Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin XXXX Study. Alpha-1 Protocol.

@entity1 @entity370 @entity8693 @entity1030
UNASSIGNED: Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The Genomic Research in Alpha-1 Antitrypsin @entity370 a1 Study is a prospective, multicenter, cross-sectional study of adults older than age 35 years with PiZZ or PiMZ alpha-1 antitrypsin genotypes. It is designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define @entity1030 ( @entity1030 ) phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; and blood microRNA and blood mononuclear cell RNA and DNA profiling. We will rely on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ @entity1 on or off alpha-1 antitrypsin augmentation therapy, PiMZ @entity1 not on augmentation therapy, and control @entity1 from the Subpopulations and Intermediate Outcome Measures in @entity1030 Study who match on FEV1 and age will be compared. In the primary analysis, we will determine if the PiZZ individuals on augmentation therapy have a difference in lower respiratory tract microbes identified compared with matched PiZZ individuals who are not on augmentation therapy. By characterizing the microbiome in @entity8693 ( @entity8693 ), we hope to define new phenotypes of @entity1030 that explain some of the diversity of clinical presentations. As a unique genetic cause of @entity1030 , @entity8693 may inform typical @entity1030 pathogenesis, and better understanding of it may illuminate the complex interplay between environment and genetics. Although the biologic approaches are hypothesis generating, the results may lead to development of novel biomarkers, better understanding of @entity1030 phenotypes, and development of novel diagnostic and therapeutic trials in @entity8693 and @entity1030 . Clinical trial registered with www.clinicaltrials.gov (NCT01832220).
