Emily K Wu1,2, Sophia Eliseeva1,3, Homaira Rahimi2,4, Edward M Schwarz2,5, Steve N Georas1,3. 1. a Department of Microbiology and Immunology , University of Rochester School of Medicine and Dentistry , Rochester , New York , USA. 2. b Center for Musculoskeletal Research , University of Rochester School of Medicine and Dentistry , Rochester , New York , USA. 3. c Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester School of Medicine and Dentistry , Rochester , New York , USA. 4. d Department of Pediatrics , University of Rochester School of Medicine and Dentistry , Rochester , New York , USA. 5. e Department of Orthopaedics , University of Rochester School of Medicine and Dentistry , Rochester , New York , USA.
Abstract
Purpose: Micro-computed tomography (µCT) is increasingly being used on animal models as a minimally-invasive longitudinal outcome measure of pulmonary disease progression. However, while imaging can elucidate macroscopic structural changes over the whole lung, µCT is unable to describe the mechanical changes and functional impairments imposed by progressive disease, which can only be measured via pulmonary function tests (PFTs). The tumor necrosis factor-transgenic (TNF-Tg) mouse model of rheumatoid arthritis (RA) develops pulmonary pathology that mimics many aspects of the inflammatory interstitial lung disease (ILD) seen in a subset of patients with RA. Prior studies using µCT imaging of these mice found increased pulmonary density, characteristic of restrictive disease; however, there have been conflicting reports in the literature regarding the obstructive versus restrictive phenotype of this model. Our study looks to 1) define the functional impairments and 2) characterize the restrictive/obstructive nature of the disease found in this model. Materials and Methods: In this study, we performed PFTs at end-stage ILD, and paired these findings with µCT results, correlating radiology to functional parameters. TNF-Tg and WT littermates of both sexes underwent µCT imaging and PFT testing at 5.5 months-old. Spearman's correlation analyses were performed comparing lung tissue volume (LTV) to PFT parameters of gas exchange and tissue stiffness. Results: Compared to WT, TNF-Tg mice had impaired gas exchange capacity, increased respiratory resistance, and reduced lung compliance, elastance, and inspiratory capacity, indicating increased tissue stiffness and compromised pulmonary function. LTV was also consistently higher in TNF-Tg lungs. Conclusions: These findings demonstrate that: 1) TNF-Tg mice display a restrictive pathology, and 2) in vivo µCT is a valid outcome measure to infer changes in pulmonary mechanical and functional parameters.
Purpose: Micro-computed tomography (µCT) is increasingly being used on animal models as a minimally-invasive longitudinal outcome measure of pulmonary disease progression. However, while imaging can elucidate macroscopic structural changes over the whole lung, µCT is unable to describe the mechanical changes and functional impairments imposed by progressive disease, which can only be measured via pulmonary function tests (PFTs). The tumor necrosis factor-transgenic (TNF-Tg) mouse model of rheumatoid arthritis (RA) develops pulmonary pathology that mimics many aspects of the inflammatory interstitial lung disease (ILD) seen in a subset of patients with RA. Prior studies using µCT imaging of these mice found increased pulmonary density, characteristic of restrictive disease; however, there have been conflicting reports in the literature regarding the obstructive versus restrictive phenotype of this model. Our study looks to 1) define the functional impairments and 2) characterize the restrictive/obstructive nature of the disease found in this model. Materials and Methods: In this study, we performed PFTs at end-stage ILD, and paired these findings with µCT results, correlating radiology to functional parameters. TNF-Tg and WT littermates of both sexes underwent µCT imaging and PFT testing at 5.5 months-old. Spearman's correlation analyses were performed comparing lung tissue volume (LTV) to PFT parameters of gas exchange and tissue stiffness. Results: Compared to WT, TNF-Tg mice had impaired gas exchange capacity, increased respiratory resistance, and reduced lung compliance, elastance, and inspiratory capacity, indicating increased tissue stiffness and compromised pulmonary function. LTV was also consistently higher in TNF-Tg lungs. Conclusions: These findings demonstrate that: 1) TNF-Tg mice display a restrictive pathology, and 2) in vivo µCT is a valid outcome measure to infer changes in pulmonary mechanical and functional parameters.
Authors: Jeffrey A Sparks; Shun-Chiao Chang; Katherine P Liao; Bing Lu; Alexander R Fine; Daniel H Solomon; Karen H Costenbader; Elizabeth W Karlson Journal: Arthritis Care Res (Hoboken) Date: 2016-06 Impact factor: 4.794
Authors: Evelien Schurgers; Freya Mertens; Jeroen A J Vanoirbeek; Stéphanie Put; Tania Mitera; Ellen De Langhe; Alfons Billiau; Peter H M Hoet; Benoit Nemery; Erik Verbeken; Patrick Matthys Journal: Eur J Immunol Date: 2012-10-16 Impact factor: 5.532
Authors: Emily K Wu; Robert D Ambrosini; R Matthew Kottmann; Christopher T Ritchlin; Edward M Schwarz; Homaira Rahimi Journal: Curr Rheumatol Rev Date: 2019
Authors: Natalie J Serkova; Kristine Glunde; Chad R Haney; Mohammed Farhoud; Alexandra De Lille; Elizabeth F Redente; Dmitri Simberg; David C Westerly; Lynn Griffin; Ralph P Mason Journal: Cancer Res Date: 2020-12-01 Impact factor: 13.312