Abstract
Chronic obstructive pulmonary disease (COPD) is a frequent respiratory disease. However, its pathophysiology remains partially elucidated. Epithelial remodeling including alteration of the cilium is a major hallmark of COPD, but specific assessments of the cilium have been rarely investigated as a diagnostic tool in COPD. Here we explore the dysregulation of the ciliary function (ciliary beat frequency (CBF)) and differentiation (multiciliated cells formation in air-liquid interface cultures) of bronchial epithelial cells from COPD (n = 17) and non-COPD patients (n = 15). CBF was decreased by 30% in COPD (11.15 +/− 3.37 Hz vs. 7.89 +/− 3.39 Hz, p = 0.037). Ciliary differentiation was altered during airway epithelial cell differentiation from COPD patients. While the number of multiciliated cells decreased (p < 0.005), the number of primary ciliated cells increased (p < 0.05) and primary cilia were shorter (p < 0.05). Altogether, we demonstrate that COPD can be considered as a ciliopathy through both primary non-motile cilia modifications (related to airway epithelial cell repair and remodeling) and motile cilia function impairment (associated with decrease sputum clearance and clinical respiratory symptoms). These observations encourage considering cilia-associated features in the complex COPD physiopathology and highlight the potential of cilia-derived biomarkers for diagnosis.
Highlights
Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by persistent respiratory symptoms and airflow limitation [1], mainly caused by tobacco smoke and pollutants exposure
We did not assess the functionality of the cilia and we only characterized the alteration of ciliogenesis during differentiation on airway epithelial cells isolated from nasal polyp samples
We hypothesized that the homeostasis of motile cilia function and bronchial airway epithelial ciliated cell differentiation are both orchestrated by primary ciliogenesis
Summary
Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by persistent respiratory symptoms and airflow limitation [1], mainly caused by tobacco smoke and pollutants exposure. We previously explored ciliary dysfunction in COPD regarding airway epithelium differentiation from bronchial cells. We did not assess the functionality of the cilia and we only characterized the alteration of ciliogenesis during differentiation on airway epithelial cells isolated from nasal polyp samples. We hypothesized that the homeostasis of motile cilia function (explored by ciliary beat frequency) and bronchial airway epithelial ciliated cell differentiation are both orchestrated by primary ciliogenesis. Their alterations in COPD patients may originate from dysregulation of primary cilia, an organelle often neglected as a diagnostic tool in respiratory diseases except in the context of primary ciliary dyskinesia [13]
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