Another copd update

Gurmeet Singh, MD
• Education
▫ 1990-1997 : General Practitioner, Universitas Kristen Krida Wacana, Jakarta
▫ 1999-2002 : Family Doctor (Member), Public Health, Universitas Indonesia, Jakarta
▫ 2006-2010 : Post Graduate in Internal Medicine, Universitas Indonesia, Jakarta
▫ 2013-2015 : Trainee in Respirology and Critical Care Division, Internal Medicine, Cipto Mangunkusumo
▫ April-June 2014 : Trainee, Department of Pulmonary, Critical Care & Sleep Medicine Vardhman Mahavir Medical
College & Safdarjang Hospital, New Delhi (21th April to 17th June,2014)
• Employment:
▫ 2001-2004 : General Practioner, Wamena General Hospital, Wamena, Papua-Indonesia
▫ 2004-2005 : Head of Tiom Public Health Center, Wamena, Papua-Indonesia
▫ 2002-2004 : Teaching Staff, Nursing School, Wamena, Papua-Indonesia
▫ 2012-2014 : Supervisor (Internist) Primary Health Center, Tanah Abang
▫ 2011 - present : Staff of Respirology and Critical Illness Division, Internal Medicine, RSCM
▫ 2011 – present : Respirology Consultant at MRCCC Siloam Hospitals Semanggi
▫ 2014 - present : Honorary Editor Indonesian Journal of Chest Critical and Emergency Medicine
▫ 2014 - present : Board Staff Member of National Health Insurance Regional Central Jakarta
▫ 2015 - present : Head of 24 Hour Executive Clinic RSCM Kencana
• Organization :
▫ 1997 - present : Member of Indonesian Medical Doctor Society
▫ 2011 - present : Member of Indonesian Society of Internal Medicine
▫ 2011 - present : Member of Indonesian Society of Respirology (PERPARI)
▫ 2016 – present : Member of World Association Bronchoscopy and Interventional Pulmonology (WABIP)
▫ 2016 – present : Member of Indonesian Society of Emergency Medicine (PKGDI)

The Role of Small Airways in COPD
Gurmeet Singh, MD
Bandung Integrated Respiratory Care IV, 2016
Division of Respirology and Critical Illness
Department of Internal Medicine Universitas Indonesia
Cipto Mangunkusumo Hospital

Many questions remain regarding the
role of small airways in lung disease
• Should spirometry be routinely performed ?
• How does the role small airways in COPD ?
• How does the disease progress ?
• Are routine imaging assessments worthwhile ?

COPD is a Major Burden on Healthcare
Resources and the Economy
• COPD affects 210 million people
worldwide
• Lack of awareness for screening &
effective treatment  increasing
burden to health care
• It is predicted to become the third
leading cause of global mortality by
2030
1. Uyainah A. Small Airways in COPD: How to Treat? [Presentation] Pertemuan Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016.
2. WHO. The Top Ten Cause of Death. Available from http://www.who.int/mediacentre/factsheets/fs310/en/ [Accessed 10th August 2016]
Indonesia ?
There are many people with
undiagnosed COPD

DEFINITION OF COPD
• Global Initiative for Chronic Obstructive Lung
Disease (GOLD) 2015
▫ Preventable and treatable disease
▫ Characterized: persistent airflow limitation,
progressive
▫ Chronic inflammatory response in the airways and
lung to noxious particles of gases
© 2015 Global Initiative for Chronic Obstructive Lung Disease

Patophysiological Changes in COPD
“Patophysiological changes in COPD: central airways, small
peripheral airways, pulmonary parenchyma,
pulmonary vasculature”
Airflow Limitation in COPD :
AIRFLOW
LIMITATION
Small Airways Diseases
• Airway inflammation
• Airway fibrosis, luminal plugs
• Increased airway resistance
Parenchymal Destruction
• Loss alveolar
attachments
• Decrease of elastic recoil
Uyainah A. Small Airways in COPD: How to Treat? [Presentation] Pertemuan Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016
Structural changes
Narrowing of the small airways
Chronic Bronchitis Emphysema

Risk Factors for COPD
• Lung growth and
development
• Gender
• Age
• Respiratory infections
• Socioeconomic status
• Asthma/Bronchial
hyperreactivity
• Chronic Bronchitis
• Genes
• Exposure to particles
 Tobacco smoke
 Occupational dusts,
organic, and inorganic
 Indoor air pollution from
heating and cooking with
biomass in poorly
ventilated dwellings
 Outdoor air pollution

EXPOSURE TO RISK
FACTORS
tobacco
occupation
indoor/outdoor pollution
SPIROMETRY: Required to establish
diagnosis
Global Strategy for Diagnosis, Management and Prevention of COPD
Diagnosis of COPD
SYMPTOMS
chronic cough
shortness of breath
sputum
Post broncholidator FEV1/FVC < 0.70  persistent airflow
limitation / COPD

ASESSMENT OF COPD
• Assess symptoms
▫ Use COPD Assessment Test (CAT), Clinical COPD
Questionnaire (CCQ), or British Medical Research
Council (mMRC) scale
• Assess degree of airflow limitation using spirometry
• Assess risk of exacerbation
• Assess comorbidities
• Combined assessment of COPD
▫ Combining symptoms, airflow limitation, and
excacerbation to improve management of COPD

Patients with COPD normally show a decrease in FEV1 and FVC
There is only weak correlation between FEV1, symptoms, and impairement of a patient’s health quality of live. Within any given
cathegory, patient may have anything between relatively well preserved to very poor health status.

