BRONCHIECTASIS IN ALPHA-1 ANTITRYPSIN DEFICIENCY: A SINGLE-CENTER REVIEW

Abstract

SESSION TITLE: Asthma and Comorbid Disease SESSION TYPE: Original Investigations PRESENTED ON: 10/10/2018 08:45 AM - 09:45 AM PURPOSE: Alpha-1 Antitrypsin Deficiency (A1ATD) is a genetic disease that results in abnormal alpha-1 antitrypsin protein polymers which cannot be released from hepatocytes. This results in low circulating alpha-1 antitrypsin and hepatotoxicity. Alpha-1 antitrypsin has a protective effect in the lungs by neutralizing pro-inflammatory enzymes, such as neutrophil elastase, and sufficiently low levels can result in emphysema.1 Bronchiectasis has also been associated with A1ATD since the original description of the disease.2 Augmentation therapy has been shown to have beneficial pulmonary effects in patients with emphysema, but outcome data in patients with bronchiectasis and the effects of augmentation therapy is lacking. METHODS: Patients with A1ATD and alpha-1 carrier status evaluated at Mayo Clinic Rochester from January 1, 2000 to October 1, 2016 were included in this retrospective review. Data relating to demographics, exacerbations, spirometry, and other causes of bronchiectasis were extracted. Patients with fewer than 12 months of augmentation therapy were excluded from outcome comparisons. RESULTS: 122 patients were included in the final analysis, of which 47 (38.5%) had bronchiectasis. 10 patients with bronchiectasis had MZ or MS genotypes. Compared to those without bronchiectasis, patients with bronchiectasis had a higher mean baseline rate of pulmonary exacerbations (0.73/year vs. 0.28/year, p=0.003). 34 patients received augmentation therapy, including 18 patients with bronchiectasis. Compared to patients without bronchiectasis who also received augmentation, those with bronchiectasis had a faster mean rate of decline in DLCO (-0.56 vs. +0.51 mL/min/mmHg/year, p=0.010), and a higher mean rate of post-treatment exacerbations (+1.28/year vs +0.5/year, p=0.011). Comparing patients with bronchiectasis and emphysema who did and did not receive augmentation, those who received augmentation therapy had more exacerbations compared to their baseline (+0.53/year vs. -0.31/year, p=0.019) and lower mean baseline percent predicted forced expiratory volume in one second (FEV1%) (46.5% vs. 67.8%, p=0.006) and DLCO (12.9 vs. 18.9 mL/min/mmHg, p=0.015), although the change over time was not significantly different. CONCLUSIONS: Bronchiectasis is a common finding in A1ATD, and is not exclusive to patients with ZZ genotypes. Patients with bronchiectasis in this cohort had higher rates of pulmonary exacerbations, regardless of treatment with augmentation therapy. CLINICAL IMPLICATIONS: The role of augmentation therapy for patients with bronchiectasis in the absence of emphysema is unclear and warrants additional studies. DISCLOSURES: No relevant relationships by Megan Dulohery Scrodin, source=Web Response No relevant relationships by Gregory Stroh, source=Web Response