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Article: New and emerging minimally invasive techniques for lung volume reduction.

Maxfield, Roger A

2004 Volume 125, Issue 2, Page(s) 777–783

Abstract: Lung volume reduction surgery (LVRS) has been shown to improve pulmonary function, exercise capacity, quality of life, and survival in selected patients with heterogeneous emphysema. However, LVRS is a major surgical procedure with potential morbidity ... ...

Abstract	Lung volume reduction surgery (LVRS) has been shown to improve pulmonary function, exercise capacity, quality of life, and survival in selected patients with heterogeneous emphysema. However, LVRS is a major surgical procedure with potential morbidity and mortality. Minimally invasive techniques are emerging to achieve lung volume reduction without open thoracotomy. Devices and techniques under study include one-way bronchial valves inserted via fiberoptic bronchoscopy to promote atelectasis in emphysematous lung, promotion of focal atelectasis and fibrosis by bronchoscopic injection of polymers into emphysematous regions of lung, bronchopulmonary fenestrations to enhance expiratory flow, and thoracoscopic plication or compression of emphysematous lung. The goal of all of these procedures is to replicate the benefit of LVRS without the trauma, risks, and extended recovery of open LVRS. Refinement and application of these techniques will allow patients with emphysema and their physicians and surgeons to choose from a number of viable options for lung volume reduction.
MeSH term(s)	Bronchoscopy ; Female ; Humans ; Male ; Minimally Invasive Surgical Procedures/adverse effects ; Minimally Invasive Surgical Procedures/methods ; Pneumonectomy ; Postoperative Complications ; Prognosis ; Pulmonary Emphysema/diagnosis ; Pulmonary Emphysema/mortality ; Pulmonary Emphysema/surgery ; Respiratory Function Tests ; Risk Assessment ; Severity of Illness Index ; Survival Rate ; Thoracic Surgery, Video-Assisted/methods ; Thoracoscopy/methods ; Treatment Outcome
Language	English
Publishing date	2004-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1378/chest.125.2.777
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Article: Molecular testing guidelines for lung adenocarcinoma: Utility of cell blocks and concordance between fine-needle aspiration cytology and histology samples.

Heymann, Jonas J / Bulman, William A / Maxfield, Roger A / Powell, Charles A / Halmos, Balazs / Sonett, Joshua / Beaubier, Nike T / Crapanzano, John P / Mansukhani, Mahesh M / Saqi, Anjali

CytoJournal

2014 Volume 11, Page(s) 12

Abstract: Background: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive ... ...

Abstract	Background: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive procedures are being performed, and identification of lung adenocarcinoma driver mutations has led to the implementation of targeted therapies. Advances in molecular techniques enable use of scant tissue, including cytology specimens. In addition, per recently published consensus guidelines, cytology-derived cell blocks (CBs) are preferred over direct smears. Yet, limited comparison of molecular testing of fine-needle aspiration (FNA) CBs and corresponding histology specimens has been performed. This study aimed to establish concordance of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) virus homolog testing between FNA CBs and histology samples from the same patients. Materials and methods: Patients for whom molecular testing for EGFR or KRAS was performed on both FNA CBs and histology samples containing lung adenocarcinoma were identified retrospectively. Following microdissection, when necessary, concordance of EGFR and KRAS molecular testing results between FNA CBs and histology samples was evaluated. Results: EGFR and/or KRAS testing was performed on samples obtained from 26 patients. Concordant results were obtained for all EGFR (22/22) and KRAS (17/17) mutation analyses performed. Conclusions: Identification of mutations in lung adenocarcinomas affects clinical decision-making, and it is important that results from small samples be accurate. This study demonstrates that molecular testing on cytology CBs is as sensitive and specific as that on histology.
Language	English
Publishing date	2014-05-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2158838-7
ISSN	1742-6413 ; 0974-5963
ISSN (online)	1742-6413
ISSN	0974-5963
DOI	10.4103/1742-6413.132989
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Article ; Online: Molecular testing guidelines for lung adenocarcinoma

Jonas J. Heymann / William A. Bulman / Roger A. Maxfield / Charles A. Powell / Balazs Halmos / Joshua Sonett / Nike T. Beaubier / John P. Crapanzano / Mahesh M. Mansukhani / Anjali Saqi

CytoJournal, Vol 11, Iss 1, Pp 12-

Utility of cell blocks and concordance between fine-needle aspiration cytology and histology samples

