Differential changes in quality of life components over 5 years in chronic obstructive pulmonary disease patients

Figures & data

Figure 1 The frequency distributions of the annual change in SGRQ (units/year).

Notes: The calculated annual change in the SGRQ activity score is 1.22±3.53 (mean ± SD) (A), symptom score is −1.96±4.22 (B).
Abbreviation: SGRQ, St George’s Respiratory Questionnaire; SD, standard deviation.

Figure 2 The relationship between the annual change in postbronchodilator FeV₁.

Note: The annual change in SGRQ total score is negatively correlated with the annual change in FEV₁ (r=−0.27, P<0.001, n=261).
Abbreviations: FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire.

Figure 3 The changes in the total and three component scores of the SGRQ during follow-up.

Notes: Annual changes in the total score of SGRQ from baseline classified by annual change in FEV₁ (ml/year) during follow-up; The change from baseline in the SGRQ total score (mean ΔSGRQ ± SE) at 4-year follow-up: ΔSGRQ in rapid FEV₁ decliners, 5±2; slow FEV₁ decliners, 0±1, or FEV₁ sustainers, −4±2, and at 5-year follow-up: ΔSGRQ in rapid FEV₁ decliners, 5±2; slow FEV₁ decliners, 0±1; or FEV1 sustainers, −4±2 (A). Annual changes in the activity scores (B), symptom scores (C), and impact scores (D) of the SGRQ classified by annual change in postbronchodilator FEV₁ (ml/year) during follow-up are shown. P-values represent one-way analysis of variance with post hoc comparisons using Tukey’s multiple comparison tests at each year.
Abbreviations: FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire; ΔSGRQ, change from baseline in the SGRQ; SE, standard error.

Table 1 Annual changes in the total and three component scores of SGRQ classified by annual rates of decline in FEV₁ during follow-up

SGRQ component	Group (change in FEV1)	Estimate (change in SGRQ score)	SE	t-value	P-value
Total score	Rapid decliners	1.33	0.34	3.93	<0.001
	Slow decliners	0.21	0.25	0.84	0.401
	Sustainers	−0.94	0.33	−2.88	0.006
	All subjects	0.24	0.18	1.38	0.169
Activity score	Rapid decliners	2.76	0.47	5.82	<0.001
	Slow decliners	0.86	0.32	2.72	0.008
	Sustainers	0.22	0.47	0.48	0.632
	All subjects	1.23	0.24	5.09	<0.001
Symptom score	Rapid decliners	−0.17	0.48	−0.36	0.723
	Slow decliners	−1.49	0.43	−3.50	0.001
	Sustainers	−2.96	0.48	−6.16	<0.001
	All subjects	−1.50	0.27	−5.47	<0.001
Impact score	Rapid decliners	0.97	0.37	2.64	0.011
	Slow decliners	0.35	0.28	1.22	0.226
	Sustainers	−0.98	0.34	−2.88	0.006
	All subjects	0.16	0.19	0.85	0.398

Notes: The changes in the SGRQ score of each group were analyzed using a linear mixed-effects model (fixed effects = year; random effects = id, id×year); Estimate: a positive value means annual deterioration of SGRQ, a negative value means annual improvement of SGRQ.

Abbreviations: FEV₁, forced expiratory volume in 1 second; SE, standard error; SGRQ, St George’s Respiratory Questionnaire.

Table 2 Results of unadjusted and adjusted linear mixed-effects models to identify which variables at baseline were predictive of the annual change in SGRQ activity and symptom scores at 5 years

Variable	Unadjusted model		Adjusted model
	Estimate (95% CI)	P-value	Estimate (95% CI)	P-value
Activity score
Age*	0.86 (0.02, 0.15)	<0.001	0.73 (0.00, 0.14)	0.031
BMI	−0.21 (−0.36, −0.06)	0.005	−0.17 (−0.34, −0.02)	0.032
DLco (mL/min/mmHg)	−0.15 (−0.25, −0.05)	0.003	−0.06 (−0.18, 0.06)	0.357
Symptom score
Age^†	0.82 (0.01, 0.15)	<0.001	0.63 (−0.01, 0.14)	0.104
Sex (male)#	1.42 (0.26, 2.56)	0.016	1.60 (0.46, 2.74)	0.006
Reversibility (%)‡	−0.44 (−0.08, −0.04)	0.030	−0.56 (−0.10, −0.02)	0.005
Dlco (mL/min/mmHg)	−0.12 (−0.24, −0.01)	0.030	−0.11 (−0.23, 0.01)	0.074

