A longitudinal study of alpha1-antitrypsin phenotypes and decline in FEV1 in a community population

Chest. 2003 May;123(5):1435-40. doi: 10.1378/chest.123.5.1435.


Background: It is well-known that the homozygous deficiency of alpha(1)-antitrypsin, phenotype PiZZ, is associated with an increased risk of COPD. However, studies evaluating the association between the heterozygous forms of the alpha(1)-antitrypsin phenotype PiMZ and rapid decline in lung function, both in patient and community populations, have yielded conflicting results.

Study objective: To assess the relationship between alpha(1)-antitrypsin phenotypes and decline in FEV(1) values of 2,016 adult subjects in a community population in Tucson, AZ.

Design and methods: Prospective cohort study. Standardized questionnaires and lung function measurements were administered 1.5 to 2 years apart during 12 surveys.

Results: The frequency distribution for PiMM, PiMS, and PiMZ phenotypes did not differ significantly by physician-confirmed diagnoses of emphysema, chronic bronchitis, or asthma. There was no statistically significant difference in mean FEV(1) slope values between PiMM, PiMS, and PiMZ phenotypes (-22.5, -21, and -7 mL per year, respectively). After controlling for smoking and other potential confounders, the FEV(1) slope was associated with an initial FEV(1) level and age for the initial questionnaire but not with the different phenotypes. Selecting cutoff values, we identified rapidly declining and nondeclining subgroups, based on the percent predicted changes in FEV(1). They also were not associated with alpha(1)-antitrypsin phenotypes.

Conclusions: We conclude that the data from this longitudinal community study suggest that having the PiMZ phenotype is not a significant risk factor for an accelerated decline in FEV(1).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Forced Expiratory Volume*
  • Humans
  • Longitudinal Studies
  • Lung Diseases, Obstructive / etiology
  • Lung Diseases, Obstructive / physiopathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phenotype*
  • Prospective Studies
  • Risk Factors
  • Smoking
  • alpha 1-Antitrypsin Deficiency / genetics*
  • alpha 1-Antitrypsin Deficiency / physiopathology*