Chronic cough as a novel phenotype of chronic obstructive pulmonary disease

Figures & data

Table 1 Baseline characteristics of patients with chronic obstructive pulmonary disease according to the presence of chronic cough

	Total	Chronic cough
		(+)	(−)	P-value
Patients	1,613	377 (23.4%)	1,236 (76.6%)
Age, years	72.6 ± 7.9	71.8 ± 7.8	72.9 ± 7.9	0.02
Male sex	1,380 (91.6%)	317 (89.8%)	1,063 (92.2%)	0.16
BMI, kg/m^2	23.1 ± 8.9	22.5 ± 3.2	23.2 ± 10.0	0.14
Smoking status
Current	434 (27.1%)	126 (33.5%)	308 (25.1%)	0.001
Amount, PY	43.8 ± 25.0	44.8 ± 24.8	43.5 ± 25.1	0.41
Previous AE	405 (25.2%)	122 (32.5%)	283 (23.0%)	<0.001
Laboratory
WBC,/μL	7,750 ± 2,675	7,950 ± 2,942	7,690 ± 2,579	0.13
Eosinophil, %	3.4 ± 3.6	3.4 ± 3.3	3.5 ± 3.7	0.61
Hb, g/dL	14.2 ± 1.5	14.2 ± 1.5	14.2 ± 1.6	0.86
Pulmonary function
FEV1, % predicted	59.2 ± 18.3	55.8 ± 17.4	60.2 ± 18.4	<0.001
FVC, % predicted	84.6 ± 18.3	83.9 ± 18.5	84.8 ± 18.2	0.39
DLCO, % predicted	74.6 ± 23.8	69.3 ± 20.9	76.3 ± 24.5	<0.001
Quality of life
mMRC score	1.45 ± 0.93	1.71 ± 0.98	1.38 ± 0.90	<0.001
0	189 (11.8%)	31 (8.3%)	158 (12.8%)	<0.001
1	770 (47.9%)	147 (39.2%)	623 (50.5%)
2	408 (25.4%)	108 (28.8%)	300 (24.3%)
3	211 (13.1%)	79 (21.1%)	132 (10.7%)
4	30 (1.9%)	10 (2.7%)	20 (1.6%)
CAT score	15.4 ± 7.9	19.3 ± 8.5	14.2 ± 7.3	<0.001
SGRQ-C
Symptom	44.6 ± 20.5	57.2 ± 21.1	40.6 ± 18.6	<0.001
Activity	46.0 ± 23.1	52.6 ± 24.8	43.9 ± 22.1	<0.001
Impact	24.1 ± 19.7	33.4 ± 23.1	21.2 ± 17.5	<0.001
Total	34.1 ± 18.9	43.1 ± 21.3	31.2 ± 17.1	<0.001
6MWD, m	373.8 ± 116.1	379.7 ± 101.7	371.9 ± 120.2	0.27

Note: Data were represented as mean ± standard deviation, or frequency (%).

Abbreviations: BMI, body mass index; PY, pack year; AE, acute exacerbation; WBC, white blood cell count; Hb, hemoglobin; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; DL_CO, diffusing capacity of the lungs for carbon monoxide; mMRC, modified Medical Research Council Dyspnea scale; CAT, COPD Assessment Test; SGRQ-C, COPD-specific version of Saint George’s Respiratory Questionnaire; 6MWD, 6-minute walk distance.

Figure 1 Distribution of patients according to presence of chronic cough and chronic sputum production in the study cohort of patients with chronic obstructive pulmonary disease.

Figure 2 Comparison of dyspnea, quality of life, and lung function between patients with COPD with chronic cough and those without chronic cough.

Abbreviations: COPD, chronic obstructive pulmonary disease; mMRC, modified Medical Research Council Dyspnea scale; CAT, COPD Assessment Test; SGRQ-C, COPD-specific version of St George’s Respiratory Questionnaire; FEV₁, forced expiratory volume in 1 second.

Figure 3 Distribution of GOLD severity stages in patients with chronic obstructive pulmonary disease with chronic cough and those without chronic cough.

