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IAJPS 2017, 4 (06), 1481-1486 Sai Krishna G et al ISSN 2349-7750




Available online at: Review Article

Sai Krishna G*1, Divyanjali P1, Sumathi K2, Komal Krishna T3
Department of Pharmacy Practice, JSS College of Pharmacy, Mysore, Karnataka, India.
Department of Pharmacy, SIMS College of Pharmacy, Guntur, Andhra Pradesh, India.
Department of Physiotherapy, JSS College of Physiotherapy, Mysore, Karnataka, India.
Asthma–COPD overlap syndrome (ACOS) is a clinical condition which is characterized by chronic airway
inflammation and persistent airflow obstruction with several features usually associated with COPD and asthma
respectively. Therefore ACOS is identified by the features that it shares both asthma and COPD. It is crucial to
define asthma, COPD and ACOS, as notable clinical entities, since they share common pathologic and functional
features. Patients with ACOS have the combined risk factors of smoking and atopy, and are generally younger than
patients with COPD and experience acute exacerbations with higher frequency and greater severity than COPD
alone. Pharmacotherapeutic considerations require an integrated approach, a consensus international definition of
ACOS is needed to design prospective, randomized clinical trials to evaluate specific drug interventions on
important outcomes such as lung function, acute exacerbations, quality of life and mortality.
Key words: Asthma, Chronic obstructive pulmonary disease, ACOS, elderly patients, under diagnosed.
Corresponding Author:
Sai Krishna G, QR code
Sitharam nagar, 2nd lane, 8-22-17, Guntur, A.P, India.
Contact: +91 7899880892.

Please cite this article in press as Sai Krishna G et al, Asthma-COPD Overlap Syndrome (ACOS) - An Under
Diagnosed Clinical Condition among Geriatrics, Indo Am. J. P. Sci, 2017; 4(06). Page 1481
IAJPS 2017, 4 (06), 1481-1486 Sai Krishna G et al ISSN 2349-7750

INTRODUCTION: [1] more frequent exacerbations, hospitalization, worse
Asthma and Chronic Obstructive Pulmonary Disease health-related quality of life, and higher healthcare
(COPD) are major public health concerns. There are costs than either disease alone. There is a critical
typically characterized as different disease conditions need to better define the management and treatment
with unique epidemiological features as well as of this syndrome. [2]
pathophysiological mechanisms. Asthma is an
allergic disease that often develops during childhood, SIGNS AND SYMPTOMS
although it can also be diagnosed in adult life. It is  Chronic cough or wheezing with or without
characterized by airway hyper-responsiveness (AHR) sputum (early symptom)
that leads to intermittent and usually reversible  Dyspnoea or exercise intolerance (late
airway obstruction, whereas COPD is a chronic symptom)
respiratory disease that is typically linked to smoking  Reduction in daily activities of living
tobacco, usually presents in subjects older than forty (physical deconditioning)
years of age, and is characterized by progressive and  Frequent need for inhaled salbutamol
irreversible airway obstruction. These definitions  Frequent acute exacerbations despite
allow asthma and COPD to be recognized as distinct adherence to standard pharmacotherapy
disease entities. However, this concept needs to be  Labored breathing
re-evaluated as many epidemiological studies have  Wheezing
shown that asthma and COPD may coexist, or at least
 Coughing, with or without mucus
one condition may evolve into the other creating a
condition commonly described as Asthma-COPD  Tightness in the chest
Overlap Syndrome. It is a syndrome in which older Patients with Asthma-COPD overlap syndrome are
usually differentiated by increased reversibility of
adults with a significant smoking history have
airflow obstruction, increased response to inhaled
features of asthma in addition to their COPD as it
corticosteroids and bronchial, eosinophilic, systemic
characterized by a functional and pathological
inflammation when compared with COPD patients.
overlap between asthma and COPD.
The concurrence of incompletely reversible airflow
obstruction (diagnostic feature of COPD) and RISK FACTORS
Risk factors for coexisting asthma and COPD include
increased airflow variability (one of the symptom of
ageing, smoking, atopy (e.g. hay fever) and chronic
asthma) is common among elderly population with
respiratory symptoms (>65years). People with ACOS asthma. The coexistence of COPD and asthma in
have worse outcomes than COPD or Asthma alone. elderly patients are not always due to cigarette
ACOS represents a distinct clinical phenotype with smoking. In some people with many years of poor
control, persistent airflow limitation may develop as
a complication of long-term asthma. [4]

