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. 2023 Nov;78(11):2906-2920.
doi: 10.1111/all.15776. Epub 2023 Jun 7.

Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation

Ali Versi  1 , Fransiskus Xaverius Ivan  2 , Mahmoud I Abdel-Aziz  3 , Stewart Bates  4 , John Riley  4 , Frederic Baribaud  5 , Nazanin Zounemat Kermani  1 , Paolo Montuschi  6 , Sven-Erik Dahlen  7 , Ratko Djukanovic  8   9 , Peter Sterk  3 , Anke H Maitland-Van Der Zee  3 , Sanjay H Chotirmall  2   10 , Peter Howarth  8 , Ian M Adcock  1 , Kian Fan Chung  1 ; U-BIOPRED consortium
Collaborators, Affiliations

Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation

Ali Versi et al. Allergy. 2023 Nov.

Abstract

Background: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma.

Methods: Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs).

Results: α-diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α-diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and β-diversities were stable at one year.

Conclusions: Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation.

Keywords: Haemophilus influenzae; Moraxella catarrhalis; Tropheryma whipplei; severe asthma; α-diversity.

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References

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