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Sunday, February 14, 2010

Hypnosis could help children with emotional breathing problems

Hypnosis could help children with emotional breathing problems

February 14, 9:13 AMCharlotte Health and Happiness ExaminerKathleen Blanchard RN

Children with breathing problems such as asthma and cystic fibrosis could benefit from hypnosis that can alleviate discomfort during procedures, and calm symptoms that have emotional components associated with respiratory disease.

Hypnosis, combined with regular medical treatment could help children with habitual cough that may experience feelings of shortness of breath or other uncomfortable sensations that could be emotional in origin.

In a paper published in Pediatric Asthma, Allergy & Immunology, Ran D. Anbar, MD, Professor of Pediatrics at SUNY Upstate Medical University, in Syracuse, NY suggests that hypnosis should be considered for children whose respiratory symptoms are brought about as the result of a mind-body component.

Children with asthma who hyperventilate, breathe noisily, cough disruptively, or otherwise have emotionally triggered respiratory symptoms could be calmed with hypnosis. Coughing out of habit or vocal cord dysfunction that produces a high pitched noise with breathing but can have psychological roots, found to be absent during sleep might be indicative that hypnosis can relieve symptoms of asthma of breathing difficulty triggered by emotions."Dr. Anbar has added hypnosis to our therapeutic toolbox.

When breathing problems have a large mind-body component, resolution with hypnosis can dramatically reduce the need for expensive testing and medications," says Harold Farber, MD, MSPH, Editor of Pediatric Asthma, Allergy Immunology, and Associate Professor of Pediatrics, Section of Pulmonology, at Baylor College of Medicine, Houston, TX.

Hypnosis for children with asthma or other breathing disorders should always be performed by a medical professional warns Anbar. Only individuals with special training in hypnosis therapy should be considered to help alleviate respiratory symptoms of asthma in children triggered by emotions.

Hypnosis could produce physiologic that alleviate symptoms related to asthma and respiratory problems that include chest pain, or feelings that something is “stuck” in the throat, and hperventilation. The author suggests that hypnosis could be used before expensive testing for otherwise unexplained feelings of difficulty breathing in children by helping teach breathing techniques that could alleviate symptoms and produce physiologic changes related to emotional distress associated with asthma or cystic fibrosis.

Pediatric Asthma, Allergy, and ImmunologyDOI: 10.1089/pai.2009.0025


Using Avandia in treating CF

Defective signaling pathway sheds light on cystic fibrosis

February 14, 2010 -->

In a study that could lead to new therapeutic targets for patients with the cystic fibrosis, a research team from the University of California, San Diego School of Medicine has identified a defective signaling pathway that contributes to disease severity. In the study, published in the journal Nature Medicine, the researchers report that defective signaling for a protein called the peroxisome proliferator-activated receptor-γ (PPAR-γ) accounts for a portion of disease symptoms in cystic fibrosis, and that correction of the defective pathway reduces symptoms of the disease in mice.

In the paper published in the February 14 edition of the journal, lead investigator Gregory Harmon, MD, study supervisor Christopher Glass, MD, PhD, professor of cellular and molecular medicine, and colleagues show that both mice and cells from patients with CF<>

"Cystic fibrosis results from a genetic mutation in a channel, or membrane pore, that facilitates the transport of chloride and bicarbonate electrolytes from inside the cell to the spaces outside the cell," said Harmon. "Loss of the cystic fibrosis pore channel results in inflammation and mucus accumulation. It also results in dehydration of the cell surfaces that make up the lining spaces inside the lungs and other affected organs, such as the intestinal tract."

Exactly how the process occurs has been a matter of intense scientific scrutiny; yet despite numerous therapeutic advances, individuals with the disease continue to endure a shortened lifespan. "Someone born in the 1990s with cystic fibrosis is expected to live to an age of around 40," Harmon added.

Working with isolated cells from mice and human cell lines from patients with the disease, Harmon identified that multiple genes affected by PPAR-γ were reduced in cystic fibrosis. When the researchers treated mice with cystic fibrosis with the drug rosiglitazone, a thiazolidinedione drug that binds and activates PPAR-γ, gene expression was largely normalized and survival improved. The drugs also corrected part of the inflammatory process in the tissue. Deleting the PPAR-γ in the intestine of mice worsened the disease, leading to mucus accumulation in the intestine. Additionally, the researchers found that activating PPAR-γ could increase bicarbonate production in the intestinal tissue by increasing the activity of bicarbonate-producing enzymes called carbonic anhydrases.

