Endobronchial Ultrasound is Useful in the Assessment of Bronchial Wall Changes Related to Bronchial Thermoplasty

Figures & data

Figure 1 Decreased thickness of airway wall layers after BT as measured by endobronchial ultrasonography (EBUS).

Notes: (a) Representative EBUS image of the bronchus RB10 and the schematic outline of bronchial wall layers with major structural components highlighted. (b) The thickness of L1, L2 and L3–5 layers in asthma patients before BT and 12 months after the procedure. Data shown as medians and quartiles (n = 11; 2-sided exact Wilcoxon matched-pairs signed rank test).

Table 1 Clinical Characteristics of Patients Before and After BT

	Before BT	After BT	P-value Median Difference 95% CI
Number of asthma exacerbations (in the last 12 months)	6 (3–8)	1 (1–3)	0.005 −4 (−5;-1)
Number of exacerbations requiring hospitalization (in the last 12 months)	1 (1–5)	0 (0–0)	0.018 −1 (−3;0)
ACT (score)	15 (12–19)	18 (16–24)	0.006 3 (1;5)
AQLQ (score)	4.2 (3.2–5.4)	5.6 (4.4–6.1)	0.028 0.7 (0.2;1.5)
Patients treated with OCSs (n, %)	8 (72.7%)	7 (63.6%)	0.343
OCSs dose (mg/d)	8 (0–16)	4 (0–16)	0.400
ICSs dose (µg/d)	2200 (1800–2400)	1500 (800–2400)	0.074
FEV1/FVC (%)	61.3 (53.1–68.2)	66.2 (61.4–68.5)	0.041 3.9 (1.1;7.2)
FEV1 (% predicted)	62.0 (47.3–70.0)	68.5 (50.0–73.8)	0.091
FEV1 reversibility (%)	7 (2.8–18.6)	2.9 (1.3–8.9)	0.086
Blood eosinophil count (cells/µL)	150 (60–210)	150 (30–260)	0.929
Serum IgE (IU/mL)	64.1 (40.6–188.0)	78.2 (41.9–216.0)	1.000
α-SMA (%)^a	10.1 (8.0–13.0)	3.8 (1.3–5.8)	0.002 −4.9 (−10.1;-1.7)

Notes: Data are presented as medians (0.25–0.75 quartiles). Significant values of exact 2-sided Wilcoxon matched-pairs signed rank test (at P<0.01 are marked bold). For significant differences median difference with 95% CI are indicated. ^aExpressed as the percentage of positive stained α-SMA area to the total biopsy area. Statistically significant results are marked in bold.

Abbreviations: ACT, Asthma Control Test; AQLQ, Asthma Quality of Life Questionnaire; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; OCSs, oral corticosteroids (recounted for methylprednisolone); ICSs, inhaled corticosteroids (recounted for fluticasone propionate).

Table 2 Correlation Between the Decrease in Thickness of Bronchial Layers and Other Parameters

	Decrease in the Thicknesses of the Layers (mm)
	L1	L2	L3–5	L1+L2+L3–5
Improvement in ACT	r=0.516, P=0.104	r=0.055, P=0.873	r=0.157, P=0.645	r=0.198, P=0.559
Improvement in AQLQ	r=0.118, P=0.729	r=0.000 P=1.000	r=0.136, P=0.689	r=0.118, P=0.729
Decrease in exacerbations	r=0.335, P=0.314	r=0.390, P=0.236	r=0.289, P=0.389	r=0.294, P=0.381
Improvement in FEV1 (%)	r=0.373, P=0.259	r=0.527, P=0.096	r=0.291, P=0.385	r=0.309, P=0.355

Note: r, Spearman`s rank correlation coefficient.

Abbreviations: ACT, Asthma Control Test; AQLQ, Asthma Quality of Life Questionnaire; FEV₁, forced expiratory volume in 1 second.

Table 3 Histological Analysis of Bronchial Biopsies Before and After BT

Characteristics	Before BT	After BT	P-value
RBM (µm)	6.7 (6.2–8.4)	6.6 (5.5–7.3)	0.206
α-SMA (%)^a	10.1 (8.0–13.0)	3.8 (1.3–5.8)	0.002
MUC5AC (%)^b	21.2 (16.7–30.9)	20.7 (11.6–23.1)	0.812
NE	14.2 (9.0–63.8)	24.7 (7.7–48.5)	0.748
ECP	1.4 (0–2.2)	1.2 (0.2–2.1)	0.361
Tryptase	4.2 (2.0–5.0)	0.8 (0.2–3.5)	0.310
CD3	63.4 (43–93.4)	104 (40.4–148.8)	0.320
CD4	22.2 (8.0–35.7)	41.1 (16.4–92.1)	0.193
CD1a	0 (0–0.2)	0 (0–0.5)	0.250
CD20	1.4 (0.6–21.2)	2.2 (1.5–30)	0.133
CD56	1.2 (0.4–1.8)	0.4 (0–1.2)	0.132

Notes: Data are presented as medians (0.25–0.75 quartiles). ^aExpressed as the percentage of positive stained α-SMA area to the total biopsy area. ^bPercentage of epithelial cells positive for MUC5AC, the remaining results (NE and following) are presented as the ratio of the number of positive cells to the number of visual fields. Statistically significant results are marked in bold.

Abbreviations: RBM, reticular basement membrane; MUC5AC, Mucin-5AC; ECP, eosinophil cationic protein; NE, neutrophil elastase.

Figure 2 Bronchial wall histology changes related to BT.

Notes: (a) Representative histological images of bronchial biopsy samples showing reduction in airway smooth muscle (ASM) after BT at 12 months follow-up. α-SMA staining, hematoxylin-eosin counterstain; 100x magnification. Asterisk indicates fibrous connective tissue. (b) Reduction in the ASM (expressed as the percentage of cross-section surface area) before and after BT. (c) No change in the thickness of reticular basement membrane (RBM) after BT. Data shown as medians and quartiles (n = 11; 2-sided exact Wilcoxon matched-pairs signed rank test).