Abbreviation: GOLD, Global Initiative for Obstructive Lung Disease.

Table 2 Clinical characteristics of patients with chronic obstructive pulmonary disease exhibiting cough, sputum production, or both

	A	B	C	D	P-value (A vs C)	P-value (B vs C)	P-value (C vs D)
	C(−)S(−)	C(−)S(+)	C(+)S(−)	C(+)S(+)
Patients	1,006 (62.4%)	230 (14.3%)	84 (5.2%)	293 (18.2%)
Age, years	72.9 ± 7.8	72.5 ± 8.8	71.5 ± 8.9	71.7 ± 7.7	0.11	0.31	0.82
Male sex	950 (90.9%)	232 (95.1%)	74 (88.1%)	275 (90.2%)	0.38	0.04	0.55
BMI, kg/m^2	23.3 ± 10.6	23.2 ± 3.4	22.6 ± 3.5	22.5 ± 3.2	0.47	0.55	0.91
Smoking status
Current	261 (23.1%)	87 (34.0%)	30 (33.7%)	107 (33.3%)	0.02	>0.99	>0.99
Amount, PY	43.3 ± 24.8	43.3 ± 26.5	40.4 ± 24.7	45.4 ± 24.4	0.31	0.37	0.12
Previous AE	232 (20.5%)	70 (27.3%)	23 (25.6%)	110 (34.3%)	0.27	0.78	0.09
Laboratory
WBC	7,610 ± 2,494	7,870 ± 2,720	8,010 ± 2,439	7<880 ± 3<008	0.23	0.72	0.73
Neutrophil, %	59.3 ± 26.5	59.9 ± 14.1	59.9 ± 12.9	60.0 ± 13.0	0.83	0.99	0.99
Eosinophil, %	3.4 ± 3.4	3.7 ± 4.6	3.4 ± 2.8	3.5 ± 3.7	0.46	0.48	0.76
Hb	14.2 ± 1.6	14.1 ± 1.7	14.2 ± 1.5	14.2 ± 1.5	0.81	0.63	0.71
Pulmonary function
FEV1, %	61.4 ± 19.5	62.4 ± 19.1	57.7 ± 18.8	56.4 ± 18.0	0.09	0.05	0.57
FVC, %	84.6 ± 18.6	85.4 ± 17.5	83.3 ± 17.2	83.5 ± 19.3	0.53	0.37	0.92
DLCO, %	77.0 ± 23.9	76.0 ± 25.8	71.3 ± 18.5	69.2 ± 21.6	0.05	0.16	0.52
QOL
mMRC	1.33 ± 0.87	1.47 ± 0.99	1.58 ± 0.90	1.73 ± 0.99	0.01	0.31	0.16
0	153 (13.5%)	36 (14.0%)	8 (8.9%)	26 (8.1%)
1	599 (52.8%)	115 (44.6%)	38 (42.2%)	124 (38.5%)
2	255 (22.5%)	66 (25.6%)	29 (32.2%)	93 (28.9%)
3	116 (10.2%)	33 (12.8%)	14 (15.6%)	69 (21.4%)
4	12 (1.1%)	8 (3.1%)	1 (1.1%)	10 (3.1%)
CAT	13.7 ± 7.2	15.7 ± 7.5	16.9 ± 7.9	19.7 ± 8.4	<0.001	0.19	0.003
SGRQ-C
Symptom	38.0 ± 17.5	48.6 ± 54.9	54.9 ± 19.6	57.6 ± 21.8	<0.001	0.01	0.22
Activity	42.9 ± 22.2	44.2 ± 22.2	52.4 ± 22.5	51.6 ± 25.2	<0.001	0.01	0.77
Impact	20.1 ± 16.9	23.5 ± 19.0	31.6 ± 22.1	33.3 ± 23.2	<0.001	<0.001	0.46
Total	29.9 ± 16.7	33.8 ± 18.0	41.7 ± 19.6	42.8 ± 21.6	<0.001	<0.001	0.62

Note: Data were represented as mean ± standard deviation, or frequency (%).

Abbreviations: C, cough; S, sputum; BMI, body mass index; PY, pack year; AE, acute exacerbation; WBC, white blood cell count; Hb, hemoglobin; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; DL_CO, diffusing capacity of the lungs for carbon monoxide; QOL, quality of life; mMRC, modified Medical Research Council Dyspnea scale; CAT, COPD Assessment Test; SGRQ-C, COPD-specific version of St George’s Respiratory Questionnaire.

Table 3 Multivariate analysis for the effects of chronic cough and chronic phlegm on the lung function, dyspnea, and quality of life in patients with chronic obstructive pulmonary disease

Adjusted values	Cough			Sputum
	(+)	(−)	P-values	(+)	(−)	P-values
FEV1, %	57.3 ± 1.3	60.9 ± 0.8	0.02	58.5 ± 0.9	59.8 ± 1.2	0.37
DLCO, %	70.8 ± 1.8	76.9 ± 1.1	0.02	72.2 ± 1.3	74.6 ± 1.7	0.28
mMRC	1.87 ± 0.11	1.49 ± 0.07	0.003	1.78 ± 0.10	1.60 ± 0.09	0.18
CAT	20.0 ± 0.94	15.6 ± 0.6	<0.001	19.6 ± 0.8	16.3 ± 0.7	0.003
SGRQ-C
Symptom	57.5 ± 2.3	45.8 ± 1.5	<0.001	57.1 ± 2.0	47.0 ± 1.9	<0.001
Activity	58.7 ± 2.7	46.2 ± 1.7	<0.001	54.3 ± 2.4	51.1 ± 2.2	0.32
Impact	38.5 ± 2.3	24.5 ± 1.5	<0.001	34.8 ± 2.1	28.9 ± 1.9	0.04
Total	47.8 ± 2.2	34.5 ± 1.4	<0.001	44.4 ± 1.9	38.6 ± 1.8	0.03

Notes: FEV₁ (% predicted) and DL_CO (%) were adjusted by age, smoking status, smoking amount, and chronic cough or phlegm in each model. mMRC, CAT, and SGRQ-C scores were adjusted by age, sex, smoking status, history of exacerbation, FEV₁ (% predicted) in addition to chronic cough or phlegm in each model.

Abbreviations: FEV₁, forced expiratory volume in 1 second; DL_CO, diffusing capacity of the lungs for carbon monoxide; mMRC, modified Medical Research Council Dyspnea scale; CAT, COPD Assessment Test; SGRQ-C, COPD-specific version of St George’s Respiratory Questionnaire.

Table 4 Univariate and multivariate analyses for factors contributing to future AE of chronic obstructive pulmo nary disease

	Univariate			Multivariate
	OR	95% CI	P-value	OR	95% CI	P-value
Age, years	1.04	1.02–1.05	<0.001	1.04	1.02–1.06	<0.001
Male sex	1.02	0.64–1.62	0.94	–	–	–
BMI, kg/m^2	0.99	0.96–1.02	0.58	–	–	–
Current smoker	0.81	0.60–1.09	0.17	0.90	0.65–1.25	0.54
Previous AE	1.95	1.49–2.56	<0.001	1.72	1.28–2.30	<0.001
FEV1, % predicted	0.98	0.97–0.99	<0.001	0.98	0.97–0.99	<0.001
Chronic cough	1.52	1.15–2.02	0.004	1.56	1.08–2.24	0.02
Chronic sputum	1.16	0.88–1.51	0.29	0.92	0.65–1.30	0.63

Abbreviations: OR, odds ratio; CI, confidence interval; BMI, body mass index; AE, acute exacerbation; FEV₁, forced expiratory volume in 1 second.

Figure 4 ROC analysis for the prediction of future acute exacerbation of chronic obstructive pulmonary disease.

Notes: Model 1 was constructed using the GOLD 2011 guidelines. Model 2 was constructed using the GOLD 2017 guidelines. Model 3 was constructed by adding chronic cough to the GOLD 2017 guidelines.
Abbreviations: ROC, receiver operating characteristic; GOLD, Global Initiative for Obstructive Lung Disease.