RT Journal Article SR Electronic T1 Non-typeable Haemophilus influenzae airways infection: the next treatable trait in asthma? JF European Respiratory Review JO EUROPEAN RESPIRATORY REVIEW FD European Respiratory Society SP 220008 DO 10.1183/16000617.0008-2022 VO 31 IS 165 A1 Mary Ashley Brown A1 Maisha Jabeen A1 Gurpreet Bharj A1 Timothy S.C. Hinks YR 2022 UL http://err.ersjournals.com/content/31/165/220008.abstract AB Asthma is a complex, heterogeneous condition that affects over 350 million people globally. It is characterised by bronchial hyperreactivity and airways inflammation. A subset display marked airway neutrophilia, associated with worse lung function, higher morbidity and poor response to treatment. In these individuals, recent metagenomic studies have identified persistent bacterial infection, particularly with non-encapsulated strains of the Gram-negative bacterium Haemophilus influenzae. Here we review knowledge of non-typeable H. influenzae (NTHi) in the microbiology of asthma, the immune consequences of mucosal NTHi infection, various immune evasion mechanisms, and the clinical implications of NTHi infection for phenotyping and targeted therapies in neutrophilic asthma. Airway neutrophilia is associated with production of neutrophil chemokines and proinflammatory cytokines in the airways, including interleukin (IL)-1β, IL-6, IL-8, IL-12, IL-17A and tumour necrosis factor. NTHi adheres to and invades the lower respiratory tract epithelium, inducing the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes. NTHi reduces expression of tight-junction proteins, impairing epithelial integrity, and can persist intracellularly. NTHi interacts with rhinoviruses synergistically via upregulation of intracellular cell adhesion molecule 1 and promotion of a neutrophilic environment, to which NTHi is adapted. We highlight the clinical relevance of this emerging pathogen and its relevance for the efficacy of long-term macrolide therapy in airways diseases, we identify important unanswered questions and we propose future directions for research.In recent microbiome studies non-typeable H. influenzae has been the dominant pathogen in asthma. NTHi persists in inflamed airways, activates innate immune responses to drive neutrophilia, and likely explains the efficacy of long-term macrolide therapy. https://bit.ly/3O8Adlu