Predicting treatable traits for long-acting bronchodilators in patients with stable COPD

Figures & data

Figure 1 Study design.

Abbreviations: LABA, long-acting β-2 agonist; LAMA, long-acting muscarinic antagonist.

Table 1 Baseline clinical characteristics of study patients

Traits	n=65
Age, years, mean ± SD	67.4±8.2
Smoking status
Ex-smoker, n (%)	45 (69.2)
Current smoker, n (%)	20 (30.8)
Cigarette smoking, pack-years, mean ± SD	41.9±19.2
mMRC dyspnea grade, n (%)
0	2 (3.1)
1	51 (78.4)
2	10 (15.4)
3	2 (3.1)
COPD assessment test, total score, mean ± SD	9.9±6.2
Body mass index, kg/m^2, mean ± SD	24.2±2.6
Post-bronchodilator FEV1, %predicted, mean ± SD	69.8±9.6
Bronchodilator reversibility,a %predicted value, mean ± SD	4.5±4.6
Diffusing capacity, %predicted, mean ± SD	73.6±16.1
Total lung capacity, %predicted value, mean ± SD	93.6±14.2
RV/TLC, %, mean ± SD	35.1±10.1

Note:

a Bronchodilator reversibility is defined by an FEV₁ change after inhalation of 200 μg salbutamol (%predicted).

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; mMRC, modified Medical Research Council; RV, residual volume; TLC, total lung capacity.

Figure 2 Study flow.

Table 2 Linear regression models for predicting FEV₁ changes after LABA, using clinical traits

Models	Variables							R^2
1	Age	BMI	Intensity of smoking	CAT score	Post-BD FEV1	BDRa	RV/TLC	0.281
2	Age		Intensity of smoking	CAT score	Post-BD FEV1	BDR	RV/TLC	0.281
3	Age			CAT score	Post-BD FEV1	BDR	RV/TLC	0.279
4	Age			CAT score	Post-BD FEV1	BDR		0.268
5				CAT score	Post-BD FEV1	BDR		0.261
6					Post-BD FEV1	BDR		0.231

Note:

a BDR is defined by an FEV₁ change after inhalation of 200 μg salbutamol (%predicted).

Abbreviations: BD, bronchodilator; BDR, bronchodilator reversibility; BMI, body mass index; CAT, chronic obstructive pulmonary disease assessment test; FEV₁, forced expiratory volume in 1 second; LABA, long-acting β-2 agonist; RV, residual volume; TLC, total lung capacity.

Table 3 Linear regression models for predicting FEV₁ changes after LAMA, using clinical traits

Models	Variables							R^2
1	Age	BMI	Intensity of smoking	CAT score	Post-BD FEV1	BDRa	RV/TLC	0.205
2		BMI	Intensity of smoking	CAT score	Post-BD FEV1	BDR	RV/TLC	0.202
3		BMI	Intensity of smoking	CAT score	Post-BD FEV1	BDR		0.200
4		BMI		CAT score	Post-BD FEV1	BDR		0.178
5		BMI		CAT score		BDR		0.158
6				CAT score		BDR		0.121

Note:

a BDR is defined by an FEV₁ change after inhalation of 200 μg salbutamol (%predicted).

Abbreviations: BD, bronchodilator; BDR, bronchodilator reversibility; BMI, body mass index; CAT score, chronic obstructive pulmonary disease assessment test score; FEV₁, forced expiratory volume in 1 second; LAMA, long-acting muscarinic antagonist; RV, residual volume; TLC, total lung capacity.

Table 4 Linear regression models for predicting FEV₁ changes after LABA and LAMA, using gene expressions

	LABA (R^2=0.158, p=0.018)			LAMA (R^2=0.404, p<0.001)
	Regression coefficient	p-value		Regression coefficient	p-value
CLN8	−176.7	0.136	C1orf115	235.9	0.006
PCSK5	−247.4	0.045	KIAA1618	143.1	0.047
SKP2	188.6	0.176	PRKX	−320.3	0.014
			RHOQ	256.8	0.000

Abbreviations: FEV₁, forced expiratory volume in 1 second; LABA, long-acting β-2 agonist; LAMA, long-acting muscarinic antagonist.

Table 5 Linear regression models for predicting FEV₁ changes after LABA and LAMA, using damaged-gene scores

	LABA (R^2=0.318, p<0.001)			LAMA (R^2=0.199, p=0.007)
	Regression coefficient	p-value		Regression coefficient	p-value
EPG5	126.9	0.059	FBN3	−165.4	0.020
FNBP4	−135.7	0.051	FDFT1	122.0	0.123
SCN10A	−106.0	0.034	ZBED6	254.7	0.057
SPTBN5	−170.7	0.014

Abbreviations: FEV₁, forced expiratory volume in 1 second; LABA, long-acting β-2 agonist; LAMA, long-acting muscarinic antagonist.

Table 6 Linear regression models for predicting FEV₁ changes after LABA and LAMA, using clinical traits, gene expressions, and damaged-gene scores

	LABA (R^2=0.512, p<0.001)			LAMA (R^2=0.575, p<0.001)
	Regression coefficient	p-value		Regression coefficient	p-value
Post-BD FEV1	−4.9	0.031	CAT score	−2.3	0.602
BDR	9.4	0.058	BDR	6.8	0.224
CLN8	68.9	0.275	C1orf115	268.7	0.004
PCSK5	−104.6	0.136	KIAA1618	34.9	0.675
SKP2	−115.2	0.018	PRKX	−159.9	0.233
EPG5	−191.8	0.007	RHOQ	272.0	0.000
FNBP4	−97.3	0.352	FBN3	−162.0	0.016
SCN10A	−150.3	0.179	FDFT1	92.1	0.235
SPTBN5	145.5	0.256	ZBED6	274.5	0.014

Abbreviations: BD, bronchodilator; BDR, bronchodilator reversibility; CAT, chronic obstructive pulmonary disease assessment test; FEV₁, forced expiratory volume in 1 second; LABA, long-acting β-2 agonist; LAMA, long-acting muscarinic antagonist.