Info from the Internet

Information from the Internet…

Compiled By Laura Tillman

This issue brings a potpourri of articles from the Internet


Lung Transplantation for Cystic Fibrosis: Ten Years of Experience. M.T. Aratari, F. Venuta, T. De Giacomo, E.A. Rendina, M. Anile, D. Diso, F. Francioni, S. Quattrucci, M. Rolla, F. Pugliese, V. Liparulo, M. Di Stasio, C. Ricella, S. Tsagkaropoulos, G. Ferretti and G.F. Coloni. Transplantation Proceedings. Volume 40, Issue 6, July-August 2008, Pages 2001-2002

Lung transplantation represents the only therapeutic option for patients affected by end-stage cystic fibrosis (CF). We performed 76 lung transplantations in 73 patients from 1996-2007. The mean time on the waiting list was 10 ± 6 months. The median follow-up after the transplantation was 69.3 months. Twenty-one transplants (27.6%) were performed under cardiopulmonary bypass. Perioperative mortality, excluding retransplants, was 16.4% (12 patients) and the causes of death were sepsis, primary graft failure, and myocardial infarction. The overall survival was 74.5% ± 5%, 62.9% ± 5%, 54.1% ± 6%, and 43.4% ± 6% at 1, 3, 5, and 10 years, respectively. The accurate selection of potential recipients and the correct timing of referral and transplantation are factors that play crucial roles to obtain satisfactory results in term of improvement of quality of life and long-term survival.

Should lung transplant recipients routinely perform airway clearance techniques? A randomized trial. Prue E. MUNRO, Brenda M. BUTTON, Michael BAILEY, Helen WHITFORD, Samantha J. ELLIS AND Gregory I. SNELL. Respirology Published Online: 20 Aug 2008 Despite the widespread use of airway clearance (AC) techniques to clear excessive secretions and improve lung function, little is known about their efficacy following lung transplantation (LTx). This study compared the effects of two AC strategies (proactive vs reactive) on a range of clinical outcomes following LTx. A prospective randomized trial was conducted. Uncompli­cated patients were recruited 1 month postoperatively.

Patients performed AC using positive expiratory pressure either twice daily (proactive strategy) or only in the presence of chest infection (reactive strategy). Lung function (FEV1 and FVC), CXR (Brasfield score) and bronchoscopic airway characteristics (anastomotic healing, patency and secretions) were assessed at 1, 2 and 3 months postoperatively. Adherence was measured. No significant differences for any outcome were found between the two groups. The vast majority of patients had fully healed, 100% patent anastomoses without secretions at 3 months. There were no significant differences between the two groups in airway characteristics and the incidence of chest infection. Adherence to both strategies was high (84% proactive, 100% reactive). Proactive AC following lung transplantation was not associated with a reduced incidence of respiratory infection, alteration of CXR findings or improvement in airway characteristics.

Clostridium difficile colitis in cystic fibrosis patients with and without lung transplantation. C. Theunissen, C. Knoop, C. Nonhoff, B. Byl, M. Claus, C. Liesnard, M.J. Estenne, M.J. Struelens, F. Jacobs. Transpl Infect Dis 2008: 10: 240-244.

Despite a large carriage rate of Clostridium difficile among cystic fibrosis (CF) patients, C. difficile associated disease (CDAD) is rather rare. CF patients who undergo lung transplantation are at a higher risk of developing CDAD and seem to present more often atypical and/or complicated disease. CDAD should be part of the differential diagnosis in case of digestive symptoms, even in the absence of diarrhea, and requires early treatment.

Impact of Burkholderia Infection on Lung Transplantation in Cystic Fibrosis. Susan Murray, Jeffery Charbeneau, Bruce C. Marshall, and John J. LiPuma. Am. J. Respir. Crit. Care Med. 2008 Transplant candidates infected with different Burkholderia species did not have statistically different mortality rates. Among transplant recipients infected with B. cenocepacia, only those infected with non-epidemic strains had significantly greater post-transplant mortality compared to uninfected patients. Hazards were similar between uninfected transplant recipients and those infected with B. multivorans. Transplant recipients infected with B. gladioli had significantly greater post-transplant mortality than uninfected patients. Once hazards for species/strain were included, lung allocation scores of B. multivorans-infected transplant candidates were comparable to uninfected candidate scores, while those of candidates infected with non-epidemic B. cenocepacia or B. gladioli were lower. Post-transplant mortality among CF patients infected with Burkholderia varies by infecting species. This variability should be taken into account in evaluating lung transplantation candidates.


