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Am Fam Physician. 2000;61(1):203

Nocturnal symptoms affect more than 70 percent of patients with asthma and can have a significant impact on sleep quality. Studies have shown that most asthma deaths occur at night or in the early morning hours. The goal of nocturnal asthma therapy is to maintain pulmonary function as close as possible to normal without disturbing sleep patterns. As the incidence of asthma increases, more research is needed on how best to control these nocturnal symptoms. Clinical studies have shown that salmeterol and theophylline decrease nocturnal asthma symptoms, but the latter medication affects sleep quality. Wiegand and associates compared the effectiveness of salmeterol with extended-release theophylline in relieving nocturnal asthma symptoms and also examined the way each agent affected sleep quality.

Adults with nocturnal asthma symptoms, including coughing, wheezing and chest tightness or shortness of breath causing awakening at least two times a week, were eligible for the study. Patients also were required to have a 15 percent or greater variation of peak expiratory flow (PEF) on at least three of the 10 days before the study. After initial screening, patients were sent home with a diary to record morning and evening PEF levels, nocturnal awakenings, nocturnal symptom ratings and albuterol use. After seven to 10 days, patients began a theophylline titration period until they achieved a serum concentration of 10 to 20 mg per mL. After a theophylline washout period, patients were randomized into salmeterol, theophylline or placebo control groups, with a crossover during the study. Sleep studies were performed during the treatment phase to evaluate sleep quality. Any adverse events related to treatment were also recorded.

Of the 38 patients enrolled in the study, 19 were randomized to study treatment. Overnight forced expiratory volume in one second (FEV1) values were preserved better with salmeterol than with theophylline or placebo. Salmeterol also was associated with fewer nocturnal awakenings and less use of albuterol for symptom control when compared with theophylline or placebo. Global sleep scores improved with salmeterol when compared with theophylline, but sleep studies were similar across groups. Diary card information revealed that improved PEF levels were maintained over the entire study period, and the percentage of nights in which albuterol was needed was lower with salmeterol than with theophylline or placebo. In addition, salmeterol was associated with fewer adverse events than theophylline.

The authors conclude that salmeterol is superior to theophylline in controlling nocturnal asthma and results in fewer adverse events. Salmeterol improved PEF levels, maintained overnight lung function and decreased the need for albuterol therapy. In addition, sleep quality improved with salmeterol; theophylline did not provide this benefit.

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