title: Blunted Hypercapnic Respiratory Drive Response in Subjects With Late-Onset Pompe Disease.
abstract: BACKGROUND
  Patients with late-onset Pompe disease develop progressive hypercapnic respiratory failure that can be disproportionate to the respiratory muscle compromise and/or thoracic restriction. Although recent studies have reported the presence of a blunted hypercapnic respiratory response in some subjects with neuromuscular disorders and chronic hypercapnia, no study has evaluated the integrity of the respiratory drive in subjects with late-onset Pompe disease. Thus, we endeavor to determine the CO2 rebreathing response in subjects with late-onset Pompe disease.
  
  
  METHODS
  Respiratory muscle strength was assessed by measuring the maximum inspiratory pressure, and the maximum expiratory pressure. The maximum inspiratory pressure reflects the strength of the diaphragm and other inspiratory muscles, whereas the maximum expiratory pressure reflects the strength of the abdominal muscles and other expiratory muscles. We studied the hypercapnic drive response (measured as the ratio of the change in airway-occlusion pressure 0.1 s after the start of inspiration and end-tidal PCO2 in 13 subjects with late-onset Pompe disease and 51 healthy controls.
  
  
  RESULTS
  Overall inspiratory muscle strength was within normal limits or slightly diminished in the late-onset Pompe disease group. Five subjects (38.5%) were chronically hypercapnic, and 9 (69.2%) had an increased breath-holding time. Compared with controls, the change in airway-occlusion pressure 0.1 s/change in end-tidal CO2 pressure slope (hypercapnic respiratory drive) was lower in the late-onset Pompe disease group (median 0.050 [interquartile range 0.027-0.118] vs 0.183 [0.153-0.233], P < .001). Nine subjects (69.2%) had a blunted change in airway-occlusion pressure 0.1 s/change in end-tidal carbon dioxide pressure slope.
  
  
  CONCLUSIONS
  Subjects with late-onset Pompe disease had an impaired hypercapnic respiratory drive response. The clinical impact of this phenomenon in this subject subset deserves further investigation.
authors.affiliation: Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina. eldevito@gmail.com.
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: De Vito
authors.affiliation: Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Sergio G
authors.initials: SG
authors.lastname: Monteiro
authors.affiliation: Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Aruj
mesh_terms: D000293:Adolescent; D000328:Adult; D002245:Carbon Dioxide / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D006935:Hypercapnia / Q000209:etiology / Q000503:physiopathology*; D000067562:Late Onset Disorders / Q000150:complications / Q000503:physiopathology*; D008297:Male; D000072277:Maximal Respiratory Pressures; D008875:Middle Aged; D053580:Muscle Strength; D012131:Respiratory Insufficiency / Q000209:etiology / Q000503:physiopathology*; D015656:Respiratory Mechanics / Q000502:physiology*; D012132:Respiratory Muscles / Q000503:physiopathology; D055815:Young Adult
chemical_list: D002245:Carbon Dioxide
keywords: central chemoreception; control of breathing; hypercapnia; hypercapnic respiratory drive; late-onset Pompe disease; respiratory under responsiveness to hypoxia and hypercapnia