Publications

2022
Thatipelli S, Kershaw KN, Colangelo LA, Gordon-Larsen P, Jacobs DR, Dransfield MT, Meza D, Rosenberg SR, Washko GR, Parekh TM, Carnethon MR, Kalhan R. Neighborhood Socioeconomic Deprivation in Young Adulthood and Future Respiratory Health: The CARDIA Lung Study. Am J Med 2022;135(2):211-218.e1.Abstract
PURPOSE: There are limited data on the relationship between neighborhood level factors and their association with lung health independent of individual socioeconomic status. We sought to determine whether baseline neighborhood level socioeconomic deprivation in young adults is associated with greater 20-year decline in lung function and higher risk of future lung disease, independent of baseline individual income, education, and smoking status. METHODS: This multicenter population-based cohort study included 2689 participants in Coronary Artery Risk Development in Young Adults (CARDIA) for whom neighborhood deprivation was determined at year 10 (baseline for study) and who had complete lung function measurements at years 10 and 30. Baseline neighborhood deprivation was defined using 1990 Census blocks as a combination of 4 factors involving median household income, poverty level, and educational achievement. The outcomes were decline in lung function over 20 years (year 10 to 30) and odds of emphysema (year 25). RESULTS: In multivariable regression models, greater baseline neighborhood deprivation was associated with greater decline in lung function (-2.34 mL/year excess annual decline in forced expiratory volume in 1 second (FEV1) in the highest versus lowest deprivation quartile (P = .014)). Furthermore, baseline neighborhood deprivation was independently associated with greater odds of emphysema (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.42-6.30). CONCLUSIONS: Residence in neighborhoods with greater socioeconomic deprivation in young adulthood, independent of individual income and smoking, is associated with greater 20-year decline in forced expiratory volume in 1 second and higher risk of future emphysema.
Trivedi AP, Hall C, Goss CW, Lew D, Krings JG, McGregor MC, Samant M, Sieren JP, Li H, Schechtman KB, Schirm J, McEleney S, Peterson S, Moore WC, Bleecker ER, Meyers DA, Israel E, Washko GR, Levy BD, Leader JK, Wenzel SE, Fahy JV, Schiebler ML, Fain SB, Jarjour NN, Mauger DT, Reinhardt JM, Newell JD, Hoffman EA, Castro M, Sheshadri A. Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts. Radiology 2022;304(2):450-459.Abstract
Background Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes. Purpose To determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes. Materials and Methods A retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models. Results A total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P < .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P < .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P < .001). Conclusion Quantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.
Sanders JL, Axelsson G, Putman R, Menon A, Dupuis J, Xu H, Wang S, Murabito J, Vasan R, Araki T, Nishino M, Washko GR, Hatabu H, O'Connor G, Gudmundsson G, Gudnason V, Hunninghake GM. The relationship between interstitial lung abnormalities, mortality, and multimorbidity: a cohort study. Thorax 2022;Abstract
BACKGROUND: Interstitial lung abnormalities (ILAs) are associated with increased mortality. It is unclear whether multimorbidity accounts for the mortality association or how strongly ILA is associated with mortality relative to other common age-associated diseases. We determined the association of ILA with all-cause mortality adjusted for multimorbidity, compared mortality associated with ILA and prevalent cardiovascular disease (CVD), diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease and cancer and also determined the association between ILA and these diseases. METHODS: We measured ILA (none, indeterminant, definite) using blinded reads of CT images, prevalent chronic diseases and potential confounders in two observational cohorts, the Framingham Heart Study (FHS) (n=2449) and Age, Gene/Environment Susceptibility - Reykjavik Study (AGES-Reykjavik) (n=5180). We determined associations with mortality using Cox proportional hazards models and between ILA and diseases with multinomial logistic regression. RESULTS: Over a median (IQR) follow-up of 8.8 (1.4) years in FHS and 12.0 (7.7) years in AGES-Reykjavik, in adjusted models, ILAs were significantly associated with increased mortality (HR, 95% CI 1.95, 1.23 to 3.08, p=0.0042, in FHS; HR 1.60, 1.41 to 1.82, p<0.0001, in AGES-Reykjavik) adjusted for multimorbidity. In both cohorts, the association of ILA with mortality was of similar magnitude to the association of most other diseases. In adjusted models, ILAs were associated only with prevalent kidney disease (OR, 95% CI 1.90, 1.01 to 3.57, p=0.0452) in FHS and with prevalent CVD (OR 1.42, 1.12 to 1.81, p=0.0040) in AGES-Reykjavik. CONCLUSIONS: ILAs were associated with mortality adjusted for multimorbidity and were similarly associated with increased mortality compared with several common chronic diseases. ILAs were not consistently associated with the prevalence of these diseases themselves.
