Role of Inhaled Corticosteroids in COPD

Role of Inhaled Corticosteroids in COPD
Prof.Gamal Rabie,MD,FCCP
Professor of pulmonary medicine , Assuit University

Agenda
• New Definition and overview.
• Diagnosis and assessment.
• Therapeutic Options.
• Manage stable COPD ( New pharmacological algorithms ).
• Role of Symbicort in the management of COPD.

Definition of COPD
COPD is a common preventable and treatable disease that is
characterized by persistent respiratory symptoms and airflow
limitation that is due to airway and/or alveolar abnormalities
usually caused by significant exposure to noxious particles or
gases.

Global Initiative for Chronic Obstructive Lung Disease 2017
2017

Mechanisms Underlying Airflow Limitation in COPD
Small Airways Disease
•Airway inflammation
•Airway fibrosis, luminal plugs
•Increased airway resistance
( Chronic bronchitis )
Parenchymal Destruction
•Loss of alveolar attachments
•Decrease of elastic recoil
( Emphysema )
AIRFLOW LIMITATION

Loss of elasticity of the lung

Etiology , pathobiology and pathology of COPD leading to airflow
limitation and clinical manifestations
Pathobiology
Impaired lung growth
Accelerated decline
Lung injury
Lung & systematic inflammation
Etiology
Smoking & pollutants
Host factors
Pathology
Small airway disorders or abnormalities
 Emphysema
Systemic effect
Air flow limitation
Persistent airflow limitation
Clinical manifestations
Symptoms
Exacerbations
Comorbidities

Burden & prevalence of COPD
• COPD is a leading cause of morbidity and mortality worldwide.
• The burden of COPD is projected to increase in coming decades due to continued
exposure to COPD risk factors and the aging of the world’s population.
• COPD is associated with significant economic burden.
• Based on BOLD , it’s estimated that number of COPD cases was 384 million in 2010 ,
global prevalence 11.7 % , 3 million deaths annually.
• By 2030 there may be 4.5 million deaths annually from COPD & related conditions.
BOLD : Burden of obstructive lung diseases

Risk Factors for COPD
Genes
Infections
Socio-economic
status
Aging Populations
Asthma & airway hyper-
reactivity
Chronic bronchitis

Diagnosis and Assessment: Key Points
• COPD should be considered in any patient who had :
          1) Dyspnea
          2) Chronic cough
          3) Sputum production and / or a history of exposure to risk
factors for the disease.
• Spirometry is required to make the diagnosis .

Assessment of COPD
• Assess symptoms
• Assess degree of airflow limitation using spirometry
• Assess risk of exacerbations
• Assess comorbidities

The characteristic symptoms of COPD are chronic and progressive
dyspnea, cough and sputum production that can be variable from
day-to-day.
Dyspnea: Progressive, persistent and characteristically worse with
exercise.
Chronic cough: May be intermittent and may be unproductive.
Chronic sputum production: COPD patients commonly cough up
sputum.
Symptoms of COPD

Assess symptoms
•COPD Assessment Test ( CAT).
•Clinical COPD Questionnaire ( CCQ).
•mMRC Breathlessness scale.

COPD Assessment Test (CAT)
An 8-item measure of health
status impairment in COPD.

Modified MRC (mMRC) Questionnaire
Self-administered questionnaire developed to
measure clinical control in patients with COPD

1) From your clinical practice , which patient questionnaire you rely
on in the assessment of symptoms ?
A- COPD Assessment Test ( CAT).
B- mMRC Breathlessness scale.
C- Both of the above.
D- Rely on presenting symptoms & history.

