@article{pmid36929883,

title = {Direct estimation of regional lung volume change from paired and single CT images using residual regression neural network},

author = {Sarah E Gerard and Muhammad F A Chaudhary and Jacob Herrmann and Gary E Christensen and Raúl San José Estépar and Joseph M Reinhardt and Eric A Hoffman},

doi = {10.1002/mp.16365},

issn = {2473-4209},

year  = {2023},

date = {2023-09-01},

journal = {Med Phys},

volume = {50},

number = {9},

pages = {5698--5714},

abstract = {BACKGROUND: Chest computed tomography (CT) enables characterization of pulmonary diseases by producing high-resolution and high-contrast images of the intricate lung structures. Deformable image registration is used to align chest CT scans at different lung volumes, yielding estimates of local tissue expansion and contraction.nnPURPOSE: We investigated the utility of deep generative models for directly predicting local tissue volume change from lung CT images, bypassing computationally expensive iterative image registration and providing a method that can be utilized in scenarios where either one or two CT scans are available.nnMETHODS: A residual regression convolutional neural network, called Reg3DNet+, is proposed for directly regressing high-resolution images of local tissue volume change (i.e., Jacobian) from CT images. Image registration was performed between lung volumes at total lung capacity (TLC) and functional residual capacity (FRC) using a tissue mass- and structure-preserving registration algorithm. The Jacobian image was calculated from the registration-derived displacement field and used as the ground truth for local tissue volume change. Four separate Reg3DNet+ models were trained to predict Jacobian images using a multifactorial study design to compare the effects of network input (i.e., single image vs. paired images) and output space (i.e., FRC vs. TLC). The models were trained and evaluated on image datasets from the COPDGene study. Models were evaluated against the registration-derived Jacobian images using local, regional, and global evaluation metrics.nnRESULTS: Statistical analysis revealed that both factors - network input and output space - were significant determinants for change in evaluation metrics. Paired-input models performed better than single-input models, and model performance was better in the output space of FRC rather than TLC. Mean structural similarity index for paired-input models was 0.959 and 0.956 for FRC and TLC output spaces, respectively, and for single-input models was 0.951 and 0.937. Global evaluation metrics demonstrated correlation between registration-derived Jacobian mean and predicted Jacobian mean: coefficient of determination (r ) for paired-input models was 0.974 and 0.938 for FRC and TLC output spaces, respectively, and for single-input models was 0.598 and 0.346. After correcting for effort, registration-derived lobar volume change was strongly correlated with the predicted lobar volume change: for paired-input models r was 0.899 for both FRC and TLC output spaces, and for single-input models r was 0.803 and 0.862, respectively.nnCONCLUSIONS: Convolutional neural networks can be used to directly predict local tissue mechanics, eliminating the need for computationally expensive image registration. Networks that use paired CT images acquired at TLC and FRC allow for more accurate prediction of local tissue expansion compared to networks that use a single image. Networks that only require a single input image still show promising results, particularly after correcting for effort, and allow for local tissue expansion estimation in cases where multiple CT scans are not available. For single-input networks, the FRC image is more predictive of local tissue volume change compared to the TLC image.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35933282,

title = {Perinodular Parenchymal Features Improve Indeterminate Lung Nodule Classification},

author = {Axel H Masquelin and Thayer Alshaabi and Nick Cheney and Raúl San José Estépar and Jason H T Bates and C Matthew Kinsey},

doi = {10.1016/j.acra.2022.07.001},

issn = {1878-4046},

year  = {2023},

date = {2023-06-01},

journal = {Acad Radiol},

volume = {30},

number = {6},

pages = {1073--1080},

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.nnMATERIALS 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.nnRESULTS: 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.nnCONCLUSIONS: 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).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35777957,

title = {The relationship between interstitial lung abnormalities, mortality, and multimorbidity: a cohort study},

author = {Jason Leigh Sanders and Gisli Axelsson and Rachel Putman and Aravind Menon and Josée Dupuis and Hanfei Xu and Shuai Wang and Joanne Murabito and Ramachandran Vasan and Tetsuro Araki and Mizuki Nishino and George R Washko and Hiroto Hatabu and George O'Connor and Gunnar Gudmundsson and Vilmundur Gudnason and Gary M Hunninghake},

doi = {10.1136/thoraxjnl-2021-218315},

issn = {1468-3296},

year  = {2023},

date = {2023-06-01},

journal = {Thorax},

volume = {78},

number = {6},

pages = {559--565},

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.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSIONS: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37039685,

title = {Quantitative CT Evaluation of Emphysema Progression over 10 Years in the COPDGene Study},

author = {David Baraghoshi and Matthew Strand and Stephen M Humphries and Raúl San José Estépar and Gonzalo Vegas Sanchez-Ferrero and Jean-Paul Charbonnier and Rudolfs Latisenko and Edwin K Silverman and James D Crapo and David A Lynch},

doi = {10.1148/radiol.222786},

issn = {1527-1315},

year  = {2023},

date = {2023-05-01},

journal = {Radiology},

volume = {307},

number = {4},

pages = {e222786},

abstract = {Background Long-term studies of chronic obstructive pulmonary disease (COPD) can evaluate emphysema progression. Adjustment for differences in equipment and scanning protocols of individual CT examinations have not been studied extensively. Purpose To evaluate emphysema progression in current and former smokers in the COPDGene cohort over three imaging points obtained at 5-year intervals accounting for individual CT parameters. Materials and Methods Current and former cigarette smokers enrolled between 2008 and 2011 from the COPDGene study were prospectively followed for 10 years between 2008 and 2020. Extent of emphysema as adjusted lung density (ALD) from quantitative CT was measured at baseline and at 5- and 10-year follow-up. Linear mixed models adjusted for CT technical characteristics were constructed to evaluate emphysema progression. Mean annual changes in ALD over consecutive 5-year study periods were estimated by smoking status and baseline emphysema. Results Of 8431 participants at baseline (mean age, 60 years ± 9 [SD]; 3905 female participants), 4913 were at 5-year follow-up and 1544 participants were at 10-year follow-up. There were 4134 (49%) participants who were current smokers, and 4449 (53%) participants had more than trace emphysema at baseline. Current smokers with more than trace emphysema showed the largest decline in ALD, with mean annual decreases of 1.4 g/L (95% CI: 1.2, 1.5) in the first 5 years and 0.9 g/L (95% CI: 0.7, 1.2) in the second 5 years. Accounting for CT noise, field of view, and scanner model improved model fit for estimation of emphysema progression ( < .001 by likelihood ratio test). Conclusion Evaluation at CT of emphysema progression in the COPDGene study showed that, during the span of 10 years, participants with pre-existing emphysema who continued smoking had the largest decline in ALD. Adjusting for CT equipment and protocol factors improved these longitudinal estimates. Clinical trial registration no. NCT00608764 © RSNA, 2023  See the editorial by Parraga and Kirby in this issue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36856146,

title = {Gene polymorphisms associated with heterogeneity and senescence characteristics of sarcopenia in chronic obstructive pulmonary disease},

author = {Amy H Attaway and Annette Bellar and Nicole Welch and Jinendiran Sekar and Avinash Kumar and Saurabh Mishra and Umur Hatipoğlu and Merry-Lynn McDonald and Elizabeth A Regan and Jonathan D Smith and George Washko and Raúl San José Estépar and Peter Bazeley and Joe Zein and Srinivasan Dasarathy},

doi = {10.1002/jcsm.13198},

issn = {2190-6009},

year  = {2023},

date = {2023-04-01},

journal = {J Cachexia Sarcopenia Muscle},

volume = {14},

number = {2},

pages = {1083--1095},

abstract = {BACKGROUND: Sarcopenia, or loss of skeletal muscle mass and decreased contractile strength, contributes to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). The severity of sarcopenia in COPD is variable, and there are limited data to explain phenotype heterogeneity. Others have shown that COPD patients with sarcopenia have several hallmarks of cellular senescence, a potential mechanism of primary (age-related) sarcopenia. We tested if genetic contributors explain the variability in sarcopenic phenotype and accelerated senescence in COPD.nnMETHODS: To identify gene variants [single nucleotide polymorphisms (SNPs)] associated with sarcopenia in COPD, we performed a genome-wide association study (GWAS) of fat free mass index (FFMI) in 32 426 non-Hispanic White (NHW) UK Biobank participants with COPD. Several SNPs within the fat mass and obesity-associated (FTO) gene were associated with sarcopenia that were validated in an independent COPDGene cohort (n = 3656). Leucocyte telomere length quantified in the UK Biobank cohort was used as a marker of senescence. Experimental validation was done by genetic depletion of FTO in murine skeletal myotubes exposed to prolonged intermittent hypoxia or chronic hypoxia because hypoxia contributes to sarcopenia in COPD. Molecular biomarkers for senescence were also quantified with FTO depletion in murine myotubes.nnRESULTS: Multiple SNPs located in the FTO gene were associated with sarcopenia in addition to novel SNPs both within and in proximity to the gene AC090771.2, which transcribes long non-coding RNA (lncRNA). To replicate our findings, we performed a GWAS of FFMI in NHW subjects from COPDGene. The SNP most significantly associated with FFMI was on chromosome (chr) 16, rs1558902A > T in the FTO gene (β = 0.151, SE = 0.021, P = 1.40 × 10 for UK Biobank |β= 0.220, SE = 0.041, P = 9.99 × 10 for COPDGene) and chr 18 SNP rs11664369C > T nearest to the AC090771.2 gene (β = 0.129, SE = 0.024, P = 4.64 × 10 for UK Biobank |β = 0.203, SE = 0.045, P = 6.38 × 10 for COPDGene). Lower handgrip strength, a measure of muscle strength, but not FFMI was associated with reduced telomere length in the UK Biobank. Experimentally, in vitro knockdown of FTO lowered myotube diameter and induced a senescence-associated molecular phenotype, which was worsened by prolonged intermittent hypoxia and chronic hypoxia.nnCONCLUSIONS: Genetic polymorphisms of FTO and AC090771.2 were associated with sarcopenia in COPD in independent cohorts. Knockdown of FTO in murine myotubes caused a molecular phenotype consistent with senescence that was exacerbated by hypoxia, a common condition in COPD. Genetic variation may interact with hypoxia and contribute to variable severity of sarcopenia and skeletal muscle molecular senescence phenotype in COPD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36490389,

