Figures
- Figure 1
Study flow diagram with the use of the official PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow chart.
- Figure 2
Occurrence of morning symptoms. a) In all studied chronic obstructive pulmonary disease (COPD) patients. b) Occurrence of different morning symptoms in COPD patients experiencing symptoms. c) Symptomatic COPD patients who report the morning as worst time of the day for that symptom (results for at waking and the rest of the morning are combined). #: Classification of airflow limitation according to Global initiative for Chronic Obstructive Lung Disease (GOLD); ¶: “severe” was defined in this study as regular use of COPD medication plus a third level of breathlessness or above using the Medical Research Council dyspnoea scale and one or more exacerbations in the preceding 12 months +: in all included COPD patients.
Tables
- 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.
- Table 2
Influence of morning symptoms on physical activity
First author [ref.] Stage of COPD Definition of the morning Method to evaluate morning symptoms and activity limitations Physical activity limitation associated with morning symptoms Self-reported limitations Conclusion Bateman [15] Moderate to severe As described in the EMSCI and NiSCI Questionnaires (EMSCI and NiSCI) for the patients 90.6% of all patients with COPD NA Most COPD patients with morning symptoms considered that their symptoms affect their morning activities Stephenson [20] All stages Time of getting out of bed and approximately 11:00 h A 30-min questionnaire for patients about morning symptoms and the impact on morning activities 60.4%# Work§ More than half of patients considered that their symptoms affect their morning activities Miravitlles [16] All stages Time of getting out of bed and approximately 11:00 h Patients filled out a Night-time, Morning and Daytime Symptoms of COPD questionnaire, developed by the sponsor Patients who are sedentary experience more symptoms in any part of the day (also in the morning); p<0.05 NA In each part of the day (morning, daytime, night time) there was an significant association between symptoms and a low physical activity level O’Hagan [19] All stages Not defined Online questionnaire consisting predefined questions for patients 34–79%# have problems with common morning activities; 56–70%# with more physically demanding activities Self-care, domestic activities and work§ Morning symptoms can severely compromise patients’ ability to perform, even simple tasks. Half of the patients had made changes to their morning routines Roche [17] All stages Symptoms that are present when getting up in the morning, thus those symptoms present on waking, rather than those persisting through the morning Questionnaires with predefined questions. Physicians gave information about severity grade of the symptoms; patients about the impact on daily life Impact on normal activities was higher in those with morning symptoms (3.96 versus 3.29+; p=0.007) Self-care and work§ Impact on daily activities was significantly higher in patients with morning symptoms than without Kim [18] Severe to very severe Not defined Patients filled out the CSQ. Those who reported morning symptoms, subsequently completed the MAQ 57% of all patients with COPD Self-care and domestic activities§ 57% of COPD patients had considerable impact on their morning activities Kessler [22] Severe to very severe In the morning, after waking up and later in the morning Interview over the telephone. Predefined questions developed by the sponsor 35.4–41.0% of patients that experience any symptom felt that morning symptoms affect morning activities Self-care§ There was an association between morning symptoms and the impact on activities Partridge [21] All stages From the time they woke up until they were dressed, had breakfast and were ready to start the day Predefined questions were answered by the patient by an internet interview 37% of all COPD patients and 73% of the severe¶ COPD patients regarded problems associated with morning routines as bothersome. 74% of all COPD patients and 96% of the severe¶ patients reported that they took longer to complete their morning routines Self-care and domestic activities§ Many patients considered the impact of COPD on morning activities to be extensive COPD: chronic obstructive pulmonary disease; CSQ: clinical symptom questionnaire; EMSCI: early-morning symptoms of COPD instrument; MAQ: morning activity questionnaire; NiSCI: night-time symptoms of COPD instrument. #: in patients with morning symptoms; ¶: “severe” was defined in this study as regular use of COPD medication plus a third level of breathlessness or above using the Medical Research Council dyspnoea scale and one or more exacerbations in the preceding 12 months; +: measured on a 7-point Likert scale of 0=no impact to 7=constant impact; §: more detailed information in supplementary table S3.
- Table 3
Impact of medication on morning symptoms and physical activity
First author [ref.] Medication Morning symptoms Physical activity limitation associated with morning symptoms Effect medication on morning symptoms Effect intervention/medication on physical activity limitation due to morning symptoms Bateman [15] Aclidinium bromide/formoterol 94.4% of all patients 90.6% of all patients FDC 400/12 µg on severity scores: −0.23 units (−17.0%); aclidinium 400 µg: −0.14 units (−10.7%); formoterol 12 µg: −0.17 units (−13.6%) p<0.0001 versus aclidinium and p<0.01 versus formoterol#. Individual morning symptoms: p<0.05 versus aclidinium for cough and difficulty bringing up phlegm, and versus both monotherapies for wheezing and shortness of breath Improvements in limitation of early morning activities: p<0.05 versus aclidinium and p<0.05 versus formoterol O’Hagan [19] Patients were allowed to select any of their applied medication Morning symptoms was an inclusion criterion in this study Impact on normal activities was higher in those with morning symptoms compared to those without (3.96 versus 3.29; p<0.007) 79% of COPD patients who feel medications provides relief from symptoms in the morning enough 33% of patients considered “improvement of ability to carry out morning activities” a key treatment goal. 21% of patients feel medication provides improvement in the ability to carry out morning activities Kim [18] No standard treatment for COPD was defined by the study protocol 57% of all patients 57% of all patients LAMA and ICS plus LABA were used significantly less frequent in patients with morning symptoms. LAMA was a preventive factor for the presence of morning symptoms Severity of all morning activities were significantly reduced after 2 months follow-up COPD: chronic obstructive pulmonary disease; FDC: fixed-dose combination; LAMA: long-acting muscarinic antagonists; ICS: inhaled corticosteroids; LABA: long-acting β2-agonist. #: symptom severity measured on a score from 0 (no symptoms) to 4 (very severe symptoms).
Supplementary Material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Supplementary material ERR-0033-2016_Supplement
Supplementary table S2 ERR-0033-2016_Supplementary_table_S2
Supplementary table S3 ERR-0033-2016_Supplementary_table_S3
