Development of a novel remote patient monitoring system: the advanced symptom management system for radiotherapy to improve the symptom experience of patients with lung cancer receiving radiotherapy.

PubMed

Maguire, Roma; Ream, Emma; Richardson, Alison; Connaghan, John; Johnston, Bridget; Kotronoulas, Grigorios; Pedersen, Vibe; McPhelim, John; Pattison, Natalie; Smith, Allison; Webster, Lorraine; Taylor, Anne; Kearney, Nora

2015-01-01

The use of technology-enhanced patient-reported outcome measures to monitor the symptoms experienced by people with cancer is an effective way to offer timely care. This study aimed to (a) explore the feasibility and acceptability of the Advanced Symptom Management System with patients with lung cancer receiving radiotherapy and clinicians involved in their care and (b) assess changes in patient outcomes during implementation of the Advanced Symptom Management System with patients with lung cancer receiving radiotherapy in clinical practice. A repeated-measures, single-arm, mixed-methods study design was used involving poststudy interviews and completion of patient-reported outcome measures at baseline and end of treatment with 16 patients with lung cancer and 13 clinicians who used this mobile phone-based symptom monitoring system. Only rarely did patients report problems in using the handset and they felt that the system covered all relevant symptoms and helped them to manage their symptoms and effectively communicate with clinicians. Clinical improvements in patient anxiety, drowsiness, and self-care self-efficacy were also observed. Clinicians perceived the use of "real-time" risk algorithms and automated self-care advice provided to patients as positively contributing to clinical care. Reducing the complexity of the system was seen as important to promote its utility. Although preliminary, these results suggest that monitoring patient symptoms using mobile technology in the context of radiotherapy for lung cancer is feasible and acceptable in clinical practice. Future research would be most beneficial if the use of this technology was focused on the postradiotherapy phase and expanded the scope of the system to encompass a wider range of supportive care needs.

No adverse lung effects of 7- and 28-day inhalation exposure of rats to emissions from petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without particulate filter - the FuelHealth project.

PubMed

Magnusson, Pål; Oczkowski, Michał; Øvrevik, Johan; Gajewska, Malgorzata; Wilczak, Jacek; Biedrzycki, Jacek; Dziendzikowska, Katarzyna; Kamola, Dariusz; Królikowski, Tomasz; Kruszewski, Marcin; Lankoff, Anna; Mruk, Remigiusz; Brunborg, Gunnar; Instanes, Christine; Gromadzka-Ostrowska, Joanna; Myhre, Oddvar

2017-04-01

Increased use of biofuels raises concerns about health effects of new emissions. We analyzed relative lung health effects, on Fisher 344 rats, of diesel engine exhausts emissions (DEE) from a Euro 5-classified diesel engine running on petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without diesel particulate filter (DPF). One group of animals was exposed to DEE for 7 days (6 h/day), and another group for 28 days (6 h/day, 5 days/week), both with and without DPF. The animals (n = 7/treatment) were exposed in whole body exposure chambers. Animals breathing clean air were used as controls. Genotoxic effects of the lungs by the Comet assay, histological examination of lung tissue, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury, and mRNA markers of inflammation and oxidative stress were analyzed. Our results showed that a minor number of genes related to inflammation were slightly differently expressed in the exposed animals compared to control. Histological analysis also revealed only minor effects on inflammatory tissue markers in the lungs, and this was supported by flow cytometry and ELISA analysis of cytokines in BALF. No exposure-related indications of genotoxicity were observed. Overall, exposure to DEE with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF. Overall, exposure to DEE from a modern Euro 5 light vehicle engine run on B20 fuel with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF.

Lung cancer disparities and African-Americans.

PubMed

Sin, Mo-Kyung

2017-07-01

African-Americans, as historically disadvantaged minorities, have more advanced stages of cancer when diagnosed, lower survival rates, and lower rates of accessing timely care than do Caucasians. Lung cancer incidence and mortality, in particular, are high among African-Americans. The U.S. Preventive Services Task Force recently released an evidence-based lung cancer screening technology called low-dose computerized tomography. High-risk African-Americans might benefit greatly from such screening but not many are aware of this technology. Public health nurses can play a key role in increasing awareness of the technology among African-American communities and encouraging qualified African-Americans to obtain screening. This study discusses issues with lung cancer and smoking among African-Americans, a recently released evidence-based lung cancer screening technology, and implications for public health nurses to enhance uptake of the new screening technology among high-risk African-Americans. © 2017 Wiley Periodicals, Inc.

