Diagnosis of Diseases of

Chronic Airflow Limitation:

Asthma
COPD and
Asthma - COPD
Overlap Syndrome
(ACOS)

Visit the GINA website at www.ginasthma.org

2014 Global Initiative for Asthma
Visit the GOLD website at www.goldcopd.org
2014 Global Initiative for Chronic Obstructive Lung Disease

Based on the Global Strategy for Asthma

Management and Prevention and the Global Strategy
for the Diagnosis, Management and Prevention of
Chronic Obstructive Pulmonary Disease.
2014

GLOBAL INITIATIVE FOR ASTHMA

GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE

Diagnosis of Diseases of Chronic Airflow Limitation:

Asthma, COPD and Asthma-COPD Overlap Syndrome
(ACOS)

GINA reports are available at http://www.ginasthma.org

GOLD reports are available at http://www.goldcopd.org
Global Initiative for Asthma

Diagnosis of Diseases of Chronic Airflow Limitation:

Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS)
TABLE OF CONTENTS
PREFACE

KEY POINTS

OBJECTIVE

DEFINITIONS

Table 1. Current definitions of asthma and COPD, and clinical description of ACOS
STEP-WISE APPROACH TO DIAGNOSIS OF PATIENTS WITH RESPIRATORY SYMPTOMS
Step 1: Does the Patient Have Chronic Airways Disease?

4
4
4

Clinical history
Physical examination
Radiology
Screening questionnaires
Step 2: The Syndromic Diagnosis of Asthma, COPD and ACOS in an Adult Patient

a. Assemble the features that favor a diagnosis of asthma or of COPD

b. Compare the number of features in favor of a diagnosis of asthma or a diagnosis of COPD
c. Consider the level of certainty around the diagnosis of asthma or COPD, or whether there
are features of both suggesting Asthma-COPD Overlap Syndrome
Table 2a. Usual features of asthma, COPD and ACOS
Table 2b. Features that favor asthma or COPD

6
6

Step 3: Spirometry

Step 4: Commence Initial Therapy

Table 3. Spirometric measures in asthma, COPD and ACOS

Step 5: Referral for Specialized Investigations (if necessary)
Table 4. Summary of syndromic approach to diseases of chronic airflow limitation
Table 5. Specialized investigations sometimes used in distinguishing asthma and COPD
REFERENCES

8
8
9
10
11

Diagnosis of Diseases of Chronic Airflow Limitation:

Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS)
PREFACE
In children and young adults, the differential diagnosis in patients with respiratory symptoms is different from
that in older adults. Once infectious disease and non-pulmonary conditions (e.g. congenital heart disease, vocal
cord dysfunction) have been excluded, the most likely chronic airway disease in children is asthma. This is often
accompanied by allergic rhinitis. In adults (usually after the age of 40 years) COPD becomes more common, and
distinguishing asthma with chronic airflow limitation from COPD becomes problematic.1-4
A significant proportion of patients who present with symptoms of a chronic airways disease have features of both
asthma and COPD.5-9 Several diagnostic terms, most including the word overlap, have been applied to such patients,
and the topic has been extensively reviewed.4,6,10,11 However, there is no generally agreed term or defining features for
this category of chronic airflow limitation, although a definition based upon consensus has been published for overlap
in patients with existing COPD.12
In spite of these uncertainties, there is broad agreement that patients with features of both asthma and COPD
experience frequent exacerbations,6 have poor quality of life, a more rapid decline in lung function and high
mortality,6,13 and consume a disproportionate amount of healthcare resources14 than asthma or COPD alone. In these
reports, the proportion of patients with features of both asthma and COPD is unclear and will have been influenced
by the inclusion criteria used. However, prevalence rates between 15 and 55% have been reported, with variation by
gender and age.8,13,15 Concurrent doctor-diagnosed asthma and COPD has been reported in between 15 and 20% of
patients.7,10,16,17
This document has been developed by the Science Committees of both GINA and GOLD, based on a detailed
review of available literature and consensus. It provides an approach to distinguishing between asthma, COPD
and the overlap of asthma and COPD, for which the term Asthma COPD Overlap Syndrome (ACOS) is proposed10
Rather than attempting a formal definition of ACOS, this document presents features that identify and characterize
ACOS, ascribing equal weight to features of asthma and of COPD. A simple approach to initial treatment of ACOS
is also included. It is acknowledged that within this description of ACOS will lie a number of phenotypes that may in
due course be identified by more detailed characterization on the basis of clinical, pathophysiological and genetic
identifiers.18-20 The primary objective of this approach is to inform clinical practice, based on current evidence.

