COPD

Alexandru Corlateanu, MD. PhD

Department of Respiratory Medicine, State
University of Medicine and Pharmacy "Nicolae
Testemitanu",
Chisinau, Moldova
 Worlds Top Ten Killers:
WHO

2
ABC of COPD
2009
4 horsemen of the
ERS Web Conference, February 3rd,

Apocalypse

CHD
CVD
COPD
Lung cancer

IRCCS Veruno
Vasnetov
3 ,1887
Divisione di Pneumologia Riabilitativa
 COPD: CURRENT PROBLEMS
COPD is a major health issue causing a
huge social and economic problem
There is little awareness of this problem
among the general public, media, health
care, bio-medical research communities
and governments.
COPD is underestimated,
underdiagnosed and undertreated.
 SUMMARY OF PRESENTATION

Burden of Disease
Definition(s)
Diagnosis and differential diagnosis
Staging
Aetiology and Risk Factors
 SUMMARY OF PRESENTATION

Burden of Disease
Definition(s)
Diagnosis and differential diagnosis
Staging
Aetiology and Risk Factors
Prevalence of COPD

European Lung White Book, 2003

Mortality of COPD

European Lung White Book, 2003

 Leading Causes of Deaths
U.S. 2001
Cause of Death Number

1.
Heart Disease 699,697
2. Cancer
3. Cerebrovascular disease (stroke)
553,251
4. Respiratory Diseases (COPD)
163,601
5. Accidents
123,974
6. Diabetes
97,707
7. Pneumonia and influenza 62,123
71,252
8. Alzheimers disease
9. Nephritis
53,679
10. Septicemia
26,295
All other causes of death
32,275
 Future Mortality Worldwide
1990 2020
Ischemic heart disease
Cerebrovascular disease
Lower resp infection 3rd
Diarrheal disease
Perinatal disorders
COPD 6th
Tuberculosis
Measles Stomach Canc
Road traffic accidents HIV
Lung cancer Suicide

Murray & Lopez. Lancet

1997
Worlds Top Ten Killers: WHO

11
Worlds Top Ten Killers: WHO

12
Disability adjusted life years (DALYs)
lost worldwide 1990 and 2020
Murray C, WHO 1996

1990 2020
Lower respiratory infections 1
Diarrheal disease 2
Perinatal period conditions 3
Depressions 4 2

Ischemic hearth disease 1

5
Cerebovascular disease 4
6
3
Traffic accidents 7
12 5
COPD
 Burden of COPD: Key Points

COPD is a leading cause of morbidity and mortality

worldwide and results in an economic and social burden
that is both substantial and increasing.
COPD prevalence, morbidity, and mortality vary across
countries and across different groups within countries.
The burden of COPD is projected to increase in the
coming decades due to continued exposure to COPD risk
factors and the changing age structure of the worlds
population.
 SUMMARY OF PRESENTATION

Burden of Disease
Definition(s)
Diagnosis and differential diagnosis
Staging
Aetiology and Risk Factors
 NOSOLOGY: How do you define a
disease?

By the etiologic agent Tuberculosis

By the anatomical site interested
Pleurisy
By a pathophyisiological pattern

COPD
 COPD DEFINITION (S)

CO PD
P a th o p h y s io lo g ic a l d e fin itio n

C h r o n ic b r o n c h itis Em physem a
C lin ic a l d e fin itio n A n a to m ic a l d e fin itio n
 DEFINITIONS OF COPD
reduced maximum
expiratory flow and slow
forced emptying of the
lungs; features which do
not change markedly over
several months. Most of the
airflow limitation is slowly
progressive and
irreversible.
ERS 1995
airflow obstruction due
to emphysema or chronic
bronchitis..
ATS 1995
..a disease state characterized
by airflow limitation that is not
fully reversible. The airflow
limitation isusually both
progressive and associated with
an abnormal inflammatory
response of the lungs to
noxious particles or gases.
GOLD 2001
ATS/ERS position paper definition
Chronic Obstructive Pulmonary Disease
(COPD) is a preventable and treatable disease
state characterized by airflow limitation that is
not fully reversible. The airflow limitation is
usually progressive and is associated with an
abnormal inflammatory response of the lungs
to noxious particles or gases, primarily
caused by cigarette smoking. Although COPD
affects the lungs, it also produces significant
systemic consequences.
 Global Strategy for Diagnosis, Management and Prevention
of COPD

Definition of COPD 2011

COPD, a common preventable and
treatable disease, is characterized by
persistent airflow limitation that is
usually progressive and associated
with an enhanced chronic
inflammatory response in the airways
and the lung to noxious particles or
gases.
Exacerbations and comorbidities
 COPD:
4 Key points in the definition
Airflow limitation

Not fully reversible

Usually progressive

Inflammatory response to noxious agents

 Spirometry: Normal and COPD
0
FEV1 FVC FEV1/ FVC
Normal 4.150 5.200 80 %
1 COPD 2.350 3.900 60 %

2
FEV1
Liter

3
COPD
4 FVC
FEV1

5 Normal
FVC
1 2 3 4 5 6 Seconds
 COMPONENTS OF AIRFLOW
LIMITATION
Fibrosis and narrowing of airways irreversible
Destruction of alv. attachments, septa irreversible
Airway inflammation reversible
Smooth muscle contraction reversible
Dynamic hyperinflation reversible
 COPD = irreversible airflow
obstruction
Defined with the measurement of indices of
airflow obstruction after inhalation of
bronchodilator drugs.
In addition, a glucocorticosteroid (GCS)
reversibility test, after a treatment trial with
oral GCS, may be applied.
If airflow obstruction is fully reversible with
inhalation of bronchodilator, it is NOT COPD
COPD versus chronic bronchitis, emphysema
and asthma
Viegi G, Chest, 2004
THEORETICAL MODEL OF THE DECLINE OF LUNG
FUNCTION RELATED TO TOBACO CONSUMPTION

non smokers: 20-30 ml/year

FEV1 % predicted

smokers: > 40
ml/year Former
smokers

AGE (years)

Fletcher et al, BMJ, 1977, modified

 ASTHMA COPD
Allergens Cigarette smoke

Y Y
Y

Ep cells Mast cell Alv macrophage Ep cells

CD4+ cell Eosinophil CD8+ cell Neutrophil

(Th2) (Tc1)

Bronchoconstriction Small airway narrowing

AHR Alveolar destruction

Airflow Limitation
Reversible Irreversible

Source: Peter J. Barnes,

 Neutrophils in severe
Macrophages in
COPD
mild/moderate COPD

CD8+ cells in
mild/moderate COPD
 Bronchial biopsy Bronchial biopsy
Stable COPD (E.E.) Exacerbated COPD (E.E.)

