Dysfunctional Bronchial Cilia Are a Feature of Chronic Obstructive Pulmonary Disease (COPD)

Figures & data

Table 1. Patient characteristics.

	Controls	COPD total
N	12	16
Age (years)	49.8 ± 7.2	63.8 ± 3.9***
Sex (%males)	100	100
Ethnicity (%)
Chinese	58.3	81.25
Malay	16.7	6.25
Indian	8.3	6.25
Others	16.7	6.25
Current smokers (%)	50.0	68.8
Pack-years (years)	16.6 (14.1–18.8)	40 (35.8–48.5)***
CAT score	–	13.2 ± 6.4
mMRC score	–	1.0 (0.75–1.0)
Chronic bronchitis (%)	–	31.2
SGRQ (total score)	–	29.6 (16.7–50.3)
Exacerbations in past year (n)	–	1.0 (0–2.3)
BMI (kg/m^2)	25.8 ± 3.9	22.8 ± 4.1
FEV1 (% pred)	101.9 ± 16.6	73.4 ± 14.1***
FEV1/FVC (%)	83.0 ± 4.8	59.0 ± 6.4***
D CO (% pred)	–	59.2 ± 17.6
K CO (% pred)	–	62.8 ± 12.8
Bronchiectasis on CT-thorax (n)	–	1

Values are mean ± standard deviation (SD), median (interquartile range). IFE: infrequent exacerbator; FE: frequent exacerbator; CAT: COPD assessment test range 0 (best) to 40 (worst score); mMRC: MRC dyspnoea score has range 1 to 5 (higher score indicates more dyspnoea); SGRQ: St. George Respiratory Questionnaire with range 0 (best) to 100 (worst score); BMI: body mass index; FEV₁: forced expiratory volume in one second; % pred: percentage of predicted value; D_CO: transfer factor for carbon-monoxide; K_CO: transfer factor for carbon-monoxide corrected for alveolar volume. p Values represent: ***p < 0.001 vs. controls.

Figure 1. Legend: Bronchial ciliary function in COPD and controls. (A) CBF: ciliary beat frequency, (B) dyskinesia index, (C) immotility index. ***p < 0.001.

Table 2. Ciliary function in COPD and controls.

	Controls N = 12	COPD N = 16
CBF (Hz)	8.5 (7.7–8.9)	6.8 (6.1–7.2)***
Dyskinesia Index (%)	14.5 (11.2–16.9)	73.8 (60.7–89.8)***
Immotility index (%)	0	0 (0–1.4)

Values are median (interquartile range). CBF: ciliary beat frequency; FE: frequent exacerbator; IFE: infrequent exacerbator. p Value represent: ***p < 0.001 vs. controls.

Figure 2. Legend: transmission electron microscopy (TEM) images of ciliated respiratory epithelium from a healthy ex-smoking control subject (A) showing normal mitochondria (arrow), and a patient with COPD (B–F) showing significant loss of cilia (B), abnormal mitochondria (C), projecting cell (D), cytoplasmic bleb (E) and dead cell (F). Internal scale bar = 2 µm.

Table 3. Ultrastructure of bronchial epithelium in COPD and controls.

	Controls N = 12	COPD N = 16
Ciliated cells (%)	72.3 (68.4–81.4)	75 (70.6–76.7)
Unciliated cells (%)	18.3 (7.6–23.3)	17.7 (15–20.8)
Mucus cells (%)	6.6 (2.7–9.8)	6.7 (5–8.3)
Dead cells (%)	19.8 (17.9–45.1)	51.2 (39.7–55.7)*
Dynein arm defects (%)	2.1 (0.7–6.8)	3 (0–6.1)
Microtubular defects (%)	2.8 (1.5–13.1)	7.6 (5.6–14.8)
Ciliary orientation (degrees)	12.6 (11.6–17.9)	16.8 (15.9–19.4)
Ciliated cells with loss of cilia (%)	5.5 (2.4–18.6)	87.7 (64.5–100)**
Cells extruding from the surface (%)	6.0 (5.6–13.3)	100 (44.3–100)**
Cells with cytoplasmic blebbing (%)	9.8 (5.4–13.2)	70.4 (62.5–78)**
Cells with mitochondrial damage (%)	67.9 (60.1–70.9)	70.1 (66.7–77.8)
Cells with projections (%)	8.5 (5.9–20.0)	66.7 (43.7–72.2)**

Values are median (interquartile range). CBF: ciliary beat frequency; FE: frequent exacerbator; IFE: infrequent exacerbator. p Values represent: *p < 0.05 vs. controls,**p < 0.01 vs. controls.