Exhaled Hydrogen Sulfide Predicts Airway Inflammation Phenotype in COPD

Abstract

BACKGROUND: The role of exhaled H 2 S as a marker of airway inflammation and its relationship with COPD severity remain to be determined. METHODS: Airway inflammation was classified in 77 COPD subjects based on the presence of inflammatory cells in induced sputum. We investigated the association between disease phenotype and exhaled H 2 S, lung function, and plasma levels of several inflammatory factors, including tumor necrosis factor alpha, interleukin-8, and leukotriene B 4 . RESULTS: In total, 33.77% of enrolled COPD subjects were diagnosed with eosinophilia. These subjects had a longer disease course, smoked fewer cigarettes, and experienced more frequent exacerbation events before study enrollment. However, they also had worse lung function and larger residual volume, they demonstrated greater changes in FEV 1 following bronchodilator inhalation. Although levels of plasma inflammatory factors did not significantly differ between subjects with and without eosinophilia, subjects without eosinophilia had significantly higher levels of exhaled H 2 S (9.19 ؎ 2.74 vs 7.24 ؎ 1.68 parts per billion, P ‫؍‬ .01). Furthermore, exhaled H 2 S levels were negatively correlated with induced sputum eosinophils (r ‫؍‬ ؊0.45, P ‫؍‬ .05), and positively correlated with inspiratory capacity in COPD subjects (r ‫؍‬ 0.51, P ‫؍‬ .026), but did not correlate significantly with plasma inflammatory factors. A cut-off value of 7.10 parts per billion of exhaled H 2 S predicted a non-eosinophilic phenotype with 68.6% sensitivity and 77.9% specificity. CONCLUSIONS: Exhaled levels of H 2 S were lower in subjects with eosinophilia. Increased levels of exhaled H 2 S predicted a non-eosinophilic phenotype in our study population. Key words: chronic obstructive pulmonary disease; airway inflammation phenotype; eosinophilia; hydrogen sulfide. [Respir Care 2015;60(2):251-258.

International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors

“…This may be part of the physiological elimination process, but, more importantly, increased H 2 S levels in exhaled air have been demonstrated when animals or human volunteers were subjected to therapeutic doses of H 2 S donors (Insko et al, 2009;Toombs et al, 2010). Increased exhaled H 2 S has been demonstrated in asthmatic patients (Zhang et al, , 2015 and in septic patients (Bee et al, 2017). Exhaled H 2 S measurements may be one potential future way to monitor exposure to H 2 S donating agents, with one of its benefits being the ability to obtain an immediate read-out (as opposed to methods using H 2 S derivatization of blood or plasma and subsequent biochemical detection).…”

Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders

“…Notably, the intravenous administration of Na 2 S (0.005–0.20 mg/kg, infused over 1 min) to healthy human volunteers increased blood sulfide and thiosulfate concentrations, as well as exhaled H 2 S gas ( Toombs et al, 2010 ). Clinically, the elevated amount of exhaled H 2 S gas by patients was used to predict a non-eosinophilic phenotype of chronic obstructive pulmonary disease ( Zhang et al, 2015 ) and the airway inflammation of asthma ( Zhang et al, 2014 ).…”

Imbalance of Endogenous Hydrogen Sulfide and Homocysteine in Chronic Obstructive Pulmonary Disease Combined with Cardiovascular Disease

“…The production of H 2 S in mammalian cells is attributable to three endogenous enzymes: cystathionine β-synthase (CBS), cystathionineγ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) ( Kajimura et al, 2012 ). H 2 S plays an important role in respiratory diseases ( Chen et al, 2005 , 2011 ; Chung, 2014 ; Zhou et al, 2014 ; Zhang et al, 2015 ) and CVDs ( Chen et al, 2007 ; Gao et al, 2015 ). Homocysteine (Hcy) is the main substrate to generate endogenous H 2 S in the body, high homocysteine is a risk factor in the cardiovascular system ( Humphrey et al, 2008 ; Cioni et al, 2016 ; Liu et al, 2016 ; Luo et al, 2017 ).…”