Volume 149, Issue 5, Pages 1181-1196 (May 2016) A Systematic Review With Meta-Analysis of Dual Bronchodilation With LAMA/LABA for the Treatment of Stable COPD  Luigino Calzetta, PhD, Paola Rogliani, MD, Maria Gabriella Matera, MD, Mario Cazzola, MD  CHEST  Volume 149, Issue 5, Pages 1181-1196 (May 2016) DOI: 10.1016/j.chest.2016.02.646 Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 1 Preferred reporting items for systematic reviews and meta-analyses flow diagram for identifying studies included in the meta-analysis on the influence of long-acting muscarinic antagonist/long-acting β2-agonist combinations vs at least one monocomponent, on trough FEV1, transitional dyspnea index, and St. George’s Respiratory Questionnaire score in COPD patients. CHEST 2016 149, 1181-1196DOI: (10.1016/j.chest.2016.02.646) Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 2 Overall forest plot meta-analysis of the impact of long-acting muscarinic antagonist/long-acting β2-agonist combinations on trough FEV1 and subgroup analysis performed on lower and higher doses of aclidinium (A), formoterol (F), glycopyrronium (G), indacaterol (I), olodaterol (O), tiotropium (T), umeclidinium (U), and vilanterol (V). Because of the scarce number of studies, the subgroup analysis of the glycopyrronium/formoterol combination was performed vs glycopyrronium and formoterol administered as monocomponents. The doses of medications are expressed as micrograms and results as the mean difference (mL) vs monocomponents. CHEST 2016 149, 1181-1196DOI: (10.1016/j.chest.2016.02.646) Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 3 Forest plot meta-analysis of the impact of approved doses of long-acting muscarinic antagonist/long-acting β2-agonist combinations on trough FEV1. Data are expressed as mean difference (mL) vs monocomponents. See Figure 2 legend for expansion of abbreviations. CHEST 2016 149, 1181-1196DOI: (10.1016/j.chest.2016.02.646) Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 4 Forest plot meta-analysis of the impact of long-acting muscarinic antagonist/long-acting β2-agonist combinations on TDI (A) and SGRQ (B). Data are expressed as mean difference vs monocomponents. SGRQ = St. George's Respiratory Questionnaire; TDI = transitional dyspnea index. See Figure 2 legend for expansion of other abbreviations. CHEST 2016 149, 1181-1196DOI: (10.1016/j.chest.2016.02.646) Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 5 Overall (A) and approved doses (B) forest plot meta-analyses of the impact of long-acting muscarinic antagonist/long-acting β2-agonist combinations on cardiac adverse events in COPD patients. Data are expressed as OR vs monocomponents. See Figure 2 legend for expansion of abbreviations. CHEST 2016 149, 1181-1196DOI: (10.1016/j.chest.2016.02.646) Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 6 Funnel plots (left panels) and graphical representation of Egger test (right panels) for the impact on trough FEV1 of approved doses of A/F 400/12 μg (A, B); G/I 15.6/27.5 μg and 50/110 μg (C, D); T/O 5/5 μg (E, F); and U/V 62.5/25 μg (G, H) combinations vs monocomponents. *Y-intercept significantly (P < .1) different from zero. SND = standard normal deviation. See Figure 2 legend for expansion of other abbreviations. CHEST 2016 149, 1181-1196DOI: (10.1016/j.chest.2016.02.646) Copyright © 2016 American College of Chest Physicians Terms and Conditions

Figure 7 Funnel plots (left panels) and graphical representation of Egger test (right panels) for the impact on cardiac adverse events of approved doses of A/F 400/12 μg (A, B), G/I 15.6/27.5 μg and 50/110 μg (C, D), T/O 5/5 μg (E, F), and U/V 62.5/25 μg (G, H) combinations vs monocomponents. See Figure 2 and 6 legends for expansion of abbreviations. CHEST 2016 149, 1181-1196DOI: (10.1016/j.chest.2016.02.646) Copyright © 2016 American College of Chest Physicians Terms and Conditions