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, E. K. Silverman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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).

Original languageEnglish (US)
Pages (from-to)1005-1013
Number of pages9
JournalAmerican Journal of Epidemiology
Volume170
Issue number8
DOIs
StatePublished - Oct 1 2009

Fingerprint

alpha 1-Antitrypsin Deficiency
Forced Expiratory Volume
Chronic Obstructive Pulmonary Disease
Protease Inhibitors
Genotype
Bronchodilator Agents
Chronic Bronchitis
Lung Diseases
Smoking
Demography
Lung
Autosomal Recessive alpha-1-Antitrypsin Deficiency

Keywords

  • Alpha-1-antitrypsin deficiency
  • Genetics
  • Polymorphism, single nucleotide
  • Pulmonary disease, chronic obstructive

ASJC Scopus subject areas

  • Epidemiology

Cite this

Castaldi, P. J., Demeo, D. L., Kent, D. M., Campbell, E. J., Barker, A. F., Brantly, M. L., ... Silverman, E. K. (2009). Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency. American Journal of Epidemiology, 170(8), 1005-1013. https://doi.org/10.1093/aje/kwp216

Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency. / Castaldi, P. J.; Demeo, D. L.; Kent, D. M.; Campbell, E. J.; Barker, A. F.; Brantly, M. L.; Eden, E.; McElvaney, N. G.; Rennard, S. I.; Stocks, J. M.; Stoller, J. K.; Strange, C.; Turino, G.; Sandhaus, R. A.; Griffith, J. L.; Silverman, E. K.

In: American Journal of Epidemiology, Vol. 170, No. 8, 01.10.2009, p. 1005-1013.

Research output: Contribution to journalArticle

Castaldi, PJ, Demeo, DL, Kent, DM, Campbell, EJ, Barker, AF, Brantly, ML, Eden, E, McElvaney, NG, Rennard, SI, Stocks, JM, Stoller, JK, Strange, C, Turino, G, Sandhaus, RA, Griffith, JL & Silverman, EK 2009, 'Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency', American Journal of Epidemiology, vol. 170, no. 8, pp. 1005-1013. https://doi.org/10.1093/aje/kwp216
Castaldi PJ, Demeo DL, Kent DM, Campbell EJ, Barker AF, Brantly ML et al. Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency. American Journal of Epidemiology. 2009 Oct 1;170(8):1005-1013. https://doi.org/10.1093/aje/kwp216
Castaldi, P. J. ; Demeo, D. L. ; Kent, D. M. ; Campbell, E. J. ; Barker, A. F. ; Brantly, M. L. ; Eden, E. ; McElvaney, N. G. ; Rennard, S. I. ; Stocks, J. M. ; Stoller, J. K. ; Strange, C. ; Turino, G. ; Sandhaus, R. A. ; Griffith, J. L. ; Silverman, E. K. / Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency. In: American Journal of Epidemiology. 2009 ; Vol. 170, No. 8. pp. 1005-1013.
@article{9046fb740ab34af88fa437c8baa406f6,
title = "Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency",
abstract = "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).",
keywords = "Alpha-1-antitrypsin deficiency, Genetics, Polymorphism, single nucleotide, Pulmonary disease, chronic obstructive",
author = "Castaldi, {P. J.} and Demeo, {D. L.} and Kent, {D. M.} and Campbell, {E. J.} and Barker, {A. F.} and Brantly, {M. L.} and E. Eden and McElvaney, {N. G.} and Rennard, {S. I.} and Stocks, {J. M.} and Stoller, {J. K.} and C. Strange and G. Turino and Sandhaus, {R. A.} and Griffith, {J. L.} and Silverman, {E. K.}",
year = "2009",
month = "10",
day = "1",
doi = "10.1093/aje/kwp216",
language = "English (US)",
volume = "170",
pages = "1005--1013",
journal = "American Journal of Epidemiology",
issn = "0002-9262",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency

AU - Castaldi, P. J.

AU - Demeo, D. L.

AU - Kent, D. M.

AU - Campbell, E. J.

AU - Barker, A. F.

AU - Brantly, M. L.

AU - Eden, E.

AU - McElvaney, N. G.

AU - Rennard, S. I.

AU - Stocks, J. M.

AU - Stoller, J. K.

AU - Strange, C.

AU - Turino, G.

AU - Sandhaus, R. A.

AU - Griffith, J. L.

AU - Silverman, E. K.

PY - 2009/10/1

Y1 - 2009/10/1

N2 - 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).

AB - 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).

KW - Alpha-1-antitrypsin deficiency

KW - Genetics

KW - Polymorphism, single nucleotide

KW - Pulmonary disease, chronic obstructive

UR - http://www.scopus.com/inward/record.url?scp=70349696529&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349696529&partnerID=8YFLogxK

U2 - 10.1093/aje/kwp216

DO - 10.1093/aje/kwp216

M3 - Article

C2 - 19726494

AN - SCOPUS:70349696529

VL - 170

SP - 1005

EP - 1013

JO - American Journal of Epidemiology

JF - American Journal of Epidemiology

SN - 0002-9262

IS - 8

ER -