• Assess symptoms
• Assess degree of airflow limitation using spirometry
• Assess risk of exacerbations
• Assess comorbidities
Use spirometry for grading severity
according to spirometry, using four
grades split at 80%, 50% and 30% of
predicted value

Assessment of airflow limitation

Common FVL Shapes
Normal Young or quitter Poor effort
Hesitation Knee Coughing

Reporting Standards
• Largest FVC obtained from all acceptable efforts should be
reported.
• Largest FEV1 obtained from all acceptable trials should be reported.
• May or may not come from largest FVC effort.
• All other flows, should come from the effort with the largest sum of
FEV 1 & FVC.
• PEF should be the largest value obtained from at least 3 acceptable
maneuvers.

Pre & Post Bronchodilator Studies: Withholding
Medications

Reversibility
Reversibility of airways obstruction can be assessed with the use of
bronchodilators.
• > 12% increase in the FEV1 and 200 ml improvement in FEV1
OR
• > 12% increase in the FVC and 200 ml improvement in FVC.

1-First Step, Check quality of the test
1- Start:
Good start: Extrapolated volume (EV) < 5% of FVC or 0.15 L
Poor start: Extrapolated volume (EV) ≥5% of FVC or ≥ 0.15 L
2- Termination:
No early termination :Tex ≥ 6 s
Early termination : Tex < 6 s

2- Look at …………FEV1/FVC
< LLN(70%)
Obstructive or Mixed
≥ LLN(70%)
Restrictive or Normal
3- Look at FEV1 To detect degree
Mild > 70%
Mod 50-69 %
Severe 35-49%
Very severe < 35%

3- Postbronchodilator FEV1/FVC
>LLN or 70%
Asthma
< LLN or 70%
COPD

4- Reversibility test of FEV1
> 12%, 200 ml
Reversible
(Asthma)
< 12% ,200 ml
Irreversible (COPD)

5- Look at TLC
≥80 – 120 % Pure
obstruction
< 80 % Mixed

Classification of Severity of Airflow Limitation in
COPD*
In patients with FEV1/ FVC < 0.70:
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

2) From your clinical practice , what is the frequency of using spirometer
in your diagnosis ?
A- Very high
B- High
C- Medium
D- Low
E- I don’t use

Assess Risk of Exacerbations
To assess risk of exacerbations use history of exacerbations and
spirometry:
•Two or more exacerbations within the last year or an FEV1 < 50 %
of predicted value are indicators of high risk.
•One or more hospitalizations for COPD exacerbation should be
considered high risk.

Assess COPD Comorbidities
COPD patients are at increased risk for:
• Cardiovascular diseases
• Osteoporosis
• Respiratory infections
• Anxiety and Depression
• Diabetes
• Lung cancer
• Bronchiectasis
These comorbid conditions may influence mortality and
hospitalizations and should be looked for routinely, and treated
appropriately

Revised combined COPD assessment
• A refinement of the ABCD assessment tools is proposed that separates spirometric
grades from the “ ABCD “ groups
• ABCD groups will be derived exclusively from patient symptoms & exacerbations
history
• Spirometery in conjugation with patient symptoms & exacerbation history remains
vital for :
1) Diagnosis
2) Prognostication
3) Therapeutic approaches

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

Therapeutic Options: COPD Medications
Beta2-agonists
Short-acting beta2-agonists
Long-acting beta2-agonists
Anticholinergics
Short-acting anticholinergics
Long-acting anticholinergics
Combination short-acting beta2-agonists + anticholinergic in one inhaler
Methylxanthines
Inhaled corticosteroids
Combination long-acting beta2-agonists + corticosteroids in one inhaler
Systemic corticosteroids
Phosphodiesterase-4 inhibitors

• LABAs and LAMAs are preferred over short-acting agents except for patients with
only occasional dyspnea (Evidence A).
• Patients may be started on single long-acting bronchodilator therapy or dual long-
acting bronchodilator therapy, In patients with persistent dyspnea on one
bronchodilator treatment should be escalated to two (Evidence A).
• Inhaled bronchodilators are recommended over oral bronchodilators (Evidence A).
• Theophylline is not recommended unless other long-term treatment bronchodilators
are unavailable or unaffordable (Evidence B).
Key Points for the Use of bronchodilators

