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J Thorac Dis. 2018 Mar;10(3):1753-1764. doi: 10.21037/jtd.2018.02.13.

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis.

Journal of thoracic disease

Zhuang-Gui Chen, Ying-Ying Li, Zhao-Ni Wang, Ming Li, Hui-Fang Lim, Yu-Qi Zhou, Liang-Ming Cai, Ya-Ting Li, Li-Fen Yang, Tian-Tuo Zhang, De-Yun Wang

Affiliations

  1. Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
  2. Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.
  3. Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Institute of Respiratory Diseases of Sun Yat-sen University, Guangzhou 510630, China.
  4. Department of Pulmonary Diseases, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510700, China.
  5. Division of Respiratory & Critical Care Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore.

PMID: 29707330 PMCID: PMC5906310 DOI: 10.21037/jtd.2018.02.13

Abstract

BACKGROUND: Aberrant epithelial remodeling and/or abnormalities in mucociliary apparatus in airway epithelium contribute to infection and inflammation. It is uncertain if these changes occur in both large and small airways in non-cystic fibrosis bronchiectasis (non-CF bronchiectasis). In this study, we aim to investigate the histopathology and inflammatory profile in the epithelium of bronchi and bronchioles in bronchiectasis.

METHODS: Excised lung tissue sections from 52 patients with non-CF bronchiectasis were stained with specific cellular markers and analyzed by immunohistochemistry and immunofluorescence to assess the epithelial structures, including ciliated cells and goblet cells morphology. Inflammatory cell counts and ciliary proteins expression levels of centrosomal protein 110 (CP110) and dynein heavy chain 5, axonemal (DNAH5) were assessed.

RESULTS: Epithelial hyperplasia is found in both bronchi and bronchioles in all specimens, including hyperplasia and/or hypertrophy of goblet cells. The median cilia length is longer in hyperplastic epithelium [bronchi: 8.16 (7.03-9.14) µm, P<0.0001; bronchioles: 7.46 (6.41-8.48) µm, P<0.0001] as compared to non-hyperplastic epithelium (bronchi: 5.60 µm; bronchioles: 4.89 µm). Hyperplastic epithelium is associated with overexpression of CP110 and decreased intensity of DNAH5 expression in both bronchial and bronchiolar epithelium. Though infiltration of neutrophils is predominant (63.0% in bronchi and 76.7% in bronchioles), eosinophilic infiltration is also present in the mucosa of bronchi (30.8%) and bronchioles (54.8%).

CONCLUSIONS: Aberrant epithelial remodeling with impaired mucociliary architecture is present in both large and small airways in patients with refractory non-CF bronchiectasis. Future studies should evaluate the interplay between these individual components in driving chronic inflammation and lung damage in patients.

Keywords: Epithelial remodeling; bronchiectasis; mucociliary; non-cystic fibrosis; pathology

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

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