Chronic Obstructive

Pulmonary Disease
 Global COPD – the ever rising Burden
GOLD 2011-16 GOLD 2017
Approximately 210 The global burden of
million1 people have COPD cases was estimated
COPD to be 384 million2

• Global prevalence of COPD is 11.7%

• Currently 3 million annual deaths due to COPD.
• Deaths in 2030 might be 4.5 million deaths annually.
1. World Health Organisation: Global surveillance, prevention and control of chronic respiratory diseases, 2007
http://www.who.int/respiratory/publications/global_surveillance/en/
2. Journal of Global Health 2015; 5(2) : 020415 2
 COPD in India – the ever rising Burden

1971 2011

6.45 million 14.84 million1

Burden has more than
doubled in these 4
decades

Crude estimates suggest that 30 million people suffer from COPD in India2

3
1. J Assoc Physicians India. 2012; 60 Suppl:14-16 I 2. J Assoc Physicians India. 2012; 60 Suppl:5-7
 COPD Facts from India

Percentage
85 Every 1 in 2 COPD
patients gets
hospitalized at least
85% once in a year

15 feared for worsening of

symptoms due to weather
change.
1 in 3 COPD patients is a
never smoker

89%
patients visited
46% are exposed to biomass doctor for
54% worsening
smoke
symptoms

4
The COPD Patients Survey, Oral Presentation no. 8, Presented at NAPCON, November 24-27, 2016, Mumbai, India
 COPD in India - Economic impact

A m o u n t in c ro re s
Increased impact on economical
burden
60,000 48306
40,000 35337
25124
20,000
0
Increased risk of hospitalizations

Increased risk of
exacerbations

COPD under-
treatment

COPD delayed
diagnosis 5
 GOLD 2017: Updated COPD definition includes persistent
respiratory symptoms and airflow limitation

GOLD 20161 GOLD 20172

COPD, a common preventable and treatable COPD is a common, preventable and treatable
disease, is characterized by persistent disease that is characterized by persistent
airflow limitation that is usually respiratory symptoms and airflow limitation
progressive and associated with an that is due to airway and/or alveolar
enhanced chronic inflammatory abnormalities usually caused by significant
response in the airways and the lung to exposure to noxious particles or gases
noxious particles or gases

1. GOLD 2016 6
COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease 2. GOLD 2017
Healthy Respiratory System
Smooth muscle
Bronchial tube
Alveoli

Open bronchial tube

Smooth muscle

Carbon
dioxide
leaves
blood Oxygen enters
supple blood supply

Blood vessel

Normal Alveoli
7
 COPD Affected Lungs
In COPD, the bronchial
tubes become inflamed
and clogged with
Bronchoconstriction
mucus, which narrows
the airways and makes
Inflammation it more difficult to get air
into and out of the
Increased mucus lungs. Also, the
muscles around the
airways constrict,
squeezing the airways
and making them even
tighter (this is called
Alveoli
bronchoconstriction).
8
 Risk factors for COPD in India

Known risk factors

Smoking Hookah Bidi Chillum

More than 70% use

Known but not biomass fuel for
noticed cooking purposes

Chullah smoke Occupational Mosquito coils?

exposure

Arising Risk factors Tuberculosis, Chronic persistent poorly treated asthma, Childhood RTIs,
Poverty, Nutrition

9
J Assoc Physicians India. 2012; 60 Suppl:17-21 I J Assoc Physicians India. 2012; 60 Suppl:5-7
Pathogenesis

• Oxidative stress
• Protease- antiprotease imbalance
• Inflammatory cells
• Inflammatory mediators
• Fibrosis

10
Pathophysiology

12
COPD: A Multi-component disease

13
 Patients report COPD symptoms to doctors mostly
when it affects their daily routine – Delayed reporting

Increased Increased sputum production

Increased cough
breathlessness and change in sputum colour

The most frequent complaint from COPD patients, and probably the most prominent symptom limiting
health status and activities of daily living, is

breathlessness (dyspnea)
14
Prim Care Respir J 2012; 21(4): 384-391
 How does COPD affect life?
Daily activities get difficult to
perform
• Walking (82.04%), climbing stairs (87.76%) and doing household
work (62.45%) were the most common activities that made
patients breathless.

