Abstract
Progression of Lung Disease in a Primary Ciliary Dyskinesia Porcine Model
American journal of respiratory and critical care medicine, Vol.211(Abstracts), pp.A7332-A7332
05/2025
DOI: 10.1164/ajrccm.2025.211.Abstracts.A7332
Abstract
RATIONALE: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder resulting in nonfunctional cilia leading to chronic infections of the lungs. Recurrent infections are thought to be responsible for structural changes (air trapping, atelectasis, and bronchiectasis) seen in nearly all adults with PCD. Previously, we have shown that DNAI1 KO PCD pigs have defective cilia and develop lung disease similar to humans shortly after birth. To understand the progression of PCD lung disease we investigated PCD pigs at 6, 9, and 12 months of age. We hypothesized lung disease in older PCD pigs would mimic that of humans with PCD and worsen over time.METHODS: Thoracic computed tomography (CT) scans were acquired from PCD and WT pigs at 6, 9, and 12 months of age with a dual source high-resolution multi-row detector CT scanner (Canon Aquilion ONE, 120 kVp, 400 mA, slice thickness 0.5 mm, slice spacing 0.3 mm). At each time point, a total lung capacity (TLC) scan was acquired at 25 cm H2O and a functional residual capacity (FRC) scan was acquired at 0 cm H2O. We analyzed differences in lung densitometry using the free open-source software 3D Slicer (version 4.13.0, NA-MIC, NIH). Lung samples were collected for histological analysis, and bronchoalveolar lavage (BAL) was conducted to quantify cellular, cytokine, and bacterial components in both healthy and diseased lung regions.RESULTS: CT scans revealed atelectasis in PCD pig lungs, predominantly in dependent regions. Histology showed mucus accumulation in the airways, indicating mucus stasis and blockage as potential contributing factors. In some instances, mucus was observed moving into the respiratory bronchioles and alveolar ducts. BAL fluid analysis indicated elevated levels of IL-1α, IL-1β, IL-1ra, and IL-8 in diseased lung regions at all time points. At 9 months, cytokine profiles in healthy areas of PCD pig lungs resembled those of healthy controls, but by 12 months, these profiles resembled those of diseased lungs. Microbiological analyses corroborated these trends.CONCLUSIONS: Our study demonstrates a progression of lung disease in PCD pigs that mirrors aspects observed in human PCD patients. These findings underscore the utility of the PCD pig model in studying the early development and progression of PCD lung disease. Understanding these changes will be crucial for developing potential therapeutic strategies and interventions to manage or mitigate the progression of lung disease in PCD patients.
Details
- Title: Subtitle
- Progression of Lung Disease in a Primary Ciliary Dyskinesia Porcine Model
- Creators
- M. Rector - University of Iowa, Internal MedicineB. Hilkin - University of Iowa, Internal MedicineN. Gansemer - University of Iowa, Internal MedicineD.A. Stoltz - University of IowaJ. Zabner - University of Iowa, Pulmonary, Critical Care, and Occupational MedicineM. Abou Alaiwa - University of Iowa
- Resource Type
- Abstract
- Publication Details
- American journal of respiratory and critical care medicine, Vol.211(Abstracts), pp.A7332-A7332
- DOI
- 10.1164/ajrccm.2025.211.Abstracts.A7332
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Publisher
- AMER THORACIC SOC
- Grant note
- NIH
This abstract is funded by: NIH
- Language
- English
- Date published
- 05/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984822963702771
Metrics
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