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The Timing of Onset of Symptoms in People with Idiopathic Pulmonary Fibrosis: a UK General Population-Based Case-Control Study – Supplementary Material

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The Timing of Onset of Symptoms in People with Idiopathic Pulmonary Fibrosis: a UK General Population-Based Case-Control Study – Supplementary Material The timing of onset of symptoms in people with idiopathic pulmonary fibrosis: a UK general population-based case-control study – Supplementary material Thomas Hewson, BMedSci Tricia M McKeever, PhD Jack E Gibson, PhD Vidya Navaratnam, PhD Richard B Hubbard, DM John P Hutchinson, BMBS - Summary of patient population and Consort diagram of numbers of exclusions - Additional tables and figures for cough, consultations for heart failure, consultations for COPD, sensitivity analyses - Read codes for exclusions Summary of patient population Cases Controls n (%) n (%) Sex Male 1,301 (63.1) 4,580 (63.7) Female 761 (36.9) 2,607 (36.3) Age group <55 years 87 (4.2) 277 (3.9) 55-64 years 234 (11.4) 803 (11.2) 65-74 years 638 (30.9) 2,227 (31.0) 75-84 years 803 (38.9) 2,864 (39.9) >84 years 300 (14.6) 1,016 (14.1) Smoking category* Current 348 (18.3) 1,158 (18.2) Ex 810 (42.5) 1,923 (30.3) Never 746 (39.2) 3,269 (51.5) *based on latest record of smoking status prior to diagnosis A Consort diagram of patient selection is shown below. Controls were identified as a 4:1 incidence density sample, matched on age (year of age rather than age-band), sex and GP practice. Each case could have up to four possible controls. Consort diagram of patient selection 13,906 patients from THIN 2,801 cases 11,105 controls 1,415 patients excluded with inadequate length of data pre-diagnosis (already applied to cases 12,491 patients when selected) 2,801 cases 9,690 controls 96 patients excluded aged 40 or below 12,395 patients 2,774 cases 9,621 controls 153 cases excluded with use of amiodarone or methotrexate 12,242 patients 2,621 cases 9,621 controls 551 cases excluded with record suggesting alternative cause for pulmonary fibrosis 11,691 patients 2,070 cases 9,621 controls 2,442 further patients excluded: cases with no controls, or controls with no case (predominantly) 9,249 patients fibrosis 2,062 cases 7,187 controls Table e2 - Number of IPF cases and controls with consultations for cough within five one-year periods prior to diagnosis date Years pre- Number with Number (%) with Unadjusted OR Adjusted OR† p value diagnosis adequate records consultation for cough (95% CI) (95% CI) in each time period in each time period Control 7,187 728 (10.1) 1.00 1.00 0-1 Case 2,062 652 (31.6) 4.49 (3.95-5.12) 4.35 (3.79-4.98) <0.001 Control 6,660 591 (8.9) 1.00 1.00 1-2 Case 1,951 363 (18.6) 2.51 (2.16-2.91) 2.40 (2.06-2.81) <0.001 Control 6,187 529 (8.6) 1.00 1.00 2-3 Case 1,859 296 (15.9) 2.11 (1.80-2.48) 2.02 (1.71-2.38) <0.001 Control 5,799 433 (7.5) 1.00 1.00 3-4 Case 1,775 235 (13.2) 1.95 (1.64-2.33) 1.80 (1.51-2.16) <0.001 Control 5,351 370 (6.9) 1.00 1.00 4-5 Case 1,671 206 (12.3) 1.99 (1.65-2.40) 1.78 (1.47-2.17) <0.001 † Adjusted for smoking status Figure e1 - Number of consultations for cough for IPF cases (right panel) and single matched controls (left panel) over five years prior to diagnosis date 0 0 0 0 2 2 h h g g u u 0 o o c 5 c 1 h h t t i i w w s s n n o o i i t t a a 0 0 t t l l 0 0 u u 1 1 s s n n o o c c f f o o r r e e b b 0 m m 5 u u N N 0 0 -5 -4 -3 -2 -1 0 -5 -4 -3 -2 -1 0 Time prior to diagnosis (years) Time prior to diagnosis (years) Table e3 - Number of IPF cases and controls with consultations for heart failure within five one-year periods prior to diagnosis date Years pre- Number with Number (%) with Unadjusted OR Adjusted OR† p value diagnosis adequate records consultation for heart (95% CI) (95% CI) in each time period failure in each time period Control 7,187 94 (1.3) 1.00 1.00 0-1 Case 2,062 148 (7.2) 6.12 (4.63-8.09) 6.09 (4.43-8.37) <0.001 Control 6,660 73 (1.1) 1.00 1.00 1-2 Case 1,951 58 (3.0) 2.85 (2.00-4.06) 2.53 (1.73-3.69) <0.001 Control 6,187 35 (0.6) 1.00 1.00 2-3 Case 1,859 52 (2.8) 5.55 (3.54-8.71) 6.16 (3.73-10.18) <0.001 Control 5,799 47 (0.8) 1.00 1.00 3-4 Case 1,775 36 (2.0) 2.51 (1.60-3.94) 2.52 (1.56-4.05) <0.001 Control 5,351 33 (0.6) 1.00 1.00 4-5 Case 1,671 31 (1.9) 3.09 (1.85-5.16) 2.74 (1.57-4.77) <0.001 † Adjusted for smoking status Figure e2 - Number of consultations for heart failure for IPF cases (right panel) and single matched controls (left panel) over five years prior to diagnosis date 0 0 0 0 1 1 e e r r u u l l i i a a f f t t r r 5 5 a a 7 7 e e h h h h t t i i w w s s n n o o i i 0 0 t t 5 5 a a t t l l u u s s n n o o c c f f o o r r 5 5 e e 2 2 b b m m u u N N 0 0 -5 -4 -3 -2 -1 0 -5 -4 -3 -2 -1 0 Time prior to diagnosis (years) Time prior to diagnosis (years) Table e4 - Number of IPF cases and controls with consultations for COPD within five one-year periods prior to diagnosis date Years pre- Number with Number (%) with Unadjusted OR Adjusted OR† (95% p value diagnosis adequate records consultation for COPD (95% CI) CI) in each time period in each time period Control 7,187 136 (1.9) 1.00 1.00 0-1 Case 2,062 149 (7.2) 4.21 (3.30-5.37) 3.68 (2.83-4.79) <0.001 Control 6,660 120 (1.8) 1.00 1.00 1-2 Case 1,951 80 (4.1) 2.36 (1.76-3.16) 1.94 (1.43-2.63) <0.001 Control 6,187 97 (1.6) 1.00 1.00 2-3 Case 1,859 53 (2.9) 1.91 (1.35-2.69) 1.51 (1.05-2.17) 0.027 Control 5,799 92 (1.6) 1.00 1.00 3-4 Case 1,775 51 (2.9) 1.86 (1.30-2.65) 1.51 (1.05-2.19) 0.028 Control 5,351 68 (1.3) 1.00 1.00 4-5 Case 1,671 38 (2.3) 1.80 (1.20-2.71) 1.45 (0.94-2.23) 0.089 † Adjusted for smoking status Figure e3 - Number of consultations for COPD for IPF cases (right panel) and single matched controls (left panel) over five years prior to diagnosis date 0 0 0 0 1 1 D D P P O O 5 5 C C 7 7 h h t t i i w w s s n n o o i i t t a a t t 0 0 l l 5 5 u u s s n n o o c c f f o o r r e e b b 5 5 2 2 m m u u N N 0 0 -5 -4 -3 -2 -1 0 -5 -4 -3 -2 -1 0 Time prior to diagnosis (years) Time prior to diagnosis (years) Table e5 - Number of IPF cases and controls with consultations for breathlessness (SOB) within five one-year periods prior to diagnosis date (never smokers only) Years pre- Number with Number (%) with Odds ratio p value diagnosis adequate records consultation for SOB (95% CI) in each time period in each time period Control 1,389 72 (5.2) 1.00 0-1 Case 647 288 (44.5) 17.29 (12.01-24.89) <0.001 Control 1,280 53 (4.1) 1.00 1-2 Case 607 100 (16.5) 5.36 (3.65-7.86) <0.001 Control 1,183 45 (3.8) 1.00 2-3 Case 571 67 (11.7) 4.05 (2.64-6.22) <0.001 Control 1,107 23 (2.1) 1.00 3-4 Case 540 43 (8.0) 5.09 (2.90-8.92) <0.001 Control 1,026 15 (1.5) 1.00 4-5 Case 504 46 (9.1) 7.89 (4.15-15.01) <0.001 Table e6 - Number of IPF cases and controls with consultations for cough within five one-year periods prior to diagnosis date (never smokers only) Years pre- Number with Number (%) with Odds ratio p value diagnosis adequate records consultation for cough (95% CI) in each time period in each time period Control 1,389 144 (10.4) 1.00 0-1 Case 647 236 (36.5) 5.29 (4.06-6.90) <0.001 Control 1,280 97 (7.6) 1.00 1-2 Case 607 122 (20.1) 3.48 (2.54-4.76) <0.001 Control 1,183 109 (9.2) 1.00 2-3 Case 571 93 (16.3) 2.13 (1.55-2.91) <0.001 Control 1,107 84 (7.6) 1.00 3-4 Case 540 82 (15.2) 2.45 (1.75-3.44) <0.001 Control 1,026 72 (7.0) 1.00 4-5 Case 504 73 (14.5) 2.42 (1.69-3.48) <0.001 Table e7 - Number of IPF cases and controls with consultations for breathlessness (SOB) within five one-year periods prior to diagnosis date (excluding those with any record for heart failure or COPD prior to diagnosis date) Years pre- Number with Number (%) with Unadjusted OR Adjusted OR† p value diagnosis adequate records consultation for SOB (95% CI) (95% CI) in each time period in each time period Control 6,635 265 (4.0) 1.00 1.00 0-1 Case 1,590 628 (39.5) 19.95 (15.98-24.89) 19.00 (15.05-23.99) <0.001 Control 4,771 145 (3.0) 1.00 1.00 1-2 Case 1,500 184 (12.3) 5.17 (4.05-6.60) 4.77 (3.71-6.13) <0.001 Control 4,424 125 (2.8) 1.00 1.00 2-3 Case 1,425 118 (8.3) 3.26 (2.50-4.25) 2.91 (2.20-3.85) <0.001 Control 4,129 94 (2.3) 1.00 1.00 3-4 Case 1,359 83 (6.1) 3.00 (2.20-4.11) 2.73 (1.97-3.78) <0.001 Control 3,806 74 (1.9) 1.00 1.00 4-5 Case 1,279 73 (5.7) 3.35 (2.36-4.74) 3.17 (2.20-4.58) <0.001 † Adjusted for smoking status Table e8 - Number of IPF cases and controls with consultations for cough within five one-year periods prior to diagnosis date (excluding those with any record for heart failure or COPD prior to diagnosis date) Years pre- Number with Number (%) with Unadjusted OR Adjusted OR† p value diagnosis adequate records consultation for cough (95% CI) (95% CI) in each time period in each time period 0-1 Control 6,635 598 (9.0) 1.00 1.00 Case 1,590 492 (30.9) 5.20 (4.44-6.09) 5.09 (4.31-6.00) <0.001 1-2 Control 4,771 375 (7.9) 1.00 1.00 Case 1,500 246 (16.4) 2.44 (2.04-2.93) 2.42 (2.00-2.92) <0.001 2-3 Control 4,424 350 (7.9) 1.00 1.00 Case 1,425 195 (13.7) 1.88 (1.55-2.28) 1.84 (1.51-2.25) <0.001 3-4 Control 4,129 272 (6.6) 1.00 1.00 Case 1,359 149 (11.0) 1.78 (1.44-2.21) 1.71 (1.37-2.13) <0.001 4-5 Control 3,806 229 (6.0) 1.00 1.00 Case 1,279 136 (10.6) 1.92 (1.52-2.42) 1.71 (1.34-2.18) <0.001 † Adjusted for smoking status Read codes for exclusions 14G1.00 H/O: rheumatoid arthritis 14GC.00 History of connective tissue disease 2G27.00 O/E-hands-rheumatoid spindling 38DZ000 Disease activity score 28 joint in rheumatoid arthritis 43F1.00 Rheumatoid factor positive 66H..12 Rheumatism monitoring 66H..13 Rheumatoid arthrit.
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