Table 1: Comparison among Asthma, COPD and ACOS [5-8]
Disease Characteristics Pathophysiology First-line Add-on Therapy
 Age > 40  Moderate to severe  ICS  LAMA
 Non smoker airflow obstruction  ICS +  LTRA
 Women > men  FEV1/FVC < 0.70 LABA  Theophylline
 Typical atopy present  FEV1 < 68%  Omalizumab
Asthma  Exercise limited in  DLCO normal  Prednisone
between attacks  FeNO > 50ppb
 Dependence on  Exacerbations >3/year
prednisone  Sputum eosinophils
 Frequent present
(Hallmark feature)

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 Age ≥ 65  Chronic airflow  Bronchodil  ICS
 Past or current smoker obstruction ators  Roflumilast
 No atopy  FEV1/FVC < 0.70  LAMA/LA  Theophylline
 Exercise very limited  FEV1 < 50% BA/
 Oxygen dependence  DLCO < 80% both
COPD  Exacerbations and  FeNO < 25ppb  Smoking
exercise intolerance  Hyperinflation present cessation
(Hallmark feature)  Exacerbations >2/year  Pulmonary
 Infrequent nocturnal Rehabilitati
awakenings on

 Age 40-65 Moderate to severe  ICS/LAMA  LTRA
 Past or current smoker airflow obstruction /  Omalizumab
 Atopy present  FEV1/FVC < 0.70 LABA/all  Prednisone
 Exercise very limited FEV1 < 68%  Smoking  Roflumilast
ACOS  Very frequent  DLCO normal cessation  Theophylline
exacerbations  FeNO > 25-50ppb  Pulmonary
(Hallmark feature)  Hyperinflation present Rehabilitati
 Exacerbations > 3- on
 Frequent nocturnal
FEV- Forced Expiratory Volume, FVC- Forced Vital Capacity, DLCO- Diffusing Capacity of the lung for Carbon
monoxide, FeNO- Fractional exhaled Nitric Oxide, ICS- Inhaled Cortico Steroids, LABA- Long-Acting Beta
Agonists, LAMA- Long-Acting Muscarinic Antagonists, LTRA- Leukotriene Receptor Antagonists.

