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We determined the phenotypes associated with a low \u03b1\u2010diversity microbiome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Metagenomic sequencing was performed on sputum samples from SA participants. A threshold of 2 standard deviations below the mean of \u03b1\u2010diversity of mild\u2010moderate asthma and healthy control subjects was used to define those with an abnormal abundance threshold as relative dominant species (RDS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      Fifty\u2010one out of 97 SA samples were classified as RDSs with\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      RDS being most common (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a016), followed by\n                      <jats:italic>Actinobacillus unclassified<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010),\n                      <jats:italic>Veillonella unclassified<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a09)\n                      <jats:italic>, Haemophilus aegyptius<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a09)\n                      <jats:italic>, Streptococcus pseudopneumoniae<\/jats:italic>\n                      (\n                      <jats:italic>n\u00a0=\u00a07<\/jats:italic>\n                      ),\n                      <jats:italic>Propionibacterium acnes<\/jats:italic>\n                      (\n                      <jats:italic>n\u00a0=\u00a05), Moraxella catarrhalis<\/jats:italic>\n                      (\n                      <jats:italic>n\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a05<\/jats:italic>\n                      ) and\n                      <jats:italic>Tropheryma whipplei<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05).\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      RDS had the highest duration of disease, more exacerbations in previous year and greatest number on daily oral corticosteroids. Hierarchical clustering of RDSs revealed a C2 cluster (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a09) of highest relative abundance of exclusively\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      RDSs with longer duration of disease and higher sputum neutrophil counts associated with enrichment pathways of MAPK, NF\u2010\u03baB, TNF, mTOR and necroptosis, compared to the only other cluster, C1, which consisted of 7\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      RDSs out of 42. Sputum transcriptomics of C2 cluster compared to C1 RDSs revealed higher expression of neutrophil extracellular trap pathway (NETosis), IL6\u2010transignalling signature and neutrophil activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We describe a\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      cluster of the highest relative abundance associated with neutrophilic inflammation and NETosis indicating a host response to the bacteria. This phenotype of severe asthma may respond to specific antibiotics.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70007","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T23:55:52Z","timestamp":1724716552000},"source":"Crossref","is-referenced-by-count":22,"title":["A severe asthma phenotype of excessive airway\n                    <i>Haemophilus influenzae<\/i>\n                    relative abundance associated with sputum neutrophilia"],"prefix":"10.1002","volume":"14","author":[{"given":"Ali","family":"Versi","sequence":"first","affiliation":[{"name":"National Heart &amp; Lung Institute Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Azim","sequence":"additional","affiliation":[{"name":"Respiratory Department, Faculty of Medicine Southampton University  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fransiskus Xaverius","family":"Ivan","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud I","family":"Abdel\u2010Aziz","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Amsterdam University Medical Centers University of Amsterdam  Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Bates","sequence":"additional","affiliation":[{"name":"Respiratory Therapeutic Unit GSK  Stockley Park UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Riley","sequence":"additional","affiliation":[{"name":"Respiratory Therapeutic Unit GSK  Stockley Park UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohib","family":"Uddin","sequence":"additional","affiliation":[{"name":"AstraZeneca BioPharmaceuticals R&amp;D  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-3861","authenticated-orcid":false,"given":"Nazanin","family":"Zounemat Kermani","sequence":"additional","affiliation":[{"name":"National Heart &amp; 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