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COPDThe New Epidemic
Peter Lin MD CCFPDirector Primary Care InitiativesCanadian Heart Research Centre
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Conflict Disclosure Information
Speaker: Dr. Peter Lin
Title of Talk: COPD – The New Epidemic
Financial Disclosure Company
Grants / Research Support None
Speakers Honorarium Astrazeneca, BMS, Takeda Boeringher Ingelheim, AbbottEli Lilly, Amgen, Mylan, Janssen Forest Laboratories, J&J, Merck, Novartis, Pfizer, Servier, Sanofi
Consulting Fees None
Patents None
Other None
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Mitigating Potential Bias
• Only published data will be presented in this program and recommendations will be based on published Guidelines
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Learning Objectives:
By the end of this workshop you will be able to:
1. Make appropriate diagnosis2. Understand appropriate testing3. Be able to incorporate guidelines into the
management of your patients4. Understand the role of new therapies for the
management of your patients
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Percent Change in Age-Adjusted Death Rates, U.S., 1965 – 1998 (Proportion of 1965 Rate)
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Air trapping
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Mr. CO
• 76 year old man• Short of breath• Had Negative Cardiac workup• Smoker 40 pk years• Coughs most days – some sputum• Meds: • ARB, Statin, ASA, Vitamins
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EXPOSURE TO RISK FACTORS
tobaccotobaccooccupationoccupation
indoor/outdoor pollutionindoor/outdoor pollution
SPIROMETRY: Required to establish diagnosis
SPIROMETRY: Required to establish diagnosis
Global Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis of COPDGlobal Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis of COPD
SYMPTOMS
chronic coughchronic coughshortness of breathshortness of breath
sputum sputum
© 2013 Global Initiative for Chronic Obstructive Lung Disease
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11
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Focus on Vital Capacity (VC)
12
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Spirometry: Normal Trace Showing FEV1 and FVC
1 2 3 4 5 6
1
2
3
4
Volu
me,
lite
rs
Time, sec
FVC5
1
FEV1/FVC = 0.8
© 2013 Global Initiative for Chronic Obstructive Lung Disease
FVC = 5LFEV1 = 4L
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Spirometry: Mr. COVo
lum
e, li
ters
Time, seconds
5
4
3
2
1
1 2 3 4 5 6
Normal
Obstructive< 0.70
© 2013 Global Initiative for Chronic Obstructive Lung Disease
FEV1/FVC = 0.56
FVC = 3.2L
FEV1 = 1.8L
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Mr. CO
• Walking can’t keep up with his wife
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Assessing Disability in COPDAssessing Disability in COPD
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Mr. CO
• FEV1 is 70% predicted
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Global Strategy for Diagnosis, Management and Prevention of COPDClassification of Severity of Airflow Limitation in COPD* based on FEV1
GOLD 1: Mild FEV1 > 80% predicted
GOLD 2: Moderate 50% < FEV1 < 80% predicted
GOLD 3: Severe 30% < FEV1 < 50% predicted
GOLD 4: Very Severe FEV1 < 30% predicted
*Based on Post-Bronchodilator FEV1
© 2013 Global Initiative for Chronic Obstructive Lung Disease
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Global Strategy for Diagnosis, Management and Prevention of COPDClassification of Severity of Airflow Limitation in COPD* based on FEV1
GOLD 1: Mild FEV1 > 80% predicted
GOLD 2: Moderate 50% < FEV1 < 80% predicted
GOLD 3: Severe 30% < FEV1 < 50% predicted
GOLD 4: Very Severe FEV1 < 30% predicted
*Based on Post-Bronchodilator FEV1
© 2013 Global Initiative for Chronic Obstructive Lung Disease
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Global Strategy for Diagnosis, Management and Prevention of COPDClassification of Severity of Airflow Limitation in COPD* based on FEV1
GOLD 1: Mild FEV1 > 80% predicted
GOLD 2: Moderate 50% < FEV1 < 80% predicted
GOLD 3: Severe 30% < FEV1 < 50% predicted
GOLD 4: Very Severe FEV1 < 30% predicted
*Based on Post-Bronchodilator FEV1
© 2013 Global Initiative for Chronic Obstructive Lung Disease
Mr. CO FEV1 = 70%
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Mr. CO
• 5 years he had 3 exacerbations
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What is the impact of exacerbations on mortality?