Stolz D, Mkorombindo T, Schumann DM, Agusti A, Ash SY, Bafadhel M, Bai C, Chalmers JD, Criner GJ, Dharmage SC, Franssen FME, Frey U, Han ML, Hansel NN, Hawkins NM, Kalhan R, Konigshoff M, Ko FW, Parekh TM, Powell P, Rutten-van Mölken M, Simpson J, Sin DD, Song Y, Suki B, Troosters T, Washko GR, Welte T, Dransfield MT. Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission. Lancet 2022;400(10356):921-972.
San José Estépar R. Artificial intelligence in functional imaging of the lung. Br J Radiol 2022;95(1132):20210527.Abstract
Artificial intelligence (AI) is transforming the way we perform advanced imaging. From high-resolution image reconstruction to predicting functional response from clinically acquired data, AI is promising to revolutionize clinical evaluation of lung performance, pushing the boundary in pulmonary functional imaging for patients suffering from respiratory conditions. In this review, we overview the current developments and expound on some of the encouraging new frontiers. We focus on the recent advances in machine learning and deep learning that enable reconstructing images, quantitating, and predicting functional responses of the lung. Finally, we shed light on the potential opportunities and challenges ahead in adopting AI for functional lung imaging in clinical settings.
McNeill J, Chernofsky A, Nayor M, Rahaghi FN, Estepar RSJ, Washko G, Synn A, Vasan RS, O'Connor G, Larson MG, Ho JE, Lewis GD. The association of lung function and pulmonary vasculature volume with cardiorespiratory fitness in the community. Eur Respir J 2022;60(2)Abstract
BACKGROUND: Cardiorespiratory fitness is not limited by pulmonary mechanical reasons in the majority of adults. However, the degree to which lung function contributes to exercise response patterns among ostensibly healthy individuals remains unclear. METHODS: We examined 2314 Framingham Heart Study participants who underwent cardiopulmonary exercise testing (CPET) and pulmonary function testing. We investigated the association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and diffusing capacity of the lung for carbon monoxide (D LCO) with the primary outcome of peak oxygen uptake (V'O2 ) along with other CPET parameters using multivariable linear regression. Finally, we investigated the association of total and peripheral pulmonary blood vessel volume with peak V'O2 . RESULTS: We found lower FEV1, FVC and D LCO were associated with lower peak V'O2 . For example, a 1 L lower FEV1 and FVC was associated with a 7.1% (95% CI 5.1-9.1%) and 6.0% (95% CI 4.3-7.7%) lower peak V'O2 , respectively. By contrast, FEV1/FVC was not associated with peak V'O2 . Lower lung function was associated with lower oxygen uptake efficiency slope, oxygen pulse slope, V'O2 at anaerobic threshold (AT), minute ventilation (V'E) at AT and breathing reserve. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peak V'O2 . CONCLUSIONS: In a large, community-based cohort of adults, we found lower FEV1, FVC and D LCO were associated with lower exercise capacity, as well as oxygen uptake efficiency slope and ventilatory efficiency. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peak V'O2 . These findings underscore the importance of lung function and blood vessel volume as contributors to overall exercise capacity.
