COPD: Pathophysiology,

Assessment and Diagnosis

The goal of this activity is to refresh doctors’ knowledge on the pathophysiology,
assessment and diagnosis of COPD. Upon completion of this module, participants
will be able to improve their understanding in these aspects:
• The burden of COPD and its underlying pathophysiology
• Identification of COPD patients in the clinic, and determination of their severity
• Differences between asthma, COPD and asthma-COPD overlap (ACO)
• How early identification and risk factor intervention can affect long-term COPD
outcomes
CPD Reviewer: Prof. Dato’ Dr Hj. Abdul Razak Muttalif
Senior Consultant Chest Physician
Institute of Respiratory Medicine
Hospital Kuala Lumpur
With contributions by: Dr Mat Zuki Mat Jaeb
Consultant Respiratory Physician
Hospital Raja Perempuan Zainab II
Dr Muventhiran Ruthranesan
Consultant Respiratory Physician
Pantai Hospital Ayer Keroh

START MODULE
Topics at a glance
• The burden of COPD
• Pathophysiology
• Assessment and diagnosis
• Differentiating between asthma,
COPD and ACO
• Benefits of early diagnosis

1
 COPD is a major health burden

Ischaemic
heart disease1

Cerebrovascular
disease1
COPD is significantly
underdiagnosed worldwide,
COPD1 including in Malaysia2
Possible reasons3:
• Lack of recognition of symptoms at the

3 rd
leading cause of
death caused by
non-communicable
≈ 500,000
Malaysians have moderate
early stage by patients and healthcare
professionals
disease1* to severe COPD 2
• Availability of spirometry tests

75 %2 25% 2

3x greater burden in
males vs females2*
• Difficulty differentiating from asthma

*in Malaysia
1. Institute for Health Metrics and Evaluation. Global burden of diseases, injuries and risk factors study 2015: GBD profile: Malaysia. Available at http://www.healthdata.org/malaysia. Accessed
on 27 March 2017. 2. Ministry of Health Malaysia. Clinical Practice Guidelines: Management of Chronic Obstructive Pulmonary Disease (2nd Edition) 2009. Available at http://www.mts.org.my/
resources/2nd%20Edition%20of%20Malaysian%20COPD%20Clinical%20Practice%20Guideline.pdf. Accessed on 27 March 2017. 3. Walters JA et al. Under-diagnosis of chronic obstructive
pulmonary disease: A qualitative study in primary care. Respir Med 2008;102(5):738–743.

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COPD pathophysiology
Etiology, pathobiology and pathology of COPD leading to
airflow limitation and clinical manifestations
COPD is characterised by persistent respiratory symptoms Etiology
• Smoking and pollutants
and airflow limitation that is due to airway and/or alveolar • Host factors
abnormalities usually caused by significant exposure to noxious
particles or gases.1 Pathobiology
• Impaired lung growth
• Accelerated decline
• Lung injury
• Lung and systemic inflammation

Alveoli Pathology
• Small airway disorders or abnormalities
• Emphysema
• Systemic effects

Bronchioles Airflow limitation Clinical manifestations

• Persistent airflow limitation • Symptoms
• Exacerbations
• Comorbidities
Adapted from GOLD 2017.

1. Global Strategy for Diagnosis, Management and Prevention of COPD 2017. Available from http://www.goldcopd.org. Accessed on 27 March 2017.

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Lung hyperinflation
Normal lung Lung with COPD
Hyperinflation due to decreased elastic
recoil of diaphragm/chest wall may be
visible on X-ray1

Reduced inspiratory capacity

1. Gibson GJ. Pulmonary hyperinflation a clinical overview. Eur Respir J 1996;9(12): 2640–2649.

4
Identifying COPD patients1
SYMPTOMS RISK FACTORS
• Dyspnoea • Host factors eg. genetic factors,
 Progressive congenital/developmental
 Worsens with exercise abnormalities, etc.
 Persistent • Tobacco smoke
• Chronic cough • Pollution (smoke from cooking/
 May be intermittent and unproductive heating fuels)
 Recurrent wheeze • Occupational exposures eg. dusts,
• Chronic sputum production vapours, fumes, gases, chemicals
 Any pattern

SPIROMETRY REQUIRED TO ESTABLISH COPD DIAGNOSIS

Adapted from GOLD 2017.

1. Global Strategy for Diagnosis, Management and Prevention of COPD 2017. Available from http://www.goldcopd.org. Accessed on 27 March 2017.

