Table 1

Overall conclusion and quality of included studies

First author [ref.]	Study design	Participants' characteristics at baseline	Overall conclusion	Quality
Bateman [15]	Pooled analysis from two phase III double-blind, randomised, parallel-group active- and placebo-controlled studies	n=3394; age ≥40 years; stable moderate-to-severe COPD	Aclidinium/formoterol 400/12 μg significantly improves 24-h symptom control compared with placebo or aclidinium or formoterol alone. The frequency of exacerbations was also reduced compared with placebo	17/25^#,¶
Stephenson [20]	Cross-sectional survey study	n=752; 60.5% female; age ≥40 years; COPD plus at least one pharmacy claim for maintenance COPD medication	The majority of the patients with night time or morning symptoms experience at least three distinct types of symptoms a week. Approximately half of them consider their symptoms to be moderate to severe. They felt that their symptoms had impact on their sleep and morning activities, and they were anxious	18/22⁺
Miravitlles [16]	Observational study	n=727; 34.2% female; age ≥40 years; current of former smokers; stable mild-to-very-severe COPD	More than half of COPD patients experience symptoms throughout the whole day. There was a significant association between night time, early morning and daytime symptoms. In each period, symptoms were associated with worse patient-reported outcomes	18/22⁺
O’Hagan [19]	Observational study	n=811; 44% female; age 30–70 years; COPD diagnosed by a physician; at least one morning symptom	Morning symptoms can severely interfere with COPD patients’ ability to perform tasks throughout the day. Half of the patients had made changes in their morning routines	15/22⁺
Roche [17]	Cross-sectional observational study	n=1489; 34.3% female; age ≥40 years; with a history of smoking, airflow obstruction and the diagnosis of COPD	39.8% of the COPD patients experience morning symptoms. Morning symptoms are associated with poorer health status, impaired daily activities and increased risk of exacerbations	16/22⁺
Kim [18]	Prospective non-interventional and observational study	n=133; 5.3% female; age >45 years; with a history of smoking; stable severe-to-very severe COPD	57% of COPD patients experience limitation in their activities due to morning symptoms. These patients also have more prevalent and severe COPD symptoms	14/22⁺
Kessler [22]	Cross-sectional observational study	n=2441; 21.5% female; age >45 years; with a history of smoking; stable severe-to-very severe COPD	Patient-perceived COPD symptoms vary over the day and the week, and have impact on activities. The morning was considered the worst time of the day	16/22⁺
Partridge [21]	Quantitative internet interviews	n=803; 44% female; age ≥40 years; with a history of smoking; all stages of COPD	COPD are worst during the morning. Many patients consider the impact of COPD on morning activities to be extensive	17/22⁺

COPD: chronic obstructive pulmonary disease; ^#: CONSORT (Consolidated Standards of Reporting Trials) was used as a tool to assess quality; ^¶: pooled analysis from two studies; ⁺: STROBE (Strengthening the Reporting of Observational studies in Epidemiology) was used as a tool used to assess quality.