric oxide (NO) has antimicrobial properties and low nasal (nNO) and exhaled NO (FENO), commonly reported in CF that may affect bacterial status. The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF.

PATIENTS AND METHODS:: Forty-three patients with CF and "severe" mutations were consecutively enrolled in a randomized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo. FENO, nNO, serum phospholipid concentrations of FA, and biomarkers of inflammation were measured before and after 3 months of supplementation.

RESULTS:: Thirty-five patients in clinically stable condition completed the study. The serum phospholipid FA pattern changed significantly in all 3 groups. An increase of the n-6 FA, arachidonic acid, was associated with a decrease of FENO and nNO. The inflammatory biomarkers, erythrocyte sedimentation rate, and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA.

CONCLUSIONS:: This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF. FENO and nNO were influenced by changes in the arachidonic acid concentration, supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways.

Tweeting my CF Routine for Raise CF Awareness

2010-07-15T09:30:00.001-04:00

Today, throughout the day, I am tweeting my Cystic Fibrosis routine to raise CF awareness.

If you don't already follow me on Twitter, I'm @CFResearch.

Yey for CF awareness!

Cayston Update WARNING: MUCUS PICTURES***

2010-07-13T09:31:00.006-04:00

*********WARNING: MUCUS PICTURES***************

After about 2 doses of Cayston, I coughed up this sucker (see below. that finger is my index finger, btw)

I am definitely a plug-cougher-upper, but rarely do I get suckers this big. The last one of this size was when I was on prednisone in February/March.

So, is it related to Cayston? I'm not sure. But that's the only thing that has changed.

Now that I've been on Cayston for 3 days, my mucus has definitely thinned, decreased in quantity and lightened in color. So we'll see how things continue to go :)

Picture of my appendix

2010-07-13T09:19:00.006-04:00

Hey guys,

It's been 5 weeks since I had my appendix removed and I forgot that I never posted a pic of my appendix from surgery.

They also took a pic of my ovary for good measure, so I'll include both on this blog post :)

To me, the appendix looks like a slug with an eye on it!

I still don't know which part is my ovary in this picture... but something looks like it's wrapped in cheese - maybe that's it?

Anyway, I was greatful to my surgeon who took these pics for me - I asked for the actual appendix but she said it had to go straight to pathology. Boooo!

Hope you all aer well :)

First dose of Cayston

2010-07-10T13:02:00.002-04:00

Well, I'm happy to report that I'm in the middle of my very first dose of Cayston.

Here is what I see as the good, the bad, and the ugly:

The Good

Unique class of nebulized antibiotic for the CF population
FDA approved (although I don't have much issue with my Colistin not being FDA approved for nebbing - we CFer's do things off label all the time... actually since my FEV1 is greater than 75% my use of Cayston is off label....)
Used through the eFlow (you all know what a fan I have been of the eFlow... been using it since 2006)
Pretty quick nebulzation time

The Bad

Tastes a bit like TOBI - I haven't been on TOBI since about 2004 and I don't miss the taste. Oh well - not that big of a deal
Stuff has to be refrigerated (but technically the PI says once the meds have been removed from the fridge, meds can remain at room temp for 28 days)
Stuff has to be mixed (Just one extra step I'll have to do in my car during my mid-day dose.... more on that later)

The Ugly

I nearly sliced my finger open trying to get the metal flap and metal ring off the cayston vial. WOW FDA and GILEAD - you thought this was safe?! Good grief
3x a day dose.... WOW. Yes, 4 hours apart is OK. Sure, I get that. But wow - for those of us who work (and even those who don't), this is a very difficult routine to get in to. I have put reminders in my iPhone and work Blackberry to doubly remind me mid-day to do my Cayston. Or else I'll forget. BLEH

Given this is my 1st dose, I might have more to add to the Good and the Bad, depending upon how the med makes me feel :) I"ll keep you posted.

Overall, I'm super happy that the CF Community has another option to treat PA!

Cystic Fibrosis (CF) Exacerbation and Insulin Treatment

2010-06-23T21:09:00.000-04:00

Cystic Fibrosis (CF) Exacerbation and Insulin Treatment

Sponsor:
Hadassah Medical Organization

Purpose
The purpose of the study is to evaluate whether insulin treatment during pulmonary exacerbation (PE) in patients with Cystic Fibrosis (CF)and normoglycemia improves their short term outcome by normalizing the glycemic profile and enhancing recovery. the investigators would like to evaluate whether insulin treatment during exacerbation improves both the general clinical condition of these patients and also has a protecting effect on ß-cells by preventing the deleterious effect of "chronic" hyperglycemia.