Notes:

* Analyzed in units of 10 years;

‡ Analyzed in units of 10%;

# 246 males: 15 females; Unadjusted and adjusted linear mixed-effects models were performed to test for the influence of variables at baseline on the slope of the annual change in SGRQ scores at 5 years (fixed effect = year, variables as follows, and interaction effects between years and variables; random effect = id, id×year). Variables age, sex, BMI, current smoking status at entry, pack-years, cough and sputum, mMRC dyspnea scale (0–4), postbronchodilator FVC, postbronchodilator FEV₁, reversibility (%), DLco, WBC, eosinophils, CRP, and IgE.

Abbreviations: BMI, body mass index; CI, confidence interval; CRP, C reactive protein; DLco, diffusing capacity for carbon monoxide; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; IgE, immunoglobulin E; mMRC, modified Medical Research Council; SGRQ, St George’s Respiratory Questionnaire; WBC, white blood cell counts.

Table 3 Results of linear mixed-effects models to identify which variables during follow-up were predictive of the annual change in SGRQ activity scores at 5 years

Variable (group)	n	Unadjusted model		Adjusted model
		Estimate (95% CI)	P-value	Estimate (95% CI)	P-value
Activity score
FeV1 annual decline
Sustainers	65	(Reference)		(Reference)
Slow decliners	131	0.64 (−0.48, 1.76)	0.263	0.49 (−0.64, 1.62)	0.393
Rapid decliners	65	2.55 (1.31, 3.78)	<0.001	2.33 (1.09, 3.58)	<0.001
DLco annual change	(mL/min/mmHg)
<25th percentile	63	(Reference)		(Reference)
25th–75th percentile	127	0.76 (−0.40, 1.93)	0.196	0.69 (−0.44, 1.83)	0.226
>75th percentile	63	1.25 (−0.06, 2.57)	0.061	0.72 (−0.58, 2.01)	0.277
Smoking status
Former smoker	203	(Reference)		(Reference)
Continuous/intermittent smoker	58	0.56 (0.03, 1.14)	0.061	0.61 (0.04, 1.18)	0.036
Annual change in BMI
<25th percentile	65	(Reference)		(Reference)
25th–75th percentile	131	1.19 (0.01, 2.37)	0.048	1.01 (−0.14, 2.15)	0.085
>75th percentile	65	1.32 (−0.01, 2.65)	0.052	0.94 (−0.36, 2.25)	0.156
Exacerbation	(Admission definition, in 5 years)
Negative	232	(Reference)		(Reference)
Positive	29	0.57 (−0.20, 1.34)	0.148	0.46 (−0.29, 1.23)	0.229
Use of anticholinergics
No use	126	(Reference)		(Reference)
Use	135	0.16 (−0.31, 0.64)	0.494	0.10 (−0.38, 0.58)	0.693
Use of beta agonists
No use	169	(Reference)		(Reference)
Use	92	0.27 (−0.22, 0.77)	0.281	0.28 (−0.23, 0.79)	0.283

Abbreviations: BMI, body mass index; CI, confidence interval; DLco, diffusing capacity for carbon monoxide; FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire.

Table 4 Results of linear mixed-effects models to identify which variables during follow-up were predictive of the annual change in SGRQ symptom scores at 5 years

