Asthma-COPD overlap: current understanding and the utility of experimental models

Abstract

Pathological features of both asthma and COPD coexist in some patients and this is termed asthma-COPD overlap (ACO). ACO is heterogeneous and patients exhibit various combinations of asthma and COPD features, making it difficult to characterise the underlying pathogenic mechanisms. There are no controlled studies that define effective therapies for ACO, which arises from the lack of international consensus on the definition and diagnostic criteria for ACO, as well as scant in vitro and in vivo data. There remain unmet needs for experimental models of ACO that accurately recapitulate the hallmark features of ACO in patients. The development and interrogation of such models will identify underlying disease-causing mechanisms, as well as enabling the identification of novel therapeutic targets and providing a platform for assessing new ACO therapies. Here, we review the current understanding of the clinical features of ACO and highlight the approaches that are best suited for developing representative experimental models of ACO.

Exploring the 175-year history of spirometry and the vital lessons it can teach us today

“…However, research since the 1980s called this into question, showing no clear cut-off between asthma and COPD in bronchodilator response, and sometimes significant post-bronchodilator changes in patients with severe emphysema [57][58][59][60]. The more recent concept of asthma COPD overlap (ACO) further complicates this binary approach to interpreting spirometry [61,62]. Given the persistent lack of a universally accepted definition for ACO, uncertain epidemiology, and significant clinical heterogeneity, the effectiveness of spirometry in diagnosing and managing patients with ACO is still being debated [62,63].…”

“…The more recent concept of asthma COPD overlap (ACO) further complicates this binary approach to interpreting spirometry [61,62]. Given the persistent lack of a universally accepted definition for ACO, uncertain epidemiology, and significant clinical heterogeneity, the effectiveness of spirometry in diagnosing and managing patients with ACO is still being debated [62,63].…”

Biologic Treatments for Asthma and Chronic Obstructive Pulmonary Disorder

“…An overview of the direct targets of each compound is available in Figure 2. A recent review by Tu and colleagues suggests that a treatable traits concept, where phenotypic or endotypic features are used to create multi-dimensional biomarker profiles for treatment that can be tested in animal models and this may drive development of newer biologics [58]. A gold-standard analysis of promising ACO treatments (such as macrolides or muscarinic antagonists) has been reviewed by Leung and Sin [59].…”

Asthma-COPD-Overlap – diagnostisches und therapeutisches Management

“…ACO ist geprägt von chronischer Atemwegsentzündung und Atemwegsremodelling, Atemwegsobstruktion und nachfolgender Symptomatik inkl. Giemen, Dyspnoe und häufigen Exazerbationen [11,12]. Zusätzlich liegen einige Asthma-Merkmale vor wie reversible Atemflusslimitation und eosinophile T2-Inflammation und einige COPD-Merkmale wie irreversible Atemwegsinflammation und neutrophile Typ 1/17-Inflammation (▶ Abb.…”

“…1). ACO-Patienten haben in den meisten Studien ausgeprägtere Symptome als Patienten mit Asthma oder COPD allein, häufiger Exazerbationen, häufiger Hospitalisierungen, einen rascheren FEV1-Verlust, mehr Komorbiditäten und teilweise auch eine erhöhte Mortalitätauch wenn die Datenlage nicht in allen Studien ganz konsistent ist [11,12].…”