Identification of exhaled volatile organic compounds that characterize asthma phenotypes: A J-VOCSA study

Maho Suzukawa; Ken Ohta; Masahiro Sugimoto; Nobuharu Ohshima; Nobuyuki Kobayashi; Hiroyuki Tashimo; Yasushi Tanimoto; Junko Itano; Goro Kimura; Shohei Takata; Takako Nakano; Takafumi Yamashita; Satoshi Ikegame; Kentaro Hyodo; Masahiro Abe; Kenji Chibana; Yosuke Kamide; Kazunori Sasaki; Hiroya Hashimoto

doi:10.1016/j.alit.2024.04.003

Identification of exhaled volatile organic compounds that characterize asthma phenotypes: A J-VOCSA study

Allergol Int. 2024 Apr 23:S1323-8930(24)00047-9. doi: 10.1016/j.alit.2024.04.003. Online ahead of print.

Authors

Maho Suzukawa¹, Ken Ohta², Masahiro Sugimoto³, Nobuharu Ohshima⁴, Nobuyuki Kobayashi⁴, Hiroyuki Tashimo⁴, Yasushi Tanimoto⁵, Junko Itano⁵, Goro Kimura⁵, Shohei Takata⁶, Takako Nakano⁶, Takafumi Yamashita⁶, Satoshi Ikegame⁶, Kentaro Hyodo⁷, Masahiro Abe⁸, Kenji Chibana⁹, Yosuke Kamide¹⁰, Kazunori Sasaki³, Hiroya Hashimoto¹¹

Affiliations

¹ Clinical Research Center, National Hospital Organization Tokyo National Hospital, Tokyo, Japan. Electronic address: suzukawamaho@gmail.com.
² Clinical Research Center, National Hospital Organization Tokyo National Hospital, Tokyo, Japan; Japan Anti-Tuberculosis Association, JATA Fukujuji Hospital, Tokyo, Japan. Electronic address: kenohta3@gmail.com.
³ Institute for Advanced Biosciences, Keio University, Yamagata, Japan; Human Metabolome Technologies, Inc., Yamagata, Japan.
⁴ Clinical Research Center, National Hospital Organization Tokyo National Hospital, Tokyo, Japan.
⁵ National Hospital Organization Minami-Okayama Medical Center, Okayama, Japan.
⁶ National Hospital Organization Fukuokahigashi Medical Center, Fukuoka, Japan.
⁷ National Hospital Organization Ibarakihigashi National Hospital, Ibaraki, Japan.
⁸ National Hospital Organization Ehime Medical Center, Ehime, Japan.
⁹ National Hospital Organization Okinawa National Hospital, Okinawa, Japan.
¹⁰ National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan.
¹¹ National Hospital Organization Nagoya Medical Center, Nagoya, Japan.

PMID: 38658257
DOI: 10.1016/j.alit.2024.04.003

Abstract

Background: Asthma is characterized by phenotypes of different clinical, demographic, and pathological characteristics. Identifying the profile of exhaled volatile organic compounds (VOCs) in asthma phenotypes may facilitate establishing biomarkers and understanding asthma background pathogenesis. This study aimed to identify exhaled VOCs that characterize severe asthma phenotypes among patients with asthma.

Methods: This was a multicenter cross-sectional study of patients with severe asthma in Japan. Clinical data were obtained from medical records, and questionnaires were collected. Exhaled breath was sampled and subjected to thermal desorption gas chromatography-mass spectrometry (GC/MS).

Results: Using the decision tree established in the previous nationwide asthma cohort study, 245 patients with asthma were divided into five phenotypes and subjected to exhaled VOC analysis with 50 healthy controls (HCs). GC/MS detected 243 VOCs in exhaled breath samples, and 142 frequently detected VOCs (50% of all samples) were used for statistical analyses. Cluster analysis assigning the groups with similar VOC profile patterns showed the highest similarities between phenotypes 3 and 4 (early-onset asthma phenotypes), followed by the similarities between phenotypes 1 and 2 (late-onset asthma phenotypes). Comparisons between phenotypes 1-5 and HC revealed 19 VOCs, in which only methanesulfonic anhydride showed p < 0.05 adjusted by false discovery rate (FDR). Comparison of these phenotypes yielded several VOCs showing different trends (p < 0.05); however, no VOCs showed p < 0.05 adjusted by FDR.

Conclusions: Exhaled VOC profiles may be useful for distinguishing asthma and asthma phenotypes; however, these findings need to be validated, and their pathological roles should be clarified.

Keywords: Asthma; Cluster analysis; Exhaled breath; Phenotype; Volatile organic compounds.