IRCCS Veruno
 (COPD) (ASTHMA)

If final diagnosis will be COPD the If final diagnosis will be asthma the
mainstay of drug treatment is based mainstay of drug treatment is based
on lon-acting bronchodilators on steroids
Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
Professor Peter J. Barnes, MD
National Heart and Lung Institute, London UK
COPD definition: 4 Key points
key point assessment
Airflow limitation (AL) Spirometry

non reversibility of AL Bronchodilation test

progression of AL Follow-up

inflammatory response Biomarker: Biopsy, BAL,

sputum, exhaled markers?
 SUMMARY OF PRESENTATION

Burden of Disease
Definition(s)
Diagnosis and differential diagnosis
Staging
Aetiology and Risk Factors
 Diagnosis of
COPD
EXPOSURE TO RISK
SYMPTOMS FACTORS
cough tobacco
sputum occupation
shortness of breath
indoor/outdoor pollution

SPIROMETRY
 What is a spirometry ??
Spirometry is a measure of airflow and
lung volumes during a forced
expiratory
maneuver from full inspiration

PFT I 40
Silhouette of Hutchinson
Performing Spirometry

From
Chest,
2002
How to do it ??

PFT I 42
1. Stand or sit up straight (The patient
places a clip over the nose )
2. Inhale maximally
3. Get a good seal around mouthpiece of
the spirometer
4. Blow out as hard as fast as possible and
count for at least 6 seconds.
5. Record the best of three trial

*pt should hold bronchodilator few hrs before the

test

PFT I 43
1. Volume Time Graph 2. Flow-volume
loops

PFT I 44
 Volume Time Graph
The volume is plotted against the time, it
.displays the expiration

PFT I 45
1. FVC
2. FEV1
3. FEV1/FVC
4. FEF25%
5. FEF75%

PFT I 46
Forced Vital Capacity (FVC)
The total amount of air expired as
quickly as possible after taking the
deepest possible breath.

PFT I 47
FEV1 :
Volume of air which can be forcibly
exhaled from the lungs in the first
second of a forced expiratory
maneuver.

PFT I 48
FEV1/FVC
Ratio of FEV1 to FVC :
It indicates what percentage of the total
FVC was expelled from the lungs during
the first second of forced exhalation
This value is critically important in the
diagnosis of obstructive and restrictive
diseases

PFT I 49
FEF25%
Amount of air that was forcibly expelled in the
first 25% of the total forced vital capacity test.
FEF75%
The amount of air expelled from the lungs during
the first (75%) of the forced vital capacity test.
FEF25%-75%
The amount of air expelled from the lungs
during the middle half of the forced vital
capacity test.

PFT I 50
Flow-volume loops

PFT I 51
Flow-volume loops
Is a plot of inspiratory

and expiratory flow in

the vertical axis
against volume in the
horizental axis, during
the performance of
maximally forced
inspiratory and
expiratory maneuvers.

PFT I 52
 The contour of the loop assists in
the diagnosis and localization of
airway obstruction as different
lung disorders produce distinct
,easily recognized pattern.

PFT I 53
PFT I 54
Useful also in assesing acceptability of the
manoeuvers:
1. Lack of early peak suggest poor effort.
2. Sudden tailing off of expiration curve suggest
that the patient stopped blowing too early
3. Cough

PFT I 55
Obstructive V/S restrictive lung
disease ???

PFT I 56
Obstructive Lung Diseases

PFT I 57
Common Obstructive Lung
Diseases
Asthma

COPD (chronic bronchitis, emphysema

and the overlap between them).

Cystic fibrosis.

PFT I 58
Airflow is reduced because the airways narrow and the FEV1-
is reduced
-Spirogram may continue to rise for more than 6 seconds
because lung take longer to empty
-FVC may also be reduced because gas is trapped behind
obstructed bronchi due to increase in intrathoracic pressure
during maneuver compresses airways causing early airway
closure and gas trapping but this reduction to a lesser extent
than FEV1

PFT I 59
FEV1 80% of predicted Normal
FEV1 60-80% of predicted mild obst.
FEV1 40-60% of predicted moderate
FEV1 40% of predicted severe
The cardinal feature is FEV1/FVC ratio If
the ratio less than 70 consider obstructed
disease .
*Predictors: Sex, Age, Ht

PFT I 60
Predictors: Sex, Age, Ht ??

The measurements are related to the following factors:

Age :
FVC and flow rates decline with age. The value of FVC
increases up to 24 years of age and remain stable to age 35.
Height :
All spirometric measurements increase with body weight. It is
due to an increase in number and/or size of alveoli relative to
airways, the larger lungs are likely to take longer than smaller
one.
Sex :
Most pulmonary function values are lower in female than male .
Weight :
A spirometric results are positively correlated with weight to
the extent that increased weight means growth or muscle
mass. Beyond this (in obesity) spirometric values (and lung
values specially ERV) decrease with greater weight.

PFT I 61
 Flow volume loop in
Obstructive lung disease

PFT I 62
 Asthma
Peak expiratory flow
reduced so maximum height
of the loop is reduced
Airflow reduces rapidly with
the reduction in the lung
volumes because the
airways narrow and the loop
become concave
Concavity may be the
indicator of airflow
obstruction and may present
before the change in FEV1
or FEV1/FVC

PFT I 63
 Emphysema
Airways may collapse
during forced expiration
because of destruction of
the supporting lung
tissue causing very
reduced flow at low lung
volume and a
characteristic (dog-leg)
appearance to the flow
volume curve

PFT I 64
 Reversibility
Improvement in FEV1 by 12-
15% or 200 ml in repeating
spirometry after treatment with
Sulbutamol 2.5mg or
ipratrobium promide by
nebuliser after 15-30 minutes
Reversibility is a characterestic
feature of B.Asthma
In chronic asthma there may
be only partial reversibility of
the airflow obstruction
While in COPD the airflow is
irriversible although some
cases showed significant
improvement.

