Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice

Thomas Glaab,Jens M Hohlfeld,Ralf Baelder,Regina Korolewitz,Armin Braun,Norbert Krug,Wayne Mitzner,Michaela Ziegert,Heinz G Hoymann

doi:10.1186/1465-9921-6-139

Abstract

BackgroundThis study seeks to compare the ability of repeatable invasive and noninvasive lung function methods to assess allergen-specific and cholinergic airway responsiveness (AR) in intact, spontaneously breathing BALB/c mice.MethodsUsing noninvasive head-out body plethysmography and the decrease in tidal midexpiratory flow (EF50), we determined early AR (EAR) to inhaled Aspergillus fumigatus antigens in conscious mice. These measurements were paralleled by invasive determination of pulmonary conductance (GL), dynamic compliance (Cdyn) and EF50 in another group of anesthetized, orotracheally intubated mice.ResultsWith both methods, allergic mice, sensitized and boosted with A. fumigatus, elicited allergen-specific EAR to A. fumigatus (p < 0.05 versus controls). Dose-response studies to aerosolized methacholine (MCh) were performed in the same animals 48 h later, showing that allergic mice relative to controls were distinctly more responsive (p < 0.05) and revealed acute airway inflammation as evidenced from increased eosinophils and lymphocytes in bronchoalveolar lavage.ConclusionWe conclude that invasive and noninvasive pulmonary function tests are capable of detecting both allergen-specific and cholinergic AR in intact, allergic mice. The invasive determination of GL and Cdyn is superior in sensitivity, whereas the noninvasive EF50 method is particularly appropriate for quick and repeatable screening of respiratory function in large numbers of conscious mice.

Highlights

This study seeks to compare the ability of repeatable invasive and noninvasive lung function methods to assess allergen-specific and cholinergic airway responsiveness (AR) in intact, spontaneously breathing BALB/c mice
The invasive determination of GL and Cdyn is superior in sensitivity, whereas the noninvasive EF50 method is appropriate for quick and repeatable screening of respiratory function in large numbers of conscious mice
Allergic BALB/C mice (n = 8) received an intraperitoneal and subcutaneous injection of soluble A. fumigatus antigens (5 μg each, Greer Laboratories Inc, Lenoir, NC, USA), dissolved in incomplete Freund's adjuvant in a volume of 0.1 ml given on day 0 and were boosted noninvasively by inhalation over 10 min in a closed chamber with 1 % of A. fumigatus aerosol dissolved in saline on day 14 (jet nebulizer, LC Star, 2.8 μm mass median aerodynamic diameter (MMAD), Pari GmbH, Starnberg, Germany)

Summary

Introduction

This study seeks to compare the ability of repeatable invasive and noninvasive lung function methods to assess allergen-specific and cholinergic airway responsiveness (AR) in intact, spontaneously breathing BALB/c mice. Asthma is a complex disease associated with reversible airway obstruction of variable degree, airway inflammation, airway hyperresponsiveness (AHR) and airway remodeling. These hallmarks of asthma are being examined in murine models, with the goal of understanding the basic cellular and genetic mechanisms of allergic inflammation that underlie the immunologic basis of the disease [1]. Existing methods for measuring respiratory function in mice in vivo include invasive and noninvasive approaches [2,3]. A novel modification to this invasive technology has enabled repetitive invasive recordings of pulmonary mechanics in conjunction with local aerosol delivery in anesthetized, orotracheally intubated, spontaneously breathing mice [4]

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