1. Publications
Association between morning symptoms and physical activity in COPD: a systematic review.
van Buul et al., Eur Respir Rev 2017.
NS Approval ID XL-1015-RD05/2017-VA
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2. Context
Methods
Results
Conclusion
Discussion
Duaklir Genuair

3. CONTEXT
Morning symptoms are common in COPD and associated with physical activity limitations3
Although maintaining physical activity is key in COPD management, factors associated with patients’ capability to engage in physical activity are not well established1,2.
Morning symptoms are common in COPD. Many COPD patients consider the morning as most troublesome part of the day, in which they experience more symptoms and physical activity limitations4.
Spina et al., Thorax. 2017; 0: 1-8. doi: /thoraxjnl
Gimeno-Santos et al., Thorax. 2014; 69: 731-9
van Buul et al., Eur Respir Rev. 2017; 26: Doi: /
Partridge et al., Curr Med Res Opin 2009; 25:

4. CONTEXT
Regular physical activity reduces the risk of mortality and hospital admissions1
Kaplan-Meier curve of time to death (all-cause mortality) according to level of regular physical activity
Adapted from Garcia-Aymerich et al., 2006
1. Garcia-Aymerich et al., Thorax. 2006; 61:

5. CONTEXT
COPD patients consider the morning as the most troublesome part of the day1
Time when COPD symptoms are worse than usual as reported by patients
74% of all COPD patients and 94% of severe COPD patients reported that they took longer to complete their morning routine.
*p < 0.001 versus midday, afternoon, evening, night and difficult to say group; p = 0.006 versus no particular time of the day; †p < 0.001 versus midday. Copyright © 2009, Informa Healthcare. Reproduced with permission of Informa Healthcare
1. Partridge et al., Curr Med Res Opin 2009;25:

6. CONTEXT
Study Objective1
Morning symptoms are common in COPD. Many COPD patients consider the morning as the most troublesome part of the day, in which they experience more symptoms and physical activity limitations.
Despite the large impact of morning symptoms on activities and quality of life, morning symptoms are not a focus of current treatment guidelines and have not been mentioned in the official European Respiratory Society Statement on physical activity in COPD.
This literature review aims to further investigate the impact of morning symptoms on COPD patients and especially on physical activity.
1. van Buul et al., Eur Respir Rev. 2017; 26: Doi: /

7. Context
Methods
Results
Conclusion
Discussion
Duaklir Genuair

8. METHODS
Study design1
This publication is the result of an electronic literature search in PubMed, Embase, Web of Science, Cochrane, CINAHL and PsycINFO. The search was performed on October 27th, There was no limitation on the date of publication.
All types of COPD studies were included, except meeting abstracts, reviews and articles from non-peer-reviewed journals. Studies were excluded when the predefined outcomes did not comprise either morning symptoms or physical activity. The quality of the studies was evaluated using the STROBE and CONSORT checklist.
The search identified 390 articles. After removing duplicates, 195 individual articles remained. After screening titles, 117 articles were considered relevant. After reading abstracts, 32 articles remained. After full read, 24 articles were excluded. 8 remaining studies were included in the systematic review.
1. van Buul et al., Eur Respir Rev. 2017; 26: Doi: /

9. METHODS
Study Selection1
Study flow diagram with use of the official PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analsyses) flow chart
1. van Buul et al., Eur Respir Rev. 2017; 26: Doi: /

10. Context
Methods
Results
Conclusion
Discussion
Duaklir Genuair

11. Morning symptoms Occurrence of morning symptoms
RESULTS
Morning symptoms
Between 39.8 and 94.4% COPD patients reported morning symptoms. They are detected among all stages of the disease1
Occurrence of morning symptoms
1. van Buul et al., Eur Respir Rev. 2017; 26: Doi: /

12. RESULTS
Morning symptoms
The most common morning symptoms were cough, sputum production and shortness of breath1
Occurrence of different morning symptoms in COPD patients experiencing morning symptoms
1. van Buul et al., Eur Respir Rev. 2017; 26: Doi: /

13. Association between morning symptoms and physical activity
RESULTS
Association between morning symptoms and physical activity
COPD patients who experience morning symptoms also report a negative impact on physical activity1
Morning activities limited by morning symptoms
1. Kim et al., Kor J Intern Med. 2012; 27:

14. RESULTS
Treatment to improve activity limitations that are associated with morning symptoms
Ability to perform morning activities is one of the patient’s expectations of treatment1
Treatment expectations
1. O’Hagan et al., Curr Med Res Opin. 2014; 30:

15. RESULTS
Treatment to improve activity limitations that are associated with morning symptoms
AB/FF significantly reduces morning symptoms and improves limitations of early morning activities1
* p<0.05
*** p<0.001
1. van Buul et al., Eur Respir Rev. 2017; 26: Doi: /

