Correlation of Activation Site and Number with the Clinical Response to Bronchial Thermoplasty

Figures & data

Table 1 Comparison of Baseline Patient Characteristics

Indicators	Group A (n=55)	Group B (n=51)	P value
Age (year)	49.67±12.11	51.31±13.67	NS
Gender (%)			NS
Male	36 (65)	34 (67)
Female	19 (35)	17 (33)
Course of disease (year)	8 (15)	10 (15)	NS
Smoking rate	32.7%	39.2%	NS
Allergy rate	25.5%	25.5%	NS
Height (cm)	162.22±9.13	162.94±8.03	NS
Weight (Kg)	61.74±11.92	62.04±11.54	NS
BMI (kg/m^2)	23.44±3.85	23.22±3.18	NS
Percentage of blood eosinophils (%)	1.8 (4.1)	2.1 (4.8)	NS
Exacerbations in 6 months	6 (6.62)	5 (5.28)	NS
FeNO (ppb)	31 (43)	41 (45)	NS
FEV1(L)	1.51±0.68	1.56±0.81	NS
FEV1 (%, predicted)	54.96±19.65	56.14±23.82	NS
FVC (L)	2.49±0.85	2.48±0.89	NS
ACQ score (point)	3.39±1.27	2.98±0.95	0.065

Notes: Group A, the group not combined with main bronchial ablation; Group B, the group combined with main bronchial ablation. Data are expressed as mean ± standard deviation or number, percentage, median [interquartile range (IQR)]; significance level at P-value < 0.05.

Abbreviations: NS, not significant; FeNO, Fractional excretion of exhaled nitrogen; FeV1, forced expiratory volume in the first second; FVC, Forced vital capacity; ACQ, Asthma Control Questionnaire; BMI, body mass index.

Table 2 Comparison of Indicators Between Responders and Non-Responders

Indicators	Responders (n=89)	Non-Responders (n=17)	P
Age (years)	48.43±12.19	61.12±11.045	0.000***
Gender [n(%)]			NS
Male	59 (66)	11 (65)
Female	30 (34)	6 (35)
Course of disease (years)	9 (16)	10 (12)	NS
Smoking rate	31.4%	58.8%	0.031*
Allergy rate	28%	11.7%	NS
Height (cm)	162.61±8.50	162.32±9.30	NS
Weight (Kg)	61.99±10.97	61.29±15.27	NS
BMI (kg/m^2)	23.39±3.34	23.08±4.50	NS
Combined with main bronchial ablation [n(%)]			NS
Yes	41 (46)	10 (59)
No	48 (54)	7 (41)
Activations in the 1st BT session	60.67±12.74	57.18±12.10	NS
Activations in the 2nd BT session	62.71±13.43	57.47±14.12	NS
Activations in the 3rd BT session	71.54±15.34	57.94±11.43	0.001**
Total activations	194.92±30.73	172.09±26.82	0.006**
Percentage of blood eosinophils (%)	2.1 (4.2)	2.1 (3.8)	NS
FeNO (ppb)	41 (48)	26 (15)	0.035*
FEV1(L)	1.67±0.72	0.84±0.39	0.000***
FEV1(%, predicted)	59.22±20.89	36.17±14.29	0.000***
FVC (L)	2.64±0.83	1.70±0.57	0.000***
ACQ score (point)	3.30±1.15	2.60±0.85	0.02*

Notes: Responder: a change in ACQ value ≥ 0.5 was used to define a clinical responder. Activations in the 1st BT session, the activation number in the first BT session; Activations in the 2nd BT session, the activation number in the second BT session; Activations in the 3rd BT session, the activation number in the third BT session; Total activations, the total activation number of the three BT sessions. Data are expressed as mean ± standard deviation or number, percentage, median [interquartile range (IQR)]. *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 1 Total activation numbers in BT responders and non-responders in main bronchial ablation and non-main bronchial ablation groups.

