Health Outcomes Associated with Lung Function Decline and Respiratory Symptoms and Disease in a Community Cohort

Figures & data

Table 1  Characteristics of the sub-cohorts for Cox proportional hazards model analysis using data for lung function level and decline

	Males		Females		Never-smokers
Data for lung function level (Examination 2)
Subjects (n,%)	5,494	44.8	6,771	55.2	2,555	20.8
Age at examination two (mean, SD^†)	56.1	12.6	56.7	12.1	56.4	13.8
Follow-up, years (mean, SD)
COPD morbidity	15.4	6.9	17.3	6.0	18.1	5.7
COPD or CHD mortality	16.9	7.9	19.3	7.0	20.0	6.7
All-cause mortality	17.1	8.1	19.5	7.2	20.3	7.0
Height, cm^† (mean, SD)	174	7	161	6	164	9
FEV1, l^† (mean, SD)	2.82	0.91	2.05	0.63	2.39	0.85
FEV1/height^2 × mean height^2, l (mean, SD)	2.57	0.75	2.17	0.60	2.42	0.67
25th percentile	2.07		1.78		2.43; 1.87^‡
Median	2.56		2.17		2.92; 2.23^‡
75th percentile	3.08		2.58		3.41; 2.65^‡
Asthma (n,%)	172	3.1	218	3.2	59	2.3
Chronic bronchitis (n,%)	872	15.9	722	10.7	148	5.8
Shortness of breath (n,%)	543	9.9	728	10.8	159	6.2
Never-smokers (n,%)	629	11.5	1,926	28.5	629; 1,926^‡	24.6; 75.4^‡
Former smokers (n,%)	1,352	24.6	1,244	18.4
Current smokers (n,%)	3,510	63.9	3,592	53.1
Data for lung function decline (Examination 1 to 2)§
Subjects (n,%)	4,253	43.9	5,426	56.1	1,822	18.8
Baseline age (mean, SD)	52.5	11.4	52.7	10.8	52.8	12.2
Follow-up, years (mean, SD)
COPD morbidity	15.2	6.9	17.3	6.0	18.2	5.6
COPD or CHD mortality	16.7	7.9	19.3	6.9	20.1	6.7
All-cause mortality	16.9	8.1	19.6	7.1	20.4	6.9
Baseline FEV1, l (mean, SD)	3.09	0.82	2.25	0.55	2.56	0.79
Baseline FEV1/height^2 × mean height^2, l (mean, SD)	2.83	0.67	2.40	0.53	2.62	0.62
Slope FEV1, ml/yr^† (mean, SD)	–62	94	–45	71	–43	80
25th percentile	–118		–95		–114; –94^‡
Median	–60		–57		–57; –40^‡
75th percentile	0		0		19; 0^‡
Slope FEV1/baseline FEV1,%/yr (mean, SD)	–2.0	3.4	–1.9	3.4	–1.5	3.4
25th percentile	–4.1		–4.1		–3.2; –3.8^‡
Median	–2.2		–2.2		–1.5; –2.0^‡
75th percentile	0.0		0.0		0.4; 0.0^‡
FEV1 below LNL^† (n,%)	743	17.4	1,016	18.7	346	19.0
FEV1 decline of 90 ml/yr or more (n,%)	1,717	40.4	1,444	26.6	505	27.7
Asthma (n,%)	125	2.9	168	3.1	40	2.2
Chronic bronchitis (n,%)	665	15.6	558	10.3	96	5.3
Shortness of breath (n,%)	401	9.4	550	10.1	104	5.7

*A total of 12,265 subjects at examination 2 and 9,679 subjects at both examinations 1 and 2.

^†SD (standard deviation), cm (centimeters), l (liters), ml/yr (milliliters/year), and LNL (Longitudinal Normal Limit).

^‡Males; females.

§Includes subjects with approximately 5 years between spirometry tests.

Table 2  Cox proportional hazards models for COPD morbidity (hospital diagnosis of COPD [ICD-8 491–492, ICD-10 J41–J44])

	Males		Females		Never-smokers
	(n = 5,442, COPD = 563)		(n = 6,735, COPD = 678)		(n = 2,548, COPD = 73)
Data for lung function level (Examination 2)	HR	95% CI	HR	95% CI	HR	95% CI
Q1 FEV1/height^2	1.00		1.00		1.00
Q2 FEV1/height^2	2.69	(1.73–4.18)	2.66	(1.85–3.83)	1.64	(0.55–4.87)
Q3 FEV1/height^2	6.10	(3.99–9.33)	5.09	(3.57–7.25)	1.41	(0.46–4.34)
Q4 FEV1/height^2	16.36	(10.67–25.07)	16.55	(11.65–23.53)	5.18	(1.81–14.80)
Asthma^†	2.21	(1.66–2.93)	1.20	(0.91–1.58)	3.69	(1.67–8.15)
Chronic bronchitis^†	2.04	(1.68–2.47)	2.05	(1.70–2.48)	2.35	(1.26–4.38)
Shortness of breath^†	2.48	(2.00–3.08)	2.77	(2.29–3.36)	2.36	(1.21–4.58)
	(n = 4,214, COPD = 442)		(n = 5,402, COPD = 537)		(n = 1,817, COPD = 49)
Data for lung function decline^‡
(Examination 1 to 2)	HR	95% CI	HR	95% CI	HR	95% CI
Q1 FEV1 slope	1.00		1.00		1.00
Q2 FEV1 slope	1.61	(1.18–2.19)	2.48	(1.89–3.27)	1.80	(0.73–4.45)
Q3 FEV1 slope	2.54	(1.87–3.45)	3.37	(2.55–4.44)	2.53	(1.01–6.33)
Q4 FEV1 slope	3.77	(2.76–5.15)	6.12	(4.63–8.10)	3.58	(1.34–9.62)
Asthma	1.41	(1.00–1.99)	0.80	(0.58–1.12)	4.45	(1.40–14.11)
Chronic bronchitis	1.92	(1.53–2.40)	2.24	(1.82–2.77)	2.00	(0.84–4.79)
Shortness of breath	2.00	(1.54–2.61)	2.22	(1.76–2.78)	0.69	(0.21–2.22)
Q1 FEV1 relative slope§	1.00		1.00		1.00
Q2 FEV1 relative slope	1.50	(1.09–2.07)	1.99	(1.48–2.68)	1.73	(0.68–4.41)
Q3 FEV1 relative slope	2.17	(1.58–3.00)	2.60	(1.95–3.46)	1.65	(0.60–4.57)
Q4 FEV1 relative slope	3.48	(2.59–4.67)	5.27	(4.06–6.85)	3.92	(1.63–9.44)
Asthma	1.32	(0.93–1.86)	0.80	(0.57–1.11)	4.39	(1.38–13.92)
Chronic bronchitis	1.95	(1.56–2.44)	2.26	(1.82–2.79)	2.03	(0.87–4.73)
Shortness of breath	2.04	(1.57–2.65)	2.21	(1.76–2.78)	0.69	(0.22–2.18)
FEV1 below LNL	2.32	(1.86–2.88)	3.01	(2.49–3.64)	2.33	(1.22–4.44)
Asthma	1.52	(1.08–2.14)	0.86	(0.62–1.20)	4.49	(1.46–13.78)
Chronic bronchitis	1.98	(1.58–2.48)	2.37	(1.91–2.93)	2.18	(0.93–5.10)
Shortness of breath	2.10	(1.62–2.74)	2.27	(1.81–2.86)	0.76	(0.24–2.39)
FEV1 decline of ≥90 ml/yr	2.11	(1.73–2.57)	2.87	(2.37–3.48)	2.32	(1.19–4.53)
Asthma	1.48	(1.05–2.09)	0.82	(0.59–1.15)	4.74	(1.56–14.46)
Chronic bronchitis	2.02	(1.61–2.52)	2.34	(1.89–2.89)	1.97	(0.81–4.80)
Shortness of breath	2.12	(1.63–2.75)	2.38	(1.90–2.98)	0.78	(0.25–2.41)

*Models adjusted for age at examination 2.

^†Asthma, chronic bronchitis, and shortness of breath represented as dichotomous variables in all models.

^‡Models adjusted for baseline age, height-adjusted baseline lung function (FEV₁/height²), and height. See Table 1 for slope and relative slope quartile values.

§FEV₁ relative slope (slope FEV₁/baseline FEV₁) and LNL (Longitudinal Normal Limit).

Figure 1  Cox proportional hazards model results by gender (⧫ = males and • = females) for (a) COPD morbidity, (b) COPD or CHD mortality, and (c) all-cause mortality. Models adjusted for baseline age, height-adjusted baseline lung function (FEV₁/height²), height, and respiratory symptoms and asthma as dichotomous variables. Relative slope is slope FEV₁/baseline FEV₁. LNL is the Longitudinal Normal Limit. See Table 1 for slope and relative slope quartile values.

Figure 2  Cox proportional hazards model using a penalized spline for the FEV₁ slope, males and females combined. The spline crossed above zero for the log HR at –54 ml/yr for (a) COPD morbidity, at –72 ml/yr for (b) COPD or CHD mortality, and at –77 ml/yr for (c) all-cause mortality. Models adjusted for baseline age, height-adjusted baseline lung function (FEV₁/height²), and height. Tick marks on the x axis represent the frequency of the various FEV₁ slope values.

