title: Gastroesophageal reflux disease as an etiology of sleep disturbance in subjects with insomnia and minimal reflux symptoms: a pilot study of prevalence and response to therapy.
abstract: BACKGROUND
  Gastroesophageal reflux disease (GERD) is a well-recognized cause of impaired sleep in patients with frequent GERD symptoms, as well as those with sleep apnea. GERD's role in sleep disturbance of minimally symptomatic patients with poor sleep quality is less clear.
  
  
  OBJECTIVE
  We aimed to define the prevalence of GERD-related sleep disturbance in minimally-symptomatic subjects with demonstrated insomnia, and to assess the changes in sleep efficiency in these subjects after vigorous acid suppression.
  
  
  METHODS
  We recruited subjects aged 18-75 years reporting at least 6 months of insomnia, and sleep difficulty at least three nights per week. Subjects with a BMI > 30, a history of snoring or ongoing use of proton pump inhibitor or H2 receptor antagonist were excluded. Subjects underwent concurrent sleep study with dual channel 24-h pH study. Sleep efficiency, defined as the percentage of time after sleep initiation that the subject actually slept, and spontaneous arousal index, defined as the number of arousals per hour, were calculated. Those with a sleep study demonstrating poor sleep quality (sleep efficiency of < 83%, and > 10 arousals/h for those aged < 45, and > 15 for those who were 45 or older) and no obstructive sleep apnea were treated with rabeprazole 20 mg PO BID x 14 days. After 14 days, the subjects underwent repeat sleep study with pH monitoring. The GERD Symptom Assessment Scale (GSAS), the Epworth Sleepiness Scale (ESS) and the Functional Outcomes of Sleep Questionnaire (FOSQ) were administered to subjects at study inception and after 2 weeks of therapy.
  
  
  RESULTS
  Twenty-four subjects reporting insomnia were enrolled, and 20 met criteria for disordered sleep and no OSA. Seventeen completed both the first and second studies, and 16 were adequate for analysis. Baseline GSAS demonstrated trivial or no reflux symptoms in the cohort (no subject scored > 8 out of 45 on GSAS, corresponding to a median rating of reflux symptoms of "not at all"). Four of 16 subjects (25%) demonstrated abnormal pH studies at baseline. All four had normalization of acid exposures on PPI. After 2 weeks of treatment, three of these four subjects had normalization of sleep efficiency, compared to 4 of 12 of the subjects with normal Johnson-DeMeester scores. Repeated measures analysis showed significant improvement in spontaneous arousal index between the first and second study for the whole group (P < 0.0035). Pre- and post-therapy ESS and FOSQ scores were not significantly different.
  
  
  CONCLUSIONS
  Despite the lack of GERD symptoms, a significant minority of subjects with sleep disturbance have abnormal acid exposures. These preliminary data suggest that aggressive treatment of GERD in such patients may result in improvement in sleep efficiency.
authors.affiliation: Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7080, USA. nshaheen@med.unc.edu
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Madanick
authors.forename: Maha
authors.initials: M
authors.lastname: Alattar
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Morgan
authors.forename: Paris H
authors.initials: PH
authors.lastname: Davis
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Galanko
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Spacek
authors.forename: Bradley V
authors.initials: BV
authors.lastname: Vaughn
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D005260:Female; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015995:Prevalence; D011446:Prospective Studies; D064750:Rabeprazole; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology / Q000209:etiology*; D007319:Sleep Initiation and Maintenance Disorders / Q000209:etiology*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064750:Rabeprazole