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

Abstract

BackgroundSputum nitrate/nitrite, which is the main component of reactive nitrogen species, is a potential biomarker of disease severity and progression in bronchiectasis. This study aimed to determine the association between nitrate/nitrite and exacerbations and airway microbiota in bronchiectasis.MethodsWe measured total nitrate/nitrite concentration in sputum samples collected from 85 patients with stable bronchiectasis, performed 16S ribosomal RNA sequencing of sputum samples and predicted the denitrification ability of airway microbiota using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Relationships between sputum total nitrate/nitrite and disease severity, exacerbations and airway microbiota were examined.ResultsHigher total sputum nitrate/nitrite was associated with more severe bronchiectasis defined by E-FACED (exacerbation, forced expiratory volume in 1 s, age, chronic colonisation byPseudomonas aeruginosa, radiological extension and dyspnoea) (p=0.003) or Bronchiectasis Severity Index (p=0.006) and more exacerbations in the prior 12 months (p=0.005). Moreover, total sputum nitrate/nitrite was significantly higher in patients with worse cough score (p=0.03), worse sputum purulence score (p=0.01) and worse Medical Research Council dyspnoea score (p=0.02). In addition, the total sputum nitrate/nitrite of theP. aeruginosacolonised (PA) group was higher than that of the non-P. aeruginosacolonised (NPA) group (p=0.04), and the relative abundance ofP. aeruginosawas positively correlated with total nitrate/nitrite (r=0.337, p=0.002). Denitrification module (M00529) was also significantly enriched in the PA group compared to the NPA group through PICRUSt analyses. Using receiver-operating characteristic analysis, total nitrate/nitrite was associated with exacerbations during 1-year follow-up (area under the curve 0.741, p=0.014).ConclusionsSputum nitrate/nitrite is a biomarker of disease severity and associated withP. aeruginosacolonisation in bronchiectasis.