significance (SPSS 16 Chicago IL). attrs :”text”:”NCT00047385″ term_id :”NCT00047385″}NCT00047385) and had no radiographic lung diseases other than emphysema. MK-8776 Subjects undergoing lung transplantation for COPD at Washington University Medical Center were consented for sampling of explanted lungs at the time of lung transplantation. Within several hours of surgery an entire explanted lung was inflated over liquid nitrogen vapor (29 30 From this lung multiple 13-mm diameter cores were acquired from 2-cm thick lung slices using a uniform {nonrandom|non-random} sampling method (29 30 Ten cores each randomly chosen from five consecutive subjects were used for alveolar macrophage analysis. Subject demographic data are included in Table 1. All of the subjects at time of transplantation had stopped smoking for at least 6 months and {none|non-e} had evidence of an acute infection. TABLE 1. SUBJECT DEMOGRAPHICS FOR LASER CAPTURE MICRODISSECTION MACROPHAGE ANALYSIS The NLST is an National Cancer Institute–sponsored trial that compares the merits of screening for lung cancer with three annual low-dose chest CT scans as opposed to three annual standard chest radiographs in heavy smokers (subjects between the ages of 55 and 74 at enrollment with at least a 30 pack-year smoking history). At our institution 879 of the subjects who had been randomized to CT scan screening and who required no further follow-up for lung nodules were identified. Automated image analysis (VIDA diagnostics Iowa City IA) was performed on the most recent preexisting CT study for each of these subjects to determine the emphysema index (EI) which was defined as the percentage of total lung with density less than ?950 Hounsfield units (HU). {Members of this cohort were invited to participate in this study which was not part of the NLST.|Members of this cohort were invited to participate in this scholarly MK-8776 study which was not part of the NLST.} Any subject with a known history of solid organ malignancy or inflammatory-immunomodulatory disorder or current oral corticosteroid use was excluded (three subjects: α1-antitrypsin [α1AT] deficiency rheumatoid arthritis and hepatitis C). From this cohort we have enrolled 38 subjects with an EI of greater than 10% into our emphysema biomarker study. {In this report we refer to this group as “emphysema-sensitive” subjects.|In this report we refer to this combined group as “emphysema-sensitive” subjects.} We have also enrolled Rabbit Polyclonal to PLCB3. 47 subjects with an EI less than 5% that we refer to as an “emphysema-resistant” control group. All testing was performed within 3 years of the NLST CT scan. Emphysema-sensitive subjects were predominantly male former smokers with at least moderate airflow MK-8776 obstruction although several did not meet GOLD criteria for COPD (Table 2). The emphysema-resistant cohort was predominantly female (Fisher exact test < 0.0005) and {nonwhite|non-white} (Fisher exact test < 0.001). The emphysema-sensitive cohort included fewer current smokers (Fisher exact test < 0.003). The resistant current smokers were significantly younger than the sensitive former smokers (ANOVA < 0.01 by Tukey test). As expected airflow obstruction as measured by post-bronchodilator FEV1 % predicted MK-8776 was lower in the emphysema-sensitive group compared with resistant former smokers and current smokers (ANOVA < 0.01 by Tukey test). TABLE 2. SUBJECT DEMOGRAPHICS FOR MONOCYTE ANALYSIS Subject Testing All protocols were approved by the human research protection office at Washington University. Permission to recruit and use preexisting CT scans was obtained from the NLST. {None of the testing MK-8776 performed for this study is sponsored by or part of the NLST.|None of the testing performed for this scholarly study is sponsored by or part of the NLST.} All subjects performed pulmonary function tests consisting of spirometry prebronchodilator and post-bronchodilator lung volumes by plethysmography diffusing capacity and a 6-minute walk test according to American Thoracic Society consensus statement guidelines (31) on the same day as blood collection at Washington University. A total of 45 ml of blood was drawn from each subject while in a sitting position and collected in K2EDTA-coated tubes (BD Vacutainer Franklin Lakes NJ). Tubes were inverted gently six times and transported at room temperature to the laboratory immediately after collection. All blood specimens were processed within 2 hours of collection. Additionally six spots of blood were placed on cards for testing for mutations that cause α1AT deficiency. α1AT testing was.