title = {Emphysema Detection in the Course of Lung Cancer Screening: Optimizing a Rare Opportunity to Impact Population Health},

author = {James L Mulshine and Carolyn R Aldigé and Laurie Fenton Ambrose and Samuel G Armato and Ricardo S Avila and Matt Cham and Raul San Jose Estepar and Sean B Fain and Lee Gazourian and David S Gierada and Charles Hatt and Claudia I Henschke and Jody Hoyos and David A Lynch and Anita K McGlothlin and Matthijs Oudkerk and Mary Pasquinelli and Paul Pinsky and Bruce Pyenson and Albert A Rizzo and Sheila M Ross and Kathryn H Schmitz and Mario Silva and Tochukwu Okwuosa and George Washko and Juan Wisnivesky and David F Yankelevitz and Javier J Zulueta},

doi = {10.1513/AnnalsATS.202207-631PS},

issn = {2325-6621},

year  = {2023},

date = {2023-04-01},

journal = {Ann Am Thorac Soc},

volume = {20},

number = {4},

pages = {499--503},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36511808,

title = {Artificial Intelligence-based CT Assessment of Bronchiectasis: The COPDGene Study},

author = {Alejandro A Díaz and Pietro Nardelli and Wei Wang and Rubén San José Estépar and Andrew Yen and Seth Kligerman and Diego J Maselli and Wojciech R Dolliver and Andrew Tsao and José L Orejas and Stefano Aliberti and Timothy R Aksamit and Kendra A Young and Gregory L Kinney and George R Washko and Edwin K Silverman and Raúl San José Estépar},

doi = {10.1148/radiol.221109},

issn = {1527-1315},

year  = {2023},

date = {2023-04-01},

journal = {Radiology},

volume = {307},

number = {1},

pages = {e221109},

abstract = {Background CT is the standard method used to assess bronchiectasis. A higher airway-to-artery diameter ratio (AAR) is typically used to identify enlarged bronchi and bronchiectasis; however, current imaging methods are limited in assessing the extent of this metric in CT scans. Purpose To determine the extent of AARs using an artificial intelligence-based chest CT and assess the association of AARs with exacerbations over time. Materials and Methods In a secondary analysis of ever-smokers from the prospective, observational, multicenter COPDGene study, AARs were quantified using an artificial intelligence tool. The percentage of airways with AAR greater than 1 (a measure of airway dilatation) in each participant on chest CT scans was determined. Pulmonary exacerbations were prospectively determined through biannual follow-up (from July 2009 to September 2021). Multivariable zero-inflated regression models were used to assess the association between the percentage of airways with AAR greater than 1 and the total number of pulmonary exacerbations over follow-up. Covariates included demographics, lung function, and conventional CT parameters. Results Among 4192 participants (median age, 59 years; IQR, 52-67 years; 1878 men [45%]), 1834 had chronic obstructive pulmonary disease (COPD). During a 10-year follow-up and in adjusted models, the percentage of airways with AARs greater than 1 (quartile 4 vs 1) was associated with a higher total number of exacerbations (risk ratio [RR], 1.08; 95% CI: 1.02, 1.15;  = .01). In participants meeting clinical and imaging criteria of bronchiectasis (ie, clinical manifestations with ≥3% of AARs >1) versus those who did not, the RR was 1.37 (95% CI: 1.31, 1.43;  < .001). Among participants with COPD, the corresponding RRs were 1.10 (95% CI: 1.02, 1.18;  = .02) and 1.32 (95% CI: 1.26, 1.39;  < .001), respectively. Conclusion In ever-smokers with chronic obstructive pulmonary disease, artificial intelligence-based CT measures of bronchiectasis were associated with more exacerbations over time. Clinical trial registration no. NCT00608764 © RSNA, 2022  See also the editorial by Schiebler and Seo in this issue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36244396,

title = {Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort study},

author = {Shyamali C Dharmage and Dinh S Bui and Eugene H Walters and Adrian J Lowe and Bruce Thompson and Gayan Bowatte and Paul Thomas and Judith Garcia-Aymerich and Debbie Jarvis and Garun S Hamilton and David P Johns and Peter Frith and Chamara V Senaratna and Nur S Idrose and Richard R Wood-Baker and John Hopper and Lyle Gurrin and Bircan Erbas and George R Washko and Rosa Faner and Alvar Agusti and Michael J Abramson and Caroline J Lodge and Jennifer L Perret},

doi = {10.1016/S2213-2600(22)00364-2},

issn = {2213-2619},

year  = {2023},

date = {2023-03-01},

journal = {Lancet Respir Med},

volume = {11},

number = {3},

pages = {273--282},

abstract = {BACKGROUND: Interest in lifetime lung function trajectories has increased in the context of emerging evidence that chronic obstructive pulmonary disease (COPD) can arise from multiple disadvantaged lung function pathways, including those that stem from poor lung function in childhood. To our knowledge, no previous study has investigated both obstructive and restrictive lifetime patterns concurrently, while accounting for potential overlaps between them. We aimed to investigate lifetime trajectories of the FEV/forced vital capacity (FVC) ratio, FVC, and their combinations, relate these combined trajectory groups to static lung volume and gas transfer measurements, and investigate both risk factors for and consequences of these combined trajectory groups.nnMETHODS: Using z scores from spirometry measured at ages 7, 13, 18, 45, 50, and 53 years in the Tasmanian Longitudinal Health Study (n=2422), we identified six FEV/FVC ratio trajectories and five FVC trajectories via group-based trajectory modelling. Based on whether trajectories of the FEV/FVC ratio and FVC were low (ie, low from childhood or adulthood) or normal, four patterns of lifetime spirometry obstruction or restriction were identified and compared against static lung volumes and gas transfer. Childhood and adulthood characteristics and morbidities of these patterns were investigated.nnFINDINGS: The prevalence of the four lifetime spirometry patterns was as follows: low FEV/FVC ratio only, labelled as obstructive-only, 25·8%; low FVC only, labelled as restrictive-only, 10·5%; both low FEV/FVC ratio and low FVC, labelled as mixed, 3·5%; and neither low FEV/FVC ratio nor low FVC, labelled as reference, 60·2%. The prevalence of COPD at age 53 years was highest in the mixed pattern (31 [37%] of 84 individuals) followed by the obstructive-only pattern (135 [22%] of 626 individuals). Individuals with the mixed pattern also had the highest prevalence of parental asthma, childhood respiratory illnesses, adult asthma, and depression. Individuals with the restrictive-only pattern had lower total lung capacity and residual volume, and had the highest prevalence of childhood underweight, adult obesity, diabetes, cardiovascular conditions, hypertension, and obstructive sleep apnoea.nnINTERPRETATION: To our knowledge, this is the first study to characterise lifetime phenotypes of obstruction and restriction simultaneously using objective data-driven techniques and unique life course spirometry measures of FEV/FVC ratio and FVC from childhood to middle age. Mixed and obstructive-only patterns indicate those who might benefit from early COPD interventions. Those with the restrictive-only pattern had evidence of true lung restriction and were at increased risk of multimorbidity by middle age.nnFUNDING: National Health and Medical Research Council of Australia, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36717002,

title = {Prevalence of abnormal spirometry in individuals with a smoking history and no known obstructive lung disease},

author = {Thuonghien V Tran and Gregory L Kinney and Alejandro Comellas and Karin F Hoth and Arianne K Baldomero and A James Mamary and Jeffrey L Curtis and Nicola Hanania and Richard Casaburi and Kendra A Young and Victor Kim and Barry Make and Emily S Wan and Alejandro A Diaz and John Hokanson and James D Crapo and Edwin K Silverman and Surya P Bhatt and Elizabeth Regan and Spyridon Fortis and  and },

doi = {10.1016/j.rmed.2023.107126},

issn = {1532-3064},

year  = {2023},

date = {2023-03-01},

journal = {Respir Med},

volume = {208},

pages = {107126},

abstract = {INTRODUCTION: Recent evidence suggests a high prevalence of undiagnosed chronic obstructive pulmonary disease (COPD). These individuals are at risk of exacerbations and delayed treatment. We analyzed an at-risk population for the prevalence of abnormal spirometry to provide clarity into who should undergo early spirometry.nnMETHODS: We analyzed data from the COPDGene study. Participants with ≥10 pack-years of smoking were included. Individuals with self-reported or physician-diagnosed COPD, asthma, chronic bronchitis, emphysema and/or were on inhalers were excluded. Parsimonious multivariable logistic regression models identified factors associated with abnormal spirometry, defined as either airflow obstruction (AFO) or preserved ratio impaired spirometry. Variables were selected for the final model using a stepwise backward variable elimination process which minimized Akaike information criterion (AIC). Similarly, during the 5-year follow-up period, we assessed factors associated with incident diagnosis of COPD.nnRESULTS: Of 5055 individuals, 1064 (21%) had undiagnosed AFO. Age, pack-years, current smoking and a history of acute bronchitis were associated with AFO while body mass index, female sex, and Black race were inversely associated. Among 2800 participants with 5-year follow-up, 532 (19%) had an incident diagnosis of COPD. Associated risk factors included mMRC ≥2, chronic productive cough, respiratory exacerbations during the follow-up period, and abnormal spirometry. Age was inversely associated.nnCONCLUSIONS: The prevalence of undiagnosed COPD is high in at-risk populations. We found multiple factors associated with undiagnosed COPD and incident diagnosis of COPD at follow up. These results can be used to identify those at risk for undiagnosed COPD to facilitate earlier diagnosis and treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35780812,

title = {Quantitative Interstitial Abnormality Progression and Outcomes in the Genetic Epidemiology of COPD and Pittsburgh Lung Screening Study Cohorts},

author = {Bina Choi and Najma Adan and Tracy J Doyle and Ruben San José Estépar and Rola Harmouche and Stephen M Humphries and Matthew Moll and Michael H Cho and Rachel K Putman and Gary M Hunninghake and Ravi Kalhan and Gabrielle Y Liu and Alejandro A Diaz and Stefanie E Mason and Farbod N Rahaghi and Carrie L Pistenmaa and Nicholas Enzer and Clare Poynton and Gonzalo Vegas Sánchez-Ferrero and James C Ross and David A Lynch and Fernando J Martinez and MeiLan K Han and Russell P Bowler and David O Wilson and Ivan O Rosas and George R Washko and Raúl San José Estépar and Samuel Y Ash and },

