Motile Cilia Number/Length, Decreased leads to CBF, Decreased

Although the majority of studies discuss the effect of shorter cilia on ciliary function, there are also reports on longer than normal cilia impairing cilia function (Jayathilake et al., 2015; Li et al., 2014b). A range of factors other than cilia length and number can influence cilia beat frequency. Often a combination of two or more factors affect ciliary function making it difficult to discern the impact of an individual factor on CBF (Toskala et al., 1995; Xie et al., 2019).

A study in nasal mucosa samples from sinusitis patients demonstrated that reduced cilia numbers account for decreased CBF. In normally ciliated samples the CBF was 11.2±3.7 Hz, in samples with some ciliated cells CBF was 8.9±6.3 Hz, and in samples with no detectable cilia CBF was 2.1±3.8 Hz (Joki S. et al., 1998).

Patients with recurrent or longstanding respiratory infections were divided into 3 groups based on mucociliary transport rates (MTR). The group with slowest MTR had the biggest number of non-ciliated columnar cells in the nasal mucosa, and the highest number of short and disoriented cilia. Loss of ciliated cells was seen in 50% of specimens with good MTR (7 to 10.8 mm per minute), in 71% with moderate MTR (3 to 6.9 mm per minute) and in 86% with poor MTR (0 to 2.9 mm per minute). The percentages of short cilia were 1% in the first group, 6% in the second, and 10% in the third. In this study, ciliary disorientation also contributed to the low MTR (Toskala et al., 1995).

Jayathilake et al. developed a two-dimensional numerical model for computing how the length of cilia is affecting fluid flow. In the model, the cilia length was reduced by 5%, 15%, 25%, and 35% from 6 µm while other parameters were kept unchanged. The average periciliary layer (PCL) velocity in stream-wise direction decreases when cilia are shortened. When the cilia are shortened by 10%, the average stream-wise PCL velocity is reduced by about 11%, while the average span-wise PCL velocity is reduced by about 62% (Jayathilake et al., 2012). In a similar study by the same group, the length of cilia was defined as 50%, 60%, 70%, 80%, 90%, 100%, 110%, 120%, 130% and 140% of the length of the healthy cilia (i.e., 6 µm). The mucus velocity reaches its maximum value when the ciliary length is around the length of the healthy cilia (or standard length of 6 µm) (Jayathilake et al., 2015).

Cilia shorter than 4 µm have anomalies in the ciliary beating periodicity. Cilia shorter than 2 µm were never found to beat periodically. Cilia between 2 and 4 µm in length exhibited more variable periodicity. Cilia with lengths between 4 and 12 µm beat periodically with conserved frequency (Bottier et al., 2018).

Mucus velocity increased in concordance with cilia number increase. Mean mucus velocity increased from 26.82 µm/s to 49.53 µm/s when cilia number grew from 10 to 24 (Lee et al., 2011).

FOR20 deletion or knockdown in zebrafish reduced the number and length of cilia. Cilia in FOR20 morphants had impaired ciliary motility. When cilia length was reduced from an average 5.5 µm to an average 3 µm due to FOR20 depletion, about 80% cilia displayed consistently paralyzed or arrhythmically beating pattern (Xie et al., 2019).

Nasal brush biopsy samples from pediatric patients with primary ciliary dyskinesia were analyzed. The median CBF was 13.4 Hz for normal ciliated epithelia, 11.4 Hz for the ciliated edge with minor projections and 8.7 Hz for the ciliated edge with major projections (Thomas et al., 2009).

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