This document discusses updates to guidelines from GOLD and GINA. Some key points discussed include: 1. The GOLD guidelines now recommend LAMA/LABA combination therapy as first-line treatment for COPD based on studies showing greater improvement in quality of life compared to individual bronchodilators or placebo. 2. Studies showed the benefits of a single-inhaler triple therapy compared to ICS/LABA therapy for advanced COPD, with reductions in exacerbations. 3. The GINA guidelines now recommend considering ICS for mild asthma to reduce exacerbations based on new evidence. Anti-IL5 monoclonal antibodies like mepolizumab and benralizumab were added as add-

1. COPD vs BA
GOLD & GINA
Updates in Guidelines
By: Dr Riham Hazem Raafat
Ass. Prof. of Chest Diseases
Ainshams University
1

2.  70 years old male with a history of dyspnea for 10 years
 Presenting with dyspnea with white productive
sputum, no fever or URI symptoms
 Skin test +ve for house dust mites, pollens, and cockroaches
 Non-smoker
 Is it COPD or Asthma ?

3. Obstructive Lung Diseases
Integrity and elasticity of lung : DESTROYED
Poor elastic recoil: Air trapping (Hyperinflation)
Problem is with expiration.
Patient has to force the air out using abdominal & intercostal muscles: EXERTION
In Spirometry: FEV1/FVC is decreased.
2

5. Symptoms

7. 10 %
COPD
have more
reversibility
5% severe
Asthma
usually episodic in
nature, does not
progress, usually
begins in early
childhood, and shows
a good response to
bronchodilators and
corticosteroids
very slowly
progressive onset
and most patients
are diagnosed in
their 60s, there is
little variability in
symptoms, and
patients show a
poor response to
bronchodilators and
corticosteroids
Airflow Limitation

10. CXR Usually Normal unless?
Abnormal
Usually in > 20 pack years
(Triggers)

11. Features suggestive of BA or COPD must fulfill at least 3 or more
of the following to settle diagnosis of one of them:
• Age of onset
• Pattern of symptoms
• Lung Function
• Lung Function between attacks
• PH/FH
• Time course
• CXR

14. GOLD
• Launched in 1997 in collaboration with the NHLBI, NIH and WHO.
• Non-biased review of the current evidence for assessment, diagnosis
and treatment of patients with COPD that can aid the clinician.
Objectives
Recommend effective management and prevention strategies.
Increase awareness among medical community, health officials and the
general public
Decrease morbidity and mortality through implementation of effective
programs
6

15. Descriptive levels of Evidence
7
Evidence
category
Sources of Evidence
A • RCT with a rich body of data
B • RCT with a limited body of data
• Meta-analysis of RCTs
C • Non-randomized trials
• Observational studies
D • Panel Consensus Judgment

16. Pathways to Diagnosis
Onset in midlife
Slowly Progressive

17. © 2019 Global Initiative for Chronic Obstructive Lung Disease

19. Refined ABCD assessment tool
4

20. Assessment of Exacerbation Risk
- COPD exacerbations are defined as an acute worsening of respiratory symptoms
that result in additional therapy.
- Classified as:
 Mild (treated with SABDs only)
 Moderate (treated with SABDs plus antibiotics and/or oral corticosteroids)
 Severe (patient requires hospitalization or visits the emergency room). Severe
exacerbations may also be associated with acute respiratory failure.
- Blood eosinophil count may also predict exacerbation rates (in patients treated with
LABA without ICS).
© 2019 Global Initiative for Chronic Obstructive Lung Disease

21. CAT: COPD Assessment Test
mdcalc.com
cattestonline.com
3
mMRCDS:
Modified Medical Research Council
Dyspnea Scale

22. Pharmacological
treatment algorithm
5
✓
✓
✓
✓
Non-Pharmacological
- Smoking Cessation
- Pulmonary Rehabilitation
- O2 Therapy / MV
- Vaccination
- Surgical/Bronchoscopic interv.
(Individualized)
High Symp
CAT > 20
Eos >300

23. Updates in Pharmacotherapy in GOLD 2019
8

24. Co-suspension technique
• New formulation:
• Drug crystals are suspended in HFAbased propellant
by engineered low-density phospholipid particles.
Ferguson GT, Hickey AJ, Dwivedi S. Co-suspension delivery technology in pressurized metered-dose
inhalers for multi-drug dosing in the treatment of respiratory diseases. Respir Med. 2018 Jan
10
ADVANTAGES
1. Porous particle + drug crystal mixtures remain afloat instead of
sedimenting
2. Prevents flocculation/aggregation of drug particles
3. Decreased DDI/DCI
4. Size: 2-3 um: optimum
5. Low spray velocity HFApropellant: decreased dysphonia

