Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 30;12(4):274-284.
doi: 10.15326/jcopdf.2025.0603.

Rationale and Design of the Alpha-1 Biomarkers Consortium Study

Monica P Goldklang  1 , Cheryl Pirozzi  2 , Igor Barjaktarevic  3 , Surya P Bhatt  4 , Sandeep Bodduluri  4 , M Bradley Drummond  5 , Laura Fonseca  1   6 , D Kyle Hogarth  7 , Alison Keaveny  6 , Zhongua Liu  1 , Noel G McElvaney  8 , Oliver J McElvaney  8 , Nadine Nuchovich  6 , Sabrina Palumbo  1 , Randel Plant  6 , Robert Sandhaus  9 , J Michael Wells  4 , Andrew Wilson  10 , Charlie Strange  11 , Jeanine M D'Armiento  1 ; Alpha-1 Biomarker Consortium Study Group
Affiliations

Rationale and Design of the Alpha-1 Biomarkers Consortium Study

Monica P Goldklang et al. Chronic Obstr Pulm Dis. .

Abstract

Rationale: Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause of chronic obstructive pulmonary disease (COPD), but considerable phenotypic variability exists among affected individuals who share disease-causing variants. Therefore, a multicenter longitudinal cohort study of 270 adult participants with PiZZ AATD will be established with a goal of examining how computed tomography (CT) imaging and serum and airway biomarkers can be used to explain differences in phenotypic manifestations and outcomes.

Methods: Study visits at enrollment, 18 months, and 36 months will obtain spirometry, patient-reported outcomes, and biosampling from blood, nasal mucosa, and sputum. Chest CT image acquisition will be utilized for whole lung and lobar estimations of emphysema based on lung density and to test novel measurements of airway remodeling and lung tissue mechanics. Dried blood spot cards will be collected if the participant experiences an acute exacerbation of COPD during the study. Genetic analysis will be performed with complete SERPINA1 sequencing, and peripheral blood mononuclear cells will be isolated to generate a repository of inducible pluripotent stem cells.

Results: The cohort will be deeply characterized, including imaging, physiology, and symptomatology, cross-sectionally and longitudinally over a 3-year follow-up period. A validation cohort from Ireland will independently enroll patients with identical procedures.

Conclusion: This is the first cohort of AATD to incorporate such detailed metrics of disease, including quantitative emphysema measures, with the overarching goal of improving the understanding of disease heterogeneity in AATD and identifying factors associated with disease severity and progression.

Keywords: alpha-1 antitrypsin deficiency; biomarkers; computed tomography; emphysema; spirometry.

PubMed Disclaimer

Conflict of interest statement

In the last 36 months, the following disclosures were provided.

MPG has contracted research support for clinical trials from Sanofi, Arrowhead, NovoNordisc, Takeda, InhibRx, Mereo, Vertex, and Grifols; research grant support from the Alpha-1 Foundation, and has been paid fees for advisory work from Takeda, GSK, Sanofi, Korro, Inhibrx, Bridge Bio, and Grifols, and received support for medical writing from Takeda.

CSP has contracted research support for clinical trials from Inhibrx, Vertex, and AstraZeneca; has received consulting fees from Takeda, and has received honoraria for lectures from Medscape, Advancing Knowledge in Healthcare, the Academy for Continued Healthcare Learning, Medscape Education, the Cleveland Clinic, the Alpha-1 Foundation, and Projects in Knowledge.

IB has contracted research support for clinical trials from Theravance and Viatris, Aerogen, Takeda, Amgen, the Alpha-1 Foundation, and Johnny Carson’s Foundation, and has received consulting fees from AstraZeneca, Sanofi, Regeneron, Grifols, Verona Pharma, Inhibrx, Takeda, Genentech, Aerogen, Theravance, and Viatris.

SBh has received consulting fees from Sanofi, Regeneron, GSK, Genentech, Boehringer Ingelheim, Apreo, AstraZeneca, Chiesi, Verona, and Merck; has received honoraria for lectures from MedScape, IntegrityCE, Integratis Communications, Illuminate Help, and Horizon CME.