Bermejo-Peláez D, San José Estépar R, Fernández-Velilla M, Palacios Miras C, Gallardo Madueño G, Benegas M, Gotera Rivera C, Cuerpo S, Luengo-Oroz M, Sellarés J, Sánchez M, Bastarrika G, Peces Barba G, Seijo LM, Ledesma-Carbayo MJ. Deep learning-based lesion subtyping and prediction of clinical outcomes in COVID-19 pneumonia using chest CT. Sci Rep 2022;12(1):9387.Abstract
The main objective of this work is to develop and evaluate an artificial intelligence system based on deep learning capable of automatically identifying, quantifying, and characterizing COVID-19 pneumonia patterns in order to assess disease severity and predict clinical outcomes, and to compare the prediction performance with respect to human reader severity assessment and whole lung radiomics. We propose a deep learning based scheme to automatically segment the different lesion subtypes in nonenhanced CT scans. The automatic lesion quantification was used to predict clinical outcomes. The proposed technique has been independently tested in a multicentric cohort of 103 patients, retrospectively collected between March and July of 2020. Segmentation of lesion subtypes was evaluated using both overlapping (Dice) and distance-based (Hausdorff and average surface) metrics, while the proposed system to predict clinically relevant outcomes was assessed using the area under the curve (AUC). Additionally, other metrics including sensitivity, specificity, positive predictive value and negative predictive value were estimated. 95% confidence intervals were properly calculated. The agreement between the automatic estimate of parenchymal damage (%) and the radiologists' severity scoring was strong, with a Spearman correlation coefficient (R) of 0.83. The automatic quantification of lesion subtypes was able to predict patient mortality, admission to the Intensive Care Units (ICU) and need for mechanical ventilation with an AUC of 0.87, 0.73 and 0.68 respectively. The proposed artificial intelligence system enabled a better prediction of those clinically relevant outcomes when compared to the radiologists' interpretation and to whole lung radiomics. In conclusion, deep learning lesion subtyping in COVID-19 pneumonia from noncontrast chest CT enables quantitative assessment of disease severity and better prediction of clinical outcomes with respect to whole lung radiomics or radiologists' severity score.
Wilson AC, Bon JM, Mason S, Diaz AA, Lutz SM, Estepar RSJ, Kinney GL, Hokanson JE, Rennard SI, Casaburi R, Bhatt SP, Irvin MR, Hersh CP, Dransfield MT, Washko GR, Regan EA, McDonald M-L. Increased chest CT derived bone and muscle measures capture markers of improved morbidity and mortality in COPD. Respir Res 2022;23(1):311.Abstract
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging and is associated with comorbid conditions including osteoporosis and sarcopenia. These extrapulmonary conditions are highly prevalent yet frequently underdiagnosed and overlooked by pulmonologists in COPD treatment and management. There is evidence supporting a role for bone-muscle crosstalk which may compound osteoporosis and sarcopenia risk in COPD. Chest CT is commonly utilized in COPD management, and we evaluated its utility to identify low bone mineral density (BMD) and reduced pectoralis muscle area (PMA) as surrogates for osteoporosis and sarcopenia. We then tested whether BMD and PMA were associated with morbidity and mortality in COPD. METHODS: BMD and PMA were analyzed from chest CT scans of 8468 COPDGene participants with COPD and controls (smoking and non-smoking). Multivariable regression models tested the relationship of BMD and PMA with measures of function (6-min walk distance (6MWD), handgrip strength) and disease severity (percent emphysema and lung function). Multivariable Cox proportional hazards models were used to evaluate the relationship between sex-specific quartiles of BMD and/or PMA derived from non-smoking controls with all-cause mortality. RESULTS: COPD subjects had significantly lower BMD and PMA compared with controls. Higher BMD and PMA were associated with increased physical function and less disease severity. Participants with the highest BMD and PMA quartiles had a significantly reduced mortality risk (36% and 46%) compared to the lowest quartiles. CONCLUSIONS: These findings highlight the potential for CT-derived BMD and PMA to characterize osteoporosis and sarcopenia using equipment available in the pulmonary setting.
