CBF, Decreased leads to MCC, Decreased

Although ciliary function is considered a primary determinant for effective MCC (Duchateau et al., 1985; Gizurarson, 2015), there is evidence that suggests that MCC can be impeded by other factors that do not affect CBF. For example, nasal CBF in cigarette smokers regularly exhaling through the nose was not significantly different from that of nonsmokers, although they exhibited significantly longer nasomuciliary clearance times compared to nonsmokers. Possible explanations offered for this discrepancy were a potential loss of cilia in the nasal epithelium or increased mucus viscoelasticity (Stanley et al., 1986). Similarly, formaldehyde exposure of rats resulted in decreased cilia numbers and slower mucus flow rates (Morgan KT et al., 1986). On the other hand, there are a number of pharmacological compounds that improve mucociliary clearance through reductions in mucus viscosity, but have no effect on CBF (Jiao and Zhang, 2019), or through increases in CBF, but have no effect on mucociliary clearance (Phillips et al., 1990).

CBF decreased sequentially with increasing SO₂ doses in dogs. CBF decreased from 6.3 ± 0.2 (SE) Hz at baseline to 5.7 ± 0.2 Hz at 5.5 ppm SO₂. Five ppm SO₂ delivered to both the trachea and tracheobronchial airways for 20 min also caused a marked decrease in mean bronchial mucociliary clearance from 53.7 ± 5.7% to 32.8 ± 7.7% after 90 min (Yeates et al., 1997).

The effects of 30-min exposure to SO₂ on mucociliary activity (MCA) and ciliary beat frequency (CBF) were studied in 31 guinea pig tracheas. A 63% reduction in mean MCA and statistically insignificant changes in CBF were recorded at concentrations of 2.5 ppm SO₂. Higher SO₂ concentrations caused further impairment of MCA as well as a dose-dependent decrease in CBF: At 5 ppm SO2, CBF decreased by 45%, at 12.5 ppm by 72%. The maximum decrease in MCA (81%) was observed with 7.5 ppm SO₂; the highest SO₂ concentration did not decrease MCA further. The decrease in MCA was associated with an impairment of CBF only at SO₂ concentrations ≥5.0 ppm (Knorst et al., 1994b).

Administration of a nebulized CBF inhibitor (0.9% NaCl) to 15 healthy volunteers significantly decreased mucociliary transport (MCT) from 7.9±1.5 mm/min (SEM) to 4.5±1.6 mm/min. Salbutamol, a CBF enhancer, significantly increased MCT from 8.0±1.4 to 12.5±1.1 mm/min (Boek et al., 2002; Boek et al., 1999). Cooling human airway epithelial cultures grown at the air-liquid interface from 37°C to 25°C over the course of approx. 20 min decreased CBF from 12 to 6 Hz and mucociliary transport (MCT) from 140 to 90 µm/s. Extending the range of temperature tested, CBF was found to increase by 0.49±0.06 Hz for every temperature increase by 1°C, and this was mirrored by an increase in MCT. MCT increased on average between 5 and 11 µm/s for every Hz increase in CBF. This study also showed that CBF decreased with increasing mucin concentration, dropping from 12.4 Hz at 2% bovine submaxillary mucin (BSM) to 10.1 Hz at 8% BSM, concurrent with a ca. 70% reduction in MCT. In addition, treatment with 10 µM basolateral forskolin reproducibly increased CBF by 19.3±2.1% and MCT by 24.4±3.1% over baseline (Sears et al., 2015). In sheep trachea CBF and mucus transport velocity (MTV) were 9.8±2.7 beats/s and 5.7±2.6 mm/min, respectively, at baseline. Temperature reductions from 37°C to 34°C caused a progressive decline in CBF (ca. –20% at 2 h and –90% at 4 h) and MTV (ca. –50% at 2 h and –90% at 4 h), which was further exacerbated by additional temperature decreases (30°C; CBF: ca. –75% at 2 h; MTV: –80% at 2 h) (Kilgour et al., 2004).

Frog palate preparations were incubated with 1.25, 2.5 and 5.0 ppm formaldehyde. At formaldehyde doses of 2.5 and 5 ppm, CBF decreased by ca. 25% compared to baseline within 30 min and by 35-50% within 60 min (Fló-Neyret et al., 2001). Incubation of frog palates with PM10 from Sao Paolo, Brazil, for up to 120 min did not affect CBF but decreased MCT at concentrations ≥1000 pg/m3 (Macchione et al., 1999) In freshly excised sheep tracheas, a 60-min incubation with 10 µM platelet-activating factor caused a 6% decrease in CBF and a dose-dependent decrease in surface liquid velocity, reaching a maximum of 63% (Seybold et al., 1990).

In patients with bronchiectasis, nasal CBF was 12.8±1.3 Hz and nasal clearance time was 31.8± 18.4 min. In comparison, in healthy controls, nasal CBF was 14.0±1.3 Hz and nasal clearance time was 17.6± 8.3 min (Rutland and Cole, 1981).

Following basolateral treatment of human sinonasal epithelial cell cultures grown at the air-liquid interface with  Myrtol®, a phytopharmaceutical mixture of distillates of rectified essential oils of eucalyptus, sweet orange, myrtle, and lemon as the active ingredients, increased CBF in a dose-dependent manner, with a maximum stimulation with 0.1% of 48±7% after 30 min. The same concentration caused a 46±16% increase in MCT at 40 min (Lai et al., 2014).

In New Zealand white rabbits exposed to 3 ppm NO₂ for 24 h, the average CBF decreased from 764 beats/min to 692 beats/min, and the transport velocity decreased from 5.23 mm/min to 3.03 mm/min (Kakinoki, 1998).

A 20-minute exposure of dogs to SO₂ caused a decrease in mean bronchial MCC after 90 min (Yeates et al., 1997).

Frog palate epithelia were incubated with 1.25, 2.5 and 5.0 ppm formaldehyde. At formaldehyde doses of 2.5 and 5 ppm, CBF decreased by ca. 25% compared to baseline within 30 min and by 35-50% within 60 min (Fló-Neyret et al., 2001).

Incubation of freshly excised sheep tracheas with 10 µM platelet-activating factor caused a maximal decrease in CBF of 6% after 60 min and decrease in surface liquid velocity of ca. 30% at 20 min, ca. 50% at 40 min and 63% after 60 min (Seybold et al., 1990).

Following basolateral treatment of human sinonasal epithelial cell cultures grown at the air-liquid interface with different concentrations of Myrtol®, CBF increased rapidly within the first 30 min and then declined thereafter. The maximum response for MCT was seen after 40 min (Lai et al., 2014).

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