Table 3  Cox proportional hazards models for COPD (ICD-8 491–492, ICD-10 J41–J44) or CHD mortality (ICD-8 410–414, and ICD-10 I20–I25)

	Males		Females		Never-smokers
	(n = 5,494, Deaths = 1,201)		(n = 6,771, Deaths = 983)		(n = 2,555, Deaths = 269)
Data for lung function level (Examination 2)	HR	95% CI	HR	95% CI	HR	95% CI
Q1 FEV1/height^2	1.00		1.00		1.00
Q2 FEV1/height^2	1.46	(1.15–1.85)	1.88	(1.38–2.57)	1.92	(0.95–3.89)
Q3 FEV1/height^2	2.02	(1.60–2.56)	2.79	(2.06–3.77)	2.54	(1.29–5.01)
Q4 FEV1/height^2	3.02	(2.38–3.84)	5.49	(4.07–7.41)	3.94	(2.00–7.76)
Asthma^†	1.14	(0.88–1.47)	0.87	(0.66–1.15)	1.03	(0.49–2.14)
Chronic bronchitis^†	1.32	(1.14–1.53)	1.62	(1.37–1.93)	1.32	(0.88–1.99)
Shortness of breath^†	2.15	(1.82–2.54)	2.30	(1.94–2.72)	1.57	(1.04–2.35)
	(n = 4,253, Deaths = 974)		(n = 5,426, Deaths = 796)		(n = 1,822, Deaths = 202)
Data for lung function decline^‡
(Examination 1 to 2)	HR	95% CI	HR	95% CI	HR	95% CI
Q1 FEV1 slope	1.00		1.00		1.00
Q2 FEV1 slope	1.20	(0.99–1.45)	1.48	(1.19–1.83)	1.17	(0.77–1.78)
Q3 FEV1 slope	1.34	(1.10–1.63)	1.73	(1.39–2.15)	1.42	(0.93–2.17)
Q4 FEV1 slope	1.91	(1.57–2.33)	2.95	(2.38–3.67)	1.42	(0.90–2.25)
Asthma	0.94	(0.70–1.27)	0.74	(0.54–1.03)	1.30	(0.56–3.03)
Chronic bronchitis	1.29	(1.10–1.52)	1.58	(1.31–1.92)	1.33	(0.80–2.22)
Shortness of breath	1.92	(1.58–2.33)	1.86	(1.52–2.28)	1.21	(0.70–2.09)
Q1 FEV1 relative slope	1.00		1.00		1.00
Q2 FEV1 relative slope	1.15	(0.94–1.40)	1.51	(1.21–1.90)	1.08	(0.69–1.67)
Q3 FEV1 relative slope	1.31	(1.07–1.60)	1.27	(1.00–1.60)	1.15	(0.74–1.80)
Q4 FEV1 relative slope	1.75	(1.45–2.11)	2.68	(2.19–3.28)	1.61	(1.06–2.43)
Asthma	0.90	(0.67–1.22)	0.68	(0.49–0.94)	1.31	(0.56–3.04)
Chronic bronchitis	1.29	(1.10–1.53)	1.60	(1.32–1.95)	1.32	(0.79–2.19)
Shortness of breath	1.95	(1.61–2.37)	1.90	(1.56–2.33)	1.17	(0.68–2.02)
FEV1 below LNL	1.56	(1.34–1.82)	2.14	(1.84–2.50)	1.34	(0.97–1.85)
Asthma	0.95	(0.70–1.28)	0.73	(0.52–1.01)	1.27	(0.55–2.95)
Chronic bronchitis	1.31	(1.11–1.54)	1.63	(1.34–1.98)	1.32	(0.79–2.21)
Shortness of breath	1.95	(1.60–2.36)	1.86	(1.51–2.27)	1.22	(0.71–2.10)
FEV1 decline of ≥90 ml/yr	1.54	(1.35–1.75)	2.12	(1.81–2.48)	1.43	(1.03–1.99)
Asthma	0.94	(0.70–1.27)	0.76	(0.55–1.05)	1.33	(0.57–3.08)
Chronic bronchitis	1.30	(1.11–1.54)	1.62	(1.33–1.96)	1.31	(0.78–2.18)
Shortness of breath	1.98	(1.63–2.39)	1.89	(1.55–2.31)	1.19	(0.69–2.05)

*Models adjusted for age at examination 2.

^†Asthma, chronic bronchitis, and shortness of breath represented as dichotomous variables in all models.

^‡Models adjusted for baseline age, height-adjusted baseline lung function (FEV₁/height²), and height. See Table 1 for slope and relative slope quartile values.

