Journal article
Early Lung Disease Exhibits Bacterial-Dependent and -Independent Abnormalities in Cystic Fibrosis Pigs
American journal of respiratory and critical care medicine, Vol.204(6), pp.692-702
06/25/2021
DOI: 10.1164/rccm.202102-0451OC
PMID: 34170795
Abstract
Rationale: While it is clear that cystic fibrosis 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 thought that, if it does, it 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) cystic fibrosis, and 3) cystic fibrosis pigs treated continuously with broad-spectrum antibiotics from birth until study completion. Disease was assessed with chest computed tomography, histopathology, microbiology, and bronchoalveolar lavage.
Measurements and main results: Disease was present by 3 weeks of age in cystic fibrosis pigs. Continuous antibiotics from birth improved chest computed tomography imaging abnormalities and airway mucus accumulation, but not airway inflammation in the cystic fibrosis pig model. However, reducing bacterial infection did not improve two disease features already present at birth in cystic fibrosis pigs, air trapping and submucosal gland duct plugging. In the cystic fibrosis sinuses, antibiotics did not prevent the development of infection, disease, or the number of bacteria but did alter the bacterial species.
Conclusions: These findings suggest that cystic fibrosis airway disease begins immediately following birth, and that early and continuous antibiotics impact some, but not all, aspects of CF lung disease development.
Keywords: anti-bacterial agents; lung physiology; mucus; multidetector computed tomography; respiratory mucosa.
Details
- Title: Subtitle
- Early Lung Disease Exhibits Bacterial-Dependent and -Independent Abnormalities in Cystic Fibrosis Pigs
- Creators
- Drake C Bouzek - The University of Iowa Roy J and Lucille A Carver College of Medicine, 12243, Iowa City, Iowa, United StatesMahmoud H Abou Alaiwa - University of Iowa, Internal MedicineRyan J Adam - University of Iowa, Internal MedicineAlejandro A Pezzulo - University of Iowa, Internal MedicineLeah R Reznikov - University of Florida, 3463, Physiological Sciences, Gainesville, Florida, United StatesDaniel P Cook - Vanderbilt University Medical Center, 12328, Department of Medicine, Nashville, Tennessee, United StatesMaria I Aguilar Pescozo - University of Iowa, Internal MedicinePatrick Ten Eyck - University of Iowa, BiostatisticsChaorong Wu - University of IowaThomas J Gross - University of Iowa, Internal MedicineDouglas B Hornick - University of Iowa, Internal MedicineEric A Hoffman - University of Iowa, RadiologyDavid K Meyerholz - University of Iowa, PathologyDavid A Stoltz - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.204(6), pp.692-702
- DOI
- 10.1164/rccm.202102-0451OC
- PMID
- 34170795
- NLM abbreviation
- Am J Respir Crit Care Med
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Language
- English
- Date published
- 06/25/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Biostatistics; Internal Medicine; Design Biostat and Ethics
- Record Identifier
- 9984130694702771
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