Elevated Serum Melatonin is Associated with the Nocturnal Worsening of Asthma

Abstract

<h2>Abstract</h2><h3>Background</h3> 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. <h3>Objective</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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, <i>P</i> = .03). Melatonin acrophase was delayed in nocturnal asthma (02:54 versus 01:58 in healthy controls, <i>P</i> = .003, and 02:15 in non-nocturnal asthma, <i>P</i> = .01). In subjects with nocturnal asthma, increasing melatonin levels were significantly and inversely correlated with overnight change in FEV₁ (<i>r</i> = −.79, <i>P</i> = .04), a relationship that was not observed in non-nocturnal asthma or healthy controls. <h3>Conclusions</h3> 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.