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Elbehairy AF, Marshall H, Naish JH, Wild JM, Parraga G, Horsley A, Vestbo J. Advances in COPD imaging using CT and MRI: linkage with lung physiology and clinical outcomes. Eur Respir J 2024; 63:2301010. [PMID: 38548292 DOI: 10.1183/13993003.01010-2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 03/16/2024] [Indexed: 05/04/2024]
Abstract
Recent years have witnessed major advances in lung imaging in patients with COPD. These include significant refinements in images obtained by computed tomography (CT) scans together with the introduction of new techniques and software that aim for obtaining the best image whilst using the lowest possible radiation dose. Magnetic resonance imaging (MRI) has also emerged as a useful radiation-free tool in assessing structural and more importantly functional derangements in patients with well-established COPD and smokers without COPD, even before the existence of overt changes in resting physiological lung function tests. Together, CT and MRI now allow objective quantification and assessment of structural changes within the airways, lung parenchyma and pulmonary vessels. Furthermore, CT and MRI can now provide objective assessments of regional lung ventilation and perfusion, and multinuclear MRI provides further insight into gas exchange; this can help in structured decisions regarding treatment plans. These advances in chest imaging techniques have brought new insights into our understanding of disease pathophysiology and characterising different disease phenotypes. The present review discusses, in detail, the advances in lung imaging in patients with COPD and how structural and functional imaging are linked with common resting physiological tests and important clinical outcomes.
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Affiliation(s)
- Amany F Elbehairy
- Department of Chest Diseases, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Division of Infection, Immunity and Respiratory Medicine, The University of Manchester and Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK
| | - Helen Marshall
- POLARIS, Imaging, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Josephine H Naish
- MCMR, Manchester University NHS Foundation Trust, Manchester, UK
- Bioxydyn Limited, Manchester, UK
| | - Jim M Wild
- POLARIS, Imaging, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Insigneo Institute for in silico Medicine, Sheffield, UK
| | - Grace Parraga
- Robarts Research Institute, Western University, London, ON, Canada
- Department of Medical Biophysics, Western University, London, ON, Canada
- Division of Respirology, Western University, London, ON, Canada
| | - Alexander Horsley
- Division of Infection, Immunity and Respiratory Medicine, The University of Manchester and Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK
| | - Jørgen Vestbo
- Division of Infection, Immunity and Respiratory Medicine, The University of Manchester and Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK
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2
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Wang JM, Bell AJ, Ram S, Labaki WW, Hoff BA, Murray S, Kazerooni EA, Galban S, Hatt CR, Han MK, Galban CJ. Topologic Parametric Response Mapping Identifies Tissue Subtypes Associated with Emphysema Progression. Acad Radiol 2024; 31:1148-1159. [PMID: 37661554 PMCID: PMC11098545 DOI: 10.1016/j.acra.2023.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/25/2023] [Accepted: 08/03/2023] [Indexed: 09/05/2023]
Abstract
RATIONALE AND OBJECTIVES Small airways disease (SAD) and emphysema are significant components of chronic obstructive pulmonary disease (COPD), a heterogenous disease where predicting progression is difficult. SAD, a principal cause of airflow obstruction in mild COPD, has been identified as a precursor to emphysema. Parametric Response Mapping (PRM) of chest computed tomography (CT) can help distinguish SAD from emphysema. Specifically, topologic PRM can define local patterns of both diseases to characterize how and in whom COPD progresses. We aimed to determine if distribution of CT-based PRM of functional SAD (fSAD) is associated with emphysema progression. MATERIALS AND METHODS We analyzed paired inspiratory-expiratory chest CT scans at baseline and 5-year follow up in 1495 COPDGene subjects using topological analyses of PRM classifications. By spatially aligning temporal scans, we mapped local emphysema at year five to baseline lobar PRM-derived topological readouts. K-means clustering was applied to all observations. Subjects were subtyped based on predominant PRM cluster assignments and assessed using non-parametric statistical tests to determine differences in PRM values, pulmonary function metrics, and clinical measures. RESULTS We identified distinct lobar imaging patterns and classified subjects into three radiologic subtypes: emphysema-dominant (ED), fSAD-dominant (FD), and fSAD-transition (FT: transition from healthy lung to fSAD). Relative to year five emphysema, FT showed rapid local emphysema progression (-57.5% ± 1.1) compared to FD (-49.9% ± 0.5) and ED (-33.1% ± 0.4). FT consisted primarily of at-risk subjects (roughly 60%) with normal spirometry. CONCLUSION The FT subtype of COPD may allow earlier identification of individuals without spirometrically-defined COPD at-risk for developing emphysema.
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Affiliation(s)
- Jennifer M Wang
- Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan (J.M.W., W.W.L., M.K.H.)
| | - Alexander J Bell
- Department of Radiology, University of Michigan, Ann Arbor, Michigan (A.J.B., S.R., B.A.H., E.A.K., S.G., C.R.H., C.J.G.)
| | - Sundaresh Ram
- Department of Radiology, University of Michigan, Ann Arbor, Michigan (A.J.B., S.R., B.A.H., E.A.K., S.G., C.R.H., C.J.G.); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (S.R.)
| | - Wassim W Labaki
- Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan (J.M.W., W.W.L., M.K.H.)
| | - Benjamin A Hoff
- Department of Radiology, University of Michigan, Ann Arbor, Michigan (A.J.B., S.R., B.A.H., E.A.K., S.G., C.R.H., C.J.G.)
| | - Susan Murray
- School of Public Health, University of Michigan, Ann Arbor, Michigan (S.M.)
| | - Ella A Kazerooni
- Department of Radiology, University of Michigan, Ann Arbor, Michigan (A.J.B., S.R., B.A.H., E.A.K., S.G., C.R.H., C.J.G.)
| | - Stefanie Galban
- Department of Radiology, University of Michigan, Ann Arbor, Michigan (A.J.B., S.R., B.A.H., E.A.K., S.G., C.R.H., C.J.G.)
| | - Charles R Hatt
- Department of Radiology, University of Michigan, Ann Arbor, Michigan (A.J.B., S.R., B.A.H., E.A.K., S.G., C.R.H., C.J.G.); Imbio, LLC, Minneapolis, Minnesota (C.R.H.)
| | - MeiLan K Han
- Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan (J.M.W., W.W.L., M.K.H.)
| | - Craig J Galban
- Department of Radiology, University of Michigan, Ann Arbor, Michigan (A.J.B., S.R., B.A.H., E.A.K., S.G., C.R.H., C.J.G.).
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Dudurych I, Muiser S, McVeigh N, Kerstjens HAM, van den Berge M, de Bruijne M, Vliegenthart R. Bronchial wall parameters on CT in healthy never-smoking, smoking, COPD, and asthma populations: a systematic review and meta-analysis. Eur Radiol 2022; 32:5308-5318. [PMID: 35192013 PMCID: PMC9279249 DOI: 10.1007/s00330-022-08600-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 12/14/2021] [Accepted: 01/29/2022] [Indexed: 11/25/2022]
Abstract
Objective Research on computed tomography (CT) bronchial parameter measurements shows that there are conflicting results on the values for bronchial parameters in the never-smoking, smoking, asthma, and chronic obstructive pulmonary disease (COPD) populations. This review assesses the current CT methods for obtaining bronchial wall parameters and their comparison between populations. Methods A systematic review of MEDLINE and Embase was conducted following PRISMA guidelines (last search date 25th October 2021). Methodology data was collected and summarised. Values of percentage wall area (WA%), wall thickness (WT), summary airway measure (Pi10), and luminal area (Ai) were pooled and compared between populations. Results A total of 169 articles were included for methodologic review; 66 of these were included for meta-analysis. Most measurements were obtained from multiplanar reconstructions of segmented airways (93 of 169 articles), using various tools and algorithms; third generation airways in the upper and lower lobes were most frequently studied. COPD (12,746) and smoking (15,092) populations were largest across studies and mostly consisted of men (median 64.4%, IQR 61.5 – 66.1%). There were significant differences between populations; the largest WA% was found in COPD (mean SD 62.93 ± 7.41%, n = 6,045), and the asthma population had the largest Pi10 (4.03 ± 0.27 mm, n = 442). Ai normalised to body surface area (Ai/BSA) (12.46 ± 4 mm2, n = 134) was largest in the never-smoking population. Conclusions Studies on CT-derived bronchial parameter measurements are heterogenous in methodology and population, resulting in challenges to compare outcomes between studies. Significant differences between populations exist for several parameters, most notably in the wall area percentage; however, there is a large overlap in their ranges. Key Points • Diverse methodology in measuring airways contributes to overlap in ranges of bronchial parameters among the never-smoking, smoking, COPD, and asthma populations. • The combined number of never-smoking participants in studies is low, limiting insight into this population and the impact of participant characteristics on bronchial parameters. • Wall area percent of the right upper lobe apical segment is the most studied (87 articles) and differentiates all except smoking vs asthma populations. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-022-08600-1.
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Affiliation(s)
- Ivan Dudurych
- Department of Radiology, EB49, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700RB, Groningen, The Netherlands
| | - Susan Muiser
- Department of Pulmonology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - Niall McVeigh
- Department of Cardiothoracic Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | - Huib A M Kerstjens
- Department of Pulmonology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - Maarten van den Berge
- Department of Pulmonology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - Marleen de Bruijne
- Department of Radiology and Nuclear Medicine, Biomedical Imaging Group Rotterdam, Erasmus MC, Rotterdam, The Netherlands
- Department of Computer Science, University of Copenhagen, Copenhagen, Denmark
| | - Rozemarijn Vliegenthart
- Department of Radiology, EB49, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700RB, Groningen, The Netherlands.
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Kitazawa S, Wijesinghe AI, Maki N, Yanagihara T, Saeki Y, Kobayashi N, Kikuchi S, Goto Y, Ichimura H, Sato Y. Predicting Respiratory Complications Following Lobectomy Using Quantitative CT Measures of Emphysema. Int J Chron Obstruct Pulmon Dis 2021; 16:2523-2531. [PMID: 34511897 PMCID: PMC8428273 DOI: 10.2147/copd.s321541] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 08/02/2021] [Indexed: 12/25/2022] Open
Abstract
Purpose In performing surgery for lung cancer, emphysema is a risk factor related to postoperative respiratory complications (PRC). However, few studies have addressed the risk of radiological emphysematous volume affecting PRC. The aim of this study was to investigate the relationship between emphysematous volume as measured on 3-dimensional computed tomography and PRC. Patients and Methods We reviewed 342 lung cancer patients undergoing lobectomy between 2013 and 2018. The percentage of low attenuation area (LAA%) was defined as the percentage of the lung area showing attenuation of −950 Hounsfield units or lower. Preoperative factors including age, sex, body mass index, smoking index, respiratory function, tumour histology, and LAA% were evaluated. PRC included pneumonia, atelectasis, prolonged air leakage, empyema, hypoxia, ischemic bronchitis, bronchopleural fistula, and exacerbation of interstitial pneumonia. Uni- and multivariable analyses were performed to investigate the relationship between independent clinical variables and postoperative adverse events. Results Median LAA% was 5.0% (range, 0–40%) and PRC was observed in 50 patients (14.6%). Patients who presented with PRC showed significantly high LAA% compared to those without complications (median: 8.1% vs 3.8%; p < 0.001). Based on univariable analysis, age, sex, smoking index, percentage of forced expiratory volume in 1 s (FEV1.0%), histology, and LAA% were significant predictors for PRC. Multivariable analysis revealed higher LAA% as a significant risk factor for PRC (odds ratio = 1.040; 95% confidence interval, 1.001–1.080; p = 0.046). Conclusion In addition to respiratory function with spirometry, LAA% can be used as a predictor of PRC.
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Affiliation(s)
- Shinsuke Kitazawa
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Ashoka Indranatha Wijesinghe
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Naoki Maki
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Takahiro Yanagihara
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yusuke Saeki
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Naohiro Kobayashi
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Shinji Kikuchi
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yukinobu Goto
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Hideo Ichimura
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yukio Sato
- Department of General Thoracic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan
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Deep radiomics-based survival prediction in patients with chronic obstructive pulmonary disease. Sci Rep 2021; 11:15144. [PMID: 34312450 PMCID: PMC8313653 DOI: 10.1038/s41598-021-94535-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 07/05/2021] [Indexed: 12/16/2022] Open
Abstract
Heterogeneous clinical manifestations and progression of chronic obstructive pulmonary disease (COPD) affect patient health risk assessment, stratification, and management. Pulmonary function tests are used to diagnose and classify the severity of COPD, but they cannot fully represent the type or range of pathophysiologic abnormalities of the disease. To evaluate whether deep radiomics from chest computed tomography (CT) images can predict mortality in patients with COPD, we designed a convolutional neural network (CNN) model for extracting representative features from CT images and then performed random survival forest to predict survival in COPD patients. We trained CNN-based binary classifier based on six-minute walk distance results (> 440 m or not) and extracted high-throughput image features (i.e., deep radiomics) directly from the last fully connected layer of it. The various sizes of fully connected layers and combinations of deep features were experimented using a discovery cohort with 344 patients from the Korean Obstructive Lung Disease cohort and an external validation cohort with 102 patients from Penang General Hospital in Malaysia. In the integrative analysis of discovery and external validation cohorts, with combining 256 deep features from the coronal slice of the vertebral body and two sagittal slices of the left/right lung, deep radiomics for survival prediction achieved concordance indices of 0.8008 (95% CI, 0.7642–0.8373) and 0.7156 (95% CI, 0.7024–0.7288), respectively. Deep radiomics from CT images could be used to predict mortality in COPD patients.
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Nagpal P, Guo J, Shin KM, Lim JK, Kim KB, Comellas AP, Kaczka DW, Peterson S, Lee CH, Hoffman EA. Quantitative CT imaging and advanced visualization methods: potential application in novel coronavirus disease 2019 (COVID-19) pneumonia. BJR Open 2021; 3:20200043. [PMID: 33718766 PMCID: PMC7931412 DOI: 10.1259/bjro.20200043] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 12/01/2020] [Accepted: 12/16/2020] [Indexed: 12/13/2022] Open
Abstract
Increasingly, quantitative lung computed tomography (qCT)-derived metrics are providing novel insights into chronic inflammatory lung diseases, including chronic obstructive pulmonary disease, asthma, interstitial lung disease, and more. Metrics related to parenchymal, airway, and vascular anatomy together with various measures associated with lung function including regional parenchymal mechanics, air trapping associated with functional small airways disease, and dual-energy derived measures of perfused blood volume are offering the ability to characterize disease phenotypes associated with the chronic inflammatory pulmonary diseases. With the emergence of COVID-19, together with its widely varying degrees of severity, its rapid progression in some cases, and the potential for lengthy post-COVID-19 morbidity, there is a new role in applying well-established qCT-based metrics. Based on the utility of qCT tools in other lung diseases, previously validated supervised classical machine learning methods, and emerging unsupervised machine learning and deep-learning approaches, we are now able to provide desperately needed insight into the acute and the chronic phases of this inflammatory lung disease. The potential areas in which qCT imaging can be beneficial include improved accuracy of diagnosis, identification of clinically distinct phenotypes, improvement of disease prognosis, stratification of care, and early objective evaluation of intervention response. There is also a potential role for qCT in evaluating an increasing population of post-COVID-19 lung parenchymal changes such as fibrosis. In this work, we discuss the basis of various lung qCT methods, using case-examples to highlight their potential application as a tool for the exploration and characterization of COVID-19, and offer scanning protocols to serve as templates for imaging the lung such that these established qCT analyses have the best chance at yielding the much needed new insights.
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Affiliation(s)
- Prashant Nagpal
- Department of Radiology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA
| | | | | | - Jae-Kwang Lim
- Department of Radiology, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Ki Beom Kim
- Department of Radiology, Daegu Fatima Hospital, Daegu, South Korea
| | - Alejandro P Comellas
- Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA, USA
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Quantitative computed tomography for predicting cardiopulmonary complications after lobectomy for lung cancer in patients with chronic obstructive pulmonary disease. Gen Thorac Cardiovasc Surg 2019; 67:697-703. [DOI: 10.1007/s11748-019-01080-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Accepted: 01/20/2019] [Indexed: 01/21/2023]
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Current Controversies in Chronic Obstructive Pulmonary Disease. A Report from the Global Initiative for Chronic Obstructive Lung Disease Scientific Committee. Ann Am Thorac Soc 2019; 16:29-39. [DOI: 10.1513/annalsats.201808-557ps] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
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Impact of pulmonary emphysema on exercise capacity and its physiological determinants in chronic obstructive pulmonary disease. Sci Rep 2018; 8:15745. [PMID: 30356114 PMCID: PMC6200804 DOI: 10.1038/s41598-018-34014-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 10/05/2018] [Indexed: 12/27/2022] Open
Abstract
Exercise limitation is common in chronic obstructive pulmonary disease (COPD). We determined the impact of pulmonary emphysema on the physiological response to exercise independent of contemporary measures of COPD severity. Smokers 40–79 years old with COPD underwent computed tomography, pulmonary function tesing, and symptom-limited incremental exercise testing. COPD severity was quantified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) by spirometry (GOLD 1–4); and symptom burden and exacerbation risk (GOLD A-D). Emphysema severity was quantified as the percent lung volume <−950 Hounsfield units. Regression models adjusted for age, gender, body size, smoking status, airflow limitation, symptom burden and exacerbation risk. Among 67 COPD subjects (age 67 ± 8 years; 75% male; GOLD 1–4: 11%, 43%, 30%, 16%), median percent emphysema was 11%, and peak power output (PPO) was 61 ± 32 W. Higher percent emphysema independently predicted lower PPO (−24 W per 10% increment in emphysema; 95%CI −41 to −7 W). Throughout exercise, higher percent emphysema predicted 1) higher minute ventilation, ventilatory equivalent for CO2, and heart rate; and 2) lower oxy-hemoglobin saturation, and end-tidal PCO2. Independent of contemporary measures of COPD severity, the extent of pulmonary emphysema predicts lower exercise capacity, ventilatory inefficiency, impaired gas-exchange and increased heart rate response to exercise.
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10
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Rice MB, Li W, Dorans KS, Wilker EH, Ljungman P, Gold DR, Schwartz J, Koutrakis P, Kloog I, Araki T, Hatabu H, San Jose Estepar R, O'Connor GT, Mittleman MA, Washko GR. Exposure to Traffic Emissions and Fine Particulate Matter and Computed Tomography Measures of the Lung and Airways. Epidemiology 2018; 29:333-341. [PMID: 29384790 PMCID: PMC6095201 DOI: 10.1097/ede.0000000000000809] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Exposure to ambient air pollution has been associated with lower lung function in adults, but few studies have investigated associations with radiographic lung and airway measures. METHODS We ascertained lung volume, mass, density, visual emphysema, airway size, and airway wall area by computed tomography (CT) among 2,545 nonsmoking Framingham CT substudy participants. We examined associations of home distance to major road and PM2.5 (2008 average from a spatiotemporal model using satellite data) with these outcomes using linear and logistic regression models adjusted for age, sex, height, weight, census tract median household value and population density, education, pack-years of smoking, household tobacco exposure, cohort, and date. We tested for differential susceptibility by sex, smoking status (former vs. never), and cohort. RESULTS The mean participant age was 60.1 years (standard deviation 11.9 years). Median PM2.5 level was 9.7 µg/m (interquartile range, 1.6). Living <100 m from a major road was associated with a 108 ml (95% CI = 8, 207) higher lung volume compared with ≥400 m away. There was also a log-linear association between proximity to road and higher lung volume. There were no convincing associations of proximity to major road or PM2.5 with the other pulmonary CT measures. In subgroup analyses, road proximity was associated with lower lung density among men and higher odds of emphysema among former smokers. CONCLUSIONS Living near a major road was associated with higher average lung volume, but otherwise, we found no association between ambient pollution and radiographic measures of emphysema or airway disease.
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11
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Ostridge K, Williams NP, Kim V, Harden S, Bourne S, Clarke SC, Aris E, Mesia-Vela S, Devaster JM, Tuck A, Williams A, Wootton S, Staples KJ, Wilkinson TMA. Relationship of CT-quantified emphysema, small airways disease and bronchial wall dimensions with physiological, inflammatory and infective measures in COPD. Respir Res 2018; 19:31. [PMID: 29458372 PMCID: PMC5819274 DOI: 10.1186/s12931-018-0734-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 02/01/2018] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND COPD is a complex, heterogeneous disease characterised by progressive development of airflow limitation. Spirometry provides little information about key aspects of pathology and is poorly related to clinical outcome, so other tools are required to investigate the disease. We sought to explore the relationships between quantitative CT analysis with functional, inflammatory and infective assessments of disease to identify the utility of imaging to stratify disease to better predict outcomes and disease response. METHODS Patients from the AERIS study with moderate-very severe COPD underwent HRCT, with image analysis determining the quantity of emphysema (%LAA<- 950), small airways disease (E/I MLD) and bronchial wall thickening (Pi10). At enrolment subjects underwent lung function testing, six-minute walk testing (6MWT), blood sampling for inflammatory markers and sputum sampling for white cell differential and microbiological culture and PCR. RESULTS 122 subjects were included in this analysis. Emphysema and small airways disease had independent associations with airflow obstruction (β = - 0.34, p < 0.001 and β = - 0.56, p < 0.001). %LAA<- 950 had independent associations with gas transfer (β = - 0.37, p < 0.001) and E/I MLD with RV/TLC (β = 0.30, p =0.003). The distance walked during the 6MWT was not associated with CT parameters, but exertional desaturation was independently associated with emphysema (β = 0.73, p < 0.001). Pi10 did not show any independent associations with lung function or functional parameters. No CT parameters had any associations with sputum inflammatory cells. Greater emphysema was associated with lower levels of systemic inflammation (CRP β = - 0.34, p < 0.001 and fibrinogen β = - 0.28, p =0.003). There was no significant difference in any of the CT parameters between subjects where potentially pathogenic bacteria were detected in sputum and those where it was not. CONCLUSIONS This study provides further validation for the use of quantitative CT measures of emphysema and small airways disease in COPD as they showed strong associations with pulmonary physiology and functional status. In contrast to this quantitative CT measures showed few convincing associations with biological measures of disease, suggesting it is not an effective tool at measuring disease activity.
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Affiliation(s)
- Kristoffer Ostridge
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. .,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
| | - Nicholas P Williams
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Viktoriya Kim
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Stephen Harden
- Department of Radiology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Simon Bourne
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.,Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital, Portsmouth, UK
| | - Stuart C Clarke
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.,Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK
| | | | | | | | - Andrew Tuck
- Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK
| | - Anthony Williams
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.,Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK
| | - Stephen Wootton
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Karl J Staples
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.,Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK
| | - Tom M A Wilkinson
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.,Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK
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Nambu A, Zach J, Kim SS, Jin G, Schroeder J, Kim YI, Bowler R, Lynch DA. Significance of Low-Attenuation Cluster Analysis on Quantitative CT in the Evaluation of Chronic Obstructive Pulmonary Disease. Korean J Radiol 2018; 19:139-146. [PMID: 29354010 PMCID: PMC5768494 DOI: 10.3348/kjr.2018.19.1.139] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 07/02/2017] [Indexed: 11/15/2022] Open
Abstract
Objective To assess clinical feasibility of low-attenuation cluster analysis in evaluation of chronic obstructive pulmonary disease (COPD). Materials and Methods Subjects were 199 current and former cigarette smokers that underwent CT for quantification of COPD and had physiological measurements. Quantitative CT (QCT) measurements included low-attenuation area percent (LAA%) (voxels ≤ -950 Hounsfield unit [HU]), and two-dimensional (2D) and three-dimensional D values of cluster analysis at three different thresholds of CT value (-856, -910, and -950 HU). Correlation coefficients between QCT measurements and physiological indices were calculated. Multivariable analyses for percentage of predicted forced expiratory volume at one second (%FEV1) was performed including sex, age, body mass index, LAA%, and D value had the highest correlation coefficient with %FEV1 as independent variables. These analyses were conducted in subjects including those with mild COPD (global initiative of chronic obstructive lung disease stage = 0-II). Results LAA% had a higher correlation coefficient (-0.549, p < 0.001) with %FEV1 than D values in subjects while 2D D-910HU (-0.350, p < 0.001) revealed slightly higher correlation coefficient than LAA% (-0.343, p < 0.001) in subjects with mild COPD. Multivariable analyses revealed that LAA% and 2D D value-910HU were significant independent predictors of %FEV1 in subjects and that only 2D D value-910HU revealed a marginal p value (0.05) among independent variables in subjects with mild COPD. Conclusion Low-attenuation cluster analysis provides incremental information regarding physiologic severity of COPD, independent of LAA%, especially with mild COPD.
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Affiliation(s)
- Atsushi Nambu
- Department of Radiology, National Jewish Health, Denver, CO 80206, USA.,Department of Radiology, Teikyo University Mizonokuchi Hospital, Kanagawa 213-8507, Japan
| | - Jordan Zach
- Department of Radiology, National Jewish Health, Denver, CO 80206, USA
| | - Song Soo Kim
- Department of Radiology, National Jewish Health, Denver, CO 80206, USA.,Department of Radiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon 35015, Korea
| | - Gongyoung Jin
- Department of Radiology, National Jewish Health, Denver, CO 80206, USA.,Department of Radiology, Chonbuk National University Hospital, Jeonju 54907, Korea
| | - Joyce Schroeder
- Department of Radiology, National Jewish Health, Denver, CO 80206, USA.,Department of Radiology and Imaging Sciences, University of Utah Health Sciences, Salt Lake City, UT 84132, USA
| | - Yu-Il Kim
- Department of Medicine, National Jewish Health, Denver, CO 80206, USA.,Department of Internal Medicine, Chonnam National University Hospital, Gwangju 61469, Korea
| | - Russell Bowler
- Division of Pulmonary Medicine, Department of Medicine, National Jewish Health, Denver, CO 80206, USA
| | - David A Lynch
- Department of Radiology, National Jewish Health, Denver, CO 80206, USA
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13
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Kumar I, Verma A, Jain A, Agarwal SK. Performance of quantitative CT parameters in assessment of disease severity in COPD: A prospective study. Indian J Radiol Imaging 2018; 28:99-106. [PMID: 29692536 PMCID: PMC5894329 DOI: 10.4103/ijri.ijri_296_17] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Both emphysematous destruction of lung parenchyma and airway remodeling is thought to contribute to airflow limitation in cases of chronic obstructive pulmonary disease (COPD). OBJECTIVE To evaluate the value of quantitative computed tomography (QCT) parameters of emphysema and airway disease with disease severity in patients with COPD. MATERIALS AND METHODS We prospectively studied 50 patients with COPD, which included nonsmokers and patients with different degrees of cumulative smoking exposure. Three QCT parameters namely LAA% (low attenuation area percentage), WA% (Wall area percentage), and pi10 were calculated as per the standard technique. Forced expiratory volume in 1 s (FEV1), BODE score, and MMRC dyspnea scale were used as measures of disease severity. RESULTS FEV1 was inversely and significantly associated with all three QCT parameters. Receiver operated characteristic curves in prediction of GOLD class 3 COPD yielded cut-off values of 12.2, 61.45, and 3.5 for LAA%, WA%, and pi10, respectively, with high sensitivities and specificities. In multiple linear regression model, however, only LAA% proved to be significantly associated with FEV1, BODE, and dyspnea. CONCLUSION QCT indices of both emphysema and airway disease influence FEV1, dyspnea, and BODE score in patients with COPD. Emphysema, however, appears to be more closely related to disease severity.
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Affiliation(s)
- Ishan Kumar
- Department of Radiodiagnosis, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Ashish Verma
- Department of Radiodiagnosis, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Avinash Jain
- Department of TB and Respiratory Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - S. K. Agarwal
- Department of TB and Respiratory Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
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14
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Campos MA, Diaz AA. The Role of Computed Tomography for the Evaluation of Lung Disease in Alpha-1 Antitrypsin Deficiency. Chest 2017; 153:1240-1248. [PMID: 29175361 PMCID: PMC6026284 DOI: 10.1016/j.chest.2017.11.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2017] [Revised: 10/15/2017] [Accepted: 11/09/2017] [Indexed: 11/28/2022] Open
Abstract
Alpha-1 antitrypsin deficiency (AATD) is characterized by low serum levels of or dysfunctional alpha-1 proteinase inhibitor. In the lung parenchyma, this results in a loss of protection against the activity of serine proteases, particularly neutrophil elastase. The resultant imbalance in protease and antiprotease activity leads to an increased risk for the development of early-onset emphysema and COPD. As in traditional smoke-related COPD, the assessment of the severity and disease progression of lung disease in AATD is conventionally based on lung function; however, pulmonary function tests are unable to discriminate between emphysema and airways disease, the two hallmark pathologic features of COPD. CT imaging has been used as a tool to further characterize lung structure and evaluate therapeutic interventions in AATD-related COPD. Moreover, recent advances in quantitative CT have significantly improved our assessment of the lung architecture, which has provided investigators and clinicians with a more detailed evaluation of the extent and severity of emphysema and airways disease in AATD. In addition, serial CT imaging measures are becoming increasingly important, as they provide a tool to monitor emphysema progression. This review describes the principles of CT technology and the role of CT imaging in assessing pulmonary disease progression in AATD, including the effect of therapeutic interventions.
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Affiliation(s)
- Michael A Campos
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami School of Medicine, Miami, FL.
| | - Alejandro A Diaz
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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15
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Cui L, Ji X, Xie M, Dou S, Wang W, Xiao W. Role of inspiratory capacity on dyspnea evaluation in COPD with or without emphysematous lesions: a pilot study. Int J Chron Obstruct Pulmon Dis 2017; 12:2823-2830. [PMID: 29033563 PMCID: PMC5628691 DOI: 10.2147/copd.s142016] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background Since forced expiratory volume in 1 second (FEV1) shows a weak correlation with patients’ symptoms in COPD, some volume parameters may better reflect the change in dyspnea symptoms after treatment. In this article, we investigated the role of inspiratory capacity (IC) on dyspnea evaluation among COPD patients with or without emphysematous lesions. Methods In this prospective study, 124 patients with stable COPD were recruited. During the baseline visit, patients performed pulmonary function tests and dyspnea evaluation using the modified Medical Research Council (mMRC) scale. Partial patients underwent quantitative computerized tomography scans under physicians’ recommendations, and emphysematous changes were assessed using the emphysema index (EI; low attenuation area [LAA]% −950). These subjects were then divided into the emphysema-predominant group (LAA% −950≥9.9%) and the non-emphysema-predominant group (LAA% −950<9.9%). After treatment for ~1 month, subjects returned for reevaluation of both pulmonary function parameters and dyspnea severity. Correlation analysis between the change in IC (ΔIC) and dyspnea (ΔmMRC) was performed. Results Correlation analysis revealed that ΔIC was negatively correlated with ΔmMRC (correlation coefficient [cc], −0.490, P<0.001) in the total study population, which was stronger than that between ΔFEV1 and ΔmMRC (cc, −0.305, P=0.001). Patients with absolute ΔmMRC >1 were more likely to exhibit a marked increase in IC (≥300 mL) than those with absolute ΔmMRC ≤1 (74.36% versus 35.29%; odds ratio [OR], 5.317; P<0.001). In the emphysema-predominant group, only ΔIC strongly correlated with ΔmMRC (cc, −0.459, P=0.005), while ΔFEV1 did not (P>0.05). Conclusion IC could serve as an effective complement to FEV1 in COPD patients undergoing dyspnea evaluation after treatment. For COPD patients with predominant emphysematous lesions, an increase in IC is particularly more suitable for explaining dyspnea relief than FEV1.
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Affiliation(s)
- Liwei Cui
- Department of Respiratory Disease, Qilu Hospital, Shandong University
| | - Xiuli Ji
- Department of Pulmonary Disease, Jinan Traditional Chinese Medicine Hospital, Jinan, People's Republic of China
| | - Mengshuang Xie
- Department of Respiratory Disease, Qilu Hospital, Shandong University
| | - Shuang Dou
- Department of Respiratory Disease, Qilu Hospital, Shandong University
| | - Wei Wang
- Department of Respiratory Disease, Qilu Hospital, Shandong University
| | - Wei Xiao
- Department of Respiratory Disease, Qilu Hospital, Shandong University
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16
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Elbehairy AF, Parraga G, Webb KA, Neder JA, O’Donnell DE. Mild chronic obstructive pulmonary disease: why spirometry is not sufficient! Expert Rev Respir Med 2017; 11:549-563. [DOI: 10.1080/17476348.2017.1334553] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Amany F. Elbehairy
- Department of Medicine, Queen’s University and Kingston General Hospital, Kingston, ON, Canada
- Department of Chest Diseases, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Grace Parraga
- Department of Medical Biophysics, Robarts Research Institute, Western University, London, Canada
| | - Katherine A. Webb
- Department of Medicine, Queen’s University and Kingston General Hospital, Kingston, ON, Canada
| | - J Alberto Neder
- Department of Medicine, Queen’s University and Kingston General Hospital, Kingston, ON, Canada
| | - Denis E. O’Donnell
- Department of Medicine, Queen’s University and Kingston General Hospital, Kingston, ON, Canada
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17
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Crossley D, Turner A, Subramanian D. Phenotyping emphysema and airways disease: Clinical value of quantitative radiological techniques. World J Respirol 2017; 7:1-16. [DOI: 10.5320/wjr.v7.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Revised: 11/23/2016] [Accepted: 01/14/2017] [Indexed: 02/06/2023] Open
Abstract
The pathophysiology of chronic obstructive pulmonary disease (COPD) and Alpha one antitrypsin deficiency is increasingly recognised as complex such that lung function alone is insufficient for early detection, clinical categorisation and dictating management. Quantitative imaging techniques can detect disease earlier and more accurately, and provide an objective tool to help phenotype patients into predominant airways disease or emphysema. Computed tomography provides detailed information relating to structural and anatomical changes seen in COPD, and magnetic resonance imaging/nuclear imaging gives functional and regional information with regards to ventilation and perfusion. It is likely imaging will become part of routine clinical practice, and an understanding of the implications of the data is essential. This review discusses technical and clinical aspects of quantitative imaging in obstructive airways disease.
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18
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Martinez CH, Diaz AA, Meldrum C, Curtis JL, Cooper CB, Pirozzi C, Kanner RE, Paine R, Woodruff PG, Bleecker ER, Hansel NN, Barr RG, Marchetti N, Criner GJ, Kazerooni EA, Hoffman EA, Ross BD, Galban CJ, Cigolle CT, Martinez FJ, Han MK. Age and Small Airway Imaging Abnormalities in Subjects with and without Airflow Obstruction in SPIROMICS. Am J Respir Crit Care Med 2017; 195:464-472. [PMID: 27564413 PMCID: PMC5378423 DOI: 10.1164/rccm.201604-0871oc] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Accepted: 08/25/2016] [Indexed: 11/16/2022] Open
Abstract
RATIONALE Aging is associated with reduced FEV1 to FVC ratio (FEV1/FVC), hyperinflation, and alveolar enlargement, but little is known about how age affects small airways. OBJECTIVES To determine if chest computed tomography (CT)-assessed functional small airway would increase with age, even among asymptomatic individuals. METHODS We used parametric response mapping analysis of paired inspiratory/expiratory CTs to identify functional small airway abnormality (PRMFSA) and emphysema (PRMEMPH) in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort. Using adjusted linear regression models, we analyzed associations between PRMFSA and age in subjects with or without airflow obstruction. We subdivided participants with normal spirometry based on respiratory-related impairment (6-minute-walk distance <350 m, modified Medical Research Council ≥2, chronic bronchitis, St. George's Respiratory Questionnaire >25, respiratory events requiring treatment [antibiotics and/or steroids or hospitalization] in the year before enrollment). MEASUREMENTS AND MAIN RESULTS Among 580 never- and ever-smokers without obstruction or respiratory impairment, PRMFSA increased 2.7% per decade, ranging from 3.6% (ages 40-50 yr) to 12.7% (ages 70-80 yr). PRMEMPH increased nonsignificantly (0.1% [ages 40-50 yr] to 0.4% [ages 70-80 yr]; P = 0.34). Associations were similar among nonobstructed individuals with respiratory-related impairment. Increasing PRMFSA in subjects without airflow obstruction was associated with increased FVC (P = 0.004) but unchanged FEV1 (P = 0.94), yielding lower FEV1/FVC ratios (P < 0.001). Although emphysema was also significantly associated with lower FEV1/FVC (P = 0.04), its contribution relative to PRMFSA in those without airflow obstruction was limited by its low burden. CONCLUSIONS In never- and ever-smokers without airflow obstruction, aging is associated with increased FVC and CT-defined functional small airway abnormality regardless of respiratory symptoms.
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Affiliation(s)
| | - Alejandro A. Diaz
- Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
| | | | - Jeffrey L. Curtis
- Division of Pulmonary and Critical Care Medicine
- Pulmonary and Critical Care Medicine Section, Medical Service, and
| | - Christopher B. Cooper
- Division of Pulmonary and Critical Care Medicine, University of California Los Angeles Medical Center, Los Angeles, California
| | - Cheryl Pirozzi
- Division of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, Utah
| | - Richard E. Kanner
- Division of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, Utah
| | - Robert Paine
- Division of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, Utah
- Division of Pulmonary and Critical Care Medicine, Veterans Affairs Medical Center, Salt Lake City, Utah
| | - Prescott G. Woodruff
- Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California
| | - Eugene R. Bleecker
- Division of Pulmonary and Critical Care Medicine, Wake Forest University, Winston-Salem, North Carolina
| | - Nadia N. Hansel
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland
| | - R. Graham Barr
- Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University, New York, New York
| | - Nathaniel Marchetti
- Department of Thoracic Medicine and Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania
| | - Gerard J. Criner
- Department of Thoracic Medicine and Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania
| | | | - Eric A. Hoffman
- Department of Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa; and
| | - Brian D. Ross
- Department of Radiology, and
- Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan
| | - Craig J. Galban
- Department of Radiology, and
- Center for Molecular Imaging, University of Michigan, Ann Arbor, Michigan
| | - Christine T. Cigolle
- Geriatric Research and Education Clinical Center, VA Ann Arbor Healthcare System, Ann Arbor, Michigan
- Department of Family Medicine, University of Michigan Health System, Ann Arbor, Michigan
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19
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Bodduluri S, Bhatt SP, Hoffman EA, Newell JD, Martinez CH, Dransfield MT, Han MK, Reinhardt JM. Biomechanical CT metrics are associated with patient outcomes in COPD. Thorax 2017; 72:409-414. [PMID: 28044005 DOI: 10.1136/thoraxjnl-2016-209544] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Revised: 11/21/2016] [Accepted: 11/25/2016] [Indexed: 01/04/2023]
Abstract
BACKGROUND Traditional metrics of lung disease such as those derived from spirometry and static single-volume CT images are used to explain respiratory morbidity in patients with COPD, but are insufficient. We hypothesised that the mean Jacobian determinant, a measure of local lung expansion and contraction with respiration, would contribute independently to clinically relevant functional outcomes. METHODS We applied image registration techniques to paired inspiratory-expiratory CT scans and derived the Jacobian determinant of the deformation field between the two lung volumes to map local volume change with respiration. We analysed 490 participants with COPD with multivariable regression models to assess strengths of association between traditional CT metrics of disease and the Jacobian determinant with respiratory morbidity including dyspnoea (modified Medical Research Council), St Georges Respiratory Questionnaire (SGRQ) score, 6-min walk distance (6MWD) and the Body Mass Index, Airflow Obstruction, Dyspnoea and Exercise Capacity (BODE) index, as well as all-cause mortality. RESULTS The Jacobian determinant was significantly associated with SGRQ (adjusted regression coefficient β=-11.75,95% CI -21.6 to -1.7; p=0.020), and with 6MWD (β=321.15, 95% CI 134.1 to 508.1; p<0.001), independent of age, sex, race, body mass index, FEV1, smoking pack-years, CT emphysema, CT gas trapping, airway wall thickness and CT scanner type. The mean Jacobian determinant was also independently associated with the BODE index (β=-0.41, 95% CI -0.80 to -0.02; p=0.039) and mortality on follow-up (adjusted HR=4.26, 95% CI 0.93 to 19.23; p=0.064). CONCLUSIONS Biomechanical metrics representing local lung expansion and contraction improve prediction of respiratory morbidity and mortality and offer additional prognostic information beyond traditional measures of lung function and static single-volume CT metrics. TRIAL REGISTRATION NUMBER NCT00608764; Post-results.
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Affiliation(s)
- Sandeep Bodduluri
- Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA
| | - Surya P Bhatt
- Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.,UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.,UAB Lung Imaging Core, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Eric A Hoffman
- Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA.,Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - John D Newell
- Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA.,Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Carlos H Martinez
- Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Mark T Dransfield
- Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.,UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.,UAB Lung Imaging Core, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Meilan K Han
- Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Joseph M Reinhardt
- Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA
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20
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DeBoer EM, Spielberg DR, Brody AS. Clinical potential for imaging in patients with asthma and other lung disorders. J Allergy Clin Immunol 2016; 139:21-28. [PMID: 27871877 DOI: 10.1016/j.jaci.2016.11.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 11/10/2016] [Accepted: 11/10/2016] [Indexed: 12/12/2022]
Abstract
The ability of lung imaging to phenotype patients, determine prognosis, and predict response to treatment is expanding in clinical and translational research. The purpose of this perspective is to describe current imaging modalities that might be useful clinical tools in patients with asthma and other lung disorders and to explore some of the new developments in imaging modalities of the lung. These imaging modalities include chest radiography, computed tomography, lung magnetic resonance imaging, electrical impedance tomography, bronchoscopy, and others.
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Affiliation(s)
- Emily M DeBoer
- University of Colorado Anschutz Medical Campus, Department of Pediatrics, and Breathing Institute, Children's Hospital Colorado, Aurora, Colo.
| | - David R Spielberg
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Alan S Brody
- Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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21
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Blasi F, Neri L, Centanni S, Falcone F, Di Maria G. Clinical Characterization and Treatment Patterns for the Frequent Exacerbator Phenotype in Chronic Obstructive Pulmonary Disease with Severe or Very Severe Airflow Limitation. COPD 2016; 14:15-22. [PMID: 27824270 DOI: 10.1080/15412555.2016.1232380] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Chronic obstructive pulmonary disease (COPD) patients experiencing several episodes of acute clinical derangement suffer from increased morbidity, mortality, and accelerated decline in lung function. Nevertheless, the relationship between co-morbidity profile and exacerbation rates in the frequent exacerbator phenotype is poorly characterized, and evidence-based management guidelines are lacking. We sought to evaluate the co-morbidity profile and treatment patterns of "frequent exacerbators" with severe or very severe airflow limitation. We conducted a cross-sectional, multicenter study in 50 Italian hospitals. Pulmonologists abstracted clinical information from medical charts of 743 COPD frequent exacerbators. We evaluated the exacerbation risk and center-related variations in diagnostic testing. One-third of patients (n = 210) underwent a bronchodilator response test, and 163 (22%) received a computerized tomography (CT) scan; 35 had a partial response to bronchodilators, while 119 had a diagnosis of emphysema; 584 (79%) lacked sufficient diagnostic testing for classification. Only 17% of patients did not have any coexistent disease. Cardiovascular conditions were the most frequent co-morbidities. A history of heart failure [odds ratio (OR): 1.89; 95% confidence interval (CI) 1.48-2.3] and affective disorders (OR: 1.66; 95% CI 1.24-2.1) was associated with the frequency of exacerbations. Center membership was strongly associated with exacerbation risk, independent of casemix (variance partition coefficient = 29.6%). Examining the regional variation in health outcomes and health care behavior may help identify the best practices, especially when evidence-based recommendations are lacking and uncertainties surround clinical decision-making.
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Affiliation(s)
- Francesco Blasi
- a Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti , University of Milan , Milan , Italy
| | - Luca Neri
- b Care Value Advanced Analytics , Fresenius Medical Care , Palazzo Pignano , Italy
| | - Stefano Centanni
- c Dipartimento di Scienze della Salute , University of Milan , Milan , Italy
| | - Franco Falcone
- d Unità Operativa di Malattie dell'Apparato Respiratorio, PneumoTisiatria , Presidio Ospedaliero Bellaria-Maggiore Azienda USL della Città di Bologna , Bologna , Italy
| | - Giuseppe Di Maria
- e Unità Operativa di Pneumologia , Azienda Ospedaliero-Universitaria Policlinico Vittorio Emanuele , Catania , Italy
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22
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Nambu A, Zach J, Schroeder J, Jin G, Kim SS, Kim YI, Schnell C, Bowler R, Lynch DA. Quantitative computed tomography measurements to evaluate airway disease in chronic obstructive pulmonary disease: Relationship to physiological measurements, clinical index and visual assessment of airway disease. Eur J Radiol 2016; 85:2144-2151. [PMID: 27776670 DOI: 10.1016/j.ejrad.2016.09.010] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2016] [Revised: 09/11/2016] [Accepted: 09/12/2016] [Indexed: 10/21/2022]
Abstract
PURPOSE To correlate currently available quantitative CT measurements for airway disease with physiological indices and the body-mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS This study was approved by our institutional review board (IRB number 2778). Written informed consent was obtained from all subjects. The subjects included 188 current and former cigarette smokers from the COPDGene cohort who underwent inspiratory and expiratory CT and also had physiological measurements for the evaluation of airflow limitation, including FEF25-75%, airway resistance (Raw), and specific airway conductance (sGaw). The BODE index was used as the index of clinical symptoms. Quantitative CT measures included % low attenuation areas [% voxels≤950 Hounsfield unit (HU) on inspiratory CT, %LAA-950ins], percent gas trapping (% voxels≤-856HU on expiratory CT, %LAA -856exp), relative inspiratory to expiratory volume change of voxels with attenuation values from -856 to -950HU [Relative Volume Change (RVC)-856 to -950], expiratory to inspiratory ratio of mean lung density (E/I-ratio MLD), Pi10, and airway wall thickness (WT), luminal diameter (LD) and airway wall area percent (WA%) in the segmental, subsegmental and subsubsegmental bronchi on inspiratory CT. Correlation coefficients were calculated between the QCT measurements and physiological measurements in all subjects and in the subjects with mild emphysema (%LAA-950ins <10%). Univariate and multiple variable analysis for the BODE index were also performed. Adjustments were made for age, gender, smoking pack years, FEF25-75%, Raw, and sGaw. RESULTS Quantitative CT measurements had significant correlations with physiological indices. Among them, E/I-ratio MLD had the strongest correlations with FEF25-75% (r=-0.648, <0.001) and sGaw (r=-0.624, <0.001) while in the subjects with mild emphysema subsegmental WA% and segmental WA% had the strongest correlation with FEF25-75% (r=-0.669, <0.001) and sGaw (r=-0.638, <0.001), respectively. The multiple variable analyses showed that RVC-856 to -950 was an independent predictor of the BODE index showing the highest R2 (0.468) as an independent variable among the QCT measurements. CONCLUSION Quantitative CT measurements of gas trapping such as E/I-ratio MLD, correlate better with physiological indices for airway disease than those of airway such as WA% or LD. In mild emphysema, however, quantitative CT measurements of airway correlate better with the physiological indices. RVC-856 to -950 is a predictor of the BODE index.
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Affiliation(s)
- Atsushi Nambu
- Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA.
| | - Jordan Zach
- Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA.
| | - Joyce Schroeder
- Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA.
| | - Gongyoung Jin
- Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA.
| | - Song Soo Kim
- Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA.
| | - Yu-Il Kim
- Department of Medicine, National Jewish Health, Denver, CO, USA.
| | | | - Russell Bowler
- Division of Pulmonary Medicine, Department of Medicine, National Jewish Health, USA.
| | - David A Lynch
- Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206, USA.
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Kirby M, van Beek EJR, Seo JB, Biederer J, Nakano Y, Coxson HO, Parraga G. Management of COPD: Is there a role for quantitative imaging? Eur J Radiol 2016; 86:335-342. [PMID: 27592252 DOI: 10.1016/j.ejrad.2016.08.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 08/26/2016] [Indexed: 11/19/2022]
Abstract
While the recent development of quantitative imaging methods have led to their increased use in the diagnosis and management of many chronic diseases, medical imaging still plays a limited role in the management of chronic obstructive pulmonary disease (COPD). In this review we highlight three pulmonary imaging modalities: computed tomography (CT), magnetic resonance imaging (MRI) and optical coherence tomography (OCT) imaging and the COPD biomarkers that may be helpful for managing COPD patients. We discussed the current role imaging plays in COPD management as well as the potential role quantitative imaging will play by identifying imaging phenotypes to enable more effective COPD management and improved outcomes.
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Affiliation(s)
- Miranda Kirby
- Department of Radiology, University of British Columbia, Vancouver, Canada; UBC James Hogg Research Center & The Institute of Heart and Lung Health, St. Paul's Hospital, Vancouver, Canada
| | - Edwin J R van Beek
- Clinical Research Imaging Centre, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Joon Beom Seo
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Republic of Korea
| | - Juergen Biederer
- Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC), Member of the German Lung Research Center (DZL), Germany; Radiologie Darmstadt, Gross-Gerau County Hospital, Germany
| | - Yasutaka Nakano
- Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Shiga, Japan
| | - Harvey O Coxson
- Department of Radiology, University of British Columbia, Vancouver, Canada; UBC James Hogg Research Center & The Institute of Heart and Lung Health, St. Paul's Hospital, Vancouver, Canada
| | - Grace Parraga
- Robarts Research Institute, The University of Western Ontario, London, Canada; Department of Medical Biophysics, The University of Western Ontario, London, Canada.
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Ostridge K, Wilkinson TMA. Present and future utility of computed tomography scanning in the assessment and management of COPD. Eur Respir J 2016; 48:216-28. [PMID: 27230448 DOI: 10.1183/13993003.00041-2016] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 03/21/2016] [Indexed: 01/08/2023]
Abstract
Computed tomography (CT) is the modality of choice for imaging the thorax and lung structure. In chronic obstructive pulmonary disease (COPD), it used to recognise the key morphological features of emphysema, bronchial wall thickening and gas trapping. Despite this, its place in the investigation and management of COPD is yet to be determined, and it is not routinely recommended. However, lung CT already has important clinical applications where it can be used to diagnose concomitant pathology and determine which patients with severe emphysema are appropriate for lung volume reduction procedures. Furthermore, novel quantitative analysis techniques permit objective measurements of pulmonary and extrapulmonary manifestations of the disease. These techniques can give important insights into COPD, and help explore the heterogeneity and underlying mechanisms of the condition. In time, it is hoped that these techniques can be used in clinical trials to help develop disease-specific therapy and, ultimately, as a clinical tool in identifying patients who would benefit most from new and existing treatments. This review discusses the current clinical applications for CT imaging in COPD and quantification techniques, and its potential future role in stratifying disease for optimal outcome.
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Affiliation(s)
- Kristoffer Ostridge
- Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK
| | - Tom M A Wilkinson
- Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, UK
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25
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Kirby M, Lane P, Coxson HO. Measurement of pulmonary structure and function. IMAGING 2016. [DOI: 10.1183/2312508x.10003415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Hardin M, Foreman M, Dransfield MT, Hansel N, Han MK, Cho MH, Bhatt SP, Ramsdell J, Lynch D, Curtis JL, Silverman EK, Washko G, DeMeo D. Sex-specific features of emphysema among current and former smokers with COPD. Eur Respir J 2015; 47:104-12. [PMID: 26541532 DOI: 10.1183/13993003.00996-2015] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 09/05/2015] [Indexed: 12/16/2022]
Abstract
Recent studies suggest that males with chronic obstructive pulmonary disease (COPD) have more emphysema than females. It is not known if these differences persist across degrees of COPD severity. Our aim was to identify sex-specific differences in quantitative emphysema within COPD subgroups based on COPD severity.We included non-Hispanic white and African-American subjects from the COPDGene study with at least 10 pack-years of smoking and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry grade II or greater. We examined sex-specific differences in log-transformed emphysema (log per cent low-attenuation area (%LAA)) by GOLD spirometry grade among subjects with early-onset COPD (<55 years old) and advanced emphysema (>25% emphysema).Compared with females, males had higher log %LAA: overall (1.97±1.4 versus 1.69±1.6, β=0.32 (0.04), p=1.34×10(-14)), and among non-Hispanic white (p=8.37×10(-14)) and African-American subjects (p=0.002). Females with early-onset COPD, severe emphysema and GOLD grade IV COPD had similar emphysema as males, but markedly fewer pack-years smoking (early-onset, p=0.01; severe emphysema and GOLD grade IV, p<0.001).This study identifies subsets of female smokers with COPD who are particularly susceptible to parenchymal destruction.
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Affiliation(s)
- Megan Hardin
- Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Marilyn Foreman
- Morehouse School of Medicine, Department of Internal Medicine, Atlanta, GA, USA
| | - Mark T Dransfield
- Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Nadia Hansel
- Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - MeiLan K Han
- University of Michigan Health System, Ann Arbor, MI, USA
| | - Michael H Cho
- Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Joe Ramsdell
- Division of Internal Medicine, University of California, San Diego, CA, USA
| | - David Lynch
- Dept of Radiology, National Jewish Health, Denver, CO, USA
| | - Jeffrey L Curtis
- University of Michigan Health System, Ann Arbor, MI, USA VA Ann Arbor Healthcare System, Ann Arbor, MI, USA
| | - Edwin K Silverman
- Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - George Washko
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Lutchmedial SM, Creed WG, Moore AJ, Walsh RR, Gentchos GE, Kaminsky DA. How Common Is Airflow Limitation in Patients With Emphysema on CT Scan of the Chest? Chest 2015; 148:176-184. [PMID: 25539080 DOI: 10.1378/chest.14-1556] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND COPD has traditionally been defined by the presence of irreversible airflow limitation on spirometry using either the GOLD (Global Initiative for Chronic Obstructive Lung Disease) or American Thoracic Society/European Respiratory Society criteria (lower limit of normal [LLN]). We have observed that some patients with clinical COPD and emphysema on chest CT scan have no obstruction on spirometry. The purpose of this study was to assess the prevalence of obstruction by GOLD and LLN criteria in patients with emphysema on CT scan and determine which radiographic criteria were associated with a clinical diagnosis of COPD. METHODS We retrospectively analyzed the clinical records and spirometry of all patients who had radiographically defined emphysema on chest CT scans completed at the University of Vermont in 2011. We compared spirometric criteria and CT scan factors with the presence of clinical COPD based on chart review. RESULTS We identified 274 patients with CT scan-defined emphysema. GOLD criteria detected obstruction in 228 patients (83%), and LLN detected obstruction in 206 patients (75%). However, GOLD failed to correctly identify 19 patients (6.9%) and LLN failed to identify 38 patients (13.9%) (average 10.4%) who had radiographic emphysema and a clinical diagnosis of COPD. Obese patients had a lower prevalence of obstruction whether classified by LLN or GOLD. Among patients with spirometric obstruction, there were greater degrees of emphysema and more severely increased airway wall thickness. Factors that were independently associated with clinical COPD were lower FVC % predicted, lower FEV1/FVC ratio, and increasing airway wall thickness. CONCLUSIONS Spirometry missed 10.4% of patients with clinical COPD who have significant emphysema on chest CT scan.
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Affiliation(s)
| | | | | | | | | | - David A Kaminsky
- Division of Pulmonary and Critical Care Medicine, Burlington, VT.
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Childhood-onset asthma in smokers. association between CT measures of airway size, lung function, and chronic airflow obstruction. Ann Am Thorac Soc 2015; 11:1371-8. [PMID: 25296268 DOI: 10.1513/annalsats.201403-095oc] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
RATIONALE AND OBJECTIVES Asthma is associated with chronic airflow obstruction. Our goal was to assess the association of computed tomographic measures of airway wall volume and lumen volume with the FEV1 and chronic airflow obstruction in smokers with childhood-onset asthma. METHODS We analyzed clinical, lung function, and volumetric computed tomographic airway volume data from 7,266 smokers, including 590 with childhood-onset asthma. Small wall volume and small lumen volume of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small wall volume, small lumen volume, FEV1, and chronic airflow obstruction (post-bronchodilator FEV1/FVC ratio < 0.7) using linear and logistic models. MEASUREMENTS AND MAIN RESULTS Compared with subjects without childhood-onset asthma, those with childhood-onset asthma had smaller wall volume and lumen volume (P < 0.0001) of segmental airways. Among subjects with childhood-onset asthma, those with the smallest wall volume and lumen volume had the lowest FEV1 and greatest odds of chronic airflow obstruction. A similar tendency was seen in those without childhood-onset asthma. When comparing these two groups, both small wall volume and small lumen volume were more strongly associated with FEV1 and chronic airflow obstruction among subjects with childhood-asthma in multivariate models. CONCLUSION In smokers with childhood-onset asthma, smaller airways are associated with reduced lung function and chronic airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).
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Kirby M, Pike D, Sin DD, Coxson HO, McCormack DG, Parraga G. COPD: Do Imaging Measurements of Emphysema and Airway Disease Explain Symptoms and Exercise Capacity? Radiology 2015; 277:872-80. [PMID: 26151081 DOI: 10.1148/radiol.2015150037] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to-moderate disease. MATERIALS AND METHODS Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA-compliant protocol and underwent spirometry and plethysmography, completed the St George's Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT). Emphysema was estimated by using the MR imaging apparent diffusion coefficient (ADC) and the relative area of the CT attenuation histogram with attenuation of -950 HU or less (RA950). Airway disease was measured by using the CT airway wall thickness of airways with an internal perimeter of 10 mm and total airway count. Ventilation defect percentage at (3)He MR imaging was used to measure ventilation. Multivariable regression models for the 6MWD and SGRQ symptom subscore were used to evaluate the relationships between physiologic and imaging measurements. RESULTS Multivariate modeling for the 6MWD in 80 patients with GOLD grade U-II COPD showed that ADC (β = 0.34, P = .04), diffusing capacity of the lung for carbon monoxide (β = 0.60, P = .0008), and residual volume/total lung capacity (β = -0.26, P = .02) were significant variables, while forced expiratory volume in 1 second (FEV1) and airway disease measurements were not. In 36 patients with GOLD grade III or IV disease, FEV1 (β = 0.48, P = .01) was the only significant contributor in a multivariate model for 6MWD. MR imaging emphysema measurements also made the greatest relative contribution to symptoms in patients with milder (GOLD grade U-II) COPD (ADC: β = 0.60, P = .005; RA950: β = -0.52, P = .02; FEV1: β = -0.45, P = .0002) and in grade III or IV disease (ADC: β = 0.95, P = .01; RA950: β = -0.62, P = .07; airway count: β = -0.49, P = .01). CONCLUSION In patients with mild-to-moderate COPD, MR imaging emphysema measurements played a dominant role in the expression of exercise limitation, while both CT and MR imaging measurements of emphysema explained symptoms.
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Affiliation(s)
- Miranda Kirby
- From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7
| | - Damien Pike
- From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7
| | - Don D Sin
- From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7
| | - Harvey O Coxson
- From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7
| | - David G McCormack
- From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7
| | - Grace Parraga
- From the James Hogg Research Centre, the University of British Columbia and the Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada (M.K., D.D.S., H.O.C.); Imaging Research Laboratories, Robarts Research Institute (D.P., G.P.), and Department of Medical Biophysics (D.P., G.P.) and Division of Respirology, Department of Medicine (D.G.M.), the University of Western Ontario, 1151 Richmond St N, London, ON, Canada N6A 5B7
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Nambu A, Zach J, Schroeder J, Jin GY, Kim SS, Kim YIL, Schnell C, Bowler R, Lynch DA. Relationships between diffusing capacity for carbon monoxide (DLCO), and quantitative computed tomography measurements and visual assessment for chronic obstructive pulmonary disease. Eur J Radiol 2015; 84:980-5. [DOI: 10.1016/j.ejrad.2015.01.010] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 01/04/2015] [Accepted: 01/13/2015] [Indexed: 11/30/2022]
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Díaz AA, Pinto-Plata V, Hernández C, Peña J, Ramos C, Díaz JC, Klaassen J, Patino CM, Saldías F, Díaz O. Emphysema and DLCO predict a clinically important difference for 6MWD decline in COPD. Respir Med 2015; 109:882-9. [PMID: 25952774 DOI: 10.1016/j.rmed.2015.04.009] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 03/17/2015] [Accepted: 04/14/2015] [Indexed: 11/25/2022]
Abstract
BACKGROUND Exercise impairment is a central feature of chronic obstructive pulmonary disease (COPD), and a minimal clinically important difference (MCID) for 6-min walk distance (6MWD) decline (>30 m) has been associated with increased mortality. The predictors of the MCID are not fully known. We hypothesize that physiological factors and radiographic measures predict the MCID. METHODS We assessed 121 COPD subjects during 2 years using clinical variables, computed tomographic (CT) measures of emphysema, and functional measures including diffusion lung capacity for carbon monoxide (DLCO). The association between an MCID for 6MWD and clinical, CT, and physiologic predictors was assessed using logistic analysis. The C-statistic was used to assess the predictive ability of the models. RESULTS Forty seven (39%) subjects had an MCID. In an imaging-based model, log emphysema and age were the best predictors of MCID (emphysema Odds Ratio [OR] 2.47 95%CI [1.28-4.76]). In a physiologic model, DLCO, age, and male gender were selected the best predictors (DLCO OR 1.19 [1.08-1.31]). The C-statistic for the ability of these models to predict an MCID was 0.71 and 0.75, respectively. CONCLUSION In COPD patients the burden of emphysema on CT scan and DLCO predict a clinically meaningful decline in exercise capacity.
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Affiliation(s)
- Alejandro A Díaz
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Victor Pinto-Plata
- Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Camila Hernández
- Department of Pulmonary Diseases, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Javier Peña
- Department of Pulmonary Diseases, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Cristóbal Ramos
- Department of Radiology, Hospital Clínico José Joaquín Aguirre, Universidad de Chile, Santiago, Chile
| | - Juan C Díaz
- Department of Radiology, Hospital Clínico José Joaquín Aguirre, Universidad de Chile, Santiago, Chile
| | - Julieta Klaassen
- Department of Diabetes, Nutrition and Metabolism, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Cecilia M Patino
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Fernando Saldías
- Department of Pulmonary Diseases, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Orlando Díaz
- Department of Pulmonary Diseases, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
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TAMURA T, SUGANUMA N, HERING KG, VEHMAS T, ITOH H, AKIRA M, TAKASHIMA Y, HIRANO H, KUSAKA Y. Relationships (II) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with ventilatory functions indices for parenchymal abnormalities. INDUSTRIAL HEALTH 2015; 53:271-9. [PMID: 25810443 PMCID: PMC4466878 DOI: 10.2486/indhealth.2014-0072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2014] [Accepted: 02/04/2015] [Indexed: 05/10/2023]
Abstract
The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects' occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades.
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Affiliation(s)
- Taro TAMURA
- Department of Environmental Health, University of Fukui
School of Medicine, Japan
| | - Narufumi SUGANUMA
- Department of Environmental Medicine, Kochi University School
of Medicine, Japan
| | - Kurt G. HERING
- Department of Diagnostic Radiology, Radiology and Nuclear
Medicine, Radiological Clinic, Miners’ Hospital, Germany
| | - Tapio VEHMAS
- Department of Radiology, Finnish Institute of Occupational
Health, Finland
| | - Harumi ITOH
- Department of Radiology, University of Fukui School of
Medicine, Japan
| | - Masanori AKIRA
- Department of Radiology, National Hospital Organization
Kinki-Chuo Chest Medical Center, Japan
| | | | | | - Yukinori KUSAKA
- Department of Environmental Health, University of Fukui
School of Medicine, Japan
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Diaz AA, Rahaghi FN, Ross JC, Harmouche R, Tschirren J, San José Estépar R, Washko GR. Understanding the contribution of native tracheobronchial structure to lung function: CT assessment of airway morphology in never smokers. Respir Res 2015; 16:23. [PMID: 25848985 PMCID: PMC4335784 DOI: 10.1186/s12931-015-0181-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Accepted: 01/26/2015] [Indexed: 11/10/2022] Open
Abstract
Background Computed tomographic (CT) airway lumen narrowing is associated with lower lung function. Although volumetric CT measures of airways (wall volume [WV] and lumen volume [LV]) compared to cross sectional measures can more accurately reflect bronchial morphology, data of their use in never smokers is scarce. We hypothesize that native tracheobronchial tree morphology as assessed by volumetric CT metrics play a significant role in determining lung function in normal subjects. We aimed to assess the relationships between airway size, the projected branching generation number (BGN) to reach airways of <2mm lumen diameter –the site for airflow obstruction in smokers- and measures of lung function including forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of vital capacity (FEF 25–75). Methods We assessed WV and LV of segmental and subsegmental airways from six bronchial paths as well as lung volume on CT scans from 106 never smokers. We calculated the lumen area ratio of the subsegmental to segmental airways and estimated the projected BGN to reach a <2mm-lumen-diameter airway assuming a dichotomized tracheobronchial tree model. Regression analysis was used to assess the relationships between airway size, BGN, FEF 25–75, and FEV1. Results We found that in models adjusted for demographics, LV and WV of segmental and subsegmental airways were directly related to FEV1 (P <0.05 for all the models). In adjusted models for age, sex, race, LV and lung volume or height, the projected BGN was directly associated with FEF 25–75 and FEV1 (P = 0.001) where subjects with lower FEV1 had fewer calculated branch generations between the subsegmental bronchus and small airways. There was no association between airway lumen area ratio and lung volume. Conclusion We conclude that in never smokers, those with smaller central airways had lower airflow and those with lower airflow had less parallel airway pathways independent of lung size. These findings suggest that variability in the structure of the tracheobronchial tree may influence the risk of developing clinically relevant smoking related airway obstruction. Electronic supplementary material The online version of this article (doi:10.1186/s12931-015-0181-y) contains supplementary material, which is available to authorized users.
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Yamasawa W, Tasaka S, Betsuyaku T, Yamaguchi K. Correlation of a decline in aerobic capacity with development of emphysema in patients with chronic obstructive pulmonary disease: a prospective observational study. PLoS One 2015; 10:e0125053. [PMID: 25909949 PMCID: PMC4409313 DOI: 10.1371/journal.pone.0125053] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 03/16/2015] [Indexed: 02/07/2023] Open
Abstract
In patients with COPD, CT assessment of emphysema and airway disease is known to be associated with lung function and 6-minute walk distance. However, it remains to be determined whether low attenuation area (LAA) on CT is associated with aerobic capacity assessed using cardiopulmonary exercise testing (CPET). In this prospective observational study, we repeatedly conducted high-resolution CT and CPET using a treadmill in 81 COPD patients over a median interval of 3.5 years. Two investigators independently scored LAA on images obtained at the aortic arch level, tracheal bifurcation level, and supradiaphragmatic level. Grades for the images of each lung were added to yield the total LAA score. Total LAA score was negatively correlated with peak aerobic capacity ([Formula: see text]) (p<0.001, r = -0.485). LAA scores of the upper (aortic arch level) and the lower (supradiaphragmatic level) lungs were both significantly associated with peak [Formula: see text]. There was a significant correlation between total LAA score and peak CO2 output ([Formula: see text]) (p<0.001, r = -0.433). Total LAA score was correlated with oxygen saturation at peak exercise (p<0.001, r = -0.634) and the estimated dead space fraction (p<0.001, r = 0.416). The mean annual change in total LAA score was significantly correlated with those in peak [Formula: see text] (p<0.001, r = -0.546) and peak [Formula: see text] (p<0.001, r = -0.488). The extent of emphysema measured by CT was associated with the results of CPET. The time-dependent changes in CPET data were also correlated with that in total LAA score. CT assessment could be a non-invasive tool to predict aerobic capacity in patients with COPD.
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Affiliation(s)
- Wakako Yamasawa
- Division of Pulmonary Medicine, Keio University School of Medicine, Tokyo, Japan
- Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Sadatomo Tasaka
- Division of Pulmonary Medicine, Keio University School of Medicine, Tokyo, Japan
- * E-mail:
| | - Tomoko Betsuyaku
- Division of Pulmonary Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Kazuhiro Yamaguchi
- Comprehensive and Internal Medicine, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
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Smith BM, Hoffman EA, Rabinowitz D, Bleecker E, Christenson S, Couper D, Donohue KM, Han MK, Hansel NN, Kanner RE, Kleerup E, Rennard S, Barr RG. Comparison of spatially matched airways reveals thinner airway walls in COPD. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS). Thorax 2014; 69:987-96. [PMID: 24928812 PMCID: PMC4198462 DOI: 10.1136/thoraxjnl-2014-205160] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND COPD is characterised by reduced airway lumen dimensions and fewer peripheral airways. Most studies of airway properties sample airways based upon lumen dimension or at random, which may bias comparisons given reduced airway lumen dimensions and number in COPD. We sought to compare central airway wall dimensions on CT in COPD and controls using spatially matched airways, thereby avoiding selection bias of airways in the lung. METHODS The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) recruited smokers with COPD and controls aged 50-79 years and 40-80 years, respectively. COPD was defined by current guidelines. Using CT image data, airway dimensions were measured for all central airway segments (generations 0-6) following 5 standardised paths into the lungs. Case-control airway comparisons were spatially matched by generation and adjusted for demographics, body size, smoking, CT dose, per cent emphysema, airway length and lung volume. RESULTS Among 311 MESA COPD participants, airway wall areas at generations 3-6 were smaller in COPD compared with controls (all p<0.001). Among 1248 SPIROMICS participants, airway wall areas at generations 1-6 were smaller (all p<0.001), and this reduction was monotonic with increasing COPD severity (p<0.001). In both studies, sampling airways by lumen diameter or randomly resulted in a comparison of more proximal airways in COPD to more peripheral airways in controls (p<0.001) resulting in the appearance of thicker walls in COPD (p<0.02). CONCLUSIONS Airway walls are thinner in COPD when comparing spatially matched central airways. Other approaches to airway sampling result in comparisons of more proximal to more distal airways and potentially biased assessment of airway properties in COPD.
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Affiliation(s)
- Benjamin M. Smith
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY
- Department of Medicine, McGill University, Montreal, Canada
| | - Eric A. Hoffman
- Departments of Radiology, Medicine and Biomedical Engineering, University of Iowa, Iowa City, IA
| | - Dan Rabinowitz
- Department of Statistics, Columbia University, New York, NY
| | - Eugene Bleecker
- Department of Medicine, Wake Forest University, Winston-Salem, NC
| | | | - David Couper
- Deparment of Biostatistics, University of North Carolina Chapel Hill, Chapel Hill, NC
| | - Kathleen M. Donohue
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY
| | - Meilan K. Han
- Department of Medicine, University of Michigan, Ann Arbor, MI
| | - Nadia N. Hansel
- Department of Medicine, Johns Hopkins University, Baltimore, MD
| | | | - Eric Kleerup
- Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, CA
| | - Stephen Rennard
- Department of Medicine, University of Nebraska Medical Center, Omaha, NE
| | - R. Graham Barr
- Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY
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Kirby M, Parraga G. Paradoxical response to bronchodilators in COPD: curious enigma or clinically important phenotype? THE LANCET RESPIRATORY MEDICINE 2014; 2:865-867. [PMID: 25217077 DOI: 10.1016/s2213-2600(14)70198-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- Miranda Kirby
- James Hogg Research Centre, University of British Columbia and Institute of Heart and Lung Health, St Paul's Hospital, Vancouver, BC, Canada
| | - Grace Parraga
- Imaging Research Laboratories, Robarts Research Institute, 1151 Richmond Street N, London, ON, Canada N6A 5B7; Department of Medical Biophysics, University of Western Ontario, London, ON, Canada.
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Petersen J, Nielsen M, Lo P, Nordenmark LH, Pedersen JH, Wille MMW, Dirksen A, de Bruijne M. Optimal surface segmentation using flow lines to quantify airway abnormalities in chronic obstructive pulmonary disease. Med Image Anal 2014; 18:531-41. [DOI: 10.1016/j.media.2014.02.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Revised: 02/04/2014] [Accepted: 02/07/2014] [Indexed: 10/25/2022]
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Castaldi PJ, San José Estépar R, Mendoza CS, Hersh CP, Laird N, Crapo JD, Lynch DA, Silverman EK, Washko GR. Distinct quantitative computed tomography emphysema patterns are associated with physiology and function in smokers. Am J Respir Crit Care Med 2013; 188:1083-90. [PMID: 23980521 PMCID: PMC3863741 DOI: 10.1164/rccm.201305-0873oc] [Citation(s) in RCA: 101] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
RATIONALE Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. OBJECTIVES To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. METHODS Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. MEASUREMENTS AND MAIN RESULTS Compared with percentage of low-attenuation area less than -950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). CONCLUSIONS Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.
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Affiliation(s)
- Peter J. Castaldi
- Channing Division of Network Medicine
- Division of General Medicine, and
| | | | | | - Craig P. Hersh
- Channing Division of Network Medicine
- Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
| | - Nan Laird
- Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; and
| | | | - David A. Lynch
- Department of Radiology, National Jewish Health, Denver, Colorado
| | - Edwin K. Silverman
- Channing Division of Network Medicine
- Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
| | - George R. Washko
- Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
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Lutey BA, Conradi SH, Atkinson JJ, Zheng J, Schechtman KB, Senior RM, Gierada DS. Accurate measurement of small airways on low-dose thoracic CT scans in smokers. Chest 2013; 143:1321-1329. [PMID: 23172175 DOI: 10.1378/chest.12-0034] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Partial volume averaging and tilt relative to the scan plane on transverse images limit the accuracy of airway wall thickness measurements on CT scan, confounding assessment of the relationship between airway remodeling and clinical status in COPD. The purpose of this study was to assess the effect of partial volume averaging and tilt corrections on airway wall thickness measurement accuracy and on relationships between airway wall thickening and clinical status in COPD. METHODS Airway wall thickness measurements in 80 heavy smokers were obtained on transverse images from low-dose CT scan using the open-source program Airway Inspector. Measurements were corrected for partial volume averaging and tilt effects using an attenuation- and geometry-based algorithm and compared with functional status. RESULTS The algorithm reduced wall thickness measurements of smaller airways to a greater degree than larger airways, increasing the overall range. When restricted to analyses of airways with an inner diameter < 3.0 mm, for a theoretical airway of 2.0 mm inner diameter, the wall thickness decreased from 1.07 ± 0.07 to 0.29 ± 0.10 mm, and the square root of the wall area decreased from 3.34 ± 0.15 to 1.58 ± 0.29 mm, comparable to histologic measurement studies. Corrected measurements had higher correlation with FEV₁, differed more between BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index scores, and explained a greater proportion of FEV1 variability in multivariate models. CONCLUSIONS Correcting for partial volume averaging improves accuracy of airway wall thickness estimation, allowing direct measurement of the small airways to better define their role in COPD.
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Affiliation(s)
- Barbara A Lutey
- Division of Medical Education, Washington University School of Medicine, St Louis, MO.
| | - Susan H Conradi
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO
| | - Jeffrey J Atkinson
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO
| | - Jie Zheng
- Division of Biostatistics, Washington University School of Medicine, St Louis, MO
| | - Kenneth B Schechtman
- Division of Biostatistics, Washington University School of Medicine, St Louis, MO
| | - Robert M Senior
- Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, MO
| | - David S Gierada
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO
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Diaz AA, Han MK, Come CE, San José Estépar R, Ross JC, Kim V, Dransfield MT, Curran-Everett D, Schroeder JD, Lynch DA, Tschirren J, Silverman EK, Washko GR. Effect of emphysema on CT scan measures of airway dimensions in smokers. Chest 2013; 143:687-693. [PMID: 23460155 DOI: 10.1378/chest.12-0039] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND In CT scans of smokers with COPD, the subsegmental airway wall area percent (WA%) is greater and more strongly correlated with FEV1 % predicted than WA% obtained in the segmental airways. Because emphysema is linked to loss of airway tethering and may limit airway expansion, increases in WA% may be related to emphysema and not solely to remodeling. We aimed to first determine whether the stronger association of subsegmental vs segmental WA% with FEV1 % predicted is mitigated by emphysema and, second, to assess the relationships among emphysema, WA%, and total bronchial area (TBA). METHODS We analyzed CT scan segmental and subsegmental WA% (WA% = 100 × wall area/TBA) of six bronchial paths and corresponding lobar emphysema, lung function, and clinical data in 983 smokers with COPD. RESULTS Compared with segmental WA%, the subsegmental WA% had a greater effect on FEV1% predicted (-0.8% to -1.7% vs -1.9% to -2.6% per 1-unit increase in WA%, respectively; P < .05 for most bronchial paths). After adjusting for emphysema, the association between subsegmental WA% and FEV1 % predicted was weakened in two bronchial paths. Increases in WA% between bronchial segments correlated directly with emphysema in all bronchial paths (P < .05). In multivariate regression models, emphysema was directly related to subsegmental WA% in most bronchial paths and inversely related to subsegmental TBA in all bronchial paths. CONCLUSION The greater effect of subsegmental WA% on airflow obstruction is mitigated by emphysema. Part of the emphysema effect might be due to loss of airway tethering, leading to a reduction in TBA and an increase in WA%.
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Affiliation(s)
- Alejandro A Diaz
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Pulmonary Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - MeiLan K Han
- University of Michigan School of Medicine, Ann Arbor, MI
| | - Carolyn E Come
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Raúl San José Estépar
- Surgical Planning Laboratory, Laboratory of Mathematics in Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA
| | - James C Ross
- Surgical Planning Laboratory, Laboratory of Mathematics in Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA
| | - Victor Kim
- School of Medicine, Temple University, Philadelphia, PA
| | - Mark T Dransfield
- Division of Pulmonary, Allergy, and Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, AL
| | - Douglas Curran-Everett
- Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, CO; Department of Biostatistics and Informatics, Colorado School of Public Health, Denver, CO
| | - Joyce D Schroeder
- Division of Radiology, National Jewish Health, University of Colorado, School of Medicine, Denver, CO
| | - David A Lynch
- Division of Radiology, National Jewish Health, University of Colorado, School of Medicine, Denver, CO
| | | | - Edwin K Silverman
- Channing Laboratory (Dr Silverman), Brigham and Women's Hospital, Boston, MA
| | - George R Washko
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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Brown RH. Registration-based metrics of lung function to describe COPD: the ultimate question of life, the universe, and everything. Acad Radiol 2013; 20:525-6. [PMID: 23570933 DOI: 10.1016/j.acra.2013.02.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Revised: 02/08/2013] [Accepted: 02/08/2013] [Indexed: 01/23/2023]
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Díaz AA, Morales A, Díaz JC, Ramos C, Klaassen J, Saldías F, Aravena C, Díaz R, Lisboa C, Washko GR, Díaz O. CT and physiologic determinants of dyspnea and exercise capacity during the six-minute walk test in mild COPD. Respir Med 2013; 107:570-9. [DOI: 10.1016/j.rmed.2012.12.011] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2012] [Revised: 12/14/2012] [Accepted: 12/17/2012] [Indexed: 10/27/2022]
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Yasui H, Inui N, Furuhashi K, Nakamura Y, Uto T, Sato J, Yasuda K, Takehara Y, Suda T, Chida K. Multidetector-row computed tomography assessment of adding budesonide/formoterol to tiotropium in patients with chronic obstructive pulmonary disease. Pulm Pharmacol Ther 2013; 26:336-41. [PMID: 23340058 DOI: 10.1016/j.pupt.2013.01.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Revised: 12/16/2012] [Accepted: 01/10/2013] [Indexed: 10/27/2022]
Abstract
BACKGROUND In patients with chronic obstructive pulmonary disease (COPD), multidetector-row computed tomography (MDCT) showed that tiotropium dilated the inner diameters in airways from the third to the sixth generation of the bronchi. Here we aimed to evaluate the morphological effect by adding a budesonide/formoterol combination to tiotropium in COPD patients using three-dimensional MDCT. METHODS Pulmonary function tests, St. George's Respiratory Questionnaire (SGRQ) and MDCT imaging studies were performed at the beginning and after budesonide/formoterol combination treatment for 12 weeks in 14 patients with COPD. RESULTS The median age was 73.5 years and the mean forced expiratory volume in 1 s (FEV1) as a percentage of the predicted value was 57.2 ± 18.3%. The luminal area in the fifth generation bronchi and the emphysema volume/CT-derived total lung volume were significantly correlated with FEV1 at baseline (r = 0.682, p < 0.02 and r = -0.868, p < 0.001, respectively). The average luminal area and wall area percentage in the third, fourth and fifth generations were correlated with the SGRQ total score. Budesonide/formoterol induced insignificant pulmonary function changes and significant symptoms improvement. CT images showed an increased inner luminal area and decreased wall area after budesonide/formoterol treatment. Average luminal area was significantly increased from 24.3 ± 9.7 to 26.0 ± 9.9 mm(2) in the third generation, 13.0 ± 6.5 to 14.7 ± 7.3 mm(2) in the fourth generation, 8.0 ± 4.8 to 9.4 ± 4.9 mm(2) in the fifth generation and 5.6 ± 2.7 to 6.7 ± 3.6 mm(2) in the sixth generation (p < 0.01). The average increase of the third generation luminal area was correlated with the FEV1 increase (r = 0.632, p < 0.03). The wall area percentage significantly decreased from 51.5 ± 9.2 to 49.1 ± 9.7 in the third generation, 56.1 ± 9.7 to 53.0 ± 11.1 in the fourth generation, and 62.3 ± 9.9 to 57.6 ± 9.8 in the fifth generation (p < 0.05). Emphysema volume/CT-derived total lung volume was unchanged with treatment. CONCLUSION MDCT demonstrated budesonide/formoterol induced bronchodilation in the non-small airway. CT imaging can evaluate drug therapeutic effect and may provide additional insights into pharmacotherapy for COPD.
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Affiliation(s)
- Hideki Yasui
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan
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Wang Z, Gu S, Leader JK, Kundu S, Tedrow JR, Sciurba FC, Gur D, Siegfried JM, Pu J. Optimal threshold in CT quantification of emphysema. Eur Radiol 2012; 23:975-84. [PMID: 23111815 DOI: 10.1007/s00330-012-2683-z] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2012] [Revised: 08/24/2012] [Accepted: 08/30/2012] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To determine the optimal threshold by quantitatively assessing the extent of emphysema at the level of the entire lung and at the level of individual lobes using a large, diverse dataset of computed tomography (CT) examinations. METHODS This study comprises 573 chest CT examinations acquired from subjects with different levels of airway obstruction (222 none, 83 mild, 141 moderate, 63 severe and 64 very severe). The extent of emphysema was quantified using the percentage of the low attenuation area (LAA%) divided by the total lung or lobe volume(s). The correlations between the extent of emphysema, and pulmonary functions and the five-category classification were assessed using Pearson and Spearman's correlation coefficients, respectively. When quantifying emphysema using a density mask, a wide range of thresholds from -850 to -1,000 HU were used. RESULTS The highest correlations of LAA% with the five-category classification and PFT measures ranged from -925 to -965 HU for each individual lobe and the entire lung. However, the differences between the highest correlations and those obtained at -950 HU are relatively small. CONCLUSION Although there are variations in the optimal cut-off thresholds for individual lobes, the single threshold of -950 HU is still an acceptable threshold for density-based emphysema quantification.
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Affiliation(s)
- Zhimin Wang
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213, USA
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Camiciottoli G, Bigazzi F, Bartolucci M, Cestelli L, Paoletti M, Diciotti S, Cavigli E, Magni C, Buonasera L, Mascalchi M, Pistolesi M. BODE-index, modified BODE-index and ADO-score in chronic obstructive pulmonary disease: relationship with COPD phenotypes and CT lung density changes. COPD 2012; 9:297-304. [PMID: 22432964 DOI: 10.3109/15412555.2012.661000] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
COPD is a heterogeneous disorder whose assessment is going to be increasingly multidimensional. Grading systems such as BODE (Body-Mass Index, Obstruction, Dyspnea, Exercise), mBODE (BODE modified in grading of walked distance), ADO (Age, Dyspnea, Obstruction) are proposed to assess COPD severity and outcome. Computed tomography (CT) is deemed to reflect COPD lung pathologic changes. We studied the relationship of multidimensional grading systems (MGS) with clinically determined COPD phenotypes and CT lung density. Seventy-two patients underwent clinical and chest x-ray evaluation, pulmonary function tests (PFT), 6-minute walking test (6MWT) to derive: predominant COPD clinical phenotype, BODE, mBODE, ADO. Inspiratory and expiratory CT was performed to calculate mean lung attenuation (MLA), relative area with density below-950 HU at inspiration (RAI(-950)), and below -910 HU at expiration (RAE(-910)). MGS, PFT, and CT data were compared between bronchial versus emphysematous COPD phenotype. MGS were correlated with CT data. The prediction of CT density by means of MGS was investigated by direct and stepwise multivariate regression. MGS did not differ in clinically determined COPD phenotypes. BODE was more closely related and better predicted CT findings than mBODE and ADO; the better predictive model was obtained for CT expiratory data; stepwise regression models of CT data did not include 6MWT distance; the dyspnea score MRC was included only to predict RA-950 and RA-910 which quantify emphysema extent. BODE reflect COPD severity better than other MGS, but not its clinical heterogeneity. 6MWT does not significantly increase BODE predictivity of CT lung density changes.
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Affiliation(s)
- Gianna Camiciottoli
- University of Florence, Department of Internal Medicine, Section of Respiratory Medicine, Florence, Italy. gianna.camiciottoli@unifi .it
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Mets OM, de Jong PA, van Ginneken B, Gietema HA, Lammers JWJ. Quantitative computed tomography in COPD: possibilities and limitations. Lung 2011; 190:133-45. [PMID: 22179694 PMCID: PMC3310986 DOI: 10.1007/s00408-011-9353-9] [Citation(s) in RCA: 87] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2011] [Accepted: 11/28/2011] [Indexed: 01/08/2023]
Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation. Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment. Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process. Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions. This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD.
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Affiliation(s)
- O M Mets
- Department of Radiology, University Medical Center Utrecht, Huispostnummer E01.132, Postbus 85500, 3508 GA Utrecht, The Netherlands.
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Rambod M, Porszasz J, Make BJ, Crapo JD, Casaburi R. Six-minute walk distance predictors, including CT scan measures, in the COPDGene cohort. Chest 2011; 141:867-875. [PMID: 21960696 DOI: 10.1378/chest.11-0870] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND Exercise tolerance in COPD is only moderately well predicted by airflow obstruction assessed by FEV(1). We determined whether other phenotypic characteristics, including CT scan measures, are independent predictors of 6-min walk distance (6MWD) in the COPDGene cohort. METHODS COPDGene recruits non-Hispanic Caucasian and African American current and ex-smokers. Phenotyping measures include postbronchodilator FEV(1) % predicted and inspiratory and expiratory CT lung scans. We defined % emphysema as the percentage of lung voxels < -950 Hounsfield units on the inspiratory scan and % gas trapping as the percentage of lung voxels < -856 Hounsfield units on the expiratory scan. RESULTS Data of the first 2,500 participants of the COPDGene cohort were analyzed. Participant age was 61 ± 9 years; 51% were men; 76% were non-Hispanic Caucasians, and 24% were African Americans. Fifty-six percent had spirometrically defined COPD, with 9.3%, 23.4%, 15.0%, and 8.3% in GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I to IV, respectively. Higher % emphysema and % gas trapping predicted lower 6MWD (P < .001). However, in a given spirometric group, after adjustment for age, sex, race, and BMI, neither % emphysema nor % gas trapping, or their interactions with FEV(1) % predicted, remained a significant 6MWD predictor. In a given spirometric group, only 16% to 27% of the variance in 6MWD could be explained by age, male sex, Caucasian race, and lower BMI as significant predictors of higher 6MWD. CONCLUSIONS In this large cohort of smokers in a given spirometric stage, phenotypic characteristics were only modestly predictive of 6MWD. CT scan measures of emphysema and gas trapping were not predictive of 6MWD after adjustment for other phenotypic characteristics.
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Affiliation(s)
- Mehdi Rambod
- Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA
| | - Janos Porszasz
- Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA
| | | | | | - Richard Casaburi
- Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA.
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Diaz AA, Come CE, Ross JC, San José Estépar R, Han MK, Loring SH, Silverman EK, Washko GR. Association between airway caliber changes with lung inflation and emphysema assessed by volumetric CT scan in subjects with COPD. Chest 2011; 141:736-744. [PMID: 21940776 DOI: 10.1378/chest.11-1026] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND An increase in airway caliber (airway distensibility) with lung inflation is attenuated in COPD. Furthermore, some subjects have a decrease in airway caliber with lung inflation. We aimed to test the hypothesis that airway caliber increases are lower in subjects with emphysema-predominant (EP) compared with airway-predominant (AP) CT scan subtypes. Additionally, we compared clinical and CT scan features of subjects with (airway constrictors) and without a decrease in airway caliber. METHODS Based on GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages and CT scan subtypes, we created a control group (n = 46) and the following matched COPD groups (n = 23 each): GOLD-2-AP, GOLD-2-EP, GOLD-4-AP, and GOLD-4-EP. From the CT scans of all 138 subjects, we measured emphysema, lung volumes, and caliber changes in the third and fourth airway generations of two bronchi. We expressed airway distensibility (ratio of airway lumen diameter change to lung volume change from end tidal breathing to full inspiration) as a global or lobar measure based on normalization by whole-lung or lobar volume changes. RESULTS Global distensibility in the third and fourth airway generations was significantly lower in the GOLD-2-EP and GOLD-4-EP groups than in control subjects. In GOLD-2 subjects, lobar distensibility of the right-upper-lobe fourth airway generation was significantly lower in those with EP than in those with AP. In multivariate analysis, emphysema was an independent determinant of global and lobar airway distensibility. Compared with nonconstrictors, airway constrictors experienced more dyspnea, were more hyperinflated, and had a higher percentage of emphysema. CONCLUSIONS Distensibility of large- to medium-sized airways is reduced in subjects with an EP CT scan subtype. Emphysema seems to alter airway-parenchyma interdependence. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.
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Affiliation(s)
- Alejandro A Diaz
- Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Department of Pulmonary Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Carolyn E Come
- Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - James C Ross
- Surgical Planning Laboratory, Laboratory of Mathematics in Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA
| | - Raúl San José Estépar
- Surgical Planning Laboratory, Laboratory of Mathematics in Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA
| | - MeiLan K Han
- Pulmonary and Critical Care, University of Michigan School of Medicine, Ann Arbor, MI
| | - Stephen H Loring
- Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Edwin K Silverman
- Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Channing Laboratory, Brigham and Women's Hospital, Boston, MA
| | - George R Washko
- Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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