Diagnosis Of Diseases Of Chronic Airflow

Limitation: Asthma, COPD and AsthmaCOPD
Overlap Syndrome
A joint project of GINA and GOLD#

KEY POINTS
Distinguishing asthma from COPD can be problematic, particularly in smokers and older adults
ACOS is identified by the features that it shares with both asthma and COPD.
A stepwise approach to diagnosis is advised, comprising recognition of the presence of
a chronic airways disease, syndromic categorization as asthma, COPD or the overlap
between asthma and COPD (the Asthma COPD Overlap Syndrome (ACOS)), confirmation by
spirometry and, if necessary, referral for specialized investigations.
Although initial recognition and treatment of ACOS may be made in primary care, referral for
confirmatory investigations is encouraged, as outcomes for ACOS are often worse than for
asthma or COPD alone.
Initial treatment should be selected to ensure that:

o Patients with features of asthma receive adequate controller therapy including inhaled

corticosteroids, but not long-acting bronchodilators alone (as monotherapy), and

o Patients with COPD receive appropriate symptomatic treatment with bronchodilators or

combination therapy, but not inhaled corticosteroids alone (as monotherapy).
The consensus-based description of the Asthma COPD Overlap Syndrome (ACOS) is intended
to stimulate further study of the character and treatments for this common clinical problem.

OBJECTIVE

This consensus-based document aims to assist clinicians to:

Identify patients who have a disease of chronic airflow limitation
Distinguish asthma from COPD and the Asthma-COPD Overlap Syndrome (ACOS)
Decide on initial treatment and/or need for referral

This chapter is excerpted from the Global Strategy for Asthma Management and Prevention, 2014. The full
report can be viewed at http//www.ginasthma.org

DEFINITIONS
Table 1. Current definitions of asthma and COPD, and clinical description of ACOS
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 2014]
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 2014]21
Asthma-COPD Overlap Syndrome (ACOS) a description for clinical use
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.
A summary of the typical characteristics of asthma, COPD and ACOS is presented in Table 2a, showing the
similarities and differences in history and investigations.

STEP-WISE APPROACH TO DIAGNOSIS OF PATIENTS WITH RESPIRATORY SYMPTOMS

Step 1: Does the patient have chronic airways disease?
A first step in diagnosing these conditions is to identify patients at risk of, or with significant likelihood of having
chronic airways disease, and to exclude other potential causes of respiratory symptoms. This is based on a detailed
medical history, physical examination, and other investigations.3,22-24
Clinical history
Features that should prompt consideration of chronic airways disease include:
History of chronic or recurrent cough, sputum production, dyspnea, or wheezing; or repeated acute lower
respiratory tract infections
Report of a previous doctor diagnosis of asthma or COPD
History of prior treatment with inhaled medications
History of smoking tobacco and/or other substances
Exposure to environmental hazards, e.g. occupational or domestic exposures to airborne pollutants
Physical examination
May be normal
Evidence of hyperinflation and other features of chronic lung disease or respiratory insufficiency
Abnormal auscultation (wheeze and/or crackles)

Radiology

May be normal, particularly in early stages

Abnormalities on chest X-ray or CT scan (performed for other reasons such as screening for lung
cancer), including hyperinflation, airway wall thickening, air trapping, hyperlucency, bullae or other
features of emphysema.
May identify an alternative diagnosis, including bronchiectasis, evidence of lung infections such as
tuberculosis, interstitial lung diseases or cardiac failure.