• Long-term treatment with ICS may be considered in association with LABAs for
patients with a history of exacerbation despite appropriate treatment with long-
acting bronchodilators (Evidence A).
• Long-term therapy with oral corticosteroids is not recommended (Evidence A).
• In patients with exacerbations despite LABA/ICS or LABA/LAMA/lCS, chronic bronchitis
and severe to very severe airflow obstruction, the addition of a PDE4 inhibitor can be
considered (Evidence B).
Key Points for the Use of anti- inflammatory agents

Key Points for the Use of anti- inflammatory agents
• In former smokers with exacerbations despite appropriate therapy, macrolides can be
considered (Evidence B )
• Statin therapy is not recommended for prevention Of exacerbations (Evidence A).
• Antioxidant mucolytics are recommended on in selected patients (Evidence A).

• Patients with severe hereditary alpha-1 antitrypsin deficiency and established
emphysema may be candidates for alpha-1 antitrypsin augmentation therapy
(Evidence B).
• Antitussives cannot be recommended (Evidence C).
• Drugs approved for primary pulmonary hypertension are not recommended for patients
with pulmonary hypertension secondary to COPD (Evidence B).
• Low-dose long acting oral and parenteral opioids may be considered for treating
dyspnea in COPD patients with severe disease (Evidence B).
Key Points for the Use of other pharmacological treatments

• Relieve symptoms
• Improve exercise tolerance
• Improve health status
• Prevent disease progression
• Prevent and treat exacerbations
• Reduce mortality
Reduce
symptoms
Reduce
risk
Manage Stable COPD: Goals of Therapy

• Avoidance of risk factors :
 Smoking cessation
 Reduction of indoor pollution
 Reduction of occupational exposure
• Influenza vaccination
Manage Stable COPD: All COPD Patients

Manage Stable COPD: Non-Pharmacological
Patient group Essential Recommended Depending on local
guidelines
A
Smoking cessation
(can include pharmacologic
treatment)
Physical activity
Flu vaccination
Pneumococcal
vaccination
B - D
Smoking cessation
(can include pharmacologic
treatment)
Pulmonary Rehabilitaion
Physical activity
Flu vaccination
Pneumococcal
vaccination

3) From your clinical practice , Pulmonary Rehabilitaion palys any role
in your non-pharmacological management of patinets group (B – D) ?
A- Yes
B-NO

Manage Stable COPD: Pharmacological treatment
algorthmis by GOLD grade
2017
Highlighted boxes and arrows indicate preferred treatment pathways

• All Group A patients should be offered
bronchodilators treatment based on it’s
effect on breathlessness ( this can be
either short- or long-acting
bronchodilator ).
• This should be continued if symptomatic
benefits is documented.
• Alternative mono bronchodilator class
may be used if needed after evaluating
effect on symptoms.
Bronchodilators
Continue , stop or
try alternative class
of bronchodilators
Evaluate effect
Group A

• Initial therapy should consist of long-acting
bronchodilator “ long-acting inhaled bronchodilators
are superior to short-acting inhaled bronchodilators
taken as needed ( prn) and are therefore
recommended.
• There is no evidence to recommend one class of long-
acting bronchodilators over another for initial relief of
symptoms in this group of patients.
• In the individual patient, the choice should depend on
the patient's perception of symptom relief.
Group B
A long – acting bronchodilators
( LABA or LAMA )
LAMA + LABA
Persistent
Symptoms

• For patients with persistent breathlessness on monotherapy—
the use of two bronchodilators is recommended.
• For patients with severe breathlessness initial therapy with two
bronchodilators may be considered.
• If the addition of a second bronchodilator does not improve
symptoms, we suggest the treatment could be stepped down
again to a single bronchodilator.
• Group B patients are likely to have comorbidities that may added
to their symptomatology and impact their prognosis and these
possibilities should be investigated.
Group B
( LABA or LAMA )
LAMA + LABA
Persistent
Symptoms

