View Abstract

A2600 - Prevalence of NTM Infection in Subjects with and Without Normal Alpha-1 Antitrypsin Genotypes
Author Block: L. V. Luna Diaz1, A. M. Guerrero2, I. Iupe1, M. Mirsaeidi2, G. E. Holt2, R. Calderon-Candelario2, M. A. Campos2; 1Jackson Memorial Hospital, Miami, FL, United States, 2Miami VA Medical Center, Miami, FL, United States.
Introduction
Alpha 1 antitrypsin (A1AT) is a glycoprotein considered a major circulating inhibitor of serine proteases that limits host tissue injury at sites of inflammation. A1AT also modulates macrophage function by limiting monocyte activation, enhancing the release of interleukin-10 and suppressing nontuberculous mycobacteria (NTM) macrophage infection. It has been reported that the frequency of abnormal A1AT alleles in subjects with documented NTM disease occurs up to 1.6 times higher than in the general US population, suggesting that A1AT may be an anti-NTM host-defense factor. Because abnormal A1AT phenotypes may constitute a risk factor for NTM pulmonary disease,we explored the prevalence of NTM infection in a population of veterans with abnormal A1AT genotypes.
Methods
We studied a population of subjects at risk for A1AT deficiency, defined as having a pre-bronchodilator airflow obstruction (forced expiratory volume in 1 second/forced vital capacity less than 70%), screened between July 2012 and December 2016 at the Miami VA Medical Center. The design was a retrospective 1:3 case-control analysis of subjects with abnormal A1AT genotypes randomly matched by age and gender to subjects with a normal genotype (MM). Information regarding demographics, clinical diagnosis, mycobacterial respiratory cultures and pulmonary function test (PFT) was obtained through chart review. Statistical analysis was performed using Chi-square test
Results
From 1,000 subjects at risk for A1AT deficiency screened, 96 subjects were found to have abnormal genotypes (9.6%) and 10 had cultures positive for NTM (1%). The abnormal A1AT alleles found were MS, MZ, MF, MI, SS, SZ and FS, but no ZZ subjects were detected. There were no differences in age, gender or smoking history, diagnosis of COPD, asthma, or pulmonary function test results between subjects with normal versus abnormal A1AT genotypes. Although not statistically significant differences were noted, the prevalence of positive NTM cultures among subjects with abnormal A1AT alleles (4.2%) was higher than in the 297 controls (2%). The extrapolated point prevalence for these groups were 4,167 per 100,000 and 2,020 per 100,000 respectively. When analyzing the distribution of NTM species between groups, M. fortuitum was found to have the highest prevalence in the abnormal A1AT genotype group.
Conclusion
The observation that the prevalence of NTM infection is doubled among subjects with abnormal A1AT genotypes is consistent with the hypothesis that A1AT may be an important anti-NTM factor. This finding suggests that NTM infection should be considered in the evaluation of symptomatic subjects with abnormal A1AT alleles.