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Saturday, December 18, 2010


16 December 2010


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



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

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.


Friday, December 3, 2010

Estrogen aggravates inflammation in PA pneumonia in CF mice

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

Sunday, November 28, 2010

Please Vote!

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.

Saturday, September 25, 2010

Improving Clinical Trials Act passes!

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

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.

Wednesday, September 22, 2010

$25 for a quick survey

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

Sunday, September 12, 2010

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

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.

Friday, September 3, 2010

Mutational spectrum of cystic fibrosis in the Lebanese population

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

Mutational spectrum of cystic fibrosis in the Lebanese population.

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.


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

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

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
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:

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.


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

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

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

Thursday, September 2, 2010

Please vote for CF Pepsi Refresh Project

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Tuesday, August 31, 2010

Pharmaxis in deal to support launch of cystic fibrosis drug

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.



Saturday, August 28, 2010

Luminex Announces Commercial Launch of New Cystic Fibrosis Test

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

Curr Opin Pulm Med. 2010 Aug 25.

Impact of cystic fibrosis on bone health.

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


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.

Saturday, August 21, 2010

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

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.

Tuesday, August 17, 2010

vitamin D may treat or prevent allergy to common mold

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."


Wednesday, August 11, 2010

Estrogen and CF women


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".


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


Tuesday, July 20, 2010

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

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.


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.

Thursday, July 15, 2010

Tweeting my CF Routine for Raise CF Awareness

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!

Tuesday, July 13, 2010

Cayston Update ****WARNING: MUCUS PICTURES*******

*********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

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 :)

Saturday, July 10, 2010

First dose of Cayston

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!

Wednesday, June 23, 2010

Cystic Fibrosis (CF) Exacerbation and Insulin Treatment

Cystic Fibrosis (CF) Exacerbation and Insulin Treatment

Hadassah Medical Organization

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:

Study Design:

Allocation: RandomizedEndpoint Classification: Efficacy StudyIntervention Model: Parallel AssignmentMasking: Open LabelPrimary Purpose: Treatment
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:

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.

Ages Eligible for Study:
10 Years and older

Genders Eligible for Study:

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

Hadassah Hospital
Jerusalem, Israel

Bronchitol Phase III Clinical Trial Results

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

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 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]

Tuesday, June 22, 2010

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

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 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.


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.


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

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.


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.