The COPD Diagnostic and

Treatment Challenge in
Daily Practice

Prof. dr. Tamsil Syafiuddin, SpP (K)

14 Agustus 2021
 Trends in Death Rates
for 6 Leading Causes of Death in United States, 1970-2002

Trends in Age-Standardized Death Rates for the 6 Leading Causes of Death

in the United States, 1970-2002

Jemal A, et al. JAMA 2005; 294:1255-1259.

 Leading causes of death globally

• At a global level, 7 of the 10 leading

causes of deaths in 2019 were
Noncommunicable diseases.

• COPD is the third contributor

• COPD is the only one that doesn't

go down

Source: WHO Global Health Estimates, 9 Desember 2020

 International Trends in chronic obstructive pulmonary disease
(COPD) mortality by region and sex, ages 50–84 years. a)
Age-standardised mortality rates; b) number of deaths.

a) b)

Joannie Lortet-Tieulent et al. Eur Respir J 2019;54:1901791

©2019 by European Respiratory Society (ERS)

 Finally, assessing changes in absolute number of
deaths between 2000 and 2015, the number of COPD
deaths increased by >10% in 11 countries, particularly
in Latin America, North America, Eastern and Southern
Europe (almost doubling in the Czech Republic and
Croatia), and decreased by >10% in 6 countries (40%
and 50% in Lithuania and Kyrgyzstan, respectively). In
the other 7 countries COPD deaths were more or less
stable (figure 1b).

©2019 by European Respiratory Society (ERS)

COPD is included in the WHO Global Action Plan for the
Prevention and Control of Noncommunicable Diseases
(NCDs) and the United Nations 2030 Agenda for Sustainable
Development.
Underdiagnose and Overdiagnose of COPD worldwide
Approximately 70% of COPD worldwide may be underdiagnosed.
Conversely, other studies have shown that between 30% and 60% of patients with a previous
physician diagnosis of COPD do not actually have the disease, and hence they have been
overdiagnosed.

Diab N, Gershon AS, Sin DD, Tan WC, Bourbeau J, Boulet LP, Aaron SD. Am J Respir Crit Care Med. 2018 Nov 1;198
 Underdiagnosis of COPD
• In the US, it has been estimated that 10–16 million
patients have been diagnosed with some form of
COPD1,2
• A further 16 million patients remain undiagnosed1,2
• There is a perception that the undiagnosed patients are
not seen by physicians. In reality most are, but they are
being missed

10–16 million diagnosed

versus

16 million undiagnosed

1
Petty TL. J Resp Dis 1997;18:365–9; 2Mannino DM et al. MMWR Surveill Summ 2002;51:1–16.
 Underdiagnosis and Misdiagnosis:
Patient Perceptions
‘I don’t need meds
for my breathing
• Patients may because it’s not a
‘I’ve been coughing when serious problem’
misunderstand or I wake up each morning,
minimize symptoms, but it’s just smoker’s
cough. This is normal and
such as fatigue, not harmful to my health’
dyspnoea and cough
• As a result, they may ‘Carrying these
not mention these groceries is
harder than it
symptoms to their used to be.
I must be old and
physicians out of shape’

Mannino DM and Braman S. Proc Am Thoracic Soc 2007;4:502–6

 The Importance of Earlier Diagnosis
to the COPD Patient

• Smoking cessation reduces decline in FEV1 and is the

most important intervention in COPD1

• However, even after cessation, inflammatory and

structural changes in the airways persist2,3

• In smokers aged >35 years, the deficit in percent

predicted FEV1 at the time of smoking cessation is not
fully recovered3

1
Anthonisen NR et al. JAMA 1994;272:1497-1505; 2GOLD. Global Strategy for the Diagnosis, Management, and Prevention
of Chronic Obstructive Pulmonary Disease. Updated 2010; 3Godtfredsen NS, et al. Eur Respir J 2008;32:844-853.
 The Importance of Earlier Diagnosis
to the COPD Patient