Screening questionnaires
Many screening questionnaires have been proposed to help the clinician identifying subjects at risk of chronic
airways disease, based on the above risk factors and clinical features.25-27 These questionnaires are usually contextspecific, so they are not necessarily relevant to all countries (where risk factors and comorbid diseases differ), to
all practice settings and uses (population screening versus primary or secondary care), or to all groups of patients
(case-finding versus self-presenting with respiratory symptoms versus referred consultation). Examples of these
questionnaires are provided on both the GINA and GOLD websites.
STEP 2. The syndromic diagnosis of asthma, COPD and ACOS in an adult patient
Given the extent of overlap between features of asthma and COPD (Table 2a), the approach proposed focuses on
the features that are most helpful in distinguishing asthma and COPD (Table 2b).
a. Assemble the features that favor a diagnosis of asthma or of COPD
From a careful history that considers age, symptoms (in particular onset and progression, variability, seasonality or
periodicity and persistence), past history, social and occupational risk factors including smoking history, previous
diagnoses and treatment and response to treatment, the features favoring the diagnostic profile of asthma or of
COPD can be assembled. The check boxes in Table 2b can be used to identify the features that are most consistent
with asthma and/or COPD. Note that not all of the features of asthma and COPD are listed, but only those that most
easily distinguish between asthma and COPD.
b. Compare the number of features in favor of a diagnosis of asthma or a diagnosis of COPD
From Table-2b, count the number of checked boxes in each column. Having several (three or more) of the features
listed for either asthma or for COPD, in the absence of those for the alternative diagnosis, provides a strong
likelihood of a correct diagnosis.27 However, the absence of any of these features has less predictive value, and
does not rule out the diagnosis of either disease. For example, a history of allergies increases the probability that
respiratory symptoms are due to asthma, but is not essential for the diagnosis of asthma since non-allergic asthma
is a well-recognized asthma phenotype; and atopy is common in the general population including in patients who
develop COPD in later years. When a patient has similar numbers of features of both asthma and COPD, the
diagnosis of ACOS should be considered.
c. Consider the level of certainty around the diagnosis of asthma or COPD, or whether there are features of
both suggesting Asthma-COPD Overlap Syndrome
In the absence of pathognomonic features, clinicians recognize that diagnoses are made on the weight of evidence,
provided there are no features that clearly make the diagnosis untenable. Clinicians are able to provide an estimate
of their level of certainty and factor it into their decision to treat. Doing so consciously may assist in the selection of
treatment and, where there is significant doubt, it may direct therapy towards the safest option - namely, treatment for
the condition that should not be missed and left untreated.

6
Airflow limitation not
fully reversible, but often
with current or historical
variability
Persistent airflow limitation

Current and/or historical variable FEV1 may be improved

airflow limitation, e.g. BD
by therapy, but post-BD
reversibility, AHR
FEV1/FVC < 0.7 persists
Persistent airflow
limitation
History of exposure to
noxious particles and
gases (mainly tobacco
smoking and biomass
fuels)
Generally, slowly
progressive over years
despite treatment

Severe hyperinflation &

other changes of COPD
Exacerbations can be
reduced by treatment. If
present, comorbidities
contribute to impairment
Neutrophils in sputum,
lymphocytes in airways,
may have systemic
inflammation

May be normal between

symptoms

Many patients have allergies

and a personal history of
asthma in childhood, and/or
family history of asthma

Often improves spontaneously

or with treatment, but may result
in fixed airflow limitation

Usually normal

Exacerbations occur, but the

risk of exacerbations can
be considerably reduced by
treatment

Eosinophils and/or neutrophils

Lung function

Lung function
between
symptoms

Past history or
family history

Time course

Chest X-ray

Exacerbations

Typical airway
inflammation

Eosinophils and/or
neutrophils in sputum.

Exacerbations may be more

common than in COPD but
are reduced by treatment.
Comorbidities can
contribute to impairment

Similar to COPD

Symptoms are partly but

significantly reduced by
treatment. Progression is
usual and treatment needs
are high

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 three 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. See Step 2 for more details.

*Syndromic diagnosis of airways disease: how to use Table 2b

Severe hyperinflation

Rapid-acting bronchodilator
treatment provides only limited
relief.
May improve spontaneously or
have an immediate response to
BD or to ICS over weeks
Normal

Symptoms slowly worsening

over time (progressive course
over years)

Heavy exposure to a risk factor:

tobacco smoke, biomass fuels

Previous doctor diagnosis of

COPD, chronic bronchitis or
emphysema

Lung function abnormal

between symptoms

Record of persistent airflow

limitation (post-bronchodilator
FEV1/FVC < 0.7)

Chronic cough and sputum

preceded onset of dyspnea,
unrelated to triggers

No worsening of symptoms over

time. Symptoms vary either
seasonally, or from year to year

Previous doctor diagnosis of

Frequently a history of
asthma
doctor-diagnosed asthma
(current or previous),
Family history of asthma, and
allergies and a family history
other allergic conditio
of asthma, and/or a history
of noxious exposures

Lung function normal between

symptoms

Record of variable airflow

limitation (spirometry, peak flow)

Symptoms triggered by
exercise, emotions including
laughter, dust or exposure to
allergens

Persistence of symptoms
despite treatment

Variation in symptoms over

Respiratory symptoms
including exertional
minutes, hours or days
dyspnea are persistent but
variability may be prominent Symptoms worse during the
night or early morning

Chronic usually
continuous symptoms,
particularly during
exercise, with better and
worse days

Symptoms may vary over time

(day to day, or over longer
periods), often limiting activity.
Often triggered by exercise,
emotions including laughter,
dust or exposure to allergens

Pattern of
respiratory
symptoms

Good and bad days but always

daily symptoms and exertional
dyspnea

Onset after age 40 years

Usually age 40 years, but

Onset before age 20 years
may have had symptoms in
childhood or early adulthood

Usually > 40 years of age

Usually childhood onset but can

commence at any age.

