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Background Exacerbations are major causes of morbidity in individuals with chronic respiratory diseases such as chronic obstructive pulmonary disease, asthma and bronchiectasis. Increasing evidence implicates respiratory viruses as predominant triggers, though the underlying immunopathogenic mechanisms remain poorly understood.Narrative This review synthesises current knowledge on the interplay between viral pathogens at the airway epithelial barrier, including structural and immunological mechanisms that may dysregulate antiviral immunity in chronic respiratory diseases. Furthermore, we discuss how perturbations in the respiratory microbiome, characterised by reduced microbial diversity, can modulate host antiviral immune defences.Conclusions Collectively, these interconnected factors create a permissive environment predisposing to viral infection and exacerbations in chronic respiratory diseases. Understanding the complex interactions between airway structure, interferon-mediated antiviral responses, inflammation and microbiota is essential for developing targeted therapies to effectively manage virus-induced exacerbations and reduce disease burden.