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Background: Studies of the effects of tobacco smoke often rely on reported exposure to cigarette smoke, a measure that is subject to bias. We describe here the relationship between parental smoking exposure as assessed by urinary cotinine excretion and lung function in children with asthma., Methods: We studied 90 children 4-14 years of age, who reported a confirmed diagnosis or symptoms of asthma. In each child, we assessed baseline pulmonary function (spirometry) and bronchial responsiveness to carbachol stimulation. Urinary cotinine was measured by HPLC with ultraviolet detection., Results: Urinary cotinine concentrations in the children were significantly correlated (P <0.001) with the number of cigarettes the parents, especially the mothers, smoked. Bronchial responsiveness to carbachol (but not spirometry test results) was correlated (P <0.03) with urinary cotinine in the children., Conclusion: Passive smoke exposure increases the bronchial responsiveness to carbachol in asthmatic children., (Copyright 1999 American Association for Clinical Chemistry)

1. The aim of the study was to determine the carbachol and albuterol responsiveness in treated and untreated asthmatic and allergic children exposed to environmental tobacco smoke assessed by urinary cotinine measurements. 2. Forty-six asthmatic and allergic children with normal spirometric values were recruited. The doubling dose, concentration of carbachol producing a 2-fold increase in specific airway resistance (SRaw) was determined and 200 micrograms of albuterol were administered via a Volumatic(R) spacer. The percentage of bronchodilatation was defined as the difference between the largest obtained SRaw and the post-beta2 SRaw divided by the largest SRaw. Data were compared by a Mann-Whitney U-test. 3. The 23 children with a high urinary cotinine, compared with the 23 children without urinary cotinine, had a decreased doubling dose (108.2+/-14.7 micrograms versus 160.9+/-19.5 micrograms; P=0.04) and an increased percentage of bronchodilatation (74.8+/-1.4% versus 68.8+/-1.8%; P=0.03). A prophylactic anti-inflammatory treatment induced a weaker bronchial reactivity to carbachol and a slightly greater bronchodilatation in children exposed to environmental tobacco smoke. 4. Environmental tobacco smoke increases bronchial reactivity in asthmatic and allergic children. This effect might be reduced by anti-inflammatory therapy. The bronchodilator response may be enhanced in exposed children and may be caused by one or several direct interactions between tobacco smoke compounds and albuterol.

The use of spacer devices is recommended in asthmatic children for inhaled therapeutics. Therefore, in vitro studies prove the dependent-device delivery of the drug. The aim of this study was to compare, in vivo, the effect of 200 micrograms of albuterol, delivered via one of the five spacer devices currently marketed in France (Aerochamber, Aeroscopic, Babyhaler with a face mask, Nebuhaler or Volumatic) and assessed by the induced peak expiratory flow (PEF) change. One hundred asthmatic children were recruited and randomized in 5 groups. The mean age was 8.9 +/- 3.3 years. Each group was comparable regardless of gender, height, weight, characteristics of asthma and baseline PEF. The maximal change in PEF was obtained with Babyhaler (14.9 +/- 12.8%; p = 0.009). The increase in PEF elicited with Aeroscopic was 9.7 +/- 10.2%. The others spacer devices did not offer a change greater than the variation of PEF in the studied population. Further studies, concerned with a measurement of drug deposition or with an assessment of its use in obstructive episodes of asthma, are required, but Babyhaler with a face mask, usually reserved to infants, deserves to be advised to older children for salbutamol intake.

Theophylline levels in plasma, erythrocytes and cantharides-induced blister fluid (BF) have been correlated with peak expiratory flow (PEF) in asthmatic patients. Nine asthmatic men received an IV infusion of 240 mg theophylline at a constant rate for 30 min. The theophylline concentrations in erythrocytes and blister fluid were 37% and 78% of those in plasma. There was not a strong correlation between erythrocyte or blister fluid penetration and the clinical effect of theophylline.

