Combined forced oscillation and forced expiration measurements in mice for the assessment of airway hyperresponsiveness

Abstract

BackgroundPulmonary function has been reported in mice using negative pressure-driven forced expiratory manoeuvres (NPFE) and the forced oscillation technique (FOT). However, both techniques have always been studied using separate cohorts of animals or systems. The objective of this study was to obtain NPFE and FOT measurements at baseline and following bronchoconstriction from a single cohort of mice using a combined system in order to assess both techniques through a refined approach.MethodsGroups of allergen- or sham-challenged ovalbumin-sensitized mice that were either vehicle (saline) or drug (dexamethasone 1 mg/kg ip)-treated were studied. Surgically prepared animals were connected to an extended flexiVent system (SCIREQ Inc., Montreal, Canada) permitting NPFE and FOT measurements. Lung function was assessed concomitantly by both techniques at baseline and following doubling concentrations of aerosolized methacholine (MCh; 31.25 - 250 mg/ml). The effect of the NPFE manoeuvre on respiratory mechanics was also studied.ResultsThe expected exaggerated MCh airway response of allergic mice and its inhibition by dexamethasone were detected by both techniques. We observed significant changes in FOT parameters at either the highest (Ers, H) or the two highest (Rrs, RN, G) MCh concentrations. The flow-volume (F-V) curves obtained following NPFE manoeuvres demonstrated similar MCh concentration-dependent changes. A dexamethasone-sensitive decrease in the area under the flow-volume curve at the highest MCh concentration was observed in the allergic mice. Two of the four NPFE parameters calculated from the F-V curves, FEV0.1 and FEF50, also captured the expected changes but only at the highest MCh concentration. Normalization to baseline improved the sensitivity of NPFE parameters at detecting the exaggerated MCh airway response of allergic mice but had minimal impact on FOT responses. Finally, the combination with FOT allowed us to demonstrate that NPFE induced persistent airway closure that was reversible by deep lung inflation.ConclusionsWe conclude that FOT and NPFE can be concurrently assessed in the same cohort of animals to determine airway mechanics and expiratory flow limitation during methacholine responses, and that the combination of the two techniques offers a refined control and an improved reproducibility of the NPFE.

Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique

“…In addition to FOT, the flexiVent system can also be used to collect other types of lung function [8][9][10] or cardiovascular Table 4. System Comparison.…”

Neutrophilic oxidative stress mediates organic dust-induced pulmonary inflammation and airway hyperresponsiveness

“…Using a constant phase model to assess respiratory system mechanics, the present study showed that OD caused dose-dependent AHR in Rn, G, and H. These data demonstrate that OD exposure affects the responses to MCh in proximal parts of the lung represented by Rn, providing information about large airway responses. Distal lung compartments, represented by G, a reflection of large and small airway narrowing, and H, which represents altered dynamic lung elastance and increases due to derecruitment of lung tissue from airway closure (40,41), were also increased by OD treatment.…”

Elimination of p19ARF‐expressing cells protects against pulmonary emphysema in mice

“…Pulmonary function tests were performed on a FlexiVent system (Scireq) as previously described (Hashimoto et al, 2016; Shalaby, Gold, Schuessler, Martin, & Robichaud, 2010). The mice were euthanized by an intraperitoneal injection of pentobarbital sodium (100 mg/kg of body weight) and connected to the FlexiVent system after tracheotomy.…”