Scanning Electron Microscopic Study of the Airways in Normal Children and in Patients with Cystic Fibrosis and Other Lung Diseases

Dl, Simel; Jp, Mastin; Pc, Pratt; Cl, Wisseman; Jd, Shelburne; Spock, Alexander; Ingram, Peter

doi:10.3109/15513818409041187

Cited by 52 publications

(26 citation statements)

References 6 publications

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“…Our histological analysis of CF lung sections revealed significant tissue remodelling, including secretory and basal cell hyperplasia, gland hypertrophy, as well as squamous metaplasia, in most patients, in agreement with previous reports [3,4,7,29,30]. Our analysis also detected areas of extended and severe epithelial shedding in 100% of analysed CF patients.…”

Section: Severity Of Epithelial Injury and Remodelling Of Cf Airwayssupporting

confidence: 92%

Improvement of defective cystic fibrosis airway epithelial wound repair after CFTR rescue

et al. 2012

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Airway damage and remodelling are important components of lung pathology progression in cystic fibrosis (CF). Although repair mechanisms are engaged to restore the epithelial integrity, these processes are obviously insufficient to maintain lung function in CF airways. Our aims were therefore to study how the basic cystic fibrosis transmembrane conductance regulator (CFTR) defect could impact epithelial wound healing and to determine if CFTR correction could improve it.Wound-healing experiments, as well as cell migration and proliferation assays, were performed to study the early phases of epithelial repair in human CF and non-CF airway cells. CFTR function was evaluated using CFTR small interferring (si)RNA and inhibitor GlyH101 in non-CF cells, and conversely after CFTR rescue with the CFTR corrector VRT-325 in CF cells.Wound-healing experiments first showed that airway cells from CF patients repaired slower than non-CF cells. CFTR inhibition or silencing in non-CF primary airway cells significantly inhibited wound closure. GlyH101 also decreased cell migration and proliferation. Interestingly, wild-type CFTR transduction in CF airway cell lines or CFTR correction with VRT-325 in CFBE-DF508 and primary CF bronchial monolayers significantly improved wound healing.Altogether our results demonstrated that functional CFTR plays a critical role in wound repair, and CFTR correction may represent a novel strategy to promote the airway repair processes in CF.

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Section: Severity Of Epithelial Injury and Remodelling Of Cf Airwayssupporting

confidence: 92%

Improvement of defective cystic fibrosis airway epithelial wound repair after CFTR rescue

et al. 2012

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“…Although CK13 is predominantly a cytoplasmic protein and expressed in the basal layer of tracheal and bronchial epithelium under normal conditions, its expression is increased in airways undergoing squamous metaplasia due to repeated injury and repair. This state is frequently observed in cystic fibrosis patients (27,40). Since CK13 is readily available on the apical surface of airway epithelium undergoing squamous metaplasia (27), we speculate that CF airways provide a suitable environmental niche for highly transmissible and potentially virulent Cbl-and adhesin-positive B. cenocepacia strains.…”

Section: Discussionmentioning

confidence: 99%

Cable Pili and the 22-Kilodalton Adhesin Are Required for Burkholderia cenocepacia Binding to and Transmigration across the Squamous Epithelium

et al. 2005

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Burkholderia cenocepacia strains expressing both cable (Cbl) pili and the 22-kDa adhesin bind to cytokeratin 13 (CK13) strongly and invade squamous epithelium efficiently. It has not been established, however, whether the gene encoding the adhesin is located in the cbl operon or what specific contribution the adhesin and Cbl pili lend to binding and transmigration or invasion capacity of B. cenocepacia. By immunoscreening an expression library of B. cenocepacia isolate BC7, we identified a large gene (adhA) that encodes the 22-kDa adhesin. Isogenic mutants lacking expression of either Cbl pili (cblA or cblS mutants) or the adhesin (adhA mutant) were constructed to assess the individual role of Cbl pili and the adhesin in mediating B. cenocepacia binding to and transmigration across squamous epithelium. Relative to the parent strain, mutants of Cbl pili showed reduced binding (50%) to isolated CK13, while the adhesin mutant showed almost no binding (0 to 8%). Mutants lacking either cable pili or the adhesin were compromised in their ability to bind to and transmigrate across the squamous epithelium compared to the wild-type strain, although this deficiency was most pronounced in the adhA mutant. These results indicate that both Cbl pili and the 22-kDa adhesin are necessary for the optimal binding to CK13 and transmigration properties of B. cenocepacia.

