Skip Navigation


American Journal of Epidemiology Advance Access originally published online on September 2, 2009
American Journal of Epidemiology 2009 170(8):1005-1013; doi:10.1093/aje/kwp216
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Appendix
Right arrow All Versions of this Article:
170/8/1005    most recent
kwp216v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Castaldi, P. J.
Right arrow Articles by Silverman, E. K.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Castaldi, P. J.
Right arrow Articles by Silverman, E. K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

American Journal of Epidemiology © The Author 2009. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Development of Predictive Models for Airflow Obstruction in Alpha-1-Antitrypsin Deficiency

P. J. Castaldi, D. L. DeMeo, D. M. Kent, E. J. Campbell, A. F. Barker, M. L. Brantly, E. Eden, N. G. McElvaney, S. I. Rennard, J. M. Stocks, J. K. Stoller, C. Strange, G. Turino, R. A. Sandhaus, J. L. Griffith and E. K. Silverman

Correspondence to Dr. Dawn L. DeMeo, Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115 (e-mail:dawn.demeo{at}channing.harvard.edu).

Received for publication January 23, 2009. Accepted for publication June 25, 2009.

Alpha-1-antitrypsin deficiency is a genetic condition associated with severe, early-onset chronic obstructive pulmonary disease (COPD). However, there is significant variability in lung function impairment among persons with the protease inhibitor ZZ genotype. Early identification of persons at highest risk of developing lung disease could be beneficial in guiding monitoring and treatment decisions. Using a multicenter, family-based study sample (2002–2005) of 372 persons with the protease inhibitor ZZ genotype, the authors developed prediction models for forced expiratory volume in 1 second (FEV1) and the presence of severe COPD using demographic, clinical, and genetic variables. Half of the data sample was used for model development, and the other half was used for model validation. In the training sample, variables found to be predictive of both FEV1 and severe COPD were age, sex, pack-years of smoking, bronchodilator responsiveness, chronic bronchitis symptoms, and index case status. In the validation sample, the predictive model for FEV1 explained 50% of the variance in FEV1, and the model for severe COPD exhibited excellent discrimination (c statistic = 0.88).

alpha-1-antitrypsin deficiency; genetics; polymorphism, single nucleotide; pulmonary disease, chronic obstructive

Abbreviations: AAT, {alpha}1-antitrypsin; COPD, chronic obstructive pulmonary disease; GSTP1, glutathione S-transferase P1; FEV1, forced expiratory volume in 1 second; IL10, interleukin-10; NOS3, nitric oxide synthase 3; SNP, single nucleotide polymorphism; TNF, tumor necrosis factor


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.