BACKGROUND: Severe α₁-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α₁-antitrypsin, but whether they have an increased risk of COPD is uncertain. METHODS: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. RESULTS: PI MZ was associated with a 3.5% lower FEV₁/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV₁/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. CONCLUSIONS: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV₁/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.
BACKGROUND: Severe α₁-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α₁-antitrypsin, but whether they have an increased risk of COPD is uncertain. METHODS: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. RESULTS: PI MZ was associated with a 3.5% lower FEV₁/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV₁/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. CONCLUSIONS: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV₁/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.
Authors: A J Sandford; T Chagani; T D Weir; J E Connett; N R Anthonisen; P D Paré Journal: Am J Respir Crit Care Med Date: 2001-02 Impact factor: 21.405
Authors: Morten Dahl; Anne Tybjaerg-Hansen; Peter Lange; Jørgen Vestbo; Børge G Nordestgaard Journal: Ann Intern Med Date: 2002-02-19 Impact factor: 25.391
Authors: Y Nakano; S Muro; H Sakai; T Hirai; K Chin; M Tsukino; K Nishimura; H Itoh; P D Paré; J C Hogg; M Mishima Journal: Am J Respir Crit Care Med Date: 2000-09 Impact factor: 21.405
Authors: Darcy D Marciniuk; P Hernandez; M Balter; J Bourbeau; K R Chapman; G T Ford; J L Lauzon; F Maltais; D E O'Donnell; D Goodridge; C Strange; A J Cave; K Curren; S Muthuri Journal: Can Respir J Date: 2012 Mar-Apr Impact factor: 2.409
Authors: Michael H Cho; Peter J Castaldi; Craig P Hersh; Brian D Hobbs; R Graham Barr; Ruth Tal-Singer; Per Bakke; Amund Gulsvik; Raúl San José Estépar; Edwin J R Van Beek; Harvey O Coxson; David A Lynch; George R Washko; Nan M Laird; James D Crapo; Terri H Beaty; Edwin K Silverman Journal: Am J Respir Crit Care Med Date: 2015-09-01 Impact factor: 21.405
Authors: Aleksandra Topic; Marija Stankovic; Aleksandra Divac-Rankov; Natasa Petrovic-Stanojevic; Marija Mitic-Milikic; Ljudmila Nagorni-Obradovic; Dragica Radojkovic Journal: Genet Test Mol Biomarkers Date: 2012-09-12
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: Robert Busch; Brian D Hobbs; Jin Zhou; Peter J Castaldi; Michael J McGeachie; Megan E Hardin; Iwona Hawrylkiewicz; Pawel Sliwinski; Jae-Joon Yim; Woo Jin Kim; Deog K Kim; Alvar Agusti; Barry J Make; James D Crapo; Peter M Calverley; Claudio F Donner; David A Lomas; Emiel F Wouters; Jørgen Vestbo; Ruth Tal-Singer; Per Bakke; Amund Gulsvik; Augusto A Litonjua; David Sparrow; Peter D Paré; Robert D Levy; Stephen I Rennard; Terri H Beaty; John Hokanson; Edwin K Silverman; Michael H Cho Journal: Am J Respir Cell Mol Biol Date: 2017-07 Impact factor: 6.914
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: Victor E Ortega; Xingnan Li; Wanda K O'Neal; Lela Lackey; Elizabeth Ampleford; Gregory A Hawkins; Philip J Grayeski; Alain Laederach; Igor Barjaktarevic; R Graham Barr; Christopher Cooper; David Couper; MeiLan K Han; Richard E Kanner; Eric C Kleerup; Fernando J Martinez; Robert Paine; Stephen P Peters; Cheryl Pirozzi; Stephen I Rennard; Prescott G Woodruff; Eric A Hoffman; Deborah A Meyers; Eugene R Bleecker Journal: Am J Respir Crit Care Med Date: 2020-03-01 Impact factor: 21.405