DIFFERENTIAL DIAGNOSIS

Definitions

Asthma
Asthma is a heterogeneous disease, usually characterized by chronic airway
inflammation. It is defined by the history of respiratory symptoms such as wheeze,
shortness of breath, chest tightness and cough that vary over time and in intensity,
together with variable expiratory airflow limitation. [GINA 2016]

COPD
COPD is a common preventable and treatable disease, characterized by persistent
airflow limitation that is usually progressive and associated with enhanced chronic
inflammatory responses in the airways and the lungs to noxious particles or gases.
Exacerbations and comorbidities contribute to the overall severity in individual
patients. [GOLD 2016]
Asthma-COPD overlap syndrome (ACOS) [a description]
Asthma-COPD overlap syndrome (ACOS) is characterized by persistent airflow
limitation with several features usually associated with asthma and several features
usually associated with COPD. ACOS is therefore identified by the features that it
shares with both asthma and COPD.

Global Initiative for Asthma

Definitions

Asthma
Asthma is a heterogeneous disease, usually characterized by chronic airway
inflammation. It is defined by the history of respiratory symptoms such as wheeze,
shortness of breath, chest tightness and cough that vary over time and in intensity,
together with variable expiratory airflow limitation. [GINA 2016]

COPD
COPD is a common preventable and treatable disease, characterized by persistent
airflow limitation that is usually progressive and associated with enhanced chronic
inflammatory responses in the airways and the lungs to noxious particles or gases.
Exacerbations and comorbidities contribute to the overall severity in individual
patients. [GOLD 2016]
Asthma-COPD overlap syndrome (ACOS) [a description]
Asthma-COPD overlap syndrome (ACOS) is characterized by persistent airflow
limitation with several features usually associated with asthma and several features
usually associated with COPD. ACOS is therefore identified by the features that it
shares with both asthma and COPD.

Global Initiative for Asthma

 Usual features of asthma, COPD and
ACOS
Feature Asthma
Age of onset Usually childhood but can
commence at any age
Pattern of Symptoms vary over time
respiratory (day to day, or over longer
symptoms period), often limiting
activity. Often triggered by
exercise, emotions
including laughter, dust, or
exposure to allergens
Lung function Current and/or historical
variable airflow limitation,
e.g. BD reversibility, AHR
Lung function May be normal
between
symptoms
COPD
Usually >40 years
Chronic usually continuous
symptoms, particularly
during exercise, with better
and worse days
FEV1 may be improved by
-
therapy, but post-BD
FEV1/FVC <0.7 persists
Persistent airflow limitation
ACOS
Usually 40 years, but may
have had symptoms as
child/early adult
Respiratory symptoms
including exertional dyspnea
are persistent, but variability
may be prominent
Airflow limitation not fully
reversible, but often with
current or historical
variability
Persistent airflow limitation
Global Initiative for Asthma
 Usual features of asthma, COPD and
ACOS (continued)
Feature Asthma
Past history or Many patients have
family history allergies and a personal
history of asthma in
childhood and/or family
history of asthma
Time course Often improves
spontaneously or with
treatment, but may result in
fixed airflow limitation
Chest X-ray
- Usually normal
Exacerbations Exacerbations occur, but
risk can be substantially
reduced by treatment
COPD
History of exposure to
noxious particles or gases
(mainly tobacco smoking or
biomass fuels)
Generally slowly progressive
over years despite treatment
Severe hyperinflation and
other changes of COPD
Exacerbations can be
reduced by treatment. If
present, comorbidities
contribute to impairment
ACOS
Frequently a history of
doctor-diagnosed
- asthma
(current or previous),
allergies, family history of
asthma, and/or a history of
noxious exposures
Symptoms are partly but
significantly reduced by
treatment. Progression is
usual and treatment needs
are high.
Similar to COPD
Exacerbations may be more
common than in COPD but
are reduced by treatment.
Comorbidities can contribute
to impairment.
Global Initiative for Asthma
 Features that (when present) favor
asthma or COPD
Feature Favors asthma Favors COPD
Age of onset qBefore age 20 years qAfter age 40 years
Pattern of qSymptoms vary overminutes, hours or days qSymptoms persist despite treatment
respiratory qWorse during night or early morning qGood and bad days, but always daily
symptoms qTriggered by exercise, emotions including symptoms and exertional dyspnea
laughter, dust, or exposure to allergens qChronic cough and sputum preceded
onset of dyspnea, unrelated to triggers
Lung function qRecord of variable airflow limitation qRecord of persistent airflow limitation
(spirometry, peak flow) (post-BD FEV1/FVC <0.7)
qNormal between symptoms qAbnormal between symptoms
Past history or qPrevious doctor diagnosis of asthma qPrevious doctor diagnosis of COPD,
family history qFamily history of asthma, and other allergic chronic bronchitis or emphysema
conditions (allergic rhinitis or eczema) qHeavy exposure to a risk factor: tobacco
smoke, biomass fuels
Time course qNo worseningof symptoms over time. qSymptomsslowly worsening over time
Symptoms vary seasonally, or from year to (progressive course over years)
year qRapid-acting bronchodilator treatment
qMay improve spontaneously, or respond provides only limited relief
immediately to BD or to ICS over weeks
Chest X-ray qNormal qSevere hyperinflation

