PT  - JOURNAL ARTICLE
AU  - Mary Ashley Brown
AU  - Maisha Jabeen
AU  - Gurpreet Bharj
AU  - Timothy S.C. Hinks
TI  - Non-typeable <em>Haemophilus influenzae</em> airways infection: the next treatable trait in asthma?
AID  - 10.1183/16000617.0008-2022
DP  - 2022 Sep 30
TA  - European Respiratory Review
PG  - 220008
VI  - 31
IP  - 165
4099  - http://err.ersjournals.com/content/31/165/220008.short
4100  - http://err.ersjournals.com/content/31/165/220008.full
SO  - EUROPEAN RESPIRATORY REVIEW2022 Sep 30; 31
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