The purpose of this study was to investigate the effect of a constant infusion rate of terbutaline on circadian bronchial peak expiratory flow rate (PEFR), heart rate and arterial pressure in patients with asthma exacerbation. Fifteen hospitalized asthmatic patients (6 females and 9 males, mean age 43.3 years, mean weight 67.0 kg) were included in this study. In order to reach the desired plasma concentrations of terbutaline immediately, a pharmacokinetic simulation was done. Based on the predicted values thus obtained, an initial 5-min bolus dose of 2.94 micrograms/kg was given to all patients at 7 a.m., i.e. at the beginning of the study. Over the following 24 h (7 a.m. to 7 a.m.), 33 micrograms/kg of terbutaline was infused intravenously at a constant rate with an electric pump. Since severe acute asthma requires corticosteroids, a 40-mg injection of methylprednisolone was given to all patients at 7 a.m. PEFR, heart rate, systolic arterial pressure, side effects and plasma terbutaline levels were recorded at 7 and 10 a.m., 1, 4, 7 and 11 p.m., and 3 and 7 a.m. the following morning. Terbutaline had a significant favorable effect on asthma exacerbation but no circadian rhythm was found in PEFR. Although terbutaline was infused at a constant rate, plasma levels depended on circadian variations.

Our study investigated the differential effects of continuous or unequal day-night terbutaline dosing on circadian bronchial patency, heart rate, and arterial pressure in severe acute asthma. Forty-five hospitalized asthmatic patients (19 women and 26 men, mean age 45.4 years, mean weight 63.5 kg) were included in this multicenter study. Three groups of patients (corresponding to three dosing schedules) were randomized; the three groups were comparable, since no statistically significant difference was detected in the age, weight, or peak expiratory flow values at the beginning of the study. In order to reach immediately the concentrations of terbutaline corresponding to the desired unequal day-night concentrations, a theoretical pharmacokinetic simulation was done to predict the outcome in terms of the plasma concentrations after the three dosing regimens; the results of this simulation allowed us to calculate the initial bolus dose to be given over 5 min to groups A, B, and C, i.e., 1.47, 2.94, and 4.41 micrograms/kg, respectively. This bolus was given to all patients at 0700 h, the beginning of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of menstrual cycle on the pharmacokinetics of theophylline has been studied in 9 female asthmatic patients. At three different times during the cycle (first, tenth and twentieth days) each subject received an i.v. infusion of 240 mg theophylline. Significant changes were found in the kinetics of theophylline according to the menstrual cycle. The maximum plasma drug concentration, minimum mean residence time, and minimum elimination half-life were observed at mid-cycle. The lowest clearance was observed at D 20. The AUC and volume of distribution did not vary significantly during the cycle.

Seven asthmatic patients were given a single placebo tablet in a first test session and then in two subsequent double blind sessions they randomly received 400 mg bevantolol or 100 mg atenolol, with at least 2 days between each of the sessions. Neither beta-blocker had any significant effect on FVC as compared to the placebo. FEV 1, however, was significantly lower 2 and 3 h after atenolol or bevantolol; there was no significant difference between the effects of the two drugs on FEV 1. Peak expiratory flow rate was reduced by bevantolol but not by atenolol, the difference reaching significance after 3 h. Fenoterol inhalation at the end of each test session always enhanced pulmonary performance, but to a lesser extent after bevantolol than after placebo or atenolol. A slower heart rate was recorded 2, 3, and 4 h after bevantolol and 3 and 4 h after atenolol; the mean 2-h value was significantly lower with atenolol than with bevantolol. No patient suffered any adverse effect. Bevantolol may be slightly less selective than atenolol.

Seven asthmatic patients were given a single placebo tablet in a first test session and then in two subsequent double blind sessions they randomly received 400 mg bevantolol or 100 mg atenolol, with at least 2 days between each of the sessions. Neither beta-blocker had any significant effect on FVC as compared to the placebo. FEV 1, however, was significantly lower 2 and 3 h after atenolol or bevantolol; there was no significant difference between the effects of the two drugs on FEV 1. Peak expiratory flow rate was reduced by bevantolol but not by atenolol, the difference reaching significance after 3 h. Fenoterol inhalation at the end of each test session always enhanced pulmonary performance, but to a lesser extent after bevantolol than after placebo or atenolol. A slower heart rate was recorded 2, 3, and 4 h after bevantolol and 3 and 4 h after atenolol; the mean 2-h value was significantly lower with atenolol than with bevantolol. No patient suffered any adverse effect. Bevantolol may be slightly less selective than atenolol. [ABSTRACT FROM AUTHOR]