Topical Salmeterol Reduces Protein Content of Nasal Lavage Fluid in Response to Allergen and Histamine Challenge: Double-Blind Cross-over Placebo-Controlled Studies in Adults

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Abstract
We have studied the effects of topical intranasal β-2-adrenoceptor agonists on nasal airflow resistance (Rnaw) and secretions. Pretreatment with salmeterol (SM) and salbutamol (SB) was given in two double-blind, placebo-controlled studies. In Protocol 1, 15 patients with allergic rhinitis were challenged with a threshold dose of allergen. Rnaw and lavage fluid total protein, albumin, mucin, lysozyme, tryptase, histamine, and eosinophil cationic protein (ECP) were measured. In Protocol 2, 20 normal subjects were challenged with ascending doses of histamine and Rnaw and lavage fluid total protein and albumin were measured. After allergen challenge, there was a significant, increase in Rnaw total protein, albumin, and tryptase. SM significantly attenuated the rise in total protein (post-allergen challenge mean 218 mcg/mL, 95% c.i. 16–447; SB 344, 45–641; placebo 365, 105–725: P = 0.036). SM significantly reduced albumin concentration at 30 minutes post-drug (post-histamine challenge geometric mean 17.1 mcg/mL, interquartile range 8.2–29.4; SB 25.1, 15.2–43.0; placebo 24.2, 16.6–37.8: P = 0.027). SM has acute effects on the nasal response to allergen in allergic rhinitis and to histamine in normal subjects. These results imply an effect on glands and blood vessels in vivo that may represent part of the drug's clinical activity.