Background
Methods
Study design
Patients
Laboratory testing and cytokine measurements
Statistics
Results
Characteristics of the patients
Stable | At-risk | P-value*† | |
---|---|---|---|
(N = 93) | (N = 11) | ||
Age, mean (SD) | 52.7 (15.4) | 51.7 (19.4) | 0.852 |
Sex, M: F, n (%) | 39 (42.0): 54 (58.0) | 3 (27.3): 8 (72.7) | 0.540 |
BMI, median (IQR) | 22.9 (20.6–26.9) | 24.6 (21.8–30.1) | 0.089 |
Smoking, n (%) | |||
Current-smoker | 8 (8.6) | 2 (18.2) | 0.454 |
Ex-smoker | 27 (29.0) | 4 (36.4) | |
Never-smoker | 58 (62.4) | 5 (45.4) | |
Asthma control, n (%) | |||
Well controlled | 29 (31.2) | 1 (9.1) |
< 0.001
|
Partially controlled | 51 (54.8) | 2 (18.2) | |
Uncontrolled | 13 (14.0) | 8 (72.7) | |
Treatment step, n (%) | |||
1 | 4 (4.3) | 0 (0.0) |
0.008
|
2 | 14 (15.1) | 0 (0.0) | |
3 | 20 (21.5) | 0 (0.0) | |
4 | 49 (52.7) | 7 (63.6) | |
5 | 6 (6.4) | 4 (36.4) | |
Oral CS use, n (%) | 6 (6.5) | 4 (36.4) |
0.011
|
Laboratory tests | |||
WBC (/μL), median (IQR) | 6300 (5000–7200) | 10,500 (6700–12,100) |
< 0.001
|
Neutrophil (/μL), median (IQR) | 3618 (2745–4772) | 8159 (3953–9196) |
< 0.001
|
Eosinophil (/μL), median (IQR) | 201 (128–334) | 79 (32–303) |
0.029
|
CRP (mg/dl), median (IQR) | 0.1 (0–0.2) | 0.1 (0–0.5) | 0.208 |
IgE (IU/ml), median (IQR) | 188 (45–533) | 185 (12–1539) | 0.841 |
IL-8 (pg/ml), median (IQR) | 13.1 (10.6–16.9) | 16.0 (9.6–22.6) | 0.612 |
IL-6 (pg/ml), median (IQR) | 1.0 (0.5–1.7) | 2.4 (1.2–3.7) |
0.035
|
Serum H2O2 (U.CARR), median (IQR) | 336 (302–380) | 379 (350–421) |
0.025
|
FeNO (ppb), median (IQR) | 24 (16–42) | 16 (11–99) | 0.302 |
EBC H2O2 (U.CARR), median (IQR) | 0.5 (0.1–1.0) | 0.5 (0.2–0.6) | 0.687 |
Lung function tests | |||
VC (L), median (IQR) | 3.1 (2.5–4.0) | 2.8 (2.5–4.0) | 0.067 |
%VC (%), mean (SD) | 107.4 (16.1) | 94.5 (18.9) |
0.016
|
FVC (L), median (IQR) | 3.0 (2.5–3.9) | 2.5 (1.9–3.6) | 0.067 |
%FVC (%), mean (SD) | 98.8 (15.6) | 87.4 (18.7) |
0.027
|
FEV1 (L), median (IQR) | 2.3 (1.8–2.9) | 1.7 (1.3–2.9) | 0.104 |
%FEV1 (%), mean (SD) | 89.6 (19.1) | 80.1 (26.1) | 0.135 |
FEV1/FVC (%), median (IQR) | 75.2 (68.4–81) | 73.6 (64.3–83.4) | 0.958 |
Serum sST2 levels and high-risk exacerbation patients
Serum sST2 levels and neutrophilic inflammation
Serum sST2 level (N = 104) | Blood neutrophil count (N = 104) | |||
---|---|---|---|---|
r
| P-value* |
r
| P-value* | |
EBC H2O2 levela | 0.281 |
0.011
| 0.074 | 0.513 |
FeNO | 0.045 | 0.653 | −0.306 |
0.002
|
Serum IL-8 level | 0.328 |
0.001
| 0.011 | 0.915 |
Serum IL-6 level | 0.089 | 0.370 | 0.384 |
0.001
|
Serum CRP level | 0.002 | 0.981 | 0.305 |
0.002
|
Serum IgE level | 0.046 | 0.643 | −0.241 |
0.014
|
Serum H2O2 level | −0.099 | 0.318 | 0.214 |
0.029
|
BMI | 0.185 | 0.060 | 0.205 |
0.037
|
WBC | 0.138 | 0.164 | 0.901 |
< 0.001
|
Blood neutrophil count | 0.129 | 0.191 | ND | ND |
Blood eosinophil count | −0.162 | 0.100 | −0.187 | 0.057 |
Blood neutrophil (%) | 0.107 | 0.278 | 0.794 |
< 0.001*
|
Blood eosinophil (%) | −0.206 |
0.036*
| − 0.409 |
< 0.001*
|
Univariate | Multivariatea | |||
---|---|---|---|---|
Hazard ratio (95% CI) | P-value | Hazard ratio (95% CI) | P-value* | |
High serum sST2 level (> 18 ng/ml) | 9.2 (2.4–34.7) | 0.001 | 5.5 (1.4–21.5) | 0.015 |
Blood neutrophiliab (> 6000 μl) | 26.6 (7.9–100.9) | < 0.001 | 18.9 (4.8–74.4) | < 0.001 |
Definition of exacerbation-risk score and the score-based phenotypes
Exacerbation-risk score | P-value* | ||||
---|---|---|---|---|---|
0 | 1 | 2 | 3 | ||
(N = 72) | (N = 19) | (N = 6) | (N = 7) | ||
Patients with exacerbation of asthma, n (%) | 1 (1.4) | 2 (10.5) | 2 (33.3) | 6 (85.7) |
< 0.001
|
Age, mean (SD) | 54.1 ± 14.6 | 56.1 ± 17.3 | 47.2 ± 20.0 | 59.7 ± 18.4 | 0.321 |
Sex, M: F, n (%) | 24 (33.8): 48 (66.7) | 13 (68.4): 6 (31.6) | 2 (33.3): 4 (66.7) | 3 (42.9): 4 (57.1) | 0.050 |
BMI, median (IQR) | 22.9 (20.6–27.4) | 23.1 (21.5–26.7) | 23.1 (19.6–28.6) | 27.9 (21.8–30.1) | 0.538 |
Smoking, n (%) | |||||
Current smoker | 8 (11.1) | 1 (5.3) | 0 (0) | 1 (28.6) | 0.527 |
Ex-smoker | 19 (26.4) | 6 (31.6) | 4 (66.7) | 2 (14.3) | |
Never-smoker | 45 (62.5) | 12 (63.2) | 2 (33.3) | 4 (57.1) | |
Asthma control, n (%) | |||||
Well controlled | 20 (27.8) | 7 (36.8) | 3 (50.0) | 0 (0) |
< 0.001
|
Partially controlled | 42 (58.3) | 9 (47.4) | 1 (16.7) | 1 (14.3) | |
Uncontrolled | 10 (13.9) | 3 (15.8) | 2 (33.3) | 6 (85.7) | |
Treatment step, n (%) | |||||
1 | 4 (5.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
0.005
|
2 | 11 (15.3) | 1 (5.3) | 1 (16.7) | 1 (14.2) | |
3 | 16 (22.2) | 4 (21.0) | 0 (0.0) | 0 (0.0) | |
4 | 39 (54.2) | 12 (63.2) | 2 (33.3) | 3 (42.9) | |
5 | 2 (2.8) | 2 (10.5) | 3 (50.0) | 3 (42.9) | |
sST2 (ng/ml), median (IQR) | 11.0 (8.8–13.0) | 21.1 (18.8–28.4) | 11.8 (11.4–14.3) | 26.4 (20.8–34.0) |
< 0.001
|
WBC (/μL), median (IQR) | 6200 (5225–6800) | 5900 (4700–7200) | 10,250 (9000–12,350) | 10,500 (9700–12,100) |
< 0.001
|
Neutrophil (/μL), median (IQR) | 3496 (2786–4268) | 3553 (2248–4650) | 6333 (6117–10,381) | 8159 (7497–9196) |
< 0.001
|
Eosinophil (/μL), median (IQR) | 199 (133–335) | 201 (45–307) | 229 (75–677) | 87 (32–303) | 0.273 |
Eosinophil (%), median (IQR) | 3.7 (2.1–6.2) | 3.4 (0.9–4.9) | 2.4 (0.6–7.4) |
1.0 (0.3–2.5) †
|
0.045
|
CRP (mg/dl), median (IQR) | 0.1 (0–0.2) | 0.0 (0–0.) | 0.1 (0–0.4) | 0.1 (0.1–0.5) | 0.195 |
IgE (IU/ml), median (IQR) | 201 (45–684) | 236 (104–330) | 60 (8–843) | 73 (3–2656) | 0.432 |
IL-8 (pg/ml), median (IQR) | 13.0 (10.5–15.8) |
21.9 (9.7–31.0) †
| 11.7 (7.9–19.8) | 16.0 (11.0–25.2) | 0.063 |
IL-6 (pg/ml), median (IQR) | 1.0 (0.5–1.8) | 0.9 (0.5–1.9) | 2.5 (1.2–8.0) | 1.8 (0.3–3.7) | 0.143 |
Serum H2O2 (U. CARR), median (IQR) | 345 (315–401) | 322 (294–356) | 341 (304–390) | 383 (336–390) | 0.182 |
FeNO (ppm), median (IQR) | 23.5 (16.0–38.3) | 24.0 (15.0–63.0) | 19.0 (13.3–49.8) | 16.0 (11.0–121.0) | 0.892 |
EBC H2O2 (U. CARR) a | 0.4 (0.0–1.0) | 0.5 (0.2–1.1) | 0.4 (0.0–0.6) | 0.6 (0.3–0.7) | 0.751 |
VC (L), median (IQR) | 2.9 (2.5–3.8) | 3.7 (2.6–4.4) | 3.7 (3.3–3.8) |
2.3 (2.0–2.9) †
| 0.079 |
%VC (%), mean (SD) | 106.7 (45.6) | 107.9 (19.5) | 114.0 (13.0) |
87.3 (14.2) ‡
|
0.014
|
FVC (L), median (IQR) | 2.9 (2.4–3.7) | 3.7 (2.5–4.4) | 3.6 (3.2–3.8) |
2.2 (1.8–2.9) †
| 0.087 |
%FVC (%), mean (SD) | 98.6 (14.6) | 97.1 (15.4) | 107.1 (15.4) |
79.4 (12.1) ‡
|
0.009
|
FEV1 (L), median (IQR) | 2.3 (1.8–2.7) | 2.5 (1.4–3.1) | 2.8 (2.0–3.0) | 1.6 (1.3–1.9) | 0.142 |
%FEV1 (%), mean (SD) | 90.1 (17.8) | 86.5 (23.5) | 97.7 (24.3) |
71.1 (22.3) ‡
| 0.063 |
FEV1/FVC (%), median (IQR) | 76.0 (69.2–81.0) | 70.3 (67.6–79.8) | 79.4 (66.0–82.0) | 73.6 (64.0–83.6) | 0.550 |