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Table 2 Histopathological evaluation of endobronchial biopsies before and after bronchial thermoplasty

From: Bronchial thermoplasty in asthma: an exploratory histopathological evaluation in distinct asthma endotypes/phenotypes

[A] All asthma patients
(N = 30)
Before 1st BT At 2nd BT 1 month after 1st BT At 3rd BT 1 month after 2nd BT P Value*
Inflammation in the stroma**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
Ν = 30
5 (16.7)
15 (50.0)
10 (33.3)
Ν = 27
5 (18.5)
13 (48.2)
9 (33.3)
Ν = 23
4 (17.4)
12 (52.2)
7 (30.4)
0.948
Tissue lymphocyte infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
Ν = 30
7 (23.3)
12 (40.0)
11 (36.7)
Ν = 27
5 (18.5)
15 (55.5)
7 (25.9)
Ν = 23
4 (17.4)
14 (60.9)
5 (21.7)
0.814
Tissue eosinophil infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
Ν = 30
14 (46.7)
7 (23.4)
9 (30.0)
Ν = 27
19 (70.3)
3 (11.1)
5 (18.5)
Ν = 23
14 (60.9)
7 (30.4)
2 (8.7)
0.149
Granulocytes in the stroma**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
Ν = 30
19 (63.3)
11 (36.4)
0
Ν = 27
21 (77.8)
6 (22.2)
0
Ν = 23
18 (78.3)
4 (17.4)
1 (4.3)
0.408
BM thickening **
Normal, n (%)
Mild-moderate, n (%)
High, n (%)
Ν = 30
1 (3.3)
19 (63.3)
10 (33.3)
Ν = 25
5 (20.0)
15 (60.0)
5 (20.0)
Ν = 23
2 (8.7)
14 (60.9)
7 (30.4)
0.148
Average ASM mass (%)
Median [IQR]
Mean (SD)
Ν = 30
13.3 [4.8–31.2]
19.0 (17.5)
Ν = 26
4.2 [0.0–15.0]
10.8 (14.8)
N = 23
2.5 [0.0–18.0]
9.6 (16.4)
0.014
Distance BM-ASM
μm, Median [IQR]
Mean (SD)
Ν = 24
73.2 [36.7–117.3]
83.9 (56.1)
N = 11
56.5 [24.9–161.8]
95.0 (86.0)
N = 8
81.6 [35.5–126.4]
95.4 (77.5)
0.987
[B] Asthma patients with blood eosinophils ≥ 300/μL
(N = 7)
Asthma patients with blood eosinophils < 300/μL
(N = 23)
Before
1st BT
At 2nd BT 1 month after
1st BT
At 3rd BT 1 month after
2nd BT
P value* Before 1st BT At 2nd BT 1 month after 1st BT At 3rd BT 1 month after 2nd BT P value*
Inflammation in the stroma**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
N = 7
2 (28.6)
2 (28.6)
3 (42.8)
N = 5
1 (20.0)
2 (40.0)
2 (40.0)
N = 5
0
2 (40.0)
3 (60.0)
0.589 N = 23
3 (13.0)
13 (56.5)
7 (30.3)
N = 22
4 (18.2)
11 (50.0)
7 (31.7)
N = 18
4 (22.2)
9 (50.0)
5 (27.9)
0.665
Tissue lymphocyte infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
N = 7
1 (14.3)
2 (28.6)
4 (57.1)
N = 5
1 (20.0)
3 (60.0)
