The United States Alpha-1 Foundation Research Registry: Genesis, Impact and Future.

The Alpha-1 Foundation Research Registry has a long history of facilitating research studies in the United States. The current contact registry is used to invite participants to research studies. However, the next generation of individuals diagnosed with alpha-1 antitrypsin deficiency may look quite different from historical cohorts. This paper uses data from the Alpha Coded Testing (ACT) study, a home genetic testing program in which deficient individuals are invited to participate in the Registry, to demonstrate the impact that selection bias can introduce into registry data. Environmental tobacco smoke (ETS) exposure is rapidly declining in the United States. We queried whether consecutive non-smokers with or without childhood ETS in ACT (N = 801) had been diagnosed with COPD more often if deficiency genes were defined in subsequent testing. The prevalence of COPD was not different between cohorts with or without ETS exposure between normal (PiMM and PiMS), moderately deficient (PiMZ, PiMNull, and PiSS), and severely deficient (PiSZ, PiZZ, PiSNull, and PiZNull) genotypes. Surprisingly, age adjusted COPD Severity Scores in this cohort were higher for individuals with normal genotypes compared to moderately (P<0.001) and severely (P = 0.04) deficient genotypes. Ascertainment bias of testing within families (which yields the highest incidence of deficiency genotypes) also finds many family members without symptoms, even over the age of 40. We conclude that the future utility of registries will depend on accurate determination of testing mechanics. Larger database initiatives using the COPD Patient Powered Research Network are described.