"For the first time, we are able to use a drug that activates bicarbonate transport without affecting chloride transport, and see improvement in the disease," Harmon said. The results provide support for the hypothesis of experts in the field such as UCSD's Paul Quinton, PhD, who has written that increasing bicarbonate in cystic fibrosis tissues could be a relevant target for future therapies.

"The finding of the reduced PPAR-γ activating prostaglandin in cystic fibrosis is exciting since it could serve as a marker to identify which patients might benefit from treatment with PPAR-&gamm activating drugs," said Glass.

Low prevalence of glucose intolerance in racially mixed children with cystic fibrosis

Pediatr Diabetes. 2010 Feb 8.

Low prevalence of glucose intolerance in racially mixed children with cystic fibrosis.

Alves C, Lima DS, Cardeal M, Santana A.

Federal University of Bahia, Salvador-Bahia, Brazil.

Alves C, Lima DS, Cardeal M, Santana A.

Objective: To evaluate glucose tolerance in racially mixed Brazilian youth with cystic fibrosis (CF).

Methods: Cross-sectional study conducted between August and September 2007, at a reference service for CF, evaluating: glycated hemoglobin (HbA1c), blood glucose, and insulin levels, before and 2 h after a glucose overload.

Results: There were 46 patients aged between 6 yr and 16 yr and 2 months (median: 9 yr and 10 months) of whom 64% were boys. Of these, 26% were Whites; 54.4% Mulattoes; and 19.6% Blacks. HbA1c was normal in all patients. Only one participant (12-yr old) had glucose intolerance. Insulin levels ranged from 1 to 23 microIU/mL (median: 4.5 microIU/mL) at baseline and from 3.2 to 192.1 microIU/mL (median: 11 microIU/mL) after a glucose overload. Insulin resistance evaluated by the HOMA index, stratified by sex and age, was present in three patients. The DeltaF508 mutation was present in only 4.3% of the sample, all of them being heterozygous.

Conclusions: The low prevalence of carbohydrate intolerance in this population is probably a result of their young age. Another possibility is the low frequency of the DeltaF508 mutation. Although not conclusive, these data suggest that in addition to age, the genotype:phenotype ratio may influence the development of glucose intolerance in patients with CF.

AMAZING workout videos + Book

For those of you who know me, I've had amazing results both with my lungs and with my body from Jillian Michaels workout videos.

My fav is the Banish Fat Boost Metabolism.

Also, I know there are quite a number of CFer's who are flabby and looking to get into shape. This book has been INCREDIBLE for me as well. I don't have a recommended website to purchase this book, but you could even go to your local library if you want to check it out.

Friday, February 5, 2010

A 1-m distance is not safe for children with cystic fibrosis at risk for cross-infection with Pseudomonas aeruginosa

Am J Infect Control. 2010 Feb 1.

A 1-m distance is not safe for children with cystic fibrosis at risk for cross-infection with Pseudomonas aeruginosa.

Festini F, Taccetti G, Galici V, Neri S, Bisogni S, Ciofi D, Braggion C.
Department of Pediatrics, Section of Nursing Sciences, University of Florence, Florence Italy.

Although maintaining a distance of 1 m between persons with cystic fibrosis (CF) is a universal recommendation to prevent respiratory cross-infections such as Pseudomonas aeruginosa, evidence supporting this preventive measure is scarce.

Examining 336 samples from 42 patients with CF collected experimentally from sterile surfaces after speaking and coughing, we found that transmission of P aeruginosa beyond 1 m is possible during both talking and coughing, although the probability is low (1.7%).

Updates on VX-770 from Vertex's Earnings Call

Here are a few updates from Vertex's Earnings Cal on 2/4/10

  • Vertex has completed planned enrollment of two of the three trials in Phase 3 registration program of VX-770, our potentiator compound

  • We are on track to have pivotal data and submit an NDA for this compound in the second half of 2011

  • We enrolled ahead of schedule the primary Phase 3 trial called STRIVE. This trial enrolled approximately 170 patients, age 12 and older with the G551D mutation.

