Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause of chronic obstructive pulmonary disease (COPD). Individuals with AATD have extremely low levels of plasma AAT, a serine protease inhibitor that inactivates neutrophil elastase and matrix metalloproteinases to maintain the protease-antiprotease balance in the lung. Although research has contributed to an understanding of the pathogenesis of AATD much remains to be defined regarding its natural history, treatment strategies and clinical course. The most fundamental barrier to effective therapeutic approaches to AATD is a lack of suitable biomarkers that are specific for disease progression or correlate with a specific disease phenotype. Furthermore, we lack a complete understanding of the genetic and phenotypic characteristics of this disease. Therefore, the present initiative will first form a prospective cohort of individuals with AATD (Alpha-1 Clinical Cohort, A1CC) and subsequently identify individuals from that cohort to enter into a biomarker study through the collaborative Alpha-1 Biomarker Research Consortium (A1BReC). In the context of the A1BReC, fundamental studies will be performed to elucidate genotype/phenotype relationships in the disease and explore further mechanistic studies in the pathogenesis of AATD. UG3 Phase: The primary goal of this phase will be in collaboration with the Alpha-1 Foundation to place the present Alpha-1 contact registry into a fully integrated and user-friendly Alpha-1 Clinical Cohort managed by the Alpha-1 Foundation. The A1CC will provide for public data access of de- identified information through an i2b2 query module. The secondary goal is to finalize the study protocol, informed consent, manual of procedures, execute clinical site contracts and gain IRB approvals for the UH3 phase of the protocol. UH3 Phase: To test the hypothesis that biomarkers in serum and sputum of a population of AATD with lung disease will correlate with imaging biomarkers that can predict prognosis and outcome of disease and identify genotype/phenotype correlations in a population of AATD patients with lung disease through comparisons with AATD patients without lung disease.
Research has contributed to an understanding of the pathogenesis of Alpha-1 antitrypsin deficiency (AATD), the first identified heritable cause of chronic obstructive pulmonary disease (COPD), however, much remains to be defined regarding its natural history, treatment strategies and clinical course. The most fundamental barrier to effective therapeutic approaches to AATD is a lack of suitable biomarkers that are specific for disease progression or correlate with a specific disease phenotype. Therefore, the present initiative will form a prospective cohort of individuals with AATD (Alpha-1 Clinical Cohort, A1CC) and identify individuals with AATD related COPD to enter into a biomarker study through the Alpha-1 Biomarker Research Consortium (A1BReC), with the goal of identifying new biomarkers and elucidating genotype/phenotype relationships in the disease.