Age of onset

ACOS

COPD

Asthma

Table 2b. Features that favor asthma or

COPD
Favors Asthma
Favors COPD

Feature

Table 2a. Usual features of asthma, COPD and ACOS

STEP 3: Spirometry
Spirometry is essential for the assessment of patients with suspected chronic disease of the airways. It must be
performed at either the initial or a subsequent visit, if possible before and after a trial of treatment. Early confirmation
or exclusion of the diagnosis may avoid needless trials of therapy, or delays in initiating other investigations.
Spirometry confirms chronic airflow limitation but is of more limited value in distinguishing between asthma with fixed
airflow obstruction, COPD and ACOS (Table 3).
Measurement of peak expiratory flow (PEF), although not an alternative to spirometry, if performed repeatedly on the
same meter over a period of 12 weeks may help to confirm the diagnosis of asthma by demonstrating excessive
variability, but a normal PEF does not rule out either asthma or COPD. A high level of variability in lung function may
also be found in ACOS.
After the results of spirometry and other investigations are available, the provisional diagnosis from the syndromebased assessment must be reviewed and, if necessary, revised. As shown in Table 3, spirometry at a single visit is
not always confirmatory of a diagnosis, and results must be considered in the context of the clinical presentation, and
whether treatment has been commenced. Inhaled corticosteroids and long-acting bronchodilators influence results,
particularly if a long withhold period is not used prior to performing spirometry. Further tests might therefore be
necessary either to confirm the diagnosis or to assess the response to initial and subsequent treatment.
STEP 4: Commence initial therapy
Faced with a differential diagnosis equally balanced between asthma and COPD (i.e. ACOS) the default position
should be to start treatment accordingly for asthma (Table 4). This recognizes the pivotal role of ICS in preventing
morbidity and even death in patients with uncontrolled asthma symptoms, for whom even seemingly mild symptoms
(compared to those of moderate or severe COPD) might indicate significant risk of a life-threatening attack10.
If the syndromic assessment suggests asthma or ACOS, or there is significant uncertainty about the diagnosis of
COPD, it is prudent to start treatment as for asthma until further investigation has been performed to confirm or
refute this initial position.
o Treatments will include an ICS (in a low or moderate dose, depending on level of symptoms).
o A long-acting beta2-agonist (LABA) should also be continued (if already prescribed), or added. However, it
is important that patients should not be treated with a LABA without an ICS (often called LABA monotherapy)
if there are features of asthma.
If the syndromic assessment suggests COPD, appropriate symptomatic treatment with bronchodilators or
combination therapy should be commenced, but not ICS alone (as monotherapy).21
Treatment of ACOS should also include advice about other therapeutic strategies16 including:
o Smoking cessation o Pulmonary rehabilitation
o Vaccinations
o Treatment of comorbidities, as advised in the respective GINA and GOLD reports.
In a majority of patients, the initial management of asthma and COPD can be satisfactorily carried out at primary
care level. However, both the GINA and GOLD strategy reports make provision for referral for further diagnostic
procedures at relevant points in patient management (see Step 5). This may be particularly important for patients
with suspected ACOS, given that it is associated with worse outcomes and greater health care utilization.

Table 3. Spirometric measures in asthma, COPD and ACOS

Spirometric variable

Asthma

COPD

ACOS

Normal FEV1/FVC pre- or

post BD

Compatible with diagnosis

Not compatible with

diagnosis

Not compatible unless

other evidence of chronic
airflow limitation

Post-BD FEV1/FVC <0.7

Indicates airflow limitation

but may improve
spontaneously or on
treatment

Required for diagnosis

(GOLD)

Usually present

FEV1 80% predicted

Compatible with diagnosis

(good asthma control
or interval between
symptoms)

Compatible with GOLD

Compatible with diagnosis
classification of mild airflow of mild ACOS
limitation (categories A or
B) if post- BD FEV1/FVC
<0.7

FEV1 <80% predicted

Compatible with diagnosis.

