Lower plasma resolvin D1 level and greater sputum eosinophilia characterize a cluster of severe asthma patients
Abstract
Severe asthma is a chronic disease of airway inflammation with substantial morbidity. Deficient specialized pro-resolving mediators (SPMs) are associated with persistent airway inflammation and impaired lung function in some patients with severe asthma. Resolvin D1 (RvD1) is an SPM agonist for inflammation resolution. Plasma RvD1 was measured longitudinally over 5 years in 23 severe asthma patients in the Severe Asthma Research Program (SARP) to identify relationships between clinical parameters, type 2 inflammation, and sputum gene expression. The majority of severe asthma patients had persistently low plasma RvD1; a smaller subgroup had higher RvD1 that fluctuated over time. Correlation analysis indicated a relationship between plasma RvD1 and sputum eosinophilia. A subgroup of severe asthma patients had low plasma RvD1 and high sputum eosinophils (RvD1 Lo SpEos Hi ); a separate subgroup had high plasma RvD1 and low sputum eosinophils (RvD1 Hi SpEos Lo ). The RvD1 Lo SpEos Hi patient cluster had increased T2 inflammation, lower lung function, and more asthma exacerbations. 42 genes were differentially expressed in RvD1 Lo SpEos Hi severe asthma sputum, including hypoxia-inducible factor 1-alpha ( HIF1A) . RvD1 significantly downregulated eosinophil HIF-1α expression in vitro. These findings identify a subset of severe asthma patients with low RvD1 and increased sputum eosinophilia, and RvD1 regulation of eosinophil activation ex vivo, suggesting a counter-regulatory role for this SPM in modulating eosinophilic T2 inflammation in asthma.
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BibTeX
@article{duvall2026lower,
title = {{Lower plasma resolvin D1 level and greater sputum eosinophilia characterize a cluster of severe asthma patients}},
author = {Melody Duvall and Yuan Sun and Hooman Mirzakhani and Stephanie Pons and Madison Dorazio and Tania Chiha and Zheng Lu and Brenda Phillips and Mark Aronica and Eugene Bleecker and Mario Castro and Suzy Comhair and Loren Denlinger and Serpil Erzurum and John Fahy and Annette Hastie and Nizar Jarjour and Purvesh Khatri and Deborah Meyers and Wendy Moore and Victor Ortega and Wanda Phipatanakul and Max Seibold and Kaharu Sumino and Sally Wenzel and Prescott Woodruff and David Mauger and Elliot Israel and Bruce Levy},
journal = {Respiratory Research},
year = {2026},
month = jul,
doi = {10.1186/s12931-026-03790-4},
url = {https://hal.science/hal-05769966v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Lower plasma resolvin D1 level and greater sputum eosinophilia characterize a cluster of severe asthma patients
AU - Melody Duvall
AU - Yuan Sun
AU - Hooman Mirzakhani
AU - Stephanie Pons
AU - Madison Dorazio
AU - Tania Chiha
AU - Zheng Lu
AU - Brenda Phillips
AU - Mark Aronica
AU - Eugene Bleecker
AU - Mario Castro
AU - Suzy Comhair
AU - Loren Denlinger
AU - Serpil Erzurum
AU - John Fahy
AU - Annette Hastie
AU - Nizar Jarjour
AU - Purvesh Khatri
AU - Deborah Meyers
AU - Wendy Moore
AU - Victor Ortega
AU - Wanda Phipatanakul
AU - Max Seibold
AU - Kaharu Sumino
AU - Sally Wenzel
AU - Prescott Woodruff
AU - David Mauger
AU - Elliot Israel
AU - Bruce Levy
PY - 2026
DA - 2026/07/10
JO - Respiratory Research
DO - 10.1186/s12931-026-03790-4
UR - https://hal.science/hal-05769966v1
AB - Severe asthma is a chronic disease of airway inflammation with substantial morbidity. Deficient specialized pro-resolving mediators (SPMs) are associated with persistent airway inflammation and impaired lung function in some patients with severe asthma. Resolvin D1 (RvD1) is an SPM agonist for inflammation resolution. Plasma RvD1 was measured longitudinally over 5 years in 23 severe asthma patients in the Severe Asthma Research Program (SARP) to identify relationships between clinical parameters, type 2 inflammation, and sputum gene expression. The majority of severe asthma patients had persistently low plasma RvD1; a smaller subgroup had higher RvD1 that fluctuated over time. Correlation analysis indicated a relationship between plasma RvD1 and sputum eosinophilia. A subgroup of severe asthma patients had low plasma RvD1 and high sputum eosinophils (RvD1 Lo SpEos Hi ); a separate subgroup had high plasma RvD1 and low sputum eosinophils (RvD1 Hi SpEos Lo ). The RvD1 Lo SpEos Hi patient cluster had increased T2 inflammation, lower lung function, and more asthma exacerbations. 42 genes were differentially expressed in RvD1 Lo SpEos Hi severe asthma sputum, including hypoxia-inducible factor 1-alpha ( HIF1A) . RvD1 significantly downregulated eosinophil HIF-1α expression in vitro. These findings identify a subset of severe asthma patients with low RvD1 and increased sputum eosinophilia, and RvD1 regulation of eosinophil activation ex vivo, suggesting a counter-regulatory role for this SPM in modulating eosinophilic T2 inflammation in asthma.
SN - 1465-9921
ER -