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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.

Saturday, June 19, 2010

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

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

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

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

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

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

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by RTT Staff Writer

For comments and feedback: contact editorial@rttnews.com

Friday, June 18, 2010

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

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

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

The oral presentation, “Denufosol Improved Lung Function in Adolescent CF Patients” (R.B. Moss, A. Schaberg, C. Deans, W. Tian, L. Smiley, N. Herje, T. Durham, F.J. Accurso), is being presented during the session, “Workshop 5: Current Clinical Trials,” on Thursday, June 17 from 3:30 - 3:45 p.m. local time (9:30 - 9:45 a.m. ET). The presentation highlights subgroup data from the pre-specified analysis of adolescent CF patients aged 12-18 years old (n=123) from Inspire’s first Phase 3 clinical trial with denufosol, TIGER-1. In this trial, denufosol significantly improved lung function versus placebo in adolescents during the 24-week double-blind portion of TIGER-1 and continued improvement in lung function was observed with open-label treatment. The change from baseline in FEV1 (Forced Expiratory Volume in One Second) for the adolescent patients treated with denufosol at the week-24 endpoint was 112 mL compared to -10 mL for placebo (p=0.013). In comparison, in the intent-to-treat (ITT) population in TIGER-1 (n=352), the change from baseline in FEV1 at the 24-week endpoint was 48 mL for denufosol compared to 3 mL for placebo (p=0.047). The rate of decline in percent predicted FEV1 for adolescent patients receiving placebo from week 0 to week 24 during the TIGER-1 trial was significantly different from zero (p <0.001;>1 for adolescent patients receiving denufosol was not significantly different from zero (p=0.134). The change from baseline for FEF25%-75% (Forced Expiratory Flow), a measure of small airways function, for the adolescent patients treated with denufosol at the week-24 endpoint was 115 mL/sec. compared to -112 mL/sec. for placebo (p=0.036).

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

About eFlow® Technology and PARI Pharma

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

About The Cystic Fibrosis Foundation

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

About Transave, Inc.

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

Thursday, June 17, 2010

MRSA and CF survival

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

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

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

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


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

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

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

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

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

New Study in JAMA Examines Impact of MRSA on Cystic Fibrosis

New Study in JAMA Examines Impact of MRSA on Cystic Fibrosis

June 16, 2010

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

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

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

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

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

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

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

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


Monday, June 14, 2010

Home sweet home

Hey guys,

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

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

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

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

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

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

Tuesday, June 8, 2010


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

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

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

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

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

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

Take care!

Monday, June 7, 2010

Appendix surgery

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

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

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

I'll keep you posted on how things go!

Thursday, June 3, 2010

Families with a Missing Piece

As many of your know, I worry that adults in the CF community focus more on their own wants and needs when it comes to the decision of having a child (as a CF parent) as opposed to what is best for the kid.

Yes, life expectancy is increasing with CF, but still we know adults die in their 20s, 30s and 40s, well before a child with a CF parent is grown.

I have heard many times "oh we have a lot of family around who can help care for the child if I die." I think these CFer's underestimate their worth to their children - nothing replaces a parent.

I often think of Jazzy, Mels' daughter, and how she must be feeling since her mom's passing. How devistating for this poor little girl to loose her mom.... it just breaks my heart.

And no, having CF isn't the same as cancer or suddenly being hit by a car. Your chances of dying from CF are much higher than the average parent being killed by cancer or being hit by a car. CF is known, prior to pregnancy (of course if you find out later you have CF after a child is born, this doesn't pertain to you).

Here is today's article from the WSJ that I feel should be required reading for all CFer's who want to be parents... the focus on the decision needs to be all about the child.


Families With a Missing Piece
A New Look at How a Parent's Early Death Can Reverberate Decades Later


For adults who were children when their parents died, the question is hypothetical but heartbreaking: "Would you give up a year of your life to have one more day with your late mother or father?"

One in nine Americans lost a parent before they were 20 years old, and for many of them, this sort of question has been in their heads ever since.

