Effect of N-acetylcysteine in COPD patients with different microsomal epoxide hydrolase genotypes

Figures & data

Table 1 Baseline characteristics of COPD patients and healthy smokers

Characteristics	COPD patients (n=219)	Control subjects (n=223)	P-value
Males/females	194/25	195/28	0.85
Age, years	70.2±7.2	69.1±6.2	0.89
Smoking, pack-years	28.1±7.2	27.2±6.6	0.83
FEV1% predicted	51.8±15.9	93.1±8.2	<0.01
FEV1/FVC	53.2±10.9	85.6±6.4	<0.01

Note: Data are presented as n or mean ± standard deviation, unless otherwise stated.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity.

Table 2 Distribution of EPHX1 genotypes in COPD patients and healthy smokers

Genotypes	COPD patients (n=219)	Control subjects (n=223)
Exon 3 polymorphism
Tyr113/Tyr113 (%)	41 (18.7)	92 (41.3)#
Tyr113/His113 (%)	140 (63.9)§	85 (38.1)
His113/His113 (%)	38 (17.4)	46 (20.6)
Exon 4 polymorphism
His139/His139 (%)	173 (79)	170 (76.2)
His139/Arg139 (%)	36 (16.4)	45 (20.2)
Arg139/Arg139 (%)	10 (4.6)	8 (3.6)

Notes: Data are presented as n (%), unless otherwise stated.

# Homozygous wild-type (Tyr113/Tyr113) in the COPD group versus the control group (P<0.001, OR 0.4, 95% CI 0.3–0.6).

§ Heterozygous (Tyr113/His113) in the COPD group versus the control group (P<0.001, OR 1.6, 95% CI 1.4–1.9).

Abbreviations: COPD, chronic obstructive pulmonary disease; EPHX1, microsom al epoxide hydrolase; CI, confidence interval; OR, odds ratio.

Table 3 Distribution of EPHX1 phenotypes in COPD patients and healthy smokers

Phenotypes	COPD patients (n=219)	Control subjects (n=223)
Fast (%)	9 (4.1)	35 (15.7)#
Normal (%)	53 (24.2)	74 (33.2)
Slow (%)	119 (54.3)§	72 (32.3)
Extremely slow (%)	38 (17.4)	42 (18.8)

Notes: Data are presented as n (%), unless otherwise stated.

# Fast activity EPHX1 phenotype in the COPD group versus the control group (P<0.001, OR 0.2, 95% CI 0.1–0.4).

§ Slow activity EPHX1 phenotype in the COPD group versus the control group (P<0.001, OR 1.4, 95% CI 1.2–1.6).

Abbreviations: COPD, chronic obstructive pulmonary disease; EPHX1, microsomal epoxide hydrolase; CI, confidence interval; OR, odds ratio.

Table 4 Baseline characteristics of patients with COPD in different EPHX1 enzyme activity groups

Characteristics	Slow activity group (n=157)	Fast activity group (n=62)	P-value
Males/females	138/19	56/6	0.10
Age, years	70.2±7.1	69.1±6.2	0.31
Smoking, pack-years	28.1±7.2	27.2±6.6	0.38
Smoking status
Ex-smoker	105	45	0.12
Current smoker	52	17
GOLD stage			0.14
1	31 (19.7%)	10 (16.1%)
2	70 (44.6%)	29 (46.8%)
3	49 (31.2%)	21 (33.9%)
4	7 (4.5%)	2 (3.2%)
Pharmacological treatments
SABA	86 (54.8%)	30 (48.4%)	0.13
LABA	9 (5.7%)	4 (6.5%)	0.08
ICS	7 (4.5%)	3 (4.8%)	0.11
SAMA	18 (11.5%)	8 (12.9%)	0.21
LAMA	32 (20.4%)	11 (17.7%)	0.09
LABA + ICS	98 (62.4%)	40 (64.5%)	0.17
Theophylline	115 (73.2%)	46 (74.2%)	0.10
Post-BD FEV1, L	1.37±0.35	1.35±0.37	0.72
Post-BD FEV1 predicted, %	59.1±16.5	58.8±16.7	0.89
Post-BD FEV1/FVC, %	53.5±10.1	52.3±12.7	0.46
BMI, kg/m^2	23.0±2.9	22.9±2.8	0.85
6MWD, min	292.1±49.9	291.5±53.1	0.94
Yearly exacerbation rate	1.80±0.78	1.76±0.76	0.70
SGRQ score
Total	36.9±12.1	38.0±13.1	0.54
Symptom	40.9±12.3	41.7±13.5	0.67
Activity	47.2±12.1	48.7±13.3	0.43
Impact	26.3±10.9	28.1±11.7	0.29