• 61.69% patients reported that COPD limited their ability to

socialize, do household work and miss work days

• 89.31% patients always or sometimes felt anxious/worried and

depressed due to COPD

15
 Clinical Course of COPD
COPD The dyspnea/inactivity
downward spiral
Expiratory flow limitation
Air trapping Dyspnea with
Exacerbations Hyperinflation activities

Breathlessness
Becomes more
sedentary to avoid
dyspnea-producing
Deconditioning Inactivity activity
(decreases activity)
HRQoL
Deconditioning
aggravates dyspnea;
Clinical manifestations patients adjust by
• Worsening of symptoms reducing activity further

• Increased risk of . Am J Med 2006;119:32–37

16
exacerbations
European Respiratory Review 2006 15: 51-57; DOI: 10.1183/09059180.00009906 COPD 2007;4:293–7
 Diagnosing COPD in patients
Age above
40 years
Is there history of exposure to risk
factors?
Patient has symptoms of: Tobacco Smoking
Cough
Occupational exposure
Sputum
Indoor pollution
Dyspnea
Outdoor pollution
Wheeze
Pulmonary Infections
Childhood history of Asthma

Confirm with
SPIROMETRY
(Fixed Ratio of
FEV1/FVC<0.7)

Adapted from Global strategy for the diagnosis, management, and prevention of Chronic Obstructive Pulmonary Disease; Global Initiative For Chronic Obstructive Lung Disease 2017 Report
COPD - Chronic Obstructive Pulmonary Disease
18
 What does a doctor look for? -- Typical signs

Barrel shaped chest

Increased severity on
COPD symptoms

Other commonly Pursed lip breathing, Increased respiratory rate, Ronchi &
observed signs wheezing, Use of accessory respiratory muscles, Low BMI

19
A significant cause of breathlessness in COPD is hyperinflation of the lungs
Assessing risk: when should spirometry be performed?

…performed in patients who

are aged >35 years, current or
ex-smokers, and who have a
chronic cough1

… offered to individuals over

… performed in patients with
35 years with tobacco/
respiratory symptoms,
occupational exposure and
particularly dyspnoea2
≥1 respiratory symptom3

1. NICE 2010
2. Qaseem A et al. Ann Intern Med 2007
3. Ulrik CS et al. Int J COPD 2011 20
 COPD Underdiagnosis Is Common

Diagnosed as COPD by
65% of physicians
65%

49%

Diagnosed as COPD by
49% of physicians

COPD symptoms in women were most

commonly misdiagnosed as asthma

Chest. 2001;119:1691-1695. 21
Early diagnosis, Preventive measures and Right
treatment -- Key to control COPD progression

22
Misdiagnosis – Might be the confounding factor
for COPD burden

• Among smokers with no prior history of obstructive lung disease,

18.7% have COPD

• Among patients currently treated with asthma therapy and no

diagnosis of COPD, 24.5% have COPD

23
Tinkelman DG, et al. J Asthma 2006;43:75–80
 Exacerbation triggers and effects
Triggers

Viruses

Bacteria Pollutants

Inflamed
Effects COPD airways

Greater airway
inflammation

Systemic Bronchoconstriction
inflammation edema, mucus

Expiratory flow
limitation

Cardiovascular Exacerbation Dynamic

comorbidity symptoms hyperinflation

COPD = chronic obstructive pulmonary disease 24

Wedzicha JA, Seemungal TA. Lancet 2007;370:786–96
 Comparison of loss of lung function in Stable COPD vs
COPD with exacerbations

100
Stage I

∆ 40 mL/yr
80
FEV1 (% predicted)

What are the key

Stage IIindicators for a doctor to predict COPD exacerbations?
∆ 47–79 mL/yr

50
Stage III
∆ 56–59 mL/yr

30
Stage IV

∆ <35 mL/yr

0
Range of average rates of FEV 1 decline in patients with COPD, according
to initial severity of airflow limitation Role of exacerbations in accelerating lung function decline

The dashed segment of the line highlights any stage or part of it where consistent information is still lacking.
COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 second
25
Int J COPD 2012;7:95–9 Lancet. 2009;374(9691):744–755
 The best predictor of future exacerbations is a history
of previous exacerbations

 Exacerbations during previous year

• OR [95% CI] (≥2 versus 0 exacerbations): 5.72 [4.47, 7.31], p<0.001
 100 mL decrease in FEV1
• OR: 1.11 [1.08, 1.14], p<0.001
 4-point increase in SGRQ-C
• OR: 1.07 [1.04, 1.10], p<0.001
 History of reflux/heartburn
• OR: 2.07 [1.58, 2.72], p<0.001
 1x109 increase in white blood cell count
• OR: 1.08 [1.03, 1.14], p=0.007