DIAGNOSIS: a. Assemble the features that favor a diagnosis of
To reach a diagnosis, imaging tests such as X-ray, asthma or COPD
CT scans, or MRI may be necessary. It also need a From a careful history which includes age, symptoms
noninvasive test called spirometry, also known as a (in particular onset and variability, progression,
pulmonary function test, which aid in measuring lung seasonality or periodicity and persistence), past
function. In 2014 the Global Initiative for Asthma history, social and occupational risk factors including
(GINA) and Global Initiative for Chronic Obstructive smoking history, previous treatment, diagnosis and
Lung Disease (GOLD) released a guideline on response to treatment, the features favoring the
ACOS. These guidelines suggest as stepwise diagnostic profile of asthma or of COPD can be
approach to diagnosis and treatment. The approach assembled.
proposed by GINA is simple and practical. [9, 10] b. Compare the number of features in account of a
diagnosis of COPD or a diagnosis of Asthma
Step-Wise Approach for Diagnosis of ACOS Having three or more characteristic feature of either
Step 1: Does the patient have chronic airways asthma or COPD useful for the correct diagnosis.
disease? However, the absence of any of these characteristic
A first step in diagnosing these conditions is to features has less predictive value, and does not rule
identify patients at risk of, or with significant out the diagnosis of either disease. For example, a
likelihood of having chronic airways disease, and to history of allergies increases the probability that
exclude other potential causes of respiratory respiratory symptoms are due to asthma, but is not
symptoms. This is based on the physical required for the diagnosis of asthma since non-
examination, detailed medical history and other allergic asthma is a well-recognized asthma
investigations. phenotype and atopy is common in the general
Step 2. The diagnosis of asthma, COPD and population including in patients who develop COPD
ACOS in an adult patient in future years. When a patient has similar symptoms
Given the extent of overlap between features of of both COPD and Asthma, the diagnosis of ACOS
asthma and COPD, the approach proposed focuses on should be considered.
the features that are most helpful in distinguishing c. Consider the level of certainty over the
asthma and COPD. diagnosis of COPD or Asthma, or whether there Page 1483
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are features of both suggesting ACOS (Asthma- If the syndromic assessment recommends asthma or
COPD overlapping syndrome) ACOS, or there is significant uncertainty about the
In the absence of pathognomonic features, clinicians diagnosis of COPD, it is advisable to start treatment
recognize that diagnoses are made on the weight of as for asthma until further investigations has been
evidence provided there are no features that clearly performed to confirm or contradict this initial
make the diagnosis unsupportable. Clinicians are able position.
to provide an estimate of their level of certainty and Treatment would include an ICS (in a low or
factor it into their decision to treat. Doing carefully moderate dose, depending on level of symptoms). A
may support in the selection of treatment and long-acting beta 2-agonist (LABA) should also be
where there is significant doubt, it may direct therapy continued (if already prescribed), or added. It is
towards the safest treatment option for the condition important that patients should not be treated with a
that should not be left untreated. LABA without an ICS (often called LABA
Step 3: Spirometry monotherapy) if there are features of asthma.
Spirometry is required for the assessment of patients If the syndromic assessment recommends COPD,
with suspected disease of the airways. It should be appropriate symptomatic treatment with
performed at the initial or a subsequent visit, if bronchodilators or combination therapy should be
possible before and after a trial of treatment. Early recommended, but not ICS alone as monotherapy
confirmation of the diagnosis may avoid unrequired Step 5: Criteria for specialized investigations (if
trials of therapy, or delays in initiating other necessary)
investigations. Further diagnostic evaluation and referral for expert
Spirometry verify the chronic airflow limitation but opinion is necessary in the following conditions:
is of more limited value in distinguishing between i. Patients with persistent symptoms and/or
asthma with fixed airflow obstruction, COPD and exacerbations despite treatment.
ACOS Measurement of peak expiratory flow (PEF), ii. Diagnostic uncertainty, especially if an
eventhough it is not an alternative to spirometry, if it alternative diagnosis e.g. bronchiectasis,
is performed repeatedly over a period of 1–2 weeks bronchiolitis, post-tuberculous scarring,
may help to confirm the diagnosis of asthma, but a pulmonary fibrosis, pulmonary hypertension,
normal peak expiratory flow does not rule out either and other causes of respiratory symptoms
asthma or COPD. A high degree of variability in lung needs to be excluded.
function may also be found in ACOS. iii. Patients with suspected asthma or COPD in
After obtaining the results of other investigations and whom atypical or additional signs or
spirometry, the provisional diagnosis from the symptoms e.g. significant weight loss, night
syndrome based assessment must be reviewed and if sweats, haemoptysis, fever or other structural
necessary it should be revised. Spirometry at a single lung disease suggest an additional pulmonary
visit should not be considered for diagnosis, and diagnosis. This should be efficient early
results must be considered in the relation of the referral, without necessarily waiting for a trial
clinical presentation of the patient, and whether of treatment for asthma or COPD.
treatment has been commenced. long-acting iv. When chronic airways disease is suspected but
bronchodilators and Inhaled corticosteroids syndromic features of both asthma and COPD
influence results, particularly if a long withhold are few.
period is not used prior to performing spirometry. v. Patients with comorbidities that may interfere
Further investigations might be necessary either to with the assessment and management of their
assess or confirm the diagnosis or to assess the airways disease.
response to initial and subsequent treatment. vi. Referral may also be appropriate for problems
Step 4: Commence initial therapy arising during on-going treatment of asthma,
Experience with a differential diagnosis equally COPD or ACOS, as outlined in the GOLD
balanced between COPD and asthma (i.e. ACOS) the and GINA strategy reports.
default position should start the treatment
accordingly for asthma. This recognizes the vital role MANAGEMENT OF ASTHMA-COPD
of ICS in preventing morbidity and mortality in OVERLAP SYNDROME [11]
patients with uncontrolled asthma symptoms, for Goals of treatment of ACOS should be to control or
whom even clearly having ‘mild’ symptoms (when reduce symptoms and impairment, and to reduce
compared to the patients with moderate or severe risks such as acute exacerbations, decline in lung
symptoms of COPD) which might indicate function and adverse effects from medicines.
significant risk of a life-threatening attack. Treatment should be started as for asthma. The
Australian Asthma Handbook recommends treatment Page 1484
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with long-term inhaled corticosteroids (ICS) to c) LAMAs
reduce the risk of asthma flare-ups in addition to a LAMAs are considered first-line therapy for the
long-acting bronchodilator in patients with coexisting management of COPD. Recent evidence has also
asthma and COPD. Treatment should also include: suggested a role in the treatment of asthma. They
a) Smoking cessation generally take long to have an effect than LABA
b) Pulmonary rehabilitation bronchodilators. These medications significant
c) Vaccinations (such as flu, pneumonia, and reduce the risk of acute COPD exacerbations,
whooping cough) improve exercise tolerance and effectively control
d) Allergen avoidance symptoms such as dyspnoea.
e) Treatment of comorbidities Long-acting muscarinic antagonist (anticholinergic)
f) Disease management training agents include tiotropium and newer agents like
g) Healthy eating and nutrition education aclidinium, glycopyrronium and umeclidinium.
h) Oxygen therapy (if neccecery) etc., These newer agents are as effective as tiotropium.
Patient education and self-management, within d) LABA/LAMA (Double therapy)
cognitive function, has been shown to reduce New combination products containing a LABA and
hospitalizations for exacerbations and infections. LAMA include, Indacaterol/glycopyrronium
Pharmacological management (110/50), Vilanterol/umeclidinium.
Medications used for the treatment of ACOS include e) ICS, LAMA and LABA (Triple therapy)
those recommended in guidelines for asthma and In patients who have frequent exacerbations (2 or
COPD. Short-acting beta-agonists (SABAs) more in previous 12 months) and have a FEV1 less
(salbutamol, terbutaline) are used for immediate than 50% predicted may benefit from all three classes
relief of symptoms of asthma and COPD, on an ‘as of medicines or ‘triple therapy’: ICS, LAMA and
needed’ basis. The use of short-acting muscarinic LABA.
antagonists (SAMAs) or anticholinergic f) Other therapies
bronchodilator such as ipratropium (Atrovent In more severe cases of ACOS, theophylline or
Metered Aerosol) is primarily used for quick relief of roflumilast may be added. Omalizumab, a IgE
COPD symptoms. [11] selective humanized monoclonal Antibody, is
a) Inhaled corticosteroids indicated for the management of Moderate-severe
Inhaled corticosteroids are very effective anti- allergic asthma in adults. The benefit in COPD and
inflammatory drugs in the management of asthma ACOS has not been tested.
and are indicated as combination therapy in COPD Patients with features of asthma should be prescribed
when FEV1 <50% predicted and patient has had 2 or adequate therapy to control the condition including
more exacerbations in the previous 12 months). inhaled corticosteroids, but not long-acting
Inhaled corticosteroids in order of increasing potency bronchodilators alone. Patients with COPD should
include, Beclomethasone, Budesonide, Ciclesonide, receive appropriate symptomatic treatment with
Fluticasone propionate, Fluticasone furoate. Inhaled bronchodilators or combination therapy, but not
corticosteroids can be delivered in combination with inhaled corticosteroids as monotherapy. Many
long-acting beta2-agonists (LABAs) and/or long- patients will require triple therapy with inhaled
acting muscarinic antagonists (LAMAs). corticosteroids, long-acting beta2-agonists and long-
b) LABAs acting muscarinic antagonists, as well as short-acting
LABAs significantly reduce asthma exacerbations, bronchodilators as relievers. The greater choice of
and are the preferred add-on drug to low-dose ICS in medications and devices provides new fixed dose
the treatment of asthma. LABAs include salmeterol, combinations with once or twice daily dosing. The
indacaterol, eformoterol, olodaterol and vilanterol. selection of therapy should consider ease of use,
It is important to note that LABAs without an inhaled efficiency and patient preferences.
corticosteroid should not be prescribed in patients
with ACOS. Combination inhaled DISCUSSION:
corticosteroid/long-acting beta-2 agonist (LABA) in There are many disease conditions which are common
a single inhaler include: but under diagnosed in our daily life. This includes
 Budesonide/eformoterol diseases as familiar as Tired All The Time Syndrome
 Fluticasone propionate/salmeterol (Chronic Fatigue Syndrome), Beauty Parlour
 Fluticasone propionate/eformoterol Syndrome, Fat Wallet Syndrome, Male Breast
 Fluticasone furoate/vilanterol etc. Cancer, Selfie syndrome and many more are of Page 1485
IAJPS 2017, 4 (06), 1481-1486 Sai Krishna G et al ISSN 2349-7750

