Characteristics of the study population
This pooled analysis comprised of 8,686 COPD patients (Figure 1, cohort selection). Table 1 presents the baseline characteristics of the study population. The mean baseline age was 51.9 years (SD=9.1); 37% were women; and 56% were current smokers. The average BMI at baseline was 25.8 kg/m2 (SD=4.3). The median follow-up time was 2 years. A total of 3,674 (42%) patients were in GOLD Grade 1; 5,012 (58%) were in GOLD Grade 2.
Table 1. Baseline characteristics of the study population
|
Total
|
Calverley
|
CCLS
|
ECLIPSE
|
EUROSCOPE
|
ISOLDE
|
LHS
|
Szafranski
|
Patient, N(%)
|
8,686 (100)
|
90 (1.0)
|
231 (2.7)
|
1,500 (17.3)
|
982 (11.3)
|
260 (3.0)
|
5,591 (64.4)
|
32 (0.4)
|
Age, y (SD)
|
51.9 (9.1)
|
62.4 (9.4)
|
58.9 (9.1)
|
60.2 (9.0)
|
52.5 (7.6)
|
63.9 (8.0)
|
48.4 (6.8)
|
66.3 (8.5)
|
Women, N(%)
|
3,229 (37.2)
|
25
(27.8)
|
94
(40.7)
|
665 (44.3)
|
276 (28.1)
|
81 (31.2)
|
2,085 (37.3)
|
3 (9)
|
Current smoker , N(%)
|
4,849 (55.9)
|
29
(32.2)
|
175 (75.8)
|
426 (28.7)
|
982 (100)
|
126 (48.5)
|
3,096 (55.4)
|
15
(46.9)
|
GOLD grade, N(%)
|
|
|
|
|
|
|
|
|
1
|
3,674 (42.3)
|
12 (13.3)
|
105 (45.5)
|
575 (38.3)
|
354 (36.0)
|
9 (3.5)
|
2,619 (46.8)
|
0 (0)
|
2
|
5,012 (57.7)
|
78 (86.7)
|
126 (54.5)
|
925 (61.7)
|
628 (64.0)
|
251 (96.5)
|
2,972 (53.2)
|
32 (100)
|
FEV1
|
|
|
|
|
|
|
|
|
Absolute, Litre
|
2.62
(0.73)
|
1.84 (0.48)
|
2.54 (0.80)
|
2.35 (0.96)
|
2.60 (0.62)
|
1.83 (0.44)
|
2.75 (0.63)
|
1.62 (0.29)
|
% predicted
|
77.8 (14.4)
|
63.7 (13.5)
|
79.6 (15.6)
|
81.6 (25.6)
|
74.6 (11.6)
|
61.9 (8.6)
|
78.4 (9.1)
|
56.0 (6.0)
|
BMI, kg/m2
|
25.7 (4.3)
|
25.9 (5.3)
|
25.5 (4.2)
|
27.3 (5.4)
|
24.5 (3.3)
|
25.2 (4.3)
|
25.5 (3.9)
|
26.0 (5.3)
|
BMI category, N(%)
|
|
|
|
|
|
|
|
|
Underweight
(BMI<18.5)
|
163 (1.9)
|
5 (5.6)
|
3 (1.3)
|
30 (2.0)
|
21 (2.1)
|
13 (5.0)
|
90 (1.6)
|
1 (3.1)
|
Normal
(BMI 18.5-25.0)
|
3,945 (45.4)
|
41 (45.6)
|
118 (50.1)
|
510 (34.0)
|
555 (56.5)
|
118 (45.4)
|
2,589 (46.3)
|
14 (43.8)
|
Overweight
(BMI 25.1-30.0)
|
3,340 (38.5)
|
27 (30.0)
|
71 (30.7)
|
589 (39.3)
|
354 (30.0)
|
93 (35.8)
|
2,194 (39.2)
|
12 (37.5)
|
Obese
(BMI>30.1)
|
1,238 (14.3)
|
17 (18.9)
|
39 (16.9)
|
371 (24.7)
|
52 (5.3)
|
36 (13.8)
|
718 (12.8)
|
5 (15.6)
|
Follow-up, mo
|
36 (median)
|
|
|
|
|
|
|
|
BMI, body mass index, CCLS, City Lung Study, ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints Study, EUROSCOPE, European Respiratory Society study on COPD, GOLD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric grades, ISOLDE, Inhaled Steroids in Obstructive Lung Disease in Europe, LHS, Lung Health Study, mo, moth, N, number, SD, standard deviation, y, year.
