Effects of ipratropium bromide on hypertonic saline provocations in human nasal mucosa

induced by the proinflammatory stimuli, but showed tendency to be induced after 72h of stimulation. We conclude that although GROand IL-8 were inducible by Pseudomonas supernatants, there might be a different regulation pathway in chemokine expression. 2 ~ Effects of Ipratropium Bromide on Hypertonic Saline Provoca~ll~lF tions in Human Nasal Mucosa Uyenphuong H Le, James N Baraniuk, Mustaq Ali, Kristina Naranch, Dan Clauw, Atsushi Yuta, Sheen-Yie Fang, Yong-Jin Park, Ana Velarde, Abby Pheiffer, Eddie Hwang, Ron Finnegan Georgetown University, Washington, DC BACKGROUND: The mechanisms of action of hypertonic saline in airways are poorly resolved. OBJECTIVE: To determine the role of cholinergic reflexes in human nasal hypertonic saline provocation. METHOD: Ipratropium bromide (2 puffs of 0.6%, n = 24) or saline placebo (n = 46) were administered to both nostrils. Thirty minutes later unilateral, escalating doses of hypertonic saline (100 btl per nostril of 1 times normal saline [I×NS], 3×NS, 6×NS, 12×NS, and 24×NS [21.6%]) were applied to one nostril at 5 min intervals. I×NS was always administered to the contralateral nostril. After each interval, 12 sprays (1 ml) of I×NS were used to obtain separate left and right nostril secretions. Symptoms, nasal lavage mucus constituents, and acoustic rhinometry were assessed 5 min after each dose. RESULTS: After the 30 rain baseline period, challenge with lxNS caused significantly different results for ipratropium compared to placebo. Ipratropium significantly increased the sensation of nasal blockage (0.65 _ 0.38 cm on 10 cm linear analog scale vs. 0.10 + 0.10 for placebo, p = 0.0003, ANOVA), mucin polysaccharide: lysozyme ratio (45.2 _+ 22.8 vs. 12.7 + 4.1 for placebo, p = 0.008). Ipratropium decreased total protein (299 + 69 ~g/ml vs. 479 + 83 ~tg/ml for placebo, p = 0.01 ), and lysozyme (22.8 _+ 0.10 ~g/ml vs. 37.0 _+ 7.3 ktg/ml for placebo, p = 0.008) concentrations. Hypertonic saline induced dose-dependent sensations of pain intensity, block and drip, pain duration, lysozyme and mucin polysaccharide secretion, but had no effect on plasma exudation (albumin, IgG). Ipratropium pretreatment augmented the hypertonic saline-induced sensation of block (p < 0.02 at 12×NS and 24×NS compared to placebo), increased incremental lysozyme secretion at 3×NS and higher doses (p < 0.03) and, decreased the mucin polysaccharide: lysozyme ratio. This ratio did not change after placebo pretreatment. Pretreatments had no effect on mucin polysaccharide release. Contralateral sensations, concentrations and ratios were unchanged indicating systemic parasympathetic reflexes were not activated. CONCLUSIONS: Ipratropium pretreatment augmented neural mechanisms leading to an increase in the sensation of nasal blockage. Ipratropium decreased basal lysozyme concentrations suggesting that cholinergic tone was responsible for "spontaneous" serous cell exocytosis. In contrast, basal mucin polysaccharide release was not altered, suggesting that other neural or mucosal mediators contributed to mucous and/or goblet cell exocytosis. The presumed nociceptive neurogenic responses of the unilateral hypertonic saline overcame the ipratropium effects on block and lysozyme, caused dose-dependent pain and glandular secretion, but did not induce unilateral or bilateral cholinergic reflexes. 2~ ' 7 Evaluation of Nasal Responses to Fel D1 by Acoustic RhinomeI E try as a Test of Cat Allergy Jose A Martinez*, Martin Y Desrosiers*, Sophie Desrosiers*, Elyess Khemici*, Martin Blaquiere§ *Center Hospitalier de l'Universite de Montreal, Montreal, QC, Canada §Universit6 de Montrral, Montreal, QC, Canada INTRODUCTION: Diagnosis of allergic rhinitis to cat dander has relied upon history and demonstration of sensitivity to Fel D1 by epicutaneous testing. Some question has arisen as to whether epicutaneous testing accurately detects disease in the target organ. We have previously reported (Larivee, 1999) a method for sensitive, reproducible assessment of nasal congestive responses to histamine using acoustic rhinometry (AR). As part of an investigative effort into the mechanisms of non-allergic rhinitis (NAR), acoustic rhinometry was used to assess whether responses to nasal challenge with cat allergen could reliably demonstrate sensitisation. PURPOSE: To characterise the congestive nasal response to cat allergen challenge in both individuals with known cat allergy and non-rhinitic, non-allergic population. To determine a reliable effective challenge dose and congestive response threshold for positive congestive responses allowing differentiation between the two groups. METHOD: Twelve cat-allergic (presence of nasal symptoms on exposure to cat and positive skin tests) and seven normal subjects (absence of nasal symptoms and negative skin tests) underwent bilateral nasal challenges with 300 microliters of increasing concentrations of Fel D1 dissolved in PBS. (50 -10 000 PNU). Congestive responses were assessed using acoustic rhinometry, (AR) and expressed as percent change from baseline. Responses were evaluated using ANOVA and the two groups compared with t-test for unpaired groups. Range of confidence (ROC) analysis was used to compare sensitivity and specificity of each concentration. RESULTS: Challenge with increasing concentrations of cat allergen produced dose-dependant nasal congestion in cat allergic subjects only. This was maximal at the 10 000 PNU strength. A 25% response 10 minutes after challenge predicted allergy with a sensitivity and specificity of 100%. CONCLUSION: Cat allergen challenges produced dose-dependant congestion in sensitive subjects. A 25% reduction in nasal volume l0 minutes after challenge at the cumulative 10 000 PNU concentration reliably predicts sensitisation, and could be used for diagnosis of cat allergy. These findings will be evaluated for single-dose challenges and used for further investigation of undiagnosed cat allergy in non-allergic rhinitics. Funding: Internal funding. 2 ~ Q Nasal Inspiratory Peak Flow Rates After Cold Stimulation of the i I L ] l Feet in Allergic Rhinitis and Normals Renata Witkowska, Alan Wolff, Kumar Patel, Stanley Weiss, Leonard Bielory UMDNJ, Newark, NJ The response of the nasal mucosa to cold stimulation of the feet in allergic rhinitis (AR) is inconsistently reported. Previous studies compared normal controls with rhinitis patient, but both allergic and non-allergic rhinitis (NAR) were included in the group. One study in Japan separated AR from NAR, but used acoustic rhinometry. Nasal patency can be studied by rhinomanometry as well as by nasal inspiratory peak flow rate (NIPF). Comparison of these two methods in assessment of airway resistance showed significant correlations, but NIPF rate is more easily performed. We decided to evaluate whether this reponse could be detected by measuring NIPF. This prospective study was performed on 15 subjects with allergic rhinitis and 37 healthy controls. They immersed their feet in cold water (13 19 °C) for 5 minutes. NIPF rate was measured at baseline and 1 and 5 minutes after the baseline. The NIPF was measured with the In-check model. The data were analyzed using the student T-test. The data are shown on the table. Our data confirms that cooling of feet in allergic rhinitis reduces nasal resistance and we could detect this change using nasal inspiratory peak flow rate. However, there was no significant difference in the cold pressor test between normal and AR populations.