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1 Supplementary Online Content Deslée G, Mal H, Dutau H, et al; REVOLENS Study Group. Lung volume reduction coil treatment vs usual care in patients with severe emphysema: the REVOLENS randomized clinical trial. JAMA. doi: /jama etable 1. Unit Costs Used for the Economic Evaluation etable 2. Relationships Between Heterogeneous/Homogeneous Emphysema and Changes at 6 Months in the 6-Minute Walk Test, Lung Function, and Quality of Life in the Coil Group etable 3. Lung Volume Reduction Coil Procedures etable 4. Non-Serious Adverse Events ebox. Inclusion and Exclusion Criteria efigure 1. Step-by-Step Coil Treatment Procedure in a Single Representative Patient (62 Year-Old Man, 26% FEV 1 and Homogeneous Emphysema) efigure 2. Lung Volume Reduction Coil (BTG/PneumRx) With a Fully-Deployed Length of 125 mm efigure 3. Chest X Ray Post Bilateral Coil Treatment From a Single Representative Patient efigure 4A. Changes at 6 Months From Baseline in the 6-Minute Walk Test in the Coil Group (Blue) and Usual Care Group (Red) for Each Individual efigure 4B. Changes at 12 Months From Baseline in the 6-Minute Walk Test in the Coil Group (Blue) and Usual Care Group (Red) for Each Individual efigure 5A. Incremental Cost and Effectiveness of Coil Treatment Compared to Usual Care: Cost Effectiveness Plan for Incremental Costs and Incremental Quality Adjusted Life Years (QALYs) at 12 Months efigure 5B. Cost-Effectiveness Acceptability Curve Showing the Probability That Coil Treatment Is Cost-Effective Compared to Usual Care This supplementary material has been provided by the authors to give readers additional information about their work.

2 etable 1. Unit Costs Used for the Economic Evaluation Coil (per unit) Catheter Unit cost 1, Source Manufacturer OR /hour 239 Hospital accounting Staff time /hour Range: Ministry of health Transportation Range: National tariffs CT scanner 25 National tariff Chest X-ray 21 National tariff Consultations Range: National tariff Monitoring tests Range: National tariff Home oxygen /week 77 National tariff Unit cost US$ Source Coil (per unit) Catheter 1,8891,114 Manufacturer OR US$/hour 317 Hospital accounting Staff time US$/hour Range: Ministry of health Transportation Range: National tariffs CT scanner 33 National tariff Chest X-ray 28 National tariff Consultations Range: National tariff Monitoring tests Range: National tariff Home oxygen US$/week 102 National tariff Costs were drawn from the hospital cost study undertaken yearly by the French Ministry of Health and which records actual costs for all patients admitted to a sample of hospitals based on a combination of itemized resources and activity-based costing. Cost of the medical devices was the manufacturer's price. Staff costs were estimated from gross salaries and operating room costs from the hospital accounting systems. Costs of hospital stays were estimated using the average national cost of each patient s DRG (diagnosis-related group), adjusted for actual length of stay (LOS) and resources consumed during hospitalization. Re-hospitalizations and non-hospital costs were based on tariffs. Costs are in US$, US$1 = in 2014in purchasing power parity (OECD Purchasing parity power for

3 etable 2. Relationships Between Heterogeneous/Homogeneous Emphysema and Changes at 6 Months in the 6-Minute Walk Test, Lung Function, and Quality of Life in the Coil Group Changes from Heterogeneous a Homogeneous Difference (CI P value baseline (n=17) (n=33) 95%) 6-minute walk +28 (-18;+75) +13 (-17;+43) 15 (-37 to +67).84 test, m % change (-7.1;+28.8) +8.7 (-5.3;+22.7) 2.1 (-19.1 to +23.3).88 FEV 1, L ( (-0.12 to ;+0.11) (+0.01;+0.14) +0.05) % change +6 (-1;+15) +10 (+3;+18) -4 (-14 to +6).55 FVC, L ( (-0.36 to ;+0.41) (+0.08;+0.49) +0.19) % change +14 (+2;+23) +15 (+5;+24) -2 (-15 to +12).99 RV, L (-0.80;+0.01) (-0.80;-0.30) 0.15 (-0.29 to ) % change -6 (-12;-1) -9 (-13;-5) 3 (-4 to +9).43 SGRQ, pts b -12 (-19; -6) -10 (-17;-3) -2 (-11 to +7).83 Values are shown as mean (CI 95%). P value (two-sided testing). a A visual score from 0 to 4 was assigned to each lobe, based on the extent of tissue destruction, where 0= no emphysema, 1= 1 to 25% emphysematous, 2= 26 to 50%, 3= 51 to 75%, and 4= >75%. Emphysema was classified as heterogeneous in there was a difference >1 point between ipsilateral lobes. b The Saint George s Respiratory Questionnaire has 3 component domains (impact, activity, symptoms) measuring quality of life. Higher scores indicate worse quality of life. NOTES: FEV 1 =forced expiratory volume in one second; FVC=forced vital capacity; RV=residual volume; SGRQ=St. George s Respiratory Questionnaire.

