Alpha-1 Antitrypsin Levels and Phenotypes in Patients with Asthma and COPD in Appalachian East Tennessee

Alpha-1 Antitrypsin Deficiency (A1ATD) is associated with an increased risk of emphysema and chronic obstructive pulmonary disease (COPD). In view of the high prevalence of chronic respiratory diseases in East Tennessee and limited data on A1AT phenotypes in this area, we determined A1AT allele frequency among patients with COPD, asthma, or asthma-COPD overlap (ACO) in our clinic population.

We conducted an IRB-approved retrospective analysis of patient demographics, medical history, comprehensive pulmonary function tests (PFTs), and serum A1AT levels and phenotypes in a cohort of general pulmonary clinic patients with COPD, asthma, or ACO at the University of Tennessee Medical Center in Knoxville, TN. We employed descriptive and nonparametric statistical methods for data analysis, and an alpha value < 0.05 was considered statistically significant.

In this cohort of 177 patients (mean age 63.2 ± 11.9 years), most were white (94.4%), female (59.3%), former or current smokers (79.1%), and homozygous for the normal PiMM A1AT phenotype (78.5%). Heterozygous A1AT phenotypes PiMS, PiMZ, PiSZ, and PiXZ were found in 23.9%, 20%, and 8.3% of patients with COPD, ACO, and asthma, respectively. Compared with PiMM, serum A1AT levels were significantly lower with PiMZ, PiSZ, and PiXZ phenotypes (p < 0.001). PFTs did not differ among A1AT phenotypes. In fact, there was a weak negative correlation between serum A1AT levels and forced vital capacity (r = -0.29; p = 0.01) and diffusion capacity for carbon monoxide (r = -0.27; p = 0.03).

Among our East Tennessee cohort with COPD, asthma, or ACO, we found a 2- to 6-fold higher prevalence of heterozygous A1AT phenotypes than a national survey of US veterans. Further investigation through larger, prospective, population-based studies is needed to determine the clinical relevance of the higher prevalence of A1AT heterozygotes in this region.