  • We have other completed planned enrollment, approximately 120 patients in the DISCOVER trial, which is primarily a safety study evaluating patients with the delta F 508 mutation.

  • ENVISION trial which is enrolling younger patients with the G551D mutation, age 6 years to 11 years is ongoing and on track to complete enrollment in the first half of 2010.

  • We expect that all patients in the STRIVE and DISCOVER trials will have received their first dose of 770 or placebo by the end of February.

  • Patients in STRIVE are being dosed for 48 weeks with a primary efficacy and evaluating FEB1 [ph] for 24 weeks. At this time it is our expectation to conduct a study through 48 weeks, which puts us on a time line of submitting an NDA in the second half of 2011.

  • So my personal assumption and belief is 770 has a broader use than just G551D patients. And the reason for that is because we have preclinical data that show potentiation is possible for a lot of different mutated channels. And so far preclinical data translated very nicely into the clinical performance.


Wednesday, February 3, 2010

CF Investigational Drug VX-809 Shows Encouraging Resultsin Phase 2a Trial

CF Investigational Drug VX-809 Shows Encouraging Resultsin Phase 2a Trial

(from the CFF)
February 3, 2010

Vertex Pharmaceuticals Incorporated announced today results from a Phase 2a trial of VX-809, an oral investigational drug that aims to correct the basic defect in cystic fibrosis. VX-809 was found to be well-tolerated and to reduce sweat chloride levels — a key indicator of CF.

The 28-day, Phase 2a trial of VX-809 examined the drug in cystic fibrosis patients who have the Delta F508 gene mutation, the most common mutation in CF. The study focused primarily on the safety and tolerability of the drug and changes in sweat chloride.

A reduction in sweat chloride levels in the Phase 2a data suggests that VX-809 may improve the function of CFTR, the faulty protein in CF.“These are very exciting and important results in our effort to find ways to treat the basic defect in cystic fibrosis,” said Robert J. Beall, Ph.D., president and CEO of the CF Foundation. “The VX-809 data further supports our hypothesis that small molecules can be used to treat the underlying genetic cause of cystic fibrosis.”

The data from this trial pave the way for future studies of VX-809, including testing the therapy in combination with VX-770. Also developed by Vertex, VX-770 is an oral investigational drug that showed encouraging Phase 2 results in restoring the function of CFTR in patients with the G551D mutation of CF.

Research in the laboratory suggests that using two therapies in combination may increase CFTR function in cells with the Delta F508 mutation when compared to using a single therapy alone.
The first trial examining VX-809 and VX-770 in combination in cystic fibrosis patients is currently in the planning phases, and is expected to begin in the United States in the second half of 2010.

In addition, Vertex is further reviewing the Phase 2a data and may explore the option of studying VX-809 as a single drug in higher doses in a separate clinical trial.

Through its Therapeutics Development Program, the CF Foundation collaborated with Vertex to discover and develop VX-809 and VX-770, investing approximately $76 million in the effort. This represents the largest single investment in CF drug discovery by the Foundation.


Vertex press release

Vertex Announces Results from Phase 2a Trial of VX-809 Targeting the Defective Protein Responsible for Cystic Fibrosis

-VX-809 was well-tolerated at all dose levels when dosed once daily for 28 days-

-Statistically significant changes observed in measurement of sweat chloride suggest increased CFTR activity- -Data support planned combination trial of VX-809 and VX-770 in second half of 2010 for CF patients with the F508del mutation- \

CAMBRIDGE, Mass., Feb 03, 2010 (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced results from a preliminary analysis of data from a 28-day Phase 2a clinical trial of VX-809 in patients with cystic fibrosis (CF) who are homozygous for the F508del mutation. VX-809, an oral investigational Cystic Fibrosis Transmembrane Conductance Regulator protein (CFTR) corrector, was well-tolerated across all four dose groups studied. In the trial, VX-809 showed a statistically significant decline in sweat chloride at both the 100 mg and 200 mg once-daily doses, suggesting that the activity of the CFTR protein was increased in patients during dosing. Additionally, VX-809 demonstrated a dose response in change in sweat chloride across the four dose groups. On the basis of these results, Vertex plans to initiate a combination trial of VX-809 and VX-770, an investigational CFTR potentiator, in the second half of 2010. VX-809 and VX-770 were developed with support from Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit affiliate of the Cystic Fibrosis Foundation.