doi = {10.1016/j.chest.2022.06.030},

issn = {1931-3543},

year  = {2023},

date = {2023-01-01},

journal = {Chest},

volume = {163},

number = {1},

pages = {164--175},

abstract = {BACKGROUND: The risk factors and clinical outcomes of quantitative interstitial abnormality progression over time have not been characterized.nnRESEARCH QUESTIONS: What are the associations of quantitative interstitial abnormality progression with lung function, exercise capacity, and mortality? What are the demographic and genetic risk factors for quantitative interstitial abnormality progression?nnSTUDY DESIGN AND METHODS: Quantitative interstitial abnormality progression between visits 1 and 2 was assessed from 4,635 participants in the Genetic Epidemiology of COPD (COPDGene) cohort and 1,307 participants in the Pittsburgh Lung Screening Study (PLuSS) cohort. We used multivariable linear regression to determine the risk factors for progression and the longitudinal associations between progression and FVC and 6-min walk distance, and Cox regression models for the association with mortality.nnRESULTS: Age at enrollment, female sex, current smoking status, and the MUC5B minor allele were associated with quantitative interstitial abnormality progression. Each percent annual increase in quantitative interstitial abnormalities was associated with annual declines in FVC (COPDGene: 8.5 mL/y; 95% CI, 4.7-12.4 mL/y; P < .001; PLuSS: 9.5 mL/y; 95% CI, 3.7-15.4 mL/y; P = .001) and 6-min walk distance, and increased mortality (COPDGene: hazard ratio, 1.69; 95% CI, 1.34-2.12; P < .001; PLuSS: hazard ratio, 1.28; 95% CI, 1.10-1.49; P = .001).nnINTERPRETATION: The objective, longitudinal measurement of quantitative interstitial abnormalities may help identify people at greatest risk for adverse events and most likely to benefit from early intervention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35930450,

title = {Suspected Interstitial Lung Disease in COPDGene Study},

author = {Jonathan A Rose and Aravind A Menon and Takuya Hino and Akinori Hata and Mizuki Nishino and David A Lynch and Ivan O Rosas and Souheil El-Chemaly and Benjamin A Raby and Samuel Y Ash and Bina Choi and George R Washko and Edwin K Silverman and Michael H Cho and Hiroto Hatabu and Rachel K Putman and Gary M Hunninghake},

doi = {10.1164/rccm.202203-0550OC},

issn = {1535-4970},

year  = {2023},

date = {2023-01-01},

journal = {Am J Respir Crit Care Med},

volume = {207},

number = {1},

pages = {60--68},

abstract = { Although interstitial lung abnormalities (ILA), specific patterns of incidentally-detected abnormal density on computed tomography, have been associated with abnormal lung function and increased mortality, it is unclear if a subset with incidental interstitial lung disease (ILD) accounts for these adverse consequences.  To define the prevalence and risk factors of suspected ILD and assess outcomes.  Suspected ILD was evaluated in the COPDGene (Chronic Obstructive Pulmonary Disease Genetic Epidemiology) study, defined as ILA and at least one additional criterion: definite fibrosis on computed tomography, FVC less than 80% predicted, or DL less than 70% predicted. Multivariable linear, longitudinal, and Cox proportional hazards regression models were used to assess associations with St. George's Respiratory Questionnaire, 6-minute-walk test, supplemental oxygen use, respiratory exacerbations, and mortality.  Of 4,361 participants with available data, 239 (5%) had evidence for suspected ILD, whereas 204 (5%) had ILA without suspected ILD. In multivariable analyses, suspected ILD was associated with increased St. George's Respiratory Questionnaire score (mean difference [MD], 3.9 points; 95% confidence interval [CI], 0.6-7.1;  = 0.02), reduced 6-minute-walk test (MD, -35 m; 95% CI, -56 m to -13 m;  = 0.002), greater supplemental oxygen use (odds ratio [OR], 2.3; 95% CI, 1.1-5.1;  = 0.03) and severe respiratory exacerbations (OR, 2.9; 95% CI, 1.1-7.5;  = 0.03), and higher mortality (hazard ratio, 2.4; 95% CI, 1.2-4.6;  = 0.01) compared with ILA without suspected ILD. Risk factors associated with suspected ILD included self-identified Black race (OR, 2.0; 95% CI, 1.1-3.3;  = 0.01) and pack-years smoking history (OR, 1.2; 95% CI, 1.1-1.3;  = 0.0005).  Suspected ILD is present in half of those with ILA in COPDGene and is associated with exercise decrements and increased symptoms, supplemental oxygen use, severe respiratory exacerbations, and mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36229050,

title = {Bronchial gene expression alterations associated with radiological bronchiectasis},

author = {Ke Xu and Alejandro A Diaz and Fenghai Duan and Minyi Lee and Xiaohui Xiao and Hanqiao Liu and Gang Liu and Michael H Cho and Adam C Gower and Yuriy O Alekseyev and Avrum Spira and Denise R Aberle and George R Washko and Ehab Billatos and Marc E Lenburg and },

doi = {10.1183/13993003.00120-2022},

issn = {1399-3003},

year  = {2023},

date = {2023-01-01},

journal = {Eur Respir J},

volume = {61},

number = {1},

abstract = {OBJECTIVES: Discovering airway gene expression alterations associated with radiological bronchiectasis may improve the understanding of the pathobiology of early-stage bronchiectasis.nnMETHODS: Presence of radiological bronchiectasis in 173 individuals without a clinical diagnosis of bronchiectasis was evaluated. Bronchial brushings from these individuals were transcriptomically profiled and analysed. Single-cell deconvolution was performed to estimate changes in cellular landscape that may be associated with early disease progression.nnRESULTS: 20 participants have widespread radiological bronchiectasis (three or more lobes). Transcriptomic analysis reflects biological processes associated with bronchiectasis including decreased expression of genes involved in cell adhesion and increased expression of genes involved in inflammatory pathways (655 genes, false discovery rate <0.1, log fold-change >0.25). Deconvolution analysis suggests that radiological bronchiectasis is associated with an increased proportion of ciliated and deuterosomal cells, and a decreased proportion of basal cells. Gene expression patterns separated participants into three clusters: normal, intermediate and bronchiectatic. The bronchiectatic cluster was enriched by participants with more lobes of radiological bronchiectasis (p<0.0001), more symptoms (p=0.002), higher SERPINA1 mutation rates (p=0.03) and higher computed tomography derived bronchiectasis scores (p<0.0001).nnCONCLUSIONS: Genes involved in cell adhesion, Wnt signalling, ciliogenesis and interferon-γ pathways had altered expression in the bronchus of participants with widespread radiological bronchiectasis, possibly associated with decreased basal and increased ciliated cells. This gene expression pattern is not only highly enriched among individuals with radiological bronchiectasis, but also associated with airway-related symptoms in those without discernible radiological bronchiectasis, suggesting that it reflects a bronchiectasis-associated, but non-bronchiectasis-specific lung pathophysiological process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36599111,

title = {Associations Between Muscle Weakness and Clinical Outcomes in Current and Former Smokers},

author = {Richard H Zou and S Mehdi Nouraie and Harry B Rossiter and Merry-Lynn McDonald and Dawn L DeMeo and Stefanie Mason and George R Washko and Punam K Saha and Barry J Make and Richard Casaburi and Elizabeth A Regan and Jessica Bon and },

doi = {10.15326/jcopdf.2022.0365},

issn = {2372-952X},

year  = {2023},

date = {2023-01-01},

journal = {Chronic Obstr Pulm Dis},

volume = {10},

number = {1},

pages = {112--121},

abstract = {INTRODUCTION: Smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of muscle weakness. There are limited data describing weakness in smokers with normal spirometry and preserved ratio-impaired spirometry (PRISm), 2 subgroups at risk of respiratory symptom burden and activity limitations. In this study, we evaluated the associations of 2 weakness measures, sit-to-stand (STS) and handgrip strength (HGS), with clinical outcomes in smokers with COPD, normal spirometry, and PRISm.nnMETHODS: We evaluated 1972 current and former smokers from the COPD Genetic Epidemiology (COPDGene) cohort with STS and HGS measurements at their 10-year study visit. Multivariable regression modeling was used to assess associations between weakness measures and the 6-minute walk distance (6MWD) test, the St George's Respiratory Questionnaire (SGRQ), the Short-Form-36 (SF-36), severe exacerbations, and prospective mortality, reported as standardized coefficients (β), odds ratios (ORs), or hazard ratios (HRs).nnRESULTS: Compared with HGS, STS was more strongly associated with the 6MWD (β=0.45, <0.001 versus. β=0.25, <0.001), SGRQ (β=-0.24, <0.001 versus β=-0.18, <0.001), SF-36 Physical Functioning (β=0.36, <0.001 versus β=0.25, <0.001), severe exacerbations (OR 0.95, =0.04 versus OR 0.97, =0.01), and prospective mortality (HR 0.83, =0.001 versus HR 0.94, =0.03). Correlations remained after stratification by spirometric subgroups. Compared with males, females had larger magnitude effect sizes between STS and clinical outcomes.nnCONCLUSIONS: STS and HGS are easy to perform weakness measures that provide important information about functional performance, health-related quality of life, severe exacerbations, and survival in smokers, regardless of spirometric subgroup. This iterates the importance of screening current and former smokers for weakness in the outpatient setting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36308869,

title = {Wasserstein-based texture analysis in radiomic studies},

author = {Zehor Belkhatir and Raúl San José Estépar and Allen R Tannenbaum},

doi = {10.1016/j.compmedimag.2022.102129},

issn = {1879-0771},

year  = {2022},

date = {2022-12-01},

journal = {Comput Med Imaging Graph},

volume = {102},

pages = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36116143,

title = {Pulmonary arterial pruning is associated with CT-derived bronchiectasis progression in smokers},

author = {Wojciech R Dolliver and Wei Wang and Pietro Nardelli and Farbod N Rahaghi and Jose L Orejas and Diego J Maselli and Andrew Yen and Kendra Young and Gregory Kinney and Raul San José Estépar and Alejandro A Diaz},

doi = {10.1016/j.rmed.2022.106971},

issn = {1532-3064},

year  = {2022},

date = {2022-10-01},

journal = {Respir Med},

volume = {202},

pages = {106971},

abstract = {Loss of small pulmonary arteries measured as the ratio of blood vessel volume in arteries <5 mm 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35638925,