PFT I 65
 Interpretation of PFTs
Step 1. Look at the Flow-Volume loop to
determine acceptability of the test, and look for
upper airway obstruction pattern.
Step 2. Look at the FEV1 to determine if it is
normal ( 80% predicted).
Step 3. Look at FVC to determine if it is within
normal limits ( 80%).
Step 4. Look at the FEV1/FVC ratio to determine
if it is within normal limits ( 70%).

PFT I 66
Step 5. Look at FEF25-75% (Normal ( 60%)
If FEV1, FEV1/FVC ratio, and FEF25-75% all are
normal, the patient has a normal PFT.

If both FEV1 and FEV1/FVC are normal, but

FEF25-75% is 60% ,then think about early
obstruction or small airways obstruction.

PFT I 67
 If FEV1 80% and FEV1/FVC 70%, there is
obstructive defect, if FVC is normal, it is pure
obstruction. If FVC 80% , possibility of
additional restriction is there.
If FEV1 80% , FVC 80% and FEV1/FVC
70% , there is restrictive defect, get lung
volumes to confirm.

PFT I 68
Examples

PFT I 69
A 66 year old female complains
of cough after dust exposure

Meas Ref Pred%

FVC 2.2 2.58 85

FEV1 1.79 1.85 97

FEV1/FVC 81 72

FEF 25-75 1.82 2.23 82

PEF 5.67 5.2 109

PFT I 70
Normal Spirometry

PFT I 71
PFT I 72
 Flow volume loop suggestive of obstructive
disease
Spirometry showed Severe Obstructive defect
with no response to bronchodilator
Increased FVC could be because of Airtrapping
or could be combined obstructive and restrictive
defect to confirm need to do Lung Volume
diagnosis :

COPD
PFT I 73
A 75 year old female has a history
of dyspnea and palpitations

Meas Ref Pred%

FVC 2.62 2.82 93

FEV1 1.45 1.98 72

FEV1/FVC 55 69

FEF25-75 0.43 2.20 20

PEF 4.50 5.48 82

PFT I 74
Mild Obstructive defect

PFT I 75
Restrictive Lung Diseases

PFT I 76
A. Intrinsic Restrictive Lung
Disorders

1. Sarcoidosis
2. Idiopathic pulmonary fibrosis
3. Interstitial pneumonitis
4. Tuberculosis
5. Pnuemonectomy (loss of lung)
6. Pneumonia

PFT I 77
 B. Extrinsic Restrictive Lung Disorders

1. Scoliosis, Kyphosis
2. Ankylosing Spondylitis
3. Pleural Effusion
4. Pregnancy
5. Gross Obesity
6. Tumors
7. Ascites
8. Pain on inspiration - pleurisy, rib fractures

PFT I 78
C. Neuromuscular Restrictive Lung
Disorders

1. Generalized Weakness malnutrition

2. Paralysis of the diaphragm
3. Myasthenia Gravis
4. Muscular Dystrophy
5. Poliomyelitis
6. Amyotrophic Lateral Sclerosis

PFT I 79
 Full expantion of the
lung is limited and
therefore the FVC is
reduced
FEV1 may be reduced
because the stiffness of
fibrotic lungs increases
the expiratory pressure
FEV1/FVC will be Normal
or Increased

*if you suspect restrictive

pattern you must check
TLC

PFT I 80
 Flow volume loop in
Restrictive lung disease

PFT I 81
 Flow volume loop in
Restrictive lung
disease :
Full lung expantion is
prevented by fibrotic tissue
in the lung parenchyma and
the FVC is reduced .
Elastic recoil may increased
by fibrotic tissue lead to
increase the airflow
Both FEV1 and FVC may be
reduced because the lungs
are small and stiff ,but the
peak expiratory flow may be
preserved or even higher
than predicted leads to
tall,narrow and steep flow
volume loop in expiratory
phase.

PFT I 82
PFT I 83
PFT I 84
Example

PFT I 85
Obstructive & restrictive defects

Paramet Obstructio Restrictio

er n n
FEV1 Reduced Reduced
FVC Normal Reduced
FEV1/FV Reduced Normal
C

PFT I 86
COPD: 4 DIAGNOSTIC CRITERIA
Progressive symptoms: cough, sputum
production, wheeze, and/or dyspnea.
History of significant tobacco consumption.
Airflow obstruction : FEV1 and FEV1/FVC
after bronchodilator drug inhalation,
showing irreversible obstruction.
Exclusion of other causes of airflow
obstruction
 COPD: SYMPTOMS AND SIGNS
Cough
Sputum production
Breathlessness
Wheezing
Adaptive behaviuor
Other symptoms (e.g. chest
pain, ankle sweling, anorexia
and weight loss due to
muscle wasting,
psychological distress and
psychiatric morbidity)
Normal physical ex. OR
Respiratory distress signs
as: tachypnea, cyanosis,
activation of acessory
respiratory muscles, pursed-
lips breathing, barrel chest
deformity, inward
displacement of lower ribs
during inspiration (Hoovers
sign).
Percussion and palpation not
very useful
Diminished breath sound
with adventitious sounds
 DIFFERENTIAL DIAGNOSIS
Asthma
Congestive Heart Failure
Bronchiectasis
Tuberculosis
Bronchiolitis (obliterative and diffuse)
 ASTHMA COPD
Sensitizing agent Noxious agent