"This Phase 2a trial evaluated the potential effect of an oral compound to improve trafficking of the defective CFTR protein, and its results represent an encouraging step forward in the development of new therapies to treat the underlying cause of CF in patients with the most common CFTR mutation, known as F508del," said J.P. Clancy, M.D., Director of the Pediatric Pulmonary Center at the University of Alabama at Birmingham and Principal Investigator for the VX-809 Phase 2a trial. "In the trial, VX-809 was well-tolerated across the dose groups, and statistically significant changes in sweat chloride, an important biomarker of CFTR activity, were observed at certain dose levels. There is high interest in the CF community in new approaches to CF therapy, and we look forward to the future exploration of VX-809 and VX-770 as part of a novel combination regimen aimed at treating the majority of CF patients."

"While the median predicted age of survival for patients with CF has increased to more than 37 years of age, there are no approved therapies that directly target the underlying defect of this disease," said Robert J. Beall, Ph.D., President and Chief Executive Officer of the Cystic Fibrosis Foundation. "We believe that compounds such as VX-770 and VX-809 represent a promising potential approach to future CF treatment, and the results announced today for VX-809 support future clinical trials of this compound, including a planned clinical trial in combination with VX-770 expected to begin later this year."

About the Phase 2a Trial

The preliminary results reported today are from a randomized, double-blind, placebo-controlled, multiple dose Phase 2a clinical trial that enrolled 89 patients aged 18 or older who are homozygous for the F508del CFTR mutation. Patients in the trial received one of four doses of VX-809, or placebo, in addition to standard therapies for 28 days. The primary endpoint of the trial was to evaluate the safety and tolerability of VX-809. Multiple secondary endpoints were utilized to evaluate any effect of VX-809 on CFTR function or lung function.

Safety Evaluation

Through 28 days of 25 mg, 50 mg, 100 mg and 200 mg once-daily dosing, VX-809 was well-tolerated. In the trial, one patient discontinued treatment in each of the VX-809 treatment arms due to adverse events. Respiratory-related adverse events were the most commonly reported adverse event in the trial. Safety and tolerability were the primary endpoints of the trial, and a detailed safety analysis is ongoing.

Evaluation of CFTR Activity

At both the 100 mg and 200 mg dose levels, a statistically significant decline in sweat chloride, a secondary endpoint, was observed in analyses comparing each patient to baseline and to placebo. Additionally, a dose response for change in sweat chloride was observed across all four dose groups. The mean change in sweat chloride compared to placebo for each of the dose groups is as follows:

Treatment Arm
Mean Change in Sweat Chloride Compared to Placebo*

*Across the arms of the trial, patients' mean baseline sweat chloride measurements were approximately 100 mmol/L, which is consistent with sweat chloride measurements of patients who are homozygous for the F508del mutation.

Elevated sweat chloride levels are a diagnostic hallmark that occur in all CF patients and result directly from defective CFTR activity in epithelial cells in the sweat duct. The amount of chloride in the sweat is measured using a standard test. Patients with CF typically have elevated sweat chloride levels in excess of 60 mmol/L, while normal values are less than 40 mmol/L.

"This trial was meant to provide clinical data for VX-809 to inform the direction of future development for this compound," said Dr. Robert Kauffman, Vertex's Senior Vice President, Clinical Development and Chief Medical Officer. "Based on data generated in this Phase 2a trial, we plan to move forward with a proof-of-concept clinical trial of VX-809 dosed in combination with VX-770 in the F508del patient population, planned for the second half of 2010. We are pleased with the safety and biomarker data observed in this preliminary analysis, which, together with the Phase 2 data for VX-770, could contribute to the future treatment of CF with novel CFTR modulators."

The trial also included additional secondary endpoints, including exploratory endpoints, to evaluate CFTR function, including CFTR trafficking, and lung function. The trial was not powered to demonstrate a statistically significant effect in these additional secondary endpoints. Additional sub-analyses of the secondary endpoints are ongoing to determine any potential trends in other measures of CFTR-dependent chloride ion transport, such as nasal potential difference; or CFTR maturation, as measured by an exploratory Western blot assay, however no statistically significant changes in these measures were observed in the preliminary analysis of data from this trial. As expected, the results did not show any change in lung function, as measured by FEV1.