1 (20.0)
N = 5
0
4 (80.0)
1 (20.0)
0.279 N = 23
6 (26.1)
10 (43.5)
7 (30.4)
N = 22
4 (18.2)
12 (54.5)
6 (27.1)
N = 18
4 (22.2)
10 (55.5)
4 (22.3)
0.836
Tissue eosinophil infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
N = 7
4 (57.1)
1 (14.3)
2 (28.6)
N = 5
3 (60.0)
0
2 (40.0)
N = 5
2 (40.0)
3 (60.0)
0
0.980 N = 23
10 (43.5)
6 (26.0)
7 (30.4)
N = 22
16 (72.7)
3 (13.6)
3 (13.6)
N = 18
12 (66.7)
4 (22.2)
2 (11.2)
0.109
Granulocytes in the stroma**
Absence, n (%)
Mild-moderate n (%)
High, n (%)
N = 7
6 (85.7)
1 (14.3)
0
N = 5
4 (80.0)
1 (20.0)
0
N = 5
4 (80.0)
1 (20.0)
0
0.949 N = 23
13 (56.5)
10 (43.5)
0
N = 22
17 (77.3)
5 (22.7)
0
N = 18
14 (77.8)
3 (16.7)
1 (5.6)
0.280
BM thickening **
Normal, n (%)
Mild-moderate, n (%)
High, n (%)
N = 7
1 (14.3)
3 (42.8)
3 (42.8)
N = 5
1 (20.0)
2 (40.0)
2 (40.0)
N = 5
1 (20.0)
2 (40.0)
2 (40.0)
0.821 N = 23
1 (4.3)
15 (65.2)
7 (30.4)
N = 20
4 (20.0)
13 (65.0)
3 (15.0)
N = 18
1 (5.6)
12 (66.7)
5 (27.8)
0.126
Average ASM mass (%)
Median [IQR]
Mean (SD)
N = 7
43.3 [10.5–50.0]
33.3 (20.1)
N = 5
10.0 [5.0–12.5]
9.0 (5.5)
N = 5
1.0 [0.0–10.3]
4.3 (7.7)
0.009 N = 23
12.5 [1.3–20.0]
14.7 (14.4)
N = 21
2.5 [0.0–21.7]
11.2 (16.3)
N = 18
2.5 [0.0–20.0]
10.3 (17.2)
0.248
Distance BM-ASM μm
Median [IQR]
Mean (SD)
N = 7
67.7 [45.0–79.0]
63.7 (20.1)
N = 1
296.0
296.0
N = 1
114.3
114.3
ǂ N = 17
76.0 [33.7–136.0]
92.2 (64.3)
N = 10
55.5 [23.7–123.9]
74.9 (57.3)
N = 7
75.8 [32.6–130.4]
92.7 (83.4)
0.770
[C] Asthma patients with Atopy (N = 19) Asthma patients without atopy (N = 11)
Before 1st BT At 2nd BT 1 month after 1st BT At 3rd BT 1 month after 2nd BT P Value* Before 1st BT At 2nd BT 1 month after 1st BT At 3rd BT 1 month after 2nd BT P Value*
Inflammation in the stroma**
Absence, n (%)
Mild-moderate, n (%)
Severe, n (%)
N = 19
5 (26.3)
6 (31.6)
8 (42.2)
N = 17
4 (23.5)
7 (41.2)
6 (35.3)
N = 13
2 (15.4)
7 (53.9)
4 (30.8)
0.972 N = 11
0
9 (81.8)
2 (18.2)
N = 10
1 (10.0)
6 (60.0)
3 (30.0)
N = 10
2 (20.0)
5 (50.0)
3 (30.0)
0.942
Tissue lymphocyte infiltration**
Absence, n (%)
Mild-moderate, n (%)
Severe, n (%)
N = 19
4 (21.1)
6 (31.6)
9 (47.4)
N = 17
4 (23.5)
8 (47.1)
5 (29.5)
N = 13
2 (15.4)
8 (61.6)
3 (23.1)
0.516 N = 11
3 (27.3)
6 (54.5)
2 (18.2)
N = 10
1 (10.0)
7 (70.0)
2 (20.0)
N = 10
2 (20.0)
6 (60.0)
2 (20.0)
0.800
Tissue eosinophil infiltration**
Absence, n (%)
