Comparison of <i>inducible nitric oxide synthase </i><scp>mRNA</scp> expression in different airway portions and association with nitric oxide parameters from patients with asthma

Abstract

Abstract Background Fractional exhaled nitric oxide concentration (Fe NO ) is widely used to support diagnosis and monitoring of bronchial asthma ( BA ). Tsoukias and George proposed a two‐compartment model (2 CM ) for assessing the alveolar concentration of NO , referred to as CANO (2 CM ), while Condorelli et al proposed a model based on the trumpet shape of the airway tree and axial diffusion ( TMAD ), referred to as CANO ( TMAD ). In addition, Högman et al proposed non‐linear model, referred to as CANO (non‐linear). Objective We examined associations between the expression of inducible nitric oxide synthase ( iNOS ) mRNA in airway cells ( AC s) by bronchoscopy and NO ‐parameters calculated by the three methods and identified which of them accurately reflected expression of iNOS mRNA from different airway portions. Methods We retrospectively analysed data of 18 patients with stable, mild‐moderate asthma, including 10 steroid‐naïve BA (sn BA ) patients. Samples were obtained from airway brushings and bronchoalveolar lavage ( BAL ). Expressions of iNOS protein in tissue samples were evaluated by immunostaining. The iNOS mRNA in AC s was measured by qPCR . NO ‐parameters calculated by the three methods above and evaluated whether they were associated with iNOS mRNA in AC s derived from proximal (2nd carina), distal (10‐15th) airways and alveolar regions. Results Immunostaining revealed expression of iNOS proteins mainly in epithelial cells in the airways, while it was mainly expressed in macrophages in the alveolar region in the sn BA group. The iNOS mRNA expression was increased in both proximal and distal AC s in the sn BA group compared with steroid‐treated BA group (st BA ). CANO (2 CM ) negatively associated with FEV 1 (%predicted) and also associated with iNOS mRNA in distal AC s significantly. However, CANO ( TMAD ) and CANO (non‐linear) showed no correlation with lung function nor iNOS mRNA expression in any portions of ACs. Conclusions These results suggested that CANO (2 CM ) reflected distal airway inflammation in steroid‐naïve asthma.