Computer-aided detection systems to improve lung cancer early diagnosis: state-of-the-art and challenges

NASA Astrophysics Data System (ADS)

Traverso, A.; Lopez Torres, E.; Fantacci, M. E.; Cerello, P.

2017-05-01

Lung cancer is one of the most lethal types of cancer, because its early diagnosis is not good enough. In fact, the detection of pulmonary nodule, potential lung cancers, in Computed Tomography scans is a very challenging and time-consuming task for radiologists. To support radiologists, researchers have developed Computer-Aided Diagnosis (CAD) systems for the automated detection of pulmonary nodules in chest Computed Tomography scans. Despite the high level of technological developments and the proved benefits on the overall detection performance, the usage of Computer-Aided Diagnosis in clinical practice is far from being a common procedure. In this paper we investigate the causes underlying this discrepancy and present a solution to tackle it: the M5L WEB- and Cloud-based on-demand Computer-Aided Diagnosis. In addition, we prove how the combination of traditional imaging processing techniques with state-of-art advanced classification algorithms allows to build a system whose performance could be much larger than any Computer-Aided Diagnosis developed so far. This outcome opens the possibility to use the CAD as clinical decision support for radiologists.

21 CFR 868.5610 - Membrane lung for long-term pulmonary support.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Membrane lung for long-term pulmonary support. 868... SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5610 Membrane lung for long-term pulmonary support. (a) Identification. A membrane lung for long-term pulmonary support...

21 CFR 868.5610 - Membrane lung for long-term pulmonary support.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Membrane lung for long-term pulmonary support. 868... SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5610 Membrane lung for long-term pulmonary support. (a) Identification. A membrane lung for long-term pulmonary support...

RGS17: an emerging therapeutic target for lung and prostate cancers

PubMed Central

Bodle, Christopher R; Mackie, Duncan I; Roman, David L

2013-01-01

Ligands for G-protein-coupled receptors (GPCRs) represent approximately 50% of currently marketed drugs. RGS proteins modulate heterotrimeric G proteins and, thus, GPCR signaling, by accelerating the intrinsic GTPase activity of the Gα subunit. Given the prevalence of GPCR targeted therapeutics and the role RGS proteins play in G protein signaling, some RGS proteins are emerging as targets in their own right. One such RGS protein is RGS17. Increased RGS17 expression in some prostate and lung cancers has been demonstrated to support cancer progression, while reduced expression of RGS17 can lead to development of chemotherapeutic resistance in ovarian cancer. High-throughput screening is a powerful tool for lead compound identification, and utilization of high-throughput technologies has led to the discovery of several RGS inhibitors, thus far. As screening technologies advance, the identification of novel lead compounds the subsequent development of targeted therapeutics appears promising. PMID:23734683

Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.

PubMed

Shafii, Alexis E; Mason, David P; Brown, Chase R; Vakil, Nakul; Johnston, Douglas R; McCurry, Kenneth R; Pettersson, Gosta B; Murthy, Sudish C

2012-01-01

Extracorporeal membrane oxygenation (ECMO) is rarely used as a bridge to lung transplantation (BTT) because of its associated morbidity and mortality. However, recent advancements in perfusion technology and critical care have revived interest in this application of ECMO. We retrospectively reviewed our utilization of ECMO as BTT and evaluated our early and midterm results. Nineteen patients were placed on ECMO with the intent to transplant of which 14 (74%) were successfully transplanted. Early and midterm survival of transplanted patients was 75% (1 year) and 63% (3 years), respectively, with the most favorable results observed in interstitial lung disease patients supported in the venovenous configuration. Extracorporeal membrane oxygenation-bridged transplant survival rates were equivalent to nonbridged recipients, but early morbidity and mortality are high and the failure to bridge to transplant is significant. Overall, successfully bridged patients can derive a tangible benefit, albeit with considerable consumption of resources.

A Novel Growth Factor and Anti-Apoptotic Agent for Promoting Lung Development and Treating Lung Disease | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a new therapeutic strategy for lung cancer using secretoglobin family 3A member 2 (SCGB3A2), as a cell proliferative and anti-apoptotic agent. SCGB3A2 can be used to inhibit lung damage that results from treatment with anti-cancer agents. NCI seeks parties to license or co-develop this technology.