title = {Traction Bronchiectasis/Bronchiolectasis on CT Scans in Relationship to Clinical Outcomes and Mortality: The COPDGene Study},

author = {Akinori Hata and Takuya Hino and Rachel K Putman and Masahiro Yanagawa and Tomoyuki Hida and Aravind A Menon and Osamu Honda and Yoshitake Yamada and Mizuki Nishino and Tetsuro Araki and Vladimir I Valtchinov and Masahiro Jinzaki and Hiroshi Honda and Kousei Ishigami and Takeshi Johkoh and Noriyuki Tomiyama and David C Christiani and David A Lynch and Raúl San José Estépar and George R Washko and Michael H Cho and Edwin K Silverman and Gary M Hunninghake and Hiroto Hatabu and },

doi = {10.1148/radiol.212584},

issn = {1527-1315},

year  = {2022},

date = {2022-09-01},

journal = {Radiology},

volume = {304},

number = {3},

pages = {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;  = .01]; TBI-1: coefficient, 3.3 [95% CI: 1.1, 5.6;  = .003]; TBI-2: coefficient, 7.6 [95% CI: 4.0, 11;  < .001]; TBI-3: coefficient, 32 [95% CI: 17, 48;  < .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;  = .049]; TBI-2-3: HR, 3.8 [95% CI: 2.6, 5.6;  < .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 . See also the editorial by Lee and Im in this issue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36075255,

title = {Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission},

author = {Daiana Stolz and Takudzwa Mkorombindo and Desiree M Schumann and Alvar Agusti and Samuel Y Ash and Mona Bafadhel and Chunxue Bai and James D Chalmers and Gerard J Criner and Shyamali C Dharmage and Frits M E Franssen and Urs Frey and MeiLan Han and Nadia N Hansel and Nathaniel M Hawkins and Ravi Kalhan and Melanie Konigshoff and Fanny W Ko and Trisha M Parekh and Pippa Powell and Maureen Rutten-van Mölken and Jodie Simpson and Don D Sin and Yuanlin Song and Bela Suki and Thierry Troosters and George R Washko and Tobias Welte and Mark T Dransfield},

doi = {10.1016/S0140-6736(22)01273-9},

issn = {1474-547X},

year  = {2022},

date = {2022-09-01},

journal = {Lancet},

volume = {400},

number = {10356},

pages = {921--972},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35850124,

title = {The low flyers: persistent airflow limitation in young adults},

author = {Francesca Polverino and George R Washko and Ronina A Covar and Eric B Hysinger and Tillie L Hackett and Surya P Bhatt and Guy Brusselle and Shyamali C Dharmage},

doi = {10.1016/S2213-2600(22)00250-8},

issn = {2213-2619},

year  = {2022},

date = {2022-09-01},

journal = {Lancet Respir Med},

volume = {10},

number = {9},

pages = {819--822},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35115336,

title = {Interstitial lung abnormalities are associated with decreased mean telomere length},

author = {Rachel K Putman and Gisli Thor Axelsson and Samuel Y Ash and Jason L Sanders and Aravind A Menon and Tetsuro Araki and Mizuki Nishino and Masahiro Yanagawa and Elías F Gudmundsson and Dandi Qiao and Raúl San José Estépar and Josée Dupuis and George T O'Connor and Ivan O Rosas and George R Washko and Souheil El-Chemaly and Benjamin A Raby and Vilmundur Gudnason and Dawn L DeMeo and Edwin K Silverman and Hiroto Hatabu and Immaculata De Vivo and Michael H Cho and Gunnar Gudmundsson and Gary M Hunninghake},

doi = {10.1183/13993003.01814-2021},

issn = {1399-3003},

year  = {2022},

date = {2022-08-01},

journal = {Eur Respir J},

volume = {60},

number = {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).nnMETHODS: 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.nnRESULTS: 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).nnCONCLUSION: ILA are associated with decreased MTL.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34996832,

title = {The association of lung function and pulmonary vasculature volume with cardiorespiratory fitness in the community},

author = {Jenna McNeill and Ariel Chernofsky and Matthew Nayor and Farbod N Rahaghi and Raul San Jose Estepar and George Washko and Andrew Synn and Ramachandran S Vasan and George O'Connor and Martin G Larson and Jennifer E Ho and Gregory D Lewis},

doi = {10.1183/13993003.01821-2021},

issn = {1399-3003},

year  = {2022},

date = {2022-08-01},

journal = {Eur Respir J},

volume = {60},

number = {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.nnMETHODS: 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 (FEV), forced vital capacity (FVC), FEV/FVC and diffusing capacity of the lung for carbon monoxide ( ) with the primary outcome of peak oxygen uptake (' ) along with other CPET parameters using multivariable linear regression. Finally, we investigated the association of total and peripheral pulmonary blood vessel volume with peak ' .nnRESULTS: We found lower FEV, FVC and   were associated with lower peak ' . For example, a 1 L lower FEV 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 ' , respectively. By contrast, FEV/FVC was not associated with peak ' . Lower lung function was associated with lower oxygen uptake efficiency slope, oxygen pulse slope, ' at anaerobic threshold (AT), minute ventilation (') at AT and breathing reserve. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peak ' .nnCONCLUSIONS: In a large, community-based cohort of adults, we found lower FEV, FVC and   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 ' . These findings underscore the importance of lung function and blood vessel volume as contributors to overall exercise capacity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35471111,

title = {Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts},

author = {Abhaya P Trivedi and Chase Hall and Charles W Goss and Daphne Lew and James G Krings and Mary Clare McGregor and Maanasi Samant and Jered P Sieren and Huashi Li and Ken B Schechtman and Joshua Schirm and Stephen McEleney and Sam Peterson and Wendy C Moore and Eugene R Bleecker and Deborah A Meyers and Elliot Israel and George R Washko and Bruce D Levy and Joseph K Leader and Sally E Wenzel and John V Fahy and Mark L Schiebler and Sean B Fain and Nizar N Jarjour and David T Mauger and Joseph M Reinhardt and John D Newell and Eric A Hoffman and Mario Castro and Ajay Sheshadri and },

doi = {10.1148/radiol.210363},

issn = {1527-1315},

year  = {2022},

date = {2022-08-01},

journal = {Radiology},

volume = {304},

number = {2},

pages = {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;  < .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,  < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2,  < .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;  < .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  See also the editorial by Verschakelen in this issue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35849828,

title = {Comparing Racial Differences in Emphysema Prevalence Among Adults With Normal Spirometry: A Secondary Data Analysis of the CARDIA Lung Study},

author = {Gabrielle Y Liu and Sadiya S Khan and Laura A Colangelo and Daniel Meza and George R Washko and Peter H S Sporn and David R Jacobs and Mark T Dransfield and Mercedes R Carnethon and Ravi Kalhan},

doi = {10.7326/M22-0205},

issn = {1539-3704},

year  = {2022},

date = {2022-08-01},

journal = {Ann Intern Med},

volume = {175},

number = {8},

pages = {1118--1125},

abstract = {BACKGROUND: Computed tomography (CT) imaging complements spirometry and may provide insight into racial disparities in respiratory health.nnOBJECTIVE: To determine the difference in emphysema prevalence between Black and White adults with different measures of normal spirometry results.nnDESIGN: Observational study using clinical data and spirometry from the CARDIA (Coronary Artery Risk Development in Young Adults) study obtained in 2015 to 2016 and CT scans done in 2010 to 2011.nnSETTING: 4 U.S. centers.nnPARTICIPANTS: Population-based sample of Black and White adults.nnMEASUREMENTS: Self-identified race and visually identified emphysema on CT in participants with different measures of "normal" spirometry results, calculated using standard race-specific and race-neutral reference equations.nnRESULTS: A total of 2674 participants (485 Black men, 762 Black women, 659 White men, and 768 White women) had both a CT scan and spirometry available for analysis. Among participants with a race-specific FEV between 80% and 99% of predicted, 6.5% had emphysema. In this group, emphysema prevalence was 3.9-fold (95% CI, 2.1- to 7.1-fold; 15.5% vs. 4.0%) higher among Black men than White men and 1.9-fold (CI, 1.0- to 3.8-fold; 6.6% vs. 3.4%) higher among Black women than White women. Among participants with a race-specific FEV between 100% and 120% of predicted, 4.0% had emphysema. In this category, Black men had a 6.4-fold (CI, 2.2- to 18.7-fold; 13.9% vs. 2.2%) higher prevalence of emphysema than White men, whereas Black and White women had a similar prevalence of emphysema (2.6% and 2.0%, respectively). The use of race-neutral equations to identify participants with an FEV percent predicted between 80% and 120% attenuated racial differences in emphysema prevalence among men and eliminated racial differences among women.nnLIMITATION: No CT scans were obtained during the most recent study visit (2015 to 2016) when spirometry was done.nnCONCLUSION: Emphysema is often present before spirometry findings become abnormal, particularly among Black men. Reliance on spirometry alone to differentiate lung health from lung disease may result in the underrecognition of impaired respiratory health and exacerbate racial disparities.nnPRIMARY FUNDING SOURCE: National Institutes of Health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34996830,

title = {  variants are associated with chronic bronchitis in smokers},

author = {Aabida Saferali and Dandi Qiao and Wonji Kim and Karen Raraigh and Hara Levy and Alejandro A Diaz and Garry R Cutting and Michael H Cho and Craig P Hersh and },

doi = {10.1183/13993003.01994-2021},

issn = {1399-3003},

year  = {2022},

date = {2022-08-01},

journal = {Eur Respir J},

volume = {60},

number = {2},

abstract = {INTRODUCTION: Loss-of-function variants in both copies of the cystic fibrosis transmembrane conductance regulator () gene cause cystic fibrosis (CF); however, there is evidence that reduction in CFTR function due to the presence of one deleterious variant can have clinical consequences. Here, we hypothesise that  variants in individuals with a history of smoking are associated with chronic obstructive pulmonary disease (COPD) and related phenotypes.nnMETHODS: Whole-genome sequencing was performed through the National Heart, Lung, and Blood Institute TOPMed (TransOmics in Precision Medicine) programme in 8597 subjects from the COPDGene (Genetic Epidemiology of COPD) study, an observational study of current and former smokers. We extracted clinically annotated  variants and performed single-variant and variant-set testing for COPD and related phenotypes. Replication was performed in 2118 subjects from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study.nnRESULTS: We identified 301 coding variants within the  gene boundary: 147 of these have been reported in individuals with CF, including 36 CF-causing variants. We found that CF-causing variants were associated with chronic bronchitis in variant-set testing in COPDGene (one-sided p=0.0025; OR 1.53) and in meta-analysis of COPDGene and ECLIPSE (one-sided p=0.0060; OR 1.52). Single-variant testing revealed that the F508del variant was associated with chronic bronchitis in COPDGene (one-sided p=0.015; OR 1.47). In addition, we identified 32 subjects with two or more  variants on separate alleles and these subjects were enriched for COPD cases (p=0.010).nnCONCLUSIONS: Cigarette smokers who carry one deleterious  variant have higher rates of chronic bronchitis, while presence of two  variants may be associated with COPD. These results indicate that genetically mediated reduction in CFTR function contributes to COPD related phenotypes, in particular chronic bronchitis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35469934,