Mild-moderate, n (%)
Severe, n (%)
N = 19
10 (52.6)
3 (15.8)
6 (31.6)
N = 17
12 (70.6)
2 (11.8)
3 (17.7)
N = 13
6 (46.2)
6 (46.2)
1 (7.7)
0.420 N = 11
4 (36.4)
4 (36.4)
3 (27.3)
N = 10
7 (70.0)
1 (10.0)
2 (20.0)
N = 10
8 (80.0)
1 (10.0)
1 (10.0)
0.198
Granulocytes in the stroma**
Absence, n (%)
A few, n (%)
Many, n (%)
N = 19
13 (68.4)
6 (31.6)
0
N = 17
13 (76.5)
4 (23.5)
0
N = 13
10 (76.9)
3 (23.1)
0
0.783 N = 11
6 (54.5)
5 (45.5)
0
N = 10
8 (80.0)
2 (20.0)
0
N = 10
8 (80.0)
1 (10.0)
1 (10.0)
0.444
BM thickening **
Normal, n (%)
Mild-moderate, n (%)
Severe, n (%)
N = 19
1 (5.3)
12 (63.2)
6 (31.6)
N = 15
2 (13.3)
9 (60.0)
4 (26.7)
N = 13
8 (61.5)
0
5 (38.5)
0.522 N = 11
0
7 (63.6)
4 (36.4)
N = 10
3 (30.0)
6 (60.0)
1 (10.0)
N = 10
2 (20.0)
7 (70.0)
1 (10.0)
0.146
Average ASMC mass (%)
Median [IQR]
Mean (SD)
N = 19
13.3 [1.3–30.0]
18.5 (17.9)
N = 16
4.2 [0.0–11.9]
7.8 (9.8)
N = 13
0.0 [0.0–9.4]
4.8 (7.7)
0.012 N = 11
13.3 [5.0–35.0]
19.9 (17.4)
N = 10
6.3 [0.0–31.3]
15.5 (20.2)
N = 10
4.2 [0.9–25.6]
15.9 (22.4)
0.424
Distance BM-ASMC μm
Median [IQR]
Mean (SD)
N = 13
79.0 [54.4–119.8]
94.3 (64.7)
N = 5
111.3 [35.3–232.5]
129.4 (109.4)
N = 2
100.8
100.8 (18.9)
0.547 N = 11
71.5 [33.5–124.5]
71.6 (43.8)
N = 6
55.5 [20.5–110.4]
66.4 (55.3)
N = 6
59.9 [28.8–163.0]
93.5 (91.3)
0.896
[D] Asthma patients with allergy (N = 16) Asthma patients without allergy (N = 14)
Before
1st BT
At 2nd BT 1 month after
1st BT
At 3rd BT 1 month after 2nd BT P value* Before 1st BT At 2nd BT 1 month after
1st BT
At 3rd BT 1 month after
2nd BT
P value*
Inflammation in the stroma**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
N = 16
3 (18.8)
8 (50.0)
5 (31.2)
N = 14
2 (14.3)
5 (35.7)
7 (50.0)
N = 13
2 (15.4)
7 (53.8)
4 (30.8)
0.588 N = 14
2 (14.3)
7 (50.0)
5 (35.7)
N = 13
3 (23.1)
8 (61.5)
2 (15.4)
N = 10
2 (20.0)
5 (50.0)
3 (30.0)
0.410
Tissue lymphocyte infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
N = 16
4 (25.0)
7 (43.7)
5 (31.3)
N = 14
2 (14.3)
7 (50.0)
5 (35.7)
N = 13
2 (15.4)
9 (69.2)
2 (15.4)
0.698 N = 14
3 (21.4)
5 (35.7)
6 (42.9)
N = 13
3 (23.1)
8 (61.5)
2 (15.4)
N = 10
2 (20.0)
5 (50.0)
3 (30.0)
0.488
Tissue eosinophil infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
N = 16
7 (43.7)
4 (25.0)
5 (31.2)
N = 14
9 (64.3)
1 (7.1)
4 (28.6)
N = 13
7 (53.8)
5 (38.5)
1 (7.7)
0.536 N = 14
7 (50.0)
3 (21.4)
