Exhaled Nitric Oxide in Asthma: Variability, Relation to Asthma Severity, and Peripheral Blood Lymphocyte Cytokine Expression

Shome GP, Starnes JD 3rd, Shearer M, et al. J Asthma. 2006;43:95–99 PURPOSE OF THE STUDY. To measure and compare exhaled nitric oxide (eNO) levels in patients with asthma and healthy volunteers, to study peripheral blood lymphocyte cytokine expression, and to study the relationship between eNO and intracellular cytokine expression. STUDY POPULATION. A total of 36 subjects were enrolled onto the study, with 19 asthmatic patients and 17 healthy control subjects. METHODS. At least once per week for 4 weeks, patients with asthma visited the clinic and underwent a detailed history, physical examination, spirometry, and eNO-level measurement. These patients were maintained on established pharmacologic therapy regimens. A blood sample was taken and analyzed by flow cytometry. eNO was measured by using an NO analyzer. Univariate linear regression analysis was used to determine correlations between continuous variables and eNO concentrations. RESULTS. eNO levels were significantly elevated in patients with moderate-to-severe asthma compared with those in healthy subjects (18.53 ± 2.00 vs 5.90 ± 0.90 ppb). With treatment, eNO levels in patients with moderate-to-severe asthma decreased to levels near those of the healthy subjects by 4 weeks. Interferon γ expression was decreased in patients with moderate-to-severe asthma. An elevated eNO level was also associated with decreased interleukin 4 and interleukin 13 cytokine expression in CD8 lymphocytes. CONCLUSIONS. eNO levels were elevated in patients with moderate-to-severe asthma. With 4 weeks of treatment, eNO levels in patients with moderate-to-severe asthma were no different from those in the control subjects. There was decreased interferon γ expression by the CD4- and CD8-positive peripheral blood lymphocytes of patients with moderate-to-severe asthma. Elevated eNO levels were associated with suppression of both T-helper 1 and 2 cytokine expression by the peripheral blood lymphocyte, suggesting a systemic immunomodulatory effect. REVIEWER COMMENTS. This study adds to the growing information on the utility of eNO levels to monitor asthma-treatment response. It demonstrates how eNO can be used to measure the reduction in airway inflammation as a response to treatment primarily in patients with moderate-to-severe asthma. At this point, it is not clear what the implications are of the association between elevated eNO levels and cytokine suppression.