FEV1 = forced expiratory volume in 1 s; OR = odds ratio; SGRQ-C = St George’s Respiratory Questionnaire for COPD patients
26
Hurst J, et al. N Engl J Med 2010:363:1128–38
 Is it asthma or COPD?
Feature Asthma COPD
Age (Onset) Any age Usually after 40 yrs
Night time awakenings Yes Uncommon
Smoking No/May be Yes(Majorly)
Cough Usually in episodes Throughout the day

Airway Limitation Episodic, Reversible Progressive, not fully reversible

Predominant Inflammatory mediators Eosinophils Neutrophils

Diurnal variability Common Uncommon

First line of treatment Inhaled corticosteroids Inhaled bronchodilators

Past history or family history History of allergy, childhood asthma and/or History of exposure to noxious particles
family history of asthma or gases (mainly tobacco smoking and
biomass exposure)

Time course Often improves spontaneously or with Generally progressive over period of time
treatment

Common spirometry variable used for Bronchodilator Reversibility Test, Post BD Spirometry, Post BD ratio of FEV1/FVC
diagnosis increase in FEV1 ≥12% and 400 mL from <0.7 confirms COPD
baseline (marked reversibility)

Adapted from Global Strategy for Asthma Management and Prevention 2017 GINA Report available on www.ginaasthma.org
COPD - Chronic Obstructive Pulmonary Disease 27
For managing COPD, GOLD
guidelines play a key role

28
 The change in GOLD guidelines…

2007 2011 2017

• Assessment and Treatment based
• Assessment and treatment based
on
on lung function (FEV1) • Spirometry (Lung Function)
• Symptoms
• Risk of exacerbations
• Assessment based
Spirometry/Symptoms/Exacerbatio
n history
• Treatment based entirely on
• Symptoms
• Risk of exacerbations

29
The refined assessment tool
Step 3

Step 2
Group
Step 1 Grade Assess
Assess Symptoms and Risk
Diagnose
Airflow Limitation
FEV1/FVC<0.7, ≥2

Exacerbation history
or
Confirms COPD Grade FEV1 1 leading to C D
(% predicted) hospitalization

1 ≥80
2 50-79
1 not leading
3 30-49 to A B
hospitalization
4 <30

Symptoms

Spirometry Outcomes In-clinic Outcomes

Adapted from Global strategy for the diagnosis, management, and prevention of Chronic Obstructive Pulmonary Disease; Global Initiative For Chronic Obstructive Lung Disease 2017 Report
COPD - Chronic Obstructive Pulmonary Disease 30
COPD
Assessment
Test
(CAT)

Total score can range from 0-40 31

mMRC breathlessness scale

0
“I only get breathless with strenuous exercise”

1 “I get short of breath when hurrying on the level or walking up a

slight hill”

2 “I walk slower than people of the same age on the level because of
breathlessness or have to stop for breath when walking at my own
pace on the level”

3 “I stop for breath after walking about 100 yards or after a few
minutes on the level”

4 “I am too breathless to leave the house” or “I am breathless when

dressing or undressing”

32
mMRC – modified medical research council
33
 So how to manage COPD?

Treat the stable COPD patient

Prevent the progression to exacerbation

Treatment of exacerbations

Prolong the time to next exacerbation

34
Key Points of recommendations
• Long term ICS monotherapy not recommended
• LABA/LAMA preferred
• Inhaled over oral
• Antioxidant mucolytics only in selected patients
• Statin therapy not recommended

35
 Can we withdraw ICS in patients at low risk exacerbation
who gets stabilized after taking long acting bronchodilators?

• Withdrawal of inhaled corticosteroids can be safe in COPD patients at low risk of exacerbation.

• In OPTIMO1 & WISDOM2 trials COPD patients, on maintenance therapy with bronchodilators &

ICS, FEV1>50% predicted, & <2 exacerbations/year were evaluated after withdrawing ICS

• OPTIMO Trial – Did not observe any deterioration of lung function symptoms, & exacerbation

rate between the two groups at baseline and at 6 months

• WISDOM Trial – No difference in exacerbation rate

1. N Engl J Med. 2014 Oct 2;371(14):1285-94

36
2. Respir Res. 2014 Jul 8;15:77
Prolong the time to next
exacerbation

Role of inhaled steroids in COPD

Not to be used alone in COPD

Moderate to severe COPD, > 2 exacerbations / year,

An asthmatic component

Look for blood eosinophils

37
 Goals of COPD treatment

COPD
Patient

Reduce
Reduce Risk
Symptoms

New COPD management approach

can be used in any clinical setting
Current Treatment Strategy
anywhere in the world.

Adapted from Global strategy for the diagnosis, management, and prevention of Chronic Obstructive Pulmonary Disease; Global Initiative For Chronic Obstructive Lung Disease 2017 Report 38
COPD - Chronic Obstructive Pulmonary Disease
GOLD 2017 GOLD 2017

Assess

LABA+LAMA

Further
Exacerbation(s)
Long acting brochodilator
LABA/LAMA

High Risk,
GROUP A Less Symptoms GROUP D High Risk,
More Symptoms

(highlighted pathways in green indicate preferred treatment options)

39
Long term treatment with ICS/LABA may be considered in
patients with history of exacerbations
GOLD 2017 GOLD 2017
Consider Roflumilast, if
patient has
chronic bronchitis and FEV1 Consider Macrolide
LABA+LAMA ICS+LABA < 50% predicted (in former Smokers)

Further
Further Exacerbation(s)
Exacerbation(s)
ICS+LABA+LAMA Persistent
Symptoms/ Further
Exacerbation(s)
Further
Exacerbation(s)
LAMA
LAMA LABA+LAMA ICS+LABA
High Risk,
GROUP C Less Symptoms GROUP D High Risk,
More Symptoms
(highlighted pathways in green indicate preferred treatment options)
(highlighted pathways in green indicate preferred treatment options)

40
Oxygen Therapy
• SaO2 < 88% or PaO2 < 7.3Kpa
• SaO2 > 88% with evidence of PH, CCF, Polycythemia

41
Other Approaches
• LVRS
• BLVR
• Bullectomy
• EBV
• NIV

42
Non pharmacological
• Education
• Exercise
• Vaccination
• Nutrition
• End of life and palliative care
• Hypoxemia treatment
• Hypercapnia treatment

43
 A COPD patients journey
COMMUNICATIO COORDINATION COLLABORATION
N

Community
Some COPD Patient Types to Initial First Choice of Pharmacologic Management Nonpharmacologic Collaborative
consider
based
therapy Care Approach Exacerbations
clinicians of COPD According to Patient Group*
• Misdiagnosed
• Diagnosed but untreated Assessment of Reduction of risk, Smoking cessation Patient Education Home management
or not aptly treated COPD Influenza vaccination Vaccination Hospital/ED
• Undiagnosed & Exercise management
Untreated
Pulmonary Rehabilitation

Identif Reduce Managing Managing

y Diagnose Risk stable Manage
stable Maintenance
/Screen Factors disease exacerbations
disease

Assess
&
Monitor
Disease 44
MANAGEMENT OF EXACERBATIONS

45
Underdiagnosis and Misdiagnosis Increase the risk of
COPD exacerbation in stable COPD patient

Exacerbation- a Major Break in the life

46
 What is exacerbation and its impact?
COPD exacerbations lead to:

An exacerbation of COPD is an acute event Decline in lung function1

characterized by a worsening of the patient’s
respiratory symptoms that is beyond normal
day-today variations and leads to a change Increased symptoms
(breathlessness)2
in medication –Till GOLD 2016
Worsening health status3

Increased risk
“An acute worsening of respiratory of hospitalization4

symptoms that results in additional

therapy” – GOLD 2017

4,5
Increased risk of mortality

47
1. Thorax 2002; 57:847-52. 2 Eur Respir J 2003; 22:931-6. 3. Am J Respir Crit Care Med 1998; 157:1418-22.
4. Chest 2003; 124:459-67. 5. Thorax 2005; 60:925-31.
Classification of Exacerbations Introduced in GOLD 2017

According to GOLD 2017, exacerbations are now classified as:

Type of Exacerbation If treated with

Mild Only SABD
Moderate SABD + Antibiotics and/or Oral Corticosteroids
Severe Patient requires hospitalization or has an emergency room visit
SABD: Short Acting Bronchodilators

48
Stable COPD management
and prevention of Symptoms
progression to
exacerbation

Treat exacerbation Exacerbation Decline in lung

function if no
exacerbations
Prolong the time to next
Exacerbation
exacerbation
Deterioration
Exacerbation

Drugs/Surgery/LTOT/
Pulmonary rehabilitation End of Life

Graph - Disease Trajectory of a Patient with COPD

49
 Key points for management of
exacerbation
SABA with or without SAMA are recommended as initial bronchodilators to treat an acute
exacerbation

Systemic Corticosteroids can improve lung function, Oxygenation and shorten recovery time and
hospitalization duration. Duration of therapy should not be more than 5-7 days

Antibiotics when indicated, can shorten recovery time, reduce the risk of early relapse, treatment
failure, and hospitalization duration. Duration of therapy should be 5-7 days

Methylxanthines were not recommended due to its increased side effects

NIV should be first mode of ventilation used in COPD patients with acute respiratory failure as it
improves gas exchange, reduces work of breathing and the need for intubation, decreases
hospitalization duration and improves survival
50
Prolong the time to next
exacerbation

In a COPD patient with 2 or more exacerbations despite

treatment with LAMA+ ICS/LABA, specify the add-on
agent you feel is useful:

1. Roflumilast
2. N-acetylcysteine
3. Low dose macrolide
4. Theophylline

51
Prolong the time to next
exacerbation

Other commonly used drugs

Oral Drugs
• Not recommended as first line therapy; Only as add‑on in patients
Methylxanthines
symptomatic despite optimum inhaled therapy
Theophylline
Doxofylline • Regular monitoring for side effects or drug-interactions- smaller
Acebrophylline
therapeutic window

Mucolytics
N-acetyl Cysteine
Ambroxol Add-on in patients with more sputum

Other drugs
Roflumilast
Add-on in severe patients with history of exacerbations

52
 Measures of Success for Treatment of COPD

• 1. Objective physiological assessments

• A. Pulmonary function tests – Spirometry
• B. Exercise capacity - Six Minute Walk or Shuttle walk

• 2. Patient- or evaluator-reported outcome measures

• A. Symptom scores
• B. Activity scales - Medical Research Council dyspnea score, Borg Scale, and
Baseline Dyspnea Index/Transitional Dyspnea Index
• C. Health-related quality-of-life - SGRQ and the Chronic Respiratory
Questionnaire
53
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071575.pdf accessed on 18th June, 2016
Treat exacerbation

Treatment of exacerbations
• STEROIDS
- Oral Prednisolone 10mg/d x 7 days

• ANTIBIOTICS
- If sputum amount increase / change in color
- Depending on suspected strain – 4th generation Quinolones-Moxifloxacin /
Amox-Clavulonic acid

• OXYGEN
- Low dose continuous oxygen

54
 When to discharge from hospital?

Patient should be clinically stable for at least 24-48 hours,

Should be able to eat and sleep comfortably,
Should be ambulatory for activities of daily living.
In addition,
minimal requirement of short‑acting bronchodilators, and
the patient should be able to use long‑acting bronchodilators

55
Lung India. 2013;30(3):228-67
When to call for Follow-up and what to check ?

 In COPD, accurate diagnosis, and a good prescription is not enough

 Patients should be followed‑up 4-6 weeks after discharge from hospital.
 Emphasis should be laid on smoking cessation, the inhaler technique
checked, and the effectiveness of each medication monitored

Smoking cessation Inhaler technique checked Effectiveness of each medication monitored

If not given an adequate monitoring plan,

chances of losing the patient to follow-up

56
Lung India. 2013;30(3):228-67
 Comorbidities ?

Consider If the patient presents with

Cardio-vascular disease (e.g. ischemic heart breathlessness, chest pain, palpitations and feet edema
disease, hypertension)

Skeletal muscle dysfunction weakness and pain in limbs, has reduced strength and
stamina
 
COPD increases the risk of mortality in co-morbid conditions
Osteoporosis backache, vertebral fractures and complains of hip - and
knee-pain

Diabetes mellitus polydipsia, polyuria, recurrent UTI and general weakness

Depression anxiety and worry

Anemia general weakness
57
JAPI 2012; 60 (Suppl):27-30
New Therapies
• Drugs to Control Smoking
• Inhaled Bronchodilators/ICS
• Anti-infective / Anti inflammatory
• Miscellaneous
Drug to aid smoking cessation
• Anti-nicotine vaccines
• E-cigarettes
• Inhaled nicotine
• Cytisine
• Taranabant
• D3 Antagonist
• Selegiline
Inhaled bronchodilators/ ICS
• ULABAs
• New LAMAs
• Combinations of ULABAs and new LAMAs
Anti-infective / Anti inflammatory
• Azithromycin
• EM704 ( Non macrolide antibiotic)
• Pulsed Moxifloxacin
• Palivizumab
Miscellaneous
• NF-κB inhibitors
• Adhesion molecule inhibitors
• Interleukin-10
• p38 mitogen activated protein (MAP) kinase inhibitors
• Phosphoinositide-3 kinase (PI-3K) inhibitors
• Endogenous antiproteases
• Protease inhibitors