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

Rationale: 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.

Objectives: 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.

Measurement and main 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).

Trial registration: ClinicalTrials.gov NCT00692198.

Keywords: Long-term Oxygen Treatment Trial; alpha-1 antitrypsin deficiency; desaturation; oxygenation.

Figure 1.

Exercise desaturation eligibility evaluation using oximetry data from the 6-minute-walk. LOTT = Long-term Oxygen Treatment Trial.

Figure 2.

Percent of oxygen saturation as measured by pulse oximetry points below saturation cut points of 90, 89, and 88%. (A) Severe alpha-1 antitrypsin deficiency (AATD) (blue) versus usual chronic obstructive pulmonary disease (COPD) (red). (B) Mild/moderate AATD (blue) versus usual COPD (red).