Asthmatic airway inflammation COPD airway inflammation

CD4+ T-lymphocytes CD8+ T-lymphocytes
Eosinophils Macrophages
Neutrophils

Completely Airflow limitation Completely

reversible Partially reversible ? irreversible
 Differential Diagnosis:
COPD and Asthma
COPD ASTHMA
Onset in mid-life Onset early in life (often
childhood)
Symptoms slowly
progressive Symptoms vary from day to day
Long smoking history Symptoms at night/early morning
Dyspnea during exercise Allergy, rhinitis, and/or eczema
also present
Largely irreversible airflow
limitation Family history of asthma
Largely reversible airflow
limitation
 DIFFERENTIAL DIAGNOSIS
Asthma History
Congestive Heart Failure Cardiac US
Bronchiectasis HRCT
Tuberculosis AFB in smear
Bronchiolitis (obliterative and diffuse)
HRCT
 SUMMARY OF PRESENTATION

Burden of Disease
Definition(s)
Diagnosis and differential diagnosis
Staging
Aetiology and Risk Factors
 Classification of COPD
Stage I: Mild
Severity
FEV /FVC < 0.70
GOLD 2008

FEV1 > 80% predicted

Stage II: Moderate FEV1/FVC < 0.70

50% < FEV1 < 80% predicted

Stage III: Severe FEV1/FVC < 0.70

30% < FEV1 < 50% predicted

Stage IV: Very Severe FEV1/FVC < 0.70

FEV1 < 30% predicted or
FEV1 < 50% predicted plus
chronic respiratory failure
 COPD and Spirometry
Diagnosis of COPD requires spirometry, i.e a
post-bronchodilator FEV 1/FVC </= 70%.
Spirometric classification predicts
development of exacerbations, health status,
utilisation of health care resources and
mortality.
In the single patient, clinical judgement is
important in the assessment of severity (e.g.
co-morbidity).
 Global Strategy for Diagnosis, Management and Prevention of
COPD

Assessment of COPD:
Determine
Goalsthe severity of the disease, its
impact on the patients health status and
the risk of future events (for example
exacerbations) to guide therapy.
Consider the following aspects of the
disease separately:
current level of patients symptoms
severity of the spirometric abnormality
frequency of exacerbations
presence of comorbidities.
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

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

Assess comorbidities
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

Symptoms of COPD
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.
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using
spirometry
COPD Assessment Test (CAT)
Assess risk of exacerbations
Assess comorbidities or
Clinical COPD Questionnaire (CCQ)
or
mMRCBreathlessnessscale
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

Assessment of Symptoms
COPD Assessment Test (CAT):An 8-item
measure of health status impairment in
COPD
(http://catestonline.org).

Clinical COPD Questionnaire (CCQ):

Self-administered questionnaire
developed to measure clinical control in
patients with COPD
(http://www.ccq.nl).
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

Assessment of Symptoms
Breathlessness Measurement using the
Modified British Medical Research
Council (mMRC) Questionnaire: relates
well to other measures of health
statusand predicts future mortality risk.

2014 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of
COPD

Modified MRC (mMRC)Questionnaire

2014 Global Initiative for Chronic Obstructive Lung Disease

 Global Strategy for Diagnosis, Management and Prevention of
COPD

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

2014 Global Initiative for Chronic Obstructive Lung Disease

 Global Strategy for Diagnosis, Management and Prevention
of COPD

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
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

Assessment of COPD
Assess symptoms
Assess degree of airflow limitation
using spirometry
Assess risk of exacerbations
Assess comorbidities
Usehistory of exacerbations and spirometry.
Twoexacerbations or more within the last year
or an FEV1 < 50 % of predictedvalueare
indicators of highrisk. Hospitalization for a COPD
exacerbationassociated with increasedrisk of death.
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention
of COPD

Assess Risk of
Exacerbations
To assessrisk of exacerbationsusehistory
of exacerbations and spirometry:
Two or more exacerbationswithinthe last
yearor an FEV1 < 50 % of
predictedvalueareindicators of highrisk.
One or more hospitalizations for COPD
exacerbationshouldbeconsideredhighrisk.

2014 Global Initiative for Chronic Obstructive Lung Disease

 Global Strategy for Diagnosis, Management and Prevention of
COPD

CombinedAssessment of
COPD
Assess symptoms
Assess degree of airflow limitation
using spirometry
Assess risk of exacerbations

Combinetheseassessments for the

purpose of improving management of
COPD
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD
(GOLD Classification of Airfow Limitation))
CombinedAssessment of COPD
2
4 or
(C) (D)

(Exacerbation history)
>1
3 leading
to

Risk
Risk

hospital
2
(A) (B) admission

1 1
0 (not
leading
CAT < 10 CAT > 10
Symptoms to
mMRC 01 mMRC > 2 hospital
Breathlessness
admission)
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

CombinedAssessment of
COPD
Assess symptoms first
If CAT < 10 ormMRC 0-1:
(C) (D) Less
Symptoms/breathlessness
(A or C)

(A) (B) If CAT >10 or mMRC> 2:

More
CAT < 10 CAT >10
Symptoms/breathlessness
(B or D)
Symptoms
mMRC 01mMRC > 2
Breathlessness 2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD

CombinedAssessment of
COPD
Assess risk of exacerbations next
(GOLD Classification of Airflow Limitation)

2 If GOLD 3 or 4 or 2
4 or exacerbations per year
(C) (D) > 1 leading or > 1 leading to

(Exacerbation history)
to hospital hospital admission:
3
High Risk (C or D)

Risk
admission
Risk

If GOLD 1 or 2 and only

2
0 or 1 exacerbations
(A) (B) 1 (not
leading per year (not leading to
1 to hospital admission):
hospital Low Risk (A or B)
CAT < 10 CAT >10
admission)
Symptoms
0
mMRC01 mMRC > 2
Breathlessness 2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of
COPD
(GOLD Classification of Airfow Limitation))
CombinedAssessment of COPD
2
4 or
(C) (D)

(Exacerbation history)
>1
3 leading
to

Risk
Risk

hospital
2
(A) (B) admission

1 1
0 (not
leading
CAT < 10 CAT > 10
Symptoms to
mMRC 01 mMRC > 2 hospital
Breathlessness
admission)
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management
and Prevention of COPD

