Your browser doesn't support javascript.
loading
A severe asthma phenotype of excessive airway Haemophilus influenzae relative abundance associated with sputum neutrophilia.
Versi, Ali; Azim, Adnan; Ivan, Fransiskus Xaverius; Abdel-Aziz, Mahmoud I; Bates, Stewart; Riley, John; Uddin, Mohib; Zounemat Kermani, Nazanin; Maitland-Van Der Zee, Anke-H; Dahlen, Sven-Eric; Djukanovic, Ratko; Chotirmall, Sanjay H; Howarth, Peter; Adcock, Ian M; Chung, Kian Fan.
Afiliación
  • Versi A; National Heart & Lung Institute, Imperial College London, London, UK.
  • Azim A; Respiratory Department, Faculty of Medicine, Southampton University, Southampton, UK.
  • Ivan FX; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
  • Abdel-Aziz MI; Department of Pulmonary Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • Bates S; Respiratory Therapeutic Unit, GSK, Stockley Park, UK.
  • Riley J; Respiratory Therapeutic Unit, GSK, Stockley Park, UK.
  • Uddin M; AstraZeneca BioPharmaceuticals R&D, Gothenburg, Sweden.
  • Zounemat Kermani N; National Heart & Lung Institute, Imperial College London, London, UK.
  • Maitland-Van Der Zee AH; Department of Pulmonary Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • Dahlen SE; Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
  • Djukanovic R; Respiratory Department, Faculty of Medicine, Southampton University, Southampton, UK.
  • Chotirmall SH; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
  • Howarth P; Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore, Singapore.
  • Adcock IM; Respiratory Department, Faculty of Medicine, Southampton University, Southampton, UK.
  • Chung KF; National Heart & Lung Institute, Imperial College London, London, UK.
Clin Transl Med ; 14(9): e70007, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39187935
ABSTRACT

BACKGROUND:

Severe asthma (SA) encompasses several clinical phenotypes with a heterogeneous airway microbiome. We determined the phenotypes associated with a low α-diversity microbiome.

METHODS:

Metagenomic sequencing was performed on sputum samples from SA participants. A threshold of 2 standard deviations below the mean of α-diversity of mild-moderate asthma and healthy control subjects was used to define those with an abnormal abundance threshold as relative dominant species (RDS).

FINDINGS:

Fifty-one out of 97 SA samples were classified as RDSs with Haemophilus influenzae RDS being most common (n = 16), followed by Actinobacillus unclassified (n = 10), Veillonella unclassified (n = 9), Haemophilus aegyptius (n = 9), Streptococcus pseudopneumoniae (n = 7), Propionibacterium acnes (n = 5), Moraxella catarrhalis (n = 5) and Tropheryma whipplei (n = 5). Haemophilus influenzae 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 = 9) of highest relative abundance of exclusively Haemophilus influenzae RDSs with longer duration of disease and higher sputum neutrophil counts associated with enrichment pathways of MAPK, NF-κB, TNF, mTOR and necroptosis, compared to the only other cluster, C1, which consisted of 7 Haemophilus influenzae RDSs out of 42. Sputum transcriptomics of C2 cluster compared to C1 RDSs revealed higher expression of neutrophil extracellular trap pathway (NETosis), IL6-transignalling signature and neutrophil activation.

CONCLUSION:

We describe a Haemophilus influenzae 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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Esputo / Haemophilus influenzae / Neutrófilos Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Transl Med Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Esputo / Haemophilus influenzae / Neutrófilos Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Transl Med Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos