Allergen-Induced Bronchoconstriction in Asthmatic Children (8)
Figure 3A shows that inhalation of mite allergen extract-induced bronchospasm in all of seven mite-sensitive asthmatic children. Importantly, the allergen-induced bronchoconstriction could be inhibited by a prior inhalation of BN52021 in three of seven patients (Fig 3B), and the threshold of allergen sensitivity was increased in each patient after inhalation of BN52021.
Table 2 shows the effect of aerosol BN52021 on the PAF-induced changes of peripheral WBC counts. Total numbers of WBC, neutrophil, and eosinophil counts were decreased markedly 5 minutes after PAF inhalation in both normal subjects and asthmatic children, but they returned to nearly normal value at 10 minutes. The decrease of eosinophil and neutrophil counts after PAF inhalation was greater in asthmatics than in normal subjects. Prior inhalation of BN52021 could inhibit PAF-induced decrease in eosinophil and neutrophil counts in normal, but not in asthmatic children. ampicillin antibiotic
In human and in animal models, PAF is a potent bronchoconstrictor no matter whether given intravenously or by aerosol. We observed similar results in this study. The magnitude of decrease of FEVj and the frequency of response to PAF inhalation were much greater in asthmatics than in normal controls (Fig 1).
Table 2—The Effects of Aerosolized BN52021 on the Platelet-Activating Factor (PAF)-Induced Decrease of WBC, Neutrophils, and Eosinophils, (Mean±SD) in the Peripheral Blood in Normal and Asthmatic Children
|ExperimentalProtocol||Time after Experiment, min||Total WBC||Neutrophils||Eosinophils|
(n = 7)
|0||7,560 ±456||11,280±576||4,210 ±246||5,120 ±314||218 ± 48||758 ±149|
|510||4,540 ±201 6,640 ±360||7,550 ±394 8,070 ±416||1,940 ± 192 3,840 ±256||2,240 ±196 4,100± 252||137 ± 39t 236 ±57||247 ±75 495 ± 93|
|BN520211||0||7,890 ±510||12,680 ±634||4,060 ±343||5,750 ±410||246 ±53||821± 205|
|IPAF(n = 7)||510||6,940 ±398 7,640 ±420||8,870 ±650 11,420 ±598||3,450 ±285 4,120 ±246||3,040 ± 298 5,100±447§||195 ±42 258 ±66||422 ±95 690 ±164|
Figure 3. Protection of BN52021 on allergen-induced bronchoconstriction. Each subject (represented by one line) inhaled either placebo (A) or BN52021 (B) in a double-blind, crossover fashion and then performed allergen challenge. BN52021 was able to prevent three of seven asthmatic children from allergen-induced bronchoconstriction, and there was a rightward shift of allergen sensitivity after BN52021 inhalation. Each line represented the response of one subject and the same symbol was used for a particular patient in A and B, indicating the different responses of the same subject to allergen challenge performed before and after inhalation of BN52021.