المؤلفون: Harris, Elex S., Novak, Lea, Fernandez-Petty, Courtney M., Lindgren, Natalie R., Baker, Shenda M., Birket, Susan E., Rowe, Steven M.

المساهمون: National Heart, Lung, and Blood Institute, Cystic Fibrosis Foundation, National Institutes of Health

المصدر: Journal of Cystic Fibrosis ; volume 22, issue 6, page 1104-1112 ; ISSN 1569-1993

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Pediatrics, Perinatology and Child Health

الإتاحة: https://doi.org/10.1016/j.jcf.2023.08.011Test
https://api.elsevier.com/content/article/PII:S1569199323008822?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1569199323008822?httpAccept=text/plainTest

المؤلفون: Keith, Johnathan D., Henderson, Alexander G., Fernandez-Petty, Courtney M., Davis, Joy M., Oden, Ashley M., Birket, Susan E.

المساهمون: National Heart, Lung, and Blood Institute Cystic Fibrosis Foundation

المصدر: Frontiers in Physiology ; volume 13 ; ISSN 1664-042X

الوصف: Cystic fibrosis (CF) airway disease is characterized by excessive and accumulative mucus in the airways. Mucociliary clearance becomes defective as mucus secretions become hyperconcentrated and viscosity increases. The CFTR-knockout (KO) rat has been previously shown to progressively develop delayed mucociliary transport, secondary to increased viscoelasticity of airway secretions. The humanized-G551D CFTR rat model has demonstrated that abnormal mucociliary clearance and hyperviscosity is reversed by ivacaftor treatment. In this study, we sought to identify the components of mucus that changes as the rat ages to contribute to these abnormalities. We found that Muc5b concentrations, and to a lesser extent Muc5ac, in the airway were increased in the KO rat compared to WT, and that Muc5b concentration was directly related to the viscosity of the mucus. Additionally, we found that methacholine administration to the airway exacerbates these characteristics of disease in the KO, but not WT rat trachea. Lastly we determined that at 6 months of age, CF rats had mucus that was adherent to the airway epithelium, a process that is reversed by ivacaftor therapy in the hG551D rat. Overall, these data indicate that accumulation of Muc5b initiates the muco-obstructive process in the CF lung prior to infection.

الإتاحة: https://doi.org/10.3389/fphys.2022.884166Test

المؤلفون: Vijaykumar, Kadambari, Hui Min Leung, Barrios, Amilcar, Fernandez-Petty, Courtney M., Solomon, George M., Hathorne, Heather Y., Wade, Justin D., Monroe, Kathryn, Slaten, Katie Brand, Qian Li, Leal Jr., Sixto M., Moates, Derek B., Pierce, Hannah M., Olson, Kristian R., Currier, Paul, Foster, Sam, Marsden, Doug, Tearney, Guillermo J., Rowe, Steven M.

المصدر: American Journal of Respiratory Cell & Molecular Biology; Nov2023, Vol. 69 Issue 5, p592-595, 16p

مصطلحات موضوعية: CILIA & ciliary motion, MUCOCILIARY system, COVID-19, SUMATRIPTAN, COVID-19 pandemic

مستخلص: The article investigates the impact of COVID-19 on respiratory mucosa using micro-optical coherence tomography (μOCT).Topics include the use of μOCT imaging, manifestations of respiratory epithelial cell dysfunction, and the potential application of ciliary imaging in understanding early pathogenic mechanisms and evaluating disease progression and therapeutic response.

المؤلفون: Leung, Hui Min, Birket, Susan E., Hyun, Chulho, Ford, Timothy N., Cui, Dongyao, Solomon, George M., Shei, Ren-Jay, Adewale, Adegboyega Timothy, Lenzie, Andrew R., Fernandez-Petty, Courtney M., Zheng, Hui, Palermo, Justin H., Cho, Do-Yeon, Woodworth, Bradford A., Yonker, Lael M., Hurley, Bryan P., Rowe, Steven M., Tearney, Guillermo J.

المساهمون: National Institutes of Health, Cystic Fibrosis Foundation

المصدر: Science Translational Medicine ; volume 11, issue 504 ; ISSN 1946-6234 1946-6242

الوصف: Micro-optical coherence tomography with an intranasal imaging probe detects defects in the mucociliary transport of people with cystic fibrosis.

الإتاحة: https://doi.org/10.1126/scitranslmed.aav3505Test

المؤلفون: Birket, Susan E., Davis, Joy M., Fernandez-Petty, Courtney M., Henderson, Alexander G., Oden, Ashley M., LiPing Tang, Hui Wen, Jeong Hong, Lianwu Fu, Chambers, Andre, Fields, Alvin, Zhao, Gojun, Tearney, Guillermo J., Sorscher, Eric J., Rowe, Steven M., Tang, LiPing, Wen, Hui, Hong, Jeong, Fu, Lianwu

المصدر: American Journal of Respiratory & Critical Care Medicine; 11/1/2020, Vol. 202 Issue 9, p1271-1282, 12p

مصطلحات موضوعية: ANIMAL models in research, RATIONALE (Episcopal vestment), CYSTIC fibrosis, LUNG diseases, CLINICAL trials, LAXATIVES, MUCUS, BIOLOGICAL models, RESEARCH, PHENOLS, ANIMAL experimentation, RESEARCH methodology, EVALUATION research, MEDICAL cooperation, RATS, COMPARATIVE studies, IMPACT of Event Scale, RESEARCH funding, QUINOLONE antibacterial agents, MEMBRANE proteins

مستخلص: Rationale: Animal models have been highly informative for understanding the characteristics, onset, and progression of cystic fibrosis (CF) lung disease. In particular, the CFTR-/- rat has revealed insights into the airway mucus defect characteristic of CF but does not replicate a human-relevant CFTR (cystic fibrosis transmembrane conductance regulator) variant.Objectives: We hypothesized that a rat expressing a humanized version of CFTR and harboring the ivacaftor-sensitive variant G551D could be used to test the impact of CFTR modulators on pathophysiologic development and correction.Methods: In this study, we describe a humanized-CFTR rat expressing the G551D variant obtained by zinc finger nuclease editing of a human complementary DNA superexon, spanning exon 2-27, with a 5' insertion site into the rat gene just beyond intron 1. This targeted insertion takes advantage of the endogenous rat promoter, resulting in appropriate expression compared with wild-type animals.Measurements and Main Results: The bioelectric phenotype of the epithelia recapitulates the expected absence of CFTR activity, which was restored with ivacaftor. Large airway defects, including depleted airway surface liquid and periciliary layers, delayed mucus transport rates, and increased mucus viscosity, were normalized after the administration of ivacaftor.Conclusions: This model is useful to understand the mechanisms of disease and the extent of pathology reversal with CFTR modulators. [ABSTRACT FROM AUTHOR]

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