25. 1. LABA+LAMA has greater improvement in quality of life
compared to placebo or its individual bronchodilator
components
Martinez FJ et al., Efficacy and Safety of Glycopyrrolate/Formoterol Metered Dose Inhaler Formulated
Using Co-Suspension Delivery Technology in Patients With COPD. Chest. 2017 Feb 11

26. LABA+LAMA combination
Martinez FJ et al., Efficacy and Safety of Glycopyrrolate/Formoterol Metered Dose Inhaler Formulated
Using Co-Suspension Delivery Technology in Patients With COPD. Chest. 2017 Feb 12
• Efficacy and safety data from 9 DB-RCTs evaluated GP MDI at doses 0.6 to 144ug and
FF MDI at doses 2.4 to 19.2 ug supported selection on GFF (18/9.6 ug) MDI for Phase III
evaluation
• Time period: 24 weeks
• Patients:
 Age group: 40-80 years
 Moderate to severe COPD
 Can continue OCS, ICS or PDE-4 inhibitors
PINNACLE-1
(2103 pts.)
PINNACLE-2
(1615 pts.)
GFF MDI 526 510
GP MDI 451 439
FF MDI 449 437
Placebo 219 223
Tiotropium* 451 N/A
*Open- label (EMA: Active comparator)
Adm. via DPI

27. Results: Lung Functions
Martinez FJ et al., Efficacy and Safety of Glycopyrrolate/Formoterol Metered Dose Inhaler Formulated
Using Co-Suspension Delivery Technology in Patients With COPD. Chest. 2017 Feb 13
GFF MDI 126 ml GP MDI 66 ml FF MDI 62 ml
PL MDI -24 ml
TIO 105 ml
GFF MDI 116 ml GP MDI 63 ml FF MDI 61 ml
PL MDI 13 ml
150
91
86
-7
122
137
80
8
82
1º 1º

28. Results: Treatment difference (1º)
14
Resp. Q’naire (on a scale of 0 to100, with lower scores: better functioning)
Other parameters measured:
1. Average use of Rescue Albuterol (Daily andNighttime)
2. No. of exacerbations
CONCLUSION: IMPROVED EFFICACY, SIMILAR SAFETY PROFILE
Martinez FJ et al., Efficacy and Safety of Glycopyrrolate/Formoterol Metered Dose Inhaler Formulated
Using Co-Suspension Delivery Technology in Patients With COPD. Chest. 2017 Feb
PINNACLE-1 PINNACLE-2
GFF MDI GP MDI FF MDI PL MDI TIO GFF MDI GP MDI FF MDI PL MDI
Change
(Baseline Vs. Wk 24)
- 3.3 -1.0 -2.7 -0.8 -2.6 -3.0 -2.2 -2.3 -1.2
Rx difference
(GFF MDI Vs. Others)
N/A -2.33** -0.64 -2-52* -0.73 N/A -0.78 -0.66 -1.72

29. 2. Double blind RCT reported benefits of single-inhaler triple therapy
compared with ICS/LABA therapy in patients with advanced COPD
Lipson DA et al., FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic
Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Aug 15
FULFIL: Lung Function and Quality of Life Assessment in COPD with Closed TripleTherapy

30. Results
16
24 weeks (ITT) 54 weeks (EXT)
OD triple
therapy#
BD ICS/LABA## Vs. OD triple
therapy#
BD ICS/LABA## Vs.
n 911 899 210 220
Change from
baseline FEV1
142 ml -29 ml p<0.001 126 ml -53 ml p<0.001
Mean change
from baseline
SGRQ score
-6.6 -4.3 p<0.001 -4.6 -1.9 p = 0.065
(Maybe due to small
sample size)
Reduction in
exacerbation rate
N/A
Lipson DA et al., FULFIL Trial: Once-Daily Triple Therapy for Patients with Ch
35% reduction; 95%CI, 14–51; (p=0.002) versus dual
ICS/LABA therapy
ronic Obstructive Pulmonary Disease. Am J
Respir Crit Care Med. 2017Aug
# fluticasone furoate 100/umeclidinium 62.5/vilanterol 25 ug
## budesonide 400/formetrol 12 ug