2014 Volume 12

Abstract	Background: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive procedures are being performed, and identification of lung adenocarcinoma driver mutations has led to the implementation of targeted therapies. Advances in molecular techniques enable use of scant tissue, including cytology specimens. In addition, per recently published consensus guidelines, cytology-derived cell blocks (CBs) are preferred over direct smears. Yet, limited comparison of molecular testing of fine-needle aspiration (FNA) CBs and corresponding histology specimens has been performed. This study aimed to establish concordance of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) virus homolog testing between FNA CBs and histology samples from the same patients. Materials and Methods: Patients for whom molecular testing for EGFR or KRAS was performed on both FNA CBs and histology samples containing lung adenocarcinoma were identified retrospectively. Following microdissection, when necessary, concordance of EGFR and KRAS molecular testing results between FNA CBs and histology samples was evaluated. Results: EGFR and/or KRAS testing was performed on samples obtained from 26 patients. Concordant results were obtained for all EGFR (22/22) and KRAS (17/17) mutation analyses performed. Conclusions: Identification of mutations in lung adenocarcinomas affects clinical decision-making, and it is important that results from small samples be accurate. This study demonstrates that molecular testing on cytology CBs is as sensitive and specific as that on histology.
Keywords	Cell blocks ; cytopathology ; endobronchial ultrasound-guided ; epidermal growth factor receptor ; fine needle aspiration ; Kirsten rat sarcoma ; lung adenocarcinoma ; molecular testing ; Cytology ; QH573-671 ; Biology (General) ; QH301-705.5 ; Science ; Q
Subject code	616
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Medknow Publications
Document type	Article ; Online
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Article ; Online: The efficacy of EBUS-guided transbronchial needle aspiration for molecular testing in lung adenocarcinoma.

Jurado, Julissa / Saqi, Anjali / Maxfield, Roger / Newmark, Alexis / Lavelle, Matt / Bacchetta, Matthew / Gorenstein, Lyall / Dovidio, Frank / Ginsburg, Mark E / Sonett, Joshua / Bulman, William

The Annals of thoracic surgery

2013 Volume 96, Issue 4, Page(s) 1196–1202

Abstract: Background: The purpose of the study was to assess the efficacy of obtaining adequate cytologic specimens by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for molecular testing of lung adenocarcinomas.: Methods: This ... ...

Abstract	Background: The purpose of the study was to assess the efficacy of obtaining adequate cytologic specimens by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for molecular testing of lung adenocarcinomas. Methods: This was an institutional review board-approved study of all patients who had undergone EBUS-TBNA from April 2010 through March 2012 for the diagnosis, staging, or both of lung cancer. Patients with a diagnosis of adenocarcinoma were reflexively tested for molecular markers by polymerase chain reaction, sequencing, and fluorescence in situ hybridization (FISH). All procedures were performed with patients under conscious sedation in the bronchoscopy suite. Results: Of 205 patients who underwent EBUS-TBNA, 56 patients (24 male, 32 female) had a diagnosis of adenocarcinoma warranting molecular analysis. Molecular analysis was available for epidermal growth factor receptor (EGFR), Kirsten rat sarcoma (Kras) mutation, and anaplastic lymphoma kinase (ALK) gene rearrangement. The institution's clinical protocol involved initial testing for EGFR mutation with a reflex Kras test if the EGFR test result was negative. ALK FISH molecular testing was completed if both EGFR and Kras test results were negative. A total of 52 of 56 (93%) patients had sufficient cytologic material for complete or partial molecular testing, whereas 46 of 56 (82%) patients had sufficient material for all clinically indicated testing. EGFR, Kras, and ALK analysis yielded positive results in 5 (10%), 10 (25%), and 5 (12%) tested specimens, respectively. No complications were associated with EBUS-TBNA. Conclusions: EBUS-TBNA performed with the patient under moderate sedation can be expected to yield sufficient tissue for sequential molecular analysis in the majority of patients. In an era of targeted therapy for lung adenocarcinomas, EBUS-TBNA is effective in clinical practice for complete diagnosis, staging, and treatment planning in these patients.
MeSH term(s)	Adenocarcinoma/diagnosis ; Adenocarcinoma/pathology ; Adenocarcinoma of Lung ; Aged ; Aged, 80 and over ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Molecular Diagnostic Techniques
Language	English
Publishing date	2013-08-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2013.05.066
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Article ; Online: Lung volume reduction surgery using the NETT selection criteria.

