Table S2.

Summary of key study design information from RCTs detailing COPD exacerbation rates in Japan^10–14

Study	Study characteristics	Study center(s), recruitment period	Inclusion criteria	Definitions of COPD exacerbation
Furumoto et al (2008)10	Open-label, randomized, controlled study in patients with chronic lung disease	• Thirteen hospitals in Kyushu and Okinawa district • November 2001–April 2002	• Patients with chronic lung disease including COPD, sequelae of pulmonary tuberculosis • Previous exacerbations	Two of the three defined respiratory symptoms existed or when one of these and one additional symptom, such as a fever without any other causes or increased cough, was present
Sasaki et al (2009)11	Randomized, 12-month, observer-blind, controlled trial	• One University Hospital and three city hospitals in Miyagi prefecture • October 2005–March 2007	• Patients with COPD • No exacerbation criteria for inclusion or exclusion	Acute and sustained worsening of COPD symptoms requiring changes to regular treatment
Fukuchi et al (2011)12	Randomized, double blinded, placebo controlled study (UPLIFT)	• Multicenter study	• Patients with COPD • Age ≥40 years • Post-FEV1% pred: ≤70% • Post-FEV1/FVC: ≤70% • Smoking history ≥10 pack-years • No exacerbation 4 weeks before screening	An increase in or the new onset of more than one respiratory symptom (cough, sputum, sputum purulence, wheezing, or dyspnea) lasting 3 days or more and requiring treatment with an antibiotic or a systemic corticosteroid
Fukuchi et al (2016)13	Randomized, double-blind, placebo-controlled parallel trial	• Multicenter study across 47 medical institutions in Japan • August 2012–January 2015	• Patients with COPD • Age: ≥20 to <85 years • Post-FEV1% pred: <80% • Post-FEV1/FVC: <70% • ≥1 exacerbations in the previous year • No exacerbation 7 days prior to drug administration	Worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness) leading to a change in medication
Jones et al (2016)14	Randomized, controlled, 24-week study assessing exacerbations using EXACT and physician diagnosis (COSMOS-J study)	• Multicenter study • February 2013–September 2015	• Patients with COPD (GOLD) • Age 40–80 years • Post-FEV1/FVC: <70% • Current or ex-smokers (>10 pack-years)	Physician diagnosis of exacerbation and evaluation of EXACT diary

Note: All data reported as mean±SD unless otherwise stated.

Abbreviations: EXACT, Exacerbations of Chronic Pulmonary Disease Tool; GOLD, Global initiative for chronic Obstructive Lung Disease; pred, predicted.