Reply: Worsening Asthma Control in Children Taking Lansoprazole: Possible Mechanisms
Abstract
Increased asymmetrical dimethylarginine levels were found in a preclinical model and in patients with asthma, including children (3,4).Our group discovered that the entire class of proton pump inhibitors inhibits dimethylarginine dimethylaminohydrolase, an enzyme responsible for asymmetrical dimethylarginine degradation in cells.We have demonstrated that proton pump inhibitors increase plasma asymmetrical dimethylarginine level in animals and reduce NO production in human endothelial cells and saphenous veins (5).Because endothelial NO is an antiatherogenic molecule (6), and because asymmetrical dimethylarginine is associated with increased cardiovascular risk (7), the inhibition of dimethylarginine dimethylaminohydrolase by proton pump inhibitors might be expected to increase the risk for major adverse cardiovascular events.Indeed, we have recently reported that the use of proton pump inhibitors is associated with increased cardiovascular mortality (8).As asymmetrical dimethylarginine is a nonselective NOS inhibitor, it is also possible that proton pump inhibitor-mediated accumulation of asymmetrical dimethylarginine may reduce activity of inducible NOS.Because inducible NOS participates in immune defense, its inhibition by proton pump inhibitors may reduce the clearance of pathogens.As Lang and colleagues pointed out, impaired defense against pathogens could be particularly problematic in poor metabolizers of lansoprazole.The study by Lang and colleagues, as well as our…
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