Abstract
Airway hyperresponsiveness (AHR) has been proposed as a feature of pathogenesis of eosinophilic upper airway inflammation such as allergic rhinitis (AR). The measurement system for upper AHR (UAHR) in rodents is poorly developed, although measurements of nasal resistance have been reported. Here we assessed UAHR by direct measurement of swelling of the nasal mucosa induced by intranasal methacholine (MCh) using micro-computed tomography (micro-CT). Micro-CT analysis was performed in both naïve and ovalbumin-induced AR mice following intranasal administration of MCh. The nasal cavity was segmented into two-dimensional horizontal and axial planes, and the data for nasal mucosa were acquired for the region of interest threshold. Then, a ratio between the nasal mucosa area and nasal cavity area was calculated as nasal mucosa index. Using our novel method, nasal cavity structure was clearly identified on micro-CT, and dose-dependent increased swelling of the nasal mucosa was observed upon MCh treatment. Moreover, the nasal mucosa index was significantly increased in AR mice compared to controls following MCh treatment, while ovalbumin administration did not affect swelling of the nasal mucosa in either group. This UAHR following MCh treatment was completely reversed by pretreatment with glucocorticoids. This novel approach using micro-CT for investigating UAHR reflects a precise assessment system for swelling of the nasal mucosa following MCh treatment; it not only sheds light on the mechanism of AR but also contributes to the development of new therapeutic drugs in AR patients.
Highlights
Allergic rhinitis (AR) is a type 2 T helper cell (Th2)-skewed disease accompanied by eosinophils infiltration into nasal tissue, following exposure to inhaled antigens in the upper airway in genetically predisposed individuals
We found that the structures of the nasal cavity and the paranasal sinuses could be clearly identified on 2D reconstructed images using an image analyzer for animals and a micro-CT scanner
Studies have reported the use of micro-CT to determine the anatomy of the nasal cavity and paranasal sinuses [18,19], there have been no reports of a quantitative approach to measure the degree of swelling of the nasal mucosa
Summary
Allergic rhinitis (AR) is a type 2 T helper cell (Th2)-skewed disease accompanied by eosinophils infiltration into nasal tissue, following exposure to inhaled antigens in the upper airway in genetically predisposed individuals. Allergic rhinitis is diagnosed through a typical history of three characteristic symptoms (sneezing and nasal scratching, water rhinorrhea, or nasal obstruction) and clinical examination findings: detection of eosinophils in nasal discharge, nasal provocation test using antigen, elevation of allergen-specific immunoglobulin E (IgE) antibodies, or skin prick test [1,2]. Asthma is diagnosed on the basis of clinical symptoms (wheezing and dyspnea) and clinical examination findings: index of airway responsiveness in the respiratory tract to detect airway hyperresponsiveness (AHR), bronchodilator test, exhaled nitric oxide concentrations, and/or increased serum levels of specific IgE [3]. Lower AHR (L AHR) in asthma is reflected by an increased airway resistance due to constriction of the bronchial smooth muscles following nonspecific stimulants such as methacholine (MCh) or histamine. Measurement of U AHR in AR by which indicated as nasal resistance following provocation is rarely performed in clinical practice, clinical trials using nasal peak flow or rhinomanometry have been performed [1,9,10]
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