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Assessing COPD symptoms
Dyspnoea severity: Assess using the Modified Medical Research Council (mMRC) Dyspnoea Scale1

mMRC Grade Description

0 Not troubled by breathlessness except on strenuous exercise
1 Shortness of breath when hurrying on the level or walking up a slight hill
Walks slower than people of the same age on the level because of
2
breathlessness or has to stop for breath when walking at own pace on the level
3 Stops for breath after walking about 100 m or after a few minutes on the level
4 Too breathless to leave the house or breathless when dressing or undressing

Quality of life: The COPD Assessment Test (CAT) is a simple-to-administer, validated patient questionnaire that measures
the impact of COPD on a patient’s life, and how this changes over time.2

Available at www.catestonline.org

1. Global Strategy for Diagnosis, Management and Prevention of COPD 2017. Available from http://www.goldcopd.org. Accessed on 27 March 2017. 2. COPD Assessment Test (CAT).
Available at www.catestonline.org. Accessed on 27 March 2017.

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Spirometry’s role in the diagnosis of COPD
Spirometry is required to make a definitive COPD diagnosis and also to assess the degree of airflow limitation1
The standard spirometry manoeuvre provides the following measures1:

FVC FEV1
FEV1/FVC
Forced Vital Capacity Forced Expiratory Volume in 1 Second
The total volume of air that the The ratio of FEV1 to FVC
The volume of air that the patient is able to
patient can forcibly exhale in one expressed as a decimal fraction
exhale in the first second of forced expiration
breath (eg, 0.7); previously expressed as
percentage (70%)

FEV1 and FVC are measured in liters and are also the predicted normal values based on age, height, sex and ethnicity1
Patients can also be assessed after bronchodilator therapy to determine the impact of bronchodilator therapy1

1. Spirometry for Health Care Providers 2010. Available from http://www.goldcopd.org. Accessed on 27 March 2017.

7
Types of spirometers 1

Bellows or rolling Hand-held

seal spirometers
• Large, not very portable
• Used predominantly in lung function
laboratories
• Require regular calibration
Electronic desktop spirometers
spirometers
• Compact, portable and usually quick and • Small and inexpensive, but no
easy to use printout
• Real-time visual display and paper or computer • Newer models provide % predicted
printout values if patient details are
pre-programmed
• Some require calibration, but most only need
cleaning • Good for simple screening and
are accurate for diagnosis
• Ideal for primary care usage

1. Spirometry for Health Care Providers 2010. Available from http://www.goldcopd.org. Accessed on 27 March 2017.

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Spirometry patterns
Three basic spirometry patterns to recognise1:

Normal Obstructive Restrictive Spirometry readings:

•R
 epeat spirometry procedure until
FEV1 = above 80% predicted FEV1 = below 80% predicted FEV1 = normal or mildly reduced three acceptable and repeatable
FVC = above 80% predicted FVC = normal or reduced FVC = below 80% predicted blows are obtained. Maximum of
FEV1/FVC ratio = above 0.7 (usually to a lesser degree than FEV1) FEV1/FVC ratio = normal (above 0.7) eight efforts
FEV1/FVC ratio = below 0.7 •T
 he best two out of three readings
Refer for further lung function testing should be within 150 mL or 5% of
5 5 5 5 5 5
FVC
FVC FVC each other and best
4 4 4 4 4 4
FEV
FEV
1 1
FEV1 •T
 he best readings of FEV1 and
FVC on the spirometer are usually
Volume (L)
Volume (L)

Volume (L)

Volume (L)
Volume (L)

Volume (L)
3 3 3 3 3 3
FEV1FEV
/FVC/FVC
= 4.0/4.8
= 4.0/4.8
L (0.83)
L (0.83) FEV1/FVC = 4.0/4.8 L (0.83)
recorded

Volume
Volume

Volume
1
Pre-BD
Pre-BD
FEV1FEV
/FVC
1
/FVC
= 2.0/3.5
= 2.0/3.5
L (0.57)
L (0.57)
Pre-BD FEV1/FVC = 2.0/3.5 L (0.57)
Post-BD
Post-BD
FEV1FEV
/FVC /FVC
= 2.2/4.0
= 2.2/4.0
L (0.55)
LPost-BD
(0.55) FEV1/FVC = 2.2/4.0 L (0.55)
2 2 2 2 2 2 1

1 1 1 1 1 1
-------- normal pattern

1 1 2 2 3 3 14 4 2 5 5 36 6 4 5 6 1 1 2 2 3 3 1 4 4 2 5 5 36 6 4 5 6
________ abnormal pattern
Time
Time Time
Time
Time
(seconds)
(seconds) Time (seconds) Time
Time
(seconds)
(seconds) Time (seconds)

