To evaluate the influence of aging on bronchial hyperreactivity (BHR) during the childhood period, age-related changes in bronchial reactivity to methacholine (BRm) in children from 2 to 13 yr of age were studied using the same method, employing a methacholine inhalation challenge with transcutaneous oxygen pressure (tcPO2) monitoring. Three hundred and thirty-nine asthmatic subjects (male:female = 200:139, aged [mean +/- SEM] 7.2 +/- 0.2 yr) and 107 age-matched controls (male:female = 55:52, aged 5.3 +/- 0.3 yr) were enrolled in this study. TcPO2 was measured by a tcPO2 monitor, and subsequent doses of methacholine were then doubled until a 10% decrease in tcPO2 from its baseline value was reached. The cumulative dose of methacholine at the inflection point of tcPO2 (Dmin-PO2) was considered to represent the BRm. For the sake of comparison, respiratory resistance (Rr) in subjects more than 6 yr old was measured by the oscillation technique during methacholine inhalation challenge, and the threshold point of Rr (Dmin-Rr) was also considered to represent the BRm. In the asthmatic children aged 2 to 7 yr, Dmin-PO2 decreased significantly from 12.2 +/- 2.1 to 3.1 +/- 0.8 units, but after age 8 yr the values gradually increased from 3.1 +/- 0.7 to 6.4 +/- 1.6 units. In children aged 6 to 13 yr, Dmin-Rr showed the same increase as Dmin-PO2, from 2.0 +/- 0.5 to 5.8 +/- 1.4 units. These age-related changes in BRm reflected in both Dmin-PO2 and Dmin-Rr were also seen in the age-matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

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We have studied the bronchial hyperresponsiveness of children with atopic and nonatopic asthma by methacholine inhalation challenge, using a new device, the "Astograph." Three parameters, initial respiratory resistance (Rrs cont), bronchial sensitivity (Dmin), and bronchial reactivity (St), were studied. The Rrs cont values of atopic asthma were higher than those of the disease controls (p less than 0.05), while there was no difference between nonatopic asthma and disease controls. The Dmin values of atopic and nonatopic asthma were lower than those of disease controls (p less than 0.001; p less than 0.01). The St values of atopic and nonatopic asthma were higher than those of disease controls (p less than 0.001; p less than 0.01). There was no difference of Rrs cont and Dmin between the children with atopic and nonatopic asthma. However, St of the children with nonatopic asthma was remarkably higher than that of the children with atopic asthma (p less than 0.001). These data suggested that there was a remarkable difference of bronchial response to methacholine between the children with atopic asthma and those with nonatopic asthma.

We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory drug (NSAID), on exercise-induced bronchoconstriction (EIB) in children with asthma. Nine asthmatic children (7 boys, 2 girls, with a mean +/- SEM age of 11.0 +/- 0.8 yr) with a history of EIB participated in this study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body surface area [BSA]) or placebo (0.9% saline) according to a double-blind, randomized, crossover design, and underwent an exercise challenge test 15 min after the pretreatment. Inhaled indomethacin significantly attenuated EIB. The mean maximal percent decrease in FEV1 following exercise was 36.1 +/- 5.7% after placebo and 18.0 +/- 4.6% after indomethacin pretreatment (p = 0.0310). Indomethacin also significantly reduced the mean maximal decrease in arterial oxygen saturation after exercise (p = 0.0378). The inhibition of local prostaglandin synthesis and/or ion transport in the airways may be a mechanism involved in the protective potency of inhaled indomethacin.

Airway inflammation with polymorphonuclear leukocytes (PMN) may play an important role in bronchial hyperresponsiveness (BHR). PMN generate superoxide anion (O₂^––) and other oxygen radicals that can damage lung tissue. We investigated the ability of peripheral PMN of children with bronchial asthma and control subjects to generate O₂^–– and other active oxygen species using a 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-α]pyrazin-3-one, a highly sensitive and specific chemiluminescence (CL) probe for O₂^––, and luminol-dependent CL. The ability of PMN of subjects with asthma to generate O^––₂ and other active oxygen species was significantly greater than that of PMN of control subjects when stimulated with opsonized zymosan (OZ), phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine. Furthermore, in the same asthmatic children, the generation of O₂^–– and other active oxygen species was significantly higher with attacks than without attacks when PMN were stimulated with OZ. We also demonstrated that O₂^–– generation correlated with the degree of BHR to inhaled histamine. These results suggest that PMN of asthmatic children, especially those with attacks, generate more active oxygen species than that of control subjects and that airway inflammation caused by O₂^–– may be closely related to BHR in subjects with bronchial asthma.