Inflammation is present even in the early stages

of COPD

• Airway inflammation is characterised by increased numbers

of neutrophils, macrophages and CD8+ lymphocytes1,2

• Infiltration of inflammatory cells into the airways occurs in

both early and late stages of COPD3

• As the disease progresses, the small airways fill with

inflammatory mucus exudates3
 Inflammation is present even in the
1
early stages of COPD
• Airway inflammation is characterised by increased numbers of neutrophils, macrophages
and CD8+ lymphocytes2,3
• Infiltration of inflammatory cells into airways occurs in both early and late COPD.1 As the
disease progresses, the small airways fill with inflammatory mucus exudates1
Airways with measurable
cells (%)

Neutrophils Macrophages Eosinophils CD4+ cells CD8+ cells

1. Hogg et al. New Eng J Med 2004. 2. GOLD Guideline (Updated 2009).
3. Barnes et al. Am J Respir Crit Care Med 2006
 COPD Phenotypes (NEW)

Systemic Physiologic
Low BMI Airflow limitation
Pulmonary Cachexia Dyspnea
Frequent Exacerbator Rapid decliner
ICS-responsive BD-responsiveness
Depression and Anxiety Hyperrresponsiveness
DM Hypercapneic
Cardiovasculer event Poor exercise tolerance
Osteoporosis Hyperinflation
Non-smokers Low DLCO
Pulmonary hypertensio

Radiologic
Emphysema
Airways disease

Friedlander et al, COPD 2007; 4: 355-384

The Progression of COPD
Mild COPD Severe COPD
Differential Diagnosis of COPD
Diagnosis Suggestive features
COPD Onset in mid-life
Symptoms slowly progressive
History of tobacco smoking,other smook
Asthma Early in life
Symptoms very widely from day to day
Symptoms worse at night/early morning
Allergy/Rhinitis
Family history of asthma
Obesity coexsistence

Congestive Heart Failure CXR dilated heart,pulmonary edema

Pulmonary function test restrictive

Tuberculosis Onset all ages

CXR shows lung infiltrate
Microbiological confirmation
Two Effective Methods to Identify
the Silent Population with COPD

1. Validated screening questionnaires

• e.g. COPD Population Screener™ (COPD-PS)1
• Simple and easy to use

2. Diagnostic standard spirometry

• The only recognised method for confirming diagnosis

1
Martinez FJ et al. J COPD 2008;5:85–95.
Diagnosis of COPD
Global Strategy for Diagnosis, Management and Prevention of COPD

SYMPTOMS RISK FACTORS

shortness of breath host factor
chronic cough tobacco
sputum occupation
in/outdoor pollution

SPIROMETRY is required
The presence of a post-bronchodilator FEV1/FVC < 70%
confirms the presence of the persistent airflow limitation
and thus of COPD.
GOLD 2021
 Primary Health Care
(Declaration of Alma-Ata USSR,1978)
• VI. “Primary Health Care is essential health care, based
on practical, scientifically sound socially acceptable
methods and technology made universally accessible to
individuals and families in the community, through their
full participation and at a cost that the community and the
country can afford to maintain at every stage of their
development, in the spirit of self reliance and self
determination”

• di Indonesia
• Practical : SKDI 2012
• Scientifically : GOLD 2021
 Global Strategy for Diagnosis, Management and Prevention of COPD

Therapeutic Options: Key Points

(Non Pharmacology)

▪ Smoking cessation has the greatest capacity to

influence the natural history of COPD. Health care
providers should encourage all patients who smoke
to quit.
▪ Pharmacotherapy and nicotine replacement reliably
increase long-term smoking abstinence rates.
▪ All COPD patients benefit from regular physical
activity and should repeatedly be encouraged to
remain active.
© 2021 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Bronchodilators
(Pharmacology)

