1. Asthma-COPD Overlap Syndrome (ACOS) Challenges Diagnosing ACOS
Björn Ställberg
Uppsala University
Sweden

2. Disclosure
I have received honoraria for educational activities, lectures and advisory boards from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, MEDA and TEVA

3. International guidelines
COPD
Asthma
GOLD
GINA

4. Ställberg et al. Prim Care Respir J 2014
Data from the PATHOS study
“Following the index date for the COPD diagnose,
23% of the patients received an asthma diagnosis over the follow up period”
Ställberg et al. Prim Care Respir J 2014

5. Why have some COPD patients a also an asthma diagnosis?
Incorrect COPD diagnosis from the beginning, it is asthma
Incorrect asthma diagnosis, it is COPD
Have asthma but due to high age the patient has got a COPD diagnosis.
The patient has had a diagnosis of asthma and later also developed a COPD diagnosis.
The patient have a mix of both diseases = ACOS

6. International guidelines
ACOS
COPD
Asthma
GOLD
GINA
Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and
Asthma-COPD Overlap Syndrome (ACOS) 2015 at

7. ACOS definition
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 in clinical practice by the features that it shares with both asthma and COPD
Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and
Asthma-COPD Overlap Syndrome (ACOS) 2015 at

8. Some key points from the guidelines
Some patients have clinical features of both asthma and COPD
Outcomes for ACOS are often worse than for asthma or COPD alone.
Distinguishing asthma from COPD can be problematic, particularly in smokers and older adults
A stepwise approach to diagnosis is advised
Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and
Asthma-COPD Overlap Syndrome (ACOS) 2015 at

9. Some key points from the guidelines
ACOS is not a single disease. It includes patients with different airways diseases (phenotypes) and different underlying mechanisms
Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and
Asthma-COPD Overlap Syndrome (ACOS) 2015 at

10. ACOS - an overlap syndrome
Asthma
ACOS
COPD

11. A wide definition?
Asthma
ACOS
COPD

12. A narrow definition?
Asthma
ACOS
COPD

13. Diagnosing ACOS
Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and
Asthma-COPD Overlap Syndrome (ACOS) 2015 at

14. Usual features of asthma, COPD and ACOS
Age of onset
Usually childhood but can commence at any age
Usually >40 years
Usually ≥40 years, but may have had symptoms as child/early adult
Pattern of respiratory symptoms
Symptoms vary over time (day to day, or over longer period), often limiting activity. Often triggered by exercise, emotions including laughter, dust, or exposure to allergens
Chronic usually continuous symptoms, particularly during exercise, with ‘better’ and ‘worse’ days
Respiratory symptoms including exertional dyspnea are persistent, but variability may be prominent
Lung function
Current and/or historical variable airflow limitation, e.g. BD reversibility, AHR
FEV1 may be improved by therapy, but post-BD FEV1/FVC <0.7 persists -
Airflow limitation not fully reversible, but often with current or historical variability
Lung function between symptoms
May be normal
Persistent airflow limitation

15. Usual features of asthma, COPD and ACOS (continued)
Past history or family history
Many patients have allergies and a personal history of asthma in childhood and/or family history of asthma
History of exposure to noxious particles or gases (mainly tobacco smoking or biomass fuels)
Frequently a history of doctor-diagnosed asthma (current or previous), allergies, family history of asthma, and/or a history of noxious exposures -
Time course
Often improves spontaneously or with treatment, but may result in fixed airflow limitation
Generally slowly progressive over years despite treatment
Symptoms are partly but significantly reduced by 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
Exacerbations occur, but risk can be substantially reduced by treatment
Exacerbations can be reduced by treatment. If present, comorbidities contribute to impairment
Exacerbations may be more common than in COPD but are reduced by treatment. Comorbidities can contribute to impairment.
GINA 2014, Box 5-2A (2/3)

16. Stepwise approach to diagnosis and initial treatment
For an adult who presents with respiratory symptoms:
Does the patient have chronic airways disease?
Syndromic diagnosis of asthma, COPD and ACOS
Spirometry
Commence initial therapy
Referral for specialized investigations (if necessary)

17. Features that (when present) favor asthma or COPD
Favors asthma
Favors COPD
Age of onset q
Before age 20 years
After age 40 years
Lung
function
Record of variable airflow limitation
(spirometry, peak flow)
Normal between symptoms
Record of persistent airflow limitation
(post -
BD FEV 1
/FVC <0.7)
Abnormal between symptoms
Past
history or
family history
Previous doctor diagnosis of asthma
Family history of asthma, and other allergic
conditions (allergic rhinitis or eczema)
Previous doctor diagnosis of COPD,
chronic bronchitis or emphysema
Heavy exposure to a risk factor: tobacco
smoke, biomass fuels
Chest X
ray
Normal
Severe hyperinflation
Time course
No worsening
of symptoms over time.
Symptoms vary seasonally, or from year to
year
May improve spontaneously, or respond
immediately to BD or to ICS over weeks
Symptoms
slowly worsening over time
(progressive course over years)
Rapid
acting bronchodilator treatment
provides only limited relief
Pattern of
respiratory
symptoms
Symptoms vary over
minutes, hours or days
Worse during night or early morning
Triggered by exercise, emotions including
laughter, dust, or exposure to allergens
Symptoms persist despite treatment
Good and bad days, but always daily
symptoms and exertional dyspnea
Chronic cough and sputum preceded
onset of dyspnea, unrelated to triggers

