Jay D. Eisenberg

Efficacy of aerosolized tobramycin in patients with cystic fibrosis.

BACKGROUND Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function, with low systemic toxicity. We conducted a randomized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections. METHODS Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and randomly assigned to one of two crossover regimens. Group 1 received 600 mg of aerosolized tobramycin for 28 days, followed by half-strength physiologic saline (placebo) for two 28-day period. Group 2 received placebo for 28 days, followed by tobramycin for two 28-day periods. Pulmonary function, the density of P. aeruginosa in sputum, ototoxicity, nephrotoxicity, and the emergence of tobramycin-resistant P. aeruginosa were monitored. RESULTS In the first 28-day period, treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second (9.7 percentage points higher than the value for placebo; P < 0.001), forced vital capacity (6.2 percentage points higher than the value for placebo; P = 0.014), and forced expiratory flow at the midportion of the vital capacity (13.0 percentage points higher than the value for placebo; P < 0.001). A decrease in the density of P. aeruginosa in sputum by a factor of 100 (P < 0.001) was found during all periods of tobramycin administration. Neither ototoxicity nor nephrotoxicity was detected. The frequency of the emergence of tobramycin-resistant bacteria was similar during both tobramycin and placebo administration. CONCLUSIONS The short-term aerosol administration of a high dose of tobramycin in patients with clinically stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa.

Immunogenicity of a new purified fusion protein vaccine to respiratory syncytial virus: A multi-center trial in children with cystic fibrosis

A third generation, purified fusion protein (PFP-3) vaccine was developed to prevent severe respiratory syncytial virus (RSV) disease in high-risk groups. A phase II, multi-center, adjuvant-controlled trial was performed in RSV seropositive children with cystic fibrosis (CF); 151 received the adjuvant-control and 143 received the vaccine. Details of the vaccine-induced immune response are presented. At enrollment, RSV-specific, serum antibodies were comparable between both groups. A highly sensitive and specific serum antibody vaccine profile was established for the PFP-3 vaccine. At post-vaccination and end-of-study, RSV-specific, neutralizing antibody (Nt Ab) and binding antibody (Bd Ab) to the fusion (F) protein were significantly higher in PFP-3 vaccinees. After 28 days post-vaccination, Nt Ab and Bd Ab to F protein titers declined slowly at rates of 0.23 and 0.37 log2 per month, respectively. The PFP-3 vaccine-induced a robust immune response that lasted throughout the RSV season.

Long-term follow-up of a cohort of children with alpha-1-antitrypsin deficiency

We assessed lung function, liver function, and smoking attitudes and behavior in 22 adolescents with homozygous alpha 1-antitrypsin deficiency whose condition had been detected through neonatal screening in the early 1970s. All subjects had normal lung volumes, expiratory flow rates, and diffusing capacity except for two siblings with mild asthma whose values reverted to the normal range after administration of an inhaled bronchodilator. Liver function was normal in all subjects with the exception of one boy who had an isolated elevation of alkaline phosphatase activity. Smoking attitudes, as determined by questionnaire, did not differ from those of 130 control subjects, but smoking initiation rates were significantly lower (p = 0.02). We believe that the issue of neonatal screening for alpha 1-antitrypsin deficiency should be reexamined because augmentation therapy for adults with emphysema is now available, and screening followed by family-based smoking intervention may lead to a nonsmoking life-style. The latter is especially important because the current weight of epidemiologic evidence strongly suggests that in nonsmokers with this condition, severe emphysema may never develop or, if it does, it will do so at a much later age than in smokers.

A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency

A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency

Safety of repeated intermittent courses of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis

OBJECTIVES To determine the effect of repeated doses of aerosolized recombinant human deoxyribonuclease (rhDNase) on the development of anti-rhDNase antibodies, acute allergic reactions, and pulmonary function in patients with cystic fibrosis. DESIGN A multicenter, open-label study in which 184 patients received 10 mg aerosolized rhDNase twice a day for 14 days followed by a 14-day washout period for a total of 6 treatment cycles. Serial determinations of anti-rhDNase antibodies and pulmonary functions were performed. RESULTS Detectable anti-rhDNase antibodies developed in 16 (8.7%) patients. These patients had no changes in their symptoms from the time they entered the trial. Antibodies detected were all of the IgG isotype. Increases in both forced expired volume in 1 second and forced vital capacity were noted from the beginning to the end of each cycle of treatment returning to baseline during the off-treatment period of each cycle. Seropositivity to rhDNase was not associated with allergic reactions and had no relationship on improvement in pulmonary function. CONCLUSIONS Development of anti-rhDNase antibodies occurred in a small number of patients and was not associated with side effects. Intermittent administration of rhDNase for 24 weeks to patients with cystic fibrosis was well tolerated and was not associated with anaphylaxis in any patient. Pulmonary function improved significantly during the 14-day cycles while rhDNase was administered and returned to baseline when rhDNase was discontinued.

Implementation of “Open Airways” as an educational intervention for children with asthma in an HMO

This article describes the adaptation and implementation of an existing pediatric asthma-management educational program, Open Airways, for members of a large group practice health maintenance organization. Seventy-four children ages 4 to 14 years and their families were randomized into one of seven class cohorts as part of a larger study of pediatric asthma management. The Open Airways program was modified to increase the emphasis on behavioral change and medication information and to reflect the different sociodemographic makeup of the population, compared with that for which the program was developed. Of the 74 families, 62 attended at least one class, and 47 of these attended five or more classes. Evaluations after classes suggest an increase in parental confidence in managing their childs asthma and an earlier use of medications. Health care providers may be able to adapt similar programs for successful use with their populations.