title = {Left atrial contractile strain predicts recurrence of atrial tachyarrhythmia after catheter ablation},

author = {Anne Bjerg Nielsen and Kristoffer Grundtvig Skaarup and Kasper Djernæs and Raphael Hauser and Raúl San José Estépar and Samuel Kiil Sørensen and Martin Huth Ruwald and Morten Lock Hansen and René Husted Worck and Arne Johannessen and Jim Hansen and Tor Biering-Sørensen},

doi = {10.1016/j.ijcard.2022.04.056},

issn = {1874-1754},

year  = {2022},

date = {2022-07-01},

journal = {Int J Cardiol},

volume = {358},

pages = {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.nnMETHODS: 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).nnRESULTS: 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/m), only LASct remained an independent predictor of recurrence (OR = 1.07, CI95% [1.01; 1.12], p = 0.012, per 1% decrease).nnCONCLUSION: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35861819,

title = {Association of Pulmonary Function With Late-Life Cardiac Function and Heart Failure Risk: The ARIC Study},

author = {Sergio H R Ramalho and Brian L Claggett and George R Washko and Raul San Jose Estepar and Patricia P Chang and Dalane W Kitzman and Gerson Cipriano Junior and Scott D Solomon and Hicham Skali and Amil M Shah},

doi = {10.1161/JAHA.121.023990},

issn = {2047-9980},

year  = {2022},

date = {2022-07-01},

journal = {J Am Heart Assoc},

volume = {11},

number = {14},

pages = {e023990},

abstract = {Background Pulmonary and cardiac functions decline with age, but the associations of pulmonary dysfunction with cardiac function and heart failure (HF) risk in late life is not known. We aimed to determine the associations of percent predicted forced vital capacity (ppFVC) and the ratio of forced expired volume in 1 second (FEV) to forced vital capacity (FVC; FEV/FVC) with cardiac function and incident HF with preserved or reduced ejection fraction in late life. Methods and Results Among 3854 HF-free participants in the ARIC (Atherosclerosis Risk in Communities) cohort study who underwent echocardiography and spirometry at the fifth study visit (2011-2013), associations of FEV/FVC and ppFVC with echocardiographic measures, cardiac biomarkers, and risk of HF, HF with preserved ejection fraction, and HF with reduced ejection fraction were assessed. Multivariable linear and Cox regression models adjusted for demographics, body mass index, coronary disease, atrial fibrillation, hypertension, and diabetes. Mean age was 75±5 years, 40% were men, 19% were Black, and 61% were ever smokers. Mean FEV/FVC was 72±8%, and ppFVC was 98±17%. In adjusted analyses, lower FEV/FVC and ppFVC were associated with higher NT-proBNP (N-terminal pro-B-type natriuretic peptide; both <0.001) and pulmonary artery pressure (<0.004). Lower ppFVC was also associated with higher left ventricular mass, left ventricular filling pressure, and high-sensitivity C-reactive protein (all <0.01). Lower FEV/FVC was associated with a trend toward higher risk of incident HF with preserved ejection fraction (hazard ratio [HR] per 10-point decrease, 1.31; 95% CI, 0.98-1.74; =0.07) and HF with reduced ejection fraction (HR per 10-point decrease, 1.24; 95% CI, 0.91-1.70; =0.18), but these associations did not reach statistical significance. Lower ppFVC was associated with incident HF with preserved ejection fraction (HR per 10-unit decrease, 1.21; 95% CI, 1.04-1.41; =0.013) but not with HF with reduced ejection fraction (HR per 10-unit decrease, 0.90; 95% CI, 0.76-1.07; =0.24). Conclusions Subclinical reductions in FEV/FVC and ppFVC differentially associate with cardiac function and HF risk in late life.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35672437,

title = {Deep learning-based lesion subtyping and prediction of clinical outcomes in COVID-19 pneumonia using chest CT},

author = {David Bermejo-Peláez and Raúl San José Estépar and María Fernández-Velilla and Carmelo Palacios Miras and Guillermo Gallardo Madueño and Mariana Benegas and Carolina Gotera Rivera and Sandra Cuerpo and Miguel Luengo-Oroz and Jacobo Sellarés and Marcelo Sánchez and Gorka Bastarrika and German Peces Barba and Luis M Seijo and María J Ledesma-Carbayo},

doi = {10.1038/s41598-022-13298-8},

issn = {2045-2322},

year  = {2022},

date = {2022-06-01},

journal = {Sci Rep},

volume = {12},

number = {1},

pages = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34785234,

title = {Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers},

author = {Stefanie E Mason and Rafael Moreta-Martinez and Wassim W Labaki and Matthew J Strand and Elizabeth A Regan and Jessica Bon and Ruben San Jose Estepar and Richard Casaburi and Merry-Lynn McDonald and Harry B Rossiter and Barry Make and Mark T Dransfield and MeiLan K Han and Kendra Young and Jeffrey L Curtis and Kathleen Stringer and Greg Kinney and John E Hokanson and Raul San Jose Estepar and George R Washko and },

doi = {10.1016/j.chest.2021.10.047},

issn = {1931-3543},

year  = {2022},

date = {2022-04-01},

journal = {Chest},

volume = {161},

number = {4},

pages = {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.nnRESEARCH 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?nnSTUDY 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.nnRESULTS: 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-cm 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.nnINTERPRETATION: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34890215,

title = {Artificial intelligence in functional imaging of the lung},

author = {Raúl San José Estépar},

doi = {10.1259/bjr.20210527},

issn = {1748-880X},

year  = {2022},

date = {2022-04-01},

journal = {Br J Radiol},

volume = {95},

number = {1132},

pages = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34742688,

title = {Interstitial Lung Abnormalities, Emphysema, and Spirometry in Smokers},

author = {Aravind A Menon and Rachel K Putman and Jason L Sanders and Takuya Hino and Akinori Hata and Mizuki Nishino and Auyon J Ghosh and Samuel Y Ash and Ivan O Rosas and Michael H Cho and David A Lynch and George R Washko and Edwin K Silverman and Hiroto Hatabu and Gary M Hunninghake},

doi = {10.1016/j.chest.2021.10.034},

issn = {1931-3543},

year  = {2022},

date = {2022-04-01},

journal = {Chest},

volume = {161},

number = {4},

pages = {999--1010},

abstract = {BACKGROUND: Most pulmonary conditions reduce FVC, but studies of patients with combined pulmonary fibrosis and emphysema demonstrate that reductions in FVC are less than expected when these two conditions coexist clinically.nnRESEARCH QUESTION: Do interstitial lung abnormalities (ILAs), chest CT imaging findings that may suggest an early stage of pulmonary fibrosis in individuals with undiagnosed disease, affect the association between emphysema and FVC?nnSTUDY DESIGN AND METHODS: Measures of ILA and emphysema were available for 9,579 and 5,277 participants from phases 1 (2007-2011) and 2 (2012-2016) of the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study (COPDGene), respectively. ILA were defined by Fleischner Society guidelines. Adjusted linear regression models were used to assess the associations and interactions among ILA, emphysema, measures of spirometry, and lung function.nnRESULTS: ILA were present in 528 (6%) and 580 (11%) of participants in phases 1 and 2 of COPDGene, respectively. ILA modified the association between emphysema and FVC (P < .0001 for interaction) in both phases. In phase 1, in those without ILA, a 5% increase in emphysema was associated with a reduction in FVC (-110 mL; 95% CI, -121 to -100 mL; P < .0001); however, in those with ILA, it was not (-11 mL; 95% CI, -53 to 31; P = .59). In contrast, no interaction was found between ILA and emphysema on total lung capacity or on diffusing capacity of carbon monoxide.nnINTERPRETATION: The presence of ILA attenuates the reduction in FVC associated with emphysema.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34592319,

title = {Significant Spirometric Transitions and Preserved Ratio Impaired Spirometry Among Ever Smokers},

author = {Emily S Wan and John E Hokanson and Elizabeth A Regan and Kendra A Young and Barry J Make and Dawn L DeMeo and Stefanie E Mason and Raul San Jose Estepar and James D Crapo and Edwin K Silverman},

doi = {10.1016/j.chest.2021.09.021},

issn = {1931-3543},

year  = {2022},

date = {2022-03-01},

journal = {Chest},

volume = {161},

number = {3},

pages = {651--661},

abstract = {BACKGROUND: Emerging data from longitudinal studies suggest that preserved ratio impaired spirometry (PRISm), defined by proportionate reductions in FEV 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).nnRESEARCH QUESTION: Are individuals with PRISm enriched for transitions associated with substantial changes in lung function?nnSTUDY 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 (FEV < 80% predicted with FEV/FVC ratio ≥ 0.7), Global Initiative for Chronic Obstructive Lung Disease grade 0 (FEV ≥ 80% predicted and FEV/FVC ≥ 0.7), and obstruction (FEV/FVC < 0.7). Significant transition status was affirmative if a subject belonged to two or more spirometric categories and had > 10% change in FEV % 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, FEV % predicted, current smoking, pack-years, BMI, and ever-positive bronchodilator response.nnRESULTS: 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 FEV alone (regardless of change in FVC % predicted) was used to define significant transitions.nnINTERPRETATION: PRISm is an unstable group, with frequent significant transitions to both obstruction and normal spirometry over time.nnCLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT000608764; URL: www.nnCLINICALTRIALS: gov.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34530700,

title = {Prevalence and Population Attributable Risk for Early Chronic Obstructive Pulmonary Disease in U.S. Hispanic/Latino Individuals},