4 etable 3. Lung Volume Reduction Coil Procedures Number of procedures, No. Total number of coils, No. Number of coils per procedure, No. 1 st coil treatment (n=50) 2 nd coil treatment (n=47) Number of coils per size 100 mm, No. (%) 125 mm, No. (%) Location of the coils Right upper lobe, No. (%) Left upper lobe, No. (%) Right lower lobe, No. (%) Left lower lobe, No. (%) Middle lobe, No. (%) Procedure time, min 1 st coil treatment, min 2 nd coil treatment, min (1) 9.7 (1) 555 (57.8) 405 (42.2) 406 (42.3) 350 (36.5) 123 (12.8) 81 (8.4) 0 (0) 56 (18) 51 (16) Time between 1 st and 2 nd coil treatment, days 53 (17) Values are shown as mean (Standard Deviation), or number (No.) and percentage (%) when indicated.

5 etable 4. Non-Serious Adverse Events Coil treatment (n=50) 30 days >30 days- 12 months Usual care (n=50) 12 months COPD exacerbation a 53 Mild hemoptysis Thoracic pain 9 3 b 6 Pneumonia Other pulmonary events c Cardiovascular Other non-pulmonary events Total Data are displayed as number of events. AEs are stratified by occurrence within 30 days or after 30 days to 12 months post treatment a. Two COPD exacerbation occurred before any coil treatment and were included in the > 1 month coil treatment. b. One thoracic pain occurred before any coil treatment, and was included in the >30 days-12 months Coil. c. In the coil group: 30 days: cough (n=3), bronchospasm (n=1), dyspnea (n=1), bacteria on bronchial aspiration pre-coil treatment without respiratory symptoms (n=1); >30 days: dyspnea (n=1), pulmonary nodule (n=1). In the SOC group: cough (n=1), dyspnea (n=1).

6 ebox. Inclusion and Exclusion Criteria Inclusion Criteria: Bilateral emphysema on Chest CT Scan Post bronchodilator FEV 1 < 50 % predicted Total Lung Capacity > 100 % predicted Residual Volume > 220 % predicted Dyspnea score between 2 and 4 based on the mmrc scale Stopped cigarette smoking for more than 8 weeks Pulmonary rehabilitation within the previous twelve months Consent form signed Covered by Medical Insurance Exclusion Criteria: Post bronchodilator FEV 1 < 15% predicted Post-bronchodilator change in FEV 1 > 20% Severe recurrent respiratory infections requiring more than 2 hospitalization stays within the past twelve months COPD exacerbation requiring hospital stay within 3 months Pulmonary Hypertension (Pulmonary systolic pressure >50 mmhg on cardiac echo) Patient unable to perform a 6-min walking test in room air (no restriction on distance) Giant bulla of more than 1/3 of the lung field on Chest CT Strictly homogeneous emphysema on Chest CT (investigator interpreted) Clinically significant bronchiectasis Past history of lobectomy, lung volume reduction surgery, lung transplantation Any extrapulmonary diseases compromising survival or evaluation within the protocol (severe cardiac disease, severe renal insufficiency, cancer ) Lung carcinoma or pulmonary nodule on CT scan requiring Chest CT scan follow-up Contraindication to general anesthesia Oral anticoagulant treatment with vitamin K antagonists Allergy to nitinol Inclusion in another study assessing respiratory treatments Patient protected by the law

7 e-figure 1. Step-by-Step Coil Treatment Procedure in a Single Representative Patient (62 Year-Old Man, 26% FEV 1 and Homogeneous Emphysema)

8 efigure 2. Lung Volume Reduction Coil (BTG/PneumRx) With a Fully-Deployed Length of 125 mm

9 efigure 3. Chest X Ray Post Bilateral Coil Treatment From a Single Representative Patient Ten coils were placed in each right and left upper lobes in a 56 year-old male with 27% FEV 1, 265 % residual volume, and homogeneous emphysema.

10 efigure 4A. Changes at 6 Months From Baseline in the 6-Minute Walk Test in the Coil Group (Blue) and Usual Care Group (Red) for Each Individual Changes in the 6-minute walk test (meters) from baseline Subject (n=44 in each group)

11 efigure 4B. Changes at 12 Months From Baseline in the 6-Minute Walk Test in the Coil Group (Blue) and Usual Care Group (Red) for Each Individual Cahnges in the 6-minute walk test (meters) from baseline Subject (Coil group, n=43; Usual care group, n=44)

12 efigure 5A. Incremental Cost and Effectiveness of Coil Treatment Compared to Usual Care: Cost Effectiveness Plan for Incremental Costs and Incremental Quality Adjusted Life Years (QALYs) at 12 Months Difference in mean total cost (US$) Difference in mean QALYs The scatter plot has 98.8 % of the replications to the right of the vertical axis and above the horizontal axis, indicating higher cost for greater effectiveness of coil treatment. The average study-based ICER belongs to the 95% confidence interval bootstrap [663,496; 1,327,212]..

13 efigure 5B. Cost-Effectiveness Acceptability Curve Showing the Probability That Coil Treatment Is Cost-Effective Compared to Usual Care Probability cost-esffective Willingness to pay (US$) per QALY gained Costs are in US$, US$1 = in 2014 in purchasing power parity (OECD Purchasing parity power for