Vertex expects to report additional results of this Phase 2a trial at a medical meeting in 2010.
Future Development Plans for VX-809

Based on the Phase 2 data announced today, Vertex plans to initiate a combination trial of VX-809 with the CFTR potentiator VX-770 in patients with the most common CFTR mutation, F508del, in the second half of 2010. In in vitro studies, a combination regimen of VX-770 and VX-809 has been shown to increase CFTR activity when compared to dosing of VX-770 or VX-809 as single agents. In addition, Vertex is conducting further analyses of the Phase 2a data and may explore the option to evaluate VX-809 doses of greater than 200 mg when dosed as a single agent.

About VX-809 and VX-770

VX-809 is a novel oral CFTR corrector drug candidate aimed at increasing the concentration of F508del CFTR proteins at the cell surface. Vertex recently completed a Phase 2a trial of VX-809, as announced today.

Vertex is also developing VX-770, a novel oral CFTR potentiator drug candidate aimed at increasing the activity of defective CFTR proteins at the cell surface. Vertex is currently conducting the ENDEAVOR Phase 3 registration program of VX-770, an investigational Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) potentiator compound for the treatment of CF. The program consists of three ongoing clinical trials, known as STRIVE, ENVISION and DISCOVER, and is designed to evaluate the utility of VX-770 across different age groups and genotypes, including children as young as six years of age.

Patients interested in further information about clinical trials of VX-809 or VX-770 should visit www.clinicaltrials.gov or http://www.cff.org/clinicaltrials.

Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)
Vertex initiated its CF research program in 1998 as a part of a collaboration with CFFT, the non-profit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Vertex and CFFT expanded the agreement in 2000 and again in 2004, and in March 2006, entered into a collaboration for the accelerated development of VX-770. In addition to the development collaboration for VX-770, in January 2006 Vertex and CFFT entered into an expanded research collaboration to develop novel corrector compounds. Vertex has received approximately $75 million from CFFT to support CF research and development efforts.

Pig Lungs Could Be Transplanted Into Humans by 2015

Pig Lungs Could Be Transplanted Into Humans by 2015

Tuesday, February 02, 2010

Pig lungs could be transplanted into humans following an Australian medical breakthrough bringing new hope to patients awaiting life-saving operations.

Until now pig organs have been incompatible with human blood, meaning the blood would clot almost immediately and could not pass through the lungs.

But scientists at Melbourne's St Vincent's Hospital were able to remove a section of swine DNA called the Gal gene and add human DNA to control blood clotting and rejection in humans.

They have kept pig lungs functioning with human blood, paving the way for animal-human transplants — called xenotransplantation — in as little as five years.

Dr. Glenn Westall said the discovery made in the past three months meant pig-human lung transplants were a real prospect.

"The blood went into the lungs without oxygen and came out with oxygen, which is the exact function of the lungs," he said.

"This is a significant advance compared to the experiments that have been performed over the past 20 years."

Approximately 900 lung transplants are performed each year in the United States, according to the Cystic Fibrosis Foundation.


Study of VX-770 on Midazolam and Rosiglitazone and the Effect of Fluconazole on VX-770

Study of VX-770 on Midazolam and Rosiglitazone and the Effect of Fluconazole on VX-770

Vertex Pharmaceuticals Incorporated

Information provided by:
Vertex Pharmaceuticals Incorporated

The objectives of this study are to evaluate the effects of VX-770 on Midazolam and Rosiglitazone, and the effect of Fluconazole on VX-770.

