Asthma‐COPD Overlap and Asthma Progressing to COPD: Are We Using the Right Diagnostic Approaches and Pathways?

There have been significant advances in precision medicine utilizing 'omics' technology in asthma and chronic obstructive pulmonary disease (COPD). This has helped to delineate the clinical evolution and current and future development of therapies for both asthma and COPD. What is now needed is an even clearer understanding of the two disorders, but reports have underlined that there remains considerable ambiguity about these diseases.1-5 One key aspect may be erroneous interpretation of the joint Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy documents on the concept of Asthma COPD Overlap (ACO) and the spirometric definition of COPD by GOLD.6, 7 A definitive diagnosis of asthma can also be challenging. We write to provoke and stimulate discussion in this important area (Table 1). 1. The spirometry criteria of ACO by GINA-GOLD and that for COPD by GOLD are considered definitive. The criteria for both are not evidence based. 2. Bronchodilator responsiveness (BDR) is considered diagnostic of asthma. Bronchodilator responsiveness is a feature of COPD as well and, in certain circumstances, asthmatics may not demonstrate bronchodilator responsiveness. 3. A patient with COPD is also diagnosed with ACO based on a history of asthma. A prior history of asthma may be a misdiagnosis or erroneous. 4. ACO can be diagnosed in people with asthma who demonstrate persistent airflow limitation (PAL). PAL is due to uncontrolled inflammation/airway remodelling and does not need to invoke co-existing COPD. 5. Asthmatics who smoke are labelled as having coexistent COPD-thus ACO. Asthmatics that smoke may develop PAL due to unresolved inflammation that can mimic COPD spirometrically. 6. ACO can develop in asthmatics without risk factors for COPD. Without a risk factor, an overlap diagnosis cannot be established. 7. Asthma can progress to COPD. This is impossible without an additional risk-factor for COPD. What is frequently described are asthmatics developing PAL, which is misdiagnosed as COPD. The determination of the degree of bronchodilator responsiveness (BDR) is important in the evaluation of obstructive lung disease. There are various criteria to express the BDR but the most widely used are those of the joint American Thoracic Society-European Respiratory Society (ATS-ERS) Task Force; significant-responsiveness is denoted by a change of >12% of the baseline (FEV1) and >200 mL absolute change.2 BDR gained regulatory importance as American and European medical agencies required that COPD patients included in clinical trials meet the definition of irreversible airflow limitation whilst, axiomatically, asthmatics had to demonstrate responsiveness on lung function testing.12 Although historically used to diagnose asthma, none of these spirometry definitions and BDR are sensitive or sufficiently specific to differentiate asthma from COPD. Numerous longitudinal surveillance studies of asthmatics assert that some people develop COPD.21 What may be described are subsets that develop PAL and spirometry that is consistent with the GOLD spirometry definition of COPD. However, PAL may simply reflect uncontrolled inflammation and/or airway remodelling, factors such as non-adherence with treatment or other environmental exposures. Taking this reasoning into account, it may be best to intensify asthma therapy, improve adherence and manage comorbidities—rather than to resort to therapies aimed at an additional diagnosis of COPD. In summary, we argue that asthma and COPD are different respiratory diseases, each with a distinct pathogenesis, patterns of airway inflammation and pathology. For a diagnosis of ACO there needs to be verifiable asthma and diagnostic features of COPD (chronic bronchitis and/or emphysema on clinical or radiological grounds) with a verified risk factor (predominantly cigarette smoking). There are bound to be differences of opinion about ACO and aspects such as clinical expression, diagnosis and treatment and we welcome collegial feedback. Coenraad Frederik Nicolaas Koegelenberg received speaker fees from AstraZeneca and GlaxoSmithKline. Elvis Malcolm Irusen received speaker fees from AstraZeneca and GlaxoSmithKline, and served as a paid respiratory expert for GlaxoSmithKline. Danica Meiring has nothing to disclose.