Assessment of acquired mucociliary clearance defects using micro‐optical coherence tomography

Abstract

Background Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance (MCC) in sinonasal epithelium, which may lead to chronic rhinosinusitis (CRS). Abnormal chloride (Cl−) transport is one such mechanism that contributes to this disorder and can be acquired secondary to environmental perturbations, such as hypoxia at the tissue surface. The objective of this study was to assess the technological feasibility of the novel micro-optical coherence tomography (μOCT) imaging technique for investigating acquired MCC defects in cultured human sinonasal epithelial (HSNE) cells. Methods Primary HSNE cell cultures were subjected to a 1% oxygen environment for 12 hours to induce acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Ion transport characteristics were assessed with pharmacologic manipulation in Ussing chambers. ASL, periciliary fluid (PCL), and ciliary beat frequency (CBF) were evaluated using μOCT. Results Amiloride-sensitive transport (ΔISC) was greater in cultures exposed to hypoxia (hypoxia: −13.2 ± 0.6 μA/cm2; control: −6.5 ± 0.1 μA/cm2; p < 0.01), whereas CFTR-mediated anion transport was significantly diminished (hypoxia: 28.6 ± 0.3 μA/cm2; control: 36.2 ± 1.6 μA/cm2; p < 0.01), consistent with acquired CFTR dysfunction and sodium hyperabsorption. Hypoxia diminished all markers of airway surface function microanatomy as observed with μOCT, including ASL (hypoxia: 5.0 ± 0.4 μm; control: 9.0 ± 0.9 μm; p < 0.01) and PCL depth (hypoxia: 2.5 ± 0.1 μm; control: 4.8 ± 0.3 μm; p < 0.01), and CBF (hypoxia: 8.7 ± 0.3 Hz; control: 10.2 ± 0.3 Hz; p < 0.01). Conclusion Hypoxia-induced defects in epithelial anion transport in HSNE led to predictable effects on markers of MCC measured with novel μOCT imaging. This imaging method represents a technological leap forward and is feasible for assessing acquired defects impacting the airway surface.

Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis

“…In this study, CF mucus strands often failed to detach from submucosal glands or became tethered to nearby anchored strands rather than exhibiting normal elasticity and release from the glands as was seen in non‐CF piglet tracheas . While this was demonstrated when there was a genetic absence of functional cystic fibrosis transmembrane conductance regulator (CFTR), acquired CFTR deficiency in non‐CF patients likely contributes to continued pathogenicity in diseases of the airway, including chronic obstructive pulmonary disease and CRS . Thick abundant mucus is a hallmark of inflamed and/or infected sinuses.…”

“…Mucociliary clearance (MCC) is the primary innate defense mechanism by which inhaled particulate matter is eliminated from the airways . Proper functioning of MCC relies on 2 equally important constituents: mucus production and mucus transport, both of which are contingent upon normal ciliary beating, adequate hydration of airway surface liquid (ASL), periciliary liquid (PCL), and mucus viscosity . Abnormalities in any 1 of these critical components may result in dysfunctional MCC, irrespective of the underlying etiology.…”

Resveratrol and ivacaftor are additive G551D CFTR‐channel potentiators: therapeutic implications for cystic fibrosis sinus disease

“…25 Maximal Cl − secretion was augmented with both agents (resveratrol+ivacaftor, 32.2+/−1.17 vs. resveratrol, 10.73+/−0.84 vs. ivacaftor, 21.29+/−0.85 vs. DMSO, 3.88+/−0.85; p<0.001) to levels consistent with what is detected in non-CF HSNE. 26–28 …”

Effect of Cellulose Powder on Human Nasal Epithelial Cell Activity and Ciliary Beat Frequency

“…A previous study showed that cellular activities such as DNA replication may depend on oxygen concentration, so hypoxia might result in a decrease in the rate of cell proliferation [20]. In other studies, it was found that mucus hypersecretion can lead directly to the obstruction of the airways, resulting in poor mucociliary clearance and poor tissue oxygenation [21, 22]. These findings have lent support to the fact that high concentrations of CP may considerably impair the airway epithelial function by forming a thickened gel on the epithelial surface.…”