4 (28.6)
N = 13
10 (76.9)
2 (15.4)
1 (7.7)
N = 10
7 (70.0)
2 (20.0)
1(10.0)
0.245
Granulocytes in the stroma**
Absence, n (%)
Mild-moderate n (%)
High, n (%)
N = 16
10 (62.5)
6 (37.5)
0
N = 14
10 (71.4)
4 (28.6)
0
N = 13
9 (69.2)
3 (23.1)
1 (7.7)
0.862 N = 14
9 (64.3)
5 (35.7)
0
N = 13
11 (84.6)
2 (15.4)
0
N = 10
9 (90.0)
1 (10.0)
0
0.304
BM thickening **
Normal, n (%)
Mild-moderate, n (%)
High, n (%)
N = 16
0
10 (62.5)
6 (37.5)
N = 14
3 (21.4)
6 (42.9)
5 (35.7)
N = 13
2 (15.4)
8 (61.5)
3 (23.1)
0.216 N = 14
0
10 (71.4)
4 (28.6)
N = 11
1 (9.1)
9 (81.8)
1 (9.1)
N = 10
0)
6 (60.0)
4 (40.0)
0.274
Average ASM mass (%)
Median [IQR]
Mean (SD)
N = 16
20.0 [9.2–44.6]
25.1 (18.8)
N = 14
6.0 [0–15.0]
9.2 (11.2)
N = 13
0 [0–2.9]
4.0 (7.8)
0.001 N = 14
11.1 [1.2–17.1]
12.1 (13.3)
N = 12
4.2 [0–25.0]
12.6 (18.5)
N = 10
10.6 [2.0–20.0]
15.5 (20.9)
0.626
Distance BM-ASM μm
Median [IQR]
Mean (SD)
N = 12
69.6 [30.1–78.3]
67.4 (42.2)
N = 6
74.9 [23.7–195.4]
108.7 (105.6)
N = 2
46.6
46.6 (41.3)
0.667 N = 12
91.3 [48.5–129.4]
100.4 (64.9)
N = 5
54.5 [29.0–140.2]
78.5 (62.6)
N = 6
100.8 [41.3–163.0]
111.6 (82.5)
0.850
[E] Asthma patients with relevant smoke exposure (N = 10) Asthma patients without relevant smoke exposure (N = 20)
Before 1st BT At 2nd BT 1 month after
1st BT
At 3rd BT 1 month after 2nd BT P value* Before 1st BT At 2nd BT 1 month after 1st BT At 3rd BT 1 month after 2nd BT P value*
Inflammation in the stroma**
Absence, n (%)
Mild-Moderate, n (%)
High, n (%)
Ν = 10
1 (10.0)
6 (60.0)
3 (30.0)
Ν = 10
3 (30.0)
3 (30.0)
4 (40.0)
Ν = 7
1 (14.3)
6 (87.7)
0
0.593 Ν = 20
4 (20.0)
9 (45.0)
7 (35.0)
Ν = 17
2 (11.8)
10 (58.8)
5 (29.4)
Ν = 16
3 (18.8)
6 (37.5)
7 (43.7)
0.945
Tissue lymphocyte infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
Ν = 10
3 (30.0)
4 (40.0)
3 (30.0)
Ν = 10
3 (30.0)
4 (40.0)
3 (30.0)
Ν = 7
1 (14.3)
6 (87.7)
0
0.915 Ν = 20
4 (20.0)
8 (40.0)
8 (40.0)
Ν = 17
2 (11.8)
11 (64.7)
4 (23.5)
Ν = 16
3 (18.8)
8 (50.0)
5 (31.2)
0.897
Tissue eosinophil infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
Ν = 10
5 (50.0)
0
5 (50.0)
Ν = 10
8 (80.0)
0
2 (20.0)
Ν = 7
5 (71.4)
2 (28.6)
0
0.233 Ν = 20
9 (45.0)
7 (35.0)
4 (20.0)
Ν = 17
11 (64.7)
3 (17.6)
3 (17.6)
Ν = 16
9 (56.2)
5 (31.3)
2 (12.5)
0.544
Granulocytes in the stroma**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
Ν = 10
7 (70.0)
