56 research outputs found
Differences in Respiratory Symptoms and Lung Structure Between Hispanic and Non-Hispanic White Smokers: A Comparative Study
Background: Prior studies have demonstrated that U.S. Hispanic
smokers have a lower risk of decline in lung function and
chronic obstructive pulmonary disease (COPD) compared with
non-Hispanic whites (NHW). This suggests there might be
racial-ethnic differences in susceptibility in cigarette
smoke-induced respiratory symptoms, lung parenchymal
destruction, and airway and vascular disease, as well as in
extra-pulmonary manifestations of COPD. Therefore, we aimed to
explore respiratory symptoms, lung function, and pulmonary and
extra-pulmonary structural changes in Hispanic and NHW smokers.
Methods: We compared respiratory symptoms, lung function, and
computed tomography (CT) measures of emphysema-like tissue,
airway disease, the branching generation number (BGN) to reach a
2-mm-lumen-diameter airway, and vascular pruning as well as
muscle and fat mass between 39 Hispanic and 39 sex-, age- and
smoking exposure-matched NHW smokers. Results: Hispanic smokers
had higher odds of dyspnea than NHW after adjustment for COPD
and asthma statuses (odds ratio[OR] = 2.96; 95% confidence
interval [CI] 1.09-8.04), but no significant differences were
found in lung function and CT measurements. Conclusions: While
lung function and CT measures of the lung structure were
similar, dyspnea is reported more frequently by Hispanic than
matched-NHW smokers. It seems to be an impossible puzzle but
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Comparison of Single-Shot Echo-Planar and Line Scan Protocols for Diffusion Tensor Imaging
Rationale and Objectives: Both single-shot diffusion-weighted echo-planar imaging (EPI) and line scan diffusion imaging (LSDI) can be used to obtain magnetic resonance diffusion tensor data and to calculate directionally invariant diffusion anisotropy indices, ie, indirect measures of the organization and coherence of white matter fibers in the brain. To date, there has been no comparison of EPI and LSDI. Because EPI is the most commonly used technique for acquiring diffusion tensor data, it is important to understand the limitations and advantages of LSDI relative to EPI. Materials and Methods: Five healthy volunteers underwent EPI and LSDI diffusion on a 1.5 Tesla magnet (General Electric Medical Systems, Milwaukee, WI). Four-mm thick coronal sections, covering the entire brain, were obtained. In addition, one subject was tested with both sequences over four sessions. For each image voxel, eigenvectors and eigenvalues of the diffusion tensor were calculated, and fractional anisotropy (FA) was derived. Several regions of interest were delineated, and for each, mean FA and estimated mean standard deviation were calculated and compared. Results: Results showed no significant differences between EPI and LSDI for mean FA for the five subjects. When inter-session reproducibility for one subject was evaluated, there was a significant difference between EPI and LSDI in FA for the corpus callosum and the right uncinate fasciculus. Moreover, errors associated with each FA measure were larger for EPI than for LSDI. Conclusion: Results indicate that both EPI- and LSDI-derived FA measures are sufficiently robust. However, when higher accuracy is needed, LSDI provides smaller error and smaller inter-subject and inter-session variability than EPI
COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease
Background:Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality.
Methods:Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined.
Results:Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics.
Conclusions:A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop
Clinical, physiologic, and radiographic factors contributing to development of hypoxemia in moderate to severe COPD:a cohort study
Background: Hypoxemia is a major complication of COPD and is a strong predictor of mortality. We previously identified independent risk factors for the presence of resting hypoxemia in the COPDGene cohort. However, little is known about characteristics that predict onset of resting hypoxemia in patients who are normoxic at baseline. We hypothesized that a combination of clinical, physiologic, and radiographic characteristics would predict development of resting hypoxemia after 5-years of follow-up in participants with moderate to severe COPD Methods: We analyzed 678 participants with moderate-to-severe COPD recruited into the COPDGene cohort who completed baseline and 5-year follow-up visits and who were normoxic by pulse oximetry at baseline. Development of resting hypoxemia was defined as an oxygen saturation ≤88% on ambient air at rest during follow-up. Demographic and clinical characteristics, lung function, and radiographic indices were analyzed with logistic regression models to identify predictors of the development of hypoxemia. Results: Forty-six participants (7%) developed resting hypoxemia at follow-up. Enrollment at Denver (OR 8.30, 95%CI 3.05–22.6), lower baseline oxygen saturation (OR 0.70, 95%CI 0.58–0.85), self-reported heart failure (OR 6.92, 95%CI 1.56–30.6), pulmonary artery (PA) enlargement on computed tomography (OR 2.81, 95%CI 1.17–6.74), and prior severe COPD exacerbation (OR 3.31, 95%CI 1.38–7.90) were independently associated with development of resting hypoxemia. Participants who developed hypoxemia had greater decline in 6-min walk distance and greater 5-year decline in quality of life compared to those who remained normoxic at follow-up. Conclusions: Development of clinically significant hypoxemia over a 5-year span is associated with comorbid heart failure, PA enlargement and severe COPD exacerbation. Further studies are needed to determine if treatments targeting these factors can prevent new onset hypoxemia. Trial registration COPDGene is registered at ClinicalTrials.gov: NCT00608764 (Registration Date: January 28, 2008) Electronic supplementary material The online version of this article (doi:10.1186/s12890-016-0331-0) contains supplementary material, which is available to authorized users
Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD
Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group
Non-emphysematous chronic obstructive pulmonary disease is associated with diabetes mellitus
Background: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients. Methods: Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis. Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%. Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%). Results: Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized. Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St. George's Respiratory Questionnaire score 43 vs 31, p < 0.0001). Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use. The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study. Conclusions: Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes. COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa
Physicochemical and microbiological evaluation of corrientes artisanal cheese during ripening
Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline:Five-Year Follow-up in Adult Smokers From the COPDGene Study
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Diffusion tractography of the fornix in schizophrenia
Background: White matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in pathophysiology of schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from the hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provides a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix diffusion anisotropy in schizophrenia. Methods: DTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age, parental socioeconomic status, and handedness. Regions of interest were drawn manually, blind to group membership, to guide tractography, and Fractional Anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. The Doors and People test (DPT) was used to evaluate visual and verbal memory, combined recall and combined recognition. Results: Analysis of variance was performed and findings demonstrated a difference between patients with schizophrenia and controls for fornix FA (P=0.006). Protected post-hoc independent sample t-tests demonstrated a bilateral FA decrease in schizophrenia, compared with control subjects (left side: P=0.048; right side P=0.006). Higher fornix FA was statistically significantly correlated with DPT and measures of combined visual memory (r=.554, p=.026), combined verbal memory (r=.647, p=.007), combined recall (r=.516, p=.041), and combined recognition (r=.710, p=.002) for the control group. No such statistically significant correlations were found in the patient group. Conclusions: Our findings show the utility of applying DTI and tractography to study white matter fiber tracts in vivo in schizophrenia. Specifically, we observed a bilateral disruption in fornix integrity in schizophrenia, thus broadening our understanding of the pathophysiology of this disease
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