16. Context
Methods
Results
Conclusion
Discussion
Duaklir Genuair

17. Morning symptoms, an important factor in COPD management1
CONCLUSION
Morning symptoms, an important factor in COPD management1
Across all disease stages, COPD patients experience morning symptoms that are negatively associated with physical activity.
This suggests that physicians should include the evaluation of morning symptoms in their clinical assessment and they should include the control of morning symptoms as a goal of treatment.
1. van Buul et al., Eur Respir Rev. 2017; 26: Doi: /

18. Context
Methods
Results
Concluions
Discussion
Duaklir Genuair

19. Patients suffer from breathlessness during activities6
DISCUSSION
Symptoms limit COPD patient’s physical activities, even early in the disease, leading to a worse prognosis1-5
Patients suffer from breathlessness during activities6
Patients limit their activities to avoid symptoms6
Deconditioning aggravates symptoms6
Increase of hospital admissions and mortality3
Jones et al., Int J Chron Obstruct Pulmon Dis. 2016; 11(Spec ISS): 13-20
Troosters et al., Respir Res. 2013; 14(1): 115
Garcia-Aymerich et al., Thorax. 2006; 61:
Watz et al., Eur Respir J. 2009; 33:
Shrikrishna et al., Eur Respir J. 2012; 40:
Reardon et al., Am J Med. 2006; 119(10 suppl 1):32-37

20. DISCUSSION
COPD patients suffer most from symptoms during morning, evening and night-time1
*p < 0.001 versus midday, afternoon, evening, night and difficult to say group; p = 0.006 versus no particular time of the day; †p < 0.001 versus midday. Copyright © 2009, Informa Healthcare. Reproduced with permission of Informa Healthcare
1. Partridge et al., Curr Med Res Opin 2009;25:

21. DISCUSSION
Coughing, bringing up phlegm or mucus and breathlessness are the most reported symptoms during early-morning1
Prevalence of individual COPD symptoms throughout the 24-hour day in the week before baseline (N = 727). COPD, Chronic obstructive pulmonary disease
1. Miravitlles et al., Resp Res. 2014;15:122

22. CODP Patients are more active between 7 am and 8 pm1
DISCUSSION
CODP Patients are more active between 7 am and 8 pm1
Mean min-by-min physical activity pattern (all data, 7 d) of all patients. Presented as mean ± SEM.
METs: Mean metabolic equivalents of task level.
1. Demeyer et al., Chest, 2014; 146(2):318-27

23. Early-morning symptoms impact activities1
DISCUSSION
Early-morning symptoms impact activities1
Impact of early morning symptoms on morning activities during the past week
39.6%
22.4%
19.0%
12.3%
6.7%
1. Stephenson J et al., Int J COPD 2015;10:

24. Self-reported limitations due to morning symptoms1
DISCUSSION
Self-reported limitations due to morning symptoms1
Limitations in morning activities
Domestic activities*
O’Hagan P et al., Curr Med Res Opin 2014; 30: 301–314
* In patients with morning symptoms

25. Self-reported limitations due to morning symptoms1
DISCUSSION
Self-reported limitations due to morning symptoms1
Limitations in daily activities‡
Roche N et al., COPD 2013; 10: 679–686
‡ % of COPD patients whose rest of days are impacted by morning symptoms

26. DISCUSSION
Morning symptoms are associated with poorer health status, impaired daily activities and increased risk of exacerbations1
1. Roche N et al., COPD. 2013;10:

27. Context
Methods
Results
Conclusion
Discussion
Duaklir Genuair

28. DUAKLIR GENUAIR
Duaklir Genuair
Duaklir Genuair reduces breathlessness & overall symptoms during night time, early-morning and daytime1,2
Duaklir Genuair reduces limitation of early-morning activities1
Duaklir Genuair delays the time to the first moderate or severe exacerbation and reduces the rate of moderate of severe exacerbations1,2
Bateman et al., Respir Res. 2015; 16(1): 92
SmPC Duaklir Genuair (340/12), latest edition
Duaklir is not indicated for sleep impairment

29. DUAKLIR GENUAIR
Duaklir® Genuair® significantly improves breathlessness versus mono-components, demonstrating this improvement night time, early-morning and daytime1
Bateman et al., Respir Res. 2015; 16(1): 92
* Figure shows data on improvement of dyspnea during daytime

30. DUAKLIR GENUAIR
Duaklir® Genuair® significantly improves overall symptoms versus mono-components, demonstrating this improvement night time, early-morning and daytime1
Bateman et al., Respir Res. 2015; 16(1): 92

31. DUAKLIR GENUAIR
Duaklir® Genuair® significantly reduces the limitation of early-morning activities versus mono-components1
* p<0.05
*** p<0.001
Bateman et al., Respir Res. 2015; 16(1): 92

32. DUAKLIR GENUAIR
Duaklir® Genuair® delays the time to the first moderate or severe exacerbation and reduces the rate of moderate or severe exacerbations1
Bateman et al., Respir Res. 2015; 16(1): 92
* Figure shows data on rate reduction

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NS Approval ID XL-1015-RD05/2017-VA