Early Lung Disease Exhibits Bacteria-Dependent and -Independent Abnormalities in Cystic Fibrosis Pigs.

Autor: Bouzek DC; Department of Internal Medicine., Abou Alaiwa MH; Department of Internal Medicine.; Pappajohn Biomedical Institute., Adam RJ; Department of Internal Medicine.; Department of Biomedical Engineering., Pezzulo AA; Department of Internal Medicine.; Pappajohn Biomedical Institute., Reznikov LR; Department of Internal Medicine., Cook DP; Department of Internal Medicine., Aguilar Pescozo MI; Department of Internal Medicine., Ten Eyck P; Institute for Clinical and Translational Science., Wu C; Institute for Clinical and Translational Science., Gross TJ; Department of Internal Medicine., Hornick DB; Department of Internal Medicine., Hoffman EA; Department of Biomedical Engineering.; Department of Radiology., Meyerholz DK; Department of Pathology, and., Stoltz DA; Department of Internal Medicine.; Pappajohn Biomedical Institute.; Department of Biomedical Engineering.; Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Health Care, Iowa City, Iowa.
Jazyk: angličtina
Zdroj: American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2021 Sep 15; Vol. 204 (6), pp. 692-702.
DOI: 10.1164/rccm.202102-0451OC
Abstrakt: Rationale: Although it is clear that cystic fibrosis (CF) airway disease begins at a very young age, the early and subsequent steps in disease pathogenesis and the relative contribution of infection, mucus, and inflammation are not well understood. Objectives: As one approach to assessing the early contribution of infection, we tested the hypothesis that early and continuous antibiotics would decrease the airway bacterial burden. We believed that, if they do, this might reveal aspects of the disease that are more or less sensitive to decreasing infection. Methods: Three groups of pigs were studied from birth until ∼3 weeks of age: 1 ) wild-type, 2 ) CF, and 3 ) CF pigs treated continuously with broad-spectrum antibiotics from birth until study completion. Disease was assessed with chest computed tomography, histopathology, microbiology, and BAL. Measurements and Main Results: Disease was present by 3 weeks of age in CF pigs. Continuous antibiotics from birth improved chest computed tomography imaging abnormalities and airway mucus accumulation but not airway inflammation in the CF pig model. However, reducing bacterial infection did not improve two disease features already present at birth in CF pigs: air trapping and submucosal gland duct plugging. In the CF sinuses, antibiotics did not prevent the development of infection or disease or the number of bacteria but did alter the bacterial species. Conclusions: These findings suggest that CF airway disease begins immediately after birth and that early and continuous antibiotics impact some, but not all, aspects of CF lung disease development.
Databáze: MEDLINE