Haemophilus influenzae in the airways: canary in the coal mine or driver of disease?

Abstract

Introduction: overgrowth and colonization by non-typeable Haemophilus influenzae (NTHi) is a common feature of increasing disease severity, treatment resistance and increased susceptibility to disease exacerbations across chronic airways diseases (CADs). Whether NTHi is a driver of respiratory disease or reflects that the damaged airway has become a permissive environment for growth remains to be proven.

Areas covered: in this review, we discuss the potential roles of hypermutation, biofilm formation and intracellular living in allowing NTHi to adapt to living in the lungs of individuals with CADs. Furthermore, we also highlight immunological, structural and mucosal changes in the lungs themselves that can create a permissive niche for NTHi colonization. Given the significance of the host-pathogen interaction in the pathophysiology of CADs, we also consider which host and bacterial mechanisms may serve as potential targets for novel therapeutics. To achieve this we performed a comprehensive literature search through PubMed to identify studies reporting on NTHi in chronic airways diseases published up to 31 November 2025.

Expert opinion: a deeper understanding of the dynamic interactions between NTHi and the diseased airway may help identify novel diagnostic and therapeutic interventions that can be effective across multiple CADs.

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Identifiers

ORCID for Jodie Ackland: orcid.org/0000-0003-3120-3620

ORCID for Karl J. Staples: orcid.org/0000-0003-3844-6457

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