Ginsburg, Mark E / Thomashow, Byron M / Yip, Chun K / DiMango, Angela M / Maxfield, Roger A / Bartels, Matthew N / Jellen, Patricia / Bulman, William A / Lederer, David / Brogan, Francis L / Gorenstein, Lyall A / Sonett, Joshua R

The Annals of thoracic surgery

2011 Volume 91, Issue 5, Page(s) 1556–60; discussion 1561

Abstract: Background: The National Emphysema Treatment Trial (NETT) proved that lung volume reduction surgery (LVRS) was safe and effective in patients with certain clinical characteristics and using defined inclusion-exclusion criteria. Based on the selection ... ...

Abstract	Background: The National Emphysema Treatment Trial (NETT) proved that lung volume reduction surgery (LVRS) was safe and effective in patients with certain clinical characteristics and using defined inclusion-exclusion criteria. Based on the selection criteria developed in that trial, we performed bilateral LVRS on 49 patients during the period of February 2004 until May 2009. Methods: Forty-nine patients underwent lung volume reduction by either median sternotomy (10) or video-assisted thoracoscopic surgery (39) selected according to NETT described parameters. Preoperative characteristics were the following: mean (±SD) age 62.5±6.6 years, preoperative FEV1 (forced expiratory volume in the first second of expiration) 691 cc (±159), % of predicted FEV1 25.3 (±6.2), preoperative Dlco (diffusing capacity of lung for carbon monoxide) 7.6 (±2.7), and % of predicted DLCO 27% (±7.3). All patients had upper lobe predominant disease and either low exercise capacity (n=23) or high exercise capacity (n=26) as defined by the NETT. Results: There was no operative or 90-day mortality. Median length of stay was 8 days (interquartile range=6 to 10). Two patients required reintubation and tracheostomy but were decannulated prior to discharge. The BODE index (body mass index, airflow obstruction, dyspnea, and exercise capacity), a multidimensional predictor of survival in chronic obstructive pulmonary disease, improved -2.3 (±1.5, p<0.0001) (missing data: 5 of 42, 11.9%) and the FEV1 improved 286 cc (±221, p<0.0001), both 1 year after surgery. Probability of survival was 0.98 (95% CI [confidence interval]=0.94 to 1) at 1 year, and 0.95 (95% CI=0.88 to 1) at 3 years. Conclusions: Surgical lung volume reduction for emphysema can be performed in patients using selection criteria developed by the NETT with very low surgical risk and excellent midterm results. Surgical LVRS is the standard against which other nonsurgical treatments for advanced emphysema should be judged.
MeSH term(s)	Aged ; Cohort Studies ; Confidence Intervals ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Length of Stay ; Male ; Middle Aged ; Pain, Postoperative/physiopathology ; Patient Selection ; Pneumonectomy/adverse effects ; Pneumonectomy/methods ; Postoperative Complications/mortality ; Postoperative Complications/physiopathology ; Pulmonary Emphysema/diagnosis ; Pulmonary Emphysema/mortality ; Pulmonary Emphysema/surgery ; Respiratory Function Tests ; Retrospective Studies ; Risk Assessment ; Severity of Illness Index ; Sternotomy/methods ; Survival Analysis ; Thoracic Surgery, Video-Assisted/methods ; Treatment Outcome
Language	English
Publishing date	2011-05
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2011.01.054
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Article ; Online: Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial.

Sciurba, Frank C / Criner, Gerard J / Strange, Charlie / Shah, Pallav L / Michaud, Gaetane / Connolly, Timothy A / Deslée, Gaëtan / Tillis, William P / Delage, Antoine / Marquette, Charles-Hugo / Krishna, Ganesh / Kalhan, Ravi / Ferguson, J Scott / Jantz, Michael / Maldonado, Fabien / McKenna, Robert / Majid, Adnan / Rai, Navdeep / Gay, Steven /

Dransfield, Mark T / Angel, Luis / Maxfield, Roger / Herth, Felix J F / Wahidi, Momen M / Mehta, Atul / Slebos, Dirk-Jan

JAMA

2016 Volume 315, Issue 20, Page(s) 2178–2189

Abstract: Importance: Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation.: Objective! ...

Abstract	Importance: Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. Objective: To determine the effectiveness and safety of endobronchial coil treatment. Design, setting, and participants: Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. Interventions: Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. Main outcomes and measures: The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St George's Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. Results: Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs -7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St George's Respiratory Questionnaire score improved -8.9 points (97.5% CI, -∞ to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. Conclusions and relevance: Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. Trial registration: clinicaltrials.gov Identifier: NCT01608490.
MeSH term(s)	Aged ; Bronchoscopy ; Exercise Tolerance ; Female ; Forced Expiratory Volume ; Hospitalization ; Humans ; Lung/physiopathology ; Male ; Middle Aged ; Pneumonia/etiology ; Prostheses and Implants/adverse effects ; Pulmonary Emphysema/physiopathology ; Pulmonary Emphysema/therapy ; Quality of Life ; Single-Blind Method ; Treatment Outcome
Language	English
Publishing date	2016-05-18
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2016.6261
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Article: Detection of lung cancer using weighted digital analysis of breath biomarkers.

Phillips, Michael / Altorki, Nasser / Austin, John H M / Cameron, Robert B / Cataneo, Renee N / Kloss, Robert / Maxfield, Roger A / Munawar, Muhammad I / Pass, Harvey I / Rashid, Asif / Rom, William N / Schmitt, Peter / Wai, James

Clinica chimica acta; international journal of clinical chemistry

2008 Volume 393, Issue 2, Page(s) 76–84

Abstract: Background: A combination of biomarkers in a multivariate model may predict disease with greater accuracy than a single biomarker employed alone. We developed a non-linear method of multivariate analysis, weighted digital analysis (WDA), and evaluated ... ...

Abstract	Background: A combination of biomarkers in a multivariate model may predict disease with greater accuracy than a single biomarker employed alone. We developed a non-linear method of multivariate analysis, weighted digital analysis (WDA), and evaluated its ability to predict lung cancer employing volatile biomarkers in the breath. Methods: WDA generates a discriminant function to predict membership in disease vs no disease groups by determining weight, a cutoff value, and a sign for each predictor variable employed in the model. The weight of each predictor variable was the area under the curve (AUC) of the receiver operating characteristic (ROC) curve minus a fixed offset of 0.55, where the AUC was obtained by employing that predictor variable alone, as the sole marker of disease. The sign (+/-) was used to invert the predictor variable if a lower value indicated a higher probability of disease. When employed to predict the presence of a disease in a particular patient, the discriminant function was determined as the sum of the weights of all predictor variables that exceeded their cutoff values. The algorithm that generates the discriminant function is deterministic because parameters are calculated from each individual predictor variable without any optimization or adjustment. We employed WDA to re-evaluate data from a recent study of breath biomarkers of lung cancer, comprising the volatile organic compounds (VOCs) in the alveolar breath of 193 subjects with primary lung cancer and 211 controls with a negative chest CT. Results: The WDA discriminant function accurately identified patients with lung cancer in a model employing 30 breath VOCs (ROC curve AUC=0.90; sensitivity=84.5%, specificity=81.0%). These results were superior to multilinear regression analysis of the same data set (AUC=0.74, sensitivity=68.4, specificity=73.5%). WDA test accuracy did not vary appreciably with TNM (tumor, node, metastasis) stage of disease, and results were not affected by tobacco smoking (ROC curve AUC=0.92 in current smokers, 0.90 in former smokers). WDA was a robust predictor of lung cancer: random removal of 1/3 of the VOCs did not reduce the AUC of the ROC curve by >10% (99.7% CI). Conclusions: A test employing WDA of breath VOCs predicted lung cancer with accuracy similar to chest computed tomography. The algorithm identified dependencies that were not apparent with traditional linear methods. WDA appears to provide a useful new technique for non-linear multivariate analysis of data.
MeSH term(s)	Biomarkers/analysis ; Breath Tests ; Humans ; Lung Neoplasms/diagnosis ; Multivariate Analysis
Chemical Substances	Biomarkers
Language	English
Publishing date	2008-03-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2008.02.021
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Article: Detection of lung cancer with volatile markers in the breath.

Phillips, Michael / Cataneo, Renee N / Cummin, Andrew R C / Gagliardi, Anthony J / Gleeson, Kevin / Greenberg, Joel / Maxfield, Roger A / Rom, William N

Chest

2003 Volume 123, Issue 6, Page(s) 2115–2123

Abstract: Study objectives: To evaluate volatile organic compounds (VOCs) in the breath as tumor markers in lung cancer. Alkanes and monomethylated alkanes are oxidative stress products that are excreted in the breath, the catabolism of which may be accelerated ... ...

Abstract	Study objectives: To evaluate volatile organic compounds (VOCs) in the breath as tumor markers in lung cancer. Alkanes and monomethylated alkanes are oxidative stress products that are excreted in the breath, the catabolism of which may be accelerated by polymorphic cytochrome p450-mixed oxidase enzymes that are induced in patients with lung cancer. Design: Combined case-control and cross-sectional study. Setting: Five academic pulmonary medicine services in the United States and the United Kingdom. Patients and participants: One hundred seventy-eight bronchoscopy patients and 41 healthy volunteers. Intervention: Breath samples were analyzed by gas chromatography and mass spectroscopy to determine alveolar gradients (ie, the abundance in breath minus the abundance in room air) of C4-C20 alkanes and monomethylated alkanes. Measurements: Patients with primary lung cancer (PLC) were compared to healthy volunteers, and a predictive model was constructed using forward stepwise discriminant analysis of the alveolar gradients. This model was cross-validated with a leave-one-out jackknife technique and was tested in two additional groups of patients who had not been used to develop the model (ie, bronchoscopy patients in whom cancer was not detected, and patients with metastatic lung cancer [MLC]). Results: Eighty-seven of 178 patients had lung cancer (PLC, 67 patients; MLC, 15 patients; undetermined, 5 patients). A predictive model employing nine VOCs identified PLC with a sensitivity of 89.6% (60 of 67 patients) and a specificity of 82.9% (34 of 41 patients). On cross-validation, the sensitivity was 85.1% (57 of 67 patients) and the specificity was 80.5% (33 of 41 patients). The stratification of patients by tobacco smoking status, histologic type of cancer, and TNM stage of cancer revealed no marked effects. In the two additional tests, the model predicted MLC with a sensitivity of 66.7% (10 of 15 patients), and it classified the cancer-negative bronchoscopy patients with a specificity of 37.4% (34 of 91 patients). Conclusions: Compared to healthy volunteers, patients with PLC had abnormal breath test findings that were consistent with the accelerated catabolism of alkanes and monomethylated alkanes. A predictive model employing nine of these VOCs exhibited sufficient sensitivity and specificity to be considered as a screen for lung cancer in a high-risk population such as adult smokers.
MeSH term(s)	Alkanes/metabolism ; Biomarkers, Tumor/analysis ; Breath Tests/methods ; Bronchoscopy ; Case-Control Studies ; Cross-Sectional Studies ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/secondary ; Male ; Middle Aged ; Organic Chemicals/analysis ; Sensitivity and Specificity ; Volatilization
Chemical Substances	Alkanes ; Biomarkers, Tumor ; Organic Chemicals
Language	English
Publishing date	2003-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1378/chest.123.6.2115
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Article: Prediction of lung cancer using volatile biomarkers in breath.

Phillips, Michael / Altorki, Nasser / Austin, John H M / Cameron, Robert B / Cataneo, Renee N / Greenberg, Joel / Kloss, Robert / Maxfield, Roger A / Munawar, Muhammad I / Pass, Harvey I / Rashid, Asif / Rom, William N / Schmitt, Peter

Cancer biomarkers : section A of Disease markers

2007 Volume 3, Issue 2, Page(s) 95–109

Abstract: Background: Normal metabolism generates several volatile organic compounds (VOCs) that are excreted in the breath (e.g. alkanes). In patients with lung cancer, induction of high-risk cytochrome p450 genotypes may accelerate catabolism of these VOCs, so ... ...

