This document discusses the treatment of COPD patients with a focus on LABA/LAMA combinations. It begins by defining COPD and outlining its common characteristics and risk factors. It then discusses GOLD guidelines for diagnosing and assessing COPD severity. The document recommends starting treatment with a LABA like indacaterol and considering switching to a LABA/LAMA combination like indacaterol/glycopyrronium which has been shown to reduce exacerbation rates and delay time to first exacerbation compared to other treatments. It also discusses considerations for ICS use and inhaler device selection. Finally, it addresses how COVID-19 impacts COPD patients and how treatment can continue safely during the pandemic.

1. Bring The Right Bronchodilators
for COPD Patients
Focusing on LABA/LAMA
Presented by : dr. Alma Thahir Pulungan, Sp.P, FISR

2. Definition COPD
“Chronic Obstructive Pulmonary Disease (COPD) is a common,
preventable and treatable disease that is characterized by
symptoms of persistent breathing and limited air flow caused by
the airways and / or alveolar abnormalities which are usually
caused by significant exposure to harmful particles or gases.”
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/

3. Common Characteristic in COPD
chronic bronchitis
emphysema
• The most common forms of COPD are chronic bronchitis
and emphysema
• Both are chronic illnesses that impair airflow in the lungs
• Most cases of COPD are related to cigarette smoking
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/ ; 2. Harvard Health Publishing, 2017; access from https://www.health.harvard.edu/a_to_z/chronic-obstructive-pulmonary-disease-copd-a-to-z

4. COPD Risk Factors
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/
Several factors can influence the development of COPD disease are

5. COPD in Indonesia

6. Diagnosis in COPD
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/

7. GOLD 2021 Latest Update :
Why Eosinophil Important in
COPD ???

8. COPD vs Asthma
COPD1,2 Asthma1,2
Onset Mid-life Early in life (often childhood)
Symptoms Slowly progressive
Dyspnea during
exercise
Vary widely from day to day
Worse at night / early morning
Airflow limitation Largely irreversible Largely reversible
Main risk factors
for development
History of tobacco
smoking or exposure to
other types of smoke
Exposure to allergens, infections,
diet, tobacco smoke,
socioeconomic
Additional
features
Allergy, rhinitis ,and/or eczema
also present
Family history of asthma
COPD shares a number of similarities with asthma but the diseases differ in a variety of ways
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/; 2. GINA Update 2019

9. Cellular & Molecular Differences Between
COPD vs Asthma
Peter J. Barnes, 2017, Clinical Science

10. ICS Use
Overview of potential risks associated with ICS in COPD
Price D, et al. Prim Care Respir J 2013

11. ICS Consideration
Factors to consider when initiating ICS treatment in combination with long acting bronchodilators
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/

12. Refined assessment of COPD : GOLD 2021
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/

13. Management Cycle of COPD : GOLD 2021
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/
Review
• Symptoms: Dyspnea
• Exacerbations
Adjust
• Escalate
• Switch inhaler device or
molecules
• De-escalate
Assess
• Inhaler technique and adherence
• Non-pharmacological approaches
(including pulmonary
rehabilitation and self-
management education)

14. Initial Treatment :
With LABA (Indacaterol)

15. Initial Treatment : GOLD 2021
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/

16. MOA Indacaterol
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/
Indacaterol secara langsung menginduksi
bronkodilatasi melalui stimulasi Reseptor β2
Memperbaiki Fungsi
Paru-Paru
Bekerja cepat
Sejak 5 menit pertama
Bertahan selama
24jam
Dengan efektifitas Ultra LABA (Indacaterol) dapat memaksimalkan efek bronkodilatasi pada pasien PPOK

17. Data are LSM
p<0.001 for both indacaterol doses versus placebo at all time points; p<0.001 for salbutamol versus placebo at all time points; p<0.01 for salmeterol/fluticasone (S/F) versus placebo at all time
points; †p<0.05, ††p<0.01, †††p<0.001 for indacaterol versus S/F;
‡‡‡p<0.001 indacaterol versus salbutamol; §p<0.05, §§p<0.01 for salbutamol versus S/F.
INSURE – Indacaterol fast onset in the first 5min
Balint, B., et al., 2010. Int J of COPD, 5, p.311

18. 18
Data are LSM±SE
INTENSITY – Indacaterol improve TDI score and higher
number of patient with MCID compare to Tiotropium
Buhl, R. et al., 2011. European Respiratory Journal, 38(4), pp.797-803
TDI : Transition Dyspnea Index
MCID : Minimal Clinically Important Differences

19. 19
Data are LSM±SE
INTENSITY – number of puff and days with rescue
medication improvement in Indacaterol
Buhl, R. et al., 2011. European Respiratory Journal, 38(4), pp.797-803

20. Switching Considerations :
To LABA/LAMA
(Indacaterol/Glycopyrronium)

21. Follow up Treatment : GOLD 2021
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/

22. Disease Trajectory of COPD
Symptoms
Exacerbations
Exacerbtionis
Exacerbastions
Deterioration
End of life
Adapted from Editorials British Journal of General Practice, Dec 2004

23. MOA : LABA & LAMA
Patalano, F., et al. Eur Respir Rev 2014

24. Direct Switch to Exacerbations
IND/GLY significantly reduced the rate of all exacerbations vs SFC over 52 weeks
Wedzicha JA, et al. N Engl J Med 2016

25. Direct Switch to Delayed Time to Exacerbations
IND/GLY significantly delayed time to the first exacerbation vs SFC in any type of exacerbation
Wedzicha JA, et al. N Engl J Med 2016
16% risk
reduction

26. Safety : Adverse Event
IND/GLY less pneumonia event compares to SFC
Wedzicha JA, et al. N Engl J Med 2016
Variable
IND/GLY 110/50 μg q.d.
(N=1678)
SFC 50/500 μg b.i.d.
(N=1680)
Number (percent)
Patients with ≥1 adverse event 1459 (86.9) 1498 (89.2)
Adverse events that occurred in ≥3% of either treatment group†
Worsening of chronic obstructive pulmonary disease 1299 (77.4) 1374 (81.8)
Nasopharyngitis 197 (11.7) 195 (11.6)
Viral upper respiratory tract infection 132 (7.9) 138 (8.2)
Bacterial upper respiratory tract infection 125 (7.4) 168 (10.0)
Lower respiratory tract infection 82 (4.9) 98 (5.8)
Upper respiratory tract infection‡ 81 (4.8) 83 (4.9)
Pneumonia 53 (3.2) 80 (4.8)*
Cough 50 (3.0) 51 (3.0)
Dyspnea 49 (2.9) 51 (3.0)
Influenza 35 (2.1) 56 (3.3)
Oral candidiasis 20 (1.2) 71 (4.2)
Serious adverse event§ 308 (18.4) 334 (19.9)
Death 24 (1.4) 24 (1.4)
Patients who discontinued because of adverse event 126 (7.5) 143 (8.5)
Patients who discontinued because of serious adverse event 85 (5.1) 87 (5.2)
Patients who discontinued because of nonserious adverse event 49 (2.9) 70 (4.2)

27. Direct Switching Consideration :
To LABA/LAMA
(Indacaterol/Glycopyrronium)

28. CRYSTAL Study : Direct Switching
Vogelmeier CF, et al. Respiratory Research (2017) 18:140

29. CRYSTAL Study : Direct Switching
Vogelmeier CF, et al. Respiratory Research (2017) 18:140
Direct switch from LABA/ICS or LABA or LAMA to IND/GLY show significant improvements

