Is There Loss of a Protective Muscarinic Receptor Mechanism in Asthma: Results

Is There Loss of a Protective Muscarinic Receptor Mechanism in Asthma: ResultsExperimental Protocol
Each subject was studied on five occasions separated by at least 72 h. On experiment day 1, after obtaining baseline pulmonary (unction test results, a control bronchial provocation test with histamine was performed to establish PD*, to histamine. Normal subjects in whom PDg„ was not achieved even with 5 mg/ml concentration of histamine were excluded from the study to avoid problems with statistical analysis. On experiment days 2 to 5 the following combination of histamine and methacholine challenges were performed in a random sequence: methacholine-histamine; histamine-methacholine; methacholine-methacholine and hista-mine-histamine. After the first challenge, the subject was allowed to recover spontaneously. The second challenge was performed approximately 1 h later when the subject s SGaw level had returned to within 90 percent of the prechallenge baseline. Simultaneous dose-response curves and PD*, values for each challenge were obtained for comparative analysis. In five normal subjects, dose-response to histamine was repeated on two additional days, after prior exposure to a lower dose of methacholine (5 breath units, ie, equivalent to methacholine PDM of asthmatic patients), or following pretreatment with inhaled ipratropium bromide (36p.g).

Statistical Analysis
Data were expressed as mean ± SE. For PDV„ the data were analyzed by a nonparametric test, ie, the Wilcoxon signed rank tests for paired samples. Baseline pulmonary function tests between the two groups were compared by an unpaired f-test. The level of significance was accepted at p<.05 (beta= .01, alpha = .05).
Baseline Pulmonary Function

These results are shown in Table 1. Asthmatic subjects had evidence of mild airway obstruction as shown by significantly lower SGaw, FEV, and forced vital capacity. The SGaw was comparable on different experiment days within each group. The mean±SE post-diluent values of SGaw on experiment days 2-5 were 0.21±0.02, 0.21±0.02, 0.20±0.02, and 0.19 ±0.01 s*cmH20_I, respectively, for normal subjects, and 0.11 ±0.03, 0.13±0.02, 0.11 ±0.02 and 0.12±0.02 scmHgO’1, respectively, for asthmatic patients.
In both groups, the baseline PD^ values of methacholine and histamine were highly reproducible on two different days (normal subjects: histamine PD^, 13.7 ±3.1 and 16.7 ±3.7 breath units; methacholine PD50,13.9 ± 2.8 and 16.9 ±3.6 breath units. Asthmatic patients: histamine PDso, 3.6 ±2.5 and 3.4 ±2.5 breath units; PD^ methacholine, 4.9±3.3 and 4.3 ±2.5 breath units). The control values of PD50 of histamine and methacholine were significantly lower in the asthmatic group.
Table 1—Baseline Pulmonary Function Thsts of Normal and Asthmatic Subjects

Subjects 6.7 2.8 4.9 4.1 83% 1.81 0.20
SE 0.7 0.3 0.5 0.3 1.9 0.2 0.02
(103) (99) (108) (105) (138)
Patients 6 4.1 3.4* 2.5* 72% 2.4 0.11*
SE 1.2 0.7 0.6 0.4 4.8 0.3 0.02
(116) (130) (78) (70) (224)

Category: Asthma

Tags: Asthma, Methacholine, muscarinic receptor