Drug: novorapid / humalog short acting insulinDrug: Novo Rapid Insulin (Novonordisk)

Study Type:
Interventional

Study Design:

Allocation: RandomizedEndpoint Classification: Efficacy StudyIntervention Model: Parallel AssignmentMasking: Open LabelPrimary Purpose: Treatment
O
fficial Title:
Evaluation of Glucose Tolerance and Insulin Treatment in Non Diabetic Patients With Cystic Fibrosis During Acute Pulmonary Exacerbation

Primary Outcome Measures:
delta Forced Expiratory Volume in 1 second (FEV1%) predicted [ Time Frame: day 0 of the pulmonary exacerbation, to day 14 of the pulmonary exacerbation ] [ Designated as safety issue: No ]
change in lung function parameter %FEV1 predected from baseline before the exacerbatio to day 0, the day of hospitalization due to the pulmonary exacerbation and to day 14, after 2 weeks of Intra Venous (IV)Antibiotic therapy, due to Pulmonary Exacerbation (PE).

Secondary Outcome Measures:
change in Body Mass Index (BMI) [ Time Frame: baseline BMI will be compared with BMI on day 0- the day of hospitalization due to the pulmonary exacerbation, and to day 14, after 2 weeks of Intra Venous (IV)Antibiotic therapy, due to Pulmonary Exacerbation (PE). ] [ Designated as safety issue: No ]
weight and hight will be measured on arrival to hospital (day 0)of the pulmonary exacerbation and again on day 14 of the pulmonary exacerbation and. BMI will be calculated and compared to BMI perior to the exacerbation

Estimated Enrollment:
30

Study Start Date:
June 2010

Estimated Study Completion Date:
December 2015

Estimated Primary Completion Date:
June 2015 (Final data collection date for primary outcome measure)

insulin: Experimental
patients who will get insulin with main meals during Intravenous (IV) antibiotic therapy due to pulmonary exacerbation

Drug: novorapid / humalog short acting insulin

1-4 units will be injected Subcutaneously (SC), before every main meal. Drug: Novo Rapid Insulin (Novonordisk)

Novo Rapid Insulin (Novonordisk) will be administered before each main meal 1-4 units depends on the patients weight Detailed Description:

The life expectancy of patients with cystic fibrosis (CF) has increased over the last decades due to improved understanding of the disease and new treatments. CF patients who live longer develop glucose intolerance and cystic fibrosis related diabetes (CFRD), in fact, routine annual screening by Oral Glucose Tolerance Tests (OGTT) shows that the prevalence of CFRD increases with age. CFRD is primarily an insulinopenic condition characterized by an impaired and delayed insulin secretion, as a consequence of fibrosis in the exocrine pancreatic tissue that compromises the ß-cell function.

The occurrence of CFRD is significantly related to increased morbidity and mortality. Based on data from the CF Patients Registry in the USA, the mortality rate of patients with CFRD is six-fold higher than that of patients without CFRD.

Our pilot study proved that during pulmonary exacerbation (PE), CF patients with Normal Glucose Tolerance (NGT) exhibited early latent diabetic glucose intolerance in Oral Glucose Tolerance Test(OGTT) which becomes completely normalized 3-4 weeks after resolution of PE. These patients who are considered to be normoglycemic may experience relatively long periods of hyperglycemia during recurrent events of pulmonary infections. Chronically increased glucose values during PE have an adverse impact on pulmonary function both during PE and in the long-term. Hyperglycemia may increase the duration and extent of recovery from PE. Furthermore it may impair the ability to overcome lung infections by directly stimulating the growth of respiratory pathogens. Finally, hyperglycemia per-se during stressful conditions may worsen the general outcome.

Insulin therapy is considered routine treatment for patients with CFRD. In addition to normalizing glucose levels, insulin has a beneficial effect on general pulmonary function and nutritional status, possibly due to its anabolic effect. No routine or formal guidelines for treating PE hyperglycemia are currently available. Normal Glucose Tolerance (NGT)patients, who are hyperglycemic during PE only, are generally not intensively treated for this condition, except if the treating physician decides on interventional insulin treatment. Some patients may experience relatively long periods of hyperglycemia during recurrent events of pulmonary infections.

