Melatonin improves sleep and reduces nitrite in the exhaled breath condensate in cystic fibrosis--a randomized, double-blind placebo-controlled study.

Cystic fibrosis (CF) is a chronic progressive disorder characterized by repeated episodes of respiratory infection. Impaired sleep is common in CF leading to reduced quality of life. Melatonin, a secretory product of the pineal gland, has an important function in the synchronization of circadian rhythms, including the sleep-wake cycle, and has been shown to possess significant anti-oxidant properties. To evaluate the effects of exogenous melatonin on sleep and inflammation and oxidative stress markers in CF, a randomized double-blind, placebo-controlled study initially involving 20 patients with CF was conducted. One individual failed to conclude the study. All subjects were clinically stable when studied and without recent infectious exacerbation or hospitalization in the last 30 days. Groups were randomized for placebo (n = 10; mean age 12.1 +/- 6.0) or 3 mg melatonin (n = 9; mean age 16.6 +/- 8.26) for 21 days. Actigraphy was performed for 6 days before the start of medication and in the third week (days 14-20) of treatment. Isoprostane and nitrite levels were determined in exhaled breath condensate (EBC) at baseline (day 0) and after treatment (day 21). Melatonin improved sleep efficiency (P = 0.01) and tended to improve sleep latency (P = 0.08). Melatonin reduced EBC nitrite (P = 0.01) but not isoprostane. In summary, melatonin administration reduces nitrite levels in EBC and improves sleep measures in clinically stable CF patients. The failure of melatonin to reduce isoprostane levels may have been a result of the low dose of melatonin used as a treatment.

Nocturnal hypoxia and sleep disturbances in cystic fibrosis.

Disrupted sleep and nocturnal hypoxia are common in cystic fibrosis (CF). However, the predictors of nocturnal hypoxia in CF are still controversial. In order to identify the risk factors for nocturnal desaturation and sleep disturbances, we carried out a clinical and polysomnographic investigation of CF patients. We studied 30 clinically stable CF cases with clinical lung disease (mean age = 12.8; mean FEV1 = 65.2), 10 CF cases without significant lung disease (mean age = 13.3; mean FEV1 = 99.8), and 20 controls (mean age = 15.5). Patients were evaluated by spirometry, 6-min walk test, the Shwachman-Kulczycki (S-K) score, and full overnight polysomnography. Cases with clinical lung disease had lower body mass index, forced vital capacity, and S-K scores. During sleep, five CF cases with clinical lung disease (15%) had SaO(2) <90% during more than 30% of total sleep time and 11 cases (36.6%) had a nadir SaO(2) below 85%. FEV1 values for CF cases with clinical lung disease were related to nadir SaO(2) (P < 0.03) and to mean SaO(2) (P = 0.02). A receiver operating characteristic (ROC) analysis determined FEV1 at 64% to be predictive of nocturnal desaturation as defined by minimum SaO(2) <85% (sensitivity = 92.3%; specificity = 77.3%) or SaO(2) <90% for 30% of sleep time (sensitivity = 81.8%; specificity = 85.2%). Frequency of impaired sleep was not different in CF cases with (N = 2) and without significant lung disease (N = 5, P = 0.53). Sleep architecture was not significantly different between the two groups. Sleep apnea was present in three CF cases with clinical lung disease and in one case without significant lung disease. In summary, desaturation during sleep can be predicted by FEV1 <64% with good sensitivity and specificity. There are no significant differences in sleep architecture between clinically stable CF cases with and without significant lung disease.