CombinedAssessme
nt of COPD
When assessing risk, choose the highest risk
according to GOLD grade or exacerbation
history. One or more hospitalizations for COPD
exacerbations should be considered high risk.)
Patien Characteristic SpirometricCla Exacerbations CAT mMRC
t ssification per year
Low Risk
A GOLD 1-2 1 < 10 0-1
Less Symptoms
Low Risk
B GOLD 1-2 1 > 10 >2
More Symptoms
High Risk
C GOLD 3-4 >2 < 10 0-1
Less Symptoms
High Risk >2
D GOLD 3-4 >2 > 10
More Symptoms
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention
of COPD

Assess COPD
COPD patients are at increased risk for:
Comorbidities
Cardiovasculardiseases
Osteoporosis
Respiratoryinfections
AnxietyandDepression
Diabetes
Lungcancer
Bronchiectasis
These comorbid conditions may influence mortality and
hospitalizations and should be looked for routinely,
and treated appropriately.
2014 Global Initiative for Chronic Obstructive Lung Disease
 COPD and Co-Morbidities

COPD patients are at increased risk for:

Myocardial infarction, angina
Osteoporosis
Respiratory infection
Depression
Diabetes
Lung cancer
 COPD and Co-Morbidities

COPD has significant extrapulmonary

(systemic) effects including:

Weight loss

Nutritional abnormalities

Skeletal muscle dysfunction

BODE INDEX

Celli B et al. NEJM 2004

 SUMMARY OF PRESENTATION

Burden of Disease
Definition(s)
Diagnosis and differential diagnosis
Staging
Aetiology and Risk Factors
 Aetiology of COPD
Current understanding of the etiology of
COPD is based on the concept of risk
factor for the disease.

It implies that having a specific risk

factor increases the probability to
develop the disease.
RISK FACTORS FOR COPD
Host factors Exposures
Genetic factors Smoking
Socioeconomic status
Airway hyper-
reactivity, IgE and Occupational,Environ-
asthma mental pollution
Perinatal events and
Lung growth
childhood illness
Recurrent broncho-
pulmonary infections
Nutritional factors
 COPD: evidence for
genetic determinants
Alpha-1 antitrypsin deficiency is
associated with a genetic COPD
Pulmonary function tests in the general
population and in twins suggest a genetic
contribution to variation in pulmonary
function.
There is a higher rate of airflow
obstruction in relatives of COPD patients
than in control subjects.
 Z
(G A)

5' 3'
IA IB IC II III IV V

Z-variant a 1AT

Reduced proteinase Loop-sheet polymers

inhibitory capacity (aggregation, reduced secretion)

Inflammation Proteolytic activity Impaired

resulting in destruction hepatocyte function

Emphysema Levercirrhosis
 THE CLINICAL SPECTRUM OF
AAT DEFICIENCY LUNG DISEASE
AAT deficiency may present as a panlobular
emphysema in young smokers.

However, it may present as chronic bronchitis,

COPD, bronchiectasis, asthma.

WHO recommends screening for AAT deficiency

in every COPD and asthma patient WHO Bulletin 1997
 TOBACCO AND COPD
Tobacco smoking is the best known risk factor
for the development of COPD.
Roughly 20% of smokers develop COPD, with
variable degree of mixing between CB and E,
although recent evidence suggests that this
fraction could be even higher.
Current understanding of the pathogenesis of
COPD relies on the chronic inflammatory (and
immune?) reaction taking place in the airways
of smokers.
 COPD CANDIDATE GENES
Proteases/Antiproteases: Immunological factors:
alpha 1-antitrypsin, alpha HLA, TNF, AB0, Ig, IFN
1-antichimotrypsin, SLPI,
neutrophil elastase; Dutch hypothesis: IL-4,
Oxidants/Antioxidants: IL-5, IgE, beta-adrenergic
SOD, HEOX, cNOS; receptor;
Inflammatory mediators: Cystic fibrosis
IL-8, CXCR-1, CXCR-2,
MCP, CCR5, CCR2, component: CFTR
LTB4;
Category Candidate gene Support assn Do not support
assn

Protease/Anti- PiMZ Lieberman (1986) Bruce (1984)

protease

A1AT 3 Flanking Kalsheker (1990) Sandford (1997)

region

Antichymotrypsin Poller (1992) Sandford (1998)

Oxidant/Anti- Microsomal Epoxide Smith (1997) Yim (2000)

oxidant Hydrolase

Heme-Oxigenase-1 Yamada (2000) He (2002)

Glutathione S1- Yishii (1999) Yim (2002)

Transferase P1

Other candidates CFTR Gervais (1993) Arlich (1995)

ABO Blood group Cohen (1980) Vestbo (1993)

Vitamin D binding Schellenberg (1998) Kaufmann(1983)

protein

TNF-alpha Sakao (2001) Higham (2000)

 Occupational and
environmental risk factors
A number of occupational dusts and
chemicals may cause COPD, or they
may have an additional effect to
increase the risk of COPD.

It may be helpful to think of a persons

exposure as the total burden of inhaled
particles.
 The effect of dust or gas exposure on the incidence
of asthma and respiratory symptoms when adjusted
for gender, age, and smoking
Adjusted OR

3,0

2,0

1,5

1,2

1,0

0,8

Asthma Morning Chronic Phlegm Dyspnea Wheezing

cough cough cough grade 2

Eagan TM, AJRCCM 2002

Total burden of inhaled particles
Tobacco smoke (cigarette or other,
pack-years)
Occupational dusts and chemicals
Environmental tobacco smoke (passive
smoke, particularly during early life or
during foetal life)
Indoor/Outdoor air pollution

Additive effect
 Goals of COPD treatment

improve / prevent symptoms

reduce frequency and

severity of exacerbations

improve health status

improve exercise tolerance

GOLD 2008
 Therapy at each stage of COPD
I: Mild II: Moderate III: Severe IV: Very severe
FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70
FEV1 80% pred. 50% FEV1< 80% pred. 30% FEV < 50% pred. FEV1 < 30% pred. or
1
FEV1 < 50% plus
chronic respiratory
failure

Active reduction of risk factor(s); influenza vaccination

GOLD, 2008
www.goldcopd.com
Effective COPD management
Reduction of risk factors
Evidence

Smoking cessation
A

Vaccination

influenza
A
pneumococci
D

Occupational hygiene
inhaled noxa B
 Disease modifying interventions in COPD
Smoking cessation
82


