Abstract
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.
Highlights
Obesity is generally associated with an increased incidence of medical problems and overall mortality [1,2,3]
The heat moisture exchange filter adjacent to the Y connector was removed and no humidification was added to the ventilatory circuit. 20 minutes later, exhaled breath condensate (EBC) samples were immediately placed in regular ice, volume measured and aliquoted into vials pre-washed with deionized water and frozen at -80C until analysis
No significant differences were found between the two Body Mass Index (BMI) groups in terms of age, gender, height and American Society of Anesthesiologists (ASA) classification (Table 1)
Summary
Obesity is generally associated with an increased incidence of medical problems and overall mortality [1,2,3]. Repeated studies report a decreased incidence and/or reduced mortality from the acute respiratory distress syndrome (ARDS) [1215] in obese patients compared to normal weight individuals, a few conflicting findings exist [15,16]. Obesity has been associated with a delayed ARDS onset during an ICU stay [15] and lower plasma inflammatory markers during ARDS development [17] We have labeled this unexplained phenomenon as the “obesityARDS paradox” [18,19]. These observations are intriguing even though many of these studies leading to this paradox suffer from their retrospective nature, exclusion of morbidly obese patients, the overall low incidence of ARDS and the lack of accurate information about possible respiratory, metabolic and cardiovascular comorbidities often associated with obesity. 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
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