Variable (group)	n	Unadjusted model		Adjusted model
		Estimate (95% CI)	P-value	Estimate (95% CI)	P-value
Symptom score
FEV1 annual decline
Rapid decliners	65	(Reference)		(Reference)
Slow decliners	131	−1.32 (−2.58, −0.06)	0.040	−1.04 (0.41, 2.06)	0.117
Sustainers	65	−2.79 (−4.21, −1.37)	<0.001	−2.90 (1.28, 3.12)	<0.001
DLco annual change	(mL/min/mmHg)
<25th percentile	63	(Reference)		(Reference)
25th–75th percentile	127	−0.63 (−1.97, 0.71)	0.354	−0.92 (−2.23, 0.39)	0.171
>75th percentile	63	−0.08 (−1.59, 1.44)	0.919	−0.57 (−2.07, 0.94)	0.457
Smoking status
Former smoker	203	(Reference)		(Reference)
Continuous/intermittent smoker	58	0.02 (−0.65, 0.68)	0.963	0.04 (−0.62, 0.69)	0.906
Annual change in BMI
<25th percentile	65	(Reference)		(Reference)
25th–75th percentile	131	0.85 (−0.49, 2.19)	0.211	0.49 (−0.83, 1.82)	0.464
>75th percentile	65	0.04 (−1.47, 1.55)	0.960	−0.13 (−1.64, 1.38)	0.868
Exacerbation	(Admission definition, in 5 years)
Negative	232	(Reference)		(Reference)
Positive	29	1.28 (0.42, 2.15)	0.004	1.45 (0.57, 2.33)	0.002
Use of anticholinergics
No use	126	(Reference)		(Reference)
Use	135	−0.11 (−0.64, 0.43)	0.690	0.11 (−0.44, 0.67)	0.689
Use of beta agonists
No use	169	(Reference)		(Reference)
Use	92	0.50 (−0.06, 1.06)	0.081	−0.60 (−1.18, −0.02)	0.049

Notes: Unadjusted and adjusted linear mixed-effects models were used to test for the influence of variables during follow-up on the slope of the annual change in the SGRQ scores at 5 years (fixed effect = year, variables as below, and interaction effects between years and variables; random effect = id, id×year); Estimate: the annual difference in SGRQ scores compared with reference group. A positive value means annual deterioration of SGRQ, a negative value means annual improvement of SGRQ.

Abbreviations: BMI, body mass index; CI, confidence interval; DLco, diffusing capacity for carbon monoxide; FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire.

Figure S1 The frequency distributions of the annual change in SGRQ.

Note: The calculated annual change in the SGRQ total score (units/year) is 0.06 ± 2.64 (mean ± SD).

Abbreviation: SGRQ, St George’s Respiratory Questionnaire.

Table S1 Clinical characteristics of phenotypes between the follow-up group and dropouts at baseline

	Follow-up group (n=193)	Dropouts (n=68)	P-value
SGRQ total score	29.7±1.2	38.0±2.0	<0.01
SGRQ symptom score	42.7±1.6	46.0±2.7	0.29
SGRQ activity score	39.8±1.7	50.9±2.8	<0.01
SGRQ impact score	19.8±1.2	28.1±2.0	<0.01
Age (y)	68.7±0.6	72.0±0.9	<0.01
BMI (kg/m^2)	22.6±0.2	21.3±0.4	0.01
Pack-years	64.5±2.2	57.3±3.6	0.09
mMRC dyspnea scale	1.4±0.1	1.6±0.1	0.09
Post-bronchodilator FEV1 (%)	64.9±1.6	63.9±2.7	0.73
DLco (mmol/min/mmHg)	12.4±4.6	10.7±4.9	<0.01
Kco (mmol/min/mmHg)	2.9±1.1	2.5±1.1	0.02
White blood cell count (cells/mm^3)	6,139±107	6,039±180	0.63
Blood eosinophil count (cells/mm^3)	194±10	215±16	0.27
CRP (mg/dL)	0.25±0.04	0.46±0.07	0.01
Serum total IgE (IU/mL)	217±42	217±70	0.99

Note: P-values were calculated using Student’s t-test.

Abbreviations: BMI, body mass index; CRP, C reactive protein; DLco, carbon monoxide diffusing capacity; FEV₁, forced expiratory volume in 1 second; IgE, immunoglobulin E; Kco, carbon monoxide transfer coefficient; mMRC, modified Medical Research Council; SGRQ, St George’s Respiratory Questionnaire.

Table S2 Characteristics of subjects with COPD classified by annual rates of decline in FEV₁ at baseline

	Classified by annual change in FEV (mL/year)				P-value
	All patients (n=261)	Rapid decliners (n=65)	Slow decliners (n=131)	Sustainers (n=65)
Age, y	70±8	69±6	70±8	68±9	0.11
Female sex, n (%)	15 (5)	1 (2)	10 (8)	4 (6)	0.22
BMI (kg/m^2)	22±3	21±3*	22±3	23±4	0.017
Current smoker at entry, n (%)	73 (28)	13 (20)	40 (31)	20 (31)	0.26
Pack-years at entry	63±30	67±27	64±33	55±25	0.05
FEV (l)	1.75±0.67	1.76±0.62	1.71±0.66	1.84±0.67	0.42
FEV1 (%predicted)	65±22	64±21	64±22	66±23	0.74
DLco (mmol/min/mmHg)	12±5	11±5*	12±5*	14±4	0.003
Any cardiovascular disease, n (%)	58 (22)	17 (26)	27 (21)	14 (22)	0.67
Ischemic heart disease, n (%)	18 (7)	3 (5)	8 (6)	7 (10)	0.36
Diabetes, n (%)	12 (5)	1 (2)	7 (5)	4 (6)	0.31

