The Current State of Knowledge on Asthma-COPD Overlap (ACO) in Clinical and Experimental Research: What Do We Know So Far?

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Background

Asthma and chronic obstructive pulmonary disease (COPD) are intricate respiratory conditions characterized by airway obstruction. Despite extensive research into both afflictions, a recently identified variant, Asthma-COPD Overlap (ACO), has been unveiled. ACO exhibits symptoms resembling COPD but responds significantly to bronchodilators. Approximately 11.1% of the population is estimated to have ACO, posing a diagnostic challenge with variability between asthma (11.1% to 61.0%) and COPD (4.2% to 66.0%) diagnoses.

Patients with ACO experience features of both asthma and COPD, enduring a heightened symptom burden, frequent exacerbations, and rapid declines in lung function, leading to increased mortality and healthcare resource utilization compared to isolated cases. Despite persistent diagnostic challenges, treatment relies on extrapolated data from asthma and COPD studies. Emerging evidence supports ACO as a distinct clinical phenotype, necessitating further research to inform recognition and treatment strategies. Current therapies, drawn from asthma and COPD data, underscore the need for specific ACO-focused approaches.

In recent years, experimental studies using asthma-COPD overlap models have significantly contributed to a deeper understanding of underlying etiological concepts. Addressing inflammatory changes, signaling pathways, oxidative stress, and airway and alveolar septum remodeling processes in ACO, our group's research highlights valuable insights. The pursuit of innovative alternatives for disease control led us to investigate the inhibitory effects of plant proteases and monoclonal antibody treatment (anti-IL-17) in asthma-COPD overlap models. Our results revealed significant improvements. We observed attenuation of crucial cytokines in the inflammatory process, reduced oxidative stress, modulation of signaling pathways, and improvements in extracellular matrix remodeling in both airways and alveolar septum.

Clinical and experimental studies have shown that the perpetuation of inflammatory processes mediated by innate and adaptive immune responses could be attenuated by exercise training, mitigating structural and functional changes that characterize asthma and COPD. In asthma, exercise training decreases the airways' hyperresponsiveness concomitant with a reduction of airway remodeling. Moreover, it was shown that these results are associated with a decrease in eosinophils and Th2 cytokines and improvement in asthma control and exercise capacity in COPD, exercise training could avoid the progression of airway obstruction in patients as well as alveolar lung destruction in rodents with a concomitant decrease of macrophages, neutrophils, and Th17 cells and cytokines.

As we progress, experimental studies continue to enrich our understanding of ACO mechanisms. Focused on the intersections between asthma and COPD, our research group provides valuable insights and identifies potential therapeutic targets. While innovations guide our investigation into specific treatments, the journey to fully understand and effectively treat ACO is in its early stages. The imperative for additional research is clear to develop safer and more effective strategies, considering the unique characteristics of this condition. Collaborative efforts among researchers are essential to unravel the complexities of ACO and offer personalized and efficient treatment approaches.
In this Research Topic, we welcome manuscripts focusing on innate immunity and inflammation, focused on the following sub-topics:

• Investigations involving lung mechanics, inflammation, pulmonary remodeling, and oxidative stress in experimental models of ACO.
• Investigations involving the effects of exercise training in innate immune response in asthma or COPD.
• Investigations involving inflammatory signaling pathways mitigated by exercise training due to the increased release of different anti-inflammatory chemokines and antioxidants.
• Investigations regarding adaptive immune response in asthma, particularly focusing on the benefits of exercise training to attenuate the Th2 and Th17 responses in the different phenotypes.
• Investigations regarding adaptive immune response in COPD, particularly focused on describing the effects of exercise training in Th1 and Th17 responses.

Keywords: Asthma, COPD, ACO, Pulmonary Disease, Oxidative Stress, Therapy, Exercise Training, Asthma COPD, Innate response, Adaptive immune response

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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