Citations

Abstract Rationale Computed tomography (CT) scanning of the lung may reduce phenotypic heterogeneity in defining subjects with chronic obstructive pulmonary disease (COPD), and allow identification of genetic determinants of emphysema severity and distribution. Objectives We sought to identify genes associated with CT scan distribution of emphysema in individuals without α1-antitrypsin deficiency but with severe COPD. Methods We evaluated baseline CT densitometry phenotypes in 282 individuals with emphysema enrolled in the Genetics Ancillary Study of the National Emphysema Treatment Trial, and used regression models to identify genetic variants associated with emphysema distribution. Measurements and Main Results Emphysema distribution was assessed by two methods—assessment by radiologists and by computerized density mask quantitation, using a threshold of −950 Hounsfield units. A total of 77 polymorphisms in 20 candidate genes were analyzed for association with distribution of emphysema. GSTP1, EPHX1, and MMP1 polymorphisms were associated with the densitometric, apical-predominant distribution of emphysema (p value range = 0.001–0.050). When an apical-predominant phenotype was defined by the radiologist scoring method, GSTP1 and EPHX1 single-nucleotide polymorphisms were found to be significantly associated. In a case–control analysis of COPD susceptibility limited to cases with densitometric upper-lobe–predominant cases, the EPHX1 His139Arg single-nucleotide polymorphism was associated with COPD (p = 0.005). Conclusions Apical and basal emphysematous destruction appears to be influenced by different genes. Polymorphisms in the xenobiotic enzymes, GSTP1 and EPHX1, are associated with apical-predominant emphysema. Altered detoxification of cigarette smoke metabolites may contribute to emphysema distribution, and these findings may lead to further insight into genetic determinants of emphysema.

Ongoing communication with cancer patients about their treatment preferences is important. A survey assessing treatment preferences was distributed to 100 cancer patients who were newly diagnosed, 100 in remission after therapy, and 60 who had failed therapy/ relapsed; 100 cancer caregivers, and 100 noncancer patients attending the cancer center for benign hematologic problems. Almost 59% of respondents preferred treatment even if the chance of cure was less than 10%. Among subjects who did not have cancer, less than 50% wanted treatment under these circumstances, whereas over 70% of cancer patients who had failed treatment or relapsed wanted treatment ( P = .0994). Multiple logistic regression analysis revealed that the adjusted odds of preferring aggressive treatment were less for those without cancer and those with newly diagnosed cancer than for respondents who had failed treatment or were in relapse. The preference for aggressive cancer treatment is related to medical condition.