Impact of mild exacerbation on COPD symptoms in a Japanese cohort

Figures & data

Table 1 Characteristics of study population

n	311
Female sex (%)	21 (6.8)
Age (years)	72.6±8.1
Smoking index (pack-years)	56.4±29.5
Current smokers (%)	38 (12.5)
BMI (kg/m^2)	22.7±3.1
FEV1/FVC (%)	52.7±11.9
%FEV1	62.9±20.7
COPD stagesa I/II/III/IV, n (%)	69/152/72/18 (22.2/48.9/23.2/5.8)
SGRQ total score	23.8 (13.7–38.4)
CAT score	11 (6–17)

Notes: Data are shown as n (%), mean ± SD, and median (interquartile range).

a Defined by Global Initiative for Chronic Obstructive Lung Disease.

Abbreviations: BMI, body mass index; CAT, COPD assessment test; FEV₁, forced expiratory volume in 1 second; FVC, forced expiratory volume; %FEV₁, ratio of predicted FEV₁; SGRQ, St George’s Respiratory Questionnaire.

Figure 1 Frequency of exacerbation with different severities over 2 years.

Notes: Patients with no (□), mild ([

]), and moderate or severe (■) exacerbations. Bars on left: proportions of patients without, and with mild, and moderate or severe exacerbations during the first year of follow-up. Bars on right: respective incidence of exacerbations in these groups during the second year of follow-up.

Table 2 Comparison of baseline characteristics among patients stratified according to severity of exacerbation

	Exacerbation free	Mild exacerbator	Moderate/severe exacerbator	P-value
Number (%)	154 (49.5)	67 (21.5)	90 (29.0)
Sex, female (%)	11 (7.1)	4 (6.0)	6 (6.7)	0.95
Age (years)	72.5±8.3	71.3±8.1	74.0±7.6	0.11
Smoking index (pack-years)	53.2±27.7	57.6±34.7	61.2±27.7	0.14
Current smokers (%)	21 (13.9)	8 (11.9)	9 (10.5)	0.73
BMI (kg/m^2)	23.0±3.2	22.8±2.9	22.0±3.0a	0.033
%FEV1	67.4±19.3	65.4±21.9	53.3±19.1a,b	<0.0001
%DLCO/VA (%) (n=235)	65.4±20.8	67.7±24.1	55.6±21.2a,b	0.0043
LAA% (n=209)	10.6 (4.7–23.5)	9.0 (5.2–19.1)	20.3 (10.3–35.8)a,b	0.0006
WA% (n=206)	54.1 (47.9–59.1)	52.2 (46.8–57.0)	50.4 (43.9–57.2)	0.2
LABA (%)	40.26	43.28	66.29a,b	0.0003
LAMA (%)	56.58	58.21	65.17	0.41
ICS (%)	26.62	32.84	47.19a	0.0048
OCS (%)	1.32	0	5.75b	0.033
PPI (%)	12.5	16.67	21.84	0.17
Clarithromycin (%)	0.65	1.49	8.9a,b	0.0014
Carbocysteine (%)	8.44	5.97	26.67a,b	<0.0001
CRP (mg/dL)	0.32±0.98	0.29±0.66	0.43±0.9	0.54
SAA (μg/mL)	17.0±69.7	11.3±16.2	23.7±65.2	0.57
WBC (μL)	6,198.6±1,520.1	6,065.0±2,084.8	6,529.1±1,944.8	0.22
Eo (%)	3.7±4.5	3.3±3.6	3.9±3.0	0.61

Notes: Data are shown as n (%) and mean ± SD.

a P<0.05 vs no exacerbation and

b P<0.05 vs mild.

Abbreviations: BMI, body mass index; CRP, C-reactive protein; DL_CO/V_A, diffusing capacity divided by the alveolar volume; Eo, eosinophil; %FEV₁, ratio of predicted forced expiratory volume in 1 second; ICS, inhaled corticosteroids; LAA%, ratio of low attenuation area; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; OCS, oral corticosteroids; PPI, proton pump inhibitor; SAA, serum amyloid A; WA%, ratio of airway wall area; WBC, white blood cell.

Table 3 Comparison of baseline comorbidities among patients stratified according to severity of exacerbation

	Prevalence (%)	Exacerbation free	Mild exacerbator	Moderate/severe exacerbator	P-value
GERD (FSSG ≥8)	33.78 (n=101)	45 (30.41)	30 (46.15)a,b	26 (30.23)	0.058
Anxiety (HADS-A ≥11)	6.62 (n=20)	10 (6.71)	4 (5.97)	6 (6.98)	0.97
Depression (HADS-D ≥11)	8.61 (n=26)	9 (6.04)	7 (10.45)	10 (11.63)	0.28
Anemia	22.76 (n=71)	27 (17.53)	17 (25.37)	27 (29.67)a	0.077
Osteoporosis	14.1 (n=32)	14 (12.07)	5 (9.26)	13 (22.81)c	0.082
Hypertension	38.41 (n=116)	61 (40.94)	22 (33.33)	33 (37.93)	0.57
Diabetes mellitus	14.57 (n=44)	23 (15.44)	6 (9.09)	15 (17.24)	0.34
Dyslipidemia	18.21 (n=55)	31 (20.81)	11 (16.67)	13 (14.94)	0.5
Hyperuricemia	8.94 (n=27)	13 (8.72)	8 (12.12)	6 (6.9)	0.53
Coronary artery disease	12.58 (n=38)	21 (14.09)	6 (9.09)	11 (12.64)	0.72
Chronic heart disease	6.62 (n=20)	10 (6.71)	6 (9.09)	4 (4.6)	0.54
Arrhythmia	10.93 (n=33)	17 (11.41)	7 (10.61)	9 (10.35)	0.6
Cerebral infarction	5.3 (n=16)	10 (6.71)	2 (3.03)	4 (4.6)	0.51
Peptic ulcer	8.61 (n=26)	11 (7.38)	5 (7.58)	10 (11.49)	0.52
Lung cancer	5.3 (n=16)	6 (4.03)	4 (6.06)	6 (6.9)	0.61
Other cancer	20.2 (n=61)	27 (18.12)	14 (21.21)	20 (22.99)	0.65
Chronic sinusitis	12.75 (n=39)	19 (12.58)	11 (16.42)	9 (10.23)	0.52
Aortic aneurysm	3.97 (n=12)	7 (4.7)	2 (3.03)	3 (3.45)	0.81
Chronic renal failure	1.61 (n=5)	1 (0.65)	3 (4.48)	1 (1.11)	0.11
Liver cirrhosis	3.02 (n=9)	5 (3.4)	1 (1.54)	3 (3.49)	0.73
Cataract	46.54 (n=101)	46 (40.35)	20 (41.67)	35 (63.64)a,c	0.013
Glaucoma	7.83 (n=17)	6 (5.31)	4 (8.33)	7 (12.5)	0.26
Prostatic hypertrophy	13.91 (n=42)	13 (8.72)	11 (16.67)	18 (20.69)a	0.029

