The role of acute and chronic respiratory colonization and infections in the pathogenesis of <scp>COPD</scp>

<jats:title>ABSTRACT</jats:title><jats:p> <jats:styled-content style="fixed-case">COPD</jats:styled-content> is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While <jats:styled-content style="fixed-case">COPD</jats:styled-content> pathogens such as <jats:italic>Haemophilus influenzae</jats:italic>, <jats:italic>Moraxella catarrhalis</jats:italic> and <jats:italic>Streptococcus pneumoniae</jats:italic> are strongly associated with acute exacerbations of <jats:styled-content style="fixed-case">COPD</jats:styled-content> (<jats:styled-content style="fixed-case">AECOPD</jats:styled-content>), the clinical relevance of these pathogens in stable <jats:styled-content style="fixed-case">COPD</jats:styled-content> patients remains unclear. Immune responses in stable and colonized <jats:styled-content style="fixed-case">COPD</jats:styled-content> patients are comparable to those detected in <jats:styled-content style="fixed-case">AECOPD</jats:styled-content>, supporting a role for chronic colonization in <jats:styled-content style="fixed-case">COPD</jats:styled-content> pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe–<jats:styled-content style="fixed-case">COPD</jats:styled-content> interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the <jats:styled-content style="fixed-case">COPD</jats:styled-content> disease state. As microbial changes associated with <jats:styled-content style="fixed-case">AECOPD</jats:styled-content>, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of <jats:styled-content style="fixed-case">COPD</jats:styled-content> and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of <jats:styled-content style="fixed-case">COPD</jats:styled-content> that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe–host interplay in <jats:styled-content style="fixed-case">COPD</jats:styled-content>. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of <jats:styled-content style="fixed-case">COPD</jats:styled-content>.</jats:p>