Abstract	Background: Normal metabolism generates several volatile organic compounds (VOCs) that are excreted in the breath (e.g. alkanes). In patients with lung cancer, induction of high-risk cytochrome p450 genotypes may accelerate catabolism of these VOCs, so that their altered abundance in breath may provide biomarkers of lung cancer. Methods: VOCs in 1.0 L alveolar breath were analyzed in 193 subjects with primary lung cancer and 211 controls with a negative chest CT. Subjects were randomly assigned to a training set or to a prediction set in a 2:1 split. A fuzzy logic model of breath biomarkers of lung cancer was constructed in the training set and then tested in subjects in the prediction set by generating their typicality scores for lung cancer. Results: Mean typicality scores employing a 16 VOC model were significantly higher in lung cancer patients than in the control group (p<0.0001 in all TNM stages). The model predicted primary lung cancer with 84.6% sensitivity, 80.0% specificity, and 0.88 area under curve (AUC) of the receiver operating characteristic (ROC) curve. Predictive accuracy was similar in TNM stages 1 through 4, and was not affected by current or former tobacco smoking. The predictive model achieved near-maximal performance with six breath VOCs, and was progressively degraded by random classifiers. Predictions with fuzzy logic were consistently superior to multilinear analysis. If applied to a population with 2% prevalence of lung cancer, a screening breath test would have a negative predictive value of 0.985 and a positive predictive value of 0.163 (true positive rate =0.277, false positive rate =0.029). Conclusions: A two-minute breath test predicted lung cancer with accuracy comparable to screening CT of chest. The accuracy of the test was not affected by TNM stage of disease or tobacco smoking. Alterations in breath VOCs in lung cancer were consistent with a non-linear pathophysiologic process, such as an off-on switch controlling high-risk cytochrome p450 activity. Further research is needed to determine if detection of lung cancer with this test will reduce mortality.
MeSH term(s)	Aged ; Area Under Curve ; Biomarkers, Tumor/analysis ; Breath Tests ; Female ; Humans ; Lung Neoplasms/diagnosis ; Male ; Models, Statistical ; Neoplasm Staging ; Organic Chemicals/analysis ; ROC Curve ; Sensitivity and Specificity
Chemical Substances	Biomarkers, Tumor ; Organic Chemicals
Language	English
Publishing date	2007-05-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2203517-5
ISSN	1574-0153 ; 1574-0153 ; 1875-8592
ISSN (online)	1574-0153
ISSN	1574-0153 ; 1875-8592
DOI	10.3233/cbm-2007-3204
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Article ; Online: Lung-volume reduction surgery for pulmonary emphysema: Improvement in body mass index, airflow obstruction, dyspnea, and exercise capacity index after 1 year.

Lederer, David J / Thomashow, Byron M / Ginsburg, Mark E / Austin, John H M / Bartels, Matthew N / Yip, Chun K / Jellen, Patricia A / Brogan, Frances L / Kawut, Steven M / Maxfield, Roger A / DiMango, Angela M / Simonelli, Paul F / Gorenstein, Lyall A / Pearson, Gregory D N / Sonett, Joshua R

The Journal of thoracic and cardiovascular surgery

2007 Volume 133, Issue 6, Page(s) 1434–1438

Abstract: Objectives: We hypothesized that lung-volume reduction surgery for pulmonary emphysema would improve body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index, a multidimensional predictor of survival in chronic obstructive ... ...

Abstract	Objectives: We hypothesized that lung-volume reduction surgery for pulmonary emphysema would improve body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index, a multidimensional predictor of survival in chronic obstructive pulmonary disease. We also aimed to identify preoperative predictors of improvement in the BODE index. Methods: In a prospective cohort study of patients undergoing lung-volume reduction surgery at our center, with the methodology of the National Emphysema Treatment Trial, we compared clinical characteristics before and 1 year after surgery with the Wilcoxon signed rank test. Changes in the BODE index were correlated with preoperative variables with the Spearman correlation coefficient. Results: Twenty-three patients with predominantly upper-lobe pulmonary emphysema underwent lung-volume reduction surgery (14 by video-assisted thoracoscopic surgery, 9 by median sternotomy). There were no postoperative or follow-up deaths. The BODE index improved from a median of 5 (interquartile range 4-5) before surgery to 3 (interquartile range 2-4) 1 year after surgery (P < .0001). Improvements were seen in the lung function and dyspnea components of the BODE index. Lower preoperative 6-minute walk distance and lower postwalk Borg fatigue scores were each associated with greater improvement in the BODE index after 1 year. Conclusion: Lung-volume reduction surgery for pulmonary emphysema improved the BODE index in patients with predominantly upper-lobe disease. Lower preoperative 6-minute walk distance correlated with greater improvement in the BODE index.
MeSH term(s)	Airway Obstruction/physiopathology ; Body Mass Index ; Dyspnea/physiopathology ; Exercise Tolerance ; Female ; Humans ; Lung Volume Measurements ; Male ; Middle Aged ; Patient Selection ; Pneumonectomy/methods ; Predictive Value of Tests ; Prospective Studies ; Pulmonary Emphysema/physiopathology ; Pulmonary Emphysema/surgery ; Respiratory Function Tests ; Risk Factors ; Severity of Illness Index ; Statistics, Nonparametric ; Survival Analysis
Language	English
Publishing date	2007-06
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	3104-5
ISSN	1097-685X ; 0022-5223
ISSN (online)	1097-685X
ISSN	0022-5223
DOI	10.1016/j.jtcvs.2006.12.062
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