Notes: The box-plot displaying the total radiofrequency activation numbers of three BT sessions in responders and non-responders of each group. The mean values are presented in small squares inside the box bodies. Group A, the group combined with main bronchial ablation; Group B, the group combined with main bronchial ablation. Blue color represents responders to BT, while the red color represents non-responders. *P < 0.05 compared with the mean value of non-responders.

Abbreviation: BT, bronchial thermoplasty.

Table 3 The Estimated Coefficients of Lasso Regression

Variables	Non-Zero Coefficients
ACQ score (point)	0.06350
FEV1(%, predicted)	0.00298
FVC	0.04522
Activations in the third BT session	0.00256
Age	−0.00378
Post-BT Prednisone	−0.03202

Notes: Post-BT Prednisone: the usage of prednisone post-BT treatment.

Table 4 Univariate Analysis for Clinical Response to BT

Variables	β	Wald	OR [95% CI]	P
Baseline ACQ score (point)	0.68	4.996	1.97 [1.08–3.58]	0.025*
Baseline FEV1 (%, predicted)	0.087	12.548	1.09 [1.04–1.14]	<0.001***
Baseline FEV1	3.214	14.155	24.87 [4.66–132.72]	<0.001***
Baseline FVC	1.874	14.184	6.51 [2.46–17.28]	<0.001***
Activations for the first BT session	0.028	1.509	1.03 [0.98–1.07]	0.219
Activations for the second BT session	0.044	3.077	1.045 [0.995–1.097]	0.079
Activations for the third BT session	0.07	9.731	1.073 [1.026–1.121]	0.002**
Total activations	0.032	7.164	1.032 [1.008–1.056]	0.007**
Whether combined with the left and right main bronchial ablation	−0.514	0.918	0.59 [0.21–1.71]	0.338

Notes: *P < 0.05; **P < 0.01; ***P < 0.001.

Abbreviations: β, regression coefficient; 95% CI, 95% confidence intervals.

Table 5 Logistic Regression for the Influencing Factors of Clinical Response to BT

Variables	β	Wald	OR [95% CI]	P
Baseline ACQ score (point)	1.895	10.604	6.65 [2.13–20.82]	0.001**
Baseline FEV1 (%, predicted)	0.086	5.386	1.09 [1.01–1.17]	0.02*
Baseline FVC	1.706	3.702	5.508 [0.97–31.32]	0.054
Constant	−11.43	13.63	0	<0.001***

Notes: *P < 0.05; **P < 0.01; ***P < 0.001.

Table 6 Parameter Estimation and Hypothesis Testing for the Influencing Factors of ACQ Improvement Before and 6 Months After BT Sessions

Parameter	Estimated Coefficient (B)	95% CI		t	P
constant	1.985	1.468	2.503	7.610	0.000***
Baseline ACQ score (point)	−1.005	−1.107	−0.902	−19.412	0.000***
Baseline FEV1(%, predicted)	−0.013	−0.018	−0.007	−4.642	0.000***

Notes: ***P < 0.001.

Figure 2 Correlation between baseline ACQ and ACQ improvement.

Notes: Linear regression analysis was performed to evaluate the relationship between the baseline ACQ and ACQ improvement from baseline. A greater baseline ACQ value resulted in a greater negative delta ACQ value (namely, the greater improvement in ACQ) (R² = 0.741, P <0.05). Delta ACQ: post-BT ACQ score minus pre-BT ACQ score.

Abbreviation: ACQ, Asthma Control Questionnaire scores.

Figure 3 Correlation between activation number in the third BT session and ACQ improvement.

Notes: Linear regression analysis was performed to evaluate the relationship between the RF_activation in the third BT session and ACQ improvement from baseline. A greater number of activation number in the third BT session indicated the greater negative delta ACQ value (namely, the greater improvement in ACQ) (R² = 0.741, P <0.05).

Abbreviation: RF, radiofrequency activation.

Table 7 Comparison Among the Cohorts with Different Activation Numbers

Groups	Cohort A (n=29)	Cohort B (n=42)	Cohort C (n=35)	P
The total activations	156.34±8.47	186.64±9.02	225.97±23.01	<0.001***
Age (year)	55.86±10.48	50.02±12.95	46.51±13.26	0.013*
Course of disease (year)	10 (24)	8 (15)	8 (8)	NS
Smoking rate	37.9%	33.3%	37.1%	NS
Allergy rate	24.1%	28.5%	22.8%	NS
Height (cm)	160.02±10.08	161.87±7.79	165.51±7.46	0.038*
Weight (Kg)	60.17±12.14	61.94±10.77	63.22±12.49	NS
BMI (kg/m^2)	23.46±3.93	23.55±3.24	22.97±3.59	NS
Percentage of blood eosinophils (%)	2.1 (3.45)	2.0 (3.45)	1.9 (6.8)	NS
FeNO (ppb)	31 (20)	33 (49)	50 (52)	0.005**
FEV1(L)	1.13±0.48	1.63±0.86	1.75±0.65	0.002**
Post-BT FEV1 (L)	1.46±0.68	2.04±0.90	2.18±0.69	0.001**
FEV1(%, predicted)	46.31±15.34	58.48±23.19	59.62±22.49	0.025*
Post-BT FEV1(%, predicted)	51.71±18.04	73.15±22.58	69.82±20.70	<0.001***
FVC (L)	2.08±0.68	2.56±0.98	2.74±0.74	0.007**
Post-BT FVC (L)	2.47±0.79	2.90±1.04	3.32±0.74	0.001**
ACQ score (point)	3.15±1.13	3.09±1.21	3.34±1.07	NS
Post-BT ACQ score (point)	1.50±0.72	1.17±0.66	1.17±0.46	0.04*
Non-responding rate (%)	34.5%	11.9%	5.7%	0.005**

Notes: Cohort A, 29 cases who received < 170 activations; Cohort B, 42 cases who received ≥ 170 to < 200 activations; Cohort C, 35 cases who received ≥ 200 activations. Data are expressed as mean ± standard deviation or number, percentage, median [interquartile range (IQR)]. *P < 0.05; **P < 0.01; ***P < 0.001.

Figure 4 Post-BT ACQ score in each cohort with different activation numbers.

Notes: The box-plot showing the distribution of ACQ scores at 6 months after BT procedure in three cohorts. The mean values are presented in small squares inside the box bodies. Cohort A, patients who received <170 activations; Cohort B, patients who received ≥170 to <200 activations; and Cohort C, patients who received ≥ 200 activations.*P < 0.05 compared with the mean value of Cohort A.

Figure 5 Post-BT FVE1 (%, predicted) in each cohort with different activation numbers.

Notes: The box-plot showing the distribution of FVE1 (%, predicted) at 6 months after BT procedure in three cohorts. *P < 0.05 compared with the Cohort A.

Abbreviations: FVE1 (%, predicted), forced expiratory volume in 1 sec (FEV1)% predicted.

Figure 6 Post-BT FEV1 in each cohort with different activation numbers.

Notes: The box-plot showing the distribution of FEV1 at 6 months after BT procedure in three cohorts. *P < 0.05 compared with the mean value of Cohort A.

Figure 7 Post-BT FVC in each cohort with different activation numbers.

Notes: The box-plot showing the distribution of FVC at 6 months after BT procedure in three cohorts. *P < 0.05 compared with the mean value of Cohort A.

Figure 8 ROC curves in predicting the clinical response to BT with different activation numbers.

Notes: RF_activation in the 1st BT, the activation number in the first BT session; RF_activation in the 2nd BT, the activation number in the second BT session; RF_activation in the 3rd BT, the activation number in the third BT session; Total activations, the total activation number of the three BT sessions.

Abbreviation: ROC, receiver operating characteristic.