50% of COPD patients are dead within 4 years of being admitted for first time with COPD1
1.Suissa S, Dell’Aniello S, Ernst P. Thorax. doi: 10.1136/thorax.jnl-2011-201518, 2.Soler-Cataluna JJ, et al. Thorax. 2005;60:925-931.
A= No Exacerbations
B= 1-2 Exacerbations
C= > 3 Exacerbations
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Suissa S et al. Thorax 2012;67:957-963
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Suissa S et al. Thorax 2012;67:957-963
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Daily rates of death (per 10 000 per day) in the 90-day period after onset of severe chronic obstructive pulmonary disease exacerbation.
Suissa S et al. Thorax 2012;67:957-963
Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.
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LAMA vs Placebo for Exacerbation
Tashkin DP, et al. N Engl J Med. 2008;359:1543-1554.
Month
29863006
19961815
14861284
12231010
983776
838634
709545
610460
2621
TiotropiumPlacebo
No. at risk
0
20
40
60
80
0
Pro
bab
ility
of
exac
erb
atio
n (
%)
6 12 18 24 30 36 42 48
*p<0.001
*
Hazard ratio: 0.86CI: 0.81-0.91
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250
200
150
100
50
0
Chan
ge from
baseline
in trou
gh FEV
1(m
L)
Week 4 Week 8 Week 12 Last visit
n=118
n=127
†
n=106 n=121
n=121n=121 n=129
* n=108* *
Formoterol (12 µg b.i.d.) + tiotropium (18 µg o.d.)
Tiotropium (18 µg o.d.)
Trough FEV1: Change from baseline
AM PMAM/PM average
Mean chan
ge in
symptom
score
0
‐0.2
‐0.4
‐0.6
‐0.8
‐1.0
‐1.2
‐1.4
‐1.6
Total COPD Symptom Score‡
*
**
LAMA vs LAMA + LABAFormoterol + Tiotropium
*p<0.05; †p<0.001 vs. tiotropium;‡ sum of scores for dyspnea (0 = none to 4 = severe), wheezing, cough, and chest ghtness (0 = none to 3 = very uncomfortable).Tashkin DP, et al.: COPD 2009; 6(1):17‐25.
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TORCH – ICS vs LABA vs Combo
Calverley PMA et al. N Engl J Med 2007;356:775-789
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0.4
0.3
0.2
0.1
0.00 15 30 45 60 75 90
Days since randomisation
Exac
erba
tions
/pat
ient
BUD/FORM + TIOPBO + TIO
62% reduction in rate of severe exacerbationRatio: 0.38 (95% CI: 0.25–0.57) P < 0.001
Poisson regression
LAMA vs LAMA + ICS + LABA
BUD/FORM=budesonide/formoterol (320/9 μg bid); PBO = placebo; TIO = tiotropium (18 μg od) Welte T, et al. Am J Respir Crit Care Med. 2009;180:741-750.
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Global Strategy for Diagnosis, Management and Prevention of COPD
Combined Assessment of COPDGlobal Strategy for Diagnosis, Management and Prevention of COPD
Combined Assessment of COPD
> 2
1
0
(C) (D)
(A) (B)
mMRC 0-1CAT < 10
mMRC > 2CAT > 10
Symptoms© 2013 Global Initiative for Chronic Obstructive Lung Disease
SAMA prnor
SABA prn
LABA or
LAMA
ICS + LABAor
LAMA
ICS + LABAand/orLAMA
Exacerbations
4
3
2
1
GOLD FEV1<50% Predicted
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Treatment of Stable COPD
© 2017 Global Initiative for Chronic Obstructive Lung Disease
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BronchodilatorLAMA or LABA
2 BronchodilatorsLAMA + LABA
Bronchodilators + ICSLAMA + LABA + ICS
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Pharmacotherapy Indicated for COPD in Canada§
B R O N C H O D I L A T O R SS H O R T ‐ A C T I N G B E T A 2 ‐ A G O N I S T S L O N G ‐ A C T I N G B E T A 2 ‐ A G O N I S T S
www.hc-sc.gc.ca accessed June 24, 2015
Budesonide/Formoterol (fumarate)
§ Chart not representative of all approved COPD medications Canada.
C O R T I C O S T E R I O D S / L O N G ‐ A C T I N G B E T A 2 ‐ A G O N I S T S
Tiotropium (bromide)/Olodaterol (hydrochloride)
Aclidinium (bromide)/Formoterol (fumarate)
DUAKLIR™Genuair 400/ 12
mcgINSPIOLTO™
Respimat 2.5/2.5 mcg
S H O R T ‐A C T I N G A N T I C H O L I N ER G I C S
Umeclidinium (bromide)
INCRUISEEllipta 62.5 mcg
L O N G ‐ A C T I N G A N T I C H O L I N E R G I C S
Umeclidinium (bromide)/Vilanterol (trifenatate)
Glycopyrronium (bromide)/Indacaterol (maleate)
Ipratropium (bromide)/Salbutamol (sulfate)
A N T I C H O L I N E R G I C S A N D L O N G ‐ A C T I N G B E T A 2 ‐ A G O N I S T S
COMBIVENTRespimat 20/100 mcg
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Treatments for COPDAbbreviation Full name Examples Brand (Device)
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterolOlodaterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)Striverdi (Respimat)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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35
Treatments for COPDAbbreviation Full name Examples Brand (Device)
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterolOlodaterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)Striverdi (Respimat)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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36
Treatments for COPDAbbreviation Full name Examples Brand (Device)
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterolOlodaterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)Striverdi (Respimat)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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37
Treatments for COPDAbbreviation Full name Examples Brand (Device)
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterolOlodaterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)Striverdi (Respimat)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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38
Treatments for COPDAbbreviation Full name Examples Brand (Device)
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterolOlodaterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)Striverdi (Respimat)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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39
Treatments for COPDAbbreviation Full name Examples Brand (Device)
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterolOlodaterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)Striverdi (Respimat)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
DeviceEfficacySafety
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1 Adapted from : Newman SP, et al. Lung Deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicine: Comparison of Respimat with conventional metered-dose inhalers with and without spacer devices. Chest1998;113: 957-963.
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Adapted from asthmameds.ca
DPI (Diskus)
Breathe out until lungs are empty
Place the mouthpiece in mouth and close lips firmly around it Breathe in as “fast” & as “hard” as you can until lungs are full Hold breath for 10s Breathe out
Slide the lever away from you as far as it will go
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Respimat
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Turbuhaler
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Devices
● Feedback on successful inhalation• Audible click when patient is inhaling sufficiently• Control window turns red when inhalation is
complete
Red & DoneGreen & Go
Tudorza® Genuair® Product Monograph, 2013
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49
Treatments for COPDAbbreviation Full name Examples Brand (Device)
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterolOlodaterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)Striverdi (Respimat)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
DeviceEfficacySafety
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LAS39: Change from baseline FEV1 by timepoint over 24 hours at Day 1
*p<0.05 aclidinium vs tiotropium This study alone does not constitute a head-to-head study to support comparative claims of aclidinium vs tiotropium. Beier et al. COPD 2013
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Aclidinium reduces COPD exacerbation (any severity) rates (24 weeks): ATTAIN
Healthcare ResourceUtilization criteria
EXACTcriteria
0.4
0.8
1.2
1.6
0.0
0.60
0.40
1.39
0.98
COPD
exacerbations
(/pt/year)
PlaceboAclidinium 400 µg BID
29%
33%
Jones et al. CHEST 2012
p<0.05
Reproduced with permission
p<0.05
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Canadian RWE
In Canada, 5255 COPD patients were treated with an ICS/LABA before matching – 3969 (76%) patients in this cohort used FLU/SAL– 36% had exacerbations pre-index– More bud/form vs. flu/sal pats. had a first ICS/LABA initiated by a specialist (8% more)– Antibiotics were not evaluated as a definition of exacerbations – Patients were tracked for 1 year
In Canada, 5255 COPD patients were treated with an ICS/LABA before matching – 3969 (76%) patients in this cohort used FLU/SAL– 36% had exacerbations pre-index– More bud/form vs. flu/sal pats. had a first ICS/LABA initiated by a specialist (8% more)– Antibiotics were not evaluated as a definition of exacerbations – Patients were tracked for 1 year
Healthcare utilisation in the first year after initiating ICS/LABA therapy
Blais L et al. Clin Ther 2010; 32 (7): 1320
Courses of oral steroids/year 0.66 0.79 0.85 (0.72, 1.00)
ED visits/year 0.16 0.23 0.75 (0.58, 0.97)
Hospital admissions/year 0.11 0.21 0.61 (0.47, 0.81)
Addition of a tiotropium prescription/year 1.63 2.01 0.71 (0.57, 0.89)
A retrospective observational propensity-matched cohort study
These slides have been supplied, on request, by AstraZeneca Scientific Affairs.