A post-bronchodilator FEV1/FVC <0.70 confirms the presence of persistent airflow limitation and thus of COPD2

1. Spirometry for Health Care Providers 2010. Available from http://www.goldcopd.org. Accessed on 27 March 2017.

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Differential diagnoses if spirometry
confirms airway obstruction 1

The main differential diagnoses are COPD and asthma

•C
 an often be differentiated through a careful clinical history and smoking or other exposure patterns

•A
 sthma diagnosis favoured if:
- FEV1 reversibility >12%, although reversibility of this magnitude and higher is seen in COPD
- A history of childhood wheezing, atopic symptoms and diurnal variation in peak flow >20% (as established by monitoring at
home 2X daily for 2 weeks)
- A therapeutic trial of prednisolone 30 mg daily for 2 weeks, or of inhaled corticosteroids for 2–4 weeks, that leads to marked
improvement in FEV1. The British NICE COPD Guidelines suggest >400 mL increase in FEV1 after treatment trial

•A
 reduced diffusing capacity in addition to airflow limitation is characteristic of emphysema

1. Spirometry for Health Care Providers 2010. Available from http://www.goldcopd.org. Accessed on 27 March 2017.

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Combined COPD assessment 1
Combine the symptomatic assessment with the spirometric classification and/or risk of exacerbation.
Information provided:
The number refers to the severity of airflow limitation (spirometric grade 1 to 4)

Spirometrically confirmed Assessment of airflow

diagnosis limitation

Post-bronchodilator FEV1
FEV1/FVC <0.7 (% predicted)

GOLD 1 ≥80

GOLD 2 50–79

GOLD 3 30–49

GOLD 4 <30
Adapted from GOLD 2017.

1. Global Strategy for Diagnosis, Management and Prevention of COPD 2017. Available from http://www.goldcopd.org. Accessed on 27 March 2017.

11
Combined COPD assessment 1
Combine the symptomatic assessment with the spirometric classification and/or risk of exacerbation.
Information provided:
Number refers to severity of airflow limitation (spirometric grade 1 to 4)
Letter refers to the (groups A to D) is on symptom burden and risk of exacerbation which can be used to guide therapy
Spirometrically confirmed Assessment of airflow Assessment of symptoms/
diagnosis limitation risk of exacerbation

FEV1
Post-bronchodilator (% predicted)
FEV1/FVC <0.7
GOLD 1 ≥80
C D
GOLD 2 50–79

GOLD 3 30–49
A B
GOLD 4 <30
mMRC 0–1 mMRC ≥2
CAT <10 CAT ≥10
Adapted from GOLD 2017. Symptoms

1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Diagnosis, Management and Prevention of COPD 2017. Available from http://www.goldcopd.org. Accessed on 27
March 2017.

12
Combined COPD assessment 1
Combine the symptomatic assessment with the spirometric classification and/or risk of exacerbation.
Information provided:
Number refers to severity of airflow limitation (spirometric grade 1 to 4)
Letter refers to (groups A to D) is on symptom burden and risk of exacerbation which can be used to guide therapy
Spirometrically confirmed Assessment of airflow Assessment of symptoms/
diagnosis limitation risk of exacerbation

FEV1 Exacerbation
Post-bronchodilator (% predicted) history
FEV1/FVC <0.7
GOLD 1 ≥80
≥2 or ≥ 1 leading to
hospital admission C D
GOLD 2 50–79

GOLD 3 30–49 0 or 1 (not

leading to hospital A B
GOLD 4 <30 admission)

mMRC 0–1 mMRC ≥2

CAT <10 CAT ≥10
Symptoms

1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Diagnosis, Management and Prevention of COPD 2017. Available from http://www.goldcopd.org. Accessed on 27
March 2017.

13
Grading COPD severity 1

Mr Amad

• FEV1 55% predicted

• CAT score 18
• History of three exacerbations in the last 12 months

Spirometrically confirmed Assessment of airflow Assessment of symptoms/

diagnosis limitation risk of exacerbation

FEV1 Exacerbation
Post-bronchodilator (% predicted) history
FEV1/FVC <0.7
GOLD 1 ≥80
≥2 or ≥ 1 leading to
hospital admission C D
GOLD 2 50–79

