Nitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects

Abstract

SummaryBackground and objective The role of nitric oxide (NO) needs to be further clarified in allergic inflammation. This study was designed to investigate the relationships between NO metabolites and eosinophil count, eosinophil cationic protein (ECP), interleukin (IL)-5 in induced sputum from asthmatics. Methods Hypertonic saline-induced sputum was obtained in 25 asthmatic subjects, among which 13 patients were examined before and after anti-asthmatic medications including steroid preparations. Ten normal subjects were enrolled as controls. Fresh expectorated sputum separated from saliva was treated with equal volume of dithiothreitol 0.1%, cytospined for cell count, and the supernatant was collected for biochemical assay. NO metabolites were assayed by using modified Griess reaction. ECP was measured by fluoroimmunoassay, and detected IL-5 by a sandwich ELISA. Results Asthmatic subjects, compared with controls, had significantly higher concentration of NO metabolites (1035.4 Ϯ 125.3 vs 557.2 Ϯ 101.5 mmol/L, P < 0.01), higher percentage of eosinophils (25.6 Ϯ 4.6 vs 1.7 Ϯ 0.2%, P < 0.01), and higher levels of ECP (1117.8 Ϯ 213.9 vs 154.6 Ϯ 47.4 mg/L, P < 0.01) in the induced sputum. IL-5 was detected more frequently in asthmatic subjects than in control subjects (11/25 [44%] vs 1/10 [10%], P < 0.05). According to asthma severity, moderate to severe asthmatic subjects (n ¼ 18) had higher level of NO metabolites (1143.8 Ϯ 156.3 vs 575.5 Ϯ 89.5 mmol/L, P < 0.01), higher levels of ECP and IL-5 (P < 0.01, respectively) in the induced sputum than in those of mild asthmatic subjects (n ¼ 7). NO metabolites, the percentage of eosinophils, the levels of ECP, and IL-5 were reduced following treatment with anti-asthmatic drugs (P < 0.01, respectively). There were significant positive correlations between NO metabolites and percentage of eosinophils or ECP (r ¼ 0.34, P < 0.05; r ¼ 0.28, P < 0.05). Negative correlations were noted between FEV 1 , FEV 1 /FVC and proportion of eosinophils, ECP, or IL-5 levels. Conclusion These findings confirmed that the level of NO metabolites was increased in the tracheobronchial secretion of asthmatic subjects and was paralleled with severity of asthma. Measurement of NO metabolites in induced sputum may be used for monitoring the degree of airway inflammation in asthmatics.

Toward point-of-care management of chronic respiratory conditions: Electrochemical sensing of nitrite content in exhaled breath condensate using reduced graphene oxide

“…In aqueous solution, NO reacts rapidly with reactive oxygen species (ROS) to form more stable nitrogen oxides, such as nitrite (NO − 2 ) and nitrate (NO − 3 ) 10 . Increased levels of NO are associated with inflammatory disease states such as asthma, COPD 11 , and cystic fibrosis 12,13 . The increased level of exhaled NO in asthma has been suggested to be due to an increased expression of inducible NO synthase (iNOS) in bronchial epithelium 14 .…”

Changes in the expression of NO synthase isoforms after ozone: the effects of allergen exposure

“…We previously demonstrated that NO metabolites were increased in tracheo-bronchial secretions of asthmatic subjects in parallel with asthma severity, and that NO metabolites in sputum are a more valuable indicator for monitoring asthmatic airway inflammation than those in serum [4,5]. …”

Eosinophilic Inflammation, Remodeling of Lower Airway, Bronchial Responsiveness and Cough Reflex Sensitivity in Non-Asthmatic Subjects with Nasal Allergy

“…And it is known that bronchial hyperresponsiveness is present in on-season seasonal AR [4, 20] and perennial AR [21] without asthma. Several studies have reported the relationship between sputum eosinophils and bronchial responsiveness to methacholine [22, 23], and FEV 1 /FVC ratio [24] in asthmatic subjects. These reports suggest that the airway remodeling partly caused by allergic inflammatory process including eosinophilic inflammation may contribute to the development of bronchial hyperresponsiveness both in seasonal AR and perennial AR patients as well as asthma.…”