Cystic fibrosis patients with

P. L. Shah, S. F. Scott, and M. E. Hod son. Report on a multicentre study using aerosolised recombinant human DNase I in the treatment of cystic fibrosis patients with severe pulmonary disease. Pediatr. FuimanoL tSuppi 9]r. 157-158 (1993). 

L A. Lester, K. McCoy, L P, McKean, R. Moss, M. L, Nash, C. P. Jue, W. Reelmaan, D, C. Stokes, and H. J. Fuchs. Aeraolized recombinant human DNase in hospitalized cystic fibrosis patients with acute pulmonary exacerbations. Am. J. Respir. Crit. Care Med. 753 1914-1917 (1996). 

E J. Accurso. Aerosolised domase alfa In cystic fibrosis patients with clinically mild tuns disease. Dornase Alia Clin, Ser. 2 1-6 (1995),... 

Christopher, F. Chase, D. Stein, K. Milne, R. rhDNase therapy for the treatment of cystic fibrosis patients with mild to moderate lung disease. J. Clin. Pharm. Ther. 

The major study that stimulated interest in the development of a commercially available inhaled tobramycin product was published in 1993 [27], In this trial, 71 cystic fibrosis patients with stable pulmonary disease were enrolled in a double-blind, placebo-controlled crossover study in which tobramycin 600 mg was nebulized (ultrasonic nebulizer) three times daily. This dose was based on a preliminary study, which showed that sputum concentrations would exceed 10 times the MIC of P. aeruginosa isolates. This concentration has been shown to overcome the competitive binding of tobramycin reported in the sputum of patients with cystic fibrosis. 

Jensen T, Pedersen SS, Game S. Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother 19 831-838, 1987. 

Bosso JA, Allen JE, Matsen JM. Changing susceptibihty of Pseudomonas aeruginosa isolates from cystic fibrosis patients with the chnical use of newer antibiotics. Antimicrob Agents Chemother 1989 33 526-528. 

Wojnarowski C, Frischer T, Hofbauer E, Grabner C, MosgoeUer W, Eichler I, Ziesche R. Cytokine expression in bronchial biopsies of cystic fibrosis patients with and without acute exacerbation. Eur Respir J 1999 14 1136. 

Gilchrist FJ, Bright-Thomas RJ, Jones AM, et al. Hydrogen cyanide concentrations in the breath of adult cystic fibrosis patients with and without Pseudomonas aeruginosa infection. J Breath res. 2013 7 026010. 

Plasma Concentrations of Vitamin A, Vitamin E, -Carotene, Vitamin C, and Selenium and Activity of Glutathione Peroxidase (GSH-Px) in Red Blood Cells of Cystic Fibrosis Patients with (CF + ) and without (CF-) Chronic Inflammation... 

Madden BP, Kariyawasam H, Siddiqi AJ, et al. Noninvasive ventilation in cystic fibrosis patients with acute or chronic respiratory failure. Eur Respir J 2002 19 310-313. 

Most studies of adenoviral vector delivery to lung have been done in either normal lung or in lungs of cystic fibrosis patients with mild lutrg disease without current exacerbation. A smaller nitmber of studies have utilized airway delivery of adenoviral vectors to animals or patients with lutrg cancer (64-66). There are fewer studies on vector delivery to acutely injitred lung. Theoretically in the... 

First clinical human gene therapy trials with polyplexes were performed using cancer vaccines based on autologous patient tumor cells. These were modified ex vivo with interleukin-2 pDNA. To obtain high level transfection rates of patient s primary tumor cells, Tf-PLL/pDNA polyplexes linked with inactivated endosomolytic adenovirus particles were applied [221]. Polymer-based in vivo human gene transfer studies were performed with PEGylated PLL polyplexes, delivering CFTR pDNA to the airway epithelium of cystic fibrosis patients [222],... 

H3. Highsmith, W. E., Chong, G. L., Orr, H. T., Perry, T. R., Shaid, D., Farber, R., Wagner, K., and Thibodeau, S. N., Frequency of the delta Phe508 mutation and correlation with XV.2c/KM-19 haplotypes in an American population of cystic fibrosis patients Results of a collaborative study. Clin. Chem. (Winston-Salem, NC) 36, 1741-1746 (1990). 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Cystic fibrosis Cystic fibrosis patients have a higher incidence of side effects (eg, fever, rash) when treated with extended-spectrum penicillins (eg, piperacillin, carbenicillin). 

One should consider infiuenza- and pneumococcal-vaccination in patients with increased risk for lower RTI including patients with chronic obstructive pulmonary disease like chronic bronchitis or emphysema and cystic fibrosis patients. It should be considered for the elderly population in general. There is no role for prophylactic antibiotic therapy in patients with frequent RTI. Attempts should be made to have those patients that smoke stop doing so. 

A 16-year-old girl, a cystic fibrosis patient, is diagnosed with a ciprofloxacin-resistant Pseudomonas aeruginosa lower respiratory tract infection. 

Retention of viscous purulent secretions, which contain high concentrations of extracellular DNA—released by degenerating leukocytes that accumulate in response to infection [24]—in the airways contributes both to reduced pulmonary function and to exacerbations of infection [24,25], Digestion of DNA polymers in purulent secretion with DNAse (dornase-a or Pulmozyme) has been shown to reduce sputum viscosity in cystic fibrosis patients. The availability of recombinant DNAse has allowed its use in an aerosol formulation to deliver the enzyme into the deep lung alveoli of CF patients. The purihed glycoprotein contains 260 amino acids with an approximate molecular weight of 37,000 daltons [26], The primary amino-acid sequence is identical to that of the... 

F. Role in therapy Pulmozyme is a mucolytic enzyme used in the treatment of cystic hbrosis. Although it is not a cure, domase alfa is an effective mucolytic for adjunctive treatment. AU compliant patients with cystic fibrosis, irrespective of disease severity, who produce purulent sputum are potential candidates for Pulmozyme therapy. It is useful for liquefying the thick mucus secreted by cystic fibrosis patients, and causes both objective improvement (as measured by pulmonary function testing) and subjective symptomatic improvement. Pulmozyme reduces the frequency of respiratory infections requiring parenteral antibiotics and improves pulmonary function. 

The ease of application, the minimization of systemic side effects, and the increased drug penetration directly into the target region resulted in extensive clinical use of iontophoresis mainly in the transdermal field. This technique has been utilized for administration of local anesthetics [2-5], sweat chloride testing in cystic fibrosis patients by transcutaneous delivery of pilocarpine [6,7], administration of vidarabine to patients with herpes orolabialis [8], fluoride administration to patients with hypersensitive dentin [9,10], and gentamicin delivery for the management of burned ears [11],... 

In a 1-week study of cystic fibrosis patients treated with aerosolized native ai-PT, it was shown that Inhibitor levels reached 8 JUnol/L, which was sufficient to completely suppress NE activity in the epithelial lining fluid [69]. Such levels were reached in several patients who were rival 1.5-3 mg/kg native ai-PI every 12 boms. In the same study it was reported dial weekly intravenous doses of 120 mg/kg native ai-PI given over a time period of one month was not sufficient to suppress NE activity in epithelial lining fluid of cystic fibrosis patients. Hus study proved that ai-PI can be delivered active as an aerosol to the lung of patients and that concentration levels can be reached that are sufficient to inhibit... 

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