Nitrosative stress in patients with asthma–chronic obstructive pulmonary disease overlap

Abstract

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 FEV 1 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 From the

Nitrosative stress in patients with asthma−chronic obstructive pulmonary disease overlap

“…3 Various airway and blood biomarkers of neutrophilic and eosinophilic inflammation might distinguish the different phenotypes of ACO. 4 The study by Kyogoku et al 5 from Japan has provided further insight into the smoking asthmatic phenotype of ACO and extends their previous studies in asthma and COPD to show that there is an increase in nitrosative stress in the airways, as measured by a greater number of sputum cells (macrophages and neutrophils) expressing 3-nitrotyrosine (3-NT). The patients classified as having ACO in the study were elderly asthmatic patients with a history of cigarette smoking.…”

“…This is likely to be due to the combination of free NO in the airways with superoxide anions generated by NOX2. In the study by Kyogoku et al, 5 FENO values were only slightly increased in asthmatic patients and patients with ACO, which might reflect a reduction in response to inhaled corticosteroids but also to increased superoxide anions in the patients with ACO, which scavenge the free NO. For this reason, FENO is not a useful biomarker of inflammation in these patients because it is reduced by oxidative stress in the same way that FENO values are reduced in normal smokers and patients with COPD.…”

Comprehensive analysis of allergen-specific IgE in COPD: Mite-specific IgE specifically related to the diagnosis of asthma-COPD overlap

“…The importance of IgE for ACO diagnosis may vary depending on the diagnostic criteria. There are various diagnostic criteria for ACO including [8,11] or not including [5,7,9] IgE.…”

“…De nition of ACO ACO was diagnosed according to the JRS Guidelines for the Management of ACO 2018 [11]. In brief, ACO was Impact on Asthma guidelines [13].…”

“…However, the diagnostic criteria of ACO did not always include IgE categories [7]. Although some recent guidelines introduced elevated levels of IgE into the diagnostic criteria [8,9], the cutoff level of IgE was not stated in the guidelines, including the Japanese Respiratory Society (JRS) published in 2018 [10,11]. Some studies compared the levels of total and several allergen-speci c IgE between ACO and pure COPD and revealed that the levels of total IgE [5] or Dermatophagoides-speci c IgE [5,12] were higher in ACO.…”