Updates on Pharmaological Management of Asthma & COPD

Updates on Pharmaological
Management of Asthma & COPD

Asthma Guidelines
5
1989
1st expert
panel
convened
1991
EPR-1
1993
GINA
founded
1995
1st GINA
guideline
1997
EPR-2
2002
Focused
update of
GINA
guideline
2002
Focused
update of
EPR-2
2006
GINA
guideline
major
revision
2007
EPR-3
2014
GINA
guideline
major
revision
EPR= National Heart, Lung, and Blood Institute (NHLBI). National Asthma
Education and Prevention Program (NAEPP). Expert Panel Report (EPR):
Guidelines for the Diagnosis and Management of Asthma
GINA= Global Initiative for Asthma.
Global Strategy for Asthma
Management and Prevention.
2011
EPR-3 quick-
reference guide
updated

Airway
inflammation
Airflow
obstruction
Bronchial
hyperresponsiveness
Symptoms
Asthma Pathophysiology
The tip of the iceberg

8
 In susceptible individuals, inflammatory symptoms
are usually associated with widespread but variable
airflow obstruction and an increase in airway
response to a variety of stimuli.
 Obstruction is often reversible, either spontaneously
or with treatment.
Asthma definition

11
• Inflammation in asthma patients can be present
during symptom-free periods:
 Symptoms resolve quickly. Inflammation,
as measured by airway hyperresponsiveness,
far longer time .
 As chronic inflammation causes an increase in
airway hyperresponsiveness, if the inflammation
is not controlled, symptoms are likely to reoccur.

12
Can asthma be cured?
Asthma is an eminently controllable illness. Indeed,
most sufferers, control is so effective that it amounts
a virtual cure. But asthma is not curable
Asthma is a long-term disease that has no cure. The
goal of asthma treatment is to control the disease.

Asthma Goals of Therapy
13
Reduce Impairment
 Prevent and control symptoms (e.g. SOB,
coughing) Reduce use of SABA for quick-relief of symptoms
 Maintain near normal pulmonary function
 Maintain normal activity levels
Reduce Risk
 Prevent acute exacerbations
 Prevent ED visits and hospitalizations
 Prevent progressive loss of lung function
 Minimize adverse effects of pharmacotherapy
www.ginasthma.org

© Global Initiative for Asthma
GINA assessment of symptom control
A. Symptom control
In the past 4 weeks, has the patient had:
Well-
controlled
Partly
controlled
Uncontrolled
• Daytime asthma symptoms more
than twice a week? Yes No
None of
these
1-2 of
these
3-4 of
these
• Any night waking due to asthma? Yes No
• Reliever needed for symptoms*
more than twice a week? Yes No
• Any activity limitation due to asthma? Yes No
GINA 2015, Box 2-2A
Level of asthma symptom control
*Excludes reliever taken before exercise, because many people take this
routinely

17
Controllers =
Medications taken
daily on a long-term
basis to keep asthma
under clinical control
due to
antiinflammatory
effects
Relievers =
Medications used
on an as-needed
basis that act
quickly to reverse
bronchoconstriction
and relieve its
symptoms
Controllers Vs Relievers

19
Controllers
 Inhaled corticosteroids
 Inhaled long-acting b2-
agonists
 leukotrienes modifiers
 Sustained release
theophylline
 Systemic
glucocorticosteroids
 Anti-IgE (Omalizumab)
Relievers
 Inhaled short acting b2-agonists
 Short acting anticholinergics
 Methylxanthines
Medications for Asthma Management

21
Inhaled therapy constitutes the cornerstone
of asthma treatment .

Step 2 Step 3 Step 4 Step 5Step 1
Asthma Education
Enviromental Control
As needed
rapid acting
2 agonists
As needed rapid acting 2 agonists
Controller
options
Select one Select one Add one or
more
Add one or
both
Low-dose ICS Low-dose ICS +
LABA
Medium or high
dose ICS+
LABA
Oral steroid
LTRA Medium or high
dose ICS
LTRA Anti-IgE
Low-dose ICS
+ LTRA
Theophylline
Low-dose ICS
+ Theophylline
INCREASEREDUCE TREATMENT STEPS
GINA 2006
As needed rapid acting B2-agonist

26
• Prescribe an inhaled short-acting β2 agonist
as short term reliever therapy for all
patients with symptomatic asthma.