Eligibility
Ages Eligible for Study:
10 Years and older

Genders Eligible for Study:
Both

Inclusion Criteria:
Confirmed diagnosis of CF according to standard criteria
Pancreatic insufficiency
Age > 10 years
Normal oral glucose tolerance test (OGTT) in the past 12 month.
Acute pulmonary exacerbation (PE) according to the treating physician requires treatment with intravenous antibiotics

Exclusion Criteria:
CF-related diabetes/impaired glucose tolerance test (IGTT) in a mixed meal tolerance test performed during full remission from pulmonary exacerbation

Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01149005

Locations
Israel
Hadassah Hospital
Jerusalem, Israel

Bronchitol Phase III Clinical Trial Results

2010-06-23T21:07:00.001-04:00

Pharmaxis can breathe easy, say the bullish

DAVID SYMONS June 24, 2010

IT WAS a case of shoot first and ask questions later when Pharmaxis shareholders responded to clinical results for Bronchitol, a drug that improves lung function in cystic fibrosis patients by reducing mucus.

For many years a darling of the biotech sector, Pharmaxis shares fell as much as 47 per cent on the announcement that the company's second phase-three study of Bronchitol fell fractionally short of recording a statistically significant increase in the amount of air that patients could exhale over one second, as compared with a control group.

But the data was otherwise impressive, building on studies showing that Bronchitol increases lung function by 6 to 8 per cent.

This is important as the greatest cause of death for cystic fibrosis patients, who have a life expectancy of about 37 years, is the cumulative effect of lung-function decreases of 1 to 2 per cent a year.

What's spooked investors is the possibility a statistical quirk will mean Bronchitol fails to receive US Federal Drug Administration approval without a further clinical study.
It's a legitimate concern, particularly in light of spectacular failures from a clutch of biotech hopefuls already this year.

However, there's little reason to think Pharmaxis is going to join the ranks of fallen stars such as Chemgenex, Avexa, and Novagen. For a start, there's universal acceptance that Bronchitol is an effective drug that will obtain FDA approval.

The only question is whether another clinical study will be required, setting the timetable back from current plans for a US market launch in early 2012 and costing about $10 million to complete.

However, sector analysts reckon there's a good chance that Bronchitol will receive FDA approval based on the data already produced.

The most pessimistic view approval as a 50:50 proposition, while others are more bullish.
Shaw Stockbroking analyst Matthias Smith left his Pharmaxis share-price target unchanged at $4.30 after drilling into the data, commenting that he would be ''very surprised if further data is required for FDA approval''.

Key to the conclusion is the demonstrated safety of Bronchitol, and an expectation that the FDA has a strong desire to find an improved treatment for America's 30,000 cystic fibrosis sufferers.
Smith sees Pharmaxis's profits growing strong once Bronchitol is launched in Europe and the US, hitting $180 million in 2015.

After staging a modest recovery in afternoon trade, Pharmaxis shares closed yesterday at $2.10, down 33 per cent, and valuing the company at about $470 million.

Real-time, once-daily monitoring of symptoms and FEV in cystic fibrosis patients - A feasibility study using a novel device

2010-06-23T21:05:00.001-04:00

Clin Respir J. 2010 Apr;4(2):74-82.

Real-time, once-daily monitoring of symptoms and FEV in cystic fibrosis patients - A feasibility study using a novel device.

Sarfaraz S, Sund Z, Jarad N.

Adult CF Centre, Department of Respiratory Medicine, Bristol Royal Infirmary, Bristol, UK.

Abstract

Abstract Background and Aims: We investigated feasibility and value of a real-time electronic monitoring system adapted for early detection of cystic fibrosis (CF) pulmonary exacerbations (P Exs).

Methods: This was a 6-month prospective study. Patients recorded once daily their symptom score and spirometry using an electronic diary. The data were sent daily to the research team in real time. P Ex was considered to be present when change in symptoms and lung function values met a preset criteria. Number of P Exs during the study was compared with a parallel period of the previous and of the following years.

Results: Only 19 patients (37.2%) completed recording that could be evaluated. A total of 53 P Exs were identified, 26 (49.0%) of which needed intravenous (IV) antibiotics. The number of total P Exs in the study year did not differ from the previous or the following year, but the number of courses of oral antibiotics was greater than those given during the previous year.

Conclusion: Remote daily monitoring of symptoms and spirometry had a poor uptake among CF patients. For those who completed the study, this method early detected P Exs that were treated with oral antibiotics that might otherwise required IV antibiotics.