author = {Fariha Khalid and Wei Wang and David Mannino and Alejandro A Diaz},

doi = {10.1513/AnnalsATS.202103-253OC},

issn = {2325-6621},

year  = {2022},

date = {2022-03-01},

journal = {Ann Am Thorac Soc},

volume = {19},

number = {3},

pages = {363--371},

abstract = { In predominantly White populations, early chronic obstructive pulmonary disease (COPD) (i.e., COPD in people aged <50 yr) has been linked to higher hospitalization rates and mortality; however, the prevalence, risk factors, and population attributable risk (PAR) of early COPD remain to be determined in non-White populations.  We aimed to examine the prevalence, risk factors, and PARs of early COPD among Hispanic/Latino individuals, the largest U.S. minority group.  We used baseline data from the Hispanic Community Health Study/Study of Latinos, a population-based probability sample of 16,415 Hispanic/Latino individuals aged 18-74 years. Participants aged <50 years were included ( = 7,323). Early COPD was defined as a forced expiratory volume in 1 second to forced vital capacity ratio less than the lower limit of normal. We used survey logistic regression analysis to identify risk factors and estimate the prevalence of early COPD. PARs of the risk factors identified were estimated.  A total of 524 participants met the criteria for early COPD, yielding a sex- and age-adjusted prevalence of 7.6% (95% confidence interval [CI], 6.8-8.6). Asthma (odds ratio [OR], 3.37; 95% CI, 2.57-4.41), smoking status (ever vs. never; OR, 1.65; 95% CI, 1.24-2.20), and chronic sinusitis (OR, 1.71; 95% CI, 1.09-2.66) were associated with increased odds of early COPD. Immigrants versus U.S.-born individuals have lower odds of early COPD (age at immigration <15 yr and living in the United States <10 yr; OR, 0.94; 95% CI, 0.39-2.27; age at immigration <15 yr and living in the United States ⩾10 yr; OR, 0.55; 95% CI, 0.37-0.84; age at immigration ⩾15 yr and living in the United States <10 yr; OR, 0.86; 95% CI, 0.57-1.30; and age at immigration ⩾15 yr and living in the United States ⩾10 yr; OR, 0.63; 95% CI, 0.42-0.95). Among smokers, pack-years was not associated with early COPD (5-9.9 vs. <5 pack-years; OR, 1.04; 95% CI, 0.59-1.82; ⩾10 vs. <5 pack-years; OR, 1.20; 95% CI, 0.74-1.94). The mean PAR for asthma, smoking status, and chronic sinusitis was 26.3% (95% CI, 22.1-30.3), 22.4% (95% CI, 17.4-27.1), and 6.9% (95% CI, 4.3-9.4), respectively.  Among U.S. Hispanic/Latino individuals, asthma is one of the most important risk factors for early COPD, followed by smoking and chronic sinusitis. Immigrants appear to have a lower risk of early COPD than U.S.-born Hispanic/Latino individuals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34509450,

title = {Neighborhood Socioeconomic Deprivation in Young Adulthood and Future Respiratory Health: The CARDIA Lung Study},

author = {Sneha Thatipelli and Kiarri N Kershaw and Laura A Colangelo and Penny Gordon-Larsen and David R Jacobs and Mark T Dransfield and Daniel Meza and Sharon R Rosenberg and George R Washko and Trisha M Parekh and Mercedes R Carnethon and Ravi Kalhan},

doi = {10.1016/j.amjmed.2021.07.048},

issn = {1555-7162},

year  = {2022},

date = {2022-02-01},

journal = {Am J Med},

volume = {135},

number = {2},

pages = {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.nnMETHODS: 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).nnRESULTS: 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 (FEV) 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).nnCONCLUSIONS: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34197782,

title = {Detection and Early Referral of Patients With Interstitial Lung Abnormalities: An Expert Survey Initiative},

author = {Gary M Hunninghake and Jonathan G Goldin and Michael A Kadoch and Jonathan A Kropski and Ivan O Rosas and Athol U Wells and Ruchi Yadav and Howard M Lazarus and Fereidoun G Abtin and Tamera J Corte and Joao A de Andrade and Kerri A Johannson and Martin R Kolb and David A Lynch and Justin M Oldham and Paolo Spagnolo and Mary E Strek and Sara Tomassetti and George R Washko and Eric S White and },

doi = {10.1016/j.chest.2021.06.035},

issn = {1931-3543},

year  = {2022},

date = {2022-02-01},

journal = {Chest},

volume = {161},

number = {2},

pages = {470--482},

abstract = {BACKGROUND: Interstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILA are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA. Early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral.nnRESEARCH QUESTION: Can consensus-based expert recommendations be identified to guide clinicians in the recognition, referral, and follow-up of patients with or at risk of developing early ILDs?nnSTUDY DESIGN AND METHODS: Pulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. The surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement.nnRESULTS: Fifty-five experts were invited and 44 participated; consensus was reached on 39 of 85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (eg, with the Lung CT Screening Reporting and Data System "S-modifier" [Lung-RADS; which indicates clinically significant or potentially significant noncancer findings]), recommending referral to a pulmonologist in the radiology report; high-resolution CT imaging and full pulmonary function tests should be ordered if nondependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules, or patchy ground-glass opacity are observed on CT imaging; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD.nnINTERPRETATION: Guidance was established for identifying clinically relevant ILA, subsequent referral, and follow-up. These results lay the foundation for developing practical guidance on managing patients with ILA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34237330,

title = {An Integrative Genomic Strategy Identifies sRAGE as a Causal and Protective Biomarker of Lung Function},

author = {Joshua Keefe and Chen Yao and Shih-Jen Hwang and Paul Courchesne and Gha Young Lee and Josée Dupuis and Joseph P Mizgerd and George O'Connor and George R Washko and Michael H Cho and Edwin K Silverman and Daniel Levy},

doi = {10.1016/j.chest.2021.06.053},

issn = {1931-3543},

year  = {2022},

date = {2022-01-01},

journal = {Chest},

volume = {161},

number = {1},

pages = {76--84},

abstract = {BACKGROUND: There are few clinically useful circulating biomarkers of lung function and lung disease. We hypothesized that genome-wide association studies (GWAS) of circulating proteins in conjunction with GWAS of pulmonary traits represents a clinically relevant approach to identifying causal proteins and therapeutically useful insights into mechanisms related to lung function and disease.nnSTUDY QUESTION: Can an integrative genomic strategy using GWAS of plasma soluble receptor for advanced glycation end-products (sRAGE) levels in conjunction with GWAS of lung function traits identify putatively causal relations of sRAGE to lung function?nnSTUDY DESIGN AND METHODS: Plasma sRAGE levels were measured in 6,861 Framingham Heart Study participants and GWAS of sRAGE was conducted to identify protein quantitative trait loci (pQTL), including cis-pQTL variants at the sRAGE protein-coding gene locus (AGER). We integrated sRAGE pQTL variants with variants from GWAS of lung traits. Colocalization of sRAGE pQTL variants with lung trait GWAS variants was conducted, and Mendelian randomization was performed using sRAGE cis-pQTL variants to infer causality of sRAGE for pulmonary traits. Cross-sectional and longitudinal protein-trait association analyses were conducted for sRAGE in relation to lung traits.nnRESULTS: Colocalization identified shared genetic signals for sRAGE with lung traits. Mendelian randomization analyses suggested protective causal relations of sRAGE to several pulmonary traits. Protein-trait association analyses demonstrated higher sRAGE levels to be cross-sectionally and longitudinally associated with preserved lung function.nnINTERPRETATION: sRAGE is produced by type I alveolar cells, and it acts as a decoy receptor to block the inflammatory cascade. Our integrative genomics approach provides evidence for sRAGE as a causal and protective biomarker of lung function, and the pattern of associations is suggestive of a protective role of sRAGE against restrictive lung physiology. We speculate that targeting the AGER/sRAGE axis may be therapeutically beneficial for the treatment and prevention of inflammation-related lung disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34270966,

title = {Quantification of Arterial and Venous Morphologic Markers in Pulmonary Arterial Hypertension Using CT Imaging},

author = {Farbod N Rahaghi and Pietro Nardelli and Eileen Harder and Inderjit Singh and Gonzalo Vegas Sánchez-Ferrero and James C Ross and Rubén San José Estépar and Samuel Y Ash and Andetta R Hunsaker and Bradley A Maron and Jane A Leopold and Aaron B Waxman and Raúl San José Estépar and George R Washko},

doi = {10.1016/j.chest.2021.06.069},

issn = {1931-3543},

year  = {2021},

date = {2021-12-01},

journal = {Chest},

volume = {160},

number = {6},

pages = {2220--2231},

abstract = {BACKGROUND: Pulmonary hypertension is a heterogeneous disease, and a significant portion of patients at risk for it have CT imaging available. Advanced automated processing techniques could be leveraged for early detection, screening, and development of quantitative phenotypes. Pruning and vascular tortuosity have been previously described in pulmonary arterial hypertension (PAH), but the extent of these phenomena in arterial vs venous pulmonary vasculature and in exercise pulmonary hypertension (ePH) have not been described.nnRESEARCH QUESTION: What are the arterial and venous manifestations of pruning and vascular tortuosity using CT imaging in PAH, and do they also occur in ePH?nnSTUDY DESIGN AND METHODS: A cohort of patients with PAH and ePH and control subjects with available CT angiograms were retrospectively identified to examine the differential arterial and venous presence of pruning and tortuosity in patients with precapillary pulmonary hypertension not confounded by lung or thromboembolic disease. The pulmonary vasculature was reconstructed, and an artificial intelligence method was used to separate arteries and veins and to compute arterial and venous vascular volumes and tortuosity.nnRESULTS: A total of 42 patients with PAH, 12 patients with ePH, and 37 control subjects were identified. There was relatively lower (median [interquartile range]) arterial small vessel volume in subjects with PAH (PAH 14.7 [11.7-16.5; P < .0001]) vs control subjects (16.9 [15.6-19.2]) and venous small vessel volume in subjects with PAH and ePH (PAH 8.0 [6.5-9.6; P < .0001]; ePH, 7.8 [7.5-11.4; P = .004]) vs control subjects (11.5 [10.6-12.2]). Higher large arterial volume, however, was only observed in the pulmonary arteries (PAH 17.1 [13.6-23.4; P < .0001] vs control subjects 11.4 [8.1-15.4]). Similarly, tortuosity was higher in the pulmonary arteries in the PAH group (PAH 3.5 [3.3-3.6; P = .0002] vs control 3.2 [3.2-3.3]).nnINTERPRETATION: Lower small distal pulmonary vascular volume, higher proximal arterial volume, and higher arterial tortuosity were observed in PAH. These can be quantified by using automated techniques from clinically acquired CT scans of patients with ePH and resting PAH.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34523824,

title = {Genetic variation in genes regulating skeletal muscle regeneration and tissue remodelling associated with weight loss in chronic obstructive pulmonary disease},

author = {Preeti Lakshman Kumar and Ava C Wilson and Alison Rocco and Michael H Cho and Emily Wan and Brian D Hobbs and George R Washko and Victor E Ortega and Stephanie A Christenson and Xingnan Li and J Michael Wells and Surya P Bhatt and Dawn L DeMeo and Sharon M Lutz and Harry Rossiter and Richard Casaburi and Stephen I Rennard and David A Lomas and Wassim W Labaki and Ruth Tal-Singer and Russel P Bowler and Craig P Hersh and Hemant K Tiwari and Mark Dransfield and Anna Thalacker-Mercer and Deborah A Meyers and Edwin K Silverman and Merry-Lynn N McDonald and },

doi = {10.1002/jcsm.12782},

issn = {2190-6009},

year  = {2021},

date = {2021-12-01},

journal = {J Cachexia Sarcopenia Muscle},

volume = {12},

number = {6},

pages = {1803--1817},

abstract = {BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach.nnMETHODS: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low BMI (BMI < 20 kg/m ). In ECLIPSE and SPIROMICS, weight loss was calculated using available longitudinal visits. Stratified analyses were performed among African American (AA) and Non-Hispanic White (NHW) participants with COPD. Single variant and gene-based analyses were performed adjusting for confounders. Fine mapping was performed using a Bayesian approach integrating genetic association results with linkage disequilibrium and functional annotation. Significant gene networks were identified by integrating genetic regions associated with weight loss with skeletal muscle protein-protein interaction (PPI) data.nnRESULTS: At the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio = 3.6, 95% confidence interval = 2.3-5.6, P = 3.2 × 10 ) among AA COPD participants in COPDGene. At the gene level in COPDGene, EFNA2 and BAIAP2 were significantly associated with weight loss in AA and NHW COPD participants, respectively. The EFNA2 association replicated among AA from SPIROMICS (P = 0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P = 0.025). The EFNA2 gene encodes the membrane-bound protein ephrin-A2 involved in the regulation of developmental processes and adult tissue homeostasis such as skeletal muscle. The BAIAP2 gene encodes the insulin-responsive protein of mass 53 kD (IRSp53), a negative regulator of myogenic differentiation. Integration of the gene-based findings participants with PPI data revealed networks of genes involved in pathways such as Rho and synapse signalling.nnCONCLUSIONS: The EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD participants. Collectively, the integrative network analyses indicated genetic variation associated with weight loss in COPD may influence skeletal muscle regeneration and tissue remodelling.},

keywords = {},

pubstate = {published},

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@article{pmid34800009,

title = {Gene expression of oxidative stress markers and lung function: A CARDIA lung study},

author = {Ramya Ramasubramanian and Ravi Kalhan and David R Jacobs and George R Washko and Lifang Hou and Myron D Gross and Weihua Guan and Bharat Thyagarajan},

doi = {10.1002/mgg3.1832},

issn = {2324-9269},

year  = {2021},

date = {2021-12-01},

journal = {Mol Genet Genomic Med},

volume = {9},

number = {12},

pages = {e1832},

abstract = {BACKGROUND: Circulating markers of oxidative stress have been associated with lower lung function. Our objective was to study the association of gene expression levels of oxidative stress pathway genes (ALOX12, ALOX15, ARG2, GSTT1, LPO, MPO, NDUFB3, PLA2G7, and SOD3) and lung function forced expiratory volume in one second (FEV ), forced vital capacity (FVC) in Coronary Artery Risk Development in Young Adults study.nnMETHODS: Lung function was measured using spirometry and the Nanostring platform was used to estimate gene expression levels. Linear regression models were used to study association of lung function measured at year 30, 10-year decline in lung function and gene expression after adjustment for center, smoking, and BMI, measured at year 25.nnRESULTS: The 10-year decline of FEV was faster in highest NDUFB3 quartile compared to the lowest (difference = -2.09%; p = 0.001) after adjustment for multiple comparisons. The 10-year decline in FEV and FVC was nominally slower in highest versus lowest quartile of PLA2G7 (difference = 1.14%; p = 0.02, and difference = 1.06%; p = 0.005, respectively). The other genes in the study were not associated with FEV or FVC.nnCONCLUSION: Higher gene expression levels in oxidative stress pathway genes are associated with faster 10-year FEV decline.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34432901,

title = {Harmonization of in-plane resolution in CT using multiple reconstructions from single acquisitions},

author = {Gonzalo Vegas-Sánchez-Ferrero and Gabriel Ramos-Llordén and Raúl San José Estépar},

doi = {10.1002/mp.15186},

issn = {2473-4209},

year  = {2021},

date = {2021-11-01},

journal = {Med Phys},

volume = {48},

number = {11},

pages = {6941--6961},

abstract = {PURPOSE: To providea methodology that removes the spatial variability of in-plane resolution using different CT reconstructions. The methodology does not require any training, sinogram, or specific reconstruction method.nnMETHODS: The methodology is formulated as a reconstruction problem. The desired sharp image is modeled as an unobservable variable to be estimated from an arbitrary number of observations with spatially variant resolution. The methodology comprises three steps: (1) density harmonization, which removes the density variability across reconstructions; (2) point spread function (PSF) estimation, which estimates a spatially variant PSF with arbitrary shape; (3) deconvolution, which is formulated as a regularized least squares problem. The assessment was performed with CT scans of phantoms acquired with three different Siemens scanners (Definition AS, Definition AS+, Drive). Four low-dose acquisitions reconstructed with backprojection and iterative methods were used for the resolution harmonization. A sharp, high-dose (HD) reconstruction was used as a validation reference. The different factors affecting the in-plane resolution (radial, angular, and longitudinal) were studied with regression analysis of the edge decay (between 10% and 90% of the edge spread function (ESF) amplitude).nnRESULTS: Results showed that the in-plane resolution improves remarkably and the spatial variability is substantially reduced without compromising the noise characteristics. The modulated transfer function (MTF) also confirmed a pronounced increase in resolution. The resolution improvement was also tested by measuring the wall thickness of tubes simulating airways. In all scanners, the resolution harmonization obtained better performance than the HD, sharp reconstruction used as a reference (up to 50 percentage points). The methodology was also evaluated in clinical scans achieving a noise reduction and a clear improvement in thin-layered structures. The estimated ESF and MTF confirmed the resolution improvement.nnCONCLUSION: We propose a versatile methodology to reduce the spatial variability of in-plane resolution in CT scans by leveraging different reconstructions available in clinical studies. The methodology does not require any sinogram, training, or specific reconstruction, and it is not limited to a fixed number of input images. Therefore, it can be easily adopted in multicenter studies and clinical practice. The results obtained with our resolution harmonization methodology evidence its suitability to reduce the spatially variant in-plane resolution in clinical CT scans without compromising the reconstruction's noise characteristics. We believe that the resolution increase achieved by our methodology may contribute in more accurate and reliable measurements of small structures such as vasculature, airways, and wall thickness.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34490723,

title = {Predictors of lung function trajectories in population-based studies: A systematic review},

author = {Daniel O Okyere and Dinh S Bui and George R Washko and Caroline J Lodge and Adrian J Lowe and Raisa Cassim and Jennifer L Perret and Michael J Abramson and E Haydn Walters and Nilakshi T Waidyatillake and Shyamali C Dharmage},

doi = {10.1111/resp.14142},

issn = {1440-1843},

year  = {2021},

date = {2021-10-01},

journal = {Respirology},

volume = {26},

number = {10},

pages = {938--959},

abstract = {Despite the growing body of evidence on lung function trajectories over the life course and their risk factors, the literature has not been systematically synthesized. Publications related to lung function trajectories were identified from PubMed, EMBASE and CINAHL databases. Two authors independently identified publications for inclusion according to predefined selection criteria. Studies that modelled lung function trajectories and reported associated exposures were included. Meta-analyses could not be conducted due to heterogeneity in the exposures and methods used to model lung function trajectories. Nine publications were eligible for inclusion of which four used group-based trajectory modelling to model lung function trajectories, while five used latent profile analysis. Studies with repeated lung function measurements over the life course identified more trajectories than others. Only one study spanning from childhood to middle age reported catch-up trajectory. The following childhood risk factors for subnormal lung function trajectories were observed in at least across two studies: low birth weight, early wheezing, asthma, allergic sensitization, eczema, allergic rhinitis, lower respiratory tract infections, family history of asthma and second-hand smoke exposure. Adult active asthma and personal cigarette smoking were observed to be associated with accelerated decline lung trajectories. Our review identified 10 risk factors associated with the growth, catch-up, reduced plateau and decline trajectories of lung function. Intervention directed at childhood asthma and infections, and tobacco smoke exposure at all ages would help promote lung health and prevent subnormal lung function trajectories.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34156303,

title = {Small Airway Disease and Emphysema Are Associated with Future Exacerbations in Smokers with CT-derived Bronchiectasis and COPD: Results from the COPDGene Cohort},

author = {Diego Jose Maselli and Andrew Yen and Wei Wang and Yuka Okajima and Wojciech R Dolliver and Christina Mercugliano and Antonio Anzueto and Marcos I Restrepo and Timothy R Aksamit and Ashwin Basavaraj and Stefano Aliberti and Kendra A Young and Gregory L Kinney and J Michael Wells and Raúl San José Estépar and David A Lynch and Alejandro A Diaz},

