scholarly journals Preclinical MRI to Quantify Pulmonary Disease Severity and Trajectories in Poorly Characterized Mouse Models: A Pedagogical Example Using Data from Novel Transgenic Models of Lung Fibrosis

2021 ◽  
pp. 100013
Author(s):  
Ian R. Stecker ◽  
Matthew S. Freeman ◽  
Sneha Sitaraman ◽  
Chase S. Hall ◽  
Peter J. Niedbalski ◽  
...  
2007 ◽  
Vol 113 (5) ◽  
pp. 243-249 ◽  
Author(s):  
Hans-Joachim Kabitz ◽  
Stephan Walterspacher ◽  
David Walker ◽  
Wolfram Windisch

Staging criteria for COPD (chronic obstructive pulmonary disease) include symptoms and lung function parameters, but the role of reduced inspiratory muscle strength related to disease severity remains unclear. Therefore the present study tested whether inspiratory muscle strength is reduced in COPD and is related to disease severity according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria and assessed its clinical impact. PImax (maximal inspiratory mouth occlusion pressure), SnPna (sniff nasal pressure) and TwPmo (twitch mouth pressure) following bilateral anterior magnetic phrenic nerve stimulation were assessed in 33 COPD patients (8 GOLD0, 6 GOLDI, 6 GOLDII, 7 GOLDIII and 6 GOLDIV) and in 28 matched controls. Furthermore, all participants performed a standardized 6 min walking test. In comparison with controls, PImax (11.6±2.5 compared with 7.3±3.0 kPa; P<0.001), SnPna (9.7±2.5 compared with 6.9±3.3 kPa; P<0.001) and TwPmo (1.6±0.6 compared with 0.8±0.4 kPa; P<0.001) were markedly lower in COPD patients. TwPmo decreased with increasing COPD stage. TwPmo was correlated with walking distance (r=0.75; P<0.001), dyspnoea (r=−0.61; P<0.001) and blood gas values following exercise (r>0.57; P<0.001). Inspiratory muscle strength, as reliably assessed by TwPmo, decreased with increasing severity of COPD and should be considered as an important factor in rating disease severity and to reflect burden in COPD.


Author(s):  
Uma Rani Adhikari ◽  
Soma Roy

Chronic obstructive pulmonary disease (COPD) is recently the most common chronic lung disease and presents a serious medical, economic, and social problem for people. A correlational survey research was adopted to identify relationship between quality of life and disease severity among Chronic Obstructive Pulmonary Disease (COPD) clients attending Pulmonary Medicine OPD in a selected hospital, Kolkata with the objectives to assess the quality of life of Chronic Obstructive Pulmonary Disease (COPD) clients and to find out correlation between disease severity and quality of life among Chronic Obstructive Pulmonary Disease (COPD) clients. Purposive sampling technique was adapted to select 138 Chronic Obstructive Pulmonary Disease (COPD) clients attending Pulmonary Medicine OPD in a tertiary care hospital, Kolkata. The structured interview schedule was used to collect on demographic data and standardized WHO QOL BREF tool was used to assess Quality of Life. Standardized GOLD criteria were used to assess disease severity of COPD clients. Reliability of the demographic data collection tool was established by inter- rater method and r was 0.77. All the tools were tried out before final data collection. The finding of the study revealed statistically non-significant relationship between all the domain of QOL and disease severity of COPD patients. Total Quality of Life score is also not significantly related with COPD Disease severity score. The study results also showed that QOL is not associated with sociodemographic characteristics. The study concluded that, there is no correlation between quality of life and disease severity.


Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 674 ◽  
Author(s):  
Chiaho Shih ◽  
Chun-Che Liao ◽  
Ya-Shu Chang ◽  
Szu-Yao Wu ◽  
Chih-Shin Chang ◽  
...  

Enterovirus 71 (EV71) is a global health threat. Children infected with EV71 could develop hand-foot-and-mouth disease (HFMD), encephalitis, paralysis, pulmonary edema, and death. At present, no effective treatment for EV71 is available. We reviewed here various mouse models for EV71 pathogenesis and therapy. Earlier studies relied on the use of mouse-adapted EV71 strains. To avoid artificial mutations arising de novo during the serial passages, recent studies used EV71 clinical isolates without adaptation. Several human receptors for EV71 were shown to facilitate viral entry in cell culture. However, in vivo infection with human SCARB2 receptor transgenic mice appeared to be more limited to certain strains and genotypes of EV71. Efficacy of oral infection in these transgenic models is extremely low. Intriguingly, despite the lack of human receptors, immunodeficient neonatal mouse models can still be infected with EV71 clinical isolates via oral or intraperitoneal routes. Crossbreeding between SCARB2 transgenic and stat1 knockout mice generated a more sensitive and user-friendly hybrid mouse model. Infected hybrid mice developed a higher incidence and earlier onset of CNS disease and death. Different pathogenesis profiles were observed in models deficient in various arms of innate or humoral immunity. These models are being actively used for antiviral research.


2010 ◽  
Vol 5 ◽  
Author(s):  
Deniz Inal-Ince ◽  
Sema Savci ◽  
Melda Saglam ◽  
Ebru Calik ◽  
Hulya Arikan ◽  
...  