"I'd give up a year of my life for just half a day with my parents," says Jonathan Herman, a 33-year-old health-care executive in New York. He lost both his parents to cancer before he was 13. "I've had friends complain that they have to drive to see their parents for Thanksgiving," he says. "I tell them: I'd do anything to spend Thanksgiving with my parents."

When polled, 57% of adults who lost parents during childhood shared Mr. Herman's yearnings, saying they, too, would trade a year of their lives. Their responses, part of a wide-ranging new survey, indicate that bereavement rooted in childhood often leaves emotional scars for decades, and that our society doesn't fully understand the ramifications—or offer appropriate resources. The complete survey of more than 1,000 respondents, set for release later this month, was funded by the New York Life Foundation on behalf of Comfort Zone Camp, a nonprofit provider of childhood bereavement camps.

Among the findings: 73% believe their lives would be "much better" if their parents hadn't died young; 66% said that after their loss "they felt they weren't a kid anymore."

Childhood grief is "one of society's most chronically painful yet most underestimated phenomena," says Comfort Zone founder Lynne Hughes, who lost both her parents before she was 13. She says she is worried that educators, doctors, and the clergy get little or no training to help them recognize signs of loneliness, isolation and depression in grieving children—and in adults who lost parents in childhood.

Students are often promoted from grade to grade, with new teachers never being informed that they're grieving. Adults visit physicians, speak of depression, but are never asked if a childhood loss might be a factor.

New research suggests it's time to pay closer attention. Children whose parents commit suicide, for instance, are three times as likely to commit suicide later in their lives, according to a just-released study by Johns Hopkins Children's Center in Baltimore. The study also found that those who lost parents young are more likely to be hospitalized for depression or to commit violent crimes.

In the 2009 memoir "The Kids Are All Right," four siblings from Bedford, N.Y., orphaned in the 1980s, described the risks in harrowing detail. They wrote of "growing up as lost souls," and turning to drugs and other troubling behaviors as coping mechanisms.

It's a common story. Gary Jahnke, 31, of Hastings, Minn., was 13 when his mother died of cancer. "I gave up on my good grades and dropped out of high school," he says. "I didn't do anything except drink, do drugs and be depressed. I was confused and angry, and adults didn't know how to help me. I had a good relationship with my dad, but he was also grieving." Mr. Jahnke credits his wife with helping him on his "upward climb," and says his 2-month-old daughter has given his life purpose.

Support groups, which grieving adults often find helpful, seem less beneficial to bereaved children, says Holly Wilcox, a psychiatric epidemiologist who led the Hopkins study. Children are more apt to be buoyed by engaging in normal kid activities with supportive peers, and by receiving attention from adult relatives or friends who encourage them to talk about their feelings.

At the same time, the mental-health issues of grieving kids need to be better monitored by primary-care physicians in the days, months and years after their parents die, Dr. Wilcox says.

When surveyed about how they processed their grief, adults whose parents died when they were young speak of touchstones. They were helped by looking at old videos with surviving family members, by listening to favorite music and by writing memories of their parents in journals. Some chafed at more-formal approaches; 33% said talking to therapists or school guidance counselors were the "least helpful" activities.

The early loss of a parent can make some people more resilient, responsible and independent, the research shows. But there are risks there, too. Kids who get through by being stoic and behaving like adults often "pay a fierce price—namely their childhoods," says Ms. Hughes. They focus on trying to keep their surviving parent happy or on stepping up to handle the responsibilities of their deceased parent.

Donica Salley, a 50-year-old cosmetics sales director in Richmond, Va., understands well the ramifications of losing a parent. When she was 13, her 44-year-old father drowned while on vacation in the Bahamas. "That was the onset of my depression," she says. "My mom tried to fill the void and the hurt by buying me things."

Two years ago, Ms. Salley's husband died after falling off the roof of their house while cleaning the gutters. He was also 44. Their 17-year-old son has since attended a Comfort Zone camp. "It's a safe haven for him," Ms. Salley says. "There's something about being with people who've been through it. When my father died, I didn't know anyone who'd lost a parent. I was alone."

The weekend bereavement camps, held in five states and serving 2,500 children a year, are designed "to catch kids at the beginning of their grief journeys," Ms. Hughes says. About half of the camp's 5,000 volunteers are adults who lost parents when they were young.