• Initial therapy should consist of a single long acting
bronchodilator, in two head to head comparisons the
tested LAMA was superior to the LABA regarding
exacerbation prevention, therefore we recommend
starting therapy with a LAMA in this group.1
• Patients with persistent exacerbations may benefit
from adding a second long acting bronchodilator
(LABA/LAMA) or using a combination of a long acting
beta 2- agonist and an inhaled corticosteroid
(LABA/ICS). 1
• As ICS increases the risk for developing pneumonia in
some patients, our primary choice is LABA/LAMA.1
EMA : Europe , Middle east & Asia
1-Global Initiative for Chronic Obstructive Lung Disease 2017
2-http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2016/04/WC500205577.pdf 6 December 2016
3-Suissaet al (2013) Thorax 2013;68:1029–1036
Group C
LAMA
LAMA + LABA LABA + ICS
Further
exacerbation(s)
• EMA supports the risk/benefit profile of ICS-containing therapies in COPD “there should be
no change to the way in which these medicines are used.” 2
• Risk of patients with COPD developing serious pneumonia is particularly elevated and dose-
dependent with fluticasone propionate use, and comparatively much lower with
budesonide.3
• No prospective head-to-head studies have been performed to determine relative risk of
adverse events between ICS-containing treatments

We recommend starting therapy with a LABA/LAMA
combination because:
•In studies with patient reported outcomes as the primary
endpoint LABA/LAMA combinations showed superior
results compared to the single substances.
“If a single bronchodilator is chosen as Initial
treatment, a LAMA is preferred for exacerbation prevention
based on comparison to LABAs “
•A LABA/LAMA combination was superior to a LABA/ICS
combination in preventing exacerbations other patient
reported outcomes in Group D patients.
Wedzicha et al. (2016) N Engl J Med. DOI: 10.1056/NEJMoa1516385
It is important to note:
Three-quarters of patients in the FLAME study were in GOLD Group D, only 19.3% of patients overall
had a history of 2 or more moderate or severe exacerbations in the previous 12 months
Group D
LAMA LAMA + LABA LABA + ICS
LAMA
+ LABA
+ ICS
Consider Roflumilast
if FEV1 50% pred.˂
And patient has
chronic bronchitis
Consider
macrolides in
former smokers
Further exacerbation(s)
Further
exacerbation(s)
Persistent
Symptoms / further
exacerbation(s)

• In some patients initial therapy with LABA/ICS
may be the first choice.
• These patients may have a history and/or
findings suggestive of asthma-COPD overlap.
• High blood eosinophil counts may also be
considered as a parameter to support the use
of ICS, although this is still under debate
Group D
LAMA
+ LABA
+ ICS
if FEV1 50% pred.˂
And patient has
chronic bronchitis
Consider
macrolides in
former
smokers
Further
exacerbation(s)
Persistent
Symptoms / further
exacerbation(s)

In patients who develop further exacerbations
on LABA/LAMA therapy we suggest two
alternative pathways:
•Escalation to LABA/LAMA/ICS.
“Studies are underway comparing the effects
of LABA/LAMA vs. LABA/LAMA/ICS for
exacerbation prevention. “
•If LABA/ICS therapy does not positively
impact exacerbations/symptoms a LAMA can
be added.
Group D
LAMA
+ LABA
+ ICS
if FEV1 50% pred.˂
And patient has
chronic bronchitis
Consider
macrolides in
former
smokers
Further
exacerbation(s)
Persistent
Symptoms / further
exacerbation(s)

