Helen C. Kaulbach

Substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide increase in nasal secretions after allergen challenge in atopic patients

BACKGROUND There is suggestive evidence that neuropeptides participate in allergic reactions. Substance P (SP) and calcitonin gene-related peptide (CGRP) are released by sensory nerves, whereas vasoactive intestinal peptide (VIP) is released mainly by parasympathetic nerves. Both sets of nerves are thought to be stimulated by allergic inflammation. The aim of this study was to assess nasal secretions to determine whether SP, CGRP, and VIP were increased after allergen challenge. METHODS Eight patients with allergic rhinitis were challenged nasally with 1 mg histamine or increasing doses of allergen. Nasal lavages were collected into a cocktail of protease inhibitors in order to restrict neuropeptide degradation. Radioimmunoassay for SP, CGRP, and VIP were performed on each sample. RESULTS All patients had immediate clinical reactions to both histamine and allergen challenges, and seven patients experienced a later allergic reaction. After histamine challenge, SP and CGRP did not increase significantly above baseline in the nasal lavages, whereas VIP did (p < 0.02). In contrast, SP, CGRP, and VIP all significantly increased immediately after allergen challenge and returned to baseline within 2 hours. At the clinical peak of the late allergic reaction, SP, but not CGRP or VIP, was increased slightly but significantly (p < 0.01). CONCLUSIONS Thus SP, CGRP, and VIP are found in nasal secretions after allergen challenge, which confirms that neuropeptides are released in human beings during allergic reactions. The selective stimulation of VIP secretion by histamine challenge suggests that histamine-induced cholinergic reflexes induce the release of VIP. These data support the suggestion that neuropeptides may be partly responsible for some of the nasal symptoms of allergy.

Nasal secretions in response to acetylsalicylic acid

BACKGROUND Acetylsalicylic acid (ASA) induces rhinorrhea in a subset of patients with asthma or chronic rhinosinusitis or both and nasal polyps. The underlying mechanism of the reaction is obscure. METHODS To assess the nasal response to ASA challenge, four groups of patients were challenged orally with ASA: group A (10 ASA-sensitive patients); group B (nine patients with nasal polyps and histories of tolerance to ASA); group C (nine ASA-tolerant patients with chronic allergic rhinitis); and group D (eight healthy nonatopic subjects). RESULTS Nasal lavages obtained before and after ASA challenge were assayed for proteins (total protein, lactoferrin, lysozyme, albumin) and inflammatory mediators (histamine, prostaglandin D2, and leukotriene C4). ASA challenges induced severe rhinorrhea and congestion and significant increases in mean concentrations of all measured nasal proteins in group A. Histamine and prostaglandin D2 rose, but not significantly. In the two control groups with chronic rhinitis, ASA induced increases in the concentration of proteins and histamine. Leukotriene C4 concentrations were significantly elevated in nasal lavages after ASA challenge in groups A and C only. In group D no symptoms or changes in nasal proteins were observed after aspirin challenge. CONCLUSIONS These observations suggest that production of lipoxygenase products of arachidonate may induce glandular secretions that may participate in the clinical changes associated with ASA sensitivity.

Estimation of nasal epithelial lining fluid using urea as a marker.

BACKGROUND The luminal surface of respiratory mucous membranes is lined with an epithelial lining fluid (ELF) layer. Previous attempts to determine ELF volumes in airways have used dyes or freely diffusible molecules such as urea, yet have not led to a universally accepted method. The nasal mucous membrane provides an accessible area to examine whether urea is an appropriate marker of respiratory ELF volume. METHODS AND RESULTS Collection of undiluted nasal secretions after either glandular stimulation or induction of vascular permeability confirmed that plasma urea and nasal urea concentrations are equivalent. Baseline ELF volume was calculated as 800 microliters/nostril. The calculated molar concentrations of urea in ELF did not vary with either methacholine or histamine challenge. CONCLUSIONS These data indicate the plasma, interstitial, glandular, and ELF urea concentrations are equivalent and, therefore, that urea is a useful marker of ELF volume in the nasal mucosa.

Effects of nedocromil sodium on allergen-induced rhinitis in humans

Sixteen patients with allergic rhinitis were recruited into a double-blind crossover protocol studying the immediate effect of nedocromil sodium (NS) on the pattern of nasal symptoms and secretions after allergen challenge. After pretreatment with placebo or NS, allergen challenge resulted in pruritus, rhinorrhea, nasal congestion, and/or sneezing within 10 minutes in 12 of 16 subjects. Prostaglandin D2 (PGD2), a marker of mast cell degranulation, increased proportionately with symptom scores, remaining above the 95% confidence interval for 120 minutes after both pretreatments. No difference in PGD2 between the NS-treatment and placebo-treatment days was observed. Protein markers extravasated through the vasculature (albumin and IgG) or secreted by mucosal glands (lactoferrin) were assayed. Total protein, albumin, IgG, and lactoferrin all remained greater than 95% confidence interval for 100 minutes after allergen challenge in the placebo-pretreated group and 120 minutes in the NS-pretreated group. Although there appeared to be a trend for lower secretion of PGD2, albumin, and IgG in the NS-treated group, the overall differences did not achieve statistical significance. This protocol revealed that two topical 130 microliter doses of a 1% solution of NS failed to significantly reduce allergen-induced symptoms, PGD2 generation, or secretion of albumin, IgG, or lactoferrin when NS was compared with placebo. The anti-inflammatory and mast cell-stabilizing effects of NS may require more prolonged pretreatment before provocation to be effective.