Chest
Volume 123, Issue 5, May 2003, Pages 1435-1440
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Clinical Investigations
ANTITRYPSIN
A Longitudinal Study of α1-Antitrypsin Phenotypes and Decline in FEV1 in a Community Population

https://doi.org/10.1378/chest.123.5.1435Get rights and content

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.

Section snippets

Materials and Methods

Details of the study design have been published previously.1121 Briefly, the data are derived from the Tucson Epidemiologic Study of Airways Obstructive Diseases. The study included subjects who were selected from a random, stratified cluster sample of white, non-Mexican-American households in Tucson, AZ, in 1972. There were 12 follow-up surveys over a period of 20 to 22 years. Standardized questionnaires assessing respiratory symptoms and disease history, occupation, smoking history, and

Results

The basic α1-antitrypsin phenotype distribution was similar to frequencies reported by other authors,101418 and did not differ significantly by sex, smoking status, emphysema, chronic bronchitis, or asthma diagnoses. The frequency for PiMZ did not differ significantly between rapid-decliners and nondecliners (Table 1). Means for FEV1 slope, initial FEV1 measurements, age at initial survey, and number of years of follow-up were not significantly different among the different phenotypes (Table 2

Discussion

Sandford et al20 analyzed the association between the increased risk of rapid decline in lung function and having the PiMZ phenotype. The odds ratio (OR) was 2.8 comparing 283 rapid decliners (mean ΔFEV1, −154 ± 3 mL per year) to 308 nondecliners (mean ΔFEV1, +15 ± 2 mL per year). This association was stronger when family history of COPD was taken into account (OR, 9.7). Potential confounders like age, sex, and initial level of lung function were adjusted for in a logistic regression. Study

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    This research was supported in part by National Institutes of Health fellowship grant No. HL10506–02 (to GES).

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