Drug: VX-770

Phase I

Study Design:
Treatment, Non-Randomized, Open Label, Uncontrolled, Crossover Assignment, Pharmacokinetics Study

Official Title:
An Open-Label Phase 1 Study to Examine the Effect of VX-770 on Midazolam and Rosiglitazone and the Effect of Fluconazole on VX-770 in Healthy Subjects

Primary Outcome Measures:
Midazolam, Rosiglitazone and VX 770 pharmacokinetic (PK) parameter [ Time Frame: 11 days ] [ Designated as safety issue: No ]

Fluconazole and VX 770 PK parameters [ Time Frame: 10 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
1´ hydroxy midazolam PK parameters in plasma [ Time Frame: 11 days ] [ Designated as safety issue: No ]

Safety as measured by adverse events, physical examinations, vital signs, ECGs, and clinically significant laboratory assessments [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

Metabolites PK parameters in plasma [ Time Frame: 21 days ] [ Designated as safety issue: No ]

Estimated Enrollment:

Study Start Date:
February 2010

Estimated Study Completion Date:
March 2010

Estimated Primary Completion Date:
March 2010 (Final data collection date for primary outcome measure)

VX-770: Experimental
Drug: VX-770

In period 1, subjects will receive a single oral dose of midazolam (2 mg) and on Day 1 and Day 8. Subjects will receive single oral dose of rosiglitazone 4 mg and on Day2 and Day 9. Subjects will receive multiple doses of VX-770 150 mg q12h Day 3-10. Drug: VX-770

In period 2, subjects will receive 150 mg VX-770 q12h orally from Day 1 through the morning of Day 8. On the morning of Period 2 Day 1, subjects will receive a 400 mg loading dose of fluconazole. Thereafter, subjects will receive 200 mg fluconazole qd orally from Day 2 through Day 9.

Ages Eligible for Study:
18 Years to 55 Years

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must be male or female and between 18 and 55 years of age.
Subjects must be judged to be in good health.
Subjects must have a body mass index (BMI) from 18 to 30 kg/m2.

Exclusion Criteria:
History of any illness that, in the opinion of the investigator or the subject's general practitioner, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject.

Subjects who have human immunodeficiency virus (HIV), hepatitis C, or active hepatitis B.
Female subjects and female partner(s) of male subjects who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last dose of study drug.
History of cardiovascular disease, hypoglycemia, or edema.

Contact: Medical Monitor

United States, Florida
Covan CRU, Inc.
Daytona Beach, Florida, United States, 32117

Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Principal Investigator:
H. Frank Farmer, MD
Covance CRU, Inc.

Tuesday, February 2, 2010

Long-term clarithromycin in cystic fibrosis

Turk J Pediatr. 2009 Sep-Oct;51(5):416-23.

Long-term clarithromycin in cystic fibrosis: effects on inflammatory markers in BAL and clinical status.

Doğru D, Dalgiç F, Kiper N, Ozçelik U, Yalçin E, Aslan AT, Gürcan N, Saricaoğlu F, Gür D, Karayazgan Y, Firat P.

Pediatric Pulmonary Medicine Unit, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Macrolides have antiinflammatory effects that are potentially useful in cystic fibrosis (CF). In this placebo-controlled, randomized, double-blind crossover study, 18 CF patients were randomized to receive either clarithromycin (CM) (Group 1) or placebo (Group 2) for three months.

After 15 days, the treatments were crossed over. Bronchoalveolar lavage (BAL) was obtained in the beginning and at the end of each treatment period. T

here was no significant difference in median cell counts and median cytokine levels at baseline, after CM use and after placebo use between the two groups.

In Group 2, the median neutrophil elastase (NE) level decreased with CM.

Patients had less acute pulmonary exacerbations and median clinical score decreased with CM in both groups. Median z-scores for weight increased with CM in Group 2.

We could not demonstrate a fall in proinflammatory cytokines in BAL; however, some improvement in clinical status could be shown with three-month CM.

CFTR gene mutation and lung cancer risk

Lung Cancer. 2010 Jan 28.

Cystic fibrosis transmembrane conductance regulator gene mutation and lung cancer risk.

Li Y, Sun Z, Wu Y, Babovic-Vuksanovic D, Li Y, Cunningham JM, Pankratz VS, Yang P.

Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.

The cystic fibrosis transmembrane conductance regulator (CFTR) holds an important role in retaining lung function, but its association with lung cancer is unclear. A case-control study was conducted to determine the possible associations of the genetic variants in the CFTR gene with lung cancer risk.

