The duration and magnitude of the effect of inhaled formoterol (12 micrograms) against exercise-induced bronchoconstriction (EIB) was compared with that of inhaled salbutamol (200 micrograms) and that of placebo in 15 children with asthma and EIB in a double-blind, double-dummy, within-patient, placebo-controlled study. The treatments were given by metered dose aerosol on three different days. The exercise test was performed at the 3rd and the 12th hour after dosing. The magnitude of the blocking effect was assessed both by evaluating the lowest FEV1 reading obtained within an hour after each exercise test and by considering the percent decrease below the baseline FEV1 measured before drug administration. Comparison of the lowest values obtained during the hour after each exercise test shows that formoterol was significantly better than both salbutamol (p = 0.022), and placebo (p = 0.001) in limiting exercise-induced bronchoconstriction after the first exercise test (3 h after dosing), while no difference was observed between salbutamol and placebo (p = 0.198). After the second exercise test (12 h after dosing), formoterol again proved to be more effective than both salbutamol (p = 0.008) and placebo (p = 0.001), and no significant difference was observed between salbutamol and placebo (p = 0.391). The evaluation of the mean percentage decrease in FEV1 confirmed the results in favor of formoterol in both the exercise tests. No adverse effects were reported in any treatment group. The protection against EIB is significantly more prolonged after formoterol than after salbutamol, and persists for 12 h after dosing.

Changes of diurnal variation of peak expiratory flow rate (%PEF variation) and their relationship with bronchial hyperresponsiveness (BHR) to methacholine (PC20) were evaluated in 12 children with mild-to-moderate asthma and house-dust mite allergy, during successive periods of stay in a mite-free environment at high altitude (1756 m) and at their home at sea level. The children remained at the high altitude from October until the end of December; then they spent a 3-week period at home and returned to high altitude residence in January. PEF was measured daily, in the morning and in the evening, during the 3 months' stay at high altitude and them for 10 days after the return in January. PC20 was assessed in 8/12 children, once a month from October to December, and at the return in January. Mean absolute PEF values did not change significantly throughout the study. From October to December, patients showed a significant decrease of mean %PEF variation (P = 0.04), while PC20 showed an increase (P = 0.05). After the 3 weeks at home, both %PEF variation (P = 0.03) and PC20 (P = 0.05) significantly worsened. The correlation between PC20 values and mean %PEF variation in the 2 days before and after each methacholine test was r = -0.63 (P = 0.001). Our data suggest that there is a beneficial effect of a prolonged stay in a mite-free environment, on both PEF variability and BHR, also in asthmatic children with good pulmonary function. PEF variability and bronchial responsiveness to methacholine were significantly correlated also for small changes of the two variables.

To determine the reproducibility of the delayed response to exercise and its effect on bronchial hyperreactivity, we had 26 asthmatic children perform treadmill exercise challenge on two occasions 1 week apart. Both challenges were preceded by 2 control days and 1 histamine challenge day, and were followed by another histamine challenge day. Peak expiratory flow rate (PEFR) was measured hourly for 12 hours on each control day and for 12 hours after each exercise or histamine challenge. During the first week, five patients showed a late reaction (PEFR change > 15%) after exercise, which was present in only two of them the following week. These two patients, however, also showed a spontaneous fall > 15% of PEFR from baseline during the other control study days. A similar pattern was seen in two other patients who had a late response during the second exercise challenge but not during the first. No significant change occurred in histamine PC-20 FEV1 between before and after the exercise challenges. An apparent late asthmatic response after exercise challenge may represent a within-day fluctuation in pulmonary mechanics that develops spontaneously in children with asthma.

In the present study we evaluated the allergenicity and immunogenicity of a whey partially hydrolysate formula (PHF) in a guinea pig model. Nine groups of 10 guinea pigs received either a conventional milk formula (CMF) or PHF for 37 days. After intravenous (i.v.) challenge with either beta-lactoglobulin (beta-L) or ultracentrifuged (u)CMF, animals fed CMF showed, respectively, 80% and 100% fatal reactions, whereas animals fed PHF showed no reactions when i.v. challenged both with beta-L and uPHF. Eighty percent fatal reactions, and 10%, respectively, of severe and mild reactions have been observed in the CMF-fed, casein-challenge group. In contrast, only one (10%) mild reaction occurred in the PHF-fed, casein-challenged group. When challenged with u-pasteurized cow's milk (uPCM), CMF-fed animals showed 86% fatal reactions and 14% mild reactions, whereas PHF-fed ones presented 70% no reactions, 20% mild reactions, and one (10%) fatal reaction. Animals fed CMF showed a significantly higher level of specific IgG against cow's milk antigens than PHF-fed ones, which, however, presented higher levels of antibodies than a water-supplemented control group. The present results confirm that PHF is less sensitizing than CMF in a guinea pig model.

To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG), administered by metered dose inhaler (MDI) with a 700 mL holding chamber (Fisonair Fisons UK) in preventing bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water (UNDW), 12 asthmatic children were studied in a randomized, double-blind, placebo-controlled, intrapatient study. Following a baseline challenge with UNDW, the protective effect of NS, SCG, or placebo was evaluated in each subject. Cumulative doses of delivered nebulized water producing a 20% fall in forced expiratory volume in 1 sec (PD20 UNDW) was measured. Mean (+/- SD) PD20 UNDW was 4.83 (+/- 4.84), 10.16 (+/- 7.05), 1.58 (+/- 0.5), and 15.93 (+/- 0.23) respectively, for baseline, and placebo, SCG, and NS-treated groups. A significant (P < 0.05) protection from UNDW induced bronchoconstriction by NS was observed in comparison with placebo, while no such effect was evident when the children were treated with SCG.