Protective Effect of Choline Theophyllinate on Histamine, Acetylcholine, and Propranolol-Induced Airflow Obstruction

Abstract

The protective effect of choline theophyllinate, 600 mg orally, was studied by examining the effects on inhaled histamine, acetylcholine, and propranolol in 19 asthmatic patients. Only 9 of them showed a propranolol threshold. This bronchodilator significantly increased the threshold values of histamine and acetylcholine, but showed no protective effect on propranolol thresholds. The histamine threshold changed from 22.5 ± (SD)^1.2 to 2^{3.8 ± 1.0} mg/ml (p < 0.001). With acetylcholine an initial value of 24.2 ± 1.4 mg/ml was determined, which changed to 2^{5.5 ± 1.1} mg/ml (p < 0.01). The propranolol threshold changed from 1.17% ± 0.40 to 1.36% ± 0.40 indicating that theophylline has no statistically significant protective effect on propranolol inhalation. The re-producibility of the challenges was assessed in 8 control patients. A placebo did not significantly change the initial airway reactivity to the three agents. The protective effect of choline theophyllinate on histamine and acetylcholine correlated with the initial degree of reactivity on both agents (r = -0.60; p < 0.01 and r = -0.84; p < 0.001, respectively), whereas no significant correlation with the degree of bronchodilation was observed. The latter observation indicates that the protective effect of theophylline does not depend on its bronchodilating activity.

Relationship of Serum Theophylline Concentrations to Histamine-Induced Bronchospasm

“…Baseline values of FEV| were not significantly different before placebo or theophylline (table III). Serum theophylline concentration (table IV) was significantly elevated at 4h (9.49 ± 2.79mg/1; p<0.05), 8h (12.09 ± 2.10 mg/l; p < 0.01 ) and 12 h (9.28 ± 3.03 mg/1; p<0.05) when compared to 12 …”

“…This bronchial hyperreactivity to various sti muli characterizes the asthmatic disease. During the past years several studies have been done, in which the protective effect of theophylline against several stimuli, ex ercise [1][2][3][4][5][6][7][8][9][10], histamine [11][12][13][14] and methacoline [12,13,15] challenge was inves tigated. The results are often contradictory and all the studies are not strictly compar able because of a number of differences in experimental design.…”

Effect of Dietary Caffeine on Airway Reactivity in Asthma

“…One might also specu late that caffeine has a lesser effect on air way reactivity than other methylxanthines, and in particular theophylline. In fact, Koëter et al [21] have found a clearcut protective effect of relatively low doses of theophylline in asthmatics with revers ible airway obstruction. The results of other studies, however, are rather conflict ing.…”

Effect of different bronchodilators on airway smooth muscle responsiveness to contractile agents.

“…Table 3 Concentrations of atropine sulphate, glycopyrrolate, and ipratropium bromide producing tracheal contractions equal to 50% of the maximal response (EC,^) (numbers - [6] > 1 x IOA [6] 3-5 x 1ICr5(0-6) [8] SubstanceP - [6] > 1 x 103 [5] 1-1 x 10-'(1-1) [5] Leukotriene C4…”

“…- [8] > 1 x 104 [7] 2-9 x 10-'(0-4) [5] LeukotrieneD4 - [8] > 1 x 10-3 [8] 3-1 x 10' (0-6) [5] Ovalbumin - [6] > 1 x 1IV [12] 5-2 x 10-'(1-9) [5] Bradykinin - [12] > 1 x 10-3 [10] 3-2 x 1I-(1-0) [9] Lys-bradykinin - [6] > 1 x 10-4 [6] 3-6 x 10-5 (0-9) [5] Met-lys-bradykinin…”