Notes: Values are means ± SD; other values are numbers (%); P-values represent one-way analysis of variance with post hoc comparisons using Tukey’s multiple comparison tests;

* P<0.05 versus sustainers.

Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; DLco, carbon monoxide diffusing capacity; FEV₁, forced expiratory volume in 1 second; SD, standard deviation.

Table S3 Characteristics of subjects with COPD classified by annual rates of decline in FEV at baseline

	Rapid decliners (n=65)	Slow decliners (n=131)	Sustainers (n=65)	P-value
SGRQ total score	31±17	32±17	31±19	0.84
SGRQ activity score	43±20	43±22	45±22	0.70
SGRQ symptom score	41±23	45±22	39±25	0.18
SGRQ impact score	21±16	22±16	23±18	0.85
mMRC dyspnea scale	1.4±0.1	1.5±0.1	1.3±0.1	0.27
Cough and sputum, n (%)	7 (11)	11 (8)	11 (17)	0.22

Notes: Values are means ± SD; other values are numbers (%); P-values represent one-way analysis of variance.

Abbreviations: COPD, chronic obstructive pulmonary disease; SGRQ, St George’s Respiratory Questionnaire; mMRC, modified Medical Research Council.

Table S4 Results of unadjusted and adjusted linear mixed-effects models to identify which variables at baseline were predictive of the annual change in SGRQ total scores at 5 years

Total score baseline variable	Unadjusted model		Adjusted model
	Estimate (95% CI)	P-value	Estimate (95% CI)	P-value
Age*	0.93 (0.05, 0.14)	<0.001	0.75 (0.03, 0.12)	0.002
BMI	−0.15 (−0.25, −0.04)	0.007	−0.10 (−0.22, 0.01)	0.081
Cough and sputum	−0.57 (−1.13,0.00)	0.047	−0.50 (−1.03, 0.03)	0.066
FEV1 (%predicted)‡	−0.25 (−0.04, −0.01)	0.002	−0.20 (−0.37, −0.00)	0.017
DLco (ml/min/mmHg)	−1.50 (−0.22,−0.08)	<0.001	−0.04 (−0.12, 0.05)	0.419
Eosinophils (μL)§	−0.33 (−0.00, −0.00)	0.013	−0.24 (−0.00, 0.00)	0.066

Notes:

* Analyzed in units of 10 years;

‡ Analyzed in units of 10%;

§ Analyzed in units of 100.

Abbreviations: BMI, body mass index; CI, confidence interval; DLco, carbon monoxide diffusing capacity; FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire.

Table S5 Results of unadjusted and adjusted linear mixed-effects models to identify which variables at baseline were predictive of the annual change in SGRQ impact scores at 5 years

Variable	Unadjusted models		Adjusted models
	Estimate (95% CI)	P-value	Estimate (95% CI)	P-value
Age*	0.83 (0.03, 0.13)	0.001	0.61 (0.01, 0.11)	0.021
BMI	−0.12 (−0.24, −0.00)	0.042	−0.07 (−0.19, 0.06)	0.312
FVC (%predicted)‡	−0.23 (−0.04, −0.00)	0.026	−0.02 (−0.03, 0.03)	0.857
FEV1 (%predicted)‡	−0.33 (−0.05, −0.02)	<0.001	−0.03 (−0.05, 0.00)	0.052
DLco (ml/min/mmHg)	−0.15 (−0.23, −0.07)	<0.001	−0.04 (−0.14, 0.05)	0.369
Eosinophils (μl)§	−0.35 (−0.00, −0.00)	0.017	−0.31 (−0.01, 0.00)	0.028

Notes:

* Analyzed in units of 10 years;

‡ Analyzed in units of 10%;

§ Analyzed in units of 100.

Abbreviations: BMI, body mass index; CI, confidence interval; DLco, carbon monoxide diffusing capacity; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; SGRQ, St George’s Respiratory Questionnaire.