31
 The use of short-acting inhaled beta2-agonists on
a daily basis, or increasing use, indicates
inadequate asthma control & the need for
additional long term control therapy.

32
 Increasing use of SABA treatment or the use of SABA > 3
3 doses a week for symptom relief (not prevention of
EIB) generally indicates inadequate asthma control and
the need for initiating or intensifying anti-inflammatory
therapy.
 Regularly scheduled, daily, chronic use of SABA is not
recommended.

34
 Good asthma control is associated with little or no need for
short-acting β2 agonist.
 Anyone prescribed more than one short acting bronchodilator
inhaler device a month should be identified and have their
asthma assessed urgently and measures taken to improve
asthma control if this is poor.

Beclomethasone
Budesonide
Fluticasone
Inhaled corticosteroids

38
• Inhaled corticosteroids are the recommended &
most effective preventer drug for adults and children
with asthma , for achieving overall treatment goals.

41
Beclomethasone
Dipropionate 100
ug/dose
Beclomethasone
Dipropionate 50 ug/dose

48
ICS usage as a preventer therapy should be
explained to the parents in simple, plain terms.

49
Pharmacokinetics of Inhaled Drugs

51
1. Oropharyngeal candidiasis
2. Hoarseness
3. Coughing
To reduce the potential for adverse affects:
 Use the lowest dose necessary to maintain control.
 Administer with spacers/holding chambers.
 Advise patients to (Rinse with water , gargle and
spit out) after inhalation.
Local side effects

56
Aerochamber spacer With mouth piece
Aerochamber spacer with mask

58
Fate of inhaled drugs – Good Technique
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
80%
20%
Schematic representation of potential dose distribution
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Adapted from Barnes et al. AJRCCM 1998;157:S1-S53

59
Fate of inhaled drugs – Good Technique
Swallowed
GI tract
Deposited in lung
Lungs
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
80%
20%
Schematic representation of potential dose distribution
Adapted from Barnes et al. AJRCCM 1998;157:S1-S53
Swallowed
GI tract
Deposited in lung
Lungs
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
95%
5%
Schematic representation of potential dose distributionAdapted from Barnes et al. AJRCCM 1998;157:S1-S53
Fate of inhaled drugs – Poor Technique

60
 Inhaled medications is a waste of money if not used
properly
 Poor technique is a barrier to good asthma control
 Check at each visit
 Don’t rely on patient’s knowledge – ask them to
demonstrate

62
 Stepping down therapy once asthma is controlled is
recommended , but often not implemented leaving
some patients overtreated.
 Patients should be maintained at the lowest possible
dose of inhaled corticosteroid.
 Reduction in inhaled corticosteroid dose should be
as patients deteriorate at different rates.

63
Stepping down therapy
 Reductions should be considered every three months,
decreasing the dose by approximately 25–50% each
 Regular review of patients as treatment is stepped
is important .

64
GINA 2016
 When controlled on low-dose inhaled glucocorticosteroids:
switch to once-daily dosing (((
 Consider stopping controller treatment only if there have
been no symptoms for 6–12 months, and patient has no
risk factors . Provide a written asthma action plan, and
monitor closely.
 Complete cessation of ICS in adults is not advised as the
risk of exacerbations is increased

Treatment Options for adult Patients
Not Controlled on low dose Inhaled Steroids
Patients not controlled on Low dose ICS
Increase the
dose of inhaled
steroid
Add leukotriene
receptor
antagonists
Add long-acting
beta2-agonists
Add
theophylline

Stepwise Therapy- GINA 2017
Before stepping up, check:
 Diagnosis
 Adherence
69
Inhaler technique
Modifiable risk factors
www.ginasthma.org
Stepping up is a “Therapeutic Trial”
 Sustained step up (2-3 months)
 Short-term step up (1-2 weeks)
 Day-today adjustment

78
 Long-acting inhaled β2 agonists should only be started
in patients who are already on inhaled corticosteroids,
and the inhaled corticosteroid should be continued.
 The benefits of these medicines used in conjunction with
ICS in the control of asthma symptoms outweigh any
apparent risks.
Safety Of LABA

1. Recent data indicating a possible increased risk of asthma
Related death associated with use of LABA in a
small group of individuals has resulted in increased
emphasis on the message that:
2. LABA should not be used as monotherapy in asthma & must
only be used in combination with an appropriate dose of
ICS.

