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).
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).
Authors: Inga-Cecilie Sørheim; Per Bakke; Amund Gulsvik; Sreekumar G Pillai; Ane Johannessen; Per I Gaarder; Edward J Campbell; Alvar Agustí; Peter M A Calverley; Claudio F Donner; Barry J Make; Stephen I Rennard; Jørgen Vestbo; Emiel F M Wouters; Peter D Paré; Robert D Levy; Harvey O Coxson; David A Lomas; Craig P Hersh; Edwin K Silverman Journal: Chest Date: 2010-07-01 Impact factor: 9.410
Authors: Marilyn G Foreman; Carla Wilson; Dawn L DeMeo; Craig P Hersh; Terri H Beaty; Michael H Cho; John Ziniti; Douglas Curran-Everett; Gerard Criner; John E Hokanson; Mark Brantly; Farshid N Rouhani; Robert A Sandhaus; James D Crapo; Edwin K Silverman Journal: Ann Am Thorac Soc Date: 2017-08
Authors: Auyon J Ghosh; Brian D Hobbs; Matthew Moll; Aabida Saferali; Adel Boueiz; Jeong H Yun; Frank Sciurba; Lucas Barwick; Andrew H Limper; Kevin Flaherty; Gerard Criner; Kevin K Brown; Robert Wise; Fernando J Martinez; David Lomas; Peter J Castaldi; Vincent J Carey; Dawn L DeMeo; Michael H Cho; Edwin K Silverman; Craig P Hersh Journal: Am J Respir Crit Care Med Date: 2022-02-01 Impact factor: 21.405
Authors: Kevin Molloy; Craig P Hersh; Valerie B Morris; Tomás P Carroll; Catherine A O'Connor; Jessica A Lasky-Su; Catherine M Greene; Shane J O'Neill; Edwin K Silverman; Noel G McElvaney Journal: Am J Respir Crit Care Med Date: 2014-02-15 Impact factor: 21.405
Authors: I Suárez-Lorenzo; F Rodríguez de Castro; D Cruz-Niesvaara; E Herrera-Ramos; C Rodríguez-Gallego; T Carrillo-Diaz Journal: Clin Transl Allergy Date: 2018-11-02 Impact factor: 5.871