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A Longitudinal Study of ₁-Antitrypsin Phenotypes and Decline in FEV₁ in a Community Population^*

Graciela E. Silva, MPH; Duane L. Sherrill, PhD; Stefano Guerra, MD, MPH and Robert A. Barbee, MD, FCCP

^* From the Arizona Respiratory Center, University of Arizona, College of Medicine, Tucson, AZ. At the time of the study, Dr. Guerra was a fellow from the Institute of Respiratory Diseases, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico Hospital, University of Milan, Milan, Italy.

Correspondence to: Duane L. Sherrill, PhD, Arizona Respiratory Center, University of Arizona, 1501 N Campbell Ave, PO Box 245073, Tucson, AZ 85724-5073; e-mail duane{at}resp-sci.arizona.edu

Background: It is well-known that the homozygous deficiency of ₁-antitrypsin, phenotype PiZZ, is associated with an increased risk of COPD. However, studies evaluating the association between the heterozygous forms of the 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 ₁-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 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 FEV₁.

Key Words: ₁-antitrypsin • asthma • chronic bronchitis • protease inhibitors • pulmonary emphysema • trypsin inhibitors

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