GOLD 3 30–49 0 or 1 (not

leading to hospital A B
GOLD 4 <30 admission)

mMRC 0–1 mMRC ≥2

CAT <10 CAT ≥10

Adapted from GOLD 2017. Symptoms

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Grading COPD severity 1

Mr Amad

• FEV1 55% predicted

• CAT score 18
• History of three exacerbations in the last 12 months

Spirometrically confirmed Assessment of airflow Assessment of symptoms/

diagnosis limitation risk of exacerbation

FEV1 Exacerbation
Post-bronchodilator (% predicted) history
FEV1/FVC <0.7
GOLD 1 ≥80
≥2 or ≥ 1 leading to
hospital admission C D
GOLD 2 50–79

GOLD 3 30–49 0 or 1 (not

leading to hospital A B
GOLD 4 <30 admission)

Mr Amad is a GOLD grade 2, group D mMRC 0–1

patient. CAT <10
CAT =10

Symptoms

1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Diagnosis, Management and Prevention of COPD 2017. Available from http://www.goldcopd.org. Accessed on 27
March 2017.

15
Differentiating between asthma, COPD & ACO 1

Clinical features Asthma COPD ACO

Usually age ≥40 years, but may have had symptoms in childhood or
Age of onset Usually early childhood (may have onset at any age) Usually >40 years old
early adulthood

Pattern of respiratory Chronic, usually continuous symptoms, with ‘better’ and Respiratory symptoms including exertional dyspnoea are
Symptoms may vary over time
symptoms ‘worse’ days persistent but variability may be prominent

Current and/or historical variable airflow limitation,

FEV1 may be improved by therapy, but post-bronchodilator Airflow limitation not fully reversible, but often with current or
Lung function eg, bronchodilator reversibility, airway hyper-
FEV1/FVC <0.7 persists historical variability
responsiveness

Lung function
May be normal between symptoms Persistent airflow limitation Persistent airflow limitation
between symptoms

Frequently a history of doctor-diagnosed asthma (current or

Past history or Many patients have allergies and a personal history of History of exposure to noxious particles and gases
previous), allergies and a family history of asthma, and/or a history
family history asthma in childhood, and/or family history of asthma (mainly tobacco smoking and biomass fuels)
of noxious exposures
Symptoms partly but significantly reduced by treatment.
Time course Often improves spontaneously or with treatment Generally, slowly progressive over years despite treatment
Progression is usual and treatment needs are high

Chest X-ray Usually normal Severe hyperinflation and other changes of COPD Similar to COPD

Exacerbations may be more common than in COPD but

Exacerbations occur, but risk can be considerably Exacerbations can be reduced by treatment.
Exacerbations are reduced by treatment. Comorbidities can contribute to
reduced by treatment If present, comorbidities contribute to impairment
impairment

Typical airway Neutrophils and/or eosinophils in sputum, lymphocytes in

Eosinophils and/or neutrophils Eosinophils and/or neutrophils in sputum
inflammation airways, may have systemic inflammation

Adapted from Diagnosis of Diseases of Chronic Air Flow Limitation: Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS) 2015.

1. Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease. Diagnosis of Diseases of Chronic Air Flow Limitation: Asthma, COPD and Asthma-COPD Overlap
Syndrome (ACOS) 2015. Available at http://www.msc.es/organizacion/sns/planCalidadSNS/pdf/GOLD_ACOS_2015.pdf. Accessed on 28 March 2017.

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Benefits of early diagnosis 1,2

• Primary care doctors play an important role in the early Quitting smoking at any age
identification of patients at high risk of COPD1 is beneficial to a patient’s health2
• Early diagnosis allows interventions, such as1:
100 Never smoked or not

FEV1 (% value at age 25 years)

- smoking cessation susceptible to smoke

Smoked regularly
- reduction of exposure to occupational dusts, 75 and susceptible to
the effects Stopped smoking
indoor and outdoor pollution at age 45 years

• Risk factor reduction can help delay or reduce progression 50 Onset of symptoms

Stopped smoking
and can have a significant impact on mortality1,2 at age 65 years

25 Severe disability

Death
0
25 50 75
Age (years)
Adapted from Parkes G, Greenhalgh T, Griffin M, Dent R. BMJ 2008.

1. Ministry of Health Malaysia. Clinical Practice Guidelines: Management of Chronic Obstructive Pulmonary Disease (2nd Edition), 2009.
2. Parkes G, Greenhalgh T, Griffin M, Dent R. Effect on smoking quit rate of telling patients their lung age: the Step2quit randomised controlled trial. BMJ 2008;336(7644):598–600.

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COPD: Pathophysiology, Assessment and Diagnosis

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COPD: Pathophysiology, Assessment and Diagnosis module.
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