Comparison of immunogenicity and safety of a virosome influenza vaccine with those of a subunit influenza vaccine in pediatric patients with cystic fibrosis.

The objective of this study was to compare the immunogenicity and safety of a single-dose regimen and a two-dose regimen of a trivalent virosome influenza vaccine (Inflexal Berna V) with those of a trivalent subunit influenza vaccine (Influvac) in children and adolescents with cystic fibrosis (CF). In an open, randomized, multicenter study with parallel groups, 11 young children with CF (1 to 6 years old) and 53 older children and adolescents with CF (>6 years old) were randomly assigned to one of the following immunization regimens: virosome vaccine at 0.5 ml on study day 0 or 0.25 ml on days 0 and 28 or a standard regimen of subunit vaccine, i. e., 0.5 ml on day 0 for older children and 0.25 ml on days 0 and 28 for younger children. Safety assessments, i.e., recording of systemic and local adverse events (AEs) and vital signs, were made for a 5-day observation period after each immunization. Hemagglutination inhibition (HI) titers were determined at baseline and 4 weeks after the single-dose and the two-dose immunizations, respectively. Immunogenicity was assessed according to the criteria of the European Agency for the Evaluation of Medicinal Products (EMEA). Both vaccines induced comparable HI antibody titers. Seroconversion (> or =4-fold rise in HI antibody titers, reaching a titer of > or =1:40) was achieved in 41 to 100% of the participants. Seroprotection (HI titer, > or =1:40) and a >2.5-fold increase in geometric mean titers were achieved in 100% of the participants. Thus, all three EMEA requirements for influenza vaccine efficacy were met by all treatment groups and for both vaccines. The virosome vaccine, when administered as a single dose, seemed to induce superior immunogenicity compared with the standard pediatric two-dose regimen. Totals of 42 and 57% of vaccinees receiving virosome and subunit vaccines, respectively, reported at least one local AE (predominantly pain). Totals of 84 and 71% of subjects receiving virosome and subunit vaccines, respectively, complained in response to questions of at least one systemic AE (mainly cough, fatigue, coryza, or headache). The majority of events were mild or moderate and lasted 1 or 2 days only. No obvious relationship was found between AE reporting rate and vaccine formulation, age group, or dose regimen. The relatively high AE reporting rate seemed to be partly related to the symptomatology of the underlying CF disease. In summary, the virosome and subunit vaccines induced in both age groups and against all three influenza strains an efficient immune response and were well tolerated by the children and adolescents with CF.

Ciprofloxacin as antipseudomonal treatment in patients with cystic fibrosis.

OBJECTIVE: The efficacy and safety of oral ciprofloxacin as a maintenance antipseudomonal therapy were evaluated in 44 patients with cystic fibrosis who had completed a 14-day regimen of intensive hospital therapy with intravenous ceftazidime and amikacin, supplemented by amikacin inhalation therapy. METHODS: Twenty-one patients were randomly assigned to oral ciprofloxacin alone (Group I) and 23 received ciprofloxacin plus inhaled amikacin (Group II). RESULTS: Negative sputum cultures were achieved in 34 patients (77%) at the end of intensive therapy (19 Group I and 15 Group II) and were sustained after 3 months of maintenance therapy in 5 of the 19 responders in Group I (26%) and in 8 of the 15 responders in Group II (53%). Resistance to ciprofloxacin was found in 7 of 31 (23%) sputum isolates at the end of ciprofloxacin therapy. During maintenance therapy, continued improvement in clinical symptoms was observed in 14 patients in both treatment groups; 6 in each group had further improvements whereas only 4 patients were clinical failures. There was no correlation between clinical outcome and either elimination of Pseudomonas aeruginosa from sputum culture or development of ciprofloxacin resistance. Both maintenance regimens were well-tolerated by this population of patients which included 28 children younger than 15 years of age. There were no severe or serious adverse events, no signs of quinolone-related arthropathy and no growth impairment. CONCLUSION: Ciprofloxacin was efficacious, safe and well-tolerated as maintenance antipseudomonal therapy in cystic fibrosis patients. These results suggest further evaluation of ciprofloxacin as an oral maintenance therapy is warranted.

Immunization of noncolonized cystic fibrosis patients against Pseudomonas aeruginosa.

The long-term safety and immunogenicity of a polyvalent Pseudomonas aeruginosa conjugate vaccine was evaluated in 30 noncolonized cystic fibrosis patients. Four doses were administered over 3 years, and patients were followed for a mean of 38 months. No acute or long-term adverse effects were noted. Immunization engendered a significant antibody response to all vaccine components. A decline in titers during year 3 of observation was associated with a marked rise in the isolation of P. aeruginosa. This organism was isolated repeatedly from the respiratory tract of 4 patients and only once from 7 patients. The remaining patients were repeatedly culture-negative. Only 1 patient showed clinical deterioration associated with multiple isolations of P. aeruginosa.