The value of participatory development to support antimicrobial stewardship with a clinical decision support system.

PubMed

Beerlage-de Jong, Nienke; Wentzel, Jobke; Hendrix, Ron; van Gemert-Pijnen, Lisette

2017-04-01

Current clinical decision support systems (CDSSs) for antimicrobial stewardship programs (ASPs) are guideline- or expert-driven. They are focused on (clinical) content, not on supporting real-time workflow. Thus, CDSSs fail to optimally support prudent antimicrobial prescribing in daily practice. Our aim was to demonstrate why and how participatory development (involving end-users and other stakeholders) can contribute to the success of CDSSs in ASPs. A mixed-methods approach was applied, combining scenario-based prototype evaluations (to support verbalization of work processes and out-of-the-box thinking) among 6 medical resident physicians with an online questionnaire (to cross-reference findings of the prototype evaluations) among 54 Dutch physicians. The prototype evaluations resulted in insight into the end-users and their way of working, as well as their needs and expectations. The online questionnaire that was distributed among a larger group of medical specialists, including lung and infection experts, complemented the findings of the prototype evaluations. It revealed a say/do problem concerning the unrecognized need of support for selecting diagnostic tests. Low-fidelity prototypes of a technology allow researchers to get to know the end-users, their way of working, and their work context. Involving experts allows technology developers to continuously check the fit between technology and clinical practice. The combination enables the participatory development of technology to successfully support ASPs. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

A study on volatile organic compounds emitted by in-vitro lung cancer cultured cells using gas sensor array and SPME-GCMS.

PubMed

Thriumani, Reena; Zakaria, Ammar; Hashim, Yumi Zuhanis Has-Yun; Jeffree, Amanina Iymia; Helmy, Khaled Mohamed; Kamarudin, Latifah Munirah; Omar, Mohammad Iqbal; Shakaff, Ali Yeon Md; Adom, Abdul Hamid; Persaud, Krishna C

2018-04-02

Volatile organic compounds (VOCs) emitted from exhaled breath from human bodies have been proven to be a useful source of information for early lung cancer diagnosis. To date, there are still arguable information on the production and origin of significant VOCs of cancer cells. Thus, this study aims to conduct in-vitro experiments involving related cell lines to verify the capability of VOCs in providing information of the cells. The performances of e-nose technology with different statistical methods to determine the best classifier were conducted and discussed. The gas sensor study has been complemented using solid phase micro-extraction-gas chromatography mass spectrometry. For this purpose, the lung cancer cells (A549 and Calu-3) and control cell lines, breast cancer cell (MCF7) and non-cancerous lung cell (WI38VA13) were cultured in growth medium. This study successfully provided a list of possible volatile organic compounds that can be specific biomarkers for lung cancer, even at the 24th hour of cell growth. Also, the Linear Discriminant Analysis-based One versus All-Support Vector Machine classifier, is able to produce high performance in distinguishing lung cancer from breast cancer cells and normal lung cells. The findings in this work conclude that the specific VOC released from the cancer cells can act as the odour signature and potentially to be used as non-invasive screening of lung cancer using gas array sensor devices.

New operational technology of intrauterine ventilation the fetus lungs by breathing gas

NASA Astrophysics Data System (ADS)

Urakov, A. L.; Nikityuk, D. B.; Urakova, N. A.; Kasankin, A. A.; Chernova, L. V.; Dementiev, V. B.

2015-11-01

New operational technology for elimination intrauterine hypoxia and asphyxia of the fetus using endoscopic artificial ventilation lungs by respiratory gas was developed. For intrauterine ventilation of fetal lung it is proposed to enter into the uterus a special breathing mask and wear it on the head of the fetus using the original endoscopic technology. The breathing mask, developed by us is connected with external breathing apparatus with a hose. The device is called "intrauterine aqualung". Intrauterine aqualung includes a ventilator and breathing circuit with a special fold-out breathing mask that is put on inside the uterus on the head of fetus like a mesh hat. Controlled by ultrasound the technology of the introduction of the mask inside of the uterus through the natural opening in the cervix and technology of putting on the respiratory mask on the head of the fetus with its head previa were developed. The technology intrauterine ventilation of the fetus lungs by respiratory gas was developed.

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK.

PubMed

Fisher, Andrew; Andreasson, Anders; Chrysos, Alexandros; Lally, Joanