A longitudinal study of α1-antitrypsin phenotypes and decline in FEV1 in a community population

Graciela E. Silva, Duane L. Sherrill, Stefano Guerra, Robert A. Barbee

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Background: It is well-known that the homozygous deficiency of α1-antitrypsin, phenotype PiZZ, is associated with an increased risk of COPD. However, studies evaluating the association between the heterozygous forms of the α1-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 α1-antitrypsin phenotypes and decline in FEV1 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 FEV1 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 FEV1 slope was associated with an initial FEV1 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 FEV1. They also were not associated with α1-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 FEV1.

Original languageEnglish (US)
Pages (from-to)1435-1440
Number of pages6
Issue number5
StatePublished - May 1 2003


  • Asthma
  • Chronic bronchitis
  • Protease inhibitors
  • Pulmonary emphysema
  • Trypsin inhibitors
  • α-antitrypsin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine


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