If patients treated with LABA/LAMA/ICS still have
exacerbations the following options may be
considered:
•Add roflumilast : This may be considered in patients
with an FEVI < 50% predicted and
chronic bronchitis, particularly if they have
experienced at least one hospitalization for an
exacerbation in the previous year.
•Add a macrolide : The best available evidence exists
for the use of azithromycin.
Consideration to the development of resistant organisms
should be factored into making
•Stopping ICS : Evidence showing no significant harm
from withdrawal supports this recommendation .
1-Global Initiative for Chronic Obstructive Lung Disease 2017
2-Kim et al (Magnussen et al (2014) Withdrawing ICS in COPD: WISDOM. N Engl J Med 2014;371:1285-94
3-Outcome of Inhaler Withdrawal in Patients Receiving Triple Therapy for COPD. Tuberc Respir Dis 2016;79:22-30
Group D
LAMA
+ LABA
+ ICS
if FEV1 50% pred.˂
And patient has
chronic bronchitis
Consider
macrolides in
former
smokers
Further
exacerbation(s)
Persistent
Symptoms / further
exacerbation(s)
Withdrawing ICS abruptly or inappropriately is associated with a significant decrease in
lung function, quality of life and may precipitate an increase in exacerbations and
accelerate lung function decline
Withdrawing ICS from patients on triple:
•Significant decline in trough FEV1 of 43 ml (p < 0.01)2
•Significant decline in health status (p = 0.047)2
•Numerical increase in exacerbations2
•May also accelerate FEV1 decline (54.7 vs. 10.7 ml/year, p = 0.007)3

Does the inflammatory phenotype predict response to
therapy?
In stable disease:

Phenotype Infrequent exacerbator ACOS
Exacerbator with
emphysema
Exacerbator with chronic
bronchitis
Treatment strategy* Bronchodilators
Bronchodilators
+ ICS
Bronchodilators
(in some cases + ICS)
Bronchodilators
+ ICS
No Yes
ACOS? ACOS?
No Yes NoYes
Chronic cough?
YesNo
Diagnosis of COPD and ≥2 exacerbations per year?
*Choice of treatment should be based on clinical phenotype and the intensity determined by severity
• *Choice of treatment should be based on clinical phenotype and the intensity determined by severity
• ACOS = asthma COPD overlap syndrome; GesEPOC = Guía Española de la EPOC [Spanish Guidelines for COPD]; ICS = inhaled corticosteroid‒
Miravitlles M, et al. Arch Bronconeumol 2012
Characterization of patients with COPD: GesEPOC

Sputum eosinophilia predicts response to
corticosteroids in COPD
1. Brightling CE et al. Lancet 2000; 356: 1480–5
2. Brightling CE et al. Thorax 2005; 60: 193–8
-0.05
0.00
0.05
0.10
0.15
0.20
0.25
*
Least to most
eosinophilic tertile
*p < 0.01
-0.05
0.00
0.05
0.10
0.15
0.20
**
Least to most
eosinophilic tertile
∆Post-bronchodilatorFEV1(L)
**p < 0.05
Mometasone2
Mean absolute increase in FEV1 after corticosteroids, compared with placebo
Prednisolone1

WISDOM- Blood eosinophils predict exacerbation risk
following ICS step-down
 12 month double-blind parallel-group
 6 week run-in LABA + LAMA + High dose ICS
 Step down ICS or continuation
 500mcg FP- 250mcg- 100mcg stopped at week 12
Watz et al Lancet Resp Med 2016

Bronchodilators
Continue , stop or
try alternative
class of
bronchodilators
Evaluate effect
Group A
Group C
LAMA
LAMA + LABA LABA + ICS
Further
exacerbation(s)
Group B
( LABA or LAMA )
LAMA + LABA
Persistent
Symptoms
Group D
LAMA
+ LABA
+ ICS
if FEV1 50% pred.˂
And patient has
chronic bronchitis
Consider
macrolides in
former smokers
Further
exacerbation(s)
Persistent
Symptoms / further
exacerbation(s)

