Effect of oral arginine supplementation on exhaled nitric oxide concentration in sickle cell anemia and acute chest syndrome

Introduction Decreased exhaled nitric oxide levels (FE_NO) have been described in patients with sickle cell disease (SCD) and a history of acute chest syndrome (ACS) when compared with non-ACS controls. Oral arginine supplementation has been shown to increase FE_NO in healthy participants, but its effect in SCD patients is not known. Objective To determine the effect of oral arginine intake on FE_NO in sickle cell patients with and without history of ACS, and in healthy controls. Hypothesis No differences in the FE_NO increase were seen in SCD patients with a history of ACS (ACS⁺) compared with healthy controls (HC) and SCD patients without history of ACS (ACS^-). Materials and Methods ACS⁺ (n=6), ACS- (n=9), and HC (n=7) patients were studied. At baseline, and after the administration of escalating doses of oral L-arginine (0.1, 0.2, and 0.4 g/kg), serial measurements were made of the following: FE_NO, plasma concentrations of arginine, ornithine, citrulline, aspartate, glutamate, arginine/ornithine ratio, nitrite, nitrate, heart rate (HR), respiratory rate (RR), blood pressure (BP), oxygen saturation (SpO₂), forced expiratory volume in 1 second (FEV₁), and forced vital capacity (FVC). Main Results At baseline, FE_NO did not differ among the groups. ACS^- and ACS⁺ groups were deficient in arginine, and had decreased FEV₁, FVC, and SaO₂ when compared with HC patients. After arginine supplementation, FE_NO, arginine, ornithine, citrulline, nitrite, and the arginine/ornithine ratio increased similarly in all groups. Changes from baseline for HR, BP, SpO₂, RR, FEV₁, and FVC were minimal and similar in all groups. Conclusions In contrast to our earlier study, ACS⁺ patients had similar FE_NO values when compared with ACS^- and HC patients. All SCD patients were arginine deficient at baseline and showed impairment in respiratory physiology when compared with HC patients. After arginine supplementation, FE_NO concentration increased in all groups to a similar degree, and lung function and physiologic parameters were minimally affected. The physiologic significance of alterations in FE_NO in SCD patients and its relationship to ACS predilection requires further delineation.