CAT ScoremMRC
Questionnaire

• Combined assessment of COPD
▫ Symptoms:
 Less symptoms (mMRC 0-1 or
CAT<10): patient is (A) or (C)
 More symptoms (mMRC ≥2
or CAT ≥ 10): patient is (B) or
(D)
▫ Airflow Limitation
 Low risk (GOLD 1 or 2):
patient is (A) or (B)
 High risk (GOLD 3 or 4):
patient is (C) or (D)
▫ Exacerbations
 Low risk: ≤1 per year and no
hospitalization for
exacerbation: patient is (A) or
(B)
 High risk: ≥2 per year or ≥1
with hospitalization: patient is
(C) or (D)

THERAPY
• Non-pharmacology
▫ Smoking cessation
▫ Smoking prevention
▫ Occupational
exposure
▫ Indoor and outdoor
air polution
▫ Physical activity
• Pharmacology
▫ Bronchodilators
 Beta2-agonist, anticholinergics,
theophylline, or combination
therapy
▫ Inhaled corticosteroids
 COPD patients with FEV1<60%
 Long term monotherapy non
recommended
▫ Combination inhaled
corticosteroid/bronchodilator
therapy
▫ Oral corticosteroid
 Long term not recommended
▫ Phosphodiesterase-4 inhibitors
 GOLD 3 or GOLD 4
▫ Methylxanthines

Pharmacological Therapy for Stable COPD

Does small airway inflammation or
remodeling contribute to COPD?

Small Airways
• < 2 mm in diameter and without
cartilage
• Are a major site of airflow
limitation in both asthma
and COPD
• The current techniques utilized
to assess patients for small
airway disease
• Clinicians can more effectively
phenotype patients with COPD
and small airways disease.
• This will allow new therapies
that target the small airways to
be developed
• Positively impact on the natural
progression of COPD

The small airways collapse during exhalation:
 Impeding airflow
 Trapping air in the lungs  increase residual
volume
 Reducing lung capacity

Small Airways in COPD
Derived from Figure 3 of Barnes, PJ immunology 2008: 8. 183-
192
Inflammation:
Increase in CD8 cells, neutrophils,
and langerin-positive dendritic cells
in the walls of small airways 
inflammatory response  correlate
with degree of airflow obstruction
Remodelling:
Increase in TGF-β, growth factors,
abnormal fibroblasts  fibrosis and
thickening of airway
Inflammation, fibrosis , wall thickening
+
Mucus in small airways
Airflow Obstruction
1. Uyainah A. Small Airways in COPD: How to Treat? [Presentation] Pertemuan Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016
2. Berge MVD, Hacken NHTT, Cohen J, Douma WR, Postma DS. Small Airway Disease in Asthma and COPD. CHEST 2011. 139;2:412-23.

COPD progression is associated with
increased occlusion of the small
airway lumen by inflammatory
exudates containing mucus
COPD progression is associated with
thickening of the Small Airway Wall
as a repair response to airway wall
injury
Hogg JC, et al. The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease. n engl j med 2004.350;26:2645-53.

McNulty W, Usmani OS. Techniques of assessing small airways dysfunction. European Clinical Respiratory Journal 2014, 1: 25898 -
http://dx.doi.org/10.3402/ecrj.v1.25898
Physiological and Imaging Techniques
for Assessing Small Airway

Lung Function Test for Small Airway Obstruction
Berge MVD, Hacken NHTT, Cohen J, Douma WR, Postma DS. Small Airway Disease in Asthma and COPD. CHEST 2011. 139;2:412-23.

ASSESMENT OF SMALL AIRWAYS
Spirometry • FVC, FEV1, FEV1/FVC (FEV1%)
• FEF50, FEF25-75
• DLCo : very sensitive in detecting gas exchange abnormalities. It is usually reduced in
emphysema .Help to characterize severity, but not essential to patient management
Thorax x-ray • Seldom diagnostic but valuable to exclude alternative diagnoses and establish presence of significant
comorbidities.
CT the chest • It is not routinely Recommended
• Might help in the differential diagnosis where concomitant disease are present.
• May be better able to separate gas trapping due to emphysema from gas trapping due to small
airway disease
Forced
oscillation
technique
FOT can differentiate airflow in small and large airways
by varying oscillation frequency (multifrequency FOT)
Nitrogen
washout
• For determining functional residual capacity (FRC)
Oximetry and
Arterial Blood
Gases
• Pulse oximetry can be used to evaluate a patient’s oxygen saturation and need for
supplemental oxygen therapy

Small Airways as Target Therapy
Small airways as Target Therapy
• COPD
• Asthma
• Other small airway diseases
Medication :
• Bronchodilator
• ICS
• NAC
Small airway :
• < 2 mm in diameter
and without cartilage

“ The most important determinant that can
improve the efficacy of inhaled drug delivery is
particle size. Particle size influences the total lung
and regional airways site of inhaled drug
deposition.
Particles size ~ deposit :
• > 6 µm : in the Oropharynx,
• 2 - 6 µm : target the lungs
• < 2 µm : reach the alveoli”
Deposition = Particle size
1,5µm 3µm 6µm

TAKE HOME MESSAGE
• Inflammation, remodelling, and mucus are known
to cause airflow obstruction on small airways in
COPD
• Small airway is difficult area to study because of
their relative inaccessibility and lack of a readily
available, reproducible, and noninvasive technique
to assess their function
• More studies in development of new
pharmacological therapies that target the small
airways are needed

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