ONLINE SUPPLEMENT METHODS The Odense Schoolchild study is a prospective community based study of a cohort of 1369 schoolchildren first investigated during their third grade in 1985. All forty-four public schools in the municipally of Odense were invited to participate in the study. These schools had 1680 children in the third grade. For 1411 children an informed consent was obtained from a parent. Of these 1411 children, 42 were absent on the day of examination. No efforts were made to examine these children at another time, so 1369 children contributed to the original study cohort in 1985. The distributions according on birth year was: 1974(0.1%), 1975(6.3%), 1976(88.6%) and 1977(5.0%). This analysis uses data collected when the cohort participants were aged 20 and 29 years. All data collection was performed from August through June on all occasions. Subjects were rescheduled for at least 6 weeks later if they reported a cold within the last 14 days at the day of the visit. At both examinations standing height and weight without shoes wearing light clothing were measured to calculate body mass index (BMI) in kg/m2. Asthma like symptoms were identified by the questions, asked with reference to the previous one year period: “Do you have attacks of breathing trouble with wheezing or whistling?”, “Do you have trouble breathing at night?”, “Do you have trouble breathing at all?” and “Have you had a period with cough lasting three or more days in succession?”. Cough in relation to colds was only considered if lasting two weeks or more (additional questions asked: “Do you only cough in connection with colds?” and “For how long does the cough period usually last?”). Subjects were not questioned regarding private or work place exposures. SPIROMETRY A Vitalograph Compact® pneumotachograph was used to record maximal forced expirations. The spirometer was volume calibrated daily with a 6 liter syringe. A variation of ±3% was accepted. Spirometry was performed with the subject in the standing position and without the use of a noseclip. The subjects were instructed and encouraged to perform the test with maximum effort. Baseline spirometry was considered as acceptable for both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) if the two best values were within 5% of each other. The highest values of FEV1 and FVC from all acceptable attempts were used in the analysis. The volumes are reported at body temperature, pressure and fully saturated with water vapour (BTPS). The predicted values of FEV1 and FVC were calculated by sex-specific linear regression equations derived from reference study members from the cohort with no previous history of asthma ever, no history of smoking ever, and no reported asthma-like symptoms within the previous year. Height was used as the dependent variable. Age was not used in the equations, because the study members at each assessment were all of the same age. In females at age 9: FEV1=0.02747*height-2.112; RSD=0.49, FVC=0.02903*height-2.111, RSD=0.43 In males at age 9: FEV1=0.02748*height2.0240, RSD=0.42, FVC= 0.03314*height-2.559, RSD=0.45 In females at age 20: FEV1= 0.03564*height-2.510, RSD=0.38; FVC: 0.05163*height-4.503, RSD=0.45. In males at age 20: FEV1=0.04368*height-3.212, RSD=0.51; FVC= 0.07352*height-7.496, RSD=0.64 