because females represented 75% of the never-smoker sub-cohort. (Sample sizes for the analysis of lung function decline
were smaller because members had to participate at both examinations 1 and 2.) Baseline characteristics for subjects who
were lost to follow-up by examination 2 were a higher average age, lower average FEV1/height2, and a higher percentage
of self-reported current asthma, symptoms of chronic bronchitis, and smoking.
COPD morbidity
Estimated HRs for COPD morbidity (hospital diagnosis of
COPD) are presented in Table 2. The level of lung function
(FEV1/height2) was a significant predictor of COPD morbidity for males and females starting from the second quartile.
A similar, but less significant trend was observed in never-smokers, where significance was observed only at the fourth
quartile.
A similar increasing trend in COPD morbidity risk was
seen for the FEV1 slope, except significance began at the third
quartile for never-smokers. Females had the highest HRs for
COPD morbidity for the slope, the relative slope, the LNL,
and the 90 ml/yr limit (Figure 1a). Results from the penalized
spline analysis showed that the log HR for COPD morbidity
(males and females combined) started to increase at an FEV1
slope of – 54 ml/yr (Figure 2a). The parameter for the linear
rate was highly significant (p < 0.0001).
Comparing results for the dichotomous outcomes, the
LNL was significantly associated with COPD morbidity for
all 3 sub-cohorts, as was the 90 ml/yr limit. When compared
using the AIC (45), the fit of these 2 models were similar. The
LNL limit provided a slightly better fit for females, but the 90
ml/yr limit was slightly better for males and never-smokers.
Respiratory symptoms and asthma were often significantly associated with COPD morbidity in the models with
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)
Q1 FEV1/height2
Q2 FEV1/height2
Q3 FEV1/height2
Q4 FEV1/height2
Asthma†
Chronic bronchitis†
Shortness of breath†
HR 95% CI
1.00
2.69 (1.73–4.18)
6.10 (3.99–9.33)
16.36 (10.67–25.07)
2.21 (1.66–2.93)
2.04 (1.68–2.47)
2.48 (2.00–3.08)
(n = 4,214, COPD = 442)
HR 95% CI
1.00
2.66 (1.85–3.83)
5.09 (3.57–7.25)
16.55 (11.65–23.53)
1.20 (0.91–1.58)
2.05 (1.70–2.48)
2.77 (2.29–3.36)
(n = 5,402, COPD = 537)
HR 95% CI
1.00
1.64 (0.55–4.87)
1.41 (0.46–4.34)
5.18 (1.81–14.80)
3.69 (1.67–8.15)
2.35 (1.26–4.38)
2.36 (1.21–4.58)
(n = 1,817, COPD = 49)
Data for lung function decline‡
(Examination 1 to 2)
Q1 FEV1 slope
Q2 FEV1 slope
Q3 FEV1 slope
Q4 FEV1 slope
Asthma
Chronic bronchitis
Shortness of breath
HR
95% CI
(1.18–2.19)
HR
1.00
2.48
3.37
6.12
0.80
2.24
2.22
95% CI
HR
95% CI
(1.89–3.27)
(0.73–4.45)
(1.01–6.33)
(1.34–9.62)
(1.40–14.11)
(0.84–4.79)
(0.21–2.22)
Q1 FEV1 relative slope§
Q2 FEV1 relative slope
Q3 FEV1 relative slope
Q4 FEV1 relative slope
Asthma
Chronic bronchitis
Shortness of breath
FEV1 below LNL§
Asthma
Chronic bronchitis
Shortness of breath
FEV1 decline of ≥ 90 ml/yr
Asthma
Chronic bronchitis
Shortness of breath
∗ 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).
1.00
1.50
2.17
3.48
1.32
1.95
2.04
2.32
1.52
1.98
2.10
2.11
1.48
2.02
2.12
(1.09–2.07)
(1.58–3.00)
(2.59–4.67)
(0.93–1.86)
(1.56–2.44)
(1.57–2.65)
(1.86–2.88)
(1.08–2.14)
(1.58–2.48)
(1.62–2.74)
(1.73–2.57)
(1.05–2.09)
(1.61–2.52)
(1.63–2.75)
1.00
1.99
2.60
5.27
0.80
2.26
2.21
3.01
0.86
2.37
2.27
2.87
0.82
2.34
2.38
(1.48–2.68)
(1.95–3.46)
(4.06–6.85)
(0.57–1.11)
(1.82–2.79)
(1.76–2.78)
(2.49–3.64)
(0.62–1.20)
(1.91–2.93)
(1.81–2.86)
(2.37–3.48)
(0.59–1.15)
(1.89–2.89)
(1.90–2.98)
1.00
1.73
1.65
3.92
4.39
2.03
0.69
2.33
4.49
2.18
0.76
2.32
4.74
1.97
0.78
(0.68–4.41)
(0.60–4.57)
(1.63–9.44)
(1.38–13.92)
(0.87–4.73)
(0.22–2.18)
(1.22–4.44)
(1.46–13.78)
(0.93–5.10)
(0.24–2.39)
(1.19–4.53)
(1.56–14.46)
(0.81–4.80)
(0.25–2.41)