90
Maintenance and Reliever Therapy (MART)

 Combination inhalers of salmeterol with an ICS, such as
Seretide, are not suitable for single inhaler maintenance
and reliever therapy.
 Salmeterol should not be used for the relief of acute
asthma symptoms because it has a significantly slower
onset of action than either formoterol, salbutamol or
terbutaline.
92

GINA 2015 – changes to Steps 4 and 5
© Global Initiative for AsthmaGINA 2015, Box 3-5, Steps 4 and 5
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
# Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of
exacerbations; it is not indicated in children <18 years.
Other
controller
options
RELIEVER
STEP 1 STEP 2
STEP 3
STEP 4
STEP 5
Low dose ICS
Consider low
dose ICS
Leukotriene receptor antagonists (LTRA)
Low dose theophylline*
Med/high dose ICS
Low dose ICS+LTRA
(or + theoph*)
As-needed short-acting beta2-agonist (SABA)
Low dose
ICS/LABA*
Med/high
ICS/LABA
Refer for
add-on
treatment
e.g.
anti-IgE
PREFERRED
CONTROLLER
CHOICE
Add tiotropium#
High dose ICS
+ LTRA
(or + theoph*)
Add
tiotropium#
Add low
dose OCS
As-needed SABA or
low dose ICS/formoterol**

Tiotropium
FDA approvals
2004: Handihaler® for COPD
2014: Respimat® for COPD
2015: Respimat® for asthma in ≥ 12
2017: Respimat® for asthma in ≥6
GINA 2018 Guidelines
In Steps 4 & 5 :
• Add-on therapy for adults/adolescents with a
history of exacerbations
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm; www.ginasthma.org

Children’s Healthcare of Atlanta

FOR INTERNAL USE ONLY. STRICTLY CONFIDENTIAL.
DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY.
What is the Respimat® Soft Mist™ Inhaler?
 The Respimat® Soft Mist™ Inhaler is a highly
efficient and effective inhaler developed by
Boehringer Ingelheim1,2
 It delivers a metered dosage of medication by
mechanical energy, without the use of propellants2,3
 The Respimat® Soft Mist™ Inhaler delivers
medication in a slow-moving fine mist and is
designed to overcome problems such as2,3
 Limited drug deposition in the lung
 Reliance on adequate patient coordination
for effective inhalation
 Use once daily in two consecutive puffs
(2.5 mcg per puff)1
1. Boehringer Ingelheim. Spiriva® Respimat® 2.5 mcg solution for inhalation. Summary of Product Characteristics. 2014. Available at:
https://www.medicines.org.uk/emc/medicine/20134/SPC/Spiriva+Respimat+2.5+micrograms+solution+for+inhalation/. Accessed: Sept 2014;
2. Moroni-Zentgraf P. RDD Europe 2013;1:141‒152; 3. Dalby R, et al. Int J Pharm 2004;283:1‒9.
109

DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY
Respimat® unique mist
• The Respimat® unique mist has all the properties needed for deep lung deposition
Aerosol velocity: the unique mist is slow-moving, allowing it to
follow the natural curve of the throat, resulting in lower deposition
in mouth and throat1
Aerosol duration: the unique mist cloud is long-lasting (1.5 s).
Patients have enough time to breathe in the medication1
Highly respirable, fine droplets: up to 77% of the droplets are in
the fine particle fraction, helping patients get the medication deep
into the lungs2
Respimat® generates a unique mist leading to deep lung deposition
Features and benefits
1. Hochrainer 2005.
2. Ziegler 2005.

