Abstract:T. Evaluation of cigarette smokeinduced emphysema in mice using quantitative micro-computed tomography. Am J Physiol Lung Cell Mol Physiol 308: L1039-L1045, 2015. First published March 27, 2015 doi:10.1152/ajplung.00366.2014.-Chronic cigarette smoke (CS) exposure provokes variable changes in the lungs, and emphysema is an important feature of chronic obstructive pulmonary disease. The usefulness of micro-computed tomography (CT) to assess emphysema in different mouse models has been investigated, but few stud… Show more
“…One possibility is that residual volume may have increased in the female mice after chronic smoke exposure, corresponding to dynamic hyperinflation in patients with emphysema, which may reflect an increased tendency for remodelled peripheral airways to collapse at low lung volumes. In support of our observations, Sasaki and colleagues showed that female C57BL/6 mice have increased end-expiratory lung volume after 20 weeks of cigarette smoke exposure [16]. Furthermore, total lung capacity was increased in mice exposed to 16 weeks of smoke exposure compared to wild type mice [17].…”
Female smokers have increased risk of chronic obstructive pulmonary disease (COPD) compared with male smokers who have a similar history of cigarette smoke exposure. We have shown previously that chronic smoke exposure for 6 months leads to increased airway wall remodeling in female C57BL/6 mice compared with male C57BL/6 mice. These differences, however, were not evident in female ovariectomized mice exposed to cigarette smoke. Herein, we report on the pulmonary function test results from the flexiVent system, which was used to determine the potential functional consequences of the histologic changes observed in these mice. We found that tissue damping (G) was increased in female compared to male or ovariectomized female mice after smoke exposure. At low oscillating frequencies, complex input resistance (Zrs) and impedance (Xrs) of the respiratory system was increased and decreased, respectively, in female but not in male or ovariectomized female mice after smoke exposure. Quasistatic pressure-volume curves revealed a reduction in inspiratory capacity in female mice but not in male or ovariectomized female mice after smoke exposure. The remaining lung function measurements including quasistatic compliance were similar amongst all groups. This is the first study characterizing a sexual dimorphism in respiratory functional properties in a mouse model of COPD. These findings demonstrate that increased airway remodeling in female mice following chronic smoke exposure is associated with increased tissue resistance in the peripheral airways. These data may explain the importance of female sex hormones and the increased risk of airway disease in female smokers.
“…One possibility is that residual volume may have increased in the female mice after chronic smoke exposure, corresponding to dynamic hyperinflation in patients with emphysema, which may reflect an increased tendency for remodelled peripheral airways to collapse at low lung volumes. In support of our observations, Sasaki and colleagues showed that female C57BL/6 mice have increased end-expiratory lung volume after 20 weeks of cigarette smoke exposure [16]. Furthermore, total lung capacity was increased in mice exposed to 16 weeks of smoke exposure compared to wild type mice [17].…”
Female smokers have increased risk of chronic obstructive pulmonary disease (COPD) compared with male smokers who have a similar history of cigarette smoke exposure. We have shown previously that chronic smoke exposure for 6 months leads to increased airway wall remodeling in female C57BL/6 mice compared with male C57BL/6 mice. These differences, however, were not evident in female ovariectomized mice exposed to cigarette smoke. Herein, we report on the pulmonary function test results from the flexiVent system, which was used to determine the potential functional consequences of the histologic changes observed in these mice. We found that tissue damping (G) was increased in female compared to male or ovariectomized female mice after smoke exposure. At low oscillating frequencies, complex input resistance (Zrs) and impedance (Xrs) of the respiratory system was increased and decreased, respectively, in female but not in male or ovariectomized female mice after smoke exposure. Quasistatic pressure-volume curves revealed a reduction in inspiratory capacity in female mice but not in male or ovariectomized female mice after smoke exposure. The remaining lung function measurements including quasistatic compliance were similar amongst all groups. This is the first study characterizing a sexual dimorphism in respiratory functional properties in a mouse model of COPD. These findings demonstrate that increased airway remodeling in female mice following chronic smoke exposure is associated with increased tissue resistance in the peripheral airways. These data may explain the importance of female sex hormones and the increased risk of airway disease in female smokers.
“…7c). These data suggest that mild emphysema developed at 16 weeks of CS exposure in WT mice as observed in the previous report [31]. On the other hand, we found that CS exposure neither increased the lung volume nor Lm in Aldh2*2 Tg mice (Fig.…”
Section: Resultssupporting
confidence: 91%
“…All lungs were examined by micro-CT scanning followed by euthanasia and the lungs were collected and embedded in paraffin, to examine for digital and histological signs of lung damage and emphysema. Digital readings of the low attenuation area (LAA)%, CT values, and lung volumes were compared between the WT and Aldh2*2 Tg mice as previously described [31]. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Ten adult Aldh2*2 Tg mice and their WT littermates were exposed to mainstream CS using commercially available cigarettes (Marlboro, 12 mg tar/1.0 mg nicotine) as previously described [31]. Exposure to 4% CS was given for one hour/day and 5 days/week for 16 weeks.…”
Section: Methodsmentioning
confidence: 99%
“…Age-matched control mice for each group were exposed to air over the same period. Emphysema was assessed in the living animals by micro CT and after euthanasia on the histological sections, and was quantified using mean linear intercepts (Lm) [31]. …”
Background: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. Methods: We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 −/− mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 −/− mice.
BackgroundPulmonary emphysema is a part of chronic obstructive pulmonary disease, which is an irreversible chronic respiratory disease. In order to avoid further damage to lung tissue, early diagnosis and treatment of pulmonary emphysema is essential.PurposeEarly pulmonary emphysema diagnosis is difficult with conventional radiographic imaging. Recently, x‐ray phase contrast imaging has proved to be an effective and promising imaging strategy for soft tissue, due to its high sensitivity and multi‐contrast. The aim of this study is to diagnose pulmonary emphysema early utilizing an x‐ray Talbot‐Lau interferometer (TLI).MethodsWe successfully established the mouse model of emphysema by porcine pancreatic elastase treatment, and then used the established x‐ray TLI to perform imaging experiments on the mice with different treatment time. The traditional absorption CT and phase contrast CT were obtained simultaneously through TLI. The CT results and histopathology of mice lung in different treatment time were quantitatively analyzed.ResultsBy imaging mice lungs, it can be found that phase contrast has higher sensitivity than absorption contrast in early pulmonary emphysema. The results show that the phase contrast signal could distinguish the pulmonary emphysema earlier than the conventional attenuation signal, which can be consistent with histological images. Through the quantitative analysis of pathological section and phase contrast CT, it can be found that there is a strong linear correlation.ConclusionsIn this study, we quantitatively analyze mean linear intercept of histological sections and CT values of mice. The results show that the phase contrast signal has higher imaging sensitivity than the attenuation signal. X‐ray TLI multi‐contrast imaging is proved as a potential diagnostic method for early pulmonary emphysema in mice.
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