Journal article
Loss of Cystic Fibrosis Transmembrane Conductance Regulator Function Produces Abnormalities in Tracheal Development in Neonatal Pigs and Young Children
American journal of respiratory and critical care medicine, Vol.182(10), pp.1251-1261
11/15/2010
DOI: 10.1164/rccm.201004-0643OC
PMCID: PMC3001264
PMID: 20622026
Abstract
Rationale
: Although airway abnormalities are common in patients with cystic fibrosis (CF), it is unknown whether they are all secondary to postnatal infection and inflammation, which characterize the disease.
Objectives
: To learn whether loss of the cystic fibrosis transmembrane conductance regulator (CFTR) might affect major airways early in life, before the onset of inflammation and infection.
Methods
: We studied newborn
CFTR
−/−
pig trachea, using computed tomography (CT) scans, pathology, and morphometry. We retrospectively analyzed trachea CT scans in young children with CF and also previously published data of infants with CF.
Measurements and Main Results
: We discovered three abnormalities in the porcine CF trachea. First, the trachea and mainstem bronchi had a uniformly small caliber and cross-sections of trachea were less circular than in controls. Second, trachealis smooth muscle had an altered bundle orientation and increased transcripts in a smooth muscle gene set. Third, submucosal gland units occurred with similar frequency in the mucosa of CF and control airways, but CF submucosal glands were hypoplastic and had global reductions in tissue-specific transcripts. To learn whether any of these changes occurred in young patients with CF, we examined CT scans from children 2 years of age and younger, and found that CF tracheas were less circular in cross-section, but lacked differences in lumen area. However, analysis of previously published morphometric data showed reduced tracheal lumen area in neonates with CF.
Conclusions
: Our findings in newborn CF pigs and young patients with CF suggest that airway changes begin during fetal life and may contribute to CF pathogenesis and clinical disease during postnatal life.
Details
- Title: Subtitle
- Loss of Cystic Fibrosis Transmembrane Conductance Regulator Function Produces Abnormalities in Tracheal Development in Neonatal Pigs and Young Children
- Creators
- David K Meyerholz - Department of PathologyDavid A Stoltz - Department of PathologyEman Namati - Department of PathologyShyam Ramachandran - Department of PathologyAlejandro A Pezzulo - Department of PathologyAmanda R Smith - Department of PathologyMichael V Rector - Department of PathologyMelissa J Suter - Department of PathologySimon Kao - Department of PathologyGeoffrey McLennan - Department of PathologyGuillermo J Tearney - Department of PathologyJoseph Zabner - Department of PathologyPaul B McCray - Department of PathologyMichael J Welsh - Department of Pathology
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.182(10), pp.1251-1261
- DOI
- 10.1164/rccm.201004-0643OC
- PMID
- 20622026
- PMCID
- PMC3001264
- NLM abbreviation
- Am J Respir Crit Care Med
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Publisher
- American Thoracic Society
- Language
- English
- Date published
- 11/15/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984013999702771
Metrics
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