Genotypes of the most common deletion DeltaF508, one functional SNP, and eight tag SNPs in the CFTR gene were determined in 574 lung cancer patients and 679 controls. A logistic regression model, adjusting for known risk factors, was used to evaluate the association of each variant with lung cancer risk, as confirmation haplotype and sub-haplotype analyses were performed.

DeltaF508 deletion and genotypes with minor alleles in one tag SNP, rs10487372, and one functional SNP, rs213950, were inversely associated with lung cancer risk.

The results of haplotype and sub-haplotype analyses were consistent with single variant analysis, all pointing to deletion DeltaF508 being the key variant for significant haplotypes and sub-haplotypes.

Individuals with 'deletion-T' (DeltaF508/rs10487372) haplotype had a 68% reduced risk for lung cancer compared to common haplotype 'no-deletion-C' (OR=0.32; 95% CI=0.15-0.68; p=0.01).

Genetic variations in the CFTR gene might modulate the risk of lung cancer. This study, for the first time, provides evidence of a protective role of the CFTR deletion carrier in the etiology of lung cancer.

Vitamin D therapy in CF

As you may or may not know, adequate vitamin D is ESSENTIAL to calcium absorption and immune system function.

Because Vitamin D is fat soluable, many CFer's are defficient.

Do you know what your last Vitamin D test showed about your levels?

J Cyst Fibros. 2010 Jan 28.

Transient effectiveness of vitamin D(2) therapy in pediatric cystic fibrosis patients.

Green DM, Leonard AR, Paranjape SM, Rosenstein BJ, Zeitlin PL, Mogayzel PJ Jr.

Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.

BACKGROUND: The effectiveness of current treatment recommendations for vitamin D insufficiency in children with CF is unknown. Therefore, we assessed the effectiveness of vitamin D(2) 50,000IU once daily for 28days for vitamin D insufficiency.

METHODS: Retrospective chart review of pediatric CF patients from 2006-2008. Vitamin D(2) 50,000IU daily for 28days was given to patients with 25-OHD <30ng/mL and repeat 25-OHD levels were obtained after completion of therapy.

RESULTS: One hundred forty-seven levels from 97 individuals were assessed. Success of treatment was 54% (n=80/147). Seventeen of 39 patients (43%) followed for an additional 6-18months were able to maintain levels of >/=30ng/mL.

CONCLUSIONS: Vitamin D(2) 50,000IU daily for 28days was effective in correcting vitamin D insufficiency in approximately 50% of subjects. However, almost half of successfully treated patients were unable to maintain normal 25-OHD levels >6months after completion of therapy, implying that this effect is transient.

Monday, February 1, 2010

Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection

Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection

Sponsor: Gilead Sciences

The purpose of this research study is to see if an experimental drug called Aztreonam for Inhalation Solution is safe and effective to treat Burkholderia lung infections in patients with Cystic fibrosis.

Drug: Aztreonam for Inhalation solution

Study Type: Phase III

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Official Title:
Phase 3b Randomized, Double-Blind, Placebo-Controlled Two-Part Trail to Assess the Safety and Efficacy of Continuous Aztreonam for Inhalation Solution (AZLI) in Subjects With Cystic Fibrosis(CF) and Chronic Burkholderia Species Infection

Primary Outcome Measures:
Change from baseline in FEV1 percent predicted as measured by the AUCave through week 24.

Secondary Outcome Measures:
AUCave of relative change from baseline in FEV1, FVC, and FEF25 to 75 percent through week 24.

Estimated Enrollment:

Aztreonam for inhalation solution(75mg)will be administered three times a day, with at least 4 hours between doses, for up 48 hours via the PARI investigational eFlow electronic nebulizer.
lactose and sodium chloride: Placebo Comparator

Aztreonam for inhalation solution(75mg)will be administered three times a day, with at least 4 hours between doses, for up 48 hours via the PARI investigational eFlow electronic nebulizer.