The Respimat® Soft Mist™ Inhaler delivers a higher
percentage dose than pMDIs
pMDI, pressurized metered-dose inhalers.
1. Brand, Int J COPD 2008;3:76370; 2. Zierenberg B. J Aerosol Med 1999;12 Suppl 1:S1924.
SLOW INHALATION
FINE
PARTICLES
1–5 µm
Whole lung deposition was higher with Respimat® Soft Mist™ Inhaler than
with pMDI in trained patients (53% of delivered vs. 21% of metered dose)
111
TOTAL LUNG DEPOSITION
Study undertaken in patients with COPD

114

115

Chronic Obstructive Pulmonary Disease
COPD

Smoking is the Single Most Important
Risk Factor for COPD
Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive
Lung Disease (GOLD) 2008. Available from: http://www.goldcopd.org.

118
4–10%
of population
COPD is an important and increasing cause
of morbidity and mortality
Mathers 2006;
WHO 2015.
COPD remains a global health problem
COPD 5th
4th 3rd
2002 2015 2030
…leading cause of death in the world

COPD: Reality
Under
diagnosed
perceived
treated

122
GOLD 2001
GOLD 2011
GOLD 2017

COPD GOLD Guidelines
123
1998
GOLD
formed
2001
1st GOLD report
(spirometric grading)
2011
GOLD Major Revision
(ABCD multimodal grading)
2017
GOLD Major Revision
(refined ABCD
grading)
GOLD = Global Initiative for Chronic Obstructive Lung Disease

Common preventable & treatable disease
Characterized by persistent airflow limitation that is
usually progressive
Associated with an enhanced chronic inflammatory
response in the airways & the lung to noxious particles
or gases
Exacerbations & comorbidities contribute to the
overall severity in individual patients
Definition of COPD 2016

LUNG INFLAMMATION
COPD PATHOLOGY
Oxidative
stress Proteinases
Repair
mechanisms
Anti-proteinases
Anti-oxidants
Host factors
Amplifying mechanisms
Cigarette smoke
Biomass particles
Particulates
Pathogenesis of
COPD

EmphysemaObstructive Bronchiolitis

Mast cell
CD4+ cell
(Th2)
Eosinophil
Allergens
Ep cells
ASTHMA
Bronchoconstriction
AHR
Alv macrophageEp cells
CD8+ cell
(Tc1)
Neutrophil
Cigarette smoke
Small airway narrowing
Alveolar destruction
COPD
Reversible Not fully reversibleAirflow Limitation

130
Is it Inevitably All Downhill ?

COPD: Progressive Disease
อาการ/lungfunction
ระยะเวลา
Acute exacerbation

Frequent exacerbations are associated with
increased mortality
A = No exacerbations B = 1-2 exacerbations C = 3 or more exacerbations
Soler-Cataluna JJ, et al. Thorax 2005;60:925-931.
p < 0.0001
1.0
Probabilityofsurviving
0.8
0.6
0.4
0.2
0.0
0 10 20 30 40 50 60
Time (months)
A
B
C
p = 0.069
p < 0.0002

COPD is:
a multi- component disease
with systemic involvement & inflammation
Respiratory system
Systemic
inflammation
Target organs
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
COPD is: More than just a lung disorder

SYMPTOMS
Cough
Sputum
Shortness of breath
EXPOSURE TO RISK
FACTORS
Tobacco
Occupation
Indoor/outdoor pollution
SPIROMETRY
Diagnosis of COPD
èèè

Disease Management should now be focusing
on 2 key areas
1.
Goal of COPD Management

COPD Goals of Therapy
138
Reduce Symptoms
 Relieve symptoms
 Improve exercise tolerance
 Improve health status
Reduce Risk
 Prevent disease progression
 Prevent and treat exacerbations
 Reduce mortality
GOLD 2017

 Smoking cessation is the single most effective and
cost-effective intervention to reduce the risk of
developing COPD and stop its progression
(Evidence A)

Expiratory flow-limitation and lung hyperinflation that are only partially reversible
to bronchodilator therapy are pathophysiological hallmarks of COPD

