Ana Fernandez-Bustamante, Tamas Seres, Amanda Agazio, Alexander T. Pennington, Uwe Christians, Jelena Klawitter and John E. Repine
Background: Repeated observations suggest that the incidence and/or severity of the Acute Respiratory Distress Syndrome (ARDS) is lower in mildly obese humans compared to lean subjects, phenomenon called the Obesity-ARDS Paradox. A reduced lung nitrosative stress could contribute to this unexplained protection. We measured levels of nitrate, the most oxidized nitric oxide (NO) metabolite, and other related metabolites in the exhaled breath condensate (EBC) of obese (composed of both overweight or mildly obese) and normal weight patients.
Methods: We studied patients without respiratory disease immediately after starting mechanical ventilation for elective surgery. We performed targeted metabolomics analyses of EBC and blood samples. We measured concentrations of arginine, asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), nitrite, and nitrate and then analyzed their relationship to body mass index (BMI). We compared patients classified as BMI<25 (normal) or 25-34.9 (obese).
Results: 21 patients were included in the analysis: 5 with a BMI<25 and 16 with a BMI 25-34.9. Concentrations of nitrate in EBC, but not in plasma, inversely correlated with BMI. EBC nitrate levels positively correlated with EBC nitrite but not with plasma nitrate levels. EBC nitrite levels inversely correlated with plasma nitrite levels. Patients with a BMI 25-34.9 had significantly lower EBC nitrate levels than patients with a BMI<25.
Conclusion: Our results suggest a lower nitrosative stress in the lungs of overweight and mildly obese patients compared to normal weight patients. This observation deserves further evaluation as a possible contributing factor to the Obesity ARDS Paradox.
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