Gene expression profiling of bronchial brushes is associated with the level of emphysema measured by computed tomography-based parametric response mapping.
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ABSTRACT:
SUBMITTER: Rathnayake SNH
PROVIDER: S-EPMC7938773 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rationale and objectivesChronic obstructive pulmonary disease is a heterogeneous disease characterized by small airway abnormality and emphysema. We hypothesized that a voxel-wise computed tomography analytic approach would identify patterns of disease progression in smokers.Materials and methodsWe analyzed 725 smokers in spirometric GOLD stages 0-4 with two chest CTs 5 years apart. Baseline inspiration, follow-up inspiration and follow-up expiration images were spatially registered to baseline expiration so that each voxel had correspondences across all time points and respiratory phases. Voxel-wise Parametric Response Mapping (PRM) was then generated for the baseline and follow-up scans. PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH).ResultsSubjects with low baseline PRMfSAD and PRMEMPH predominantly had an increase in PRMfSAD on follow-up; those with higher baseline PRMfSAD and PRMEMPH mostly had increases in PRMEMPH. For GOLD 0 participants (n = 419), mean 5-year increases in PRMfSAD and PRMEMPH were 0.3% for both; for GOLD 1-4 participants (n = 306), they were 0.6% and 1.6%, respectively. Eighty GOLD 0 subjects (19.1%) had overall radiologic progression (30.0% to PRMfSAD, 52.5% to PRMEMPH, and 17.5% to both); 153 GOLD 1-4 subjects (50.0%) experienced progression (17.6% to PRMfSAD, 48.4% to PRMEMPH, and 34.0% to both). In a multivariable model, both baseline PRMfSAD and PRMEMPH were associated with development of PRMEMPH on follow-up, although this relationship was diminished at higher levels of baseline PRMEMPH.ConclusionA voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease.
| S-EPMC6340741 | biostudies-literature
Project description:ObjectiveEmphysema and small-airway disease are the two major components of chronic obstructive pulmonary disease (COPD). We propose a novel method of quantitative computed tomography (CT) emphysema air-trapping composite (EAtC) mapping to assess each COPD component. We analyzed the potential use of this method for assessing lung function in patients with COPD.Materials and methodsA total of 584 patients with COPD underwent inspiration and expiration CTs. Using pairwise analysis of inspiration and expiration CTs with non-rigid registration, EAtC mapping classified lung parenchyma into three areas: Normal, functional air trapping (fAT), and emphysema (Emph). We defined fAT as the area with a density change of less than 60 Hounsfield units (HU) between inspiration and expiration CTs among areas with a density less than -856 HU on inspiration CT. The volume fraction of each area was compared with clinical parameters and pulmonary function tests (PFTs). The results were compared with those of parametric response mapping (PRM) analysis.ResultsThe relative volumes of the EAtC classes differed according to the Global Initiative for Chronic Obstructive Lung Disease stages (p < 0.001). Each class showed moderate correlations with forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) (r = -0.659-0.674, p < 0.001). Both fAT and Emph were significant predictors of FEV1 and FEV1/FVC (R² = 0.352 and 0.488, respectively; p < 0.001). fAT was a significant predictor of mean forced expiratory flow between 25% and 75% and residual volume/total vital capacity (R² = 0.264 and 0.233, respectively; p < 0.001), while Emph and age were significant predictors of carbon monoxide diffusing capacity (R² = 0.303; p < 0.001). fAT showed better correlations with PFTs than with small-airway disease on PRM.ConclusionThe proposed quantitative CT EAtC mapping provides comprehensive lung functional information on each disease component of COPD, which may serve as an imaging biomarker of lung function.
| S-EPMC8484152 | biostudies-literature
Project description:Rationale and objectivesChronic obstructive pulmonary disease is a heterogeneous disease characterized by small airway abnormality and emphysema. We hypothesized that a voxel-wise computed tomography analytic approach would identify patterns of disease progression in smokers.Materials and methodsWe analyzed 725 smokers in spirometric GOLD stages 0-4 with two chest CTs 5 years apart. Baseline inspiration, follow-up inspiration and follow-up expiration images were spatially registered to baseline expiration so that each voxel had correspondences across all time points and respiratory phases. Voxel-wise Parametric Response Mapping (PRM) was then generated for the baseline and follow-up scans. PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH).ResultsSubjects with low baseline PRMfSAD and PRMEMPH predominantly had an increase in PRMfSAD on follow-up; those with higher baseline PRMfSAD and PRMEMPH mostly had increases in PRMEMPH. For GOLD 0 participants (n = 419), mean 5-year increases in PRMfSAD and PRMEMPH were 0.3% for both; for GOLD 1-4 participants (n = 306), they were 0.6% and 1.6%, respectively. Eighty GOLD 0 subjects (19.1%) had overall radiologic progression (30.0% to PRMfSAD, 52.5% to PRMEMPH, and 17.5% to both); 153 GOLD 1-4 subjects (50.0%) experienced progression (17.6% to PRMfSAD, 48.4% to PRMEMPH, and 34.0% to both). In a multivariable model, both baseline PRMfSAD and PRMEMPH were associated with development of PRMEMPH on follow-up, although this relationship was diminished at higher levels of baseline PRMEMPH.ConclusionA voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease.
| S-EPMC6704470 | biostudies-literature
Project description:Rationale: Several chronic obstructive pulmonary disease (COPD) studies have evaluated risk factors for emergency department (ED) visits or hospitalizations, and found insufficient data available about social and demographic factors that drive these behaviors. This U.S. study was designed to describe the characteristics of COPD patients with ED visits or a hospitalization and to investigate how often common COPD comorbidities are present in these individuals. Methods: Data for 7180 COPD patients regarding demographic factors, comorbidities, smoking status, and ED visits or hospitalization was obtained from the 2012 Behavioral Risk Factor Surveillance System (BRFSS) survey. Logistic regression analysis was used to adjust demographic factors and smoking status to model the correlation between patients with ED visits or hospitalizations and morbidities generating odds ratios (OR) and confidence intervals (CI). Results: Among diagnosed COPD patients in the BRFSS, 16.5% had ED visits or hospitalization in the previous year. These individuals were younger, had a lower socio-economic status (lower education, lower income, and more often unemployed) and 23.4% of the individuals could not visit a doctor because of the financial difficulties compared to 16.7% who had no visit (p<0.0001 for all comparisons). The prevalence of comorbidities was higher in those with ED visits or hospitalization compared to those without. Conclusion: In a population representative of COPD patients, lower socio-economic status and higher comorbidities are associated with ED visits or hospitalization. Studies are needed to further elucidate the complex relationship between COPD, comorbidities, and ED visits or hospitalization.
| S-EPMC5556763 | biostudies-literature
Project description:BackgroundChronic obstructive pulmonary disease (COPD) poses a substantial global health burden, demanding advanced diagnostic tools for early detection and accurate phenotyping. In this line, this study seeks to enhance COPD characterization on chest computed tomography (CT) by comparing the spatial and quantitative relationships between traditional parametric response mapping (PRM) and a novel self-supervised anomaly detection approach, and to unveil potential additional insights into the dynamic transitional stages of COPD.MethodsNon-contrast inspiratory and expiratory CT of 1,310 never-smoker and GOLD 0 individuals and COPD patients (GOLD 1-4) from the COPDGene dataset were retrospectively evaluated. A novel self-supervised anomaly detection approach was applied to quantify lung abnormalities associated with COPD, as regional deviations. These regional anomaly scores were qualitatively and quantitatively compared, per GOLD class, to PRM volumes (emphysema: PRMEmph, functional small-airway disease: PRMfSAD) and to a Principal Component Analysis (PCA) and Clustering, applied on the self-supervised latent space. Its relationships to pulmonary function tests (PFTs) were also evaluated.ResultsInitial t-Distributed Stochastic Neighbor Embedding (t-SNE) visualization of the self-supervised latent space highlighted distinct spatial patterns, revealing clear separations between regions with and without emphysema and air trapping. Four stable clusters were identified among this latent space by the PCA and Cluster Analysis. As the GOLD stage increased, PRMEmph, PRMfSAD, anomaly score, and Cluster 3 volumes exhibited escalating trends, contrasting with a decline in Cluster 2. The patient-wise anomaly scores significantly differed across GOLD stages (p < 0.01), except for never-smokers and GOLD 0 patients. In contrast, PRMEmph, PRMfSAD, and cluster classes showed fewer significant differences. Pearson correlation coefficients revealed moderate anomaly score correlations to PFTs (0.41-0.68), except for the functional residual capacity and smoking duration. The anomaly score was correlated with PRMEmph (r = 0.66, p < 0.01) and PRMfSAD (r = 0.61, p < 0.01). Anomaly scores significantly improved fitting of PRM-adjusted multivariate models for predicting clinical parameters (p < 0.001). Bland-Altman plots revealed that volume agreement between PRM-derived volumes and clusters was not constant across the range of measurements.ConclusionOur study highlights the synergistic utility of the anomaly detection approach and traditional PRM in capturing the nuanced heterogeneity of COPD. The observed disparities in spatial patterns, cluster dynamics, and correlations with PFTs underscore the distinct - yet complementary - strengths of these methods. Integrating anomaly detection and PRM offers a promising avenue for understanding of COPD pathophysiology, potentially informing more tailored diagnostic and intervention approaches to improve patient outcomes.
| S-EPMC10941845 | biostudies-literature
Project description:BackgroundFactors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult cigarette smokers.MethodsRib cage diameters and areas (calculated from the inner surface of the rib cage) in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT). CTs were analyzed with software, which allows quantification of total emphysema (emphysema%). The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models.ResultsA model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1)%, and forced vital capacity (FVC)% fit best with the rib cage measurements (R(2)?=?64% for the rib cage area variation at the lower anatomical level). Gender had the biggest impact on rib cage diameter and area (105.3 cm(2); 95% CI: 111.7 to 98.8 for male lower area). Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm(2); 95% CI: 3.0 to 7.8 for an emphysema increase of 5%). Lower rib cage areas decreased as FVC% decreased (5.1 cm(2); 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation).ConclusionsThis study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema.
| S-EPMC3729561 | biostudies-literature
Project description:BACKGROUND:Pulmonary emphysema is divided into 3 major subtypes at autopsy: centrilobular, paraseptal, and panlobular emphysema. These subtypes can be defined by visual assessment on computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics. METHODS:The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with chronic obstructive pulmonary disease (COPD) and controls ages 50-79 years with ? 10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal, and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines. RESULTS:Twenty-seven percent of 318 smokers had emphysema on CT. Interrater reliability of emphysema subtype was substantial (K: 0.70). Compared with participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with paraseptal emphysema were similar to controls, except for male predominance. Centrilobular, but not panlobular or paraseptal, emphysema was associated with greater smoking history (+21 pack-years P <.001). Panlobular, but not other types of emphysema, was associated with reduced body mass index (-5 kg/m(2); P = .01). Other than for dyspnea, these findings were independent of the forced expiratory volume in 1 second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance. CONCLUSIONS:Emphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema, but not paraseptal emphysema, have considerable symptomatic and physiological consequences.
| S-EPMC3882898 | biostudies-literature
Project description:Emphysema is visible on computed tomography (CT) as low-density lesions representing the destruction of the pulmonary alveoli. To train a machine learning model on the emphysema extent in CT images, labeled image data is needed. The provision of these labels requires trained readers, who are a limited resource. The purpose of the study was to test the reading time, inter-observer reliability and validity of the multi-reader-multi-split method for acquiring CT image labels from radiologists. The approximately 500 slices of each stack of lung CT images were split into 1-cm chunks, with 17 thin axial slices per chunk. The chunks were randomly distributed to 26 readers, radiologists and radiology residents. Each chunk was given a quick score concerning emphysema type and severity in the left and right lung separately. A cohort of 102 subjects, with varying degrees of visible emphysema in the lung CT images, was selected from the SCAPIS pilot, performed in 2012 in Gothenburg, Sweden. In total, the readers created 9050 labels for 2881 chunks. Image labels were compared with regional annotations already provided at the SCAPIS pilot inclusion. The median reading time per chunk was 15 s. The inter-observer Krippendorff's alpha was 0.40 and 0.53 for emphysema type and score, respectively, and higher in the apical part than in the basal part of the lungs. The multi-split emphysema scores were generally consistent with regional annotations. In conclusion, the multi-reader-multi-split method provided reasonably valid image labels, with an estimation of the inter-observer reliability.
| S-EPMC7572947 | biostudies-literature
Project description:In the search for specific phenotypes of chronic obstructive pulmonary disease (COPD) computed tomography (CT) derived Parametric Response Mapping (PRM) has been introduced. This study evaluates the association between PRM and currently available biomarkers of disease severity in COPD.Smokers with and without COPD were characterized based on questionnaires, pulmonary function tests, body plethysmography, and low-dose chest CT scanning. PRM was used to calculate the amount of emphysema (PRMEmph) and non-emphysematous air trapping (i.e. functional small airway disease, PRMfSAD). PRM was first compared with other biomarkers for emphysema (Perc15) and air trapping (E/I-ratioMLD). Consequently, linear regression models were utilized to study associations of PRM measurements with clinical parameters.166 participants were included with a mean ± SD age of 50.5 ± 17.7 years. Both PRMEmph and PRMfSAD were more strongly correlated with lung function parameters as compared to Perc15 and E/I-ratioMLD. PRMEmph and PRMfSAD were higher in COPD participants than non-COPD participants (14.0% vs. 1.1%, and 31.6% vs. 8.2%, respectively, both p < 0.001) and increased with increasing GOLD stage (all p < 0.001). Multivariate analysis showed that PRMfSAD was mainly associated with total lung capacity (TLC) (? = -7.90, p < 0.001), alveolar volume (VA) (? = 7.79, p < 0.001), and residual volume (? = 6.78, p < 0.001), whilst PRMEmph was primarily associated with Kco (? = 8.95, p < 0.001), VA (? = -6.21, p < 0.001), and TLC (? = 6.20, p < 0.001).PRM strongly associates with the presence and severity of COPD. PRM therefore appears to be a valuable tool in differentiating COPD phenotypes.
| S-EPMC5555031 | biostudies-literature
Project description:Alzheimer's disease (AD), the most common cause of dementia, has limited treatment options. Emerging disease modifying therapies are targeted at clearing amyloid-β (Aβ) aggregates and slowing the rate of amyloid deposition. However, amyloid burden is not routinely evaluated quantitatively for purposes of disease progression and treatment response assessment. Statistical Parametric Mapping (SPM) is a technique comparing single-subject Positron Emission Tomography (PET) to a healthy cohort that may improve quantification of amyloid burden and diagnostic performance. While primarily used in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-PET, SPM's utility in amyloid PET for AD diagnosis is less established and uncertainty remains regarding optimal normal database construction. Using commercially available SPM software, we created a database of 34 non-APOE ε4 carriers with normal cognitive testing (MMSE > 25) and negative cerebrospinal fluid (CSF) AD biomarkers. We compared this database to 115 cognitively normal subjects with variable AD risk factors. We hypothesized that SPM based on our database would identify more positive scans in the test cohort than the qualitatively rated [11C]-PiB PET (QR-PiB), that SPM-based interpretation would correlate better with CSF Aβ42 levels than QR-PiB, and that regional z-scores of specific brain regions known to be involved early in AD would be predictive of CSF Aβ42 levels. Fisher's exact test and the kappa coefficient assessed the agreement between SPM, QR-PiB PET, and CSF biomarkers. Logistic regression determined if the regional z-scores predicted CSF Aβ42 levels. An optimal z-score cutoff was calculated using Youden's index. We found SPM identified more positive scans than QR-PiB PET (19.1 vs. 9.6%) and that SPM correlated more closely with CSF Aβ42 levels than QR-PiB PET (kappa 0.13 vs. 0.06) indicating that SPM may have higher sensitivity than standard QR-PiB PET images. Regional analysis demonstrated the z-scores of the precuneus, anterior cingulate and posterior cingulate were predictive of CSF Aβ42 levels [OR (95% CI) 2.4 (1.1, 5.1) p = 0.024; 1.8 (1.1, 2.8) p = 0.020; 1.6 (1.1, 2.5) p = 0.026]. This study demonstrates the utility of using SPM with a "true normal" database and suggests that SPM enhances diagnostic performance in AD in the clinical setting through its quantitative approach, which will be increasingly important with future disease-modifying therapies.
| S-EPMC9083453 | biostudies-literature