Clinical Impact of the Bronchiectasis with Chronic Bronchitis Symptoms in COPD: Analysis of a Longitudinal Cohort

Figures & data

Table 1 Baseline Characteristics of the Subjects

Parameter (N=389)	Mean ± SD, n (%)
Age (years)	66.9 ± 7.4
Male	380 (97.7)
Smoking amount (pack-year)	45.9 ± 26.2
Current smoker	113 (29.0)
BMI (kg/m^2)	23.0 ± 3.2
6MWD (m)	427.8 ± 86.0
Dyspnea (mMRC)	1.7 ± 1.1
SGRQ	32.8± 17.6
Charlson’s comorbidity score	1.30 ± 0.67
The presence of BE	148 (38.0)
The presence of CB	129 (33.2)
Lung function
Pre BD FVC (% predicted)	78.1 ± 16.4
Post BD FVC (% predicted)	83.1 ± 15.9
Pre BD FEV1 (% predicted)	48.9 ± 15.5
Post BD FEV1 (% predicted)	54.1 ± 16.1
FEV1/FVC (%)	46.8 ± 11.1
DLco (% predicted)	77.3 ± 23.9
FEV1 decline (mL/year, n=341)	−24.73 ± 24.65
Medications (n=359)
ICS/LABA	196 (54.6)
LAMA	151 (42.1)
Other medications*	12 (3.3)
Radiologic findings
Emphysema index (%)	21.7 ±15.3
Airway Wall area (%)	17.6 ± 3.5
Air-trapping index	0.95 ± 0.03
Blood laboratory findings
Leukocyte (×10^3/μL)	7.3 ± 2.0
Blood eosinophils (cells/μL)	273.6 ± 321.4
Hemoglobin (g/dL)	14.9 ± 1.3
Platelet (×10^3/μL)	239.2 ± 62.4
Protein (g/dL)	7.1 ± 0.5
Albumin (g/dL)	4.2 ± 0.4
Cholesterol (mg/dL)	171.9 ± 61.5
Hs-CRP (mg/dL)	0.4 ± 1.0
Creatinine (mg/dL)	1.0 ± 0.2

Notes: Data are presented as n (%) or mean ± SD. *Other medications, ICS (n=6), LABA [Onbrez^® (indacaterol), n=5], Combivent^® (ipratropium bromide/salbutamol, n=1).

Abbreviations: SD, standard deviation; BMI, body mass index; 6MWD, 6-minute walk distance; mMRC, modified Medical Research Council; SGRQ, St. George’s Respiratory Questionnaire; BD, bronchodilator; BE, bronchiectasis; CB, chronic bronchitis; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; DLco, diffusing capacity of the lung for carbon monoxide; ICS, inhaled corticosteroid; LABA, long acting β2-agonist; LAMA, long acting muscarinic antagonist; hs-CRP, high-sensitivity C-reactive protein.

Figure 1 Flow diagram of enrollment.

Abbreviations: BE, bronchiectasis; CB, chronic bronchitis; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; PY, pack-years.

Table 2 Comparison of Clinical Characteristics of Four Groups

Parameter (N=389)	BE/CB (n=52)	BE-Only (n=96)	CB-Only (n=77)	No BE/CB (n=164)	Overall P value
Age (years)	66.2 ± 7.9	68.5 ± 6.2^b	65.3 ± 8.4	66.9 ± 7.2	0.035
Male	52 (100.0)	95 (99.0)	77 (100.0)^c	156 (95.1)	0.036
Smoking amount (pack-year)	44.6 ± 22.3	46.3 ± 23.8	43.9 ± 27.2	47.1 ± 28.3	0.819
Current smoker	20 (38.5)^a, c	22 (22.9)	30 (39.0)^a, c	41 (25.0)	0.002
BMI (kg/m^2)	21.6 ± 3.3^b, c	22.7 ±3.3	23.4 ± 2.6	23.5 ± 3.3	0.001
6MWD (m)	410.0 ± 85.5^b	414.8 ±98.3^b	446.3 ± 70.0	432.6 ± 83.6	0.042
Charlson’s comorbidity score	1.29 ± 0.57	1.43 ± 0.96	1.29 ± 0.56	1.23 ± 0.53	0.160
Dyspnea (mMRC)	1.98 ± 1.09^a, c	1.53 ± 1.06	1.86 ± 1.01^a, c	1.54 ± 1.07	0.012
SGRQ	41.24 ± 18.62^a, c	29.46 ± 16.11	38.41 ± 15.90	29.53 ± 17.55	<0.001
Lung function
Pre BD FVC (% predicted)	80.6 ± 20.5	79.1 ± 16.2	76.4 ± 15.5	77.4 ± 15.6	0.434
Post BD FVC (% predicted)	84.9 ± 19.6	82.4 ± 16.0	82.1 ± 13.7	83.4 ± 15.6	0.755
Pre BD FEV1 (% predicted)	46.1 ± 18.1	49.6 ± 15.9	48.4 ± 14.1	49.5 ± 15.0	0.519
Post BD FEV1 (% predicted)	50.3 ± 18.3	54.8 ± 16.9	53.4 ± 14.9	55.2 ± 15.3	0.252
FEV1/FVC (%)	43.1 ± 12.0	46.9 ± 9.9	47.3 ± 11.2	47.7 ± 11.3	0.072
DLco (% predicted)	72.5 ± 21.3	79.8 ± 24.1	77.8 ± 21.5	76.9 ± 25.6	0.384
FEV1 decline (mL/year, n=341)	−26.36 ± 25.99	−23.64 ± 21.56	−23.09 ± 29.69	−25.63 ± 23.17	0.836
Medications (n=359)
ICS/LABA	25/48 (52.1)	41/84 (48.8)	44/75 (58.7)	86/152 (56.6)	0.573
LAMA	22/48 (45.8)	38/84 (45.2)	30/75 (40.0)	61/152 (40.1)	0.803
Other medications*	1/48 (2.1)	5/84 (6.0)	1/75 (1.3)	5/152 (3.3)	0.400
Radiologic findings
EI (%)	25.5 ±15.4	21.6 ±16.2	19.6 ±14.5	21.5 ±15.2	0.257
AWA (%)	17.3 ± 3.0	18.1 ± 3.9	17.4 ± 3.9	17.4 ± 3.2	0.343
ATI	0.96 ± 0.03	0.95 ± 0.04	0.95 ± 0.03	0.94 ± 0.04	0.141
Blood laboratory findings
Leukocyte (×10^3/μL)	7.5 ± 2.0	7.2 ± 1.7	7.3 ± 2.1	7.2 ± 2.1	0.759
Blood eosinophils (cells/μL)	309.0 ± 574.1	269.7 ± 253.9	270.4 ± 233.1	266.6 ± 286.8	0.876
Hemoglobin (g/dL)	15.0 ± 1.1	14.7 ± 1.4	14.8 ± 1.1	14.9 ± 1.4	0.502
Platelet (×10^3/μL)	250.7 ± 78.0	245.3 ± 65.1	240.1 ± 49.6	231.9 ± 60.3	0.187
Protein (g/dL)	7.1 ± 0.7	7.2 ± 0.5	6.9 ± 0.4^a, c	7.1 ± 0.5	0.011
Albumin (g/dL)	4.2 ± 0.3	4.2 ± 0.6	4.2 ± 0.4	4.3 ± 0.3	0.324
Cholesterol (mg/dL)	173.9 ± 62.6	165.0 ± 70.9	157.6 ± 70.2^c	181.4 ± 49.5	0.032
Hs-CRP (mg/dL)	0.4 ± 0.5	0.6 ± 1.9	0.3 ± 0.5	0.3 ± 0.6	0.320
Creatinine (mg/dL)	1.0 ± 0.2	1.1 ± 0.2	1.0 ± 0.2	1.1 ± 0.2	0.064

Notes: Data are presented as n (%) or mean ± SD. *Other medications, ICS (n=6), LABA [Onbrez^® (indacaterol), n=5], Combivent^® (ipratropium bromide/salbutamol, n=1). ^aP value < 0.05 compared BE-only group. ^bP value < 0.05 compared CB-only group. ^cP value < 0.05 compared no BE/CB group.

Abbreviations: SD, standard deviation; BE, bronchiectasis; CB, chronic bronchitis; BMI, body mass index; 6MWD, 6-minute walk distance; mMRC, modified Medical Research Council; SGRQ, St. George’s Respiratory Questionnaire; BD, bronchodilator; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; DLco, diffusing capacity of the lung for carbon monoxide; ICS, inhaled corticosteroid; LABA, long acting β2-agonist; LAMA, long acting muscarinic antagonist; EI, emphysema index; AWA%, airway wall area percentage; ATI, air-trapping index; hs-CRP, high-sensitivity C-reactive protein.

Table 3 Comparison of Exacerbation and Death of Four Groups

Parameter	Total (n=389)	BE/CB (n=52)	BE-Only (n=96)	CB-Only (n=77)	No BE/CB (n=164)	P value
History of AE in previous 1 year	78 (20.1)	16 (30.8)^a, b	14 (14.6)	20 (26.0)	28 (17.0)	0.045
AE-COPD	239 (61.4)	32 (61.5)	54 (56.3)	50 (64.9)	103 (62.8)	0.655
Severe AE-COPD	91 (23.4)	15 (28.8)	14 (14.6)	23 (29.3)	39 (23.8)	0.077
AE-COPD/year	1.0 ± 3.1	1.0 ± 1.4	1.4 ± 5.9	0.9 ± 1.1	0.8 ± 1.4	0.545
Severe AE-COPD/year	0.1 ± 0.6	0.2 ± 0.4	0.1 ± 0.3	0.3 ± 1.1	0.1 ± 0.3	0.224
Annual exacerbator (AE/year ≥ 1)	114 (29.3)	21 (40.4)^a, b	23 (24.0)	29 (37.7)	41 (25.0)	0.037
Frequent exacerbator (AE/year ≥ 2 or severe AE)	54 (13.9)	7 (13.5)	11 (11.5)	11 (14.3)	25 (15.2)	0.863
Overall mortality	63 (16.2)	10 (19.2)	13 (13.5)	12 (15.6)	28 (17.1)	0.810

Notes: ^aP value < 0.05 compared BE-only group. ^bP value < 0.05 compared no BE/CB group.

Abbreviations: BE, bronchiectasis; CB, chronic bronchitis; AE-COPD, acute exacerbation of chronic obstructive pulmonary disease; severe AE-COPD, hospitalization or visit to ER; frequent exacerbator, AE-COPD/year ≥ 2 or severe AE-COPD/ year ≥ 1.

Figure 2 Proportion of annual exacerbators according to the presence of bronchiectasis/chronic bronchitis.

Abbreviations: annual exacerbator, AE-COPD/year ≥ 1; BE, bronchiectasis; CB, chronic bronchitis.

Table 4 Risk Factors Associated with Annual Exacerbation of COPD (Exacerbation /Year ≥ 1) in COPD Patients