31. September 2017: USFDAapproval
Grade D-COPD
Once a day oral inhalation
Enhances patient’s adherence to therapy
and reduces device errors that occur when
patients are using multiple inhalers.
C/I during exacerbation episode
Systemic S/E of steroids +
https://www.fiercepharma.com/pharma/glaxo-wins-fda-nod-for-closed-triple-therapy-
trelegy-ellipta-pegged-as-a-blockbuster
17
FDA approval for first “closed” triple therapy

32. 3- Tiotropium Effect
Improves the effectiveness of PR in increasing
exercise performance (Evidence B)

33. Exacerbation phenotype
Wedzicha JA, Roflumilast: a review of its use in the treatment of
COPD. International Journal of Chronic Obstructive Pulmonary Disease. 2016 18

34. 4. Beneficial effects of roflumilast have been reported in greater
patients with a prior history of hospitalization for an acute
exacerbation
Martinez FJ, Calverley PM, Goehring UM, Brose M, Fabbri LM, Rabe KF.Effect of roflumilast on exacerbations in
patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a
multicentre randomised controlled trial. Lancet.2015
19
When Blood Eosinophils < 100 cells/ul

35. Post-hoc analysis
Rabe KF et al., Effect of roflumilast in patients with severe COPD and a history of hospitalisation. Eur Respir J. 2017 Jul
20
• Chronic Bronchitis patients
• Patients who had previously suffered at least one serious exacerbation
Decreases
Neutrophil chemotactic factor
NF-KB translocation
Increases
IL-10
HDAC 2 expression
Non-selective PDE-4 inhibitors
PDE-4B: anti-inflammatory effects
PDE-4D: vomiting
 Rate of severe exacerbations per patient per
year by history of prior hospitalisation in the
previous year.

36. Update to Roflumilast
(Daliresp)
2017
2019
21

37. 5. Oral Macrolide for one year in patients prone to exacerbations
reduced the risk of exacerbations compared to usual care in
non current smokers.
Albert RK, Connett J, Bailey WC, et al. Azithromycin for Prevention of Exacerbations of COPD. The New
England journal of medicine. 2011;365(8):689-698. doi:10.1056/NEJMoa1104623.
22

38. Azithromycin 250 mg/day for one year
Albert RK, Connett J, Bailey WC, et al. Azithromycin for Prevention of Exacerbations of COPD. The New
England journal of medicine. 2011;365(8):689-698. doi:10.1056/NEJMoa1104623.
23
Endpoint Azithromycin Placebo
Median time to first exacerbation (days) 266 days 174 days
SGRQ -2.8 ± 12.1 -0.6 ± 11.4
Group Participants Exacerbations
Azithromycin 558 317 (57%)
Placebo 559 380 (68%)

39. After 1 year of Macrolide?
2017
2019
24

40. © 2019 Global Initiative for Chronic Obstructive Lung Disease

41. GINA
GINA guidelines 2018 27
• Launched in 1993 in collaboration with the NHLBI, NIH and WHO.
Objectives
Increase awareness of asthma
Improve management of asthma
Improve availability and accessibility of effective asthma therapy
Difference from GOLD guidelines
Meta analysis: EvidenceA

44. GINA 2018 guidelines 28
Stepwise management of Asthma
Mild Moderate

45. 29
KEY CHANGES
ICS should be considered for
patients with mild asthma
(rather than SABAalone)
• Reduces R/O
serious exacerbations.
{Reddel et al., Lancet 2017}
SC Mepolizumab
(anti-IL5 mAB) add-on Rx
for patients with severe
eosinophilic asthma

46. Anti IL-5
Nair P,Wenzel Set al.; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab inSevere
Asthma. N Engl J Med. 2017
31
*EosinophilicAsthma
*

47. Nair P,Wenzel Set al.; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of
Benralizumab in Severe Asthma. N Engl J Med. 2017 33
Results

49. Other key updates: GINA 2018
1. New Section added: Perimenstrual (catamenial) asthma
• Asthma worse perimenstrually in ~20% women
• More common in women with high BMI; often have dysmenorrhea and shorter cycles.
• Add-on treatment: OCP and/or LTRA may be helpful
2. New therapy added: HDM-SLIT (house dust mite – sublingual IT) Therapy
• When medication is discontinued, symptoms may recur. This is where allergen immunotherapy
(AIT) comes into play
• Repeated doses of a specific relevant allergen for the treatment of IgE-mediated allergicdisease
3. Evidence A: recommendation against stopping ICS during pregnancy
• Stopping ICS increases the risk of exacerbations in pregnancy
34

50. 36

51. Have a Nice Day
Thank You