No abstract

We defined the contribution of histamine and leukotrienes to allergen-induced airway obstruction in asthmatics; 12 subjects with allergic asthma underwent identical allergen bronchoprovocations on four occasions. At a control session, all subjects displayed early (EAR) and late asthmatic (LAR) reactions. The mean (+/- SE) drop in FEV1 during EAR (0-2 h) and LAR (2-12 h) was 29 +/- 2% and 28 +/- 4%, respectively. Thereafter, the influence of 1 wk randomized pretreatment with the leukotriene receptor antagonist zafirlukast (Accolate) (80 mg twice daily), the antihistamine loratadine (10 mg twice daily), and the combination of both antagonists was assessed. Expressed as AUC FEV1 in percent of the control reaction, zafirlukast reduced the response during EAR and LAR by 62 +/- 11% and 55 +/- 12%, respectively (p < 0.05 versus control). Loratadine inhibited EAR and LAR by 25 +/- 14% and 40 +/- 16%, respectively (p < 0.05 versus control). Zafirlukast was significantly more effective than loratadine during EAR but not during LAR. The combination of zafirlukast and loratadine reduced the AUC FEV1 during EAR and LAR further, by 75 +/- 8% and 74 +/- 14%, respectively (p < 0.05 versus control). The combination was significantly (p < 0.05) more effective than either drug alone during the LAR. The findings indicate that leukotrienes and histamine together mediate the major part of both the EAR and the LAR following exposure of asthmatics to allergen. Combination of leukotriene antagonism and antihistamines may represent a new strategy for treatment of airway obstruction in asthma.

The development of bronchial hyperresponsiveness (BHR) in asthma is considered to be caused by inflammation of the airway. In IgE-mediated allergy BHR is related to the occurrence of late phase reactions. We have previously shown that exposure to low doses of allergen can cause isolated late reactions. These findings are potentially of clinical importance, since exposure to low, subclinical allergen doses may lead to bronchial inflammation and increasing bronchial responsiveness without necessarily causing immediate bronchoconstriction. This study was performed to investigate whether repeated exposure to low doses of allergen could induce a change in BHR. The trial comprised two groups of five and eight patients with a history of allergic asthma. They were submitted to a series of allergen inhalations for 5-7 days. They were given the same low allergen dose (1-10 biological units) each day. Before and after the allergen exposure period histamine challenges were performed. After the week of allergen inhalation the bronchial responsiveness was increased in 11 of 13 patients.

Increased levels of exhaled carbon monoxide (fractional concentration of CO in expired gas (FE,CO)), measured with an electrochemical sensor, have been reported in patients with inflammatory airway disorders, such as asthma, rhinitis and cystic fibrosis. This study aimed to evaluate these findings by using a fast-response nondisperse infrared (NDIR) analyser, and to compare these measurements with the fractional concentration of nitric oxide in exhaled air (FE,NO). Thirty-two steroid-naïve asthmatics, 24 steroid-treated asthmatics (16 patients with allergic rhinitis, nine patients with cystic fibrosis), and 30 nonsmoking healthy controls were included. CO measurements with the NDIR analyser were performed simultaneously with nitric oxide (NO) analysis (chemiluminescence technique). After 15 s of breath-hold, single-breath exhalations over 10 s were performed at two flow rates and end-tidal plateau concentrations were registered. An electrochemical CO sensor was used independently with an exhalation to residual volume, after a 15 s breath-hold. None of the two CO analysers gave a significant increase in FE,CO in the groups of patients with inflammatory airway disorders compared to controls. FE,NO was significantly elevated in steroid-naïve asthmatics and subjects with allergic rhinitis, but not in steroid-treated asthmatics and subjects with cystic fibrosis. Reducing exhalation flow rate by 50% gave a two-fold increase in FE,NO, while FE,CO was unaffected. A significant increase was seen in FE.CO, but not in FE,NO, when comparing with and without a 10 s breath-hold. In conclusion, the fractional concentration of carbon monoxide in expired gas was not increased in any of the patient groups, while the fractional concentration of nitric oxide in expired gas was significantly elevated in patients with steroid-naïve asthma and allergic rhinitis. Moreover, carbon monoxide was unaffected by flow rate but increased with breath-hold, suggesting an origin in the alveoli rather than the conducting airways.