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

BACKGROUND

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 β2-adrenergic response. Airway GSNO levels are often low in asthma.

OBJECTIVE

We studied the effects of inhaled GSNO (iGSNO) in human asthma.

METHODS

We measured the effects and metabolism of iGSNO, with a focus on forced expiratory volume in 1 second, β2-adrenergic agonist response and fractional exhaled nitric oxide, and expression of GSNO metabolic genes from bronchoscopic biopsy samples using spatial transcriptomics.

RESULTS

iGSNO increased forced expiratory volume in 1 second and β2-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.

CONCLUSION

iGSNO could represent personalized asthma therapy, augmenting β2-adrenergic receptor agonist benefit.