Dissecting similarities and differences of exacerbations across different chronic airway diseases

Acute exacerbations (AEx) are crucial events across all chronic airway diseases (CAD); they are episodes of acute worsening of respiratory symptoms that punctuate the natural history of these diseases and are largely responsible for adverse outcomes. Preventing AEx is globally important for long-term strategies. Despite advances in understanding CAD, AEx remain challenging and a research priority. Tackling key unanswered questions will require international collaborative programmes focusing on mechanistic, translational, and clinical research.

The pathobiology of AEx is complex, involving microenvironment modification, host defence impairment, inflammation, structural changes and microbial dynamics. Studies show a link between AEx, microbiome organisation and treatment outcomes in CF, non-CF bronchiectasis, and COPD. Comparing microbial community behaviour at stable state and during AEx may provide novel insight into the airway microenvironment and its role in exacerbations.

Other mechanisms like CFTR dysfunction and structural alterations also play a role. Acquired CFTR dysfunction in diseases like COPD could amplify mucus hypersecretion, chronic inflammation, and AEx. Structural abnormalities can be reversed with treatment, particularly when started early. Different phenotypes/endotypes affect AEx risk; integrating molecular and microbial profiles has led to the identification of AEx subtypes. Studying recovery and lung repair after AEx is also crucial, as delayed recovery impacts long-term outcomes. Further work is needed to define these mechanisms and phenotypes. Key questions for the seminar include readiness to use advanced technology for AEx monitoring, the role of comorbidities, and new treatment perspectives in personalised medicine.