Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma.

Background: Fractional exhaled nitric oxide concentration (FeNO) is widely used to support diagnosis and monitoring of bronchial asthma (BA). Tsoukias and George proposed a two-compartment model (2CM) for assessing the alveolar concentration of NO, referred to as CANO(2CM), while Condorelli etal proposed a model based on the trumpet shape of the airway tree and axial diffusion (TMAD), referred to as CANO(TMAD). In addition, Hogman etal 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 (ACs) by bronchoscopy and NO-parameters calculated by the three methods and identified which of them accurately reflected expression of iNOSmRNA from different airway portions. Methods :We retrospectively analysed data of 18 patients with stable, mild-moderate asthma, including 10 steroid-naive BA (snBA) patients. Samples were obtained from airway brushings and bronchoalveolar lavage (BAL). Expressions of iNOS protein in tissue samples were evaluated by immunostaining. The iNOSmRNA in ACs was measured by qPCR. NO-parameters calculated by the three methods above and evaluated whether they were associated with iNOSmRNA in ACs 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 snBA group. The iNOSmRNA expression was increased in both proximal and distal ACs in the snBA group compared with steroid-treated BA group (stBA). CANO(2CM) negatively associated with FEV1 (%predicted) and also associated with iNOSmRNA in distal ACs significantly. However, CANO(TMAD) and CANO(non-linear) showed no correlation with lung function nor iNOSmRNA expression in any portions of ACs. Conclusions: These results suggested that CANO(2CM) reflected distal airway inflammation in steroid-naive asthma.