V
BD
 Air flowDeflation
 Improvement in flow – FEV1
 Improvement in volumes – FVC and IC
Bronchodilator therapy deflates the lung
BD = bronchodilator; V = ventilation; FEV1= forced expiratory volume in 1 second;
FVC= forced vital capacity; IC = inspiratory capacity

150
LABA
DPI Diskus Serevent®
(salmeterol)
DPI Aerolizer Foradil®
(formoterol)
DPI Breezhaler Onbrez®
(indacaterol)
SMI Respimat Striverdi®
(Olodaterol)

153
LAMA
DPI HandiHaler/
SMI Respimat
Spiriva®
(tiotropium)
DPI Breezhaler Seebri®
(glycopyrronium)
DPI Genuair Eklira®
(aclidinium)
DPI Ellipta Incruse®
(umeclidinium)
LAMA inhalers for COPD

Proskocil BJ et al. Proc Am Thorac Soc. 2005;2(4):305-310.
SMC relaxationSMC contraction
M3- muscarinic
receptors
Beta Agonists
(LABA)Anticholinergics
(LAMA)
β2-adrenergic
receptors
Mechanisms of action of bronchodilators
on airway smooth muscle

159
Fixed-dose
combination
LABA/LAMA
DPI Ellipta Anoro®
(vilanterol/umeclidinium)
DPI Breezhaler Ultibro®
(indacaterol/glycopyrroniu
m)
SMI Respimat Inspiolto®
(olodaterol/tiotropium)
DPI Genuair Duaklir®
(formoterol/aclidinium)
Combination LABA/LAMA inhalers for COPD

161
ICS/LABA
DPI Diskus Advair®
(Fluticasone/salmeterol)
DPI Turbuhaler Symbicort®
(Budesonide/formoterol)
DPI Ellipta Relvar®
(Fluticasone/vilanterol)

Combination inhalers in COPD
Symbicort 320 Turbohaler and Seretide 500 Accuhaler

166
Previous ABCD assessment 2011

Assessment of Symptoms
 Best way to assess symptoms is to use validated
questionnaires:
 Modified Medical Research Council dyspnea scale. 
MMRC
 COPD AssessmentTest  CAT

169

Refined GOLD guidelines 2017
Classification and Treatment updates

Refined A, B, C, D assessment tool: overview
(C) (D)
(A) (B)
FEV1 (% predicted)
GOLD 1 ≥ 80%
GOLD 2 50-79
GOLD 3 30-49
GOLD 4 < 30
Post-
bronchodilator
FEV1/FVC < 0.7
≥ 2 or ≥ 1
leading to
hospital
admission
0 or 1
(not leading
to hospital
admission)
Spirometrically
confirmed
diagnosis
Assessment of
airflow limitation
Assessment of
symptoms/risk
of exacerbations
Exacerbation
history
Symptoms
CAT < 10 CAT > 10
mMRC 0–1 mMRC > 2

Assessment of COPD: GOLD 2017

179
 For Group C patients, it is recommended that treatment be
started with a single long-acting bronchodilator, preferably
a LAMA ( LAMA was superior to the LABA regarding
exacerbation prevention).
 A second long-acting bronchodilator or the combination of
LABA/ICS may be used for persistent exacerbations;
 The guidelines recommend LABA/LAMA as the addition of
ICS has been shown to increase pneumonia risk in some
patients.

181
 For Group D patients, a LABA/LAMA combination is
preferred as initial therapy over LABA/ICS as these patients
may be at higher risk of developing pneumonia with ICS
use.
 For patients with high blood eosinophil counts or those with
asthma-COPD overlap, LABA/ICS could be considered first-
line therapy.