PMID: 20565480 [PubMed - in process]

Aquagenic Wrinkling Of The Palms in Cystic Fibrosis And The Cystic Fibrosis Carrier State - A Case Control Study.

2010-06-22T23:42:00.000-04:00

Br J Dermatol. 2010 Jun 18.

Aquagenic Wrinkling Of The Palms in Cystic Fibrosis And The Cystic Fibrosis Carrier State - A Case Control Study.

Gild R, Clay C, Morey S.

Princess Alexandra Hospital, Department of Dermatology, 199 Ipswich Road, Woolloongabba, Brisbane, Queensland 4102, Australia.

Abstract

Abstract Background Aquagenic wrinkling of the palms is hyperwrinkling occurring within three minutes of exposure to water. It is associated with cystic fibrosis and has been reported in a cystic fibrosis carrier.

Objectives

To ascertain if aquagenic wrinkling of the palms is a sign of the cystic fibrosis carrier state and to test for an association between Cystic Fibrosis Transmembrane Regulator protein function and time to wrinkling. Patients/Methods 21 patients, 13 carriers and 15 controls were recruited. Hands were immersed in water and time to wrinkling was measured.

An analysis of variance was performed with mean time to wrinkling as the dependent variable and cystic fibrosis status as the independent variable. Patients with a time to wrinkling of less than or equal to three minutes were defined as having aquagenic wrinkling. A test of proportions was performed to assess if the proportion of patients with aquagenic wrinkling varied between groups.

Results

Mean time to wrinkling was 11 minutes in controls, 7 minutes in carriers and 2 minutes in cystic fibrosis patients. Aquagenic wrinkling of the palms was not seen in controls, but occurred in 80% of cystic fibrosis patients and 25% of carriers. There was a significant difference between groups. (p<0.0001) Conclusions The study demonstrated that aquagenic palmar wrinkling is a sign of both cystic fibrosis and the carrier state. It suggests that time to wrinkling decreases with decreased cystic fibrosis transmembrane regulator protein function. Patients presenting with aquagenic wrinkling should be offered screening for both cystic fibrosis and the carrier state.

PMID: 20560957 [PubMed - as supplied by publisher]

Viagra / Cialis / Levitra and restoration of chloride channels in CF

2010-06-22T23:23:00.002-04:00

Eur Respir J. 2010 Jun 18.

Inhaled PDE5 inhibitors restore chloride transport in cystic fibrosis mice.

Lubamba B, Lebacq J, Reychler G, Marbaix E, Wallemacq P, Lebecque P, Leal T.
Université Catholique de Louvain Ave Hippocrate 10, Brussels, Belgium.

Abstract

Sildenafil and vardenafil, two selective inhibitors of phosphodiesterase type 5 (PDE5) are able, when applied by intraperitoneal injection, to activate chloride transport in cystic fibrosis (CF) mice homozygous for the F508del mutation.

Oral treatment with the drugs may be associated with adverse hemodynamic effects. We hypothesized that inhaled PDE5 inhibitors are able to restore ion transport in F508del-CF airway epithelium. We developed a restraint-free mouse chamber for inhalation studies. PDE5 inhibitors were nebulized for 15 minutes at concentrations adjusted from recommended therapeutic oral doses for male erectile dysfunction.

We measured in vivo nasal transepithelial potential difference 1 hour after a single inhalation of sildenafil, vardenafil or tadalafil in F508del-CF and in normal homozygous mice. After nebulization with the drugs in F508del mice, chloride transport, evaluated by perfusing the nasal mucosa with chloride-free buffer containing amiloride followed by forskolin, was normalized; the forskolin response was increased with the largest values being observed with tadalafil and intermediate values with vardenafil.

No detectable effect was observed on sodium conductance. Our results confirm the role of PDE5 inhibitors for restoring chloride transport function of F508del-CFTR protein and highlight the potential of inhaled sildenafil, vardenafil and tadalafil as a therapy for CF.

Gilead's Head-to-Head Study Of Cayston Vs. TIS In Cystic Fibrosis Patients Achieves Co-Primary Efficacy Endpoint Of Non-inferiority

2010-06-19T00:36:00.001-04:00

Gilead's Head-to-Head Study Of Cayston Vs. TIS In Cystic Fibrosis Patients Achieves Co-Primary Efficacy Endpoint Of Non-inferiority -
6/18/2010 12:51 PM ET

(RTTNews) - Gilead Sciences, Inc. (GILD: News ) said Friday that its head-to-head Phase III clinical trial of Cayston compared to tobramycin inhalation solution in cystic fibrosis patients with Pseudomonas aeruginosa achieved one of its co-primary endpoints of non-inferiority for mean percent change in forced expiratory volume in one second percent predicted after 28 days of treatment.