4) From your clinical practice , what is the first line of
pharmacological therapy regarding group D patients ?
A- LABA + ICS
B- LABA + LAMA
C- LABA + LAMA + ICS
D- LAMA only

5) From your clinical practice , what is your goal of therapy in the
management of severe or very severe COPD patients with a risk of
exacerbations ?
A- Maximise bronchodilation
B- Control inflammation
C-Both

Role of Symbicort
in
Chronic obstructive pulmonary disease Patients

Effect of treatment on lung function

SPEED study
Onset of effect: Increase in morning PEF and FEV1 after morning dose
ANOVA adjusted (for period and baseline) mean change from pre-treatment.
bid, twice daily
BUD/FORM, budesonide/formoterol
FEV1, forced expiratory volume in 1 second
FLU/SAL, fluticasone/salmeterol
PEF, peak expiratory flow
N : number of randomised patients.
0
20
40
60
80
100
120
0 5 10 15
p<0.001
p<0.001
PEFchangefrompre-dose(L/min)
Minutes after dose
FEV1changefrompre-dose(mL)
p<0.001
p<0.001
BUD/FORM320/9 μg bid
0
2
4
6
8
10
12
14
16
18
0 5 10 15
FLU/SAL 500/50 μg bid FLU/SAL 500/50 μg bid
BUD/FORM320/9 μg bid
Adapted from Partridge et al. 2009
12.0 L/min
6.3 L/min
16.3 L/min
9.8 L/min
40 mL
100 mL
110 mL
40 mL
Minutes after dose
Partridge MR, et al. Therapeutic Advances in Respiratory Disease 2009; 3: 147–157.
N = 442 N = 442

Effect of treatment on Physical Activity

CLIMB study
BUD/FORM + TIO improved change in total morning activity score versus TIO alone
BUD/FORM + TIO
Placebo + TIO
0
0.35
0.30
0.20
0.15
0.10
0.05
ChangeinCDLMtotal
score(0–5)fromrun-in
1 2 3 4 5 6 7 8 9 10 11 12
p=0.027*
p<0.001†
Weeks
0.25
*Treatment comparison from randomisation to first week of treatment.
†Treatment comparison from randomisation to last week of treatment.
CDLM: Capacity of Daily Living during the Morning questionnaire;
TIO:tiotropium
N : number of randomised patients
Adapted from Welte et al. 2009
Welte T, et al. Am J Respir Crit Care Med 2009; 180: 741–750.
N= 660

SPEED study: Morning activities
CDLM ; Capacity of Daily Living during the Morning;
FLU/SAL :fluticasone/salmeterol;
MID: minimal important difference
N : number of randomised patients.
MID
Total
Score
ChangeinCDLMquestionnaire
scoresfromrun-in
0
0.05
0.10
0.15
0.20
0.25
0.30
TO
TAL
SC
O
R
E W
ash
yourself
D
ry
yourself
G
etdressed
Eat
breakfast
W
alk
early
W
alk
late
BUD/FORM 320/9 µg bid
FLU/SAL 500/50 µg bid
p<0.05
p<0.02
p<0.02
Partridge MR, et al. Therapeutic Advances in Respiratory Disease 2009; 3: 147–157.
0.22
0.12
N = 442

Effect of treatment on quality of life

CLIMB study
Greater improvements in health status with BUD/FORM + TIO
than TIO alone
-3.8
-1.5
-4
-3
-2
-1
0
Improved
health
status
Comparisons are from randomisation to last visit.
BUD/FORM + TIO Placebo + TIO
AdjustedmeanchangeinSGRQ-Cscore
BUD/FORM: budesonide/formoterol;
SGRQ-C, St George’s Respiratory Questionnaire for patients with chronic obstructive pulmonary disease.
TIO:tiotropium
p=0.023
N= 660

