Use of mean airspace chord length to assess emphysema

Mitzner, Wayne

doi:10.1152/japplphysiol.90968.2008

Cited by 30 publications

(31 citation statements)

References 15 publications

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“…In C57BL/6 mice, elastase instillations induce well-described enlargements of airspaces. Traditionally, the effect of elastase on lung structure is quantitatively assessed using a mean chord length, recognized as the gold standard marker of the destruction of alveolar walls measured from a histological slice (2). As expected, the histomorphometric results in this study revealed significant changes in L m values between the control and elastase-instilled groups, with mean values increasing from 93 6 15 to 143 6 15 mm.…”

Section: Discussionsupporting

confidence: 76%

“…In experimentally induced emphysema, histomorphometry is used as an efficient tool in quantification of the extent of emphysema lesions (2). However, this method is terminal, and it cannot be used in longitudinal studies-to track the evolution of a disease or to monitor the treatment efficacy in subjects being exposed to pharmaceutical intervention.…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal and noninvasive assessment of emphysema evolution in a murine model using proton MRI

Żurek

Boyer

Caramelle

et al. 2011

Magnetic Resonance in Med

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Ultrashort echo time (550 ms) MR imaging was implemented to track the emphysema development in mice lung challenged with elastase. Two parameters, namely, signal intensity and T 2 *, were used to monitor the disease evolution. Nine mice were imaged before and at 24 h as well as at 3 and 8 weeks after elastase instillation. Five mice instilled with saline served as controls. At week 8, the mean normalized signal intensity 6 SD was 0.89 6 0.20 for healthy controls and 0.64 6 0.10 for animals with emphysema. Similarly, a reduced value of T 2 * (1.27 6 0.35 ms vs 0.96 6 0.18 ms) was found in the emphysema group. The mean signal intensity drop and the reduction of T 2 * were prominent at 3 weeks following elastase instillation and stabilized between 3 and 8 weeks. The results indicated an excellent agreement between MR findings and histological morphometry (signal intensity, r 5 20.78, P 5 0.004; T 2 *, r 5 20.78, P 5 0.001). This result shows that proton MRI allows structural changes at alveolar level to be monitored longitudinally. This technique, applied routinely in preclinical trials will represent a valuable tool for assessment of drug therapy efficacy. Magn Reson Med 68:898-904,

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Longitudinal and noninvasive assessment of emphysema evolution in a murine model using proton MRI

Żurek

Boyer

Caramelle

et al. 2011

Magnetic Resonance in Med

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“…Alternatively, others have suggested that because emphysema is a process of tissue destruction it is only a decrease in internal surface area that is demonstrative of emphysema (L m adjusted for lung volume represents internal surface area here) (44,63). This argument would suggest that the increase in L m in our aged mice is a morphological consequence of an increase in lung volume.…”

Section: Discussionmentioning

confidence: 81%

Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease

Sauler

Leng

Trentalange

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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The pathogenesis of chronic obstructive pulmonary disease (COPD) remains poorly understood. Cellular senescence and apoptosis contribute to the development of COPD; however, crucial regulators of these underlying mechanisms remain unknown. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that antagonizes both apoptosis and premature senescence and may be important in the pathogenesis of COPD. This study examines the role of MIF in the pathogenesis of COPD. Mice deficient in MIF (Mif(-/-)) or the MIF receptor CD74 (Cd74(-/-)) and wild-type (WT) controls were aged for 6 mo. Both Mif(-/-) and Cd74(-/-) mice developed spontaneous emphysema by 6 mo of age compared with WT mice as measured by lung volume and chord length. This was associated with activation of the senescent pathway markers p53/21 and p16. Following exposure to cigarette smoke, Mif(-/-) mice were more susceptible to the development of COPD and apoptosis compared with WT mice. MIF plasma concentrations were measured in a cohort of 224 human participants. Within a subgroup of older current and former smokers (n = 72), MIF concentrations were significantly lower in those with COPD [8.8, 95%CI (6.7-11.0)] compared with those who did not exhibit COPD [12.7 ng/ml, 95%CI (10.6-14.8)]. Our results suggest that both MIF and the MIF receptor CD74 are required for maintenance of normal alveolar structure in mice and that decreases in MIF are associated with COPD in human subjects.

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“…Indicative of impaired alveologeneis, Spp1 (2/2) mice had increased alveolar size (i.e., L m ) that was detectable as early as 4 weeks of age when the process is just completed. Increased alveolar size also implicates reduced alveolar surface area (S = 4V/L m ) for gas exchange (93). At around 4 weeks of age, the lung development is complete, and the lung assumes the structure of an adolescent lung.…”

Section: Discussionmentioning

confidence: 99%

Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice

Ganguly

Martin

Concel

et al. 2014

Am J Respir Cell Mol Biol

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Secreted phosphoprotein 1 (Spp1) is located within quantitative trait loci associated with lung function that was previously identified by contrasting C3H/HeJ and JF1/Msf mouse strains that have extremely divergent lung function. JF1/Msf mice with diminished lung function had reduced lung SPP1 transcript and protein during the peak stage of alveologenesis (postnatal day [P]14-P28) as compared with C3H/ HeJ mice. In addition to a previously identified genetic variant that altered runt-related transcription factor 2 (RUNX2) binding in the Spp1 promoter, we identified another promoter variant in a putative RUNX2 binding site that increased the DNA protein binding. SPP1 induced dose-dependent mouse lung epithelial-15 cell proliferation. Spp1(2/2) mice have decreased specific total lung capacity/body weight, higher specific compliance, and increased mean airspace chord length (L m ) compared with Spp1(1/1) mice. Microarray analysis revealed enriched gene ontogeny categories, with numerous genes associated with lung development and/or respiratory disease. Insulin-like growth factor 1, Hedgehog-interacting protein, winglessrelated mouse mammary tumor virus integration site 5A, and NOTCH1 transcripts decreased in the lung of P14 Spp1 (2/2) mice as determined by quantitative RT-PCR analysis. SPP1 promotes pneumocyte growth, and mice lacking SPP1 have smaller, more compliant lungs with enlarged airspace (i.e., increased L m ). Microarray analysis suggests a dysregulation of key lung developmental transcripts in gene-targeted Spp1 (2/2) mice, particularly during the peak phase of alveologenesis. In addition to its known roles in lung disease, this study supports SPP1 as a determinant of lung development in mice.

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Use of mean airspace chord length to assess emphysema

Cited by 30 publications

References 15 publications

Longitudinal and noninvasive assessment of emphysema evolution in a murine model using proton MRI

Longitudinal and noninvasive assessment of emphysema evolution in a murine model using proton MRI

Macrophage migration inhibitory factor deficiency in chronic obstructive pulmonary disease

Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice

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