title: Respiratory symptoms, sleep-disordered breathing and biomarkers in nocturnal gastroesophageal reflux.
abstract: Nocturnal gastroesophageal reflux (nGER) is associated with respiratory symptoms and sleep-disordered breathing (SDB), but the pathogenesis is unclear. We aimed to investigate the association between nGER and respiratory symptoms, exacerbations of respiratory symptoms, SDB and airway inflammation.
  
  
  
  Participants in the European Community Respiratory Health Survey III in Iceland with nGER symptoms (n = 48) and age and gender matched controls (n = 42) were studied by questionnaires, exhaled breath condensate (EBC), particles in exhaled air (PEx) measurements, and a home polygraphic study. An exacerbation of respiratory symptoms was defined as an episode of markedly worse respiratory symptoms in the previous 12 months.
  
  
  
  Asthma and bronchitis symptoms were more common among nGER subjects than controls (54 % vs 29 %, p = 0.01; and 60 % vs 26 %, p < 0.01, respectively), as were exacerbations of respiratory symptoms (19 % vs 5 %, p = 0.04). Objectively measured snoring was more common among subjects with nGER than controls (snores per hour of sleep, median (IQR): 177 (79-281) vs 67 (32-182), p = 0.004). Pepsin (2.5 ng/ml (0.8-5.8) vs 0.8 ng/ml (0.8-3.6), p = 0.03), substance P (741 pg/ml (626-821) vs 623 pg/ml (562-676), p < 0.001) and 8-isoprostane (3.0 pg/ml (2.7-3.9) vs 2.6 pg/ml (2.2-2.9), p = 0.002) in EBC were higher among nGER subjects than controls. Albumin and surfactant protein A in PEx were lower among nGER subjects. These findings were independent of BMI.
  
  
  
  In a general population sample, nGER is associated with symptoms of asthma and bronchitis, as well as exacerbations of respiratory symptoms. Also, nGER is associated with increased respiratory effort during sleep. Biomarker measurements in EBC, PEx and serum indicate that micro-aspiration and neurogenic inflammation are plausible mechanisms.
authors.affiliation: Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101, Reykjavik, Iceland. ossur.emilsson@medsci.uu.se.|Department of Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland. ossur.emilsson@medsci.uu.se.|Department of Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden. ossur.emilsson@medsci.uu.se.
authors.forename: Össur Ingi
authors.identifier: 0000-0002-7199-8491
authors.initials: ÖI
authors.lastname: Emilsson
authors.affiliation: Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101, Reykjavik, Iceland.|Department of Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Bryndís
authors.initials: B
authors.lastname: Benediktsdóttir
authors.affiliation: Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Ísleifur
authors.initials: Í
authors.lastname: Ólafsson
authors.affiliation: Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cook
authors.affiliation: Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101, Reykjavik, Iceland.|Department of Otolaryngology, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Sigurður
authors.initials: S
authors.lastname: Júlíusson
authors.affiliation: Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101, Reykjavik, Iceland.|Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Einar Stefán
authors.initials: ES
authors.lastname: Björnsson
authors.affiliation: Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Sunna
authors.initials: S
authors.lastname: Guðlaugsdóttir
authors.affiliation: Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Anna Soffía
authors.initials: AS
authors.lastname: Guðmundsdóttir
authors.affiliation: Department of Occupational and Environmental Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Mirgorodskaya
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Evert
authors.initials: E
authors.lastname: Ljungström
authors.affiliation: Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101, Reykjavik, Iceland.|Department of Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Erna Sif
authors.initials: ES
authors.lastname: Arnardóttir
authors.affiliation: Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101, Reykjavik, Iceland.|Department of Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Thórarinn
authors.initials: T
authors.lastname: Gíslason
authors.affiliation: Department of Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Janson
authors.affiliation: Department of Occupational and Environmental Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna-Carin
authors.initials: AC
authors.lastname: Olin
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001944:Breath Tests; D001991:Bronchitis / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology; D016022:Case-Control Studies; D002940:Circadian Rhythm; D018450:Disease Progression; D045853:Exhalation; D005260:Female; D005764:Gastroesophageal Reflux / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D006306:Health Surveys; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012119:Respiration; D012890:Sleep; D012891:Sleep Apnea Syndromes / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D015415:Biomarkers
keywords: Asthma; Bronchitis; Exhaled breath condensate; Nocturnal gastroesophageal reflux; Particles in exhaled air; Sleep-disordered breathing