Treatment of COPD: GOLD 2017
GOLD
Grade
Preferred Treatment For Continued Symptoms or
Exacerbations
A
PRN SABA or LABA
or SAMA or LAMA
Use alternative class
B LABA or LAMA LAMA + LABA
C LAMA
LAMA + LABA*
[or] LABA + ICS
D LAMA + LABA
LAMA + LABA + ICS
[or] LABA + ICS
182
*Preferred
GOLD 2017

(C)
(D)
(A) (B)
LAMA + LABA LABA + ICS
LAMA
Further
exacerbation(s)
Continue, stop or try
alternative class of
bronchodilator
A bronchodilator
Evaluate effect A long-acting
bronchodilator
(LABA or LAMA)
Persistent
symptoms
LAMA + LABA
LAMA +
LABA + ICS
Further
exacerbation(s)
Further
exacerbation(s)
Consider roflumilast
if FEV1 <50% pred.
and patient has
chronic bronchitis
Consider
macrolide
(in former
smokers)
Persistent
symptoms/further
exacerbation(s)
Treatment algorithm by GOLD groups:
No role of ICS containing treatment in Groups A and B
GOLD
Group A
and B
completely
ICS-free
In patients with a major discrepancy between the perceived level of
symptoms
and severity of airflow limitation, further evaluation is warranted
Preferred
treatment
LAMA + LABA
LABA +
ICS
LAMA

(C)
(D)
(A) (B)
LAMA
Further
exacerbation(s)
bronchodilator
A bronchodilator
bronchodilator
(LABA or LAMA)
Persistent
symptoms
LAMA + LABA
LAMA +
LABA + ICS
Further
exacerbation(s)
Further
exacerbation(s)
Consider roflumilast
if FEV1 <50% pred.
and patient has
chronic bronchitis
Consider
macrolide
(in former
smokers)
Persistent
symptoms/further
exacerbation(s)
Limited role of ICS containing treatment in Groups C & D
Preferred
treatment
LAMA + LABA
LABA +
ICS
LAMA
No
initiation
with ICS
containing
treatment
in GOLD
Groups C
and D*
*LABA/ICS may be the first choice in some patients. For example, those with
a history and/or findings suggestive of asthma-COPD overlap.

(C) (D)
(A) (B)
LAMA
Further
exacerbation(s)
bronchodilator
A bronchodilator
bronchodilator
(LABA or LAMA)
Persistent
symptoms
LAMA + LABA
LAMA +
LABA
LABA +
ICSLAMA
LAMA +
LABA + ICS
Further
exacerbation(s)
Further
exacerbation(s)
Consider
roflumilast if FEV1
<50% pred. and
patient has chronic
bronchitis
Persistent
symptoms/further
exacerbation(s)
Preferred
treatment
In patients with a major discrepancy between the perceived level of symptoms
and severity of airflow limitation, further evaluation is warranted
LAMA/LABA plays a
critical, central role
for GOLD B-D
LAMA/LABA plays a central role for GOLD B-D
Consider
macrolide
(in former
smokers)
Consider roflumilast if
FEV1 <50% pred. and
patient has chronic
bronchitis

188

ICSs in stable COPD
 ICSs do not modify the progressive decline in FEV1
or decrease mortality (level of evidence A).
 The dose response with ICS in COPD is unknown (in
contrast to asthma treatment).
 Moderate to high doses have been used in COPD
clinical trials.
1
8
9

ICS/LABA combination therapy
 Inhaled steroids not licensed for use in COPD except
as combination
 ICS must be used in combination with LABA for
patients with COPD
 ICS monotherapy only FDA approved for treatment of
asthma, not COPD
1
9
0

 ICS-containing therapies currently over-used in management
of COPD
o More than 70% of patients with COPD are currently
receiving an ICS-containing therapy but, based on
guidelines, this should be less than 20%
o ICS should be reserved for those patients in whom
additional bronchodilation is failing to control their
exacerbations
 ICS in combination with LABA have limited role in COPD
 GOLD 2015 guidelines only recommend the addition of ICS to a
LABA in patients with an increased risk of exacerbations (Groups
and D)
The use of ICS-containing therapies in COPD

The use of ICS-containing therapies in COPD
 Compared to non-ICS-containing therapies in COPD,
therapies containing ICS, eg, LABA/ICS FDC are associated
with greater risk of:
 Pneumonia
 Bone density decline and fractures
 Candidiasis and skin lesions
 Cataracts
 Evidence linking ICS-containing therapies with increased
risk of diabetes mellitus

Randomised
controlled trial
Observational
study
Systematic
review
Pneumonia X X X
Tuberculosis X
Bone fracture
(no effect on
fracture risk)
X X
Skin thinning/
easy bruising
X
Cataract X
Diabetes X
Oropharyngeal
candidiasis
X X X
Side effects of ICS in COPD and type of evidence
Price D. Prim Care Respir J 2013; 22: 92-100.