Putman RK, Axelsson GT, Ash SY, Sanders JL, Menon AA, Araki T, Nishino M, Yanagawa M, Gudmundsson EF, Qiao D, San José Estépar R, Dupuis J, O'Connor GT, Rosas IO, Washko GR, El-Chemaly S, Raby BA, Gudnason V, DeMeo DL, Silverman EK, Hatabu H, De Vivo I, Cho MH, Gudmundsson G, Hunninghake GM. Interstitial lung abnormalities are associated with decreased mean telomere length. Eur Respir J 2022;60(2)Abstract
BACKGROUND: Interstitial lung abnormalities (ILA) share many features with idiopathic pulmonary fibrosis; however, it is not known if ILA are associated with decreased mean telomere length (MTL). METHODS: Telomere length was measured with quantitative PCR in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) and Age Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) cohorts and Southern blot analysis was used in the Framingham Heart Study (FHS). Logistic and linear regression were used to assess the association between ILA and MTL; Cox proportional hazards models were used to assess the association between MTL and mortality. RESULTS: In all three cohorts, ILA were associated with decreased MTL. In the COPDGene and AGES-Reykjavik cohorts, after adjustment there was greater than twofold increase in the odds of ILA when comparing the shortest quartile of telomere length to the longest quartile (OR 2.2, 95% CI 1.5-3.4, p=0.0001, and OR 2.6, 95% CI 1.4-4.9, p=0.003, respectively). In the FHS, those with ILA had shorter telomeres than those without ILA (-767 bp, 95% CI 76-1584 bp, p=0.03). Although decreased MTL was associated with chronic obstructive pulmonary disease (OR 1.3, 95% CI 1.1-1.6, p=0.01) in COPDGene, the effect estimate was less than that noted with ILA. There was no consistent association between MTL and risk of death when comparing the shortest quartile of telomere length in COPDGene and AGES-Reykjavik (HR 0.82, 95% CI 0.4-1.7, p=0.6, and HR 1.2, 95% CI 0.6-2.2, p=0.5, respectively). CONCLUSION: ILA are associated with decreased MTL.
Nielsen AB, Skaarup KG, Djernæs K, Hauser R, San José Estépar R, Sørensen SK, Ruwald MH, Hansen ML, Worck RH, Johannessen A, Hansen J, Biering-Sørensen T. Left atrial contractile strain predicts recurrence of atrial tachyarrhythmia after catheter ablation. Int J Cardiol 2022;358:51-57.Abstract
BACKGROUND: Despite improvement in treatment strategies of atrial fibrillation (AF), a considerable number of patients still experience recurrence of atrial tachyarrhythmia (ATA) following catheter ablation (CA). This study aimed to investigate the prognostic value of left atrial (LA) deformation analysis in a large group of patients undergoing CA for AF. METHODS: This study included 678 patients with AF. Echocardiography including two-dimensional speckle tracking echocardiography (2DSTE) was performed in all patients prior to CA. Logistic regression analysis was used to assess the association between ATA recurrence and LA strain during reservoir phase (LASr), LA strain during contraction phase (LASct), and LA strain during conduit phase (LAScd). RESULTS: During one-year follow-up, 274 (40%) experienced ATA recurrence. Median age of the included study population was 63.2 years (IQR: 55.5, 69.5) and 485 (72%) were male. Patients with recurrence had lower LASr (22.6% vs. 25.1%, p = 0.001) and LASct (10.7% vs. 12.4%, p < 0.001). No difference in LAScd was observed. After adjusting for potential clinical and echocardiographic confounders LASr (OR = 1.04, CI95% [1.01; 1.07], p = 0.015, per 1% decrease) and LASct (OR = 1.06, CI95% [1.02; 1.11], p = 0.007, per 1% decrease) remained independent predictors of recurrence. However, in patients with a normal-sized LA (LA volume index<34 mL/m2), only LASct remained an independent predictor of recurrence (OR = 1.07, CI95% [1.01; 1.12], p = 0.012, per 1% decrease). CONCLUSION: In patients undergoing CA for AF, LA deformation analysis by 2DSTE could be of use in risk stratification in clinical practice regarding ATA recurrence, even in patients with a normal-sized LA.