Patients receiving Cayston had a mean increase in FEV1 percent predicted from baseline to Day 28 of 8.35% compared to 0.55% for patients receiving tobramycin inhalation solution, which meets the statistical definition of superiority. Safety results were similar across both arms of the study, with lower incidence of cough in patients receiving Cayston.

Cayston was approved by the U.S. Food and Drug Administration in February 2010 and by the Australian Therapeutic Goods Administration in January 2010. Cayston received conditional marketing authorizations in the European Union and Canada in September 2009. These conditional approvals are contingent upon results from this Phase III study.

Gilead said it plans to begin submitting data from this study to regulatory agencies later this year.

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by RTT Staff Writer

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New Data Presented At ECFS Conference Highlight Potential for Denufosol to Provide Benefit to CF Patients

2010-06-18T09:19:00.002-04:00

Jun. 17, 2010 (Business Wire) -- Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today that data is being presented on denufosol tetrasodium, an investigational therapy for cystic fibrosis (CF), during an oral presentation and poster presentations at the 33^rd Annual European Cystic Fibrosis Society (ECFS) Conference June 16 - 19, 2010 in Valencia, Spain. The data from Inspire’s first Phase 3 clinical trial with denufosol, TIGER-1, suggest that denufosol, an inhaled ion channel regulator, may ameliorate the accelerated loss of lung function in CF patients during adolescence and has the potential to provide significant benefit in lung function for those patients on minimal pharmacotherapies.

“During adolescence, CF patients are especially vulnerable to an accelerated rate of decline in lung function and there is a consequent need for therapies that delay or reduce lung function loss in this population,” stated Richard B. Moss, M.D., Professor Emeritus of Pediatric Pulmonary Medicine at Stanford University School of Medicine and Co-Director of the Children’s Health Research Program at Stanford University Medical Center. “The significant lung function improvements observed in the subgroup of adolescent patients in the TIGER-1 clinical trial suggest the potential of denufosol as an early disease-stage intervention therapy that may reduce the loss of lung function during this critical time in a CF patient’s lung disease progression.”

The oral presentation, “Denufosol Improved Lung Function in Adolescent CF Patients” (R.B. Moss, A. Schaberg, C. Deans, W. Tian, L. Smiley, N. Herje, T. Durham, F.J. Accurso), is being presented during the session, “Workshop 5: Current Clinical Trials,” on Thursday, June 17 from 3:30 - 3:45 p.m. local time (9:30 - 9:45 a.m. ET). The presentation highlights subgroup data from the pre-specified analysis of adolescent CF patients aged 12-18 years old (n=123) from Inspire’s first Phase 3 clinical trial with denufosol, TIGER-1. In this trial, denufosol significantly improved lung function versus placebo in adolescents during the 24-week double-blind portion of TIGER-1 and continued improvement in lung function was observed with open-label treatment. The change from baseline in FEV₁ (Forced Expiratory Volume in One Second) for the adolescent patients treated with denufosol at the week-24 endpoint was 112 mL compared to -10 mL for placebo (p=0.013). In comparison, in the intent-to-treat (ITT) population in TIGER-1 (n=352), the change from baseline in FEV₁ at the 24-week endpoint was 48 mL for denufosol compared to 3 mL for placebo (p=0.047). The rate of decline in percent predicted FEV₁ for adolescent patients receiving placebo from week 0 to week 24 during the TIGER-1 trial was significantly different from zero (p <0.001;>1 for adolescent patients receiving denufosol was not significantly different from zero (p=0.134). The change from baseline for FEF_25%-75%(Forced Expiratory Flow), a measure of small airways function, for the adolescent patients treated with denufosol at the week-24 endpoint was 115 mL/sec. compared to -112 mL/sec. for placebo (p=0.036).

The Company is also presenting three additional posters at the ECFS Conference. The poster presentation, “Potential of Denufosol as an Early Intervention in CF Lung Disease: Efficacy in Patients with Minimal Pharmacotherapy in a U.S. Phase 3 Clinical Trial” (F.J. Accurso, W. Tian, A. Schaberg, T. Navratil, M.S. Howenstine, T.G.

