Abstract Alpha-1 antitrypsin (A1AT) heterozygous (MZ variant) confers increased susceptibility to developing COPD in individuals who smoke. While the homozygous (ZZ) genotype has been well studied, the MZ heterozygous variant remains less understood. In particular, a direct association between MZ heterozygosity and Mycobacterium avium complex (MAC) infection has not been established. We present the first known case of cavitary and nodular MAC infection in a former smoker with the MZ genotype. A 77-year-old woman with a 100 pack-year smoking history, centrilobular emphysema predominantly affecting the upper lobes, on home oxygen therapy, and known MZ heterozygous A1AT deficiency was referred to our pulmonary clinic after chest computed tomography (CT) scan revealed scattered cavitary and non-cavitary nodules in the upper lobes, including a 1.9 cm cavitary lesion in the right upper lobe. A follow-up CT obtained two months later demonstrated a new 1.7 x 1.0 cm non-cavitary nodule in the left upper lobe, concerning for infection given the rapid interval development. Positron emission tomography-CT revealed increased metabolic activity in both the right upper lobe cavitary lesion (SUV 4.5) and the new left upper lobe nodule (SUV 4.0). Bronchoscopy with bronchial washings grew MAC and Pseudomonas aeruginosa; cytology was negative for malignancy. A mucosal biopsy of the right upper lobe also showed no evidence of malignancy. The patient was diagnosed with MAC pulmonary disease and initiated on antibiotic therapy. Clinical and radiographic follow-up is ongoing. A1AT deficiency is a genetic disorder associated with COPD, though the clinical implications of MZ heterozygosity remain poorly defined. Our patient presented with nodular and cavitary opacities and was diagnosed with MAC pulmonary disease. Given the significant smoking history, lung cancer was initially suspected, but malignancy was excluded. A1AT is a circulating serine protease inhibitor that regulates immune responses. While an association between A1AT deficiency and Mycobacterium abscessus has been reported, its link with MAC infection is not well established. Treatment of MAC pulmonary disease typically involves prolonged antibiotic therapy, though the optimal regimen remains unclear. This is the first known case of cavitary and nodular MAC infection in a former smoker with the MZ heterozygous A1AT genotype. Currently, there are no established data or guidelines for the management of A1AT deficiency presenting with MAC infection. Heightened awareness and the development of a registry to collect and analyze similar cases are warranted to facilitate the creation of standardized treatment protocols. This abstract is funded by: None
Shiraishi et al. (Fri,) studied this question.