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1.  Relationships Between Airflow Obstruction and Quantitative CT Measurements of Emphysema, Air Trapping, and Airways in Subjects With and Without Chronic Obstructive Pulmonary Disease 
AJR. American journal of roentgenology  2013;201(3):W460-W470.
OBJECTIVE
This study evaluates the relationships between quantitative CT (QCT) and spirometric measurements of disease severity in cigarette smokers with and without chronic obstructive pulmonary disease (COPD).
MATERIALS AND METHODS
Inspiratory and expiratory CT scans of 4062 subjects in the Genetic Epidemiology of COPD (COPDGene) Study were evaluated. Measures examined included emphysema, defined as the percentage of low-attenuation areas ≤ −950 HU on inspiratory CT, which we refer to as “LAA-950I”; air trapping, defined as the percentage of low-attenuation areas ≤ −856 HU on expiratory CT, which we refer to as “LAA-856E”; and the inner diameter, inner and outer areas, wall area, airway wall thickness, and square root of the wall area of a hypothetical airway of 10-mm internal perimeter of segmental and subsegmental airways. Correlations were determined between spirometry and several QCT measures using statistics software (SAS, version 9.2).
RESULTS
QCT measurements of low-attenuation areas correlate strongly and significantly (p < 0.0001) with spirometry. The correlation between LAA-856E and forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) (r = −0.77 and −0.84, respectively) is stronger than the correlation between LAA-950I and FEV1 and FEV1/FVC (r = −0.67 and r = −0.76). Inspiratory and expiratory volume changes decreased with increasing disease severity, as measured by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) staging system (p < 0.0001). When airway variables were included with low-attenuation area measures in a multiple regression model, the model accounted for a statistically greater proportion of variation in FEV1 and FEV1/FVC (R2 = 0.72 and 0.77, respectively). Airway measurements alone are less correlated with spirometric measures of FEV1 (r = 0.15 to −0.44) and FEV1/FVC (r = 0.19 to −0.34).
CONCLUSION
QCT measurements are strongly associated with spirometric results showing impairment in smokers. LAA-856E strongly correlates with physiologic measurements of airway obstruction. Airway measurements can be used concurrently with QCT measures of low-attenuation areas to accurately predict lung function.
doi:10.2214/AJR.12.10102
PMCID: PMC4067052  PMID: 23971478
air trapping; airway measurements; chronic obstructive pulmonary disease; emphysema; quantitative CT
2.  Gender Differences of Airway Dimensions in Anatomically Matched Sites on CT in Smokers 
COPD  2011;8(4):285-292.
Rationale and Objectives
There are limited data on, and controversies regarding gender differences in the airway dimensions of smokers. Multi-detector CT (MDCT) images were analyzed to examine whether gender could explain differences in airway dimensions of anatomically matched airways in smokers.
Materials and Methods
We used VIDA imaging software to analyze MDCT scans from 2047 smokers (M:F, 1021:1026) from the COPDGene® cohort. The airway dimensions were analyzed from segmental to subsubsegmental bronchi. We compared the differences of luminal area, inner diameter, wall thickness, wall area percentage (WA%) for each airway between men and women, and multiple linear regression including covariates (age, gender, body sizes, and other relevant confounding factors) was used to determine the predictors of each airway dimensions.
Results
Lumen area, internal diameter and wall thickness were smaller for women than men in all measured airway (18.4 vs 22.5 mm2 for segmental bronchial lumen area, 10.4 vs 12.5 mm2 for subsegmental bronchi, 6.5 vs 7.7 mm2 for subsubsegmental bronchi, respectively p < 0.001). However, women had greater WA% in subsegmental and subsubsegmental bronchi. In multivariate regression, gender remained one of the most significant predictors of WA%, lumen area, inner diameter and wall thickness.
Conclusion
Women smokers have higher WA%, but lower luminal area, internal diameter and airway thickness in anatomically matched airways as measured by CT scan than do male smokers. This difference may explain, in part, gender differences in the prevalence of COPD and airflow limitation.
doi:10.3109/15412555.2011.586658
PMCID: PMC3703311  PMID: 21756032
Airway dimensions; CT scan; Gender differences; Smoker
3.  Automated Telecommunication to Obtain Longitudinal Follow-up in a Multicenter Cross-sectional COPD Study 
COPD  2012;9(5):466-472.
Background
It can be challenging to maintain longitudinal follow-up of subjects in clinical studies. COPDGene is a multicenter, observational study designed to identify genetic factors associated with COPD and to characterize COPD-related phenotypes. To obtain follow-up data on patient's vital status and outcomes, the COPDGene Longitudinal Follow-up (LFU) Program was developed to supplement its parent study.
Methods/Results
We used a telecommunication system that employed automated telephone contact or web-based questions to obtain longitudinal follow-up data in our subjects. A branching questionnaire asked about exacerbations, new therapies, smoking status, development of co-morbid conditions, and general health status. Study coordinators contacted subjects who did not respond to one of the automated methods. We enrolled 10,383 subjects in the COPDGene study. As of August 29, 2011, 7,959 subjects completed 19,955 surveys. On the first survey, 68.8% of subjects who completed their survey did so by electronic means, while 31.3% required coordinator phone follow-up. On each subsequent survey the number of subjects who completed their survey by electronic means increased, while the number of subjects who required coordinator follow-up decreased. Despite many of the patients in the cohort being chronically ill and elderly, there was broad acceptance of the system with over half the cohort using electronic response methods.
Conclusions
The COPDGene LFU Study demonstrated that telecommunications was an effective way to obtain longitudinal follow-up of subjects in a large multicenter study. Web-based and automated phone contacts are accepted by research subjects and could serve as a model for LFU in future studies.
doi:10.3109/15412555.2012.690010
PMCID: PMC3698488  PMID: 22676387
COPD; COPDGene; Emphysema; Longitudinal data collection; Exacerbations; Follow-up studies; Elderly
4.  Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia 
Journal of Hematopathology  2009;2(1):27-33.
Although KIT mutations are present in 20–25% of cases of t(8;21)(q22;q22) acute myeloid leukemia (AML), concurrent development of systemic mastocytosis (SM) is exceedingly rare. We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM. In the majority of these cases, a definitive diagnosis of SM was made after chemotherapy, when the mast cell infiltrates were prominent. Deletion 9q was an additional cytogenetic abnormality in four cases. Four of the ten patients failed to achieve remission after standard chemotherapy and seven of the ten patients have died of AML. In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission. SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications.
doi:10.1007/s12308-009-0023-2
PMCID: PMC2713498  PMID: 19669220
Systemic mastocytosis; Acute myeloid leukemia; KIT mutations; Pathogenesis; Translocation (8;21); Prognosis

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