80


Smoking cessation

FEV1 [%]

78
Oxygen treatment

Rehabilitation

76

Exsmoker
74
Smoker

72
Baseline 1 2 3 4 5
Years
Scanlon et al., AJRCCM 2000
Varenicline, a nicotinic acetylcholine receptor
partial agonist for smoking cessation
1027 adult smokers Abstinence during weeks 9 - 52
Varenicline 25
titrated to 1 mg bid
[%]
Bupropion
20
titrated to 150 mg bid
Placebo
15
Smoking cessation
counseling weekly
10
12 weeks
40 week
follow-up 5

Placebo Bupropion Varenicline

Continuous abstinence
from smoking Jorenby et al., JAMA 2006
 Effectiveness of influenza vaccine
in the community - dwelling elderly
Hospitalisation for
713 872 person-seasons influenza/pneumonia Death
65 years, 1990 - 2000
[%]

-10

-20

Prevention
-30
Hospitalisation
influenza
pneumonia -40
Death
-50
Nichol et al., NEJM 2007
 Therapy at each stage of COPD
I: Mild II: Moderate III: Severe IV: Very severe
FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70
FEV1 80% pred. 50% FEV1< 80% pred. 30% FEV < 50% pred. FEV1 < 30% pred. or
1
FEV1 < 50% plus
chronic respiratory
failure
Active reduction of risk factor(s); influenza vaccination

Add Short-acting bronchodilator (when needed)

GOLD, 2008
www.goldcopd.com
 Bronchodilators in COPD
2 - agonists Theophylline Anticholinergics

short-acting short-acting
long-acting long-acting
n se cts
spo effe
re ide
+ -
l
d ua d s
i vi f an
d
in elie
o n r
n ds ptom
e pe ym
e d fs
o ic s o
Ch term
in
Cholinergic
2 2
receptor
receptors
 The Lung Health Study
FEV1 [L]
5887 COPD patients 2.8

Ipratropium 36 g tid

+ smoking


cessation
2.7
Placebo

+ smoking cessation
Placebo



2.6
5 years Ipratropium

Smoking cessation

Placebo

FEV1
2.5
Baseline 1 2 3 4 5
Anthonisen et al., JAMA 1994 Years
 Bronchodilators in COPD
Ipratropium salbutamol
534 COPD patients
1.2 Day 1 Day 85

Ipratropium
42 g q.i.d. 1

Salbutamol
200 g q.i.d. 0.8

FEV1 [AUC0-4]
Ipratropium
+ salbutamol 0.6

0.4
85 days
0.2

FEV1 [AUC0-4] 0
IPRA SALB IPRA IPRA SALB IPRA
+SALB +SALB
Combivent Study Group, Chest 1994
 2 - agonists for COPD
Regular vs. as-needed therapy
53 COPD patients
Ipratropium 15 6
40 g qid

Salbutamol use [puffs / day]

Salbutamol 5
as-needed

Dyspnea [Score]
BDP 10 4
500 g
bid
Salbutamol
3
200 g qid
Placebo
5 2

3 months 1

0 0
Salbutamol use

Cook et al., AJRCCM 2001

 Therapy at each stage of COPD
I: Mild II: Moderate III: Severe IV: Very severe
FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70
FEV1 80% pred. 50% FEV1< 80% pred. 30% FEV < 50% pred. FEV1 < 30% pred. or
1
FEV1 < 50% plus
chronic respiratory
failure
Active reduction of risk factor(s); influenza vaccination
Add Short-acting bronchodilator (when needed)

Regular treatment with one or more

Add long-acting bronchodilators (when needed)

GOLD, 2008
www.goldcopd.com
 Bronchodilators in COPD
Salmeterol vs. ipratropium
405 COPD pts.
FEV1 < 65% 0,4 Placebo Salmeterol Ipratropium

Ipratropium 0,3
4 x 36 g/day
FEV1 [L]

Salmeterol
2 x 42 g/day 0,2
Placebo

0,1
12 weeks

FEV1
0 1 2 4 6 8 10 12
Rennard et al., AJRCCM 2001 Hours
 UPLIFT: Tiotropium in COPD
Pre- und post-bronchodilator FEV1
FEV1 (L)
1.50 Tiotropium Control
* *
*
*
1.40 *
*
*
*
1.30 * Post-bronchodilator
FEV1
* * * = 47 65 mL
1.20 * *
* * * *
1.10 Pre-bronchodilator
FEV1
= 87 103 mL
1.00
0
01 6 12 18 24 30 36 42 48

Months
*p<0.0001 vs. control
Tashkin et al., NEJM 359:1543, 2008
 Tiotropium versus placebo in COPD
Pre-dose pulmonary function
Difference (T P)
(mL) Day 21
600
** Day 42
**
400
** ** * *
200

-200

-400
** **
-600
FEV1 FVC IC FRC

Flow Volume

*p < 0.001, **p < 0.0001 vs. placebo ODonnell et al., Eur Respir J 2004
ABC of COPD
2009 Exercise tolerance inERSCOPD
Web Conference, February 3rd,

Tiotropium versus placebo

Endurance Study medication
(min)
24
Rehabilitation
20
32%* 42%*

16

16%
12
*p<0.05

8
0 2 4 6 8 10 12 14 16 18 20 22 24 26

Weeks
Tiotropium (n=55)
Placebo
IRCCS Veruno (n=53) Casaburi
Divisione et al., Chest
di Pneumologia 2005
Riabilitativa
 TORCH: Post-bronchodilator FEV1
FEV1
[mL] Placebo Salmeterol
100

50

-50

-100

-150

0 24 48 72 96 120 156

Calverley et al., NEJM 2007 Weeks

 Bronchodilators in COPD
Formoterol versus theophylline
3 months
FEV1
(l)
1.6 n = 854

1.4

1.2
0 2 4 6 8 10 12 Months
Formoterol 18 g Theophylline
Formoterol 9 g Placebo Rossi et al., Chest 2002; 121: 1058 - 1069
 Bronchodilator-induced lung deflation
in COPD
[%]
23 COPD patients
static hyperinflation 15
FRC 120% pred.
10
Salmeterol
5
50 g bid
Placebo FRC
0
2 weeks Inspiratory
-5 capacity

