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

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

International guidelines COPD Asthma GOLD GINA

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

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

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

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 http://www.ginasthma.org

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 http://www.ginasthma.org

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 http://www.ginasthma.org

ACOS - an overlap syndrome Asthma ACOS COPD

A wide definition? Asthma ACOS COPD

A narrow definition? Asthma ACOS COPD

Diagnosing ACOS Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS) 2015 at http://www.ginasthma.org

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

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)

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)

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

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.

© Global Initiative for Asthma GINA 2014 © Global Initiative for Asthma

Step 3 - Spirometry Spirometric variable Asthma COPD ACOS Normal FEV 1 /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

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

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

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

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

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

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 2015:10 1745–1752

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

What is the prevalence of ACOS among COPD patients?

What is the prevalence of ACOS among COPD patients? Alshabanat A. et al. PLOS ONE. 2015.

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. 2015.

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

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

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

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

Disease impact

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

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 2015:10 1443–14540

Is it important diagnosing ACOS in primary care?