Hyperresponsiveness in the Human Nasal Airway: New Targets for the Treatment of Allergic Airway Disease

Abstract

Allergic rhinitis is a condition which affects over 15% of the population in the United Kingdom. The pathological process involves two stages: nasal inflammation, and the development of nasal airway hyperresponsiveness (AHR) to allergen and a number of other stimuli. This results in the amplification of any subsequent allergic reaction, contributing to the chronic allergic state. A number of different hypotheses have been proposed to explain the underlying mechanism of AHR, including a role for eosinophil-derived proteins, free radicals and neuropeptides. While there may be a number of independent pathways which can result in AHR, evidence obtained from both animal models and in vivo experiments in humans indicate that some mediators may interact with one another, resulting in AHR. Further research into these interactions may open new avenues for the pharmacological treatment of chronic allergic rhinitis, and possibly other allergic airway diseases.

Allergic rhinitis in children

“…Ongoing allergen exposure induces nasal airway hyperresponsiveness (NAHR), a hallmark of AR. NAHR is a pathophysiological state whereby the response of the nasal airway to both allergen and mediators (such as histamine and bradykinin) is increased compared with normal 9 . Thus, in experimental terms, the same level of exposure to antigen and other mediators results in increased nasal obstruction, tissue oedema and production of secretions.…”

“…Subsequent exposure causes the release of inflammatory mediators, generating an immediate, IgE‐dependent allergic response. About one third of patients with allergic rhinitis experience a late phase reaction 6–12 h after exposure, associated histologically with an influx of inflammatory cells (including eosinophils, neutrophils and T‐lymphocytes) to the nasal airways, where they release a variety of mediators that further exacerbate symptoms 9 . IgE, Immunoglobulin E; PAF, Platelet activating factor.…”

“…NAHR is a pathophysiological state whereby the response of the nasal airway to both allergen and mediators (such as histamine and bradykinin) is increased compared with normal. 9 Thus, in experimental terms, the same level of exposure to antigen and other mediators results in increased nasal obstruction, tissue oedema and production of secretions. While a variety of pharmacological agents can be used to treat the initial inflammatory response, only steroids are effective in preventing NAHR.…”

Clinical Effects of a Hop Water Extract on Japanese Cedar Pollinosis during the Pollen Season: A Double-Blind, Placebo-Controlled Trial

“…24) Cationic granule proteins such as major basic protein and eosinophil cationic protein that are released from eosinophils injure normal tissue. 25) In our previous in vitro study, HWE significantly inhibited histamine release from human basophilic KU812 cells. 7) Furthermore, in an in vivo study, an oral administration of HWE significantly inhibited the vascular permeability induced by compound 48/80 stimulation.…”

Pharmacological Characterization of the Novel Histamine H3-Receptor Antagonist N-(3,5-Dichlorophenyl)-N′-[[4-(1 H-imidazol-4-ylmethyl)phenyl]-methyl]-urea (SCH 79687)

“…Symptoms of the disease are pruritus, sneezing, rhinorrhea, mucosal inflammation, and nasal congestion (Turner and Foreman, 1999;Corey et al, 2000). Mast cell histamine is a principal mediator in nasal allergic responses in sensitized people (Babe and Serafin, 1996;Baraniuk, 1998;Park and Baraniuk, 2002).…”