Transave Announces Positive Phase II Results for Once-Daily Arikace(TM) in the Treatment of Cystic Fibrosis Patients Who Have Pseudomonas Lung Infections. Transave, Inc., reported positive results from a Phase II clinical trial on its lead investigational drug, Arikace (TM) (liposomal amikacin for inhalation). The compound is being developed for the treatment of cystic fibrosis (CF) patients who have lung infections due to the bacterium Pseudomonas aeruginosa. The Phase II data indicated that Arikace, delivered once daily for 28 consecutive days, produced a significant improvement in lung function, was well-tolerated, and had a side-effect profile comparable to placebo. The Phase II trial was a randomized, double-blind, placebo-controlled study of 64 patients from 15 centers in Europe. Arikace is a novel molecular entity comprised of the antibiotic amikacin, which is enclosed in nanocapsules of lipids called liposomes. Arikace was administered once daily for 28 days at 280 mg and 560 mg dosages, using a novel inhalation device, the eFlow® Electronic Nebulizer (PARI Pharma GmbH). The intent-to-treat analysis for efficacy demonstrated that Arikace, when administered once daily either at 280 mg or 560 mg for 28 days, resulted in clinically significant improvement in lung function at the end of treatment. This improvement was dose-dependent and was sustained at 28 days after completion of dosing, which was day 56 of the study. Pulmonary function (FEV1) increased significantly among patients receiving the 560 mg dose of Arikace. Arikace was well tolerated, with no differences observed in the overall rates of adverse events or drug-related adverse events between groups. Fewer serious adverse events, pulmonary exacerbations, and hospitalizations were observed in patients receiving Arikace compared to placebo. Additionally, the time to receiving anti-pseudomonal rescue treatment was prolonged for the patients in the Arikace arm, as compared to those in the placebo arm, which further confirms the clinical benefit of Arikace. 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.

Altus Pharmaceuticals Announces Achievement of Primary Endpoint in Phase 3 Efficacy Trial of Trizytek for Cystic Fibrosis Patients with Pancreatic Insufficiency. Altus Pharmaceuticals Inc. announced today that its Phase 3 efficacy trial of Trizytek(TM) (porcine-free enzymes) in patients with cystic fibrosis (CF) successfully met its primary endpoint of improvement in fat absorption. The Company released top-line results from its 163 patient, double-blind, placebo-controlled trial of Trizytek, an enzyme replacement therapy for patients with pancreatic insufficiency. Trizytek is a stable and pure combination of three active enzymes in a fixed-ratio that is designed to improve fat, protein and carbohydrate absorption in pancreatic insufficient individuals. The trial met its primary efficacy endpoint with statistical significance. In cystic fibrosis patients with exocrine pancreatic insufficiency, Trizytek demonstrated a statistically significant improvement of fat absorption over placebo through the measurement of the coefficient of fat absorption (CFA). Patients treated with Trizytek had a statistically significant improvement in CFA compared to placebo. Trizytek has the potential to be the first porcine-free enzyme replacement therapy for patients with pancreatic insufficiency. Trizytek is intended to replace missing digestive enzymes with one capsule per-meal to promote and maintain proper digestion and growth in affected patients. Altus is developing Trizytek to enhance health outcomes by offering significant patient advantages such as improved and more consistent dosing that we expect will drive better long-term compliance. Utilizing recombinant technology, Trizytek is manufactured by blending three drug substance enzymes: lipase, protease and amylase. This consistent and pure enzyme combination is designed to improve fat, protein and carbohydrate absorption in pancreatic insufficient individuals.


Inhaled Mannitol Improves Lung Function in Cystic Fibrosis. Anna Jaques, BSc, MPH; Evangelia Daviskas, MBiomedE, PhD; James A. Turton, BSc (Hons), MBBS, MMedSc; Karen McKay, PhD; Peter Cooper, BSc, MB ChB; Robert G. Stirling, MB BCh (Hons); Colin F. Robertson, MD; Peter T. P. Bye, MBBS, PhD, FCCP; Peter N. LeSouëf, MD; Bruce Shadbolt, PhD; Sandra D. Anderson, PhD, DSc and Brett Charlton, MBBS, PhD. Chest. 2008; 133:1388-1396
The airways in patients with cystic fibrosis (CF) are characterized by the accumulation of tenacious, dehydrated mucus that is a precursor for chronic infection, inflammation, and tissue destruction. The clearance of mucus is an integral component of daily therapy. Inhaled mannitol is an osmotic agent that increases the water content of the airway surface liquid, and improves the clearance of mucus with the potential to improve lung function and respiratory health. To this end, this study examined the efficacy and safety of therapy with inhaled mannitol over a 2-week period. Mannitol treatment increased FEV1 from baseline by a mean of 7.0%. Inhaled mannitol treatment over a period of 2 weeks significantly improved lung function in patients with CF. Mannitol therapy was safe and well tolerated.

