STUDY OBJECTIVES: Alveolar septal cell apoptosis may contribute to the pathogenesis of emphysema. Because tumor necrosis factor (TNF)-alpha is assumed to play an important role in the induction of apoptosis, and allele 2 of the polymorphism at position--308 in the promoter of the TNF-alpha gene has been associated with alteration of TNF-alpha secretion in vitro, we hypothesized that genotypes containing this allele would show more destructive emphysematous changes of the lung. DESIGN: The percentage ratio of the low attenuation area to the corresponding lung area was evaluated using a visual scoring system for CT findings in patients with COPD (n = 84), and these patients were classified into two groups: those with a visual score < 11 and those with a visual score > or = 11. A polymerase chain reaction-based assay was developed to determine the TNF-alpha genotype (TNF-alpha-308*1/2) between subjects with high and low visual scores on chest CT scans. RESULTS: The TNF-alpha-308*1/2 allele frequency tended to differ between patients with a visual score < 11 (0.90/0.10) and those with a visual score > or = 11 (0.81/0.19) [odds ratio, 2.15; 95% confidence interval, 0.87 to 5.30; p = 0.09]. CONCLUSION: These results indicate that the TNF-alpha-308 allele 2 may be partly associated with the extent of emphysematous changes in patients with COPD.
STUDY OBJECTIVES: Alveolar septal cell apoptosis may contribute to the pathogenesis of emphysema. Because tumor necrosis factor (TNF)-alpha is assumed to play an important role in the induction of apoptosis, and allele 2 of the polymorphism at position--308 in the promoter of the TNF-alpha gene has been associated with alteration of TNF-alpha secretion in vitro, we hypothesized that genotypes containing this allele would show more destructive emphysematous changes of the lung. DESIGN: The percentage ratio of the low attenuation area to the corresponding lung area was evaluated using a visual scoring system for CT findings in patients with COPD (n = 84), and these patients were classified into two groups: those with a visual score < 11 and those with a visual score > or = 11. A polymerase chain reaction-based assay was developed to determine the TNF-alpha genotype (TNF-alpha-308*1/2) between subjects with high and low visual scores on chest CT scans. RESULTS: The TNF-alpha-308*1/2 allele frequency tended to differ between patients with a visual score < 11 (0.90/0.10) and those with a visual score > or = 11 (0.81/0.19) [odds ratio, 2.15; 95% confidence interval, 0.87 to 5.30; p = 0.09]. CONCLUSION: These results indicate that the TNF-alpha-308 allele 2 may be partly associated with the extent of emphysematous changes in patients with COPD.
Authors: Lennart K A Lundblad; John Thompson-Figueroa; Timothy Leclair; Michael J Sullivan; Matthew E Poynter; Charles G Irvin; Jason H T Bates Journal: Am J Respir Crit Care Med Date: 2005-04-01 Impact factor: 21.405
Authors: Michael H Cho; George R Washko; Thomas J Hoffmann; Gerard J Criner; Eric A Hoffman; Fernando J Martinez; Nan Laird; John J Reilly; Edwin K Silverman Journal: Respir Res Date: 2010-03-16
Authors: Peter J Castaldi; Raúl San José Estépar; Carlos S Mendoza; Craig P Hersh; Nan Laird; James D Crapo; David A Lynch; Edwin K Silverman; George R Washko Journal: Am J Respir Crit Care Med Date: 2013-11-01 Impact factor: 21.405
Authors: Dawn L DeMeo; Craig P Hersh; Eric A Hoffman; Augusto A Litonjua; Ross Lazarus; David Sparrow; Joshua O Benditt; Gerard Criner; Barry Make; Fernando J Martinez; Paul D Scanlon; Frank C Sciurba; James P Utz; John J Reilly; Edwin K Silverman Journal: Am J Respir Crit Care Med Date: 2007-03-15 Impact factor: 21.405