Bronchodilator effects of caffeine in coffee. A dose-response study of asthmatic subjects. The effect of caffeine on exercise-induced bronchoconstriction. The bronchodilator effect of caffeine in adult asthmatics. Effect of caffeine ingestion on exhaled nitric oxide measurements in patients with asthma. Effect of dietary caffeine on airway reactivity in asthma. Effect of caffeine on histamine bronchoprovocation in asthma. Caffeine consumption decreases the response to bronchoprovocation challenge with dry gas hyperventilation.
Although caffeine is a universal drug and has multiple pharmacologic and physiologic actions in man, there are surprisingly few objective data about its effect on pulmonary function. We conducted a short-term, double-blind, randomized crossover study in nine asthmatic adults who ingested decaffeinated coffee containing varying amounts of added caffeine (mean of 0.2,2.5,5.6, and 7.2 mg/kg of body weight) on different days. The subjects also ingested decaffeinated coffee and aminophylline (200 mg) on a separate day of study. Baseline and post-drug determinations of serum levels of caffeine and theophylline, forced expired volume and flow, specific airway conductance (Gaw/VL), vital signs, and reported symptoms were obtained. Peak increases in serum caffeine concentrations (mean, 12.4 micrograms/ml +/- 1.5 micrograms/ml) occurred 45 minutes following the highest dose of caffeine (7.2 mg/kg), whereas the peak theophylline level (mean 3.8 micrograms/ml +/- 0.4 micrograms/ml) occurred 90 minutes following oral administration of aminophylline (mean theophylline, 2.6 mg/kg). Comparable peak increases in the forced expiratory volume in one second (FEV1), the forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%), and Gaw/VL occurred at 120 minutes following aminophylline and the highest dose of caffeine, indicating that caffeine is an effective bronchodilator but is only 40 percent as active as an equivalent molar dose of theophylline. Regression analysis revealed statistically significant dose-response relationships between peak increases in serum caffeine concentrations and increases in FEV1, FEF25-75%, and Gaw/VL from baseline values. These findings have diagnostic and therapeutic implications regarding the use of caffeine prior to tests of pulmonary function and as a dietary agent, alone or in combination with theophylline. The effect of caffeine on exercise-induced bronchoconstriction was examined in ten patients with bronchial asthma. Placebo and caffeine 3.5 mg/kg and 7 mg/kg were given two hours before exercise. Spirometry was taken at one and two hours following caffeine and at 5, 15, and 30 minutes following exercise. Caffeine significantly improved baseline FEV1 and prevented exercise-induced bronchoconstriction only at a dose of 7 mg/kg. Caffeine was well tolerated by the patients. These data suggest that only high doses of caffeine significantly prevent a postexercise drop in FEV1. Caffeine has been reported to result in bronchodilation in asthmatic children. Our study was designed to assess the effect of caffeine on pulmonary function in adults with asthma. We studied 8 patients: 4 men and 4 women with previously documented airway reactivity. A randomized, double-blind cross-over was used. The patients received either placebo or 5 mg/kg of caffeine in solution orally, and FEV1, FVC, FEF25-75, Vmax25 and blood for caffeine concentrations were taken at several time points for as long as 8 h after the drink. Results: there was a significant difference between caffeine and placebo for percent change in FEV1 with peak change at 1.5 h. There was also a significant difference for percent change in FEF25-75 with peak occurring at 4 h. Percent change in Vmax25 was significantly different at 3.0 h only. Peak caffeine concentration of 8.7 +/- 1.7 micrograms/ml occurred at 1 h. The data indicate that caffeine at a dose of 5 mg/kg can produce significant percentage improvement in FEV1, FEF25-75, and Vmax25 in adult asthmatics. Exhaled nitric oxide (FENO) measurements may be influenced by a number of confounding factors. Reports have offered conflicting evidence as to whether caffeine consumption increases or decreases FENO. In this study we aimed to confirm whether caffeine ingestion affects FENO in patients with asthma. On two separate days, 20 patients with asthma (10 steroid-naive and 10 steroid-treated) received a standard cup of either caffeinated or noncaffeinated coffee (15 g) (control) in a randomized, double-blind, cross-over manner. FENO measurements were obtained at baseline, and 30, 60, 120, and 180 minutes after ingestion. Serum caffeine levels were also measured at 0 and 60 minutes. No significant changes in FENO occurred after caffeine compared with the control. We conclude that caffeinated foods and beverages are unlikely to acutely influence FENO in subjects with asthma, and protocols for laboratory measurement do not need to take this factor into account. The potential influence of dietary caffeine on bronchoprovocation challenges with carbachol was examined in 7 patients with asymptomatic asthma. In a double-blind fashion placebo or caffeine (6 mg/kg body weight; equivalent to approximately 4 cups of coffee) solved in orange juice was administered, and carbachol challenges were performed. The average peak serum concentration achieved 60 min after dosing was 7.6 +/- SD 2.1 mg/l. These caffeine levels did not produce any appreciable attenuation of the bronchoconstrictor response to carbachol inhalations. It thus appears that dietary caffeine is barely a cause of erroneous interpretations of bronchoprovocation challenges with carbachol. It was recently reported that caffeine may reduce the clinical symptoms of asthma and may prevent the clinical manifestations of this disease. The effect of caffeine on histamine responsiveness is unknown. The effect of caffeine (5 mg/kg) and placebo on histamine responsiveness (the provocation concentration causing a 20% fall in FEV1, PC20) was studied in 10 subjects with mild asthma (prechallenge FEV1 84% of predicted value). The PC20 for histamine bronchoprovocation after caffeine ingestion was 2.65 (95% confidence limits 0.99, 7.10) mg/ml. After placebo the PC20 was 1.89 (0.96, 3.71) mg/ml. It is concluded that caffeine in a dose equivalent to about three cups of coffee has a very small effect, if any, on histamine bronchoprovocation in those with mild asthma. Specific instructions about not having drinks containing caffeine before histamine challenge are therefore not necessary. To determine whether caffeine consumption affects bronchoprovocation challenge (BPC).
                A prospective, double-blind, placebo-controlled, randomized, crossover trial.
                Eleven nonsmoking men, aged 18 to 42 years, with normal baseline spirometry and evidence of exercise-induced bronchospasm.
                On three separate test days, each individual received, in random order, either placebo, 5 mg/kg caffeine, or 10 mg/kg caffeine, and then underwent BPC with eucapnic voluntary hyperventilation (EVH).
                Caffeine (10 mg/kg) significantly reduced bronchoconstriction compared to placebo (p = 0.02). The reduction in bronchoconstriction correlated with the serum level of caffeine (p = 0.014).
                Caffeine decreases bronchoconstriction due to EVH. Caffeine should be eliminated from diet prior to BPC.