Decreased exhaled nitric oxide in sickle cell disease: relationship with chronic lung involvement

A deficiency in airway nitric oxide (NO) could contribute to pulmonary vaso-occlusion in sickle cell disease (SCD). We measured the fractional expired concentration of NO (FE(NO)) by chemiluminescence during a slow vital capacity maneuver against a positive pressure of 16 cm H(2)O at an expiratory flow rate of 50 mL/sec in 44 stable ambulatory adults with SCD and 30 healthy controls. A history of acute chest syndrome was present in 29 patients, and 22 complained of dyspnea. Mean +/- SD FE(NO) was significantly reduced in the SCD group compared with controls (14.8 +/- 8.4 vs. 24.9 +/- 13.5 ppb, P < 0.001). SCD patients with dyspnea had lower FE(NO) than those without dyspnea (10.1 +/- 5.7 vs. 19.6 +/- 8 ppb, P < 0.001) and those with a history of ACS had lower values than those no episodes of ACS (13.0 +/- 8.3 vs. 18.4 +/- 7.6 ppb, P < 0.05). There was a weak correlation between FE(NO) and percent-predicted DLCO (r = 0.4, P = 0.02) among the SCD patients. We conclude that exhaled NO is reduced in adults with SCD, and this may play a role in the pathogenesis of acute chest syndrome and chronic sickle cell lung disease.