ARIKACE Demonstrates Sustained Benefit in the Treatment of Cystic Fibrosis Patients Who Have Pseudomonas Lung Infections

2010-06-18T09:19:00.001-04:00

MONMOUTH JUNCTION, N.J., June 17 /PRNewswire/ -- Transave, Inc., today reported interim results from a multi-cycle Phase II open label clinical trial in cystic fibrosis (CF) patients on its lead investigational drug, ARIKACE™ (liposomal amikacin for inhalation). The data indicated that ARIKACE, delivered once daily for 28 consecutive days followed by 56 days off-treatment for four cycles demonstrated statistically significant improvement in lung function that was sustained during the 56 days off study drug. ARIKACE was well-tolerated during the four cycles. Results were presented today at the 33rd European Cystic Fibrosis Society (ECFS) Conference in Valencia, Spain, by Predrag Minic, MD, Professor of Pediatrics and Head of Pediatrics Pulmonology Department, Mother and Child Health Institute, Belgrade, Serbia, and co-lead investigator of the study.

The open label study is an extension of a previously reported randomized, placebo controlled Phase II study, and was designed to evaluate ARIKACE over multiple treatment cycles in CF patients with Pseudomonas aeruginosa lung infections. Forty nine patients were enrolled to receive ARIKACE 560 mg daily for 28 days of therapy followed by a 56-day off-treatment observation period. ARIKACE was administered once daily using an eFlow® Nebulizer System (PARI Pharma GmbH), a novel, highly efficient and portable aerosol delivery system.

"The sustained improvement in lung function with significant reduction in bacterial density over multiple treatment cycles with ARIKACE is encouraging and indicative of benefit for cystic fibrosis patients who have chronic Pseudomonas lung infections," said Renu Gupta, MD, Transave's Executive Vice President for Development and Chief Medical Officer. Dr. Gupta indicated that preparations are underway to launch Phase III studies to confirm efficacy of ARIKACE. "These results support the potential value of delivering amikacin through Transave's advanced pulmonary liposome technology designed for sustained release and penetration of the mucus and bacterial biofilm in the lungs."

Pulmonary function (FEV1) increased significantly among patients receiving 560 mg of ARIKACE, with an estimated relative change from baseline in FEV1 of 9.2% (95% CI +5.0%, +13.4%; p less than or equal to 0.0001) at the end of treatment during cycles one to four. The improvement in lung function was sustained at the end of the 56-day off-treatment period during the four cycles with an estimated relative change from baseline in FEV1 of 4.7% (95% CI +1.0%, +8.5%; p=0.015).

ARIKACE demonstrated statistically significant reduction in Pseudomonas density, including mucoid strains, which was sustained over the treatment period of four cycles for 12 months. Mucoid strains of Pseudomonas are often difficult to suppress with antibiotics and play a greater role in progression of CF lung disease.

ARIKACE was well-tolerated for four cycles of treatment over 12 months, and demonstrated adverse effects that are consistent with those expected in a population of CF patients receiving inhalation medicines.

"ARIKACE development continues to show promise in improving lung function for CF patients," said Robert J. Beall, Ph.D., President and CEO of the Cystic Fibrosis Foundation. "We are pleased to support Transave's work in potentially bringing an important new treatment option to CF patients."

Cystic Fibrosis Foundation Therapeutics, Inc., a nonprofit affiliate of the Cystic Fibrosis Foundation, provided $3.9 million to support the development of ARIKACE. The Foundation is the leading organization devoted to curing and controlling cystic fibrosis.

"A once-daily drug that may offer advantages in maintaining improvements in lung function during off-treatment periods over multiple cycles would be an important advance in the treatment of cystic fibrosis patients," said Dr. Minic. "These results show significant improvement in lung function with ARIKACE and are especially important since these patients are living in a state of chronic infection often requiring continuous treatment cycles over time.

The data presented today at the 33rd European Cystic Fibrosis Society Conference are currently available on the company's website: (http://www.transaveinc.com/NewsEvents.aspx?category=Articles&archive=false).

About ARIKACE™

ARIKACE is a form of the antibiotic amikacin, which is enclosed in nanocapsules of lipid called liposomes. This advanced pulmonary liposome technology prolongs the release of amikacin in the lungs while minimizing systemic exposure. The treatment uses biocompatible lipids endogenous to the lung that are formulated into small (0.3 micron), neutral liposomes that enable penetration of the biofilm.