30. Other Switching Consideration :
Inhaler Device (Breezhaler)

31. INHALER Study : Critical error Differ
Patients using the Breezhaler made fewer critical handling errors than using other devices
46.9
50 43.8
(39.1–48.6)
(43.0–50.8)
40
30
20 15.4
(13.0–17.8)
21.2
(17.5–25.0)
29.3
(25.6–32.9)
32.1
(27.7–36.6) 30.0
(28.5–31.6)
10
0
Breezhaler®
(n=876)
Diskus®
(n=452)
Handihaler®
(n=598)
pMDI
(n=422)
Respimat®
(n=625)
Turbohaler®
(n=420)
Total#
(n=3,393)
%
device
handing
episodes
that
involved
≥1
critical
handling
error*
Diskus® is a registered trademark of GlaxoSmithKline.
HandiHaler® and Respimat® are registered trademarks of Boehringer Ingelheim.
Turbuhaler® Is a registered trademark of AstraZeneca.
Molimard M, et al. Eur Respir J 2017;49.pii:1601794

32. INHALER Study : Inhaler Device Consideration
Error in inhaler technique is strongly correlated with severe exacerbation in COPD patients
Molimard M, et al. Eur Respir J 2017;49.pii:1601794
p<0.01
p<0.01
#exacerbation with antibiotherapy, corticotherapy, emergency room visit or hospitalization;
+ exacerbation with emergency room visits or hospitalizationca

33. Breezhaler with Mechanism Feedback (Hear, Feel & See)
Product Information Ultibro
Memudahkan
pemakaianalatdengan
benar*
Bisadigunakansemuapasien
karenaBREEZHALER
lowresistance*
Memastikanobat
dihirupsempurna*

34. GOLD 2021 Latest Update :
How GOLD react to
COVID-19 ???

35. COPD Fact in COVID-19
• COPD attribute to the worse progression and outcome of COVID-19.1
• COPD was the most strongly predictive comorbidity for:
ICU admission
pOR 17.8
(95% CI 6.56 – 48.2).2
severe disease
pOR 6.42
(95% CI 2.44 – 16.9).2
Zhao Q, et al. 2020, accepted article, 2. Jain V & Yuan JM, 2020, medRxiv

36. COVID-19 and Comorbidities
Ejaz. Et al 2020 : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402107/pdf/main.pdf
COVID-19 affected globally a large population with pneumonia-like symptoms, and the patients with other
comorbidities are utmost at the risk of infection
COPD & COVID-19
• COVID-19 illness can lead to the development of hypoxemia in
15–20% of the patients, which require ventilator support in
adverse conditions
• The transition in the inflammatory response, microbiome
imbalance, weak immunity, continual mucus production, use of
respiratory corticosteroids, and structural damages are involved
in establishing COPD
• Although earlier studies did not report a high number of COVID-
19 cases with COPD, the expression of ACE-2 receptors is
increased in this disease, contributing to the establishment of
severe symptoms among COVID-19 individuals, including
structural damage to lungs, weak immunity and hyper mucous
production
• COPD observed in 50–52.3% of the total ICU admitted COVID-19
cases, lead to high mortality among these patients with
increased mucous production and blockage of air passages

37. Differentiating COVID-19 Infection
from Daily Symptoms of COPD
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/

38. How Indonesia Government and Community React?
Physical distancing need to
happen also in Health Care
Facility.
BUT
COPD patient need to
CANNOT stop the treatment.
What can we do?

39. How We Help Our Patient Survive?
Reference : 1. GOLD, 2021 accessed from: https://goldcopd.org/2021-gold-reports/
Telemedicine
Germas and COVID-
19 Prevention
High Compliance on
Pharmacological
Therapy
High Compliance on
Non-Pharmacological
Therapy
Bi-monthly Medicine Supply

40. LABA/LAMA
(Indacaterol/Glycopyrronium)
Now available in JKN
And
LABA (Indacaterol)
Now available in PRB

41. ULTIBRO® BREEZHALER® Telah tersedia untuk pasien JKN

42. ONBREZ® BREEZHALER® Telah tersedia untuk pasien JKN dan Pasien PRB

44. THANK YOU