<p> ONLINE DATA REPOSITORY</p><p>Morbidity and Mortality associated with the Restrictive Spirometric Pattern: a Longitudinal Study</p><p>Stefano Guerra; Duane L Sherrill; Claire Venker; Christina M Ceccato; Marilyn Halonen; Fernando D Martinez</p><p>1 Covariates from Survey 1</p><p>Pack-years at survey 1 (enrollment) were computed for each participant based on responses to a series of smoking questions. We categorized subjects as ever smokers if they had at least 1 pack-year at the enrollment survey.</p><p>Before lung function tests, weight and height were measured by the study nurses with standardized equipment. Body Mass Index (BMI) was computed as weight (kg) divided by the square of height (m) . Obesity was defined as a BMI  30 Kg/m2 and being overweight as a BMI  25 and < 30 Kg/m2.</p><p>Questionnaire information was collected in survey 1 on how many years of formal education participants had completed and on whether they had physician-confirmed asthma.</p><p>Skin prick tests were completed for five allergens: house dust; Bermuda grass; tree mix; weed mix; and Dematiaceae mold mix. Positive skin prick tests were defined as a wheal at least two mm larger than the control wheal for at least one of the five tested allergens.</p><p>Eosinophils were measured as percentages from stained slides and blood eosinophilia was defined as eosinophils > 4%.</p><p>2 Table E1. ICD-9 and ICD-10 codes used to classify main causes of death.</p><p>Main Cause of Death ICD-9 codes ICD-10 codes</p><p>Heart Disease 390-398, 402, 404, 410-429 I00-I09, I11, I13, I20-I51</p><p>Cancer 140-208, 238.6 C00-C97</p><p>Lung Cancer 162 C34</p><p>COPD 490-494, 496 J40-J47</p><p>Stroke 430-438 I60-I69</p><p>Diabetes 250 E10-E14</p><p>3 Table E2. Demographic and clinical characteristics at enrollment of subjects included in each of the eight longitudinal spirometric patterns. Total N is 1798, unless otherwise specified. </p><p>Underlying Cause of Death</p><p>Consistent Recurrent Inconsistent Incident Recurrent Inconsistent Incident Mixed Normal Restrictive Restrictive Restrictive Obstructive Obstructive Obstructive Restr/Obstr P * (N = 913) (N = 69) (N = 62) (N = 126) (N = 155) (N = 54) (N = 304) (N = 115)</p><p>Age in years: mean 44  17 62  15 55  17 54  16 60  13 55  17 51  15 64  11 N/A  SD</p><p>Sex: % female 59.1 76.8 69.4 56.3 38.7 59.3 48.4 67.0 <0.001</p><p>Obesity (n = 1738): % with BMI  30 6.3 15.4 16.7 10.0 3.3 9.6 7.2 12.5 0.009 Kg/m2</p><p>Ever smoking (n = 1796): % with ≥ 1 48.4 37.7 50.0 54.0 82.6 73.6 66.3 58.3 <0.001 pack-year</p><p>Physician confirmed asthma 6.4 10.3 4.8 11.1 33.5 13.0 13.8 21.7 <0.001 (n = 1796): positive %</p><p>Eosinophilia (n = 7.1 6.3 10.9 3.2 14.0 14.0 10.7 13.8 0.01 1363): positive %</p><p>Total serum IgE in IU/ml (n = 1620): 25.2 19.3 29.1 22.8 52.2 25.7 34.7 23.3 <0.001 geometric mean</p><p>* P value for the comparison across the eight groups after adjustment for age.</p><p>4 Table E3. Sex-, age-, and BMI-adjusted Mortality Hazard Ratios and corresponding 95% Confidence Intervals associated with each of the longitudinal spirometric patterns. Total N is 1738. </p><p>Underlying Cause of Death</p><p>All-cause Heart Disease Cancer Lung Cancer COPD Stroke Diabetes adjHR (95 CI) adjHR (95% CI) adjHR (95% CI) adjHR (95% CI) adjHR (95% CI) adjHR (95% CI) adjHR (95% CI)</p><p>Consistent Normal reference reference reference reference reference reference reference (N = 883)</p><p>Recurrent Restrictive 1.7 (1.3 – 2.3) 2.1 (1.4 – 3.2) 1.0 (0.4 – 2.2) 0.7 (0.1 – 5.1) 2.1 (0.3 – 17.8) 2.6 (1.0 – 6.7) 8.2 (3.0 – 22.0) (N = 65)</p><p>Inconsistent Restrictive 1.9 (1.4 – 2.7) 2.8 (1.8 – 4.4) 1.4 (0.7 – 3.0) 1.5 (0.3 – 6.3) N/A 3.9 (1.4 – 11.0) 5.9 (1.9 – 18.9) (N = 60)</p><p>Incident Restrictive 1.3 (1.0 – 1.6) 1.7 (1.2 – 2.5) 0.8 (0.4 – 1.4) 1.3 (0.5 – 3.4) 3.9 (1.1 – 13.9) 0.5 (0.1 – 2.4) 2.9 (1.0 – 8.5) (N = 120)</p><p>Recurrent Obstructive 2.5 (2.0 – 3.0) 2.1 (1.5 – 3.1) 1.3 (0.8 – 2.2) 2.9 (1.4 – 6.0) 42.2 (17.5–101.9) 6.0 (2.9 – 12.8) 5.7 (2.1 – 15.9) (N = 153)</p><p>Inconsistent Obstructive 1.2 (0.9 – 1.7) 1.4 (0.8 – 2.4) 0.7 (0.3 – 1.8) N/A 4.6 (0.9 – 22.7) 1.5 (0.4 – 6.7) 0.9 (0.1 – 7.2) (N = 52)</p><p>Incident Obstructive 1.0 (0.8 – 1.2) 1.1 (0.8 – 1.6) 0.8 (0.6 – 1.2) 0.6 (0.3 – 1.4) 3.7 (1.3 – 10.1) 1.7 (0.8 – 3.8) 2.3 (1.0 – 5.4) (N = 293)</p><p>Mixed Restrict/Obstruct 1.4 (1.1 – 1.8) 1.7 (1.2 – 2.4) 0.6 (0.3 – 1.2) 1.1 (0.4 – 3.2) 11.5 (4.2 – 31.3) 1.0 (0.3 – 3.1) 4.6 (1.9 – 11.5) (N = 112)</p><p>N events 975 370 188 57 75 61 53* * Because only 17 subjects had diabetes identified as underlying cause of death, in Cox models for diabetes mortality events were defined as “deaths with diabetes indicated as either underlying cause of death or co-existing condition on the death certificate”. 5 Significant associations are reported in bold font. </p><p>6 Figure E1. Unadjusted survival curves associated with the six longitudinal spirometric patterns.</p><p>C-Norm: Consistent Normal</p><p>Rec-Rest: Recurrent Restrictive</p><p>Incon-Rest: Inconsistent Restrictive</p><p>Rec-Obst: Recurrent Obstructive</p><p>Incon-Obst: Inconsistent Obstructive</p><p>Mixed: Mixed Restrictive/Obstructive</p><p>7 8</p>