▪Bronchodilator medications are central to the

symptomatic management of COPD.
▪ Bronchodilators are prescribed on an as-needed or on a
regular basis to prevent or reduce symptoms.
▪ The principal bronchodilator treatments are beta2-
agonists, anticholinergics, theophylline or combination
therapy.
▪ The choice of treatment depends on the availability of
medications and each patient’s individual response
in terms of symptom relief and side effects..
© 2021 Global Initiative for Chronic Obstructive Lung Disease
 Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Bronchodilators

▪ Long-acting inhaled bronchodilators are

convenient and more effective for symptom relief
than short-acting bronchodilators.
▪Long-acting inhaled bronchodilators reduce
exacerbations and related hospitalizations and
improve symptoms and health status.
▪ Combining bronchodilators of different
pharmacological classes may improve efficacy and
decrease the risk of side effects compared to
increasing the ©dose of a single bronchodilator.
2021 Global Initiative for Chronic Obstructive Lung Disease
 Long-acting brochodilators interrupt the
“vicious cycle” in COPD
Airflow limitation Long Acting
Bronchodilators
Air trapping

Hyperinflation

Dyspnea

Activity

De-conditioning Quality of life

Adapted from Decramer M, Eur Respir Rev 2006

 Initial treatment of COPD

Definition of abbreviations: eos: blood eosinophil count in cells per microliter; mMRC: modified Medical Research
Council dyspnea questionnaire; CAT™: COPD Assessment Test™.

© 2020 Global Initiative for Chronic Obstructive Lung Disease

 Management of Exacerbations
Pharmacologic treatment

The three classes of medications most commonly used for

COPD exacerbations are:
► Bronchodilators
Although there is no high-quality evidence from RCTs, it is
recommended that short-acting inhaled beta2-agonists, with or
without short-acting anticholinergics, are the initial bronchodilators
for acute treatment of a COPD exacerbation.
► Corticosteroids
Data from studies indicate that systemic glucocorticoids in COPD
exacerbations shorten recovery time and improve lung function
(FEV1). They also improve oxygenation, the risk of early relapse,
treatment failure, and the length of hospitalization.
► Antibiotics

© 2020 Global Initiative for Chronic Obstructive Lung Disease

 Moving COPD to Individualized Medicine
GOLD 2019: Pharmacological Treatment
Approach
Initial Pharmacological
Treatment

Management Cycle
Review, Assess, Adjust

Follow-up Pharmacologic
Treatment

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2019 Report. www.goldcopd.org. © 2018 Global Initiative for Chronic Obstructive Lung
Disease, all rights reserved. Use is by express license from the owner.
 ICS+LABA

© 2020 Global Initiative for Chronic Obstructive Lung Disease

 Summary
•Identifying patients with COPD before the disease
becomes too advanced is important to optimise the
treatment and management of symptomatic patients

•Diagnosis can be made based on symptoms and risk

factors and confirmed by spirometry

•Inhaled long acting bronchodilators are the mainstay

in the management of stable COPD

•LABA + ICS , ICS is highly dependent on the patient's

phenotype
 Thank You

Professionalism means consistency of quality

(Frank Tyger)
Figure. Transforming growth factor-β (TGF-β) in chronic obstructive pulmonary
disease. TGF-β is released in a latent form that is activated by matrix
metalloproteinase-9 (MMP-9). It may then cause fibrosis directly through the effects
on fibroblasts or indirectly via the release of connective tissue growth factor (CTGF).
TGF-β may also down regulate β2-adrenoceptors on cells such as airway smooth
muscle to diminish the bronchodilator response to β-agonists.
 Pathophysiology of COPD:
Vagal Nerve System
Central
nervou
s
system

Vagus
Airway smooth muscle nerve
constriction ACh Parasympathet
ic
ganglion
ACh Submucos
Inflammator
ACh Cholinergic al
receptors gland
y
cell
mediators
Airway epithelium

Irritants Mucus
(e.g. cigarette smoke, bacteria, Hypersecretio
viruses) Adapted from: Hansel T/Barnes P. An Atlas of COPD. 2004 n