Genotype/phenotype association in cystic fibrosis: analyses of the delta F508, R553X, and 3905insT mutations.

A striking clinical phenomenon of cystic fibrosis is the heterogeneous disease expression. It must therefore be assumed that the nature of the mutations associated with cystic fibrosis might partly determine the phenotypic manifestations. The relation between the cystic fibrosis mutations delta F508, R553X, and 3905insT and clinical parameters such as sweat test electrolytes, age at chronic Pseudomonas aeruginosa colonization, Chrispin-Norman x-ray scores, and relative underweight have been investigated in 45 patients homozygous for delta F508 (delta F2), in 12 compound heterozygotes for delta F508/R553X (delta F1/RX1), in three R553X homozygotes (RX2), and in 13 patients compound heterozygous for delta F508/3905insT (delta F16). We have found significant differences between the genetically defined subgroups concerning the mean age at onset and the cumulative incidence of chronic P. aeruginosa colonization and Chrispin-Norman x-ray scores. The significant results as well as some trends regarding the relative underweight demonstrate a milder clinical course in R553X heterozygotes and more severe disease in the delta F16 group compared to delta F508 homozygotes. The three patients homozygous for R553X presented with a two-stage course showing mild progression before P. aeruginosa infection and as severe a course as the delta F16 patients after P. aeruginosa colonization at the age of 12 y. The findings presented here indicate that specific mutations can influence the severity and progression of the disease, implicating the importance of mutation and haplotype analyses. However, wide variations within the genetically homogeneous subgroups illustrate that other determinants of the clinical status do exist.

Safety and immunogenicity of Pseudomonas aeruginosa conjugate A vaccine in cystic fibrosis.

To assess the safety and immunogenicity of a Pseudomonas aeruginosa octavalent O-polysaccharide-toxin A conjugate vaccine, 22 patients (mean age 7 years) with cystic fibrosis who had no history of colonisation with P aeruginosa were immunised with the vaccine. Adverse reactions were mild and self-limiting. IgG antibody concentrations to all vaccine antigens were significantly raised after vaccination and remained so for 12 months. Immunisation produced opsonic and toxin A neutralising antibodies. A booster dose given at 12 months led to an anamnestic response. There was no significant change in clinical status after vaccination. Further work to assess efficacy in patients with cystic fibrosis can now be considered since our findings support the safety and immunogenicity of the vaccine.

Endocrinological disorders in shunted hydrocephalus.

Endocrinological findings were identified in 60% of 90 shunted patients with an isolated hydrocephalus, namely dwarfism in one third and abnormal proportions, obesity, sexual precocity and various combinations in 9-15%. Different causes of these findings were observed. But none of the cases had a malfunction of the shunt at the time of this study.

Long-term cimetidine in children with cystic fibrosis: a randomized double-blind study.

A prospective, randomized double-blind study of 38 children with cystic fibrosis (CF) was designed to evaluate the effectiveness of cimetidine in improving fat absorption and clinical condition. The treatment consisted of cimetidine or placebo, 600 mg/m2 body surface/day, over a 4-mo period. Clinical state, weight, height, skinfold thickness, lung function tests, para-aminobenzoic acid (PABA) peptide test, and plasma lipid and lipoprotein determinations were performed before and after the treatment period. Compared with age-matched healthy children, patients showed decreased cholesterol (150.2 +/- 31.2 mg/dl, mean +/- SD), decreased high density lipoprotein cholesterol (44.1 +/- 11.8 mg/dl), and decreased low density lipoprotein cholesterol (84.1 +/- 25.5 mg/dl) whereas the triglycerides and the very low density lipoprotein triglycerides were slightly elevated (118.2 +/- 33.0 mg/dl and 60.5 +/- 17.5 mg/dl, respectively). Apoprotein B and AI were slightly reduced and Apoprotein AII was in the normal range. After the 4-mo treatment no significant change in clinical condition, weight, or lipoprotein patterns could be detected between the two groups. The total PABA recovery in urine also did not change significantly (36.6 +/- 19.4% of the dosage given before versus 28.7 +/- 12.9% after 4 mo in the cimetidine group). Cimetidine gave rise to bronchoconstriction as shown by an increase in airway resistance (mean increase 14.8%) whereas the placebo group had a decreased Raw with a mean of 8.3%. Patients with CF have a dyslipoproteinemia that was not influenced by cimetidine. We conclude that cimetidine does not improve fat absorption and has, therefore, no place and no benefit in the treatment of children with CF.