respectively. In females at age 29: FEV1= 0.039*height–3.087, RSD=0.21; FVC=0.051*height-4.205, RSD=0.32. In males at age 29: FEV1=0.047*height–3.887, RSD=0.34; FVC= 0.077* height–8.048, RSD=0.50 respectively. Based on own reference equations the mean (SD) FEV1 values were 98.3 (11) and 99.4 (11) percent predicted at age 20 years and 99.1 (12) and 98.7 (11) percent predicted at age 29 years in men and women respectively. RESULTS There were no significant differences between participants included in and missing from these analysis with regard to the data collected at the beginning of the study (age 9) (table A). Nor was there a significant dropout between age 21 and 29 (data not shown). Table A. Characteristics of participants and non-participants at age 9 years. Men Women Participants NonP-value Participants NonP-value n=422 Participants n=448 Participants n=274 n=225 Age (years) 9.7 (0.39) 9.7 (0.43) 0.26 9.6 (0.41) 9.7 (0.41) 0.18 Height (m) 1.42 (6.1) 1.42 (6.2) 0.67 1.40 (6.3) 1.41 (6.3) 0.06 Weight (kg) 34.2 (6.2) 34.1 (5.9) 0.88 34.0 (5.4) 34.3 (6.6) 0.07 BMI(kg/m2) 16.9 (1.9) 16.9 (2.0) 0.97 16.8 (1.9) 17.0 (2.2) 0.15 Asthma (%) 5.4 5.2 0.85 2.3 3.3 0.45 Cardio51.3 (6.9) 51.1 (7.1) 0.79 45.0 (5.9) 44.3 (6.3) 0.18 pulmonary fitness (w/kg2) FEV1 (L) 1.87 (0.26) 1.86 (0.27) 0.09 1.73 (0.24) 1.75 (0.28) 0.26 FVC (L) 2.16 (0.30) 2.15 (0.31) 0.10 1.95 (0.26) 1.99 (0.31) 0.11 FEV1 percent of 100.2 (11) 99.7 (10) 0.87 100.0 (10) 100.0 (11) 0.81 predicted (%) FVC percent of 100.6 (11) 99.7 (10) 0.85 100.2 (10) 99.9 (11) 0.73 predicted (%) Figures are numbers and percentages (in parentheses) where not otherwise specified. Non-eligible subjects included as non-paticipants. The sex-adjusted partial correlation coefficients between measurements at age 20 and age 29 years were r=0.87 (p<0.0001) for FEV1, r=0.79 for BMI (p<0.0001), r=0.61 (p<0.0001) for cardiorespiratory fitness respectively. However, the general profile of cardiovascular risk factors worsened in both sexes from 20 to 29 years of age (Table B) with men having greater changes than women in cardio-pulmonary fitness (-8.2 versus -4.3 w/kg2 ;p<0.0001 ); Cholesterol (1.2 versus 1.0; p<0.0001); LDL (1.1 versus 0.9; p<0.0001) ; BMI (2.7 versus 2.0 kg/m2; p=0.002); Diastolic BP (11.8 versus 8.2 mmHg; p=0.001); and weight (9.1 versus 5.9 kg ;p<0.0001). Smoking and asthmalike symptoms decreased in women but not in men (p<0.0001). Table B. Characteristics of men and women at age 20 and 29 (95%CI). Pregnant women excluded. Men (n=344) Women (n=323) Age 20 Age 29 P Age 20 Age 29 p Height (m) 1.809 1.814 <0.0001 1.670 1.677 <0.0001 (1.80;1.81) (1.81;1.82) (1.66;1.68) (1.67;1.68) Weight (kg) 76.0 84.8 <0.0001 64.1 69.6 <0.0001 (75;77) (83;86) (63;65) (68;71) BMI (kg/m2) 23.2 25.9 <0.0001 23.0 24.7 <0.0001 (22.9;23.5) (25.5;26.3) (22.6;23.3) (24.2;25.2) Waist-to-hip 82.8 87.3 <0.0001 74.5 78.9 0.04 ratio (%) (82.1;83.4) (86.6;88.0) (73.8;75.2) (78.1;79.1) Cardio48.7 40.6 <0.0001 37.7 33.4 <0.0001 pulmonary (48.0;49.4) (39.8;41.4) (37.1;38.3) (32.6;24.2) fitness (w/kg2) *Cholesterol 4.3 5.1 <0.0001 4.8 4.9 0.03 (3.3;6.1) (3.7;6.9) (3.1;6.5) (3.7;6.6) *HDL 1.3 1.5 <0.0001 1.5 1.9 <0.0001 (0.9;1.8) (1.0;2.2) (1.0;2.2) (1.2;2.8) *LDL 2.5 2.7 <0.0001 2.5 2.3 <0.0001 (1.5;4.2) (1.6;4.5) (1.4;4.2) (1.2;4.0) Asthma (%) 10.3 12.3 0.39 12.1 13.9 0.52 (7.7-13.4) (9.5-15.6) (9.2-15.6) (10.6-17.6) Asthma-like 25.9 25.6 0.98 34.3 28.1 0.006 symptoms (%) (21.9-30.1) (21.7-29.7) (29.9-39.0) (21.6-29.9) Smoking (%) 35.0 35.5 0.92 37.8 29.6 0.01 (30.6-39.5) (31.2-40.0) (33.3-42.5) (25.2-34.3) *Geometric mean. CRP levels were different between the sexes. The association between CRP and other characteristics in men and women are shown by CRP quintiles in table C. At age 20 years the CRP quintiles in women were: 1: (0.13-0.42), 2 (0.43-0.94), 3: (0.95-1.80), 4: (1.81-3.75), 5: (2.76-63.4) and in men were: 1: (0.10-0.23); 2: (0.24-0.38), 3:(0.39-0.62), 4: (0.63-1.39), 5: (1.40-41.7). At age 29 years the CRP quintiles in women were: 1: (0.13-0.46), 2 (0.47-0.99), 3: (1.00-1.91), 4: (1.92-3.97), 5: (3.9872.6); and in men were 1: (0.12-0.28); 2: (0.29-0.55), 3:(0.56-0.97), 4: (0.98-1.79), 5: (1.80-32.62). Table C: Association between FEV1, FVC, BMI and cardio-respiratory fitness at age 20 and 29 and their 95% confidence intervals (95%CI) according to high-sensitive CRP at age 20 and 29 in quintiles in both sexes. Pregnant women excluded CRP at age 20 in women CRP at age 20 in men 1quintile 2quintile 3quintile 4quintile 5quintile P 1quintile 2quintile 3quintile 4quintile 5quintile n=78 n=77 n=79 n=79 n=79 trend n=78 n=80 n=80 n=79 n=81 FEV1 percent of predicted at 20 years FEV1 percent of predicted at 29 years ∆ FEV1 (mL) 101.8 (99;104) 101.5 (99;104) 16.7 (-36;70) 101.0 (99;104) 101.1 (99;104) 211.3 (131;291) 80.6 (79.2;82.1) 99.9 (98;102) 98.8 (96;101) -80.3 (-137;-33) 99.7 (97;102) 99.1 (96;102) 109.0 (43;175) 81.0 (79.5;82.5) 97.9 (96;100) 99.2 (97;102) -7.9 (-63;47) 98.3 (96;100) 100.3 (98;103) 204.7 (125;284) 81.2 (79.5;82.9) 99.6 (97;102) 100.4 (97;104) -38.0 (-106:30) 100.8 (98;103) 102.0 (99;105) 146.7 (68;226) 80.8 (79.1;82.5) 97.8 (95;101) 96.8 (93;101) -57. 0 (-121;-6) 98.0 (95;101) 99.6 (95;104) 201.5 (101;302) 78.4 (76.9;79.9) 0.16 FEV1/FVC at age 29 77.8 (76.0;79.3) 77.2 (75.5;78.9) 77.2 (75.3;79.1) 76.3 (74.3;78.2) 75.3 (73.6;77.1) BMI at age 20 (kgm-2) 21.6 (21.0;22.2) 22.0 (21.3;22.6) 23.0 (22.2;23.8) 23.8 (22.9;24.8) ∆BMI (kgm-2) 2.02 (1.29;2.75) 1.62 (0.93;2.31) 1.83 (0.89;2.78) cardio-respiratory fitness at 20 (W.kg-1) ∆cardio-respiratory fitness (W.kg-1) 40.2 (38.8;41.7) -5.10 (-6.9;-3.3) 41.1 (39.5;42.7) -6.16 (-8.0;-4.3) 36.4 (35.1;37.6) -3.42 (-5.1;-1.8) 1quintile n=80 2quintile n=77 3quintile n=82 99.0 (97;101) 100.6 (99;103) 54.2 (3;105) 98.7 (96;101) 100.4 (98.1;102.7) 229.3 (151;307) 79.7 99.9 (97;103) 98.5 (96;101) -10.2 (-66;46) 100.0 (97;103) 99.4 (97.0;101.7) 180.3 (106;255) 81.6 101.4 (98;104) 100.0 (98;103) -7.3 (-57;42) 101.7 (99;104) 102.4 (99.9;104.9) 235.6 (149;322) 80.4 FVC percent of predicted at 20 years FVC percent of predicted at 29 years ∆FVC (mL) FEV1/FVC at age 20 (%) 99.3 (97;102) 101.7 (98.9;104.5) -14.9 (-80;50) 99.6 (97;102) 102.2 (99;105) 265.2 (154;377) 84.3 (82.5;86.1) 100.6 (98;103) 100.6 (97;104) -69.2 (-151;13) 100.7 (99;103) 101.3 (98;106) 181.9 (85;279) 84.6 (83.1;86.2) 98.3 (96;100) 101.2 (98;105) -22.3 (-104;59) 98.5 (96;101) 101.8 (99;105) 256.6 (145;368) 83.7 (82.3;85.3) 97.9 (96;100) 98.0 (95;101) -86.1 (-159;-13) 98.4 (96;101) 99.8 (97;103) 173.2 (80;266) 82.9 (80.8;85.0) 96.8 (94;99) 95.0 (92;98) -211.6 (-286;-137) 100.2 (98;102) 98.0 (95;101) -15.3 (-110;79) 83.1 (81.5;84.7) 0.22 0.10 80.7 (79.1;82.3) 80.3 (78.9;81.6) 79.6 (78.1;81.2) 79.3 (77.1;81.4) 78.0 (76.0;80.2) 0.20 24.3 (23.3;25.3) <0.0001 21.7 (21.2;22.2) 22.3 (21.7;22.8) 23.4 (22.7;24.2) 23.2 (22.5;23.9) 24.9 (23.9;26.0) <0.0001 1.90 (0.92;2.88) 2.27 (1.38;3.16) 0.86 2.36 (1.89;2.82) 3.31 (2.70;3.92) 2.49 (1.73;3.25) 2.49 (1.99;2.99) 2.61 (1.91;3.30) 0.18 36.4 (35.1;37.8) -2.79 (-4.9;-0.7) 34.7 (33.2;36.2) -3.69 (-6.0;-1.4) <0.0001 51.5 (49.9;53.0) -7.83 (-9.8;-5.9) 50.2 (48.8;51.6) -10.01 (-12.1;-7.9) 49.2 (47.4;51.0) -7.36 (-9.8;-5.0) 47.9 (46.2;49.7) -7.50 (-9.4;-5.6) 45.8 (43.9;47.8) -7.39 (-9.2;-5.6) <0.0001 4quintile n=79 5quintile n=81 P trend 1quintile n=85 2quintile n=89 3quintile n=92 4quintile n=88 5quintile n=90 P trend 100.7 (98;103) 99.1 (97;101) -97.9 (-157;-59) 101.1 (98;104) 101.7 (99.3;104.0) 135.4 (66;205) 81.6 96.9 (94;100) 95.0 (94;98) -118.8 (-176;-61) 96.8 (94;100) 96.9 (94.1;99.7) 94.5 (24;165) 78.5 0.18 98.6 (96;101) 100.5 (98;103) 15.9 (-47;78) 100.1 (98;103) 102.4 (101;105) 330.0 (243;417) 84.2 99.7 (97;102) 100.5 (98;103) -67.4 (-144;9) 98.9 (97;101) 100.4 (98;103) 208.9 (117;309) 83.6 100.1 (98;103) 99.9 (97;102) -89.0 (-161;-17) 101.4 (99;104) 101.2 (99;104) 128.6 (31;227) 83.5 100.1 (97;103) 99.5 (97;102) -119.4 (-200;-39) 99.7 (97;102) 99.8 (97;102) 168.5 (65;272) 83.4 97.2 (95;100) 95.8 (93;99) -174.2 (-251;-98) 100.3 (98;103) 98.1 (96;101) 12.3 (-92;117) 84.0 0.47 0.21 0.14 0.31 0.72 0.29 0.07 0.09 CRP at age 29 in women FEV1 percent of predicted at 20 years FEV1 percent of predicted at 29 years ∆FEV1 (mL) FVC percent of predicted at 20 years FVC percent of predicted at 29 years ∆FVC (mL) FEV1/FVC at 20 years P trend 0.01 0.002 0.51 0.25 <0.0001 0.58 0.30 CRP at age 29 in men 0.005 <0.0001 0.09 0.02 0.04 0.05 0.06 0.007 0.69 0.13 <0.0001 0.93 FEV1/FVC at 29 years BMI at age 29 (kgm-2) ∆BMI (kgm-2) cardio-respiratory fitness at 29 (W.kg-1) ∆cardio-respiratory fitness (W.kg-1) (77.9;81.5) 76.2 (74.8;77.7) 21.8 (21.3;22.3) 1.82 (1.0;2.6) 36.8 (35.2;38.4) -2.28 (-4.0:-0.6) (79.8;83.3) 77.3 (76.0;78.7) 22.5 (21.6;23.4) 1.39 (0.7;2.1) 35.0 (33.2;36.9) -4.23 (-6.7;-1.7) (78.8;80.0) 76.9 (75.5;78.3) 24.0 (23.3;24.8) 1.91 (0.9;2.9) 34.5 (32.9;36.2) -2.83 (-4.7;-1.0) (80.0;83.1) 77.3 (76.0;78.6) 25.5 (24.5;26.5) 1.38 (0.4;2.3) 32.5 (30.7;34.4) -4.98 (-7.0;-3.0) (76.9;80.0) 75.8 (74.5;77.2) 29.7 (28.4;31.0) 2.24 (1.3;3.2) 28.0 (26.5;29.6) -6.83 (-8.3;-5.4) 0.44 <0.0001 0.61 <0.0001 0.006 (83.0;85.1) 80.8 (79.5;82.1) 23.5 (23.0;24.0) 5.07 (3.4;6.7) 45.1 (43.5;46.7) -6.49 (-8.2;-4.7) (82.1;85.1) 79.8 (78.3;81.2) 24.7 (24.0;25.4) 5.95 (3.9;8.0) 42.6 (41.0;44.2) -6.94 (-8.9;-4.9) (81.9;85.2) 78.8 (77.3;80.3) 25.6 (25.0;26.2) 9.89 (7.9;11.9) 41.7 (39.9;43.4) -7.36 (-9.4;-5.3) (81.9;84.9) 78.4 (77.1;79.8) 26.2 (25.3;27.1) 10.46 (8.0;12.9) 38.7 (37.1;40.4) -9.79 (-11.7;-7.8) (82.3;85.8) 79.0 (77.6;80.5) 28.3 (27.1;29.5) 11.14 (9.1;13.2) 35.5 (33.5;37.5) -10.38 (-12.1;-8.7) ∆ FEV1: FEV1 at age 29– FEV1 at age 20; ∆FVC: FVC at age 29–FVC at age 20; ∆BMI: BMI at age 29–BMI at age 20; ∆cardiorespiratory fitness: ∆cardio-respiratory fitness at age 29-cardio-respiratory fitness at age 20. P for trend for Pearson Correlation. 0.13 <0.0001 <0.0001 <0.0001 0.008