TY - JOUR
T1 - Nitrosative stress in patients with asthma–chronic obstructive pulmonary disease overlap
AU - Kyogoku, Yorihiko
AU - Sugiura, Hisatoshi
AU - Ichikawa, Tomohiro
AU - Numakura, Tadahisa
AU - Koarai, Akira
AU - Yamada, Mitsuhiro
AU - Fujino, Naoya
AU - Tojo, Yutaka
AU - Onodera, Katsuhiro
AU - Tanaka, Rie
AU - Sato, Kei
AU - Sano, Hirohito
AU - Yamanaka, Shun
AU - Itakura, Koji
AU - Mitsune, Ayumi
AU - Tamada, Tsutomu
AU - Akaike, Takaaki
AU - Ichinose, Masakazu
N1 - Funding Information:
Supported by grants from the Japan Society for the Promotion of Science (grants #16K15453, #16H05307, and #17H04180) and a grant from the Practical Research Project for Allergic Diseases and Immunology from Japan Agency for Medical Research and Development, AMED (grants #16ek0410018h0002, #16ek040036h0001, #17ek0410036h0002, and #18ek0410036h0003).
Publisher Copyright:
© 2019 American Academy of Allergy, Asthma & Immunology
PY - 2019/10
Y1 - 2019/10
N2 - Background: Asthma–chronic obstructive pulmonary disease overlap (ACO) has frequent exacerbations and a poor quality of life and prognosis compared with those of chronic obstructive pulmonary disease alone. However, the pathogenesis of ACO has not been fully elucidated yet. Objectives: The aim of this study was to investigate nitrosative stress, which causes a redox imbalance and tissue inflammation in the airways of patients with ACO, and to evaluate the relationship between nitrosative stress and the clinical course in study subjects. Methods: Thirty healthy subjects and 56 asthmatic patients participated in this study. The asthmatic patients were divided into 33 asthmatic patients and 23 patients with ACO. The study subjects had been followed prospectively for 2 years to evaluate the clinical course. Nitrosative stress was evaluated based on the production of 3-nitrotyrosine (3-NT) in sputum cells. Results: Production of 3-NT was significantly enhanced in patients with ACO compared with that in asthmatic patients. Amounts of reactive persulfides and polysulfides, newly identified powerful antioxidants, were significantly decreased in the ACO group. Baseline levels of 3-NT were significantly correlated with the frequency of exacerbations and decrease in FEV1 adjusted by age, smoking history, and blood eosinophil count. The 3-NT–positive cells were also significantly correlated with amounts of proinflammatory chemokines and cytokines. Conclusions: These findings suggested that greater nitrosative stress occurred in the airways of patients with ACO, and the degree of nitrosative stress was correlated with an impairment in the clinical course. Nitrosative stress might be related to the pathogenesis of ACO.
AB - Background: Asthma–chronic obstructive pulmonary disease overlap (ACO) has frequent exacerbations and a poor quality of life and prognosis compared with those of chronic obstructive pulmonary disease alone. However, the pathogenesis of ACO has not been fully elucidated yet. Objectives: The aim of this study was to investigate nitrosative stress, which causes a redox imbalance and tissue inflammation in the airways of patients with ACO, and to evaluate the relationship between nitrosative stress and the clinical course in study subjects. Methods: Thirty healthy subjects and 56 asthmatic patients participated in this study. The asthmatic patients were divided into 33 asthmatic patients and 23 patients with ACO. The study subjects had been followed prospectively for 2 years to evaluate the clinical course. Nitrosative stress was evaluated based on the production of 3-nitrotyrosine (3-NT) in sputum cells. Results: Production of 3-NT was significantly enhanced in patients with ACO compared with that in asthmatic patients. Amounts of reactive persulfides and polysulfides, newly identified powerful antioxidants, were significantly decreased in the ACO group. Baseline levels of 3-NT were significantly correlated with the frequency of exacerbations and decrease in FEV1 adjusted by age, smoking history, and blood eosinophil count. The 3-NT–positive cells were also significantly correlated with amounts of proinflammatory chemokines and cytokines. Conclusions: These findings suggested that greater nitrosative stress occurred in the airways of patients with ACO, and the degree of nitrosative stress was correlated with an impairment in the clinical course. Nitrosative stress might be related to the pathogenesis of ACO.
KW - 3-nitrotyrosine
KW - Nitrosative stress
KW - cystathionine β-synthase
KW - cystathionine γ-lyase
KW - reactive persulfides and polysulfides
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U2 - 10.1016/j.jaci.2019.04.023
DO - 10.1016/j.jaci.2019.04.023
M3 - Article
C2 - 31077687
AN - SCOPUS:85066443922
VL - 144
SP - 972-983.e14
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 4
ER -