Table S6 Results of linear mixed-effects models to identify which variables during follow-up were predictive of the annual change in SGRQ total scores at 5 years

Total score variable (group)	n	Unadjusted model		Adjusted model
		Estimate (95% CI)	P-value	Estimate (95% CI)	P-value
FEV1 annual decline
Sustainers	65	(Reference)		(Reference)
Slow decliners	131	1.22 (0.39, 2.04)	0.004	1.23 (0.41, 2.06)	0.004
Rapid decliners	65	2.28 (1.37, 3.18)	<0.001	2.20 (1.28, 3.12)	<0.001
DLco annual change	(ml/min/mmHg)
<25th percentile	63	(Reference)		(Reference)
25–75th percentile	127	0.61 (−0.25, 1.48)	0.162	0.50 (−0.34, 0.55)	0.241
>75th percentile	63	0.92 (−0.06, 1.89)	0.065	0.48 (−0.48, 1.43)	0.325
Smoking status
Former smoker	203	(Reference)		(Reference)
Continuous/intermittent smoker	58	0.28 (−0.15, 0.71)	0.203	0.32 (−0.09, 0.74)	0.129
Annual change in BMI
<25th percentile	65	(Reference)		(Reference)
25–75th percentile	131	0.71 (−0.17, 1.59)	0.114	0.41 (−0.43, 1.25)	0.339
>75th percentile	65	0.56 (−0.43, 1.55)	0.269	0.38 (−0.58, 1.34)	0.437
Exacerbation	(Admission definition, in 5 years)
Negative	232	(Reference)		(Reference)
Positive	29	0.78 (0.22, 1.35)	0.007	0.88 (0.32, 1.44)	0.002
Use of anticholinergics
No use	126	(Reference)		(Reference)
Use	135	0.18 (−0.17, 0.53)	0.301	0.06 (−0.29, 0.42)	0.724
Use of beta agonists
No use	169	(Reference)		(Reference)
Use	92	0.11 (−0.26, 0.48)	0.569	0.07 (−0.30, 0.45)	0.697

Abbreviations: BMI, body mass index; CI, confidence interval; DLco, carbon monoxide diffusing capacity; FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire.

Table S7 Results of linear mixed-effects models to identify which variables during follow-up were predictive of the annual change in SGRQ impact scores at 5 years

Variable (group)	n	Unadjusted models		Adjusted models
		Estimate (95% CI)	P-value	Estimate (95% CI)	P-value
FEV1 annual decline
Sustainers	65	(Reference)		(Reference)
Slow decliners	131	1.35 (0.44, 2.25)	0.004	1.36 (0.46, 2.27)	0.003
Rapid decliners	65	1.98 (0.97, 2.98)	<0.001	1.91 (0.91, 2.93)	<0.001
DLco annual change
<25th percentile	65	(Reference)		(Reference)
25–75th percentile	131	0.77 (−0.15, 1.70)	0.100	0.69 (−0.21, 1.60)	0.133
>75th percentile	65	0.99 (−0.05, 2.04)	0.062	0.64 (−0.41, 1.68)	0.232
Smoking status
Former smoker	203	(Reference)		(Reference)
Continuous/intermittent smoker	58	0.24 (−0.22, 0.71)	0.304	0.27 (−0.18, 0.73)	0.234
Annual change in BMI
<25th percentile	65	(Reference)		(Reference)
25–75th percentile	131	0.57 (−0.38, 1.52)	0.239	0.24 (−0.68, 1.15)	0.613
>75th percentile	65	0.50 (−0.58, 1.57)	0.362	0.37 (−0.68, 1.42)	0.490
Exacerbation	(Admission definition, in 5 years)
Negative	232	(Reference)		(Reference)
Positive	29	0.75 (0.14, 1.36)	0.016	0.93 (0.32, 1.54)	0.003
Use of anticholinergics
Not use	126	(Reference)		(Reference)
Use	135	0.16 (−0.22, 0.54)	0.402	−0.02 (−0.40, 0.37)	0.934
Use of beta agonists
Not use	169	(Reference)		(Reference)
Use	92	0.22 (−0.18, 0.62)	0.274	0.21 (−0.20, 0.62)	0.313

Abbreviations: BMI, body mass index; CI, confidence interval; DLco, carbon monoxide diffusing capacity; FEV₁, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire.