Abstract

In this study a direct comparison was made between non-invasive and non-ventilated unrestrained whole body plethysmography (Penh) (conscious animals) and the invasive ventilated lung resistance (RL) method (anesthetized animals) in both mild and severe allergic airway inflammation models. Mild inflammation was induced by intraperitoneal sensitization and aerosols of ovalbumin. Severe inflammation was induced by intraperitoneal sensitization using trinitrophenyl-ovalbumin, followed by intranasal challenges with IgE-allergen complexes. A significant increase in airway responsiveness to methacholine was observed in the mild inflammation group when RL was measured. Significant changes in both RL and Penh were observed in the severe inflammation groups. There was a significant increase in the number of inflammatory cells in the Broncho-Alveolar Lavage Fluid (BALF) in both the mild and severe inflammation animals. The enforced ventilation of the animals during the RL measurement further increased the number of cells in the BALF. IL-2 and RANTES levels in the BALF were higher in the severe inflammation groups compared to the mild inflammation groups. Penh gave only reliable measurements during severe airway inflammation. Measuring RL gave consistent results in both mild and severe allergic airway inflammation models however, ventilation induced an additional cell influx into the airways.

Highlights

  • Asthma is characterized by airway hyperresponsiveness and inflammation

  • Respiratory patterns can be influenced by stress Hoymann (2007), heating or humidification of the Abbreviations: BALF, Broncho-Alveolar Lavage Fluid; OVA, Ovalbumin; RL, Lung Resistance; TNP, Trinitrophenyl; VILI, Ventilator-Induced Lung Injury

  • AIRWAY FUNCTION Airway responsiveness was measured in conscious unrestrained mice (Penh) or in anesthetized ventilated animals (RL) exposed to inhaled methacholine 24 h after the last OVA or saline challenge

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Summary

Introduction

Airway inflammation is initiated and propagated by multiple inflammatory mediators such as lipid mediators, cytokines, and chemokines (O’Byrne and Inman, 2003; Barnes, 2008). Unrestrained whole body plethysmography (Penh), a noninvasive method for measurement of airway responsiveness, has been used frequently but its validity is under debate. For this method the airway function is measured with enhanced pause (Penh), an empirical and dimensionless parameter (Frazer et al, 2011). Penh is viewed as a better indicator for control of breathing (as seen in respiratory patterns) rather than an indicator for mechanical lung function (Bates and Irvin, 2003; Irvin and Bates, 2003; O’Byrne and Inman, 2003; Adler et al, 2004). Respiratory patterns can be influenced by stress Hoymann (2007), heating or humidification of the Abbreviations: BALF, Broncho-Alveolar Lavage Fluid; OVA, Ovalbumin; RL, Lung Resistance; TNP, Trinitrophenyl; VILI, Ventilator-Induced Lung Injury

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