Positive results were announced in October 2009 from pooled results of two Phase II clinical trials in the treatment of CF patients with Pseudomonas lung infections. The company also previously announced positive Phase II results in September 2009 in the treatment of non-CF bronchiectasis patients who have Pseudomonas lung infections.

Transave and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), will collaborate on the planning, design and implementation of a clinical trial beginning later this year to evaluate ARIKACE in patients with nontuberculous mycobacteria (NTM) lung disease who have failed to respond to standard, guideline-based treatment regimens. Current treatment requires lengthy multi-drug regimens that are often poorly tolerated and not very effective. No new drugs have been assessed in clinical trials for this disease in many years.

ARIKACE has been granted orphan drug status in the United States by the FDA, and has received an orphan drug designation in Europe by the European Medicines Agency for the treatment of Pseudomonas infections in patients with CF. ARIKACE has also been granted orphan drug status by the FDA for the treatment of bronchiectasis in patients with Pseudomonas or other susceptible pathogens.

About eFlow® Technology and PARI Pharma

ARIKACE is delivered by an eFlow® Nebulizer System developed by PARI Pharma and optimized specifically for ARIKACE. The eFlow Nebulizer System uses eFlow Technology to enable highly efficient aerosolization of medication including liposomal formulations via a vibrating, perforated membrane that includes thousands of laser drilled holes. Compared to other nebulization technologies, eFlow Technology produces aerosols with a very high density of active drug, a precisely defined droplet size, and a high proportion of respirable droplets delivered in the shortest possible period of time. eFlow Technology is not an ultrasonic nebulizer technology. Combined with its quiet mode of operation, small size (it fits in the palm of the patient's hand), light weight, and battery use, eFlow Technology reduces the burden of taking daily, inhaled treatments. PARI Pharma focuses on the development of aerosol delivery devices and comprehensive inhalation drug development to advance aerosol therapies where drug and device can be optimized together. Online at www.paripharma.com.

About The Cystic Fibrosis Foundation

The Cystic Fibrosis Foundation is the world's leader in the search for a cure for cystic fibrosis. The Foundation funds more CF research than any other organization and nearly every CF drug available today was made possible because of Foundation support. Based in Bethesda, Md., the Foundation also supports and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease. For more information, please visit www.cff.org.

About Transave, Inc.

Transave, Inc., is a biopharmaceutical company focused on the development of innovative inhaled pharmaceuticals for the site-specific treatment of chronic lung diseases. The company's major focus is on developing antibiotic therapy delivered via proprietary advanced pulmonary liposome technology in areas of high unmet need in lung diseases. The Transave team is dedicated to leveraging its development and commercialization expertise, along with its intellectual property, to bring life-extending and life-enhancing medicines to patients. For more information about Transave's technology and development programs, visit www.transaveinc.com.

MRSA and CF survival

2010-06-17T10:35:00.000-04:00

JAMA. 2010 Jun 16;303(23):2386-92.

Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis.

Dasenbrook EC, Checkley W, Merlo CA, Konstan MW, Lechtzin N, Boyle MP.

Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio 44106-5067, USA. ecd28@case.edu

Abstract

CONTEXT: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the respiratory tract of individuals with cystic fibrosis (CF) has increased dramatically; however, its impact on outcomes in CF is unclear. Because the time between infection with bacteria in CF and death can be decades, observational studies with long periods of follow-up are well suited to address the current gap in knowledge.

OBJECTIVE: To determine whether isolation of MRSA from the respiratory tract of CF patients is associated with worse survival compared with patients who never have a culture positive for MRSA.

DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 19,833 CF patients aged 6 to 45 years seen at centers accredited by the Cystic Fibrosis Foundation in the United States. Patients entered between January 1996 and December 2006 and were followed up through December 2008. Cox regression models with time-varying covariates were used to compare survival between CF patients with and without respiratory tract MRSA. MAIN OUTCOME MEASURE: Time from age at entry until age at death from any cause.

RESULTS: In 137,819 patient-years of observation (median, 7.3 years/patient), 2537 CF patients died and 5759 patients had MRSA detected. The mortality rate was 18.3 deaths (95% confidence interval [CI], 17.5-19.1) per 1000 patient-years in patients without MRSA and 27.7 deaths (95% CI, 25.3-30.4) per 1000 patient-years in those with MRSA. Among those with MRSA, the attributable risk percentage of death associated with MRSA was 34.0% (95% CI, 26.7%-40.4%). The unadjusted hazard ratio associated with MRSA was 1.47 (95% CI, 1.32-1.62). After adjustment for time-varying covariates associated with severity of illness, MRSA remained associated with a higher risk of death (1.27; 95% CI, 1.11-1.45).