Notes: Data are shown as n (%).

a P<0.05 vs no exacerbation.

b P<0.05 vs moderate or severe exacerbation.

c P<0.05 vs mild exacerbation.

Abbreviations: FSSG, frequency scale for the symptoms of GERD; GERD, gastroesophageal reflux disease; HADS, hospital anxiety and depression scale.

Figure 2 Annual changes in FEV₁ in three groups of patients over 2 years of follow-up.

Notes: Patients in the exacerbation-free (••▲••), mild exacerbator (–○–), and moderate/severe exacerbator (–■–) groups. Moderate/severe exacerbator vs exacerbation free, P<0.001; mild exacerbator vs exacerbation free, P=1.000; and mild exacerbator vs moderate/severe exacerbator, P=0.001.
Abbreviation: FEV₁, forced expiratory volume in 1 second.

Figure 3 Annual changes in LAA% in three groups of patients over 2 years of follow-up.

Notes: Patients in the exacerbation-free (••▲••), mild exacerbator (–○–), and moderate/severe exacerbator (–■–) groups. Moderate/severe exacerbator vs exacerbation free, P=0.228; mild exacerbator vs exacerbation free, P=1.000; and mild exacerbator vs moderate/severe exacerbator, P=0.100.
Abbreviation: LAA%, ratio of low attenuation area.

Table 4 Predictors of CAT (minimal clinical important difference; ΔCAT ≥2 per year) increase determined by multivariate logistic regression analysis

	OR (95% CI)	P-value
Airflow limitation
%FEV1 <50% vs ≥50%	2.42 (1.03–5.60)	0.042
Acute exacerbation
Mild exacerbation vs exacerbation free	2.29 (1.09–4.80)	0.028
Comorbidity
Depression (HADS-D ≥11)	1.97 (0.55–6.46)	0.282
Osteoporosis	1.92 (0.60–5.68)	0.260

Abbreviations: CI, confidence interval; CAT, COPD assessment test; %FEV₁, ratio of predicted forced expiratory volume in 1 second; HADS, hospital anxiety and depression scale; OR, odds ratio.

Figure 4 Annual changes in CAT scores in three groups of patients over 2 years of follow-up.

Notes: Patients in the exacerbation-free (••▲••), mild exacerbator (–○–), and moderate/severe exacerbator (–■–) groups. Moderate/severe exacerbator vs exacerbation free, P<0.001; mild exacerbator vs exacerbation free, P=0.014; and mild exacerbator vs moderate/severe exacerbator, P=0.493.
Abbreviation: CAT, COPD assessment test.

Figure 5 Annual changes in SGRQ total scores over 2 years of follow-up.

Notes: Patients in the exacerbation-free (••▲••), mild exacerbator (–○–), and moderate/severe exacerbator (–■–) groups. Moderate/severe exacerbator vs exacerbation free, P<0.001; mild exacerbator vs exacerbation free, P=0.041; and mild exacerbator vs moderate/severe exacerbator, P=0.013.

Abbreviation: SGRQ, St George’s Respiratory Questionnaire.

Figure 6 Annual changes in SGRQ symptoms category over 2 years of follow-up.

Notes: Patients in the exacerbation-free (••▲••), mild exacerbator (–○–), and moderate/severe exacerbator (–■–) groups. Moderate/severe exacerbator vs exacerbation free, P<0.001; mild exacerbator vs exacerbation free, P=0.002; and mild exacerbator vs moderate/severe exacerbator, P=1.000.

Abbreviation: SGRQ, St George’s Respiratory Questionnaire.

Figure 7 Annual changes in SGRQ activity category over 2 years of follow-up.

Notes: Patients in the exacerbation-free (••▲••), mild exacerbator (–○–), and moderate/severe exacerbator (–■–) groups. Moderate/severe exacerbator vs exacerbation free, P<0.001; mild exacerbator vs exacerbation free, P=0.226; and mild exacerbator vs moderate/severe exacerbator, P=0.004.

Abbreviation: SGRQ, St George’s Respiratory Questionnaire.

Figure 8 Annual changes in SGRQ impact category over 2 years of follow-up.

Notes: Patients in the exacerbation-free (••▲••), mild exacerbator (–○–), and moderate/severe exacerbator (–■–) groups. Moderate/severe exacerbator vs exacerbation free, P<0.001; mild exacerbator vs exacerbation free, P=0.064; and mild exacerbator vs moderate/severe exacerbator, P=0.008.
Abbreviation: SGRQ, St George’s Respiratory Questionnaire.