Christopher Blunt, an executive at New York Life and a camp volunteer, was 22 when his mom passed away. He tells of leading a "healing circle" discussion with eight campers, as they shared how their parents died—to suicide, a drug overdose, cancer.

One 10-year-old girl told the others about a day when she was 5 years old and got mad at her father. He came into her bedroom to kiss her good night, and she pretended she was asleep because she didn't want to talk to him. He died of a heart attack the next day. "She'd been carrying this story with her for five years," says Mr. Blunt, 48. "It's so powerful to see the raw emotions these kids share."

Some activists say it's vital to start helping young people even before their parents die. To that end, the Georgia-based Jack & Jill Late Stage Cancer Foundation provides free vacations to families in which one parent is terminally ill. The organization was founded by Jon and Jill Albert, shortly before Jill's 2006 death to cancer at age 45. Their children were then 11 and 13.

"When Jill passed away, people who lost parents when they were young told me it would be a 30-year impact for the kids," says Mr. Albert, 48. His organization, with the help of corporate sponsors, has sent 300 families on vacations.

"These trips allow families to build memories, and to take a lot of pictures and videos together," says Mr. Albert.

After their parents die, some of the children might find it painful to look at these last photos of them enjoying life as a family. But Mr. Herman, who lost his dad when he was 4 and his mother when he was 12, says such images can be a gift later in adulthood. For years, he resisted watching the video of his 9th birthday. But he now finds it cathartic to see his mother healthy, hugging him and calling his name.

"I haven't heard my father's voice since I was 4 years old," he says. "It doesn't exist [on tape]. It hurts not to hear him." He admits he feels a touch envious of children who lose parents today, because they have so many more digital images to hold on to.

For many who lost parents young, one particular birthday in their adult years is highly anticipated—and bittersweet. "My mom was 44 when she died. My dad was 45," says Ms. Hughes. "I just turned 46 in April, and it was a huge exhale for me. I had to live to 46 to break the curse."

Ms. Hughes, who has two young children, says she has made progress in dealing with her loss. She no longer fantasizes about giving up a year of her life for a day with her parents. "I wouldn't want to miss a year with my own kids."

Write to Jeffrey Zaslow at jeffrey.zaslow@wsj.com


Tuesday, June 1, 2010

Intravenous monthly pulse methylprednisolone treatment for ABPA in patients with cystic fibrosis

Journal of Cystic FibrosisVolume 8, Issue 4, July 2009, Pages 253-257

Intravenous monthly pulse methylprednisolone treatment for ABPA in patients with cystic fibrosis

Malena Cohen-Cymberknoha, Hannah Blaub, David Shoseyova, Meir Mei-Zahavb, Ori Efratic, Shoshana Armonia and Eitan Kerema, ,
aCF Centers of Hadassah Medical Center, Mount Scopus, Jerusalem, Israel
bSchneider Children's Medical Center, Petah Tikvah, Israel
cSheba Medical Center, Tel-Hashomer, Israel
Received 3 February 2009;
revised 7 April 2009;
accepted 16 April 2009.
Available online 15 May 2009.



Allergic bronchopulmonary aspergillosis (ABPA) in patients with CF is associated with frequent exacerbations and deterioration of lung function. Oral corticosteroids are standard therapy for ABPA and are associated with severe side effects. Monthly pulses of high-dose intravenous methylprednisolone (HDIVPM) are an effective therapy for autoimmune diseases with fewer side effects compared to oral prednisone, implicating its use for patients with CF who suffer from ABPA.

9 patients with CF and ABPA (4 male, 5 female, ages 7–36 years) received HDIVPM (10–15 mg/kg/d), for 3 days per month, and itraconazole, until clinical and laboratory resolution of ABPA.


All patients showed clinical and laboratory improvement (FEV1 increase, serum IgE levels and total eosinophil counts decrease) and treatment was discontinued after 6–10 pulses. Adverse effects were minor and disappeared shortly after each IV pulse therapy.

High-dose IV-pulse methylprednisolone is an effective treatment for ABPA in CF with minor side effects.