Do frequent moderate exacerbations contribute to progression of chronic obstructive pulmonary disease in patients who are ex-smokers?

Figures & data

Table 1 Characteristics of COPD patients at study entry

Sex, male/female	58/42
Age, years	68.8±7.7
Smoking history pack/year	42.8±23.5
Years since quitting smoking GOLD stage, n (%)	11.5±8.7
Mild	8 (8)
Moderate	48 (48)
Severe	28 (28)
Very severe	16 (16)
BMI, kg/m^2	26.6±3.7
mMRC
0–1 points	15 (15)
2 points	60 (60)
3 points	21 (21)
4 points	4 (4)
IC, % predicted	77.9±22.9
FVC, % predicted	90.9±22.1
FEV1, % predicted	52.6±20.6
FEV1/FVC, %	42.7±12.7
6MWD, % predicted	84.5±19.9
BODE index
0–2 points	50 (50)
3–4 points	33 (33)
5–6 points	11 (11)
7–10 points	6 (6)
Charlson comorbidity index, points	4.46± 1.84
Urine cotinine levels, ng/mL	12.9±28.5
CRQ global, points	92.4±24.4
SGRQ total, points	49.0±19.8

Notes: Values are expressed as the mean ± standard deviation or number (percent).

Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; mMRC, modified Medical Research Council; IC, inspiratory capacity; FVC, forced vital capacity; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; 6MWD, 6-minute walking distance; BODE, body mass index, airflow obstruction, dyspnea, exercise performance; SGRQ, St George’s Respiratory Questionnaire; CRQ, Chronic Respiratory Questionnaire.

Figure 1 Follow-up diagram for cohort of patients with chronic obstructive pulmonary disease.

Figure 2 Number of exacerbations per patient.

Note: Patient numbers include patients treated at our institution and in other health institutions.

Table 2 Baseline characteristics according to frequency of exacerbations in 100 patients with COPD

	Infrequent exacerbators n=51	Frequent exacerbators n=49	P-value
Male/female, n	31/20	27/22	NS
Age, years	68.8±6.5	68.8±8.8	NS
BMI, kg/m^2	26.7±3.5	26.5±4.0	NS
Smoking history, pack-years	42.5±21.1	43.1 ±26.0	NS
AE previous year	1 (0–2)	2 (1–3)	<0.001
mMRC			0.043
0–1 points	8 (16)	7 (14)
2 points	36 (71)	24 (49)
3 points	6 (12)	15 (31)
4 points	1 (2)	3 (6)
IC, % predicted	83.8±20.7	71.6±23.7	0.008
FEV1, % predicted	57.6±19.3	47.6±20.8	0.013
FVC, % predicted	96.4±21.6	85.1±21.4	0.011
FEV1/FVC, %	44.4±12.6	40.9±12.8	NS
6MWD, % predicted	87.8±16.6	80.9±22.5	0.087
GOLD			0.030
Stage I	5 (10)	3 (6)
Stage II	27 (53)	21 (43)
Stage III	17 (33)	11 (22)
Stage IV	2 (4)	14 (29)
SpO2, %	93.6±2.71	92.5±2.29	0.026
BODE index			0.027
0–2 points	29 (57)	21 (43)
3–4 points	19 (37)	14 (29)
5–6 points	2 (4)	9 (18)
7–10 points	1 (2)	5 (10)
SGRQ total, points	44.0±19.5	54.2±19.0	0.010
CRQ global, points	97.3±26.1	87.3±21.7	0.044

Notes: Values are expressed as the mean ± standard deviation, number (percent), or median (interquartile range).

Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; mMRC, modified Medical Research Council; IC, inspiratory capacity; FVC, forced vital capacity; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; 6MWD, 6-minute walking distance; BODE, body mass index, airflow obstruction, dyspnea, exercise performance; NS, not statistically significant; SGRQ, St George’s Respiratory Questionnaire; CRQ, Chronic Respiratory Questionnaire; SpO₂, peripheral capillary oxygen saturation.

Table 3 Slopes of all indices according to the random effect modeling

	Slope infrequent	Slope frequent	P-value
IC, mL	38	105	0.420
FVC%	−2.20	−1.73	0.762
FEV1, mL	−85.57	−54.72	0.129
FEV1, % predicted	−2.84	−1.7	0.212
FEV1/FVC	−1.46	−0.84	0.357
6MWD, % predicted	−2.04	−2.88	0.672
mMRC, points	−0.04	−0.04	0.259
BODE index, points	0.136	0.276	0.387
SGRQ, points	−0.74	0.73	0.331

Abbreviations: IC, inspiratory capacity; FVC, forced vital capacity; FEV₁, forced expiratory volume in 1 second; 6MWD, 6-minute walking distance; mMRC, modified Medical Research Council; BODE, body mass index, airflow obstruction, dyspnea, exercise performance; SGRQ, St George’s Respiratory Questionnaire; CRQ, Chronic Respiratory Questionnaire.

Figure 3 Lung function indices progression.

Notes: Baseline (0) and scheduled visits (every 6 months) during 2 years of follow-up; values are expressed as the mean ± one standard error. (⋄) indicates infrequent exacerbators; (■) indicates frequent exacerbators.

Abbreviations: IC, inspiratory capacity; FVC, forced vital capacity; FEV₁, forced expiratory volume in 1 second; pred, predicted.

Figure 4 Clinical indices and health status progression.

Notes: Baseline (0) and scheduled visits (every 6 months) during 2 years of follow-up; values are expressed as the mean ± one standard error. (⋄) indicates infrequent exacerbators, (■) indicates frequent exacerbators.
Abbreviations: BMI, body mass index; mMRC, modified Medical Research Council dyspnea scale; 6WD, 6-minute walking distance; BODE, body mass index, airflow obstruction, dyspnea, exercise performance; SGRQ, St George’s Respiratory Questionnaire; CRQ, Chronic Respiratory Questionnaire.

Table 4 Inhaled treatment during follow-up

Therapy	Infrequent exacerbators n=51	Frequent exacerbators n=49	P-value
LABA alone	2	5	NS
LAMA alone	5	2	NS
SABA and/or SAMA alone	20	9	0.021
LABA + ICS	14	16	NS
LABA + LAMA + ICS	10	17	0.07
ICSa	24	33	0.032

Note:

a Plus any other inhaled therapy.

Abbreviations: LABA, long-acting β agonist; LAMA, long-acting muscarinic antagonist; NS, not statistically significant; SABA, short-acting β agonist; SAMA, short-acting muscarinic antagonist; ICS, inhaled corticosteroids.