Ages Eligible for Study:
6 Years and older

Inclusion Criteria:
Male or female ≥ 6 years of age

Subjects with CF as diagnosed by one of the following:
Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test
Documented sweat sodium ≥ 60 mmol/L
Two well characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
Abnormal NPD with accompanying symptoms characteristic of CF

Chronic infection with Burkholderia spp. defined by:
One sputum culture positive for Burkholderia spp. within 6 months prior to baseline assessment,
At least 50% of sputum cultures collected at least one month apart over the previous 12 months prior to baseline assessment positive for Burkholderia spp. (minimum of 2 positive cultures), and
At least one positive sputum culture (obtained at any point in time) confirmed to be Burkholderia spp. by the CFF Burkholderia cepacia Research Laboratory and Repository at the University of Michigan (or equivalent Canadian reference laboratory)

Concomitant aerosolized antibiotic treatment: subjects receiving intermittent (alternating month on/month off) aerosolized antibiotic treatment are eligible, but must be at least 1 week into their off-treatment cycle at the time of baseline assessment.

Subjects receiving continuous aerosolized antibiotic treatment will be eligible without restriction on their aerosolized antibiotic treatment

Chest radiograph, computed tomography (CT) or magnetic resonance imaging (MRI), (most recent, obtained within 90 days of screening) without significant acute findings (e.g., infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax), and no significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or atelectasis) are allowed

Subjects (and parent/guardian as required) must be able to provide written informed consent/assent prior to any study related procedures

Ability to perform reproducible pulmonary function tests

Sexually active females of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of study drug. A highly effective method of birth control is defined as a method that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), or a vasectomized partner

Exclusion Criteria:
Administration of any investigational drug or use of any investigational device within 28 days of randomization/baseline and within six half-lives of the investigational drug (whichever is longer)
Administration of AZLI treatment within the 28 days prior to randomization/baseline

Known local or systemic hypersensitivity to monobactam antibiotics

History of lung transplantation

Abnormal renal or hepatic function results at most recent test within the previous 90 days, defined as:
AST or ALT > 5 times upper limit of normal (ULN) range
Serum creatinine > 2 times ULN

Known portal hypertension or complications of CF hepatopathy

Positive urine pregnancy test (confirmed by serum pregnancy test) at screening; all women of childbearing potential will be tested

Female of childbearing potential who is lactating or not practicing a highly effective method of birth control as defined in Section 7.8

Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment or compliance with the protocol

Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01059565
Contact: Sheila Leitzinger
Contact: Jennifer Glover
jennifer.glover@gilead.com Hide Study Locations


United States, Alabama
Pulmonary Associates of Mobile, P.C.
Mobile, Alabama, United States, 36608

United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016

United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205

United States, California
University of Southern California
Los Angeles, California, United States, 90033

United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206

United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102

United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803

United States, Florida
Tampa General Hospital
Tampa, Florida, United States, 33606

University of Miami
Miami, Florida, United States, 33136
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207

United States, Illinois
The Cystic Fibrosis Institute
Glenview, Illinois, United States, 60025

United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
UMass Medical Center
Worcester, Massachusetts, United States, 01605

United States, Michigan
Harper University Hospital/Wayne State University
Detroit, Michigan, United States, 48201
University of Michigan
Ann Arbor, Michigan, United States, 48109

United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455

United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216

United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110

United States, Nevada
Childrens Lung Specialists
Las Vegas, Nevada, United States, 89107

United States, New Jersey
Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903

Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962

United States, New Mexico
Univesity of New Mexico
Albuquerque, New Mexico, United States, 87131

United States, New York
The Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040

United States, North Carolina
UNC Chapel Hill
Chapel Hill, North Carolina, United States, 27599

United States, Ohio
Children's Hospital Medical Center of Akron

Akron, Ohio, United States, 44308
Toledo Children's Hospital/The Toledo Hospital
Toledo, Ohio, United States, 43606

United States, Oklahoma
Santiago Reyes, M.D.
Oklahoma City, Oklahoma, United States, 73112

United States, Oregon
Oregon Health and Sciences University
Portland, Oregon, United States, 97239

Kaiser Permanente Northwest
Portland, Oregon, United States, 97227

United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15201
Penn State Inst & Milton S. Hershey Med Ctr
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina
Charleston, South Carolina, United States, 29425

University of South Carolinas School of Medicine
Columbia, South Carolina, United States, 29203

United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298

Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507

United States, West Virginia
Pediatric Infectious Diseases
Morgantown, West Virginia, United States, 26506

United States, Wisconsin
Medical College of Wisconsin, Children's Hospital Wisconsin
Milwaukee, Wisconsin, United States, 53201

Canada, Ontario
St Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8