muramidase and Sneezing

Topical sodium cromoglycate is used to treat allergic diseases of the upper and lower airways. To investigate its mechanisms of action, intranasal histamine challenge was used in nine subjects with perennial allergic rhinitis. After a preliminary day where subjects' reactivity thresholds (D100) for histamine were determined, intranasal sodium cromoglycate was administered in a double-blind, placebo-controlled fashion. Graded (D100/3, D100, D100X3), sequential challenges were performed on days 1 and 21 of each course, and responses measured by changes in nasal airway resistance, sneezes, secretion volume and secretion content: total protein, lysozyme and mucin. After a single dose of sodium cromoglycate, there was no change in resistance, but secretion volumes fell significantly (3.12 ml/5 min c.i. 2.83-3.4; placebo 3.61, c.i. 3.32-3.90: P = 0.026). After a 3-week-course, there was a significant fall in resistance (4.29 cm H2O/l/s, c.i. 3.85-4.72; placebo 5.45, c.i. 5.01-5.88: P < 0.0001). No change in other parameters was observed. Thus, in perennial allergic rhinitis, intranasal sodium cromoglycate has both short- and long-term effects on nasal reactivity to histamine challenge. Acutely, there is a reduction in nasal lavage fluid volume which may be the result of reduced irritant receptor activity. After a 3-week course, there is a reduction in nasal resistance responses, a possible anti-inflammatory effect.

Topics: Administration, Intranasal; Adult; Aged; Airway Resistance; Anti-Inflammatory Agents; Cromolyn Sodium; Double-Blind Method; Female; Histamine; Humans; Male; Middle Aged; Mucins; Muramidase; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Nose; Placebos; Proteins; Rhinitis, Allergic, Perennial; Sneezing

Although nasal challenge with allergen has often been used to evaluate the efficacy of therapeutic modalities used for the treatment of allergic rhinitis, the reproducibility of this model in quantitatively evaluating efficacy has not been rigorously examined.. To examine the reproducibility of the suppressive effects of an intranasal corticosteroid on the clinical and biochemical outcomes of a nasal allergen challenge during two identical treatment periods using the same subjects.. In a single-blind study, 25 seasonal allergic subjects with positive skin tests to grass or ragweed were studied outside of their pollen season. Subjects underwent a baseline, three-dose allergen challenge. Beginning 1 week later, subjects received two 7-day courses of intranasal beclomethasone (168 microg b.i.d.) separated by a 1-month washout period. Nasal challenges with allergen were performed after each treatment period. The nasal allergic response was evaluated by counting sneezes, recording symptom scores and measuring levels of albumin (an index of vascular permeability), lysozyme (an index of serous glandular secretion) and kinins (proinflammatory peptides) in recovered nasal lavages.. Compared with the baseline challenge, each course of beclomethasone significantly reduced sneezing, symptom scores, albumin and kinins, but not lysozyme. Reproducibility analysis of the net changes from diluent challenge in the two beclomethasone treatment periods, showed the following intraclass correlation coefficients: sneezing (0.92), lysozyme (0.82), symptom scores (0.72), albumin (0.64) and kinins (0.28).. We conclude that the nasal challenge model is a reproducible method to evaluate the efficacy of anti-allergic medications. For nasal corticosteroid trials, sneezing, symptom scores and albumin levels are recommended as the most reproducibly suppressive outcome measures.

Topics: Administration, Intranasal; Adult; Albumins; Allergens; Ambrosia; Anti-Asthmatic Agents; Beclomethasone; Clinical Trials as Topic; Female; Glucocorticoids; Humans; Kinins; Male; Muramidase; Nasal Lavage Fluid; Nasal Provocation Tests; Poaceae; Reproducibility of Results; Rhinitis, Allergic, Seasonal; Sneezing; Treatment Outcome