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“…In CF, the inflammation present in the airways results in large numbers of neutrophils in the sputum. In addition, there is some evidence of squamous metaplasia in CF (12). Thus, there are likely to be relatively more squamous epithelial cells as well, affecting the ratio used for calculation of the Q score.…”

Section: Discussionmentioning

confidence: 99%

Utility of Gram Staining for Evaluation of the Quality of Cystic Fibrosis Sputum Samples

Nair

Stapp

et al. 2002

J Clin Microbiol

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The microscopic examination of Gram-stained sputum specimens is very helpful in the evaluation of patients with community-acquired pneumonia and has also been recommended for use in cystic fibrosis (CF) patients. This study was undertaken to evaluate that recommendation. One hundred one sputum samples from CF patients were cultured for gram-negative bacilli and examined by Gram staining for both sputum adequacy (using the quality [Q] score) and bacterial morphology. Subjective evaluation of adequacy was also performed and categorized. Based on Q score evaluation, 41% of the samples would have been rejected despite a subjective appearance of purulence. Only three of these rejected samples were culture negative for gram-negative CF pathogens. Correlation between culture results and quantitative Gram stain examination was also poor. These data suggest that subjective evaluation combined with comprehensive bacteriology is superior to Gram staining in identifying pathogens in CF sputum.Gram staining is considered key in the workup of sputum from patients with pneumonia and other lower respiratory tract infections (10). Unfortunately, sputum samples are often contaminated with saliva and resident oropharyngeal microbial flora. This contamination can be quantified by evaluating Gram-stained sputum samples for polymorphonuclear leukocytes and squamous epithelial cells. The resulting objective measure, called the quality (Q) score, has been validated and recommended for use in evaluating the quality of the specimen (1).Cystic fibrosis (CF) lung infections are chronic and polymicrobial, occasionally marked by exacerbations accompanied by increased, purulent sputum production and systemic symptoms. Antibiotic treatment based on sputum culture results is a mainstay of CF management. The specific use of the Gram stain for evaluating the adequacy of sputum samples from patients with CF has also been recommended (4). In addition, past literature reports excellent sensitivity, specificity, and predictive values of examination of the morphology of bacteria seen in Gram-stained specimens compared with microbiological culture techniques for the prediction of specific organisms in CF sputum samples (11).At the Therapeutic Development Network (TDN) Core Microbiology Laboratory, we have had experience processing thousands of CF respiratory samples. It is the impression of the technologists at the bench that the Q score of the Gramstained specimen is less useful than subjective evaluation of the specimens for adequacy. In addition, because specimens are solubilized and diluted prior to plating on selective media (2), it is rare that organisms are detected by Gram staining and not cultured from the sample. To validate these impressions, we performed a prospective study to compare the objective scoring (Q score) and Gram stain evaluation with subjective characterization of purulence and quantitative culture results. MATERIALS AND METHODSStudy design. The present study was a substudy in the investigation of tobramycin-containing media fo...

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Scanning Electron Microscopic Study of the Airways in Normal Children and in Patients with Cystic Fibrosis and Other Lung Diseases

Cited by 52 publications

References 6 publications

Improvement of defective cystic fibrosis airway epithelial wound repair after CFTR rescue

Improvement of defective cystic fibrosis airway epithelial wound repair after CFTR rescue

Cable Pili and the 22-Kilodalton Adhesin Are Required for Burkholderia cenocepacia Binding to and Transmigration across the Squamous Epithelium

Utility of Gram Staining for Evaluation of the Quality of Cystic Fibrosis Sputum Samples

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