This document provides information on tools and strategies for managing chronic obstructive pulmonary disease (COPD). It includes summaries of two patient cases involving COPD management. It also summarizes evidence on pulmonary rehabilitation, the effects of different COPD medication regimens, and issues with patient adherence to inhaled medications. The document aims to provide clinicians with resources and guidance for optimizing COPD treatment approaches.

1. COPD Visual Toolkit
Fernando Martinez, MD, MS
Chief, Pulmonary and Critical Care Medicine Division
Weill Cornell Medicine
Barbara Yawn, MD, MSc, FAAFP
Adjunct Professor, Dept of Family and Community Health
University of Minnesota

2.  Can provide longitudinal
picture of progress or
decline
© 2021, Global Initiative for Chronic Obstructive Lung Disease, available from www.goldcopd.org, published in Deer Park, IL, USA.

3. A Quick Functional Status Assessment
© 2021, Global Initiative for Chronic Obstructive Lung Disease, available from www.goldcopd.org, published in Deer Park, IL, USA.

4. CAT, COPD Assessment Test; eos, blood eosinophil count (cells/L); ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA,
long-acting muscarinic antagonist; mMRC, modified Medical Research Council dyspnea questionnaire.
© 2021, Global Initiative for Chronic Obstructive Lung Disease, available from www.goldcopd.org, published in Deer Park, IL, USA.

5. Factors to Consider When Initiating ICS Treatment
Agusti et al, 2018.
FACTORS TO CONSIDER WHEN INITIATING ICS TREATMENT
Factors to consider when initiating ICS treatment in combination with 1 or 2 long-acting bronchodilators
(note the scenario is different when considering ICS withdrawal):
STRONG SUPPORT CONSIDER USE AGAINST USE
• History of hospitalization(s) for
exacerbations of COPD*
• ≥2 moderate exacerbations of
COPD per year*
• Blood eosinophils >300 cells/µL
• History of or concomitant
asthma
• 1 moderate exacerbation of COPD
per year*
• Blood eosinophils 100-300 cells/µL
• Repeated pneumonia events
• Blood eosinophils <100 cells/µL
• History of mycobacterial infection
*Despite appropriate long-acting bronchodilator maintenance therapy
Note that blood eosinophils should be seen as a continuum; quoted values represent approximate cut-points; eosinophil
counts are likely to fluctuate.

6. Case 1: Jon, 58-Year-Old Smoker
Reason for visit—wife wanted “tiredness” checked out
 She says I spend too much time lazing around in house
 Retired from construction work—was “getting old” and had trouble keeping up
with job--SOB
 Told he might have COPD in ED visit for “bad cold”. Given antibiotics and
“inhaler” and “as needed rescue”—might help but seldom used.
PMH
 History of hypertension, hyperlipidemia and “prediabetes”
 Still smokes 10 cigarettes per day
 On statin, diuretic and ACE inhibitor—same dose for past 8 years.
 Trying to deal with “prediabetes” with diet and exercise—“not working well—
too tired to exercise”
ACE, angiotensin converting enzyme; ED, emergency department; PMH, past medical history; SOB,
shortness of breath.

7. Case 1: Jon, 58-Year-Old with 30-Year Smoking
History (cont.)
 Today’s evaluation:
 BP 144/92, pulse 78, resp 20, BMI 34.5,
 HEENT—nl, Chest--Decreased breath sounds, Heart—RR no murmurs
or gallops, Abd—nl, Ext-1+ edema
 mMRC is 2, CAT is 18
 Spirometry-- FEV1/FVC .62 and FEV1—62% predicted
 CXR—no mass, no cardiomegaly, no infiltrates
abd, abdomen; BMI, body mass index; BP, blood pressure; CXR, chest X-ray; FEV1/FVC, proportion of vital capacity expired in the
first second of forced expiration to full, forced vital capacity; HEENT, head, eyes, ears, nose, and throat; nl, normal; RR, regular rate.

8. Treating Jon’s COPD
 Inform and educate regarding COPD diagnosis
 An ongoing activity
 Get up to date on immunizations, check lipids and HgbA1C, support
smoking cessation.
 Pharmacotherapy
 Dual bronchodilator therapy vs LAMA alone
 Continue SABA as needed and carry with him
 Smoking cessation therapies
 Complete inhaler education and teach back.
 Give link to sites for review at home
 Follow up—see again in 6 to 12 weeks with follow up earlier if required
for lab results.
 CT lung cancer screening—ask for comments on cardiac calcification
and emphysema.
CT, computed tomography; SABA, short-acting beta agonists.