For complete therapeutic and safety information please consult the SYMBICORT ® Product Monograph.
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COPD Exacerbations
3.4
21
54
85
109
2.7
15
38
63
80
0.0 20.0 40.0 60.0 80.0 100.0 120.0 140.0 160.0
Emergencyvisits
Hospitalisations
Antibiotics
Oralsteroids
Allexacerbations
BUD/FORSAL/FLU
Rateratio(95%CI)
0.74(0.69,0.79)
0.74(0.68,0.81)
0.70(0.66,0.75)
0.71(0.65,0.78)
0.79(0.71,0.89)
Eventrateper100patient‐years
**
**
**
**
*
BUD/FOR (n=2734) or FLU/SAL (n=2734)
Adjusted yearly rates of healthcare utilisation events were compared using Poisson regression analysis. **P<0.0001; *P=0.0003 for difference. CI, confidence intervals; BUD/FOR, budesonide/formoterol; FLU/SAL, fluticasone/salmeterol
NNT = 3.4
NNT = 16
Larsson et al. J Intern Med 2013; DOI: 10.1111/joim.12067These slides have been supplied, on request, by AstraZeneca Scientific Affairs.
For complete therapeutic and safety information please consult the SYMBICORT ® Product Monograph.
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54
Treatments for COPDAbbreviation Full name Examples Brand (Device)
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
DeviceEfficacySafety
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Pneumonia Risk in COPD Patients (Stratified by ICS Type)
Singh S, Loke YJ. Curr Opin Pulm Med. 2010; 16: 118‐122.
Meta‐analysis of ICS use (studies 1‐3 yr duration)
Corticosteroid TypeFluticasone (16 studies)Budesonide (7 studies)Mometasone (1 study)
HR (95%CI)1.67 (1.47-1.89)*
1.19 (0.92-1.53) [ns]2.00 (0.83-4.81) [ns]
Corticosteroid Safer Corticosteroid Harmful0.20.1 1 5 100.5 2
Risk Ratio
*statistically significant increase with fluticasone p<0.0001[ns] = no statistically significant increase in risk detected
• The elderly and those with more severe disease and lower FEV1s are at the highest risk of pneumonia.
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Cumulative Pneumonia Rate vs Time Post IndexFluticasone/salmeterol group
Any pneumoniaHospitalised pneumonia
Budesonide/formoterol groupAny pneumoniaHospitalised pneumonia
Cum
ulat
ive
pneu
mon
ia ra
te p
er 1
00 p
atie
nts
All pneumoniasRR 1.73 (1,57; 1.90) P<0.001 NNT 23
110
0
100908070605040302010
0 1 2 3 4 5 6 7 8 9Years
Hospitalised pneumoniasRR 1.74 (1,56; 1.94) P<0.001 NNT 34
Adjusted yearly pneumonia event rates compared using Poisson regression analysis. Janson et al. BMJ 2013;346:f3306 DOI: 10.1136/bmj.f3306
These slides have been supplied, on request, by AstraZeneca Scientific Affairs.
For complete therapeutic and safety information please consult the SYMBICORT ® Product Monograph.
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BacteriaFluticasone Fluticasone/GCS-receptor
Fluticasone/salmeterol
Mucosa/Lung tissue
1. Wedzicha JA et al. AJRCCM 20082. Calverley et al. Chest 2011;139:5053. Patterson C et al Respiratory Research 2012,13:404. Ek A et al Allergy (1999). 54: 691 5. Miller-Larsson et al. AJRCCM (2000). 162: 1456. Johnsson M et al Allergy (1995) 50:s11-147. Dalby C, et al. Respir Res (2009); 10:104
An Immunosuppressant / Infection hypothesis
ASL = Airway surface liquid
BudesonideBudesonide/GCS-receptor
ASL
These slides have been supplied, on request, by AstraZeneca Scientific Affairs.
