Sputum microbiota and inflammatory subtypes in asthma, COPD, and its overlap

Chie Morimoto; Hisako Matsumoto; Natsuko Nomura; Hironobu Sunadome; Tadao Nagasaki; Susumu Sato; Atsuyasu Sato; Tsuyoshi Oguma; Isao Ito; Mariko Kogo; Keisuke Tomii; Tomoko Tajiri; Kai Ohashi; Takamitsu Tsukahara; Toyohiro Hirai

doi:10.1016/j.jacig.2023.100194

Sputum microbiota and inflammatory subtypes in asthma, COPD, and its overlap

J Allergy Clin Immunol Glob. 2023 Nov 21;3(1):100194. doi: 10.1016/j.jacig.2023.100194. eCollection 2024 Feb.

Authors

Chie Morimoto¹, Hisako Matsumoto^{1

2}, Natsuko Nomura¹, Hironobu Sunadome^{1

3}, Tadao Nagasaki^{1

3}, Susumu Sato^{1

3}, Atsuyasu Sato¹, Tsuyoshi Oguma¹, Isao Ito¹, Mariko Kogo^{1

4}, Keisuke Tomii⁴, Tomoko Tajiri^{5

6}, Kai Ohashi⁷, Takamitsu Tsukahara⁷, Toyohiro Hirai¹

Affiliations

¹ Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
² Department of Respiratory Medicine and Allergology, Faculty of Medicine, Kindai University, Osaka, Japan.
³ Department of Respiratory Care and Sleep Control Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁴ Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
⁵ Department of Respiratory Medicine, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.
⁶ Department of Respiratory Medicine, Allergy and Clinical Immunology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
⁷ Kyoto Institute of Nutrition & Pathology, Inc, Kyoto, Japan.

Abstract

Background: Airway microbiota in asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) remains unknown.

Objective: This study with ACO-enriched population aimed to clarify airway microbiota in ACO and in mixed granulocytic inflammation, often detected in ACO and chronic airway diseases.

Methods: This is an observational cross-sectional study. Patients with asthma with airflow limitation, ACO, and COPD were enrolled. Blood tests, pulmonary function, exhaled nitric oxide, and sputum tests were conducted. Sputum microbiota was evaluated using the 16S rRNA gene sequencing technique.

Results: A total of 112 patients (13 asthma, 67 ACO, and 32 COPD) were examined. There were no significant differences in α-diversity among the 3 diseases. The relative abundances of phylum Bacteroidetes, class Bacteroidia, and genus Porphyromonas were associated with decreased eosinophilic inflammation, and were significantly lower in ACO than in COPD. In a comparison of sputum inflammatory subtypes, the proportion of Haemophilus was numerically highest in the mixed granulocytic subtype, followed by the neutrophilic subtype. Likewise, the proportion of Haemophilus was the highest in the intermediate-high (2%-8%) sputum eosinophil group and lowest in the severe (≥8%) eosinophil group. Clinically, Haemophilus proportion was associated with sputum symptoms. Finally, the proportion of Streptococcus was associated with higher blood eosinophil counts and most severe airflow limitation.

Conclusions: Bacteroidia and Porphyromonas abundances in sputum are associated with the eosinophil-low phenotype, and ACO may be characterized by a decrease in these taxa. A mild elevation in sputum eosinophil does not preclude the presence of Haemophilus, which should be noted in the management of obstructive airway diseases.

Keywords: Asthma-COPD overlap; eosinophil-low; mixed granulocytic subtype; sputum microbiome.