Increased nitrosothiols in exhaled breath condensate in inflammatory airway diseases

Nitrosothiols (RS-NOs) are formed by interaction of nitric oxide (NO) with glutathione and may limit the detrimental effect of NO. Because NO generation is increased in airway inflammation, we have measured RS-NOs in exhaled breath condensate in patients with asthma, cystic fibrosis, or chronic obstructive pulmonary disease (COPD). We also measured exhaled NO and nitrite (NO2-) in the same subjects. RS-NOs were detectable in exhaled breath condensate of all subjects. RS-NOs were higher in subjects with severe asthma (0.81 +/- 0.06 muM) when compared with normal control subjects (0.11 +/- 0.02 muM, P < 0.01) and with subjects with mild asthma (0.08 <plus/minus> 0.01 muM, P < 0.01). Elevated RS-NOs values were also found in patients with cystic fibrosis (0.35 <plus/minus> 0.07 muM, p < 0.01), in those with COPD (0.24 <plus/minus> 0.04 muM, p < 0.01) and in smokers (0.46 <plus/minus> 0.09 muM, p < 0.01). In current smokers there was a correlation (r = 0.8, p < 0.05) between RS-NOs values and smoking history (pack/year). We also found elevated concentrations of NO2- in patients with severe asthma, cystic fibrosis, or COPD, but not in smokers or patients with mild asthma. This suggests that exhaled NO2- is less sensitive than exhaled RS-NOs. This study has shown that RS-NOs are detectable in exhaled breath condensate of healthy subjects and are increased in patients with inflammatory airway diseases. As RS-NOs concentrations in exhaled breath condensate vary in the different airway diseases and increase with the severity of asthma, their measurement may have clinical relevance as a noninvasive biomarker of nitrosative stress.