Puberty and prognosis of asthma and bronchial hyper-reactivity.

It is a commonly held view that pediatric asthma frequently abates during puberty. However, little data are available that associate the stage of puberty with the prognosis of asthma and bronchial hyper-reactivity (BHR). In this study, 155 children with active asthma at 10 years of age (60 girls [38.70%], 95 boys [61.3%]) were followed-up until they reached 14 years of age. The stage of puberty was assessed by parental questionnaire; in addition, serum 3-alpha-androstanediolglucuronide, as an endocrinological marker for peripheral androgen status, was measured in 107 subjects. Persistence of asthma was determined via questionnaire, lung function testing, and bronchial provocation (hyperventilation of cold, dry air). At 14 years of age, 73.3% of girls were reported to have had menarche and 40.8% of boys a voice change, and only 35.5% of the subjects had experienced acute asthma symptoms during the last 12 months, with an almost unchanged gender ratio (19 girls [34.5%], 36 boys [65.5%]) vs. that recorded at 10 years of age. The level of androstanediolglucuronide was higher in the children who reported puberty (mean+/-SD): 3.03+/-2.13 nmol/l vs. 1.89+/-1.26 nmol/l, p = 0.003. No statistically significant relationship was found between the reported signs of late puberty and loss of asthma or BHR. Likewise, no significant association was found between asthma persistence and the level of androstanediolglucuronide (2.39+/-1.75 nmol/l vs. 2.44+/-1.82 nmol/l, p = 0.84), or BHR and the level of androstanediolglucuronide (3.02+/-1.97 nmol/l vs. 2.28+/-1.67 nmol/l, p = 0.13), at 14 years of age, in girls or boys. At 14 years of age, no change in the gender ratio of children with active asthma had occurred. These results may indicate that the change in gender predominance of asthma through the second decade of life is not caused by increased loss of established asthma in boys between 10 and 14 years of age.

Adenovirus infection in cystic fibrosis patients: implications for the use of adenoviral vectors for gene transfer.

Clinical trials using replication-deficient adenovirus as vectors for gene transfer into the airways of cystic fibrosis (CF) patients are in progress. However, little is known about the prevalence of wild-type adenovirus infections in patients with cystic fibrosis and their effect on lung function. To answer these questions, serum IgG and IgM antibody titers against adenovirus type 5 were prospectively measured by an indirect immunofluorescence assay in 199 CF outpatients and in a control group of 45 healthy children and young adults. In addition, we performed pulmonary function tests when the patients were in stable clinical condition. IgM antibodies against adenovirus were present in 104 of the 199 cystic fibrosis patients (52.3%). IgG antibodies against adenovirus were detected in 192 of the 199 cystic fibrosis patients (96.5%), and were significantly higher in cystic fibrosis patients older than 7 years than in younger patients and in age matched controls. IgG antibody titers measured a second time 11.8 months later in 143 of the 199 patients had increased in 48 (33.6%) patients. In 27 of these 48 patients, who had at least a 2-fold increase in antibody titer, FVC and FEV1 decreased by 9.8% (p < 0.05) and 8.3% (p = 0.05), respectively, over 45 months. In a comparison group matched for age, sex, and chronic Pseudomonas aeruginosa infection but no increase in antibody titers, FVC and FEV1 were unchanged. The results indicate that wild-type adenovirus infections are prevalent in cystic fibrosis patients and that wild-type adenovirus infections in cystic fibrosis patients seem to be associated with deterioration in lung function. These observations may have important implications for efficacy and safety considerations when using adenoviral vectors for gene therapy.