Browsing by Subject "bronchiectasis"

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    Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways
    (American Physiological Society (APS), 2014-01-15) Gilley, Sandra K.; Stenbit, Antine E.; Pasek, Raymond C.; Sas, Kelli M.; Steele, Stacy L.; Amria, May; Bunni, Marlene A.; Estell, Kimberly P.; Schwiebert, Lisa M.; Flume, Patrick; Gooz, Monika; Haycraft, Courtney J.; Yoder, Bradley K.; Miller, Caroline; Pavlik, Jacqueline A.; Turner, Grant A.; Sisson, Joseph H.; Bell, P. Darwin; Department of Anatomy & Cell Biology, IU School of Medicine
    The mechanisms for the development of bronchiectasis and airway hyperreactivity have not been fully elucidated. Although genetic, acquired diseases and environmental influences may play a role, it is also possible that motile cilia can influence this disease process. We hypothesized that deletion of a key intraflagellar transport molecule, IFT88, in mature mice causes loss of cilia, resulting in airway remodeling. Airway cilia were deleted by knockout of IFT88, and airway remodeling and pulmonary function were evaluated. In IFT88− mice there was a substantial loss of airway cilia on respiratory epithelium. Three months after the deletion of cilia, there was clear evidence for bronchial remodeling that was not associated with inflammation or apparent defects in mucus clearance. There was evidence for airway epithelial cell hypertrophy and hyperplasia. IFT88− mice exhibited increased airway reactivity to a methacholine challenge and decreased ciliary beat frequency in the few remaining cells that possessed cilia. With deletion of respiratory cilia there was a marked increase in the number of club cells as seen by scanning electron microscopy. We suggest that airway remodeling may be exacerbated by the presence of club cells, since these cells are involved in airway repair. Club cells may be prevented from differentiating into respiratory epithelial cells because of a lack of IFT88 protein that is necessary to form a single nonmotile cilium. This monocilium is a prerequisite for these progenitor cells to transition into respiratory epithelial cells. In conclusion, motile cilia may play an important role in controlling airway structure and function.
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    Quantitative chest computerized tomography and FEV1 equally identify pulmonary exacerbation risk in children with cystic fibrosis
    (Wiley, 2018-10) Sanders, Don B.; Li, Zhanhai; Parker-McGill, Katelyn; Farrell, Philip; Brody, Alan S.; Pediatrics, School of Medicine
    Background Chest computerized tomography (CT) scores are associated with the frequency of future pulmonary exacerbations in people with cystic fibrosis (CF). However, cut‐off values to identify children with mild lung disease with different risks for frequent future pulmonary exacerbations have not been identified. Methods Chest CT scans were assessed using the Brody score for participants of the Pulmozyme Early Intervention Trial (PEIT) and Wisconsin Randomized Clinical Trial of CF Newborn Screening (WI RCT). We determined the area under the receiver operating characteristic (ROC) curve for Brody scores and forced expiratory volume in 1 s (FEV1) to compare with the frequency of pulmonary exacerbations up to 10 years later. Results There were 60 participants in the PEIT with mean (SD) age 10.6 (1.7) years at the time of the CT and 81 participants in the WI RCT with mean age 11.5 (3.0) years. The Brody score cut‐off that best identified children at‐risk for ≥0.3 annual pulmonary exacerbations was 3.6 in the PEIT and 2.1 in the WI RCT. There were no statistical differences between ROC curves for the Brody CT score and FEV1 % predicted in either study (P ≥ 0.4). Conclusions CT score cut‐off values that identify children with CF with mild lung disease at different risks for frequent pulmonary exacerbations over an extended follow up period are similar in separate cohorts. Brody scores and FEV1 % predicted have similar abilities to identify these children, suggesting that FEV1 % predicted alone may be adequate for predicting future frequency of pulmonary exacerbations.