Effect of treatment on exacerbation prevention

BUD/FORM reduces the number of exacerbations requiring
medical intervention
Meanno.of
exacerbations/patient/year
0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
BUD/FORM BUD FORM Placebo
*
*p<0.05 vs placebo
p=0.043 BUD/FORM vs. FORM
N=812
*p<0.05 vs placebo
p=0.015 BUD/FORM vs. FORM
N=1022
1.4
1.6
1.8
1.9
0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
BUD/FORM BUD FORM Placebo
*
1.4
1.6
1.8
1.9
BUD, budesonide
FORM, formoterol
1.Szafranski W, et al. Eur Respir J 2003; 21: 74–81;
2..Calverley PM, et al. Eur Respir J 2003; 22: 912–919.
Szafranski W, et al 1
Calverley PM, et al 2

CLIMB study: Rate of severe exacerbations reduced by 62%
with BUD/FORM + TIO versus TIO alone
Days since randomisation
0.4
0.2
0.1
0.0
Exacerbations/patient
0 15 30 45 60 75 90
0.3
BUD/FORM + TIO
Placebo + TIO
Cox-proportional hazards:
rate ratio 0.38
(95% CI 0.25, 0.57; p<0.001)
CI, confidence interval
TIO, tiotropium
Adapted from Welte et al. 2009
N= 660

Pathos: 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
Emergency
visits
Hospitalisations
Antibiotics
Oralsteroids
All
exacerbations
BUD/FORM
SAL/FLU
Eventrateper 100patient-years
**
**
**
**
*
Events per 100 patient/years for exacerbations in propensity matched COPD patients treated with
BUD/FORM (n=2734) or FLU/SAL (n=2734)
**P<0.0001; *P=0.0003 for difference.
CI :confidence intervals BUD/FORM :budesonide/formoterol
FLU/SAL: fluticasone/salmeterol
27 %
26 %
29 %
29 %
21 %
Journal of internal medicine 2013
Rate ratio ( 95% CI)
0.74
(0.69-0.79)
0.74
(0.69-0.81)
0.70
(0.66-0.75)
0.71
(0.65-0.78)
0.79
(0.71-0.89)

GenesGenes EnvironmentEnvironment
PathobiologyPathobiology
Clinical featuresClinical features
AmplifiedAmplified
inflammationinflammation
Susceptibility genesSusceptibility genes
• α1-antitrypsinα1-antitrypsin
• TelomeraseTelomerase
• Hedgehog signallingHedgehog signalling
• Many minor genes?Many minor genes?
Treatment response genesTreatment response genes
• Receptor polymorphismsReceptor polymorphisms
• Metabolism polymorphismsMetabolism polymorphisms
• Tissue response polymorphismsTissue response polymorphisms
Risk factorsRisk factors
• Cig smokeCig smoke
• Biomass fuelsBiomass fuels
• Air pollutionAir pollution
• Asthma?Asthma?
• NeutrophilsNeutrophils
• EosinophilsEosinophils
• MacrophagesMacrophages
• Tc1 cellsTc1 cells
• Th17 cellsTh17 cells
PathologyPathology
• Small airway obstructionSmall airway obstruction
• EmphysemaEmphysema
• MixedMixed
• Systemic inflammationSystemic inflammation
• SymptomsSymptoms
• Mucus hypersecretionMucus hypersecretion
• HyperinflationHyperinflation
• Disease progressionDisease progression
• Exacerbation frequencyExacerbation frequency
• ComorbiditiesComorbidities
Treatment responseTreatment response
• GenesGenes
• EnvironmentEnvironment
• PathobiologyPathobiology
• Disease stageDisease stage
• ComorbiditesComorbidites
TherapyTherapy
DETERMINANTS OF TREATMENT RESPONSE IN COPDDETERMINANTS OF TREATMENT RESPONSE IN COPD
Multiple disease phenotypesMultiple disease phenotypes
BiomarkersBiomarkers
of responseof response

Role of Inhaled Corticosteroids in COPD

Role of Inhaled Corticosteroids in COPD

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