18. Features that (when present) favor asthma or COPD
Favors asthma
Favors COPD
Age of onset q
Before age 20 years
After age 40 years
Lung
function
Record of variable airflow limitation
(spirometry, peak flow)
Normal between symptoms
Record of persistent airflow limitation
(post -
BD FEV 1
/FVC <0.7)
Abnormal between symptoms
Past
history or
family history
Previous doctor diagnosis of asthma
Family history of asthma, and other allergic
conditions (allergic rhinitis or eczema)
Previous doctor diagnosis of COPD,
chronic bronchitis or emphysema
Heavy exposure to a risk factor: tobacco
smoke, biomass fuels
Chest X
ray
Normal
Severe hyperinflation
Time course
No worsening
of symptoms over time.
Symptoms vary seasonally, or from year to
year
May improve spontaneously, or respond
immediately to BD or to ICS over weeks
Symptoms
slowly worsening over time
(progressive course over years)
Rapid
acting bronchodilator treatment
provides only limited relief
Pattern of
respiratory
symptoms
Symptoms vary over
minutes, hours or days
Worse during night or early morning
Triggered by exercise, emotions including
laughter, dust, or exposure to allergens
Symptoms persist despite treatment
Good and bad days, but always daily
symptoms and exertional dyspnea
Chronic cough and sputum preceded
onset of dyspnea, unrelated to triggers
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.

19. © Global Initiative for Asthma
GINA 2014
© Global Initiative for Asthma

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

21. Soler-Cataluna et al. Arch Bronconeumol. 2012;48(9):331–337
The major criteria selected were: very positive bronchodilator test (increase in FEV1 ≥15% and ≥400 ml over baseline value), eosinophilia in sputum and personal history of asthma. The minor criteria were: total high IgE, personal history of atopy and positive bronchodilator test (increase in FEV1 ≥12% and ≥200 ml over baseline value) on 2 or more occasions.
In addition, it was agreed upon that it would be necessary for there to be 2 major criteria or 1 major and 2 minor criteria to correctly diagnose this clinical entity
Soler-Cataluna et al. Arch Bronconeumol. 2012;48(9):331–337

22. Soler-Cataluna et al. Arch Bronconeumol. 2012;48(9):331–337
The major criteria selected were: very positive bronchodilator test (increase in FEV1 ≥15% and ≥400 ml over baseline value), eosinophilia in sputum and personal history of asthma. The minor criteria were: total high IgE, personal history of atopy and positive bronchodilator test (increase in FEV1 ≥12% and ≥200 ml over baseline value) on 2 or more occasions.
In addition, it was agreed upon that it would be necessary for there to be 2 major criteria or 1 major and 2 minor criteria to correctly diagnose this clinical entity
Soler-Cataluna et al. Arch Bronconeumol. 2012;48(9):331–337

23. Soler-Cataluna et al. Arch Bronconeumol. 2012;48(9):331–337

24. Finnish COPD Practical guideline
Kankaanranta H, et al. Basic & Clinical Pharmacology & Toxicology, 2015, 116, 291–307

25. Finnish COPD Practical guideline
Kankaanranta H, et al. Basic & Clinical Pharmacology & Toxicology, 2015, 116, 291–307

26. Barrecheguren M et al. International Journal of COPD 2015:10 1745–1752
Conclusion:
“ACOS patients diagnosed on the basis of a previous diagnosis of asthma differed from the remaining COPD patients, but they were similar to ACOS patients diagnosed according to more restrictive criteria, suggesting that a history of asthma before the age of 40 years could be a useful criterion to suspect ACOS in a patient with COPD until new studies more precisely define the characteristics of ACOS and provide a gold standard for diagnosis”
Barrecheguren M et al. International Journal of COPD 2015: –1752

27. van den Berge M et al. Journal of Asthma and Allergy 2016:9 27–35
Asthma-ACOS
Patients with a history of asthma who have developed fixed airflow obstruction/incompletely reversible airflow obstruction
COPD-ACOS
Smokers or ex-smokers with COPD according to the GOLD criteria who display asthmatic features with increased bronchodilator reversibility
van den Berge M et al. Journal of Asthma and Allergy 2016:9 27–35

28. What is the prevalence of ACOS among COPD patients?

29. What is the prevalence of ACOS among COPD patients?
Alshabanat A. et al. PLOS ONE

30. What is the prevalence of ACOS among COPD patients?
patients in population based studies
27% (95% CI: 0.16–0.38)
Prevalence of ACOS among COPD
patients in hospital based studies
28% (95% CI: 0.09–0.47)
Alshabanat A. et al. PLOS ONE

31. Patients with a doctor’s diagnosis of COPD in the record (n=1129) Data from the PRAXIS study

32. Patients with a doctor’s diagnosis of COPD in the record (n=1129) Data from the PRAXIS study%

33. Patients with a doctor’s diagnosis of COPD in the record (n=1129) Data from the PRAXIS study

34. Patients with a doctor’s diagnosis of COPD in the record (n=1129) Data from the PRAXIS study

35. Disease impact

36. Clinical features of subjects with COPD and asthma compared to those with COPD alone
Hardin M et al. Eur Respir J 2014; 44: 341–350

37. Disease impact
Patients with features of both asthma and COPD have worse outcomes than those with asthma or COPD alone
Frequent exacerbations
Poor quality of life
A higher overall respiratory-related morbidity
Hardin M et al. Eur Respir J 2014; 44: 341–350
M Nielsen et al. International Journal of COPD 2015: –14540

38. Is it important diagnosing ACOS in primary care?