Cystic fibrosis evaluation

McLachlan G, Davidson DJ, Stevenson BJ, et al. Evaluation in vitro and in vivo of cationic liposome-expression construct complexes for cystic fibrosis gene therapy. Gene Ther 1995 2(9) 614-622. 

A 17-year-old woman with cystic fibrosis is evaluated for knee pain. On review of systems, she also notes persistent bleeding from cuts in her skin and bleeding of her gums after brushing her teeth. Physical examination is remarkable for an obviously swollen right knee that is tender with limited range of motion. Fluid drained from the knee is bloody (hemarthrosis). Her complete blood count is normal, but prothrombin time is elevated. 

Menzin J, G. Oster, L. Davies, M. F. Drummond, W. Greiner, C. Lucioni, J. L. Merot, F. Rossi, V. D. Schulenberg, andE. Souetre. 1996. A Multinational Economic Evaluation of rhDNase in the Treatment of Cystic Fibrosis. International Journal of Technology Assessment in Health Care 12(1) 52-61. 

Newman et al. evaluated the concentration change using four different jet nebulizers, with a gentamicin solution, which is used to treat patients for cystic fibrosis. The types of nebulizers used were the Bird micronebulizer, DeVilbiss 646, Bard Inspiron mini-neb, and Medic-Aid Upmist. All were operated... 

Reed MD, Stern RC, Myers CM, Klinger JD, Yamashita TS, Blumer JL. Therapeutic evaluation of piperacillin for acute pulmonary exacerbations in cystic fibrosis. Pediatr Pulmonol 1987 3(2) 101-9. 

The role of dornase alfa in modifying bronchial secretions in patients with cystic fibrosis has been evaluated in 54 subjects aged 5 years or over (1). They were treated for 12 months with mesna by nebulizer bd and oral ambroxol (30 mg bd). Dornase alfa was then given once daily by aerosol 2.5 mg for 12 months. Mesna and ambroxol caused reductions in FEVi nd FVC (FEVi feu by 11%, FVC by 13%). After 12 months of dornase aUa, FEVi had increased by 7.7% and FVC by 5.3%. The patients found treatment with dornase alfa more acceptable than mucoljdic therapy. Hemoptysis was the only reported adverse effect, but it occurred frequently in only one patient. 

Moss RB, McClelland E, Williams RR, Hilman BC, Rubio T, Adkinson NF. Evaluation of the immunologic cross-reactivity of aztreonam in patients with cystic fibrosis who are allergic to penicillin and/or cephalosporin antibiotics. Rev Infect Dis 1991 13(Suppl 7) S598-607. 

Hammond KB, Turcios NL, Gibson LE. Clinical evaluation of the macroduct sweat collection system and conductivity analyzer in the diagnosis of cystic fibrosis. J Pediatr 1994 124 255-60. 

Fecal elastase-1 has been extensively evaluated both in cystic fibrosis and in adult pancreatic insufficiency. In children with cystic fibrosis, the test discriminates between those with and without pancreatic insufficiency. Very low elastase-1 is seen in a wide range of CFTR genotypes with undetectable enzyme (<15 pg/g of stool) in most AF508 homozygotes. Low fecal elastase (<200 pg/g) after 4... 

Cade A, Walters MP, McGinley N, Firth J, Brownlee KG, Conway SP, Littlewood JM. Evaluation of fecal pancreatic elastase-1 as a measure of pancreatic exocrine function in children with cystic fibrosis. Pediatr Puhnonol 2000 29 172-6. 

A number of antibiotics have been used as aerosol therapies. Examples include beta lactam agents, polymycin antimicrobials, neomycin, gentamicin, and tobramycin. Many of the early efforts were reported as case studies, and observations and data regarding safety and efficacy were lacking. Controlled clinical trials were not conducted until the middle of the 1980s. More recent evaluations have focused on the role of inhaled tobramycin used as suppressive therapy for cystic fibrosis patients colonized with Pseudomonas aeruginosa. 

These trials evaluated different therapies and utilized several differences in study design, making comparisons difficult. Additionally, the goals of therapy and the endpoints that were measured differed significantly. Controlled studies evaluating the use of inhaled antibiotics began to appear in the 1980s. These studies addressed primarily their use as suppressive therapy, and many were performed in patients with cystic fibrosis. 

Colistin has been evaluated as suppressive therapy in patients with cystic fibrosis. In an uncontrolled case series, the use of colistin inhaled twice daily... 

These findings prompted the development and evaluation of the currently available form of inhaled tobramycin, which is sterile and free of preservatives. The benefit of maintenance therapy with this inhaled tobramycin is supported by the results from two 24-week, multicenter, randomized, double blind, placebo-controlled clinical trials [6]. In these studies, patients with cystic fibrosis were at least six years of age, with an FEVj between 25% and 75% predicted. All subjects had evidence of colonization with Pseudomonas aeruginosa. Exclusion criteria included an elevated serum creatinine or colonization with Burkholderia cepacia, which is typically resistant to tobramycin. Subjects in the active treatment arm received inhaled tobramycin 300 mg twice daily through... 

Some progress has been made in developing alternative devices for the delivery of inhaled antimicrobial therapies. Colistin has been formulated in a dry powder inhaler and evaluated in healthy individuals and patients with cystic fibrosis [40]. Peak semm concentrations of colistin were 2.5-5 times higher when 25 mg of colistin sulfate dry powder was inhaled compared to 160 mg of colistin sulfomethate delivered by nebulization. Some patients experienced a decrease in pulmonary function and severe cough with the dry powder however, the investigators felt that this may be improved with a reduction in dose. 

Yei S, Mittereder N, Wert S, Whitsett JA, Wilmott RW, Trapnell BC. In vivo evaluation of the safety of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator cDNA to the lung. Hum Gene Ther 1994, 5, 731-744. 

Yei S, Mittereder N, Tang K, O Sullivan C, Trapnell BC. Adenovirus-mediated gene transfer for cystic fibrosis quantitative evaluation of repeated in vivo vector administration to the lung. Gene Ther 1994, 1, 192-200. 

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