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Airways hyperresponsiveness (AHR) is usually produced within days of first antigen exposure in mouse models of asthma. Furthermore, continual antigen challenge eventually results in the resolution of the AHR phenotype. Human asthma also waxes and wanes with time, suggesting that studying the time course of AHR in the allergic mouse would offer insights into the variation in symptoms seen in asthmatics. Mice were sensitized with ovalbumin (OVA) on days 0 and 14. As assessed by airway resistance (Rn), lung elastance (H) and tissue damping (G), AHR was measured post an OVA inhalation on day 21 (Short Challenge group), after three days of OVA inhalation on day 25 (Standard Challenge group) and following an OVA inhalation on day 55 in mice previously challenged on days 21–23 (Recall Challenge group). Bronchoalveolar lavage was analyzed for inflammatory cells, cytokines and protein. AHR in the Short Challenge group was characterized by an increase in Rn and neutrophil accumulation in the lavage. AHR in the Standard Challenge group was characterized by increases in H and G but by only a modest response in Rn, while inflammation was eosinophilic. In the Standard Challenge protocol, mice lacking fibrinogen were no different from control in their AHR response. AHR in the Recall Challenge group was characterized by increases only in G and H and elevated numbers of both neutrophils and eosinophils. Lavage cytokines were only elevated in the Recall Challenge group. Lavage protein was significantly elevated in all groups. The phenotype in allergically inflamed mice evolves distinctly over time, both in terms of the nature of the inflammation and the location of the AHR response. The study of mouse models of AHR might be better served by focusing on this variation rather than simply on a single time point at which AHR is maximal.

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The advent of micro-computed tomography (microCT) has provided significant advancement in our ability to generate clinically relevant assessments of lung health and disease in small animal models. As microCT use to generate outcomes analysis in pulmonary preclinical models has increased there have been substantial improvements in image quality and resolution, and data analysis software. However, there are limited published methods for standardized imaging and automated analysis available for investigators. Manual quantitative analysis of microCT images is complicated by the presence of inflammation and parenchymal disease. To improve the efficiency and limit user-associated bias, we have developed an automated pulmonary air and tissue segmentation (PATS) task list to segment lung air volume and lung tissue volume for quantitative analysis. We demonstrate the effective use of the PATS task list using four distinct methods for imaging, 1) in vivo respiration controlled scanning using a flexiVent, 2) longitudinal breath-gated in vivo scanning in resolving and non-resolving pulmonary disease initiated by lipopolysaccharide-, bleomycin-, and silica-exposure, 3) post-mortem imaging, and 4) ex vivo high-resolution scanning. The accuracy of the PATS task list was compared to manual segmentation. The use of these imaging techniques and automated quantification methodology across multiple models of lung injury and fibrosis demonstrates the broad applicability and adaptability of microCT to various lung diseases and small animal models and presents a significant advance in efficiency and standardization of preclinical microCT imaging and analysis for the field of pulmonary research.

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Author disclosures are available with the text of this article at www.atsjournals.org.

Airway resistance measurements using oscillometry provide a potential alternative to spirometry in assessing airway obstruction and dynamics due to measurements taken during tidal breathing. Oscillometry typically requires participants to form a tight seal around a mouthpiece which can prove challenging in some people. To address this challenge, we conducted a prospective study to evaluate the effect of different interfaces: mouthpiece, mouth mask and nasal mask; on respiratory impendence results from oscillometry in a cohort of healthy adults. Ten healthy adults (seven females; mean age: 38.9 years (SD ±15.5) underwent oscillometry using each of the three interfaces. We measured resistance at 5Hz (Rrs5); frequency dependence of resistance at 5 -20Hz (Rrs5-20); and reactance area (Ax). Rrs5 was not different when using the mouthpiece compared to the mouth mask (mean 2.98 cmH2O.l-1.s (SD ±0.68) vs mean 3.2 cmH2O.l-1.s (SD ±0.81; p=0.92; 95% CI -0.82 to +0.38) respectively. Nasal mask Rrs5 measurements were significant higher than mouthpiece measurements (mean 7.31 cmH2O.l-1.s; SD ±2.62; p < 0.01; 95%CI -6.91 to -1.75). With Ax5 we found a mean of 4.01 cm H2O/l (SD ±2.04) with the mouth mask compared to a mean of 4.02 cm H2O/l (SD ±1.87;p=1.0 95% CI -1.86 to +1.87) for the mouthpiece, however, we found a significant difference between the mouthpiece and nasal mask for Ax (mean= 10.71; SD ±7.0 H2O/l; p=0.04, 95% CI -12.96 to -0.43). Our findings show that oscillometry using a mouth mask may be just as effective as using a mouthpiece in assessing airway dynamics and resistance.