title: Sex and acetazolamide effects on chemoreflex and periodic breathing during sleep at altitude.
abstract: OBJECTIVE
  Nocturnal periodic breathing occurs more frequently in men than in women with various clinical and pathophysiologic conditions. The mechanisms accounting for this sex-related difference are not completely understood. Acetazolamide effectively counteracts nocturnal periodic breathing, but it has been investigated almost exclusively in men. Our aim was to explore possible determinants of nocturnal periodic breathing in a high-altitude setting both in men and in women. We hypothesized that increased hypoxic chemosensitivity in men could be associated with the development of nocturnal periodic breathing at altitude more frequently than in women, and that acetazolamide, by leftward shifting the CO2 ventilatory response, could improve nocturnal periodic breathing at altitude in a sex-independent manner.
  
  
  METHODS
  Forty-four healthy lowlanders (21 women), randomized to acetazolamide or placebo, underwent cardiorespiratory sleep studies at sea level off treatment and under treatment on the first night after arrival at a 4,559-m altitude. Hypoxic and hypercapnic chemosensitivities were assessed at sea level.
  
  
  RESULTS
  Men, more frequently than women, exhibited increased hypoxic chemosensitivity and displayed nocturnal periodic breathing at altitude. Acetazolamide leftward shifted the CO2 set point and, at altitude, improved oxygenation and reduced periodic breathing in both sexes, but to a larger extent in men. Hypoxic chemosensitivity directly correlated with the number of apneas/hypopneas at altitude in the placebo group but not in the acetazolamide group.
  
  
  CONCLUSIONS
  The greater severity of periodic breathing during sleep displayed by men at altitude could be attributed to their increased hypoxic chemosensitivity. Acetazolamide counteracted the occurrence of periodic breathing at altitude in both sexes, modifying the apneic threshold and improving oxygenation.
  
  
  BACKGROUND
  EU Clinical Trials Register, EudraCT; No.: 2010-019986-27; URL: https://www.clinicaltrialsregister.eu.
authors.affiliation: Istituto Auxologico Italiano (Drs Caravita, Faini, Lombardi, Valentini, Rossi, Bilo, and Parati and Ms Gregorini); Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Department of Cardiovascular, Neural and Metabolic Sciences, S. Luca Hospital; the Department of Health Sciences (Drs Caravita and Parati).
authors.forename: Sergio
authors.initials: S
authors.lastname: Caravita
authors.affiliation: Istituto Auxologico Italiano (Drs Caravita, Faini, Lombardi, Valentini, Rossi, Bilo, and Parati and Ms Gregorini).
authors.forename: Andrea
authors.initials: A
authors.lastname: Faini
authors.affiliation: Istituto Auxologico Italiano (Drs Caravita, Faini, Lombardi, Valentini, Rossi, Bilo, and Parati and Ms Gregorini).
authors.forename: Carolina
authors.initials: C
authors.lastname: Lombardi
authors.affiliation: Istituto Auxologico Italiano (Drs Caravita, Faini, Lombardi, Valentini, Rossi, Bilo, and Parati and Ms Gregorini).
authors.forename: Mariaconsuelo
authors.initials: M
authors.lastname: Valentini
authors.affiliation: Istituto Auxologico Italiano (Drs Caravita, Faini, Lombardi, Valentini, Rossi, Bilo, and Parati and Ms Gregorini).
authors.forename: Francesca
authors.initials: F
authors.lastname: Gregorini
authors.affiliation: Istituto Auxologico Italiano (Drs Caravita, Faini, Lombardi, Valentini, Rossi, Bilo, and Parati and Ms Gregorini).
authors.forename: Jessica
authors.initials: J
authors.lastname: Rossi
authors.affiliation: University of Milano-Bicocca; Polo Tecnologico (Dr Meriggi and Mr Di Rienzo).
authors.forename: Paolo
authors.initials: P
authors.lastname: Meriggi
authors.affiliation: University of Milano-Bicocca; Polo Tecnologico (Dr Meriggi and Mr Di Rienzo).
authors.forename: Marco
authors.initials: M
authors.lastname: Di Rienzo
authors.affiliation: Istituto Auxologico Italiano (Drs Caravita, Faini, Lombardi, Valentini, Rossi, Bilo, and Parati and Ms Gregorini).
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Bilo
authors.affiliation: Biomedical Technology Department, Fondazione Don Carlo Gnocchi Onlus; Centro Cardiologico Monzino (Dr Agostoni)IRCCS; and the Department of Clinical Sciences and Community Health University of Milan, Milan, Italy.
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Agostoni
authors.affiliation: Istituto Auxologico Italiano (Drs Caravita, Faini, Lombardi, Valentini, Rossi, Bilo, and Parati and Ms Gregorini); Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Department of Cardiovascular, Neural and Metabolic Sciences, S. Luca Hospital; the Department of Health Sciences (Drs Caravita and Parati). Electronic address: gianfranco.parati@unimib.it.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Parati
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage*; D000328:Adult; D000531:Altitude; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage; D002628:Chemoreceptor Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006935:Hypercapnia / Q000188:drug therapy* / Q000503:physiopathology; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010101:Oxygen Consumption; D017286:Polysomnography; D012890:Sleep / Q000502:physiology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide