Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency

Dawn L. DeMeo, Robert A. Sandhaus, Alan F. Barker, Mark L. Brantly, Edward Eden, N. Gerard McElvaney, Stephen Rennard, Esteban Burchard, James M. Stocks, James K. Stoller, Charlie Strange, Gerard M. Turino, Edward J. Campbell, Edwin K. Silverman

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Background: Severe α1-antitrypsin (AAT) deficiency is an autosomal recessive genetic condition associated with an increased but variable risk for chronic obstructive pulmonary disease (COPD). A study was undertaken to assess the impact of chronic bronchitis, pneumonia, asthma and sex on the development of COPD in individuals with severe AAT deficiency. Methods: The AAT Genetic Modifier Study is a multicentre family-based cohort study designed to study the genetic and epidemiological determinants of COPD in AAT deficiency. 378 individuals (age range 33-80 years), confirmed to be homozygous for the SERPINA1 Z mutation, were included in the analyses. The primary outcomes of interest were a quantitative outcome, forced expiratory volume in 1 s (FEV 1) percentage predicted, and a qualitative outcome, severe airflow obstruction (FEV1 <50% predicted). Results: In multivariate analysis of the overall cohort, cigarette smoking, sex, asthma, chronic bronchitis and pneumonia were risk factors for reduced FEV1 percentage predicted and severe airflow obstruction (p<0.01). Index cases had lower FEV1 values, higher smoking histories and more reports of adult asthma, pneumonia and asthma before age 16 than non-index cases (p<0.01). Men had lower pre- and post-bronchodilator FEV1 percentage predicted than women (p<0.0001); the lowest FEV1 values were observed in men reporting a history of childhood asthma (26.9%). This trend for more severe obstruction in men remained when index and non-index groups were examined separately, with men representing the majority of non-index individuals with airflow obstruction (71%). Chronic bronchitis (OR 3.8, CI 1.8 to 12.0) and a physician's report of asthma (OR 4.2, CI 1.4 to 13.1) were predictors of severe airflow obstruction in multivariate analysis of non-index men but not women. Conclusion: In individuals with severe AAT deficiency, sex, asthma, chronic bronchitis and pneumonia are risk factors for severe COPD, in addition to cigarette smoking. These results suggest that, in subjects severely deficient in AAT, men, individuals with symptoms of chronic bronchitis and/or a past diagnosis of asthma or pneumonia may benefit from closer monitoring and potentially earlier treatment.

Original languageEnglish (US)
Pages (from-to)805-812
Number of pages8
JournalThorax
Volume62
Issue number9
DOIs
StatePublished - Sep 1 2007

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alpha 1-Antitrypsin Deficiency
Asthma
Chronic Bronchitis
Pneumonia
Chronic Obstructive Pulmonary Disease
Smoking
Bronchodilator Agents
Multivariate Analysis
Recessive Genes
Sexual Development
Autosomal Recessive alpha-1-Antitrypsin Deficiency
Forced Expiratory Volume
Epidemiologic Studies
Cohort Studies
Physicians
Mutation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

DeMeo, D. L., Sandhaus, R. A., Barker, A. F., Brantly, M. L., Eden, E., McElvaney, N. G., ... Silverman, E. K. (2007). Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency. Thorax, 62(9), 805-812. https://doi.org/10.1136/thx.2006.075846

Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency. / DeMeo, Dawn L.; Sandhaus, Robert A.; Barker, Alan F.; Brantly, Mark L.; Eden, Edward; McElvaney, N. Gerard; Rennard, Stephen; Burchard, Esteban; Stocks, James M.; Stoller, James K.; Strange, Charlie; Turino, Gerard M.; Campbell, Edward J.; Silverman, Edwin K.

In: Thorax, Vol. 62, No. 9, 01.09.2007, p. 805-812.