Good effect of IgY against Pseudo­monas aeruginosa infections in cystic fibrosis patients. Elin Nilsson, MSc, Anders Larsson, MD, Hanne V. Olesen, MD, Per-Erik Wejåker, MSc, Hans Kollberg, MD. Pediatr Pulmonol. 2008; 43:892-899
This is an extended open study of oral prophylactic treatment with egg yolk antibodies against Pseudomonas aeruginosa, Anti-Pseudomonas IgY, of 17 Swedish patients with cystic fibrosis. They have been on prophylactic IgY treatment for up to 12 years and altogether for 114 patient years. A group of 23 Danish CF patients served as control. There has been a total absence of adverse events. Only 29 cultures have been positive for P. aeruginosa (cultures after chronic colonization not included), that is, 2.3/100 treatment months compared to 7.0/100 months in the control group (P = 0.028). In the IgY treated group only one pair of siblings (2/17) has been chronically colonized with P. aeruginosa compared to seven patients (7/23) in the control group. Atypical mycobacteria, S. maltophilia, A. xylosoxidans, and A. fumigatus have appeared only sporadically. There have been no cultures positive for B. cepacia. There was no decrease in pulmonary functions (P = 0.730) within the IgY group. Body mass index values were normal or close to normal for all IgY treated patients. In conclusion, Anti-Pseudomonas IgY has great potential to prevent P. aeruginosa infections.

Once-weekly azithromycin in cystic fibrosis with chronic Pseudomonas aeruginosa infection. Steinkamp G, Schmitt-Grohe S, Döring G, Staab D, Pfründer D, Beck G, Schubert R, Zielen S. Respir Med. 2008 Aug 11.
Data on the effects of long-term treatment with azithromycin (AZM) on inflammatory markers in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa are scarce. So far there is no pharmacokinetic and clinical data on once-weekly dosage of AZM in CF patients. In a randomised doubleblind, placebo-controlled trial, patients received AZM or placebo 1 per week for 8 weeks (AZM dosage – 20-29kg: 500 mg, 30-39kg: 750 mg, 40-49kg: 1000 mg and >/=50kg: 1250 mg) after a course of intravenous antipseudomonal antibiotics. Pulmonary function tests, the serum markers LPS-binding protein (LBP), interleukin-8 (IL-8), CRP, P. aeruginosa alginate in sputum samples and quality of life scores were evaluated. Once-weekly azithromycin ameliorated inflammatory reactions and improved quality of life. A decline of pulmonary function after cessation of IV antibiotics could not be prevented.

Improvement in clinical markers in CF patients using a reduced glutathione regimen: An uncontrolled, observational study. Alfredo Visca, Clark T. Bishop, Sterling C. Hilton and Valerie M. Hudson. Journal of Cystic Fibrosis. Article in Press
CFTR mutation, which causes cystic fibrosis (CF), has also recently been identified as causing glutathione system dysfunction and systemic deficiency of reduced glutathione (GSH). Such dysfunction and deficiency regarding GSH may contribute to the pathophysiology of CF. We followed 13 patients (age range 1–27 years) with cystic fibrosis who were using a regimen of reduced glutathione (GSH), including oral glutathione and inhaled buffered glutathione in an uncontrolled, observational study. Dosage ranged from 66–148 mg/kg/day in divided doses, and the term examined was the initial 5.5 months of GSH use (45 days of incrementally adjusted dose, plus 4 months of use at full dosage). Baseline and post-measurements of FEV1 percent predicted, BMI percentile, and weight percentile were noted, in addition to bacterial status and pulmonary exacerbations. Significant improvement in the following clinical parameters was observed: average improvement in FEV1 percent predicted (N = 10) was 5.8 percentage points (p < 0.0001), average weight percentile (N = 13) increased 8.6 points (p < 0.001), BMI percentile (N = 11) improved on average 1.22 points (p < 0.001). All patients improved in FEV1 and BMI, if measured in their case; 12 of 13 patients improved in weight percentile. Positive sputum cultures of bacteria in 11 patients declined from 13 to 5 (p < 0.03) with sputum cultures of Pseudomonas aeruginosa becoming negative in 4 of 5 patients previously culturing PA, including two of three patients chronically infected with PA as determined by antibody status. Use of a daily GSH regimen appears to be associated in CF patients with significant improvement in lung function and weight, and a significant decline in bacteria cultured in this uncontrolled study. These findings bear further clinical investigation in larger, randomized, controlled studies.

Laura Tillman has CF. She is a Director of USACFA and is the President. Her email is: