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1.  Quantitative CT of the Lungs and Airways in Healthy Non-smoking Adults 
Investigative radiology  2012;47(10):596-602.
The purposes of this study are to evaluate the normal range of quantitative CT (QCT) measures of lung attenuation and airway parameters measurements in healthy non-smoking adults and to identify sources of variation in those measures and possible means to adjust for them.
Materials and Methods
Within the COPDGene® study, 92 healthy non-Hispanic White non-smokers [29 male, 63 female, mean age 62.7 (SD 9.0), BMI 28.1 (SD 5.1)] underwent volumetric CT at full inspiration and at the end of a normal expiration. On QCT analysis (Pulmonary Workstation 2, VIDA Diagnostics), inspiratory low attenuation areas were defined as lung tissue with attenuation values ≤ −950 Hounsfield Units (HU) on inspiratory CT (LAAI-950). Expiratory low attenuation areas were defined as lung tissue ≤ −856 HU on expiratory CT (LAAE-856). We used simple linear regression to determine the impact of age and gender on QCT parameters and multiple regression to assess the additional impact of total lung capacity and functional residual capacity measured by CT (TLCCT and FRCCT), scanner type, and mean tracheal air attenuation. Airways were evaluated using measures of airway wall thickness (AWT), inner luminal area (ILA), wall area percent (WA%) and standardized thickness of an airway with inner perimeter of 10mm (Pi10).
Mean %LAAI-950 was 2.0 (SD 2.7), and mean %LAAE-856 was 9.2 (SD 6.8). Mean %LAAI-950 was 3.6 (SD 3.2) % in men, compared with 1.3 (SD 2.0) in women (P<0.001). The %LAAI-950 did not change significantly with age (P=0.08) or BMI (P=0.52). %LAAE-856 did not show any independent relationship with age (P=0.33), gender (P=0.70), or BMI (P=0.32). On multivariate analysis, %LAAI-950 showed a direct relationship to TLCCT (P=0.002) and an inverse relationship to mean tracheal air attenuation (P=0.003), and %LAAE-856 was related to age (P=0.001), FRCCT (P=0.007) and scanner type (P<0.001). Multivariate analysis of segmental airways showed that ILA and WA% were significantly related to TLCCT (P<0.001) and age (0.006). WA% was also associated with gender (P=0.05), axial pixel size (P=0.03) and slice interval (P=0.04). Lastly, AWT is strongly influenced by axial pixel size (P<0.001).
Although the attenuation characteristics of normal lung differ by age and gender, these differences do not persist on multivariate analysis. Potential sources of variation in measurement of attenuation-based quantitative CT parameters include depth of inspiration/expiration, and scanner type. Tracheal air attenuation may partially correct variation due to scanner type. Sources of variation in QCT airway measurements may include age, gender, BMI, depth of inspiration, and spatial resolution.
PMCID: PMC3703944  PMID: 22836310
Quantitative CT; Lungs; Airways; Non-smokers
2.  Demographic, Physiologic and Radiographic Characteristics of COPD Patients Taking Chronic Systemic Corticosteroids 
COPD  2012;9(1):29-35.
Long-term therapy with systemic corticosteroids is not recommended in the treatment of chronic obstructive pulmonary disease (COPD). However, experience demonstrates that some patients receive low dose therapy. Our objective was to describe the demographic, physiologic and radiologic characteristics of COPD patients treated with chronic systemic corticosteroids. We analyzed COPD subjects with GOLD I–IV disease in the COPDGene® study. Subjects were divided into two groups based on whether they reported using chronic oral steroids or not. 1264 subjects were included. 58 (4.5%) reported chronic systemic corticosteroid use. There were no differences in age, race, comorbid conditions (other than asthma), or body mass index between the groups. There was a greater proportion of GOLD III (41% vs. 26%) and IV (41% vs. 13%) subjects in the group using chronic systemic corticosteroids. This group used more respiratory medications, required more oxygen (2.31±0.21 vs. 0.59±0.05 L/min; p<0.0001), and walked less distance (245.4±17.4 vs. 367.2±3.9 meters; p<0.0001). They reported more total (1.7±0.16 vs. 0.62±0.03; p<0.0001) and severe exacerbations per year (0.41±0.05 vs. 0.18 ± 0.01; p<0.0001). BODE (5.0±0.3 vs. 2.6±0.1; p<0.0001), MMRC (3.31±0.19 vs. 1.90±0.04; p<0.0001) and SGRQ scores (54.9±2.9 vs 53.3±0.6; p<0.0001) were higher. They also had a higher percentage of emphysema (22.4±1.9 vs. 14.0±0.4; %, p=<0.0001) on CT scan. COPD patients that report using chronic systemic corticosteroids have more severe clinical, physiologic, and radiographic disease.
PMCID: PMC3764986  PMID: 22292596
Emphysema; Prednisone; Phenotype
COPD  2010;7(4):262-268.
Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes.
We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1) and rs1799895 (R213G)) in a case-control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n=389) and smoking controls from the Normative Aging Study (NAS, n=472). We examined whether the SNPs were associated with COPD status, lung function variables, and quantitative CT measurements of emphysema and airway wall thickness. Further, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n=3061) and the Boston Early-Onset COPD Study (EOCOPD, n=949).
In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p=0.029 and p=0.0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p=0.048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations.
In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies.
PMCID: PMC2923920  PMID: 20673035

Results 1-3 (3)