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
Indonesia ?
There are many people with
undiagnosed COPD

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]
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”

Structural changes
Airflow Limitation in COPD : Narrowing of the small airways
Small Airways Diseases Parenchymal Destruction
• Airway inflammation • Loss alveolar
• Airway fibrosis, luminal plugs attachments
• Increased airway resistance • Decrease of elastic recoil

AIRFLOW
LIMITATION

Chronic Bronchitis Emphysema

Uyainah A. Small Airways in COPD: How to Treat? [Presentation] Pertemuan Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016
Risk Factors for COPD
• Genes • Lung growth and
• Exposure to particles development
 Tobacco smoke • Gender
 Occupational dusts, • Age
organic, and inorganic • Respiratory infections
 Indoor air pollution from
• Socioeconomic status
heating and cooking with
biomass in poorly • Asthma/Bronchial
ventilated dwellings hyperreactivity
 Outdoor air pollution • Chronic Bronchitis

Uyainah A. Small Airways in COPD: How to Treat? [Presentation] Pertemuan Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016
 Global Strategy for Diagnosis, Management and Prevention of COPD

Diagnosis of COPD
SYMPTOMS EXPOSURE TO RISK
FACTORS
shortness of breath
tobacco
chronic cough occupation
sputum indoor/outdoor pollution

SPIROMETRY: Required to establish

diagnosis
Post broncholidator FEV1/FVC < 0.70  persistent airflow
limitation / COPD

© 2015 Global Initiative for Chronic Obstructive Lung Disease

© 2015
Uyainah A. Small Airways in COPD: How Global
to Treat? Initiative forPertemuan
[Presentation] Chronic Obstructive Lung Disease
Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016
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

© 2015 Global Initiative for Chronic Obstructive Lung Disease

 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.

© 2015 Global Initiative for Chronic Obstructive Lung Disease

 mMRC CAT Score
Questionnaire

© 2015 Global Initiative for Chronic Obstructive Lung Disease

• 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)

© 2015 Global Initiative for Chronic Obstructive Lung Disease

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

© 2015 Global Initiative for Chronic Obstructive Lung Disease

Pharmacological Therapy for Stable COPD

© 2015 Global Initiative for Chronic Obstructive Lung Disease

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

Uyainah A. Small Airways in COPD: How to Treat? [Presentation] Pertemuan Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016
The small airways collapse during exhalation:
 Impeding airflow
 Trapping air in the lungs  increase residual
volume
 Reducing lung capacity
Uyainah A. Small Airways in COPD: How to Treat? [Presentation] Pertemuan Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016
 Small Airways in COPD
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

Derived from Figure 3 of Barnes, PJ immunology 2008: 8. 183- Remodelling:

192
Increase in TGF-β, growth factors,
abnormal fibroblasts  fibrosis and
thickening of airway
Inflammation, fibrosis , wall thickening
+ Airflow Obstruction
Mucus in small airways

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 COPD progression is associated with
thickening of the Small Airway Wall increased occlusion of the small
as a repair response to airway wall airway lumen by inflammatory
injury exudates containing mucus

Hogg JC, et al. The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease. n engl j med 2004.350;26:2645-53.
 Physiological and Imaging Techniques
for Assessing Small Airway

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
 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 FOT can differentiate airflow in small and large airways

oscillation by varying oscillation frequency (multifrequency FOT)
technique
Nitrogen • For determining functional residual capacity (FRC)
washout

Oximetry and • Pulse oximetry can be used to evaluate a patient’s oxygen saturation and need for
Arterial Blood supplemental oxygen therapy
Gases

Uyainah A. Small Airways in COPD: How to Treat? [Presentation] Pertemuan Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016
 Small Airways as Target Therapy

Small airway :
• < 2 mm in diameter
and without cartilage

Small airways as Target Therapy

• COPD
• Asthma
• Other small airway diseases

Medication :
• Bronchodilator
• ICS
• NAC

Uyainah A. Small Airways in COPD: How to Treat? [Presentation] Pertemuan Ilmiah Ilmu Penyakit Dalam 2016. Jakarta. 31th July 2016
 Deposition = Particle size

“ 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”

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