MBD has received grants to his institution for research by PCORI, Vertex, Teva Pharmaceuticals, the American Lung Association, Boehringer-Ingelheim, Midmark, Inc, and the National Institutes of Health (NIH); has received consulting fees from AstraZeneca, Verona, Takdea, Becker Pharma, GSK, Stratos, Genentech, and Amgen, and serves on the medical and scientific advisory boards for the COPD Foundation and the Alpha-1 Foundation.

DKH has received honoraria for lectures for Grifols, Takeda, and Sanofi, and has received consulting fees from Advanced Infusion Care and Wave Life Sciences.

NGM has received grants for investigator-initiated studies from Grifols and the Alpha-1 Foundation, consulting fees from CSL Behring, BEAM Therapeutics, Intellia Therapeutics, and GSK, and support to attend meetings from Grifols.

OJM has received grants from the Cystic Fibrosis Foundation and the University of Washington, consulting fees from Grifols, and serves on the scientific advisory committee for Grifols.

RP has received honoraria for participation in the Takeda Educational Materials Working Group.

RS has received grant support from Inhibrx and Sanofi, consulting fees from Grifols, CSL Behring, Takeda, Korobio, Beam, Wave, and Biomarin with payments all payments directed to the not-for-profit disease management organization AlphaNet; has a pending patent through his institution for CT analysis software, is a data safety monitoring board member for Takeda, Beam, and Biomarin, and has medical director roles in the Alpha-1 Foundation, AlphaNet, and AlphaNet Canada.

JMW has clinical trial support from the NIH, Veterans Administration, ARCUS-Med, Medscape, Verona Pharma, Grifols, the Alpha-1 Foundation, Inhibrx, and the American Lung Association; has a patent with Mereo BioPharma, has received advisory board fees from AstraZeneca, Takeda, GSK, Bavarian Nordic, Krystal Biotech, Sanofi, and Verona Pharma, and has received support for medical writing from Takeda, GSK, and Verona Pharma.

AW has received consulting fees from Takeda and is the scientific director of the Alpha-1 Foundation.

CS has grants paid to the Medical University of South Carolina from the Alpha-1 Foundation, Beam, Biomarin, Grifols, Krystal, Mereo, and Takeda, and is a consultant for CSL Behring, GSK, Sanofi, and Takeda.

JMD has grants and contracts for clinical trials from Mereo, Takeda, Arrowhead, Vertex, and Inhibrx, has received consulting fees from Sanofi and Bridge Bio, and is participating in advisory boards for Sanofi and Takeda.

SBo, LF, AK, ZL, NN, and SP have no disclosures.

References

    1. DeMeo DL,Sandhaus RA,Barker AF,et al. Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency. Thorax. 2007;62(9):806-813. doi: https://doi.org/10.1136/thx.2006.075846 - PMC - PubMed
    1. DeMeo DL,Silverman EK. Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha1-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk. Thorax. 2004;59(3):259-264. doi: https://doi.org/10.1136/thx.2003.006502 - PMC - PubMed
    1. Piitulainen E,Tornling G,Eriksson S. Effect of age and occupational exposure to airway irritants on lung function in non-smoking individuals with alpha 1-antitrypsin deficiency (PiZZ). Thorax. 1997;52(3):244-248. doi: https://doi.org/10.1136/thx.52.3.244 - PMC - PubMed
    1. Stoller JK,Tomashefski J Jr,Crystal RG,et al. Mortality in individuals with severe deficiency of alpha1-antitrypsin: findings from the National Heart, Lung, and Blood Institute Registry. Chest. 2005;127(4):1196-1204. doi: https://doi.org/10.1378/chest.127.4.1196 - PubMed
    1. McElvaney NG,Stoller JK,Buist AS,et al. Baseline characteristics of enrollees in the National Heart, Lung and Blood Institute Registry of alpha 1-antitrypsin deficiency. Chest. 1997;111(2):394-403. doi: https://doi.org/10.1378/chest.111.2.394 - PubMed

LinkOut - more resources