title: Characteristics of Alpha-1 Antitrypsin-Deficient Individuals in the Long-term Oxygen Treatment Trial and Comparison with Other Subjects with Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  Alpha-1 antitrypsin deficiency (AATD) predisposes to chronic obstructive pulmonary disease, but is underrecognized. Oxygenation and exercise desaturation in individuals with AATD-associated chronic obstructive pulmonary disease has been sparsely studied. The Long-term Oxygen Treatment Trial (LOTT) permits comparing these features of individuals with AATD with alpha-1 antitrypsin-replete (called "usual chronic obstructive pulmonary disease") LOTT participants.
  
  
  OBJECTIVE
  Compare demographic, clinical, baseline oxygenation, and exercise desaturation features in participating AATD subjects with those of other LOTT subjects.
  
  
  METHODS
  LOTT is a multicenter randomized controlled trial comparing use of supplemental oxygen versus not in subjects with chronic obstructive pulmonary disease and moderate hypoxemia (resting oxygen saturation as measured by pulse oximetry, 89-93%) or normal oxygen saturation at rest and significant exercise desaturation.
  
  
  RESULTS
  Among the 597 LOTT participants with nonmissing alpha-1 antitrypsin levels, 11 (1.8%) had severe AATD and 44 (7.4%) had mild/moderate AATD. Comparison of the 11 severely AAT-deficient individuals with the 542 LOTT participants with usual chronic obstructive pulmonary disease showed that the AATD subjects were younger and despite less smoking, had lower FEV1/FVC (mean post-bronchodilator FEV1/FVC, 0.38 ± 0.06 vs. 0.46 ± 0.13; P = 0.002). Comparison with 27 age-, sex-, and FEV1-matched alpha-1 antitrypsin-normal LOTT participants showed no baseline difference in resting room air pulse oximetry saturation (AATD, 93.6% ± 2.3% vs. 92.7% ± 2.2%; P = 0.64). Exercise-related desaturation was more severe in the individuals with AATD based on desaturation to 88% or less sooner during a 6-minute-walk test, having a higher percentage of desaturation points (e.g., <90%) during exercise, and having a higher distance-saturation product (defined as the distance walked in 6 min multiplied by the nadir saturation achieved during the 6-minute-walk test).
  
  
  CONCLUSIONS
  These data suggest that individuals with AATD experience more profound desaturation with exercise than age-, sex-, race-, and FEV1-matched control subjects with usual chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00692198).
authors.affiliation: 1 Respiratory Institute, and.|2 Education Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: James K
authors.initials: JK
authors.lastname: Stoller
authors.affiliation: 1 Respiratory Institute, and.
authors.forename: Loutfi S
authors.initials: LS
authors.lastname: Aboussouan
authors.affiliation: 3 Division of Pulmonary Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Kanner
authors.affiliation: 4 Epedemiology Department, Johns Hopkins School of Public Health, Baltimore, Maryland.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Wilson
authors.affiliation: 5 Pulmonary, Allergy, Critical Care, and Sleep Medicine Division, Ohio State University, Columbus, Ohio.
authors.forename: Phil
authors.initials: P
authors.lastname: Diaz
authors.affiliation: 6 Pulmonary and Critical Care Medicine, John Hopkins, Baltimore, Maryland; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Wise
mesh_terms: D000368:Aged; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D010102:Oxygen Inhalation Therapy / Q000379:methods*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D000515:alpha 1-Antitrypsin / Q000097:blood*; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications* / Q000175:diagnosis
chemical_list: D000515:alpha 1-Antitrypsin
keywords: Long-term Oxygen Treatment Trial; alpha-1 antitrypsin deficiency; desaturation; oxygenation