S1PR1 and chronic obstructive pulmonary disease: Concerning FNG, reports showed a higher frequency of alteration of liver enzymes and cardiac arrhythmia as observed in the recent study of phase III FREEDOMS II (Calabresi et al., 2014): cardiac side effects with FNG are probably related to transient agonism to sphingosine-1-phosphate receptors on cardiomyocytes (Forrest et al., 2004).