Global Initiative for Asthma

 Stepwise approach to diagnosis and
initial treatment

For an adult who presents

with respiratory symptoms:
1. Does the patient have
chronic airways disease?
2. Syndromic diagnosis of
asthma, COPD and ACOS
3. Spirometry
4. Commence initial therapy
5. Referral for specialized
investigations (if
necessary)

GINA 2014, Box 5-4 Global Initiative for Asthma

 Step 1 Does the patient have chronic
airways disease?

GINA 2014, Box 5-4 Global Initiative for Asthma

Clinical History Physical Radiology
History of chronic Examinations May be normal,
or recurrent May be normal particularly in early
cough, sputum Evidence of stages
production, hyperinflation and Abnormalities on chest
dyspnea, or other features of X-ray or CT scan
wheezing; or chronic lung (performed for other
repeated acute disease or reasons such as
lower respiratory respiratory screening for lung
tract infections insufficiency cancer), including
Report of a Abnormal hyperinflation, airway
previous doctor auscultation wall thickening, air
diagnosis of (wheeze and/or trapping, hyperlucency,
asthma or COPD crackles) bullae or other features
History of prior of emphysema.
treatment with May identify an
inhaled alternative diagnosis,
medications including
History of smoking bronchiectasis,
tobacco and/or evidence of lung
other substances infections such as
Exposure to tuberculosis, interstitial
environmental lung diseases or cardiac
hazards, e.g. failure. Global Initiative for Asthma
GINA
GINA 2014
2014, Box 5-4 Global Initiative for Asthma
Syndromic diagnosis of airways disease
The shaded columns list features that, when present, best
distinguish between asthma and COPD.
For a patient, count the number of check boxes in each column.
If 3 or more boxes are checked for either asthma or COPD,
that diagnosis is suggested.
If there are similar numbers of checked boxes in each column,
the diagnosis of ACOS should be considered.

Global Initiative for Asthma

GINA 2014, Box 5-4 Global Initiative for Asthma
 Step 3 - Spirometry

Spirometric variable Asthma COPD ACOS

Normal FEV1/FVC Compatible with asthma Not compatible with Not compatible unless
pre- or post-BD diagnosis (GOLD) other evidence of chronic
airflow limitation
Post-BD FEV1/FVC <0.7 Indicates airflow Required for diagnosis Usual in ACOS
limitation; may improve by GOLD criteria
FEV1 =80% predicted Compatible with asthma Compatible with GOLD Compatible with mild
(good control, or interval category A or B if post- ACOS
between symptoms) BD FEV1/FVC <0.7
FEV1 <80% predicted Compatible with asthma. Indicates severity of Indicates severity of
A risk factor for airflow limitation and risk airflow limitation and risk
exacerbations of exacerbations and of exacerbations and
mortality mortality
Post-BD increase in Usual at some time in Common in COPD and Common in ACOS, and
FEV1 >12% and 200mL courseof asthma; not more likely when FEV1 is more likely when FEV1 is
from baseline (reversible always present low, but consider ACOS low
airflow limitation)
Post-BD increase in High probability of Unusual in COPD. Compatible with
FEV1 >12% and 400mL asthma Consider ACOS diagnosis of ACOS
from baseline
GINA 2014, Box 5-3 Global Initiative for Asthma
GINA 2014, Box 5-4 Global Initiative for Asthma
GINA 2014, Box 5-4 Global Initiative for Asthma
 Step 5 Refer for specialized
investigations if needed

Investigation Asthma COPD

DLCO Normal or slightly elevated Often reduced
Arterial blood gases Normal between In severe COPD, may be abnormal
exacerbations between exacerbations
Airway Not useful on its own in distinguishing asthma and COPD.
hyperresponsiveness High levels favor asthma
High resolution CT Usually normal; may show air Air trapping or emphysema; may
scan trapping and increased airway show bronchial wall thickening and
wall thickness features of pulmonary hypertension
Tests for atopy (sIgE Not essential for diagnosis; Conforms to background
and/or skin prick increases probability of prevalence; does not rule out COPD
tests) asthma
FENO If high (>50ppb) supports Usually normal. Low in current
eosinophilic inflammation smokers
Blood eosinophilia Supports asthma diagnosis May be found during exacerbations
Sputum inflammatory Role in differential diagnosis not established in large populations
cell analysis

GINA 2014, Box 5-5 Global Initiative for Asthma