Risk factor for asthma
exacerbations

An indicator of severity of
airflow limitation and risk of
future events (e.g. mortality
and COPD exacerbations)

An indicator of severity of
airflow limitation and risk of
future events (e.g. mortality
and exacerbations)

Post-BD increase in FEV1

>12% and 200 ml from
baseline (reversible airflow
limitation)

Usual at some time in

course of asthma, but may
not be present when wellcontrolled or on controllers

Common and more likely

when FEV1 is low, but
ACOS should also be
considered

Common and more likely

when FEV1 is low, but
ACOS should also be
considered

Post-BD increase in
FEV1 >12% and 400ml
from baseline (marked
reversibility)

High probability of asthma

Unusual in COPD.
Consider ACOS

Compatible with diagnosis

of ACOS

ACOS: asthma-COPD overlap syndrome; BD: bronchodilator; FEV1: forced expiratory volume in 1 second; FVC:
forced vital capacity; GOLD: Global Initiative for Obstructive Lung Disease.
STEP 5: Referral for specialized investigations (if necessary)
Referral for expert advice and further diagnostic evaluation is necessary in the following contexts:
Patients with persistent symptoms and/or exacerbations despite treatment.
Diagnostic uncertainty, especially if an alternative diagnosis (e.g. bronchiectasis, post-tuberculous scarring,
bronchiolitis, pulmonary fibrosis, pulmonary hypertension, cardiovascular diseases and other causes of
respiratory symptoms) needs to be excluded.
Patients with suspected asthma or COPD in whom atypical or additional symptoms or signs (e.g. haemoptysis,
significant weight loss, night sweats, fever, signs of bronchiectasis or other structural lung disease) suggest
an additional pulmonary diagnosis. This should prompt early referral, without necessarily waiting for a trial of
treatment for asthma or COPD.
When chronic airways disease is suspected but syndromic features of both asthma and COPD are few.
Patients with comorbidities that may interfere with the assessment and management of their airways disease.
Referral may also be appropriate for issues arising during on-going management of asthma, COPD or ACOS, as
outlined in the GINA and GOLD strategy reports.
Table 5 summarizes specialized investigations that may be used to distinguish asthma and COPD.

Table
Summary
syndromic
approach
to diseases
of chronic
limitation
Table 4.4 Summary
ofof
syndromic
approach
to diseases
of chronic
airflowairflow
limitation

Table 5. Specialized investigations sometimes used in distinguishing asthma and COPD

Box 5-5. Specialized investigations sometimes used in distinguishing asthma and COPD
Asthma

COPD

Lung function tests

DLCO

Normal (or slightly elevated).

Often reduced.

Arterial blood gases

Normal between exacerbations

May be chronically abnormal between

exacerbations in more severe forms of COPD

Airway hyperresponsiveness
(AHR)

Not useful on its own in distinguishing asthma from COPD, but high levels of AHR
favor asthma

Imaging
High resolution CT Scan

Usually normal but air trapping and Low attenuation areas denoting either air trapping
increased bronchial wall thickness or emphysematous change can be quantitated;
may be observed.
bronchial wall thickening and features of pulmonary
hypertension may be seen.

Inflammatory biomarkers
Test for atopy (specific IgE
and/or skin prick tests)

Modestly increases probability of

Conforms to background prevalence; does not rule
asthma; not essential for diagnosis out COPD

FENO

A high level (>50 ppb) in nonsmokers supports a diagnosis of

eosinophilic airway inflammation

Usually normal.
Low in current smokers.

Blood eosinophilia

Supports asthma diagnosis

May be present during exacerbations

Sputum inflammatory cell

analysis

Role in differential diagnosis is not established in large populations

5. Diagnosis of asthma, COPD and Asthma-COPD overlap syndrome

10

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12

Diagnosis of Diseases of
Chronic Airflow Limitation:

Asthma
COPD and
Asthma - COPD
Overlap Syndrome
(ACOS)

Visit the GINA website at www.ginasthma.org

2014 Global Initiative for Asthma
Visit the GOLD website at www.goldcopd.org
2014 Global Initiative for Chronic Obstructive Lung Disease

Based on the Global Strategy for Asthma

Management and Prevention and the Global Strategy
for the Diagnosis, Management and Prevention of
Chronic Obstructive Pulmonary Disease.
2014