Background and aims: Fatigue is associated with longitudinal ratings of health in patients with chronic obstructive pulmonary disease (COPD). Although the degree of airflow obstruction is often used to grade disease severity in patients with COPD, multidimensional grading systems have recently been developed. The aim of this study was to investigate the relationship between perceived and actual fatigue level and multidimensional disease severity in patients with COPD. Materials and methods: Twenty-two patients with COPD (aged 52-74 years) took part in the study. Multidimensional disease severity was measured using the SAFE and BODE indices. Perceived fatigue was assessed using the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS). Peripheral muscle endurance was evaluated using the number of sit-ups, squats, and modified push-ups that each patient could do. Results: Thirteen patients (59%) had severe fatigue, and their St George’s Respiratory Questionnaire scores were significantly higher (p < 0.05). The SAFE index score was significantly correlated with the number of sit-ups, number of squats, FSS score and FIS score (p < 0.05). The BODE index was signif- icantly associated with the numbers of sit-ups, squats and modified push-ups, and with the FSS and FIS scores (p < 0.05). Conclusions: Peripheral muscle endurance and fatigue perception in patients with COPD was related to multidimensional disease severity measured with both the SAFE and BODE indices. Improvements in perceived and actual fatigue levels may positively affect multidimensional disease severity and health status in COPD patients. Further research is needed to investigate the effects of fatigue perception and exercise training on patients with different stages of multidimensional COPD severity.


2018 ◽  
Vol 12 (4) ◽  
pp. 1023-1028 ◽  
Author(s):  
Ramin Sami ◽  
Raheleh Sadegh ◽  
Neda Esmailzadehha ◽  
Sanaz Mortazian ◽  
Masoomeh Nazem ◽  
...  

Malnutrition is one of the most important factors that lead to lower quality of life in patients suffering from chronic obstructive pulmonary disease (COPD). There are several methods for assessing malnutrition including anthropometric indexes. The aim of this study was to determine the association of anthropometric indexes with disease severity in male patients with COPD in Qazvin, Iran. This cross-sectional study was conducted on 72 male patients with COPD in Qazvin, Iran, from May to December 2014. Spirometry was performed for all participants. Disease severity was determined using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline. Body mass index (BMI), mid-arm muscle circumference (MAMC), and triceps skinfold thickness (TSF) were measured. MAMC and TSF were categorized into three subgroups as <25th P, between 25th P and 75th P, and >75th P (Where P is the abbreviation for percentile.). Data were analyzed using ANOVA and logistic regression analysis. Mean age was 60.23 ± 11.39 years. Mean BMI was 23.23 ± 4.42 Kg/m2, mean MAMC was 28.34 ± 3.72 cm2, and mean TSF was 10.15 ± 6.03 mm. Mean BMI and MAMC in the GOLD stage IV were significantly lower than other stages. Of 72, 18.1% were underweight while 6.9% were obese. The GOLD stage IV was associated with 16 times increased risk of underweight and nine times increased risk of MAMC < 25th P. Disease severity was associated with BMI and MAMC as indexes of malnutrition in patients with COPD in the present study. The GOLD stage IV was associated with increased risk of underweight and low MAMC.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Moritz von Scheidt ◽  
Yuqi Zhao ◽  
Zeyneb Kurt ◽  
Heribert Schunkert ◽  
Xia Yang ◽  
...  

Atherosclerosis is a complex and heritable disease with a vast number of interacting genes, networks and molecular pathways. Mouse genetics has been utilized as a powerful tool to study human atherosclerosis and has identified hundreds of candidate genes; recent human genetic studies have also identified hundreds of suggestive genetic loci for atherosclerotic coronary artery disease (CAD). However, commonalities and differences of biological mechanisms in atherosclerosis between humans and mice are poorly examined. In this study, we aim to provide a systematic biological overview comparing mice and humans on pathway level. We first comprehensively reviewed and summarized known mouse genes associated with atherosclerosis based on studies of genetically modified mouse models. This effort revealed 743 mouse atherosclerosis genes from over 9,000 Pubmed publications, retrieved using the terms “atherosclerosis” or “atherogenesis” and “gene” or “qtl” and “mouse” or “mice” and “apoe” or “ldlr”, and followed by manual review and confirmation of the effects on atherosclerosis. Second, we conducted pathway analysis of the mouse atherosclerosis genes using data from Biocarta, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome. We found pathways including cytokine interactions or dependency to the immune system are highly over-represented among the mouse atherosclerosis genes. Many of these pathways (e.g., metabolism of lipids and lipoproteins) converged with those reported for human GWAS loci, but also highlighted several pathways (e.g., GPCR signaling) having a hitherto unknown effect on atherosclerosis in mice. Our results suggest that although there are certain differences in individual candidate genes, mouse models remain a promising approach to identify complex molecular pathways of atherosclerosis, and insights gained from mouse genetics of atherosclerosis could be validated and transferred to CAD in humans. Future network analysis of the mouse and human genes and pathways will provide further elucidation of the shared or distinct gene-gene regulation and interactions between species. This study might provide new starting points for drug development, therapeutic treatment and prevention of atherosclerosis and CAD in humans.


Author(s):  
Olivia Mekhael ◽  
Safaa Naiel ◽  
Megan Vierhout ◽  
Aaron I. Hayat ◽  
Spencer D. Revill ◽  
...  
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