CONCLUSION: Detection of MRSA in the respiratory tract of CF patients was associated with worse survival.

New Study in JAMA Examines Impact of MRSA on Cystic Fibrosis

2010-06-17T10:32:00.001-04:00

New Study in JAMA Examines Impact of MRSA on Cystic Fibrosis

June 16, 2010

A study published today in the Journal of the American Medical Association examines the effect that methicillin-resistant Staphylococcus aureus (MRSA) has on people with cystic fibrosis. It found that chronic infection with MRSA in people with CF was associated with worse survival than those who don’t have the bacteria.

MRSA can cause infections that are resistant to some common antibiotics. More than 20 percent of people with CF have MRSA in their respiratory tract.

Of the various bacteria that cause lung infections in CF, Burkholderia cepacia complex has been most commonly associated with shortened life span. This study is the first to find a possible link between MRSA and survival rates.

The Foundation is currently funding a study to find the most effective way to treat MRSA infections in CF patients. This will lead to clinical trials to test treatments in CF patients with chronic MRSA infection and those with newly acquired MRSA.

The CF Foundation has stringent infection control standards, which were developed in partnership with CF physicians and infection control experts.

The best protection against getting MRSA and other germs is to:

Clean your hands often, use soap and water or alcohol-based hand gel;
Cough into a tissue, throw it away and then clean your hands;
Clean and disinfect nebulizers regularly;
Avoid people who are sick; and
Do not share utensils or cups.

The Foundation encourages people with CF to work closely with a cystic fibrosis physician at an accredited CF Foundation care center to address infection and treatment-related issues.

http://www.cff.org/aboutCFFoundation/NewsEvents/06-16-JAMA-Study-Examines-Impact-of-MRSA-on-CF.cfm

Home sweet home

2010-06-14T22:12:00.003-04:00

Hey guys,

I appreciate your kind words and support over the past week.

Luckily, the appendix surgery went well on the evening of 6/7. The Anesthesia and Vent did a number on my lungs, so I'm on 2 weeks of zozyn + cipro (it was zozyn+tobra by my ears began to ring so we did the switch-a-roo).

I'm home today to do IV's for another 7 days. I will definitely miss the nurses from the hospital doing my IV's for me at night...but I won't miss the gross food, hospital bugs, and yucky bed. Bleh.

So I'm going to see what I can draw on my belly from all of my scars from the inguinal hernia repair (2000), gallbladder removal (2005) and now appendix removal (2010). Connect the dots... la la la la!

Cheers to going to the ER on a Sunday night when you really don't want to and don't think you really need to.... you never know when the pesky appendix will decide to be cranky!

Oh yes.... that is the aforementioned appendix. The surgeon wouldn't save it for me to see, but promised pics. Here is one :)

Appendix-less

2010-06-08T15:41:00.002-04:00

Thank you all so much for your kind words of support, thoughts and prayers... it means so much to me!

I had my surgery last night at around 7:30pm and everything went smoothly, thank goodness!

Just 12 hours later I was up and walking around (laproscopic (sp?) surgery). My belly is still the size of Jupiter but gradually I'm passing more gas and burping.

I have cool pix of my former appendix and the cyst on my ovary that I will post once I break out of jail.

Docs needed to give me abx for the appendicitis (zozyn), so I've dedided to continue that with tobra for 2 weeks just because it's much tougher to clear mucus with my belly looking like I"m 8 months preggo. So I think I"ll be a bit more prone to infection so 2 weeks of abx it is!

Other than that, I'm super loopy on vicodin so I am seriously nodding off while writing this. I hope this post makes sense...if not, let me know and I'll try to (zzzzz) fix it. :)

Take care!

Appendix surgery

2010-06-07T10:26:00.002-04:00

I am at the ER and going to get my appendix removed here shortly.

I've had many intestinal blockages so I thought this would be it - but man it hurts a bit more than the run of the mill intestinal blockage I get.

I had some pain this morning at around 3am that woke me up - and after a few hours they discovered my cranky appendix!Please keep me in your thoughts and prayers - it should be a quick, simple surgery but with CF things can sometimes get complicated.

I'll keep you posted on how things go!