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


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.


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).
Arizona Respiratory Center, University of Arizona, College of Medicine, Tucson 85724, USA.
Graciela E
GE
Silva
Duane L
DL
Sherrill
Stefano
S
Guerra
Robert A
RA
Barbee
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008137:Longitudinal Studies; D008173:Lung Diseases, Obstructive / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics* / Q000503:physiopathology*