doi = {10.1148/radiol.2021204052},

issn = {1527-1315},

year  = {2021},

date = {2021-09-01},

journal = {Radiology},

volume = {300},

number = {3},

pages = {706--714},

abstract = {Background Chronic obstructive pulmonary disease (COPD) and bronchiectasis can overlap and share pathologic features, such as small airway disease (SAD). Whether the presence of SAD and emphysema in smokers with CT-derived bronchiectasis is associated with exacerbations is unknown. Purpose To assess whether SAD and emphysema in smokers with CT-derived bronchiectasis are associated with future exacerbations. Materials and Methods SAD and emphysema were quantified using the parametric response map method in former and current heavy smokers with and without bronchiectasis at CT from the COPDGene Study (from July 2009 to July 2018). Exacerbations were prospectively assessed through biannual follow-up. An exacerbation was defined as an increase in or new onset of respiratory symptoms treated with antibiotics and/or corticosteroids. Severe exacerbations were defined as those that required hospitalization. The association of a high burden of SAD (≥15.6%) and high burden of emphysema (≥5%) at CT with exacerbations was assessed with generalized linear mixed models. Results Of 737 participants, 387 (median age, 64 years [interquartile range, 58-71 years]; 223 women) had CT-derived bronchiectasis. During a 9-year follow-up, after adjustment for age, sex, race, body mass index, current smoking status, pack-years, exacerbations before study entry, forced expiratory volume in 1 second, or FEV, and bronchiectasis severity CT score, high burden of SAD and high burden of emphysema were associated with a higher number of exacerbations per year (relative risk [RR], 1.89 [95% CI: 1.54, 2.33] and 1.37 [95% CI: 1.13, 1.66], respectively;  ≤ .001 for both). Results were comparable among participants with bronchiectasis meeting criteria for COPD ( = 197) (RR, 1.67 [95% CI: 1.23, 2.27] for high burden of SAD and 1.51 [95% CI: 1.20, 1.91] for high burden of emphysema;  ≤ .001 for both). Conclusion In smokers with CT-derived bronchiectasis and chronic obstructive pulmonary disease, structural damage to lung parenchyma and small airways was associated with a higher number of exacerbations per year. Clinical trial registration no. NCT00608764 © RSNA, 2021.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33684789,

title = {QIBA guidance: Computed tomography imaging for COVID-19 quantitative imaging applications},

author = {Ricardo S Avila and Sean B Fain and Chuck Hatt and Samuel G Armato and James L Mulshine and David Gierada and Mario Silva and David A Lynch and Eric A Hoffman and Frank N Ranallo and John R Mayo and David Yankelevitz and Raul San Jose Estepar and Raja Subramaniam and Claudia I Henschke and Alex Guimaraes and Daniel C Sullivan},

doi = {10.1016/j.clinimag.2021.02.017},

issn = {1873-4499},

year  = {2021},

date = {2021-09-01},

journal = {Clin Imaging},

volume = {77},

pages = {151--157},

abstract = {As the COVID-19 pandemic impacts global populations, computed tomography (CT) lung imaging is being used in many countries to help manage patient care as well as to rapidly identify potentially useful quantitative COVID-19 CT imaging biomarkers. Quantitative COVID-19 CT imaging applications, typically based on computer vision modeling and artificial intelligence algorithms, include the potential for better methods to assess COVID-19 extent and severity, assist with differential diagnosis of COVID-19 versus other respiratory conditions, and predict disease trajectory. To help accelerate the development of robust quantitative imaging algorithms and tools, it is critical that CT imaging is obtained following best practices of the quantitative lung CT imaging community. Toward this end, the Radiological Society of North America's (RSNA) Quantitative Imaging Biomarkers Alliance (QIBA) CT Lung Density Profile Committee and CT Small Lung Nodule Profile Committee developed a set of best practices to guide clinical sites using quantitative imaging solutions and to accelerate the international development of quantitative CT algorithms for COVID-19. This guidance document provides quantitative CT lung imaging recommendations for COVID-19 CT imaging, including recommended CT image acquisition settings for contemporary CT scanners. Additional best practice guidance is provided on scientific publication reporting of quantitative CT imaging methods and the importance of contributing COVID-19 CT imaging datasets to open science research databases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34544259,

title = {Loss of Pulmonary Vascular Volume as a Predictor of Right Ventricular Dysfunction and Mortality in Acute Pulmonary Embolism},

author = {Jasleen Minhas and Pietro Nardelli and Syed Moin Hassan and Nadine Al-Naamani and Eileen Harder and Samuel Ash and Gonzalo Vegas Sánchez-Ferrero and Stefanie Mason and Andetta R Hunsaker and Gregory Piazza and Samuel Z Goldhaber and Aaron B Waxman and Steven M Kawut and Raúl San José Estépar and George R Washko and Farbod N Rahaghi},

doi = {10.1161/CIRCIMAGING.120.012347},

issn = {1942-0080},

year  = {2021},

date = {2021-09-01},

journal = {Circ Cardiovasc Imaging},

volume = {14},

number = {9},

pages = {e012347},

abstract = {BACKGROUND: In acute pulmonary embolism, chest computed tomography angiography derived metrics, such as the right ventricle (RV): left ventricle ratio are routinely used for risk stratification. Paucity of intraparenchymal blood vessels has previously been described, but their association with clinical biomarkers and outcomes has not been studied. We sought to determine if small vascular volumes measured on computed tomography scans were associated with an abnormal RV on echocardiography and mortality. We hypothesized that decreased small venous volume would be associated with greater RV dysfunction and increased mortality.nnMETHODS: A retrospective cohort of patients with intermediate risk pulmonary embolism admitted to Brigham and Women's Hospital between 2009 and 2017 was assembled, and clinical and radiographic data were obtained. We performed 3-dimensional reconstructions of vasculature to assess intraparenchymal vascular volumes. Statistical analyses were performed using multivariable regression and cox proportional hazards models, adjusting for age, sex, lung volume, and small arterial volume.nnRESULTS: Seven hundred twenty-two subjects were identified of whom 573 had documented echocardiography. A 50% reduction in small venous volume was associated with an increased risk of RV dilation (relative risk: 1.38 [95% CI, 1.18-1.63], <0.001), RV dysfunction (relative risk: 1.62 [95% CI, 1.36-1.95], <0.001), and RV strain (relative risk: 1.67 [95% CI, 1.37-2.04], <0.001); increased cardiac biomarkers, and higher 30-day and 90-day mortality (hazard ratio: 2.50 [95% CI, 1.33-4.67], =0.004 and hazard ratio: 1.84 [95% CI, 1.11-3.04], =0.019, respectively).nnCONCLUSIONS: Loss of small venous volume quantified from computed tomography angiography is associated with increased risk of abnormal RV on echocardiography, abnormal cardiac biomarkers, and higher risk of 30- and 90-day mortality. Small venous volume may be a useful marker for assessing disease severity in acute pulmonary embolism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34593486,

title = {Seeking diagnostic and prognostic biomarkers for childhood bacterial pneumonia in sub-Saharan Africa: study protocol for an observational study},

author = {Clarissa Valim and Yekin Ajauoi Olatunji and Yasir Shitu Isa and Rasheed Salaudeen and Sarwar Golam and Edward F Knol and Sheriffo Kanyi and Abdoulie Jammeh and Quique Bassat and Wilco de Jager and Alejandro A Diaz and Roger C Wiegand and Julio Ramirez and Marsha A Moses and Umberto D'Alessandro and Patricia L Hibberd and Grant A Mackenzie},

doi = {10.1136/bmjopen-2020-046590},

issn = {2044-6055},

year  = {2021},

date = {2021-09-01},

journal = {BMJ Open},

volume = {11},

number = {9},

pages = {e046590},

abstract = {INTRODUCTION: Clinically diagnosed pneumonia in children is a leading cause of paediatric hospitalisation and mortality. The aetiology is usually bacterial or viral, but malaria can cause a syndrome indistinguishable from clinical pneumonia. There is no method with high sensitivity to detect a bacterial infection in these patients and, as result, antibiotics are frequently overprescribed. Conversely, unrecognised concomitant bacterial infection in patients with malarial infections occur with omission of antibiotic therapy from patients with bacterial infections. Previously, we identified two combinations of blood proteins with 96% sensitivity and 86% specificity for detecting bacterial disease. The current project aimed to validate and improve these combinations by evaluating additional biomarkers in paediatric patients with clinical pneumonia. Our goal was to describe combinations of a limited number of proteins with high sensitivity and specificity for bacterial infection to be incorporated in future point-of-care tests. Furthermore, we seek to explore signatures to prognosticate clinical pneumonia.nnMETHODS AND ANALYSIS: Patients (n=900) aged 2-59 months presenting with clinical pneumonia at two Gambian hospitals will be enrolled and classified according to criteria for definitive bacterial aetiology (based on microbiological tests and chest radiographs). We will measure proteins at admission using Luminex-based immunoassays in 90 children with definitive and 160 with probable bacterial aetiology, and 160 children classified according to the prognosis of their disease. Previously identified diagnostic signatures will be assessed through accuracy measures. Moreover, we will seek new diagnostic and prognostic signatures through machine learning methods, including support vector machine, penalised regression and classification trees.nnETHICS AND DISSEMINATION: Ethics approval has been obtained from the Gambia Government/Medical Research Council Unit The Gambia Joint Ethics Committee (protocol 1616) and the institutional review board of Boston University Medical Centre (STUDY00000958). Study results will be disseminated to the staff of the study hospitals, in scientific seminars and meetings, and in publications.nnTRIAL REGISTRATION NUMBER: H-38462.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33971144,

title = {The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers},

author = {Divay Chandra and Aman Gupta and Gregory L Kinney and Carl R Fuhrman and Joseph K Leader and Alejandro A Diaz and Jessica Bon and R Graham Barr and George Washko and Matthew Budoff and John Hokanson and Frank C Sciurba and },

doi = {10.1016/j.chest.2021.04.066},

issn = {1931-3543},

year  = {2021},

date = {2021-09-01},

journal = {Chest},

volume = {160},

number = {3},

pages = {858--871},

abstract = {BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment.nnRESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers?nnSTUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV to FVC ratio, < 0.70).nnRESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts.nnINTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33834546,

title = {SNR-enhanced diffusion MRI with structure-preserving low-rank denoising in reproducing kernel Hilbert spaces},

author = {Gabriel Ramos-Llordén and Gonzalo Vegas-Sánchez-Ferrero and Congyu Liao and Carl-Fredrik Westin and Kawin Setsompop and Yogesh Rathi},

doi = {10.1002/mrm.28752},

issn = {1522-2594},

year  = {2021},

date = {2021-09-01},

journal = {Magn Reson Med},

volume = {86},

number = {3},

pages = {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.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSION: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}