Mason SE, Moreta-Martinez R, Labaki WW, Strand MJ, Regan EA, Bon J, San Jose Estepar R, Casaburi R, McDonald M-L, Rossiter HB, Make B, Dransfield MT, Han MLK, Young K, Curtis JL, Stringer K, Kinney G, Hokanson JE, Estepar RSJ, Washko GR. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers. Chest 2022;161(4):960-970.Abstract
BACKGROUND: Body composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined. RESEARCH QUESTION: Is the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics? STUDY DESIGN AND METHODS: Participants with complete data for at least one visit in the COPDGene study (n = 9,268) and the ECLIPSE study (n = 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation. RESULTS: Both cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1% (95% CI, 2.4%-3.7%; P < .001) in COPDGene, and 2.4% (95% CI, 0.9%-4.0%; P < .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA. INTERPRETATION: Longitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.
Masquelin AH, Alshaabi T, Cheney N, San José Estépar R, Bates JHT, Kinsey MC. Perinodular Parenchymal Features Improve Indeterminate Lung Nodule Classification. Acad Radiol 2022;Abstract
BACKGROUND: Radiomics, defined as quantitative features extracted from images, provide a non-invasive means of assessing malignant versus benign pulmonary nodules. In this study, we evaluate the consistency with which perinodular radiomics extracted from low-dose computed tomography images serve to identify malignant pulmonary nodules. MATERIALS AND METHODS: Using the National Lung Screening Trial (NLST), we selected individuals with pulmonary nodules between 4mm to 20mm in diameter. Nodules were segmented to generate four distinct datasets; 1) a Tumor dataset containing tumor-specific features, 2) a 10 mm Band dataset containing parenchymal features between the segmented nodule boundary and 10mm out from the boundary, 3) a 15mm Band dataset, and 4) a Tumor Size dataset containing the maximum nodule diameter. Models to predict malignancy were constructed using support-vector machine (SVM), random forest (RF), and least absolute shrinkage and selection operator (LASSO) approaches. Ten-fold cross validation with 10 repetitions per fold was used to evaluate the performance of each approach applied to each dataset. RESULTS: With respect to the RF, the Tumor, 10mm Band, and 15mm Band datasets achieved areas under the receiver-operator curve (AUC) of 84.44%, 84.09%, and 81.57%, respectively. Significant differences in performance were observed between the Tumor and 15mm Band datasets (adj. p-value <0.001). However, when combining tumor-specific features with perinodular features, the 10mm Band + Tumor and 15mm Band + Tumor datasets (AUC 87.87% and 86.75%, respectively) performed significantly better than the Tumor Size dataset (66.76%) or the Tumor dataset. Similarly, the AUCs from the SVM and LASSO were 84.71% and 88.91%, respectively, for the 10mm Band + Tumor. CONCLUSIONS: The combined 10mm Band + Tumor dataset improved the differentiation between benign and malignant lung nodules compared to the Tumor datasets across all methodologies. This demonstrates that parenchymal features capture novel diagnostic information beyond that present in the nodule itself. (data agreement: NLST-163).
Dolliver WR, Wang W, Nardelli P, Rahaghi FN, Orejas JL, Maselli DJ, Yen A, Young K, Kinney G, San José Estépar R, Diaz AA. Pulmonary arterial pruning is associated with CT-derived bronchiectasis progression in smokers. Respir Med 2022;202:106971.Abstract
Loss of small pulmonary arteries measured as the ratio of blood vessel volume in arteries <5 mm2 in cross-section to total arterial blood vessel volume (BV5a/TBVa), with lower values indicating more pruning, was associated with 5-yr progressing CT-derived bronchiectasis in smokers (Odds Ratio (OR) [95% Confidence interval], 1.28 [1.07-1.53] per 5% lower BV5a/TBVa, P = 0.007). Corresponding results in smokers with COPD were: OR 1.45 [1.11-1.89] per 5% lower BV5a/TBVa, P = 0.007. The results support a vascular factor for structural progression of bronchiectasis.
Wan ES, Hokanson JE, Regan EA, Young KA, Make BJ, DeMeo DL, Mason SE, Estepar RSJ, Crapo JD, Silverman EK. Significant Spirometric Transitions and Preserved Ratio Impaired Spirometry Among Ever Smokers. Chest 2022;161(3):651-661.Abstract
BACKGROUND: Emerging data from longitudinal studies suggest that preserved ratio impaired spirometry (PRISm), defined by proportionate reductions in FEV1 and FVC, is a heterogeneous population with frequent transitions to other lung function categories relative to individuals with normal and obstructive spirometry. Controversy regarding the clinical significance of these transitions exists (eg, whether transitions merely reflect measurement variability or noise). RESEARCH QUESTION: Are individuals with PRISm enriched for transitions associated with substantial changes in lung function? STUDY DESIGN AND METHODS: Current and former smokers enrolled in the Genetic Epidemiology of COPD (COPDGene) study with spirometry available in phases 1 through 3 (enrollment, 5-year follow-up, and 10-year follow-up) were analyzed. Postbronchodilator lung function categories were as follows: PRISm (FEV1 < 80% predicted with FEV1/FVC ratio ≥ 0.7), Global Initiative for Chronic Obstructive Lung Disease grade 0 (FEV1 ≥ 80% predicted and FEV1/FVC ≥ 0.7), and obstruction (FEV1/FVC < 0.7). Significant transition status was affirmative if a subject belonged to two or more spirometric categories and had > 10% change in FEV1 % predicted and/or FVC % predicted between consecutive visits. Ever-PRISm was present if a subject had PRISm at any visit. Logistic regression examined the association between significant transitions and ever-PRISm status, adjusted for age, sex, race, FEV1 % predicted, current smoking, pack-years, BMI, and ever-positive bronchodilator response. RESULTS: Among subjects with complete data (N = 1,775) over 10.1 ± 0.4 years of follow-up, the prevalence of PRISm remained consistent (10.4%-11.3%) between phases 1 through 3, but nearly one-half of subjects with PRISm transitioned into or out of PRISm at each visit. Among all subjects, 19.7% had a significant transition; ever-PRISm was a significant predictor of significant transitions (unadjusted OR, 10.3; 95% CI, 7.9-13.5; adjusted OR, 14.9; 95% CI, 10.9-20.7). Results were similar with additional adjustment for radiographic emphysema and gas trapping, when lower limit of normal criteria were used to define lung function categories, and when FEV1 alone (regardless of change in FVC % predicted) was used to define significant transitions. INTERPRETATION: PRISm is an unstable group, with frequent significant transitions to both obstruction and normal spirometry over time. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT000608764; URL: www. CLINICALTRIALS: gov.
Hata A, Hino T, Putman RK, Yanagawa M, Hida T, Menon AA, Honda O, Yamada Y, Nishino M, Araki T, Valtchinov VI, Jinzaki M, Honda H, Ishigami K, Johkoh T, Tomiyama N, Christiani DC, Lynch DA, San José Estépar R, Washko GR, Cho MH, Silverman EK, Hunninghake GM, Hatabu H. Traction Bronchiectasis/Bronchiolectasis on CT Scans in Relationship to Clinical Outcomes and Mortality: The COPDGene Study. Radiology 2022;304(3):694-701.Abstract
Background The clinical impact of interstitial lung abnormalities (ILAs) on poor prognosis has been reported in many studies, but risk stratification in ILA will contribute to clinical practice. Purpose To investigate the association of traction bronchiectasis/bronchiolectasis index (TBI) with mortality and clinical outcomes in individuals with ILA by using the COPDGene cohort. Materials and Methods This study was a secondary analysis of prospectively collected data. Chest CT scans of participants with ILA for traction bronchiectasis/bronchiolectasis were evaluated and outcomes were compared with participants without ILA from the COPDGene study (January 2008 to June 2011). TBI was classified as follows: TBI-0, ILA without traction bronchiectasis/bronchiolectasis; TBI-1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; TBI-2, ILA with mild to moderate traction bronchiectasis; and TBI-3, ILA with severe traction bronchiectasis and/or honeycombing. Clinical outcomes and overall survival were compared among the TBI groups and the non-ILA group by using multivariable linear regression model and Cox proportional hazards model, respectively. Results Overall, 5295 participants (median age, 59 years; IQR, 52-66 years; 2779 men) were included, and 582 participants with ILA and 4713 participants without ILA were identified. TBI groups were associated with poorer clinical outcomes such as quality of life scores in the multivariable linear regression model (TBI-0: coefficient, 3.2 [95% CI: 0.6, 5.7; P = .01]; TBI-1: coefficient, 3.3 [95% CI: 1.1, 5.6; P = .003]; TBI-2: coefficient, 7.6 [95% CI: 4.0, 11; P < .001]; TBI-3: coefficient, 32 [95% CI: 17, 48; P < .001]). The multivariable Cox model demonstrated that ILA without traction bronchiectasis (TBI-0-1) and with traction bronchiectasis (TBI-2-3) were associated with shorter overall survival (TBI-0-1: hazard ratio [HR], 1.4 [95% CI: 1.0, 1.9; P = .049]; TBI-2-3: HR, 3.8 [95% CI: 2.6, 5.6; P < .001]). Conclusion Traction bronchiectasis/bronchiolectasis was associated with poorer clinical outcomes compared with the group without interstitial lung abnormalities; TBI-2 and 3 were associated with shorter survival. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee and Im in this issue.
Belkhatir Z, San José Estépar R, Tannenbaum AR. Wasserstein-based texture analysis in radiomic studies. Comput Med Imaging Graph 2022;102:102129.Abstract
The emerging field of radiomics that transforms standard-of-care images to quantifiable scalar statistics endeavors to reveal the information hidden in these macroscopic images. The concept of texture is widely used and essential in many radiomic-based studies. Practice usually reduces spatial multidimensional texture matrices, e.g., gray-level co-occurrence matrices (GLCMs), to summary scalar features. These statistical features have been demonstrated to be strongly correlated and tend to contribute redundant information; and does not account for the spatial information hidden in the multivariate texture matrices. This study proposes a novel pipeline to deal with spatial texture features in radiomic studies. A new set of textural features that preserve the spatial information inherent in GLCMs is proposed and used for classification purposes. The set of the new features uses the Wasserstein metric from optimal mass transport theory (OMT) to quantify the spatial similarity between samples within a given label class. In particular, based on a selected subset of texture GLCMs from the training cohort, we propose new representative spatial texture features, which we incorporate into a supervised image classification pipeline. The pipeline relies on the support vector machine (SVM) algorithm along with Bayesian optimization and the Wasserstein metric. The selection of the best GLCM references is considered for each classification label and is performed during the training phase of the SVM classifier using a Bayesian optimizer. We assume that sample fitness is defined based on closeness (in the sense of the Wasserstein metric) and high correlation (Spearman's rank sense) with other samples in the same class. Moreover, the newly defined spatial texture features consist of the Wasserstein distance between the optimally selected references and the remaining samples. We assessed the performance of the proposed classification pipeline in diagnosing the coronavirus disease 2019 (COVID-19) from computed tomographic (CT) images. To evaluate the proposed spatial features' added value, we compared the performance of the proposed classification pipeline with other SVM-based classifiers that account for different texture features, namely: statistical features only, optimized spatial features using Euclidean metric, non-optimized spatial features with Wasserstein metric. The proposed technique, which accounts for the optimized spatial texture feature with Wasserstein metric, shows great potential in classifying new COVID CT images that the algorithm has not seen in the training step. The MATLAB code of the proposed classification pipeline is made available. It can be used to find the best reference samples in other data cohorts, which can then be employed to build different prediction models.
2021
Harder EM, Vanderpool R, Rahaghi FN. Advanced Imaging in Pulmonary Vascular Disease. Clin Chest Med 2021;42(1):101-112.Abstract
Although the diagnosis of pulmonary hypertension requires invasive testing, imaging serves an important role in the screening, classification, and monitoring of patients with pulmonary vascular disease (PVD). The development of advanced imaging techniques has led to improvements in the understanding of disease pathophysiology, noninvasive assessment of hemodynamics, and stratification of patient risk. This article discusses the current role of advanced imaging and the emerging novel techniques for visualizing the lung parenchyma, mediastinum, and heart in PVD.
Sweatt AJ, Reddy R, Rahaghi FN, Al-Naamani N. What's new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference. Pulm Circ 2021;11(3):20458940211040713.Abstract
In this conference paper, we review the 2020 American Thoracic Society International Conference session titled, "What's New in Pulmonary Hypertension Clinical Research: Lessons from the Best Abstracts". This virtual mini-symposium took place on 21 October 2020, in lieu of the annual in-person ATS International Conference which was cancelled due to the COVID-19 pandemic. Seven clinical research abstracts were selected for presentation in the session, which encompassed five major themes: (1) standardizing diagnosis and management of pulmonary hypertension, (2) improving risk assessment in pulmonary arterial hypertension, (3) evaluating biomarkers of disease activity, (4) understanding metabolic dysregulation across the spectrum of pulmonary hypertension, and (5) advancing knowledge in chronic thromboembolic pulmonary hypertension. Focusing on these five thematic contexts, we review the current state of knowledge, summarize presented research abstracts, appraise their significance and limitations, and then discuss relevant future directions in pulmonary hypertension clinical research.
Rahaghi FN, Pistenmaa CL. Hypercoagulation in COPD: the clot thickens. ERJ Open Res 2021;7(4)Abstract
There is a growing body of evidence that hypercoagulability is present in stable COPD, involves changes in multiple coagulation factors, and is not simply associated with major causes of inflammation and thrombosis https://bit.ly/3F5NnfN.
Ramos-Llordén G, Vegas-Sánchez-Ferrero G, Liao C, Westin C-F, Setsompop K, Rathi Y. SNR-enhanced diffusion MRI with structure-preserving low-rank denoising in reproducing kernel Hilbert spaces. Magn Reson Med 2021;86(3):1614-1632.Abstract
PURPOSE: To introduce, develop, and evaluate a novel denoising technique for diffusion MRI that leverages nonlinear redundancy in the data to boost the SNR while preserving signal information. METHODS: We exploit nonlinear redundancy of the dMRI data by means of kernel principal component analysis (KPCA), a nonlinear generalization of PCA to reproducing kernel Hilbert spaces. By mapping the signal to a high-dimensional space, a higher level of redundant information is exploited, thereby enabling better denoising than linear PCA. We implement KPCA with a Gaussian kernel, with parameters automatically selected from knowledge of the noise statistics, and validate it on realistic Monte Carlo simulations as well as with in vivo human brain submillimeter and low-resolution dMRI data. We also demonstrate KPCA denoising on multi-coil dMRI data. RESULTS: SNR improvements up to 2.7 × were obtained in real in vivo datasets denoised with KPCA, in comparison to SNR gains of up to 1.8 × using a linear PCA denoising technique called Marchenko-Pastur PCA (MPPCA). Compared to gold-standard dataset references created from averaged data, we showed that lower normalized root mean squared error was achieved with KPCA compared to MPPCA. Statistical analysis of residuals shows that anatomical information is preserved and only noise is removed. Improvements in the estimation of diffusion model parameters such as fractional anisotropy, mean diffusivity, and fiber orientation distribution functions were also demonstrated. CONCLUSION: Nonlinear redundancy of the dMRI signal can be exploited with KPCA, which allows superior noise reduction/SNR improvements than the MPPCA method, without loss of signal information.

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