9.  Continuing adjustments in
therapy are based on symptoms
and exacerbations with strategies
for each
© 2021, Global Initiative for Chronic Obstructive Lung Disease, available from www.goldcopd.org, published in Deer Park, IL, USA.

10. Case 2: Marci, 58-Year-Old with COPD
Diagnosed 3 Years Ago
 Reason for today’s visit
 Thinks she has acute bronchitis again
 Coughing, more shortness of breath and maybe coughing up “stuff”
 Using “dual therapy”—LAMA+LABA---remembers most days
 Has not refilled that red rescue ---well ever
 PMH
 FEV1 predicted of 54% at diagnosis
 Has been to ED twice this year for acute bronchitis and treated with
steroid burst and antibiotics each time
 Told to continue her dual bronchodilator therapy
 Also has hyperlipidemia, and stopped smoking 5 years ago but admits
to “vaping occasionally for stress”
Wants treatment for her current problem

11. Case 2: Marci, 58-Year-Old with COPD
Diagnosed 3 Years Ago (cont.)
 Examination today
 BP 124/72, pulse 86, resp 24, coughing frequently, pulse ox-92%, T-
99 F
 BMI 26.1
 HEENT
 URI-like inflammation
 Chest—wheezes and crackles
 Heart—RR, no murmurs or gallops
 Ext---no edema
 Could not do peak flow due to coughing
 CAT is 26, mMRC is 3 today
 CXR---no infiltrates, heart--nl
T, temperature; URI, upper respiratory infection.

12. Treating Marci’s exacerbation and more
 Treat acute exacerbation
 Oral steroid burst—probably no need for antibiotics
 Now third exacerbation in past 12 to 15 months; right side of GOLD diagram
 Add ICS to LABA + LAMA—role of eos? (GOLD and ATS differ )
 If already on triple RX---refer—can refer earlier if desired. ? Roflumilast or Azithromycin
 Even though acute issue, do check up steps
 Check inhaler technique
 Check ability and current level of adherence to daily RX
 Assess trigger or exposures---someone smoking in the house or other place she goes??
 Ask goals and discuss importance of regular follow up care.
 Consider spirometry---better now or in 6 weeks???
 Pulmonary rehab—in person or online---can be helpful to do at time of “event”
 CT lung cancer screening—ask for comments on cardiac calcification and emphysema
 Consider referral for second opinion and what you may have missed
ATS, American Thoracic Society.

13. ETHOS and IMPACT: Effect of Fixed-Dose Triple Therapy on
Moderate or Severe Exacerbations
BFF, budesonide/formoterol fumarate; BGF, budesonide/glycopyrrolate/formoterol fumarate; GFF, glycopyrrolate/formoterol fumarate; FF, fluticasone furoate; RR, rate ratio;
UMEC, umeclidinium; VI, vilanterol.
There have been no head-to-head comparative studies between both triple therapy.
Lipson et al, 2018; Rabe et al, 2020.
ETHOS: Moderate or Severe COPD Exacerbation in
the Modified Intent-to-Treat Population
IMPACT: Time-to-First-Moderate or
Severe COPD Exacerbation Analysis
FF-UMEC-VI UMEC-VI FF-VI
N 4151 2070 4134
Rate of moderate or severe
exacerbations/year
0.91 1.21 1.07
RR for triple therapy (95% –
0.75 (0.70-0.81)
P < .001
0.85 (0.80-0.90)
P < .001
BGF GFF 18/9.6 BFF 320/9.6
N 2137 2120 2131
Rate of moderate or severe
exacerbations/year
1.08 1.43 1.24
RR for BGF 320/18/9.6 (95% –
0.76 (0.69-0.83)
P < .001
0.87 (0.79-0.95)
P = .003
0
10
20
30
40
50
60
70
80
90
100
0 50 100 150 200 250 300 350
Patients
who
had
a
moderate
or
severe
exacerbation
(%)
Days since randomization
UMEC-VI FF-VI FF-UMEC-VI
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50
Cumulative
incidence
Days since randomization
GFF18/9.6 µg BFF320/9.6 µg BGF320/18/9.6 µg
Severe exacerbations were defined as worsening symptoms of COPD that required inpatient hospitalization

