Elevated serum melatonin is associated with the nocturnal worsening of asthma

Background: Increased airway inflammation at night contributes to the nocturnal worsening of asthma. In vitro studies have shown exogenous melatonin to be pro-inflammatory in asthma, but it is unknown whether endogenous melatonin levels are a controller of airway inflammation in nocturnal asthma. Objective: Our aim was to determine 24-hour patterns of serum melatonin and their relationship to overnight decline in physiology in subjects with nocturnal asthma, non-nocturnal asthma, and in healthy controls. Methods: Observational study of pulmonary physiology and melatonin levels in patients with nocturnal asthma (n = 7), non-nocturnal asthma (n = 13), and healthy controls (n = 11). Subjects maintained a constant sleep-wake regimen for 7 days. On day 8, serum melatonin was measured every 2 hours by radioimmunoassay and analyzed by cosinor modeling. The correlation between serum melatonin levels and overnight change in spirometry was evaluated by Spearman's rank correlation analysis. Results: In subjects with nocturnal asthma, peak melatonin levels were significantly elevated compared with healthy controls (67.6 ± 5.0 pg/mL versus 53.5 ± 4.0 pg/mL, P = .03). Melatonin acrophase was delayed in nocturnal asthma (02:54 versus 01:58 in healthy controls, P = .003, and 02: 15 in non-nocturnal asthma, P = .01). In subjects with nocturnal asthma, increasing melatonin levels were significantly and inversely correlated with overnight change in FEV₁ (r = -.79, P = .04), a relationship that was not observed in non-nocturnal asthma or healthy controls. Conclusions: Nocturnal asthma is associated with elevation and phase delay of peak serum melatonin levels. Elevated melatonin levels might contribute to the pathogenesis of nocturnal asthma.