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.

The Allergist's Role in Detection of Severe Alpha-1 Antitrypsin Deficiency.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) frequently presents as difficult to manage asthma or asthma with fixed obstruction and is well documented as being underdiagnosed in the population. OBJECTIVE: This study aimed to better describe allergists'/immunologists' involvement in the care of patients with AATD and whether they currently contribute to the underdiagnosis by lack of screening for the condition. METHODS: Using the Research Electronic Data Capture tool, we submitted a questionnaire to 500 patients with severe AATD (ZZ, SZ, ZNull, and FZ) through the Alpha-1 Foundation Research Registry to collect information about patient diagnosis and treatment patterns. Approximately 45% completed the questionnaire, leading to a final enrollment of 226 participants. RESULTS: Seventy-eight participants (34%) had seen an allergist, but only 11 (5%) were diagnosed with AATD by their allergist. Likewise, allergists prescribed alpha-1 augmentation therapy to only 5 (8%) of the 59 patients on augmentation therapy. Nearly 46% (n = 104) of all participants were diagnosed with either asthma (28%) or allergic disease (18%) before receiving a diagnosis of AATD. Eighteen patients had been treated with immunotherapy before their diagnosis of AATD, with 94% of these participants receiving treatment for 3 years or longer. CONCLUSIONS: Our data suggest that specialists in Allergy and Immunology should consider and screen for AATD in patients with asthma in whom spirometry does not return to normal. Furthermore, we propose allergists/immunologists are well suited to screen and treat patients with AATD.

Genetics' influence on patient experiences with a rare chronic disorder: a photovoice study of living with alpha-1 antitrypsin deficiency.

Patients with rare chronic disorders and their caregivers increasingly form communities to support and exchange social experiences. Because up to 10% of the United States population is affected by one of 5000 to 6000 rare disorders, efforts to understand the individuals and affected communities are important. This study was conducted using community-based participatory research approaches within a community of patients and caregivers living with alpha-1 antitrypsin (AAT) deficiency. Patient populations at some risk for lung transplant include individuals who smoked cigarettes and patients who underwent liver transplant in infancy and later adulthood due to accumulation of misfolded AAT within hepatocytes.