-10
Constant work
rate exercise
(75 % of Wmax) -15
ODonnell et al., ERJ 2004
 Salmeterol vs. placebo in COPD
Reduction in dyspnoea during exercise
Placebo
Dyspnoea
(Borg) Salmeterol
6 p = 0.07

0
0 1 2 3 4 5 6 7
Exercise endurance
ODonnell et al., ERJ 2004 (minutes)
 Tiotropium Formoterol
Pulmonary function
FEV1 [L]
Tiotropium 1 x 1 / day Tiotropium 1 x 1 / day
2 weeks Formoterol 2 x 1 / day Formoterol 1 x 1 / day
1.5
Tiotropium 1 x 1 / day Baseline
1.4

1.3

1.2

1.1

1.0

0.9

0 2 4 6 8 10 12 14 16 18 20 22 24 Hours
9h 15 h 21 h 3h 9h Time

van Noord et al., ERJ 2005

 Therapy at each stage of COPD
I: Mild II: Moderate III: Severe IV: Very severe
FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70
FEV1 80% pred. 50% FEV1< 80% pred. 30% FEV < 50% pred. FEV1 < 30% pred. or
1
FEV1 < 50% plus
chronic respiratory
failure
Active reduction of risk factor(s); influenza vaccination
Add Short-acting bronchodilator (when needed)
Add Regular treatment with one or more
long-acting bronchodilators (when needed)

Add Rehabilitation

GOLD, 2008
www.goldcopd.com
 Therapy at each stage of COPD
I: Mild II: Moderate III: Severe IV: Very severe
FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70
FEV1 80% pred. 50% FEV1< 80% pred. 30% FEV < 50% pred. FEV1 < 30% pred. or
1
FEV1 < 50% plus
chronic respiratory
failure
Active reduction of risk factor(s); influenza vaccination
Add Short-acting bronchodilator (when needed)
Add Regular treatment with one or more
long-acting bronchodilators (when needed)
Add Rehabilitation

Inhaled glucocorticosteroids
Add if repeated exacerbations

GOLD, 2008
www.goldcopd.com
 Inhaled corticosteroids in COPD

Main outcome Main outcome

FEV1 Exacerbations

Budesonide /
fluticasone /
triamcinolone in Meta-analyses
Budesonide in mild
moderate-severe
COPD patients
COPD patients

1998 2003
Time (years)
 Inhaled corticosteroids in COPD
751 COPD patients
(FEV1 50% pred.) Exacerbations
p < 0.001
Oral prednisone 1,5
1.5
0.6 mg / kg BW, 2 wks.
-25%
Meta-analysis: 3976 COPD patients
Fluticasone
1

Rate / year
1000 g / day
Exacerbation risk reduced by 30%
Placebo
(RR = 0.7; 95% CI: 0.58 0.84)
Alsaeedi et al., Am J Med 2002
0,5
0.5
3 years

0
FEV1 Placebo Fluticasone
Exacerbations
Burge et al., BMJ 2000
 Inhaled corticosteroids in COPD

Main outcome Main outcome

FEV1 Exacerbations

Fixed dose
combinations
Budesonide /
fluticasone /
triamcinolone in Meta-analyses
Budesonide in mild
moderate-severe
COPD patients
COPD patients

1998 2003
Time (years)
ABC of COPD ERS Web Conference, February 3rd,
2009 TOwards a Revolution in COPD Health
TORCH: Salmeterol and fluticasone in COPD
SFC combination
6112 COPD patients
FEV1 60% Exacerbations Mortality
[%]

SFC 2x 50/500 g
Salm 2x 50 g
FP 2x 500 g -10
Placebo

3 years
-20 - 17.5%
p=0.052

Mortality - 25%
p<0.001 Calverley et al.,
Exacerbations
IRCCS Veruno
-30 NEJM
Divisione di Pneumologia 2007
Riabilitativa
 TORCH: Post-bronchodilator FEV1
Adjusted mean change FEV1 (mL)

100

50

0
*
50
*
*
100

Placebo SAL FP SFC 500/50

150

0 24 48 72 96 120 156

Time (weeks)
*p < 0.001 vs placebo;

p < 0.001 vs SAL and FP Calverley et al., N Engl J Med 356:775-789, 2007
 TORCH: Risk of pneumonia
Patients [%] p<0.001 vs. placebo
20

15

10

Salmeterol-
Placebo Salmeterol Fluticasone
Fluticasone
Calverley et al., N Engl J Med 356:775-789, 2007
ABC of COPD ERS Web Conference, February 3rd,
2009
INSPIRE: Salm-FP vs. tiotropium in COPD
[%]
Exacerbations
1323 COPD patients
Post-BD FEV1 39% 1.4

1.2
Salm-FP 2x 50/500 g
1.0
Tiotropium 1x 18 g
0.8

2 years 0.6

0.4

0.2
Exacerbations

Wedzicha
IRCCS et al., AJRCCM 2008
Veruno
Salm-FP Tiotropium
Divisione di Pneumologia Riabilitativa
 Single, double, or triple therapy for COPD ?
Hospitalisations for COPD
Exacerbations
exacerbations

Pts 1 exac.
[%]
p = n.s. [n]
p = 0.01

60 60

40 40

20 20

0 0
Tio Tio Tio Tio Tio Tio
+ Salm + Salm-FP + Salm + Salm-FP
Aaron et al., Ann Intern Med 2007
 Therapy at each stage of COPD
I: Mild II: Moderate III: Severe IV: Very severe
FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70 FEV1/FVC < 0.70
FEV1 80% pred. 50% FEV1< 80% pred. 30% FEV < 50% pred. FEV1 < 30% pred. or
1
FEV1 < 50% plus
chronic respiratory
failure
Active reduction of risk factor(s); influenza vaccination
Add Short-acting bronchodilator (when needed)
Add Regular treatment with one or more
long-acting bronchodilators (when needed)
Add Rehabilitation
Add Inhaled glucocorticosteroids
if repeated exacerbations
Add Long-term O2
if chronic resp.
failure
Consider
GOLD, 2008
www.goldcopd.com surgical
treatments
 COPD is a systemic disease

Malnutrition
Weight loss

Mucociliary Structural Skeletal muscle

dysfunction changes wasting
weakness
Airflow
limitation Inflammation
Systemic
component
Osteoporosis

Cardiovascular
comorbidity
COPD: Anthropocentric management

Early diagnosis and

stage - adjusted treatment

plus

Diagnosis and treatment

of extrapulmonary manifestations

Nutritional support

Rehabilitation
 Budesonide and cardio-ischaemic events
in mild - moderate COPD [EUROSCOP]
1277 COPD patients 35 Budesonide
[n] Placebo
30
Budesonide
25

400 g bid
20
(n=634)
Placebo 15
(n=643)3 years
10

Cardio-ischaemic
events al ry al
i a i
all in a is ard on on ry r ard ia
er n g or
t o c cti or rte de o c em
v A ec y far C a o r y ha
O M s M c
Lfdahl et al., ERJ 2007 p in di is
 TORCH: Quality of life

Placebo Salmeterol Fluticasone Salm-FP

3
SGRQ Total score (Units)

0
-1

-2
-3

-4
-5
0 24 48 72 96 120 156
better
Weeks
Calverley et al., NEJM 2007;356:775
 Goals of COPD treatment

improve / prevent symptoms

reduce frequency and

severity of exacerbations

improve health status

improve exercise tolerance


GOLD, Update 2008
 FEV1 in large COPD trials

Study Current FEV1 Drug Verum Placebo Control

smoker (% PN) only
(%) at entry
Euroscop (3 yr.) 100 ~ 79 Budesonide 57 69 -

Isolde (3 yr 36-39 ~ 50 Fluticasone 50 59 -

LHS II (3.3 yr.) 90 ~ 68 Triam. 44 47 -

BRONCUS (3 yr.) 41-51 ~57 NAC 54 47 -

TORCH (3 yr.) 43 ~ 48 S/F/SFC 42/42/ 55 -

39
UPLIFT (3 yr.) 30 ~ 47 Tiotropium 37 - 42

UPLIFT (4 yr.) 30 ~ 47 Tiotropium 40 - 42

 COPD

Manage Stable COPD: Goals of

Therapy

Relieve symptoms
Improve exercise tolerance Reduce
symptoms
Improve health status

Prevent disease progression

Reduce
Prevent and treat exacerbations
risk
Reduce mortality
2014 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention
of COPD
Manage Stable COPD: All COPD
Patients
Avoidance of risk factors
- smoking cessation
- reduction of indoor pollution
- reduction of occupational exposure
Influenza vaccination

2014 Global Initiative for Chronic Obstructive Lung Disease

 Global Strategy for Diagnosis, Management and Prevention
of COPD
Manage Stable COPD: Non-
pharmacologic
Patient Essential Recommended Depending on local
Group guidelines

Smoking cessation Flu vaccination

A (canincludepharmacologi Physicalactivity Pneumococcal
ctreatment) vaccination

Smoking cessation
Flu vaccination
(canincludepharmacologi
B, C, D Physicalactivity Pneumococcal
ctreatment)
vaccination
Pulmonary rehabilitation

2014 Global Initiative for Chronic Obstructive Lung Disease

 Global Strategy for Diagnosis, Management and Prevention of
COPD
Manage Stable COPD:
PharmacologicTherapy
(Medications in each box are mentioned in alphabetical order, and
therefore not necessarily in order of preference.)
Patient Recommended Alternative choice OtherPossible
Firstchoice Treatments
LAMA
SAMA prn or
A or LABA Theophylline
SABA prn or
SABA and SAMA

LAMA
SABA and/or SAMA
B or LAMA and LABA
Theophylline
LABA

ICS +LABA LAMA and LABA or

or LAMA and PDE4-inh. or SABA and/or SAMA
C
LAMA LABA and PDE4-inh. Theophylline

ICS + LABA ICS + LABA and LAMA or

Carbocysteine
and/or ICS+LABA and PDE4-inh.or
D SABA and/or SAMA
LAMA LAMA and LABA or
Theophylline
LAMA and PDE4-inh.
 Manage Stable COPD:
PharmacologicTherapy
RECOMMENDED FIRST CHOICE

C D
GOLD 4

Exacerbations per year

ICS + LABA ICS + LABA 2 or more
or and/or or
LAMA LAMA >1
GOLD 3 leading
to
hospital
A B
GOLD 2 admission
SAMA prn LABA
or or
GOLD 1 SABA prn LAMA 1 (not
0
leading
to
CAT < 10 CAT >10 hospital
mMRC 0-1 mMRC >2
2014 Global Initiative for Chronic Obstructive Lung Disease admission)
 Manage Stable COPD:
PharmacologicTherapy
ALTERNATIVE CHOICE
C D
LAMA and LABA ICS + LABA and LAMA
GOLD 4

Exacerbations per year

or
or ICS + LABA and PDE4-inh 2 or more
LAMA and PDE4-inh or or
or LAMA and LABA >1
GOLD 3 LABA and PDE4-inh or leading
LAMA and PDE4-inh. to
hospital
A B
GOLD 2 LAMA admission
or LAMA and LABA
LABA
GOLD 1 or 1 (not
SABA and SAMA 0
leading
to
CAT < 10 CAT >10 hospital
mMRC 0-1 mMRC >2
2014 Global Initiative for Chronic Obstructive Lung Disease admission)
 Manage Stable COPD:
PharmacologicTherapy
OTHER POSSIBLE TREATMENTS
C D
Carbocysteine
GOLD 4 SABA and/or SAMA

Exacerbations per year

2 or more
SABA and/or SAMA or
Theophylline
>1
GOLD 3 Theophylline leading
to
hospital
A B
GOLD 2 admission
SABA and/or SAMA
Theophylline
GOLD 1 Theophylline
1 (not
0
leading
to
CAT < 10 CAT >10 hospital
mMRC 0-1 mMRC >2
2014 Global Initiative for Chronic Obstructive Lung Disease admission)