§FEV₁ relative slope (slope FEV₁/baseline FEV₁) and LNL (Longitudinal Normal Limit).

Table 4  Cox proportional hazards models for all-cause mortality

	Males		Females		Never-smokers
	(n = 5,494, Deaths = 3,535)		(n = 6,771, Deaths = 3,632)		(n = 2,555, Deaths = 1,181)
Data for lung function level (Examination 2)	HR	95% CI	HR	95% CI	HR	95% CI
Q1 FEV1/height^2	1.00		1.00		1.00
Q2 FEV1/height^2	1.27	(1.13–1.44)	1.39	(1.22–1.57)	1.54	(1.20–1.98)
Q3 FEV1/height^2	1.60	(1.42–1.81)	1.83	(1.62–2.07)	1.70	(1.33–2.16)
Q4 FEV1/height^2	2.31	(2.04–2.62)	2.65	(2.33–3.01)	2.15	(1.68–2.76)
Asthma^†	0.98	(0.82–1.17)	0.99	(0.83–1.18)	1.13	(0.78–1.63)
Chronic bronchitis^†	1.29	(1.18–1.40)	1.32	(1.20–1.46)	1.16	(0.94–1.44)
Shortness of breath^†	1.52	(1.36–1.70)	1.50	(1.36–1.67)	1.38	(1.11–1.70)
	(n = 4,253, Deaths = 2,842)		(n = 5,426, Deaths = 2,958)		(n = 1,822, Deaths = 860)
Data for lung function decline^‡
(Examination 1 to 2)	HR	95% CI	HR	95% CI	HR	95% CI
Q1 FEV1 slope	1.00		1.00		1.00
Q2 FEV1 slope	1.14	(1.02–1.27)	1.24	(1.12–1.39)	1.17	(0.95–1.43)
Q3 FEV1 slope	1.20	(1.08–1.35)	1.37	(1.23–1.53)	1.31	(1.06–1.61)
Q4 FEV1 slope	1.67	(1.49–1.87)	1.88	(1.68–2.10)	1.53	(1.23–1.91)
Asthma	0.87	(0.71–1.07)	0.96	(0.78–1.16)	1.15	(0.73–1.80)
Chronic bronchitis	1.24	(1.12–1.38)	1.27	(1.14–1.43)	1.10	(0.84–1.45)
Shortness of breath	1.43	(1.26–1.63)	1.36	(1.21–1.54)	1.27	(0.97–1.66)
Q1 FEV1 relative slope	1.00		1.00		1.00
Q2 FEV1 relative slope	1.10	(0.98–1.23)	1.25	(1.11–1.39)	1.18	(0.96–1.46)
Q3 FEV1 relative slope	1.23	(1.09–1.37)	1.22	(1.09–1.37)	1.13	(0.91–1.40)
Q4 FEV1 relative slope	1.55	(1.39–1.73)	1.81	(1.63–2.01)	1.59	(1.29–1.95)
Asthma	0.84	(0.68–1.04)	0.91	(0.74–1.10)	1.11	(0.71–1.74)
Chronic bronchitis	1.24	(1.12–1.37)	1.28	(1.15–1.44)	1.09	(0.83–1.44)
Shortness of breath	1.45	(1.28–1.65)	1.38	(1.22–1.55)	1.26	(0.97–1.65)
FEV1 below LNL	1.48	(1.35–1.62)	1.58	(1.46–1.72)	1.42	(1.22–1.66)
Asthma	0.87	(0.71–1.07)	0.94	(0.77–1.15)	1.11	(0.71–1.74)
Chronic bronchitis	1.25	(1.13–1.39)	1.30	(1.16–1.45)	1.11	(0.84–1.46)
Shortness of breath	1.44	(1.27–1.64)	1.36	(1.21–1.54)	1.29	(0.99–1.69)
FEV1 decline of ≥90 ml/yr	1.37	(1.27–1.48)	1.55	(1.42–1.68)	1.37	(1.17–1.61)
Asthma	0.87	(0.70–1.07)	0.97	(0.80–1.18)	1.14	(0.73–1.79)
Chronic bronchitis	1.25	(1.13–1.39)	1.29	(1.15–1.44)	1.10	(0.83–1.45)
Shortness of breath	1.47	(1.30–1.67)	1.37	(1.22–1.55)	1.29	(0.99–1.68)

*Models adjusted for age at examination 2.

^†Asthma, chronic bronchitis, and shortness of breath represented as dichotomous variables in all models.

^‡Models adjusted for baseline age, height-adjusted baseline lung function (FEV₁/height²), and height. See Table 1 for slope and relative slope quartile values.

§FEV₁ relative slope (slope FEV₁/baseline FEV₁) and LNL (Longitudinal Normal Limit).