3 (30.0)
0
Ν = 10
7 (70.0)
3 (30.0)
0
Ν = 7
5 (71.4)
2 (28.6)
0
0.981 Ν = 20
12 (60.0)
8(40.0)
0
Ν = 17
14 (82.3)
3(17.7)
0
Ν = 16
13 (81.2)
2 (12.5)
1 (6.3)
0.291
BM thickening **
Normal, n (%)
Mild-moderate, n (%)
High, n (%)
Ν = 10
0
7 (70.0)
3 (30.0)
Ν = 9
3 (33.3)
5 (55.6)
1 (11.1)
Ν = 7
0
7 (100.0)
0
0.162 Ν = 20
1 (5.0)
12 (60.0)
7 (35.0)
Ν = 16
2 (12.5)
10 (62.5)
4 (25.0)
Ν = 16
2 (12.5)
7 (43.8)
7 (43.8)
0.461
Average ASM mass (%)
Median [IQR]
Mean (SD)
Ν = 10
9.2 [1.2–22.5]
14.1 (16.8)
Ν = 10
7.5 [0.0–18.7]
13.5 (19.1)
Ν = 7
2.5 [0.0–16.2]
6.3 (8.3)
0.602 Ν = 20
17.2 [9.2–41.2]
21.5 (17.7)
Ν = 16
4.2 [0.1–10.0]
9.1 (11.7)
N = 16
2.5 [0.0–19.0]
11.1 (19.5)
0.019
Distance BM-ASM
μm, Median [IQR]
Mean (SD)
Ν = 8
80.7 [33.6–142.3]
100.8 (79.9)
Ν = 4
102.3 [28.7–249.8]
127.0 (121.5)
Ν = 3
87.4 [7.3–93.3]
78.4 (57.1)
0.864 Ν = 16
73.2 [48.5–94.2]
75.4 (40.4)
Ν = 7
54.5 [24.9–161.8]
76.7 (62.2)
Ν = 5
75.8 [38.4–187.6]
105.5 (92.5)
0.788
[F] Asthma patients with T2 subtype I (N = 12) Asthma patients with T2 subtype II (N = 9) Asthma patients with T2 subtype III (N = 4)
Before 1st BT At 2nd BT 1 month after 1st BT At 3rd BT 1 month after 2nd BT P value* Before 1st BT At 2nd BT 1 month after 1st BT At 3rd BT 1 month after 2nd BT P value* Before 1st BT At 2nd BT 1 month after 1st BT At 3rd BT 1 month after 2nd BT P value*
Inflammation in the stroma**
Absence, n (%)
Mild-Moderate, n (%)
High, n (%)
N = 12
2 (16.7)
6 (50.0)
4 (33.3)
Ν = 11
2 (18.2)
4 (36.4)
5 (45.4)
Ν = 8
2 (25.0)
2 (25.0)
4 (50.0)
0.806 Ν = 9
1 (11.1)
5 (55.6)
3 (33.3)
Ν = 8
1 (12.5)
5 (62.5)
2 (25.0)
Ν = 7
1 (14.3)
6 (85.7)
0
0.372 Ν = 4
2 (50.0)
0
2 (50.0)
Ν = 3
1 (33.3)
0
2 (66.7)
Ν = 3
0
1 (33.3)
2 (66.7)
0.344
Tissue lymphocyte infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
N = 12
4 (33.3)
4 (33.3)
4 (33.3)
Ν = 11
2 (18.2)
5 (45.4)
4 (36.4)
Ν = 8
2 (25.0)
3 (37.5)
3 (37.5)
0.810 Ν = 9
1 (11.1)
4 (44.4)
4 (44.4)
Ν = 8
1 (12.5)
5 (62.5)
2 (25.0)
Ν = 7
1 (14.3)
6 (85.7)
0
0.288 Ν = 4
1 (25.0)
1 (25.0)
2 (50.0)
Ν = 3
1 (33.3)
1 (33.3)
1 (33.3)
Ν = 3
0
2 (66.7)
1 (33.3)
0.450
Tissue eosinophil infiltration**
Absence, n (%)
Mild-moderate, n (%)
High, n (%)
N = 12
3 (25.0)
4 (33.3)
5 (41.7)
Ν = 11
7 (63.6)
1 (9.1)
3 (27.3)
Ν = 8
4 (50.0)
2 (25.0)
2 (25.0)
0.316 Ν = 9
6 (66.7)
2 (22.2)
1 (11.1)
Ν = 8
7 (87.5)
1 (12.5)
0
Ν = 7
