Table 1.

Characteristics of the Studies Included in the Meta-Analysis

Study, year	Design	Patients (Number)		Age (Mean)		Male (%)		Current Smoker (%)		Body mass Index (kg/m2)		Triple Inhaled Therapy (%)		Pre-Bronchodilator FEV1, % Predicted (Mean)		Population	Primary Outcome
Dose escalation strategy
		DE	CV	DE	CV	DE	CV	DE	CV	DE	CV	DE	CV	DE	CV
Hwang, 201513	Single-center, retrospective observational trial	59	26	69.3	71.9	100	80.8	32.2	11.5	20.9	20.1	49.2	11.5	NA	NA	Severe and very severe COPD and chronic bronchitis symptoms	The discontinuation rate and the incidence of any AEs
Park, 201914	Single-center, randomized, prospective, open-label, single-blind study	27	28	70.5	69.8	96.3	96.4	3.7	17.9	21.2	22.2	63.0	92.9	34.6	34.9	Severe and very severe COPD, smoking history, exacerbation history in previous year, and chronic bronchitis symptoms	The discontinuation rate
Watz, 201915	Multicenter, double-blind, Phase III randomized trial	441	443	64.2	64.6	72.6	76.3	48.3	44.2	26.4	26.4	NA	NA	NA	NA	Severe and very severe COPD, smoking history, exacerbation history in previous year, and chronic bronchitis symptoms	The discontinuation rate
Low-dose strategy
		LD	CV	LD	CV	LD	CV	LD	CV	LD	CV	LD	CV	LD	CV
Joo, 201816	Single-center, retrospective review of medical records	91	178	74.5	71.6	93.4	93.8	17.2	11.4	22.9	21.9	NA	NA	45.7	42.5	COPD	The discontinuation rate and the incidence of any AEs
Rabe, 200517	Multicenter, double-blind, Phase III randomized trial	576	555	65	64	73	74	46	46	26	26	NA	NA	50	51	Moderate and severe COPD and smoking history	Postbronchodilator FEV1 and St. George’s respiratory questionnaire total score

Abbreviations: AE, acute exacerbation; COPD, chronic obstructive pulmonary disease; CV, conventional; DE, dose-escalation; FEV1, forced expiratory volume in one second; LD, low dose; NR, not available.