Inhaled S-nitrosoglutathione in asthma: Airway SCoR2 expression and determinants of human bronchodilator response.

Gaston, Benjamin; Smith, Laura A; Zhao, Yi; Premont, Richard T; Yang, Fanmuyi; Chmiel, James F; Tilston-Lunel, Andrew; Twigg, Homer et al. · J Allergy Clin Immunol · 2026

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Abstract

Asthma is characterized by airway inflammation and bronchoconstriction. Recent therapies have addressed inflammation but not bronchoconstriction. S-Nitrosoglutathione (GSNO) is an endogenous smooth muscle relaxant that also affects β<sub>2</sub>-adrenergic response. Airway GSNO levels are often low in asthma. We studied the effects of inhaled GSNO (iGSNO) in human asthma. We measured the effects and metabolism of iGSNO, with a focus on forced expiratory volume in 1 second, β<sub>2</sub>-adrenergic agonist response and fractional exhaled nitric oxide, and expression of GSNO metabolic genes from bronchoscopic biopsy samples using spatial transcriptomics. iGSNO increased forced expiratory volume in 1 second and β<sub>2</sub>-adrenergic receptor response; the magnitude of increase was related, and additive, to the receptor response (P < .001). SCoR2 (AKR1A1 gene), encoding a GSNO degrading enzyme, was upregulated in airway epithelium, and higher SCoR2 expression was associated with reduced iGSNO bronchodilation. Sustained elevation in fractional exhaled nitric oxide after iGSNO, indicating reduced GSNO catabolism, was a biomarker for iGSNO effect. iGSNO could represent personalized asthma therapy, augmenting β<sub>2</sub>-adrenergic receptor agonist benefit.