4 (57.1)
3 (42.9)
0
0.287 Ν = 4
2 (50.0)
0
2 (50.0)
Ν = 3
1 (33.3)
0
2 (66.7)
Ν = 3
1 (33.3)
2 (66.7)
0
0.787
Granulocytes in the stroma**
Absence, n (%)
Mild-moderate n (%)
High, n (%)
N = 12
8 (66.7)
4 (33.3)
0
Ν = 11
9 (81.8)
2 (18.2)
0
Ν = 8
7 (87.5)
0
1 (12.5)
0.614 Ν = 9
6 (66.7)
3 (33.3)
0
Ν = 8
6 (75.0)
2 (25.0)
0
Ν = 7
5 (71.4)
2 (28.6)
0
0.878 Ν = 4
3 (75.0)
1 (25.0)
0
Ν = 3
2 (66.7)
1 (33.3)
0
Ν = 3
2 (66.7)
1 (33.3)
0
0.945
BM thickening **
Normal, n (%)
Mild-moderate, n (%)
High, n (%)
N = 12
0
10 (83.3)
2 (16.7)
Ν = 9
2 (22.2)
5 (55.6)
2 (22.2)
Ν = 8
1 (12.5)
5 (62.5)
2 (25.0)
0.786 Ν = 9
1 (11.1)
6 (66.7)
2 (22.2)
Ν = 8
1 (12.5)
6 (75.0)
1 (12.5)
Ν = 7
1 (14.3)
5 (71.4)
1 (14.3)
0.872 Ν = 4
0
1 (25.0)
3 (75.0)
Ν = 3
1 (33.3)
0
2 (66.7)
Ν = 3
0
1 (33.3)
2 (66.7)
0.350
Average ASM mass (%)
Median [IQR]
Mean (SD)
N = 12
15.1 [7.8–26.4]
17.1 (14.6)
Ν = 10
4.1 [0.8–19.2]
10.0 (12.8)
Ν = 8
9.8 [2.2–18.9]
10.6 (10.0)
0.290 N = 9
20.0 [8.1–40.0]
24.1 (20.7)
Ν = 8
5.3 [-0.5–16.0]
7.7 (9.8)
Ν = 7
0 [-3.1–9.2]
3.1 (6.6)
0.049 N = 4
26.9 [-7.1–65.1]
29.0 (22.7)
Ν = 3
10.0 [-10.6–27.3]
8.3 (7.6)
Ν = 3
0 [-2.7–4.4]
0.8 (1.4)
0.082
Distance BM-ASM μm
Median [IQR]
Mean (SD)
Ν = 10
84.8 [51.0–153.8]
102.4 (71.8)
Ν = 7
93.3 [43.9–146.8]
95.3 (55.6)
Ν = 3
75.8 [-33.2–153.5]
60.2 (37.6)
0.639 Ν = 5
71.5 [14.3–132.5]
73.4 (47.6)
Ν = 1
19.9
Ν = 1
114.3
Ν = 4
65.7 [26.6–93.7]
60.1 (21.1)
Ν = 1
296.0
Ν = 0
  1. T2 subtype I: Patients with only one T2 positive marker (allergy, or atopy, or eosinophils ≥ 300/μL)
  2. T2 subtype II: Patients with any two of T2 positive markers
  3. T2 subtype III: Patients with any three of T2 positive markers
  4. ǂCannot be determined, only 1 observation in two time points
  5. *Comparisons between values before and after BT. For categorical values, the p value was calculated using mixed multinomial (ordinal) logistic regression models, where the factor patient was included as a random effect. For continuous values, the p value was calculated using rank mixed linear regression models, where the factor patient was included as a random effect
  6. **Qualitative evaluation, 0–3 scale: 0 to < 0.5 = absence/normal, 0.5 to < 1.50 = mild-moderate, 1.5–3 = high
  7. BT bronchial thermoplasty, BM basement membrane, ASM airway smooth muscle, IQR inter quartile range, SD standard deviation