Title: Phenotype of asthmatics with increased airway S-nitrosoglutathione reductase activity.
Authors: Marozkina, Nadzeya V; Wang, Xin-Qun; Stsiapura, Vitali; Fitzpatrick, Anne; Carraro, Silvia; Hawkins, Gregory A; Bleecker, Eugene; Meyers, Deborah; Jarjour, Nizar; Fain, Sean B; Wenzel, Sally; Busse, William; Castro, Mario; Panettieri Jr, Reynold A; Moore, Wendy; Lewis, Stephen J; Palmer, Lisa A; Altes, Talissa; de Lange, Eduard E; Erzurum, Serpil; Teague, W Gerald; Gaston, Benjamin
Published In Eur Respir J, (2015 Jan)
Abstract: S-Nitrosoglutathione is an endogenous airway smooth muscle relaxant. Increased airway S-nitrosoglutathione breakdown occurs in some asthma patients. We asked whether patients with increased airway catabolism of this molecule had clinical features that distinguished them from other asthma patients. We measured S-nitrosoglutathione reductase expression and activity in bronchoscopy samples taken from 66 subjects in the Severe Asthma Research Program. We also analysed phenotype and genotype data taken from the program as a whole. Airway S-nitrosoglutathione reductase activity was increased in asthma patients (p=0.032). However, only a subpopulation was affected and this subpopulation was not defined by a "severe asthma" diagnosis. Subjects with increased activity were younger, had higher IgE and an earlier onset of symptoms. Consistent with a link between S-nitrosoglutathione biochemistry and atopy: 1) interleukin 13 increased S-nitrosoglutathione reductase expression and 2) subjects with an S-nitrosoglutathione reductase single nucleotide polymorphism previously associated with asthma had higher IgE than those without this single nucleotide polymorphism. Expression was higher in airway epithelium than in smooth muscle and was increased in regions of the asthmatic lung with decreased airflow. An early-onset, allergic phenotype characterises the asthma population with increased S-nitrosoglutathione reductase activity.
PubMed ID: 25359343
MeSH Terms: Adolescent; Adult; Aldehyde Oxidoreductases/metabolism*; Asthma/enzymology*; Biopsy; Bronchi/enzymology*; Bronchoalveolar Lavage; Bronchoscopy; Case-Control Studies; Cells, Cultured; Child; Female; Gene Expression Regulation, Enzymologic*; Genotype; Humans; Immunoglobulin E/blood; Immunohistochemistry; Interleukin-13/metabolism; Lung/enzymology; Magnetic Resonance Imaging; Male; Metabolism; Middle Aged; Muscle, Smooth/enzymology; Phenotype; Polymorphism, Single Nucleotide; Young Adult