Total sputum nitrate/nitrite is associated with exacerbations andPseudomonas aeruginosacolonization in bronchiectasis

Abstract

Sputum nitrate/nitrite, which is the main component of reactive nitrogen species (RNS), is a potential biomarker of disease severity and progression in bronchiectasis. This study aimed to determine the association between nitrate/nitrite and exacerbations, airway microbiota in bronchiectasis.We measured total nitrate/nitrite concentration in sputum samples collected from 85 patients with stable bronchiectasis, performed 16 s rRNA sequencing of sputum samples and predicted the denitrification ability of airway microbiota through PICRUSt. Relationships between sputum total nitrate/nitrite and disease severity, exacerbations and airway microbiota were examined.Higher total sputum nitrate/nitrite was associated with more severe bronchiectasis defined by E-FACED (p= 0.003) or BSI (p=0.006) and more exacerbations in prior 12 month (p=0.005). Moreover, total sputum nitrate/nitrite was also significantly higher in patients with worse cough score (p=0.03), worse sputum purulent score (p=0.01), and worse MRC score (p=0.02). In addition, the total sputum nitrate/nitrite ofP. aeruginosacolonization (PA) group was higher than that of non-P. aeruginosacolonization (NPA) group (p=0.04), meanwhile, relative abundance ofP. aeruginosawas positively correlated with the total nitrate/nitrite (r=0.337, p=0.002). Simultaneously, denitrification module (M00529) was also significantly enriched in PA group compared to NPA group through PICRUSt analyses. Using receiver-operating characteristic analysis, total nitrate/nitrite was associated with exacerbations during one year follow-up (AUC=0.741, p=0.014).Sputum nitrate/nitrite is a biomarker of disease severity and associated withP. aeruginosacolonization in bronchiectasis.