Research output: Contribution to journalArticle

DeMeo, DL, Sandhaus, RA, Barker, AF, Brantly, ML, Eden, E, McElvaney, NG, Rennard, S, Burchard, E, Stocks, JM, Stoller, JK, Strange, C, Turino, GM, Campbell, EJ & Silverman, EK 2007, 'Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency', Thorax, vol. 62, no. 9, pp. 805-812. https://doi.org/10.1136/thx.2006.075846
DeMeo DL, Sandhaus RA, Barker AF, Brantly ML, Eden E, McElvaney NG et al. Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency. Thorax. 2007 Sep 1;62(9):805-812. https://doi.org/10.1136/thx.2006.075846
DeMeo, Dawn L. ; Sandhaus, Robert A. ; Barker, Alan F. ; Brantly, Mark L. ; Eden, Edward ; McElvaney, N. Gerard ; Rennard, Stephen ; Burchard, Esteban ; Stocks, James M. ; Stoller, James K. ; Strange, Charlie ; Turino, Gerard M. ; Campbell, Edward J. ; Silverman, Edwin K. / Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency. In: Thorax. 2007 ; Vol. 62, No. 9. pp. 805-812.
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abstract = "Background: Severe α1-antitrypsin (AAT) deficiency is an autosomal recessive genetic condition associated with an increased but variable risk for chronic obstructive pulmonary disease (COPD). A study was undertaken to assess the impact of chronic bronchitis, pneumonia, asthma and sex on the development of COPD in individuals with severe AAT deficiency. Methods: The AAT Genetic Modifier Study is a multicentre family-based cohort study designed to study the genetic and epidemiological determinants of COPD in AAT deficiency. 378 individuals (age range 33-80 years), confirmed to be homozygous for the SERPINA1 Z mutation, were included in the analyses. The primary outcomes of interest were a quantitative outcome, forced expiratory volume in 1 s (FEV 1) percentage predicted, and a qualitative outcome, severe airflow obstruction (FEV1 <50{\%} predicted). Results: In multivariate analysis of the overall cohort, cigarette smoking, sex, asthma, chronic bronchitis and pneumonia were risk factors for reduced FEV1 percentage predicted and severe airflow obstruction (p<0.01). Index cases had lower FEV1 values, higher smoking histories and more reports of adult asthma, pneumonia and asthma before age 16 than non-index cases (p<0.01). Men had lower pre- and post-bronchodilator FEV1 percentage predicted than women (p<0.0001); the lowest FEV1 values were observed in men reporting a history of childhood asthma (26.9{\%}). This trend for more severe obstruction in men remained when index and non-index groups were examined separately, with men representing the majority of non-index individuals with airflow obstruction (71{\%}). Chronic bronchitis (OR 3.8, CI 1.8 to 12.0) and a physician's report of asthma (OR 4.2, CI 1.4 to 13.1) were predictors of severe airflow obstruction in multivariate analysis of non-index men but not women. Conclusion: In individuals with severe AAT deficiency, sex, asthma, chronic bronchitis and pneumonia are risk factors for severe COPD, in addition to cigarette smoking. These results suggest that, in subjects severely deficient in AAT, men, individuals with symptoms of chronic bronchitis and/or a past diagnosis of asthma or pneumonia may benefit from closer monitoring and potentially earlier treatment.",
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T1 - Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency

AU - DeMeo, Dawn L.

AU - Sandhaus, Robert A.

AU - Barker, Alan F.

AU - Brantly, Mark L.

AU - Eden, Edward

AU - McElvaney, N. Gerard

AU - Rennard, Stephen

AU - Burchard, Esteban

AU - Stocks, James M.

AU - Stoller, James K.

AU - Strange, Charlie

AU - Turino, Gerard M.

AU - Campbell, Edward J.

AU - Silverman, Edwin K.