Parameter (n=389)	Univariate Analysis			Multivariate Analysis^a
	OR	95% CI	p-value	OR	95% CI	p-value
Age, yr	1.028	0.997–1.060	0.077	1.036	1.001–1.072	0.046
BMI, Kg/m^2	0.931	0.869–0.998	0.042	1.004	0.921–1.094	0.933
Post BD FEV1 (% predicted)	0.969	0.954–0.983	<0.001	0.984	0.965–1.002	0.082
mMRC	1.403	1.140–1.727	0.001	1.187	0.922–1.530	0.184
6MWD (m)	1.000	0.997–1.002	0.728
FEV1 decline (mL/year)	1.002	0.993–1.011	0.672
The presence of bronchiectasis	1.034	0.660–1.619	1.034
Type of bronchiectasis
Cylindrical	0.733	0.440–1.220	0.232
Varicose	1.226	0.555–2.708	0.614
Cystic	0.397	0.047–3.333	0.395
Modified Bhalla score	1.051	0.994–1.111	0.078
EI (%)	1.027	1.012–1.043	0.001	1.016	0.997–1.036	0.094
Hs-CRP (mg/dL)	0.982	0.771–1.251	0.883
Blood eosinophils (cells/μL)	1.000	0.999–1.001	0.563
Four groups according to BE, CB			0.040			0.082
No BE/CB group	Reference			Reference
CB-only group	1.812	1.014–3.240	0.045	1.764	0.919–3.387	0.088
BE-only group	0.945	0.526–1.700	0.851	0.945	0.491–1.818	0.866
BE/CB group	2.032	1.053–3.921	0.034	2.110	1.016–4.382	0.045

Notes: ^aAdjusted for age, FEV₁, BMI, mMRC, EI, and four groups according to BE, CB.

Abbreviations: BD, bronchodilator; FEV₁, forced expiratory volume in 1 second; BMI, body mass index; mMRC, modified Medical Research Council; 6MWD, 6-minute walk distance; EI, emphysema index; hs-CRP, high-sensitivity C-reactive protein; BE, bronchiectasis; CB, chronic bronchitis; OR, odds ratio; CI, confidential interval.

Table 5 Risk Factors for Mortality by Cox Proportional Hazards Model

Parameter (n=389)	Univariate Analysis			Multivariate Analysis^a
	HR	95% CI	p-value	HR	95% CI	p-value
Age, yr	1.114	1.072–1.158	<0.001	1.084	1.037–1.133	<0.001
Post BD FEV1 (% predicted)	0.940	0.922–0.958	<0.001	0.978	0.956–1.002	0.069
BMI (Kg/m2)	0.769	0.711–0.832	<0.001	0.885	0.811–0.966	0.006
mMRC	2.037	1.592–2.607	<0.001	1.313	0.943–1.828	0.107
6MWD (m)	0.991	0.988–0.993	<0.001	0.996	0.993–1.000	0.030
FEV1 decline (mL/year)	1.008	0.998–1.017	0.115
Frequent exacerbation	3.582	2.105–6.095	<0.001	1.725	0.927–3.208	0.085
EI (%)	1.048	1.031–1.065	<0.001	1.013	0.993–1.033	0.193
The presence of bronchiectasis	1.143	0.684–1.910	0.610
Hs-CRP (mg/dL)	1.098	0.938–1.285	0.247
Blood eosinophils (cells/μL)	1.000	0.999–1.001	0.758
Four groups according to BE, CB			0.710
No BE/CB group	Reference
CB-only group	0.947	0.481–1.863	0.846
BE-only group	0.956	0.495–1.846	0.720
BE/CB group	1.458	0.707–3.006	0.307

Notes: ^aAdjusted for age, FEV₁, BMI, mMRC, 6MWD, frequent exacerbation, and EI.

Abbreviations: BD, bronchodilator; FEV₁, forced expiratory volume in 1 second; BMI, body mass index; mMRC, modified Medical Research Council; 6MWD, 6-minute walk distance; frequent exacerbation, >2 exacerbation or >1 admission to hospital or visiting the emergency department/year; EI, emphysema index; hs-CRP, high-sensitivity C-reactive protein; BE, bronchiectasis; CB, chronic bronchitis; HR, hazard ratio; CI, confidential interval.

Figure 3 Kaplan–Meier survival analysis among groups.

Abbreviations: BE, bronchiectasis; CB, chronic bronchitis.