The nasal responses to provocation with histamine and methacholine were compared in 20 subjects with and 20 without rhinitis. Two variables were measured: nasal airways resistance and the development of rhinorrhoea. Histamine had a greater effect than methacholine in increasing nasal airways resistance while the converse was true for rhinorrhoea. Rhinitic subjects had a significantly greater response to histamine induced changes in nasal airways resistance (p < 0'05), rhinorrhoea (p < 0-05) and methacholine induced rhinorrhoea (p < 0-01) than those without rhinitis. No significant differences were found between the two groups in methacholine induced changes in nasal airways resistance. The findings show that, like the lower airways of patients with asthma, the nasal mucosa of rhinitic subjects shows a greater responsiveness to non-specific agonists than that of non-rhinitic subjects.It is well recognised that the lower airways of subjects with asthma show a greater responsiveness to various non-specific stimuli, including the pharmacological agents histamine and methacholine, than those of subjects without asthma.' 4 The enormous number of reports on various aspects of bronchial reactivity provides a striking contrast to the limited attention devoted to the study of the upper respiratory tract. The results of studies of the upper respiratory tract have generally shown poor agreement and it remains unclear whether the nasal mucosa of patients with rhinitis is more responsive to pharmacological agonists than that of non-rhinitic subjects.5-12The nasal response to provocation can be measured in several ways.'3 A nasal challenge may cause pruritus and sneezing from stimulation of nerve endings, nasal obstruction from vascular dilatation and oedema, and rhinorrhoea from stimulation of mucosal glands.'3 14 The purpose of this study was, firstly, to re-examine whether an increased level of non-specific responsiveness of the nasal mucosa is a feature of rhinitis and, secondly, to determine whether any differences exist in the pattern of response to provocation with histamine and metha-

1 The effect of 4.4 mg azelastine administered orally on airway responsiveness, skin prick testing, daily peak expiratory flow rates and symptoms of asthma was compared with placebo in a 7 week double-blind, parallel group study of 24 patients with extrinsic asthma. The study was in two parts: a 2 week assessment period, during which all patients received placebo tablets but recorded daily peak flow rates (PEFRs) and symptoms, preceding the 7 week double-blind comparison. 2 Azelastine, 4.4 mg, significantly decreased airway responsiveness to histamine compared with placebo both after a single dose (P < 0.001), and following 7 weeks continuous treatment (P < 0.02). Airway responsiveness to methacholine was not altered by administration of azelastine compared with placebo. 3 Skin prick test weal diameters to both allergen and histamine were significantly reduced after both a single dose and following 7 weeks continuous therapy treatment with azelastine. 4 There was a significant improvement in both the mean of the morning and the evening peak flow rates recorded during the last week compared with the first week of the study in the group receiving 4.4 mg of azelastine twice daily compared with placebo. Scores for wheeze were significantly reduced during the final 3 weeks of the study in patients receiving azelastine compared both with those receiving placebo and with the first week of the study (P < 0.05, P < 0.01). Consumption of inhaled bronchodilators fell significantly during the study in the group receiving azelastine therapy (P < 0.05); no such fall occurred in the placebo treated patients. 5 A bitter metallic taste was reported by 58% of patients who received azelastine therapy.

AssTRAcr The inhibition of immediate allergen or histamine induced airflow obstruction by inhaled ketotifen, clemastine, sodium cromoglycate, and placebo was studied in two groups of asthmatic subjects. Single doses of ketotifen (0.5 mg), clemastine (0-5 mg), sodium cromoglycate (20 mg), or placebo were administered by inhalation 45 minutes before bronchial provocation testing at weekly intervals, double blind and in random order. Inhalation of ketotifen and clemastine, but not sodium cromoglycate, caused an increase in the amount of histamine which had to be administered to cause a 20% fall in FEV, from control levels (PD2Q-.FEvi) compared with placebo.The PD21FEV1 for allergen increased significantly after inhalation ot clemastine and sodium cromoglycate. Clemastine, primarily an H, receptor antagonist, inhibited airflow obstruction after inhalation of both histamine and allergen. Its inhibitory effect on allergen induced asthma did not differ significantly from that of sodium cromoglycate. Ketotifen, when inhaled in a single dose of 0-5 mg before bronchial provocation testing, showed potent antihistamine activity, but there was no evidence of any additional "antianaphylactiC" activity.

No abstract