Introduction Obesity Hypoventilation Syndrome (OHS) is conventionally defined by the combination of obesity (BMI >30 kg/m2) and daytime hypercapnia (PaCO2 >6 kPa, with no alternative explanation); sleep-disordered breathing may or may not be included in the definition. The development of ventilatory failure in obese individuals is highly variable, and the additional factors responsible have not been comprehensively studied. In obese individuals, the presence of a raised plasma standard bicarbonate (or base excess, BE – a biomarker of whole body acid-base balance, including overnight PaCO2 levels), without necessarily a raised daytime PaCO2, has been shown by us to be an intermediary stage towards overt obesity-hypoventilation syndrome. Thus we have looked for biologically plausible predictors of a raised base excess in obesity, whether or not there was also a raised PaCO2 awake.
Methods 78 obese subjects (BMI >30, mean 47 (SD 10, range 32 to 74) kg/m2) were identified from a variety of sources, regardless of their PaCO2 and acid/base status (mean levels 5.6 (SD 0.8, range 4.2 to 9.6) kPa; and 2.1 (SD 2.4, range -3.5 to 10) mmol/l respectively) and a large number of their characteristics measured. Biological plausible domains were constructed that were thought potentially to contribute to any ventilatory failure. First, the best independent predictor of the BE within each domain was found, second, the best overall independent predictors were found. The domains were as follows:
Obesity and its distribution (BMI, simple surface measures, DXA [a radiographic derivative])
Lung function (sitting/lying spirometry and forced oscillometry)
Sleep variables (AHI, ODI, mean overnight SaO2, time below 90% SaO2)
Ventilatory control (2 point responses to 15% O2 and 5% CO2)
Respiratory muscle strength (mouth pressures, sniff pressures)
Metabolic measures (e.g. leptin, adipokines, vitamin D)
Conclusions There are a number of strong predictors for the presence of a raised base excess in obesity. Significant predictors were found in each of the biological domains we studied, suggesting that the cause of ventilatory failure in obesity is likely to be multifactorial. However, reduced hypoxic poikilocapnic ventilatory drive and the presence of intra-abdominal obesity seem to be the most powerful predictors of a raised base excess in obesity.
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