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N2 - Background: Severe α1-antitrypsin (AAT) deficiency is an autosomal recessive genetic condition associated with an increased but variable risk for chronic obstructive pulmonary disease (COPD). A study was undertaken to assess the impact of chronic bronchitis, pneumonia, asthma and sex on the development of COPD in individuals with severe AAT deficiency. Methods: The AAT Genetic Modifier Study is a multicentre family-based cohort study designed to study the genetic and epidemiological determinants of COPD in AAT deficiency. 378 individuals (age range 33-80 years), confirmed to be homozygous for the SERPINA1 Z mutation, were included in the analyses. The primary outcomes of interest were a quantitative outcome, forced expiratory volume in 1 s (FEV 1) percentage predicted, and a qualitative outcome, severe airflow obstruction (FEV1 <50% predicted). Results: In multivariate analysis of the overall cohort, cigarette smoking, sex, asthma, chronic bronchitis and pneumonia were risk factors for reduced FEV1 percentage predicted and severe airflow obstruction (p<0.01). Index cases had lower FEV1 values, higher smoking histories and more reports of adult asthma, pneumonia and asthma before age 16 than non-index cases (p<0.01). Men had lower pre- and post-bronchodilator FEV1 percentage predicted than women (p<0.0001); the lowest FEV1 values were observed in men reporting a history of childhood asthma (26.9%). This trend for more severe obstruction in men remained when index and non-index groups were examined separately, with men representing the majority of non-index individuals with airflow obstruction (71%). Chronic bronchitis (OR 3.8, CI 1.8 to 12.0) and a physician's report of asthma (OR 4.2, CI 1.4 to 13.1) were predictors of severe airflow obstruction in multivariate analysis of non-index men but not women. Conclusion: In individuals with severe AAT deficiency, sex, asthma, chronic bronchitis and pneumonia are risk factors for severe COPD, in addition to cigarette smoking. These results suggest that, in subjects severely deficient in AAT, men, individuals with symptoms of chronic bronchitis and/or a past diagnosis of asthma or pneumonia may benefit from closer monitoring and potentially earlier treatment.

AB - Background: Severe α1-antitrypsin (AAT) deficiency is an autosomal recessive genetic condition associated with an increased but variable risk for chronic obstructive pulmonary disease (COPD). A study was undertaken to assess the impact of chronic bronchitis, pneumonia, asthma and sex on the development of COPD in individuals with severe AAT deficiency. Methods: The AAT Genetic Modifier Study is a multicentre family-based cohort study designed to study the genetic and epidemiological determinants of COPD in AAT deficiency. 378 individuals (age range 33-80 years), confirmed to be homozygous for the SERPINA1 Z mutation, were included in the analyses. The primary outcomes of interest were a quantitative outcome, forced expiratory volume in 1 s (FEV 1) percentage predicted, and a qualitative outcome, severe airflow obstruction (FEV1 <50% predicted). Results: In multivariate analysis of the overall cohort, cigarette smoking, sex, asthma, chronic bronchitis and pneumonia were risk factors for reduced FEV1 percentage predicted and severe airflow obstruction (p<0.01). Index cases had lower FEV1 values, higher smoking histories and more reports of adult asthma, pneumonia and asthma before age 16 than non-index cases (p<0.01). Men had lower pre- and post-bronchodilator FEV1 percentage predicted than women (p<0.0001); the lowest FEV1 values were observed in men reporting a history of childhood asthma (26.9%). This trend for more severe obstruction in men remained when index and non-index groups were examined separately, with men representing the majority of non-index individuals with airflow obstruction (71%). Chronic bronchitis (OR 3.8, CI 1.8 to 12.0) and a physician's report of asthma (OR 4.2, CI 1.4 to 13.1) were predictors of severe airflow obstruction in multivariate analysis of non-index men but not women. Conclusion: In individuals with severe AAT deficiency, sex, asthma, chronic bronchitis and pneumonia are risk factors for severe COPD, in addition to cigarette smoking. These results suggest that, in subjects severely deficient in AAT, men, individuals with symptoms of chronic bronchitis and/or a past diagnosis of asthma or pneumonia may benefit from closer monitoring and potentially earlier treatment.

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