increased concern and clinicians must be made aware 8.Gibson PG, Simpson JL. The overlap syndrome of
of these diseases for better diagnosis and asthma and COPD: what are its features and how
management. There is a deficit of medical and important is it? Thorax 2009; 64:728-35.
scientific knowledge related to these diseases. 9.GINA, 2015, Global Initiative for Management and
Physicians, researchers and healthcare professionals Prevention of Asthma.
were unaware of the under diagnosed diseases and 10.Global Initiative for Chronic Obstructive
until very recently there was no real research Pulmonary Disease (GOLD), 2015, Global Strategy
concerning issues related to the field. [12-18] for Diagnosis, Management and Prevention of
CONCLUSION: 11.Louie S, Zeki AA, Schivo M, et al. The asthma-
ACOS can be managed in primary care with the help chronic obstructive pulmonary disease overlap
of clinical pharmacist being an integral part of syndrome: Pharmacotherapeutic considerations.
supporting and educating the patients. These patients Expert Rev Clin Pharmacol 2013; 6:197-219.
require on-going education in relation to inhaler 12.Sai Krishna G, Komal Krishna T, et al. Tired All
technique, adherence to medication regimes, non- the Time: A Chronic Fatigue Syndrome. J Pharm
pharmacological interventions such as vaccinations, Pract Community Med. 2016; 2(2): 32-34.
breathing exercises and self-management. As ACOS 13.Sai Krishna G & Komal Krishna T. Selfie
patients likely to have poor outcomes when compare Syndrome: A Disease of New Era. Res Pharm Health
to patients with either COPD or asthma alone, it is Sci.2016; 2(2): 118-121.
essential that they are adequately treated and assessed 14.Sai Krishna G, Bhavani Ramesh.T, Prem
using the new guidance from GINA & GOLD. As Kumar.P. Male Breast Cancer. British Biomedical
with any chronic condition, clinical pharmacists are Bulletin, 2014; 2(1): 17-25.
in a privileged position to assist patients attain and 15.Sai Krishna G, Sai Teja.T, Komal Krishna.T, et
obtain an optimal quality of life. al. Fat Wallet Syndrome: A mini review. European
Journal of Biomedical and Pharmaceutical Sciences.
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