Note: Data are presented as n (%) or mean ± standard deviation, unless otherwise stated.

Abbreviations: COPD, chronic obstructive pulmonary disease; EPHX1, microsomal epoxide hydrolase; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; SABA, short-acting beta₂ agonist; LABA, long-acting beta₂ agonist; ICS, inhaled corticosteroid; SAMA, short-acting muscarinic antagonist; LAMA, long-acting muscarinic antagonist; BD, bronchodilator; BMI, body mass index; 6MWD, 6-minute walking distance; SGRQ, St George’s Respiratory Questionnaire; min, minutes.

Table 5 Characteristics of subjects with COPD in different EPHX1 enzyme activity groups before and after treatment with NAC for 12 months

	Baseline	After NAC
Post-BD FEV1 predicted, %
Slow activity group (n=157)	59.1±16.5	63.2±17.8#
Fast activity group (n=62)	58.8±16.7	61.9±18.4
Post-BD FEV1, L
Slow activity group (n=157)	1.37±0.35	1.46±0.39#
Fast activity group (n=62)	1.35±0.37	1.38±0.41
BMI, kg/m^2
Slow activity group (n=157)	23.0±2.9	23.1±2.7
Fast activity group (n=62)	22.9±2.8	22.8±2.7
6MWD, min
Slow activity group (n=157)	292.1±49.9	298.8±57.1
Fast activity group (n=62)	291.5±53.1	297.4±54.6
Yearly exacerbation rate
Slow activity group (n=157)	1.80±0.78	0.88±0.59§
Fast activity group (n=62)	1.76±0.76	1.21±0.60§
SGRQ score
Total
Slow activity group (n=157)	36.9±12.1	35.1±12.7
Fast activity group (n=62)	38.0±13.1	35.8±14.8
Symptom
Slow activity group (n=157)	40.9±12.3	37.8±13.1#
Fast activity group (n=62)	41.7±13.5	38.7±15.4
Activity
Slow activity group (n=157)	47.2±12.1	45.8±12.8
Fast activity group (n=62)	48.7±13.3	49.1±14.0
Impact
Slow activity group (n=157)	26.3±10.9	24.9±11.5
Fast activity group (n=62)	28.1±11.7	26.5±12.1

Notes: Data are presented as the mean ± standard, unless otherwise stated.

# Comparison of slow activity group after NAC treatment versus baseline, P<0.05.

§ Comparison of yearly exacerbation rate after NAC versus baseline, P<0.001.

Abbreviations: COPD, chronic obstructive pulmonary disease; EPHX1, microsomal epoxide hydrolase; NAC, N-acetylcysteine; BD, bronchodilator; FEV₁, forced expiratory volume in one second; BMI, body mass index; 6MWD, 6-minute walking distance; SGRQ, St George’s Respiratory Questionnaire; min, minutes.

Figure 1 FEV₁ versus NAC treatment in the two groups.

Abbreviations: FEV₁, forced expiratory volume in one second; NAC, N- acetylcysteine.

Figure 2 FEV₁ versus NAC treatment in the two subgroups of the slow activity group.

Abbreviations: FEV₁, forced expiratory volume in one second; GOLD, Global Initiative for Chronic Obstructive Lung Disease stage; NAC, N-acetylcysteine.