Endogenous Hydrogen Sulfide in Patients With COPD

Abstract

COPD is characterized by progressive airway obstruction. Recent studies showed that besides nitric oxide (NO) and carbon monoxide (CO), endogenous hydrogen sulfide (H(2)S) might be the third signaling gasotransmitter. To clarify the role of endogenous H(2)S in the pathogenesis of COPD, we investigated the relation of serum H(2)S level to severity of COPD as defined by lung function and airway inflammation. Levels of serum H(2)S and NO, lung function, and cell differential counts in induced sputum were studied in 27 patients with acute exacerbation of COPD (AECOPD), 37 patients with stable COPD, and 13 healthy subjects. Patients with AECOPD had arterial blood gas levels measured and underwent Doppler echocardiography. In addition, in order to clarify the effects of age and smoking status on serum H(2)S level, we recruited three groups who were age matched to the study group but had no airflow limitation (59 subjects). Serum H(2)S level (34.0 +/- 0.9 to 36.4 +/- 1.1 micromol/L [+/- SEM]) did not differ among healthy control subjects with different ages (56.6 to 75.0 years, respectively). Serum H(2)S level was significantly higher in patients with stable COPD than in patients with AECOPD and age-matched control subjects (p < 0.01) and correlated positively with NO level in all healthy control subjects and all patients with COPD (r = 0.352, p = 0.000). Serum H(2)S level was significantly lower in smokers than nonsmokers, both with AECOPD (p < 0.05) and healthy control subjects (p < 0.01). It was significantly lower in smokers with AECOPD than healthy smokers and smokers with stable COPD (p < 0.01). Serum H(2)S level differed and was decreased (p < 0.05) among stable COPD patients by stage of airway obstruction (p < 0.05), and it was lower in patients with stage III than stage I obstruction (p < 0.05). Serum H(2)S level in all patients with COPD and healthy control subjects correlated positively with the percentage of predicted FEV(1) value (r = 0.300, p = 0.009). It was lower in patients with AECOPD and systolic pulmonary artery pressure (PASP) > or = 35 mm Hg than those with PASP within the normal range (< 35 mm Hg) [p < 0.05] and was negatively correlated with PASP (r = - 0.561, p = 0.011). Serum H(2)S level was negatively correlated with proportion of neutrophils in sputum (r = - 0.422, p = 0.001) and positively correlated with proportion of lymphocytes (r = 0.286, p = 0.028) and macrophages (r = 0.334, p = 0.01) in all patients with COPD. Endogenous H(2)S is involved in the pathogenesis of airway obstruction in COPD, and its alteration in level may be connected with disease activity and severity.