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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 (FEV(1)) 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 FEV(1) 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 FEV(1) explained 50% of the variance in FEV(1), and the model for severe COPD exhibited excellent discrimination (c statistic = 0.88).

SUBMITTER: Castaldi PJ 

PROVIDER: S-EPMC2765363 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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

Castaldi P J PJ   DeMeo D L DL   Kent D M DM   Campbell E J EJ   Barker A F AF   Brantly M L ML   Eden E E   McElvaney N G NG   Rennard S I SI   Stocks J M JM   Stoller J K JK   Strange C C   Turino G G   Sandhaus R A RA   Griffith J L JL   Silverman E K EK  

American journal of epidemiology 20090902 8


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 inhib  ...[more]

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