Table 2 presents the gender-specific baseline characteristics and the observed rate of FEV1 decline of the combined GOLD Grades 1 and 2 samples. Male patients experienced a significantly faster decline in absolute FEV1 values compared to female patients (mL/year, -36.6 vs -29.2, p-value <0.001). Male and female patients had similar mean ages (51.8 vs. 51.9 years) and proportionality of current smokers (54% vs. 57%). However, the majority of males had normal body weight (58% of BMI between 18.5 kg/m2 and 25.0 kg/m2), whereas the majority of females were more likely to be overweight or obese (60% of had a BMI above 25.1 kg/m2). Supplemental Material Table S2 shows the observed baseline FEV1 and the rate of FEV1 decline by smoking status and BMI level. Underweight individuals (BMI <18.5 kg/m2) had a lower baseline FEV1 compared to other BMI groups (L, 2.17 vs 2.56-2.73), while obese individuals (BMI ≥30.1 kg/m2) had a slower rate of decline than those who were overweight (BMI 25.1–30.0 kg/m2), normal (BMI 18.5–25.0 kg/m2) or underweight (mL/year, -27.5 vs -34.4, -35.3, -34.6, respectively). Current smokers had a much more rapid decline than ex-smokers (mL/year, -40.9 vs -24.9).
Table 2. Observed rate of FEV1 decline according to GOLD subgroups, gender, smoking status and BMI category.
|
GOLD Grades 1 and 2
|
|
|
Male
(N=5,457)
|
Female
(N=3,229)
|
p-value*
|
Rate of FEV1 decline, mean (95% CI), mL/year
|
-36.6
(-37.6, -35.6)
|
-29.2
(-30.2, -28.1)
|
p<0.001
|
Age, y, mean (SD)
|
51.8 (8.8)
|
51.9 (9.3)
|
p=0.40
|
BMI, kg/m2, mean(SD)
|
26.3 (3.9)
|
24.8 (4.7)
|
p<0.001
|
BMI category, n(%)
|
|
|
p<0.001
|
Underweight (BMI<18.5)
|
54 (1.0)
|
109 (3.4)
|
|
Normal (BMI 18.5-25.0)
|
2,082 (38.2)
|
1,863 (57.7)
|
Overweight (BMI 25.1-30.0)
|
2,477 (45.4)
|
863 (26.7)
|
Obese (BMI>30.1)
|
844 (15.5)
|
394 (12.2)
|
Smoking status, n(%)
|
|
|
p=0.02
|
Ex-smoker
|
1,472 (45.7)
|
2,350 (43.1)
|
|
Current smoker
|
1,750 (54.3)
|
3,099 (56.9)
|
BMI, body mass index, GOLD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric grades, N, number, SD, standard deviation.
*p-values were obtained from Kruskal–Wallis test for continuous variables and Pearson chi-square test for categorical variables.
Gender-modified effects of BMI on the rate of FEV1 decline
Figures 2 illustrates the fitted dose-response relationship between BMI (x-axis) and the rate of decline in absolute FEV1values (y-axis, with confidence intervals shown in error bars) in combined GOLD Grades 1 and 2. The confidence interval of the curve was wider at both ends of the BMI scale, reflecting a greater variance of the association at extreme BMI values, probably due to the smaller number of patients at the extremes.
Gender significantly modified the relationship between BMI and FEV1 decline (p<0.001). In male patients, the dose-response curve depicted a reverse association between BMI and rate of decline in absolute FEV1 values. This relationship was mostly linear, except for a slight fluctuation in the line at a BMI of 25 kg/m2 (Figures 2). The slope of this curve showed that an increase of BMI by 1 kg/m2 reduced FEV1 decline by approximately 1.05mL/year (95% CI: 0.96, 1.14). In female patients, the slope of the curve showed that BMI had a very small (and clinically insignificant) effect: An increase of BMI of 1 kg/m2 reduced FEV1 decline by only 0.16 ml/year (95% CI: 0.11, 0.21).
In a secondary analysis, the effects of BMI were stratified by GOLD Grades and smoking status (Figure 3, upper panel, male patients [left, GOLD 1; right, GOLD 2], lower panel, female patients [left, GOLD 1, right, GOLD 2]). As for the effects of smoking, within GOLD Grade 1, the gender-specific dose-response curves appeared in parallel between current smokers and ex-smokers, though the curves were statistically different from each other (p<0.001). Within GOLD Grade 2, there was a notable narrowing of the gap at higher BMI levels between current smokers and ex-smokers. This suggests that, conditional on COPD severity and gender, the additional impact of smoking on the relationship between BMI and FEV1 decline was small in GOLD Grade 1, whereas higher BMI level appeared to have a slight protective effect on FEV1 decline in GOLD Grade 2 current smokers, in particular among male smokers. Of note, the highest risk of decline was observed in underweight male smokers with GOLD 1 disease, who experienced, on average >70 ml/year decline in FEV1 (Figure 3).