For complete therapeutic and safety information please consult the SYMBICORT ® Product Monograph.
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Water solubility(μg/mL)
Dissolution time(human BAL fluid in vitro)
Flunisolide 140 <2 min
Triamcinoloneacetonide
21 n.d.
Budesonide 16 6 min
Beclomethasone 17-propionate
16 n.d.
Fluticasone 17-propionate
0.16 >8h
Beclomethasonedipropionate
0.13 >5h
Högger and Rohdewald, Rev Contemp Pharm 1998
Dissolution Time in Airway Fluid
n.d.= no data
These slides have been supplied, on request, by AstraZeneca Scientific Affairs.
For complete therapeutic and safety information please consult the SYMBICORT ® Product Monograph.
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Water solubility(μg/mL)
Dissolution time(human BAL fluid in vitro)
Flunisolide 140 <2 min
Triamcinoloneacetonide
21 n.d.
Budesonide 16 6 min
Beclomethasone 17-propionate
16 n.d.
Fluticasone 17-propionate
0.16 >8h
Beclomethasonedipropionate
0.13 >5h
Högger and Rohdewald, Rev Contemp Pharm 1998
Dissolution Time in Airway Fluid
n.d.= no data
These slides have been supplied, on request, by AstraZeneca Scientific Affairs.
For complete therapeutic and safety information please consult the SYMBICORT ® Product Monograph.
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Two major acid and alcohol metabolites are inactive Sentellas et al, 2010Alberti et al, 2010
Gavaldà et al. 2014
Safety: Hydrolysis of LAMAs
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ICS + LABA – Advair (Diskus)
Abbreviation Full name Examples Brand
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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ICS + LABA – Symbicort (Turbuhaler)
Abbreviation Full name Examples Brand
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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ICS + LABA – Breo (Ellipta)
Abbreviation Full name Examples Brand
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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LAMA + LABA – Anoro (Ellipta)
Abbreviation Full name Examples Brand
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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LAMA + LABA – Ultibro (Breezhaler)
Abbreviation Full name Examples Brand
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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LAMA + LABA – Stiolto RespimatAbbreviation Full name Examples Brand
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterolOlodaterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)Striverdi (Respimat)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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LAMA + LABA – Duaklir (Genuair)
Abbreviation Full name Examples Brand
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
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Treatments for COPDAbbreviation Full name Examples Brand (Device)
ICS Inhaled corticosteroid
BudesonideFluticasone ProprionateFluticasone Furoate
Pulmicort (Turbuhaler)Flovent (Diskus)
(Ellipta)
LAMALAAC
Long-acting anticholinergic (also known as long-acting muscarinic antagonist)
TiotropiumGlycopyrroniumAclidinium BromideUmeclidinium
Spiriva (Respimat)Seebri (Breezhaler)Tudorza (Genuair)Incruse (Ellipta)
LABA Long-acting beta2 agonist
FormoterolSalmeterolIndacaterolVilanterol
Oxeze (Turbuhaler)Serevent (Diskus)Onbrez (Breezhaler)
(Ellipta)
SABA Short-acting beta2 agonist
SalbutamolTerbutaline
Ventolin (Diskus)Bricanyl (Turbuhaler)
SAMA Short-acting antimuscarinic Ipratropium Atrovent
DeviceEfficacySafety
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Death
Disability
Never smoked or not susceptible to smoke
Smoked regularlyand susceptible toeffects of smoke
Stopped smoking at 45 (mild COPD)
Stopped smoking at 65 (severe COPD)
FEV
1(% of v
alue at a
ge 25)
Age (years) Fletcher C et al. Br Med J. 1977;1:1645–1648.
COPD Risk & Smoking Cessation1,5,7
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Peter Lin MD CCFPDirector Primary Care InitiativesCanadian Heart Research CentreCOPD Maze
Keep COPD in DDx
Tools for Assessing Risk
Medications: Bronchodilators vs ICS
Step up: Single then dual then triple Rx
Decide based on: Device, Efficacy, Safety
Avoid Exacerbations