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 et al pr...

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Autores principales: Sato, Yoko, Chibana, Kazuyuki, Horigane, Yukiko, Uchida, Nobuhiko, Masawa, Meitetsu, Koike, Ryosuke, Nakamura, Yusuke, Watanabe, Taiji, Shiobara, Taichi, Arai, Ryo, Shimizu, Yasuo, Takemasa, Akihiro, Ishii, Yoshiki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850274/
https://www.ncbi.nlm.nih.gov/pubmed/30667100
http://dx.doi.org/10.1111/cea.13344
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author Sato, Yoko
Chibana, Kazuyuki
Horigane, Yukiko
Uchida, Nobuhiko
Masawa, Meitetsu
Koike, Ryosuke
Nakamura, Yusuke
Watanabe, Taiji
Shiobara, Taichi
Arai, Ryo
Shimizu, Yasuo
Takemasa, Akihiro
Ishii, Yoshiki
author_facet Sato, Yoko
Chibana, Kazuyuki
Horigane, Yukiko
Uchida, Nobuhiko
Masawa, Meitetsu
Koike, Ryosuke
Nakamura, Yusuke
Watanabe, Taiji
Shiobara, Taichi
Arai, Ryo
Shimizu, Yasuo
Takemasa, Akihiro
Ishii, Yoshiki
author_sort Sato, Yoko
collection PubMed
description 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 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 (ACs) 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 (snBA) 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 ACs was measured by qPCR. NO‐parameters calculated by the three methods above and evaluated whether they were associated with iNOS mRNA 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 iNOS mRNA 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 FEV (1) (%predicted) and also associated with iNOS mRNA in distal ACs 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(2CM) reflected distal airway inflammation in steroid‐naïve asthma.
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spelling pubmed-68502742019-11-18 Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma Sato, Yoko Chibana, Kazuyuki Horigane, Yukiko Uchida, Nobuhiko Masawa, Meitetsu Koike, Ryosuke Nakamura, Yusuke Watanabe, Taiji Shiobara, Taichi Arai, Ryo Shimizu, Yasuo Takemasa, Akihiro Ishii, Yoshiki Clin Exp Allergy ORIGINAL ARTICLES 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 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 (ACs) 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 (snBA) 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 ACs was measured by qPCR. NO‐parameters calculated by the three methods above and evaluated whether they were associated with iNOS mRNA 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 iNOS mRNA 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 FEV (1) (%predicted) and also associated with iNOS mRNA in distal ACs 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(2CM) reflected distal airway inflammation in steroid‐naïve asthma. John Wiley and Sons Inc. 2019-02-15 2019-05 /pmc/articles/PMC6850274/ /pubmed/30667100 http://dx.doi.org/10.1111/cea.13344 Text en © 2019 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle ORIGINAL ARTICLES
Sato, Yoko
Chibana, Kazuyuki
Horigane, Yukiko
Uchida, Nobuhiko
Masawa, Meitetsu
Koike, Ryosuke
Nakamura, Yusuke
Watanabe, Taiji
Shiobara, Taichi
Arai, Ryo
Shimizu, Yasuo
Takemasa, Akihiro
Ishii, Yoshiki
Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma
title Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma
title_full Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma
title_fullStr Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma
title_full_unstemmed Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma
title_short Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma
title_sort comparison of inducible nitric oxide synthase mrna expression in different airway portions and association with nitric oxide parameters from patients with asthma
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850274/
https://www.ncbi.nlm.nih.gov/pubmed/30667100
http://dx.doi.org/10.1111/cea.13344
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