Discontinuation of ICS reduces the risk of serious pneumonia
associated with long-term ICS use
196
* Retrospective analysis using the Quebec health insurance databases for COPD patients discontinued from ICS during 1990-2005 (n=103,386).
ICS=inhaled corticosteroid; RR=rate ratio.
Suissa S et al. Chest 2015;148(5):1177-1183.
20% reduction
after 1month
The overall risk of serious pneumonia was reduced by 37% following ICS discontinuation
50% reduction
after 4 months
0.5

1
9
7
Is ICS Withdrawal or Step Down
Therapy Possible in COPD ?

WISDOM study
The impact of stepwise withdrawal of
inhaled corticosteroids on exacerbations
in COPD patients
Magnussen H et al.: Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD
N Engl J Med 2014;371:1285-94
For internal use only – strictly confidential. Do not copy, detail or distribute externally.

1
9
9

2
0
0
WISDOM (Withdrawal of Inhaled Steroids During
Optimised bronchodilator Management) study

Study design
6-7 0
S
C
R
E
E
N
I
N
G
Treatment
52Week -6
ICS
(remained on triple therapy from run-in)
Stepwise ICS withdrawal
(remained on dual bronchodilator)
Run-in
Triple
therapy
12
R
A
N
D
O
M
I
S
A
T
I
O
N
ICS stepwise withdrawal Stable
treatmen
t
Reduced to 250 µg BID
Reduced to 100 µg BID
Reduced to 0 µg (placebo)
Fluticasone propionate 12-week
withdrawal schedule
500 µg BID
18
• Tiotropium 18 µg QD
• Salmeterol 50 µg BID
• Fluticasone propionate 500 µg BID
Triple therapy
regimen
Magnussen H et al N Engl J Med 2014;371:1285-94

 With regard to the risk of exacerbations, the majority of patients with
stable severe COPD can be satisfactorily managed with appropriate
inhaled bronchodilator therapy alone
 And even those with a higher blood eosinophil count (≥300 cells/µL or
≥4%) who may benefit from an additional treatment with ICS should
also be assessed for risks and benefits of ICS therapy
Conclusions

2
0
3

DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY.204

Features that (when present) favor asthma
or COPD
GINA 2014, Box 5-2B (3/3)
Feature Favors asthma Favors COPD
Age of onset Before age 20 years After age 40 years
Lung function Record of variable airflow limitation
(spirometry, peak flow)
Normal between symptoms
Record of persistent airflow limitation
(post-BD FEV1/FVC <0.7)
Abnormal between symptoms
Past history or
family history
Previous doctor diagnosis of asthma
Family history of asthma, and other allergic
conditions (allergic rhinitis or eczema)
Previous doctor diagnosis of COPD,
chronic bronchitis or emphysema
Heavy exposure to a risk factor: tobacco
smoke, biomass fuels
Chest X-ray Normal Severe hyperinflation
Time course No worseningof symptoms over time.
Symptoms vary seasonally, or from year to
year
May improve spontaneously, or respond
immediately to BD or to ICS over weeks
Symptomsslowly worsening over time
(progressive course over years)
Rapid-acting bronchodilator treatment
provides only limited relief
Pattern of
respiratory
symptoms
Symptoms vary overminutes, hours or days
Worse during night or early morning
Triggered by exercise, emotions including
laughter, dust, or exposure to allergens
Symptoms persist despite treatment
Good and bad days, but always daily
symptoms and exertional dyspnea
Chronic cough and sputum preceded
onset of dyspnea, unrelated to triggers

“Make everything as
simple as possible,
but not one bit
simpler”
Einstein

Updates on Pharmaological Management of Asthma & COPD

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