14. 0
0.5
1
1.5
2
2.5
3
3.5
0 50 100 150 200 250 300 350
Days since randomization
UMEC-VI FF-VI FF-UMEC-VI
0
0.5
1
1.5
2
2.5
3
0 10 20 30 40 50
Cumulative
incidence
Days since randomization
GFF 18/9.6 µg BFF 320/9.6 µg BGF 320/18/9.6 µg
ETHOS and IMPACT: Effect of Fixed-Dose Triple Therapy on
Mortality
IMPACT: Death from Any Cause On/Off Treatment
(Including Additional Vital Status Data)
ETHOS: All-Cause Deaths (Final Retrieved
Dataset, ITT Population)
Severe exacerbations were defined as worsening symptoms of COPD that required inpatient hospitalization.
IMPACT: the primary outcome of reduction for the annual rate of moderate or severe COPD exacerbations with FF/UMEC/VI vs. FF/VI or UMEC/VI during treatment was met.
ETHOS: the primary outcome of reduction for the annual rate of moderate or severe COPD exacerbations with BUD/GLY/FOR (2 doses of Bud 160µg or 360µg) vs. BUD/FOR or
GLY/FOR during treatment was met.
Lipson et al, 2020; Martinez et al, 2021.
FF-UMEC-VI UMEC-VI FF-VI
N 4151 2070 4134
RR for triple therapy (95% CI)
(Including off-treatment)
–
0.72 (0.53-0.99)
P < .042
0.89 (0.67-
1.16) P < .387
BGF
320/18/9.6
GFF 18/9.6 BFF 320/9.6
N 2137 2120 2131
RR for BGF 320/18/9.6 (95% CI)
(On and off treatment)
–
0.51 (0.33-0.80)
P = .0111
0.72 (0.44-1.16)
P = .1721

15. IMPACT Subgroup Analysis
Effects of Prior Exacerbation History and Eosinophil Count on
Efficacy
AECOPD, acute exacerbation of COPD; FF, fluticasone furoate; UMEC, umeclidinium; VI, vilanterol
Halpin et al, 2020.
Single moderate AECOPD
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0 100 200 300 400 500 600
Blood eosinophil count at screening cells μg-1
Annual
rate
of
exacerbations
Severe AECOPD
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0 100 200 300 400 500 600
Blood eosinophil count at screening cells μg-1
Annual
rate
of
exacerbations
Frequent moderate AECOPD
0.0
0.5
1.0
1.5
2.0
2.5
3.0
0 100 200 300 400 500 600
Blood eosinophil count at screening cells μg-1
Annual
rate
of
exacerbations
FF/UMEC/VI
UMEC/VI
FF/VI

16. Martinez et al, 2021.
All-Cause Mortality in ETHOS Throughout the Study
Strongly Suggests Benefit Is Not an ICS Withdrawal
Effect

17. Non-Pharmacological Therapy of Stable COPD
Patient Essential Recommended Local Guidelines
A Smoking cessation Physical activity Flu and
pneumococcal
vaccination
B, C, D Smoking cessation
Pulmonary
Physical activity Flu and
pneumococcal
vaccination
www.goldcopd.org

18. Pulmonary Rehabilitation Improves Dyspnea
4 2 2 4
Behnke 2000a
Cambach 1997
Favors Control Favors Treatment
Goldstein 1994
Mean Difference
(95% CI)
2.26 (1.34, 3.18)
1.20 (0.36, 2.04)
0.66 (0.12, 1.20)
0
Gosselink 2000
Griffiths 2000
Gell 1995
0.82 (0.17, 1.47)
1.18 (0.85, 1.51)
1.30 (0.64, 1.96)
Gell 1998
Hernandez 2000
Simpson 1992
1.00 (0.20, 1.80)
0.78 (0.02, 1.54)
1.20 (0.37, 2.03)
Singh 2003
Wijkstra 1994
Total
0.88 (0.35, 1.41)
0.90 (0.13, 1.67)
1.06 (0.85, 1.26)
Lacasse et al, 2006.

19. Adherence to Inhaled Medications Is Low
 Patients with COPD often stop using their
medication
 Abandon treatment soon after initiation1,2
 Over 12 months, 50% of patients with COPD took <30% of doses3
 Over 12 months, doses taken was higher for ICS/LABA at 49%4
 90 days prior to COPD hospitalization only 41% filled
COPD prescriptions5
1. Bender, 2014; 2. Wurst et al, 2014; 3. Davis et al, 2017; 4. Bogart et al, 2019; 5. Baker et al, 2014.

20. Adherence Requires Good Inhaler Technique
 Correct use of inhaled medication
 Prospective observational study of 244
patients with COPD followed for 1 month
after hospital discharge
 Diskus controller with electronic recording
device
 Only 6% had adherence >80%
 51% of doses involved ≥1 critical technique
error
Sulaiman et al, 2017.
Error type Mean/patient
Low peak inspiratory flow 10.0
Multiple inhalations 4.8
Multiple errors 2.3
Blister present, no inhale
detected
1.5
Exhaling into the mouthpiece 1.1
Others 1.0
Total 20.7

21. Proper Inhaler Technique
1. Metered dose inhaler with/without spacer
 http://www.cdc.gov/asthma/inhaler_video
2. All inhaler types
 https://www.copdfoundation.org/Learn-
More/Educational-Materials-
Resources/Educational-Video-Series.aspx

22. Thank You for Joining Us!
 We are excited to see the impact of this educational
activity on patient care in COPD
 In 4 weeks, you will receive a follow-up survey to see if
you’ve been able to implement any of your intended
changes as a result of what you learned today
 If you have any questions, send us an email:
contact@cmespark.com

23. References
 Agusti A, Fabbri LM, Singh D, et al (2018). Inhaled corticosteroids in COPD: friend or foe? Eur Respir J. 2018;52(6):1801219.
DOI:10.1183/13993003.01219-2018
 Baker CL, Zou KH & Su J (2014). Long-acting bronchodilator use after hospitalization for COPD: an observational study of health
insurance claims data. Int J COPD. 9:431-39. DOI:10.2147/COPD.S59322
 Bender BG (2014). Nonadherence in chronic obstructive pulmonary disease patients: what do we know and what should we do
next? Curr Opin Pulm Med. 20(2):132-37. DOI:10.1097/MCP.0000000000000027
 Bogart M, Stanford RH, Laliberté F, et al (2019). Medication adherence and persistence in chronic obstructive pulmonary disease
patients receiving triple therapy in a USA commercially insured population. Int J COPD. 14:343-52. DOI:10.2147/COPD.S184653
 Davis JR, Wu B, Kern DM, et al (2017). Impact of nonadherence to inhaled corticosteroid/LABA therapy on COPD exacerbation
rates and healthcare costs in a commercially insured US Population. Am Health Drug Benefits. 10(2):92-102.
 Halpin DMG, Dransfield MT, Han MK, et al (2020). The effect of exacerbation history on outcomes in the IMPACT trial. Eur Respir J.
55(5):1901921. DOI:10.1183/13993003.01921-2019
 Lacasse Y, Goldstein R, Lasserson TJ & Martin S (2006). Pulmonary rehabilitation for chronic obstructive pulmonary disease.
Cochrane Database Syst Rev. 18(4):CD003793.
 Lipson DA, Barnhart F, Brealey N, et al (2018). once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J
Med. 378:1671-80. DOI:10.1056/NEJMoa1713901
 Lipson DA, Crim C, Criner GJ, et al (2020). Reduction in all-cause mortality with fluticasone furoate/umeclidinium/vilanterol in
patients with chronic obstructive pulmonary disease. Am J Respir Crit Car Med. 201(12):1508-16. DOI:10.1164/rccm.201911-
2207OC

24.  Martinez FJ, Rabe KF, Ferguson GT, et al (2021). Reduced all-cause mortality in the ETHOS trial of
budesonide/glycopyrrolate/formoterol for chronic obstructive pulmonary disease. a randomized, double-blind, multicenter, parallel-
group study. Am J Respir Crit Car Med. 203(5):553-64. DOI:10.1164/rccm.202006-2618OC
 Rabe KF, Martinez FJ, Ferguson GT, et al (2020). Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD.
N Engl J Med. 383:35-48. DOI:10.1056/NEJMoa1916046
 Sulaiman I, Cushen B, Greene G, et al (2017). Objective assessment of adherence to inhalers by patients with chronic obstructive
pulmonary disease. Am J Respir Crit Care Med. 195(10):1333-43. DOI:10.1164/rccm.201604-0733OC
 Wurst KE, St Laurent S, Mullerova H & Davis KJ (2014). Characteristics of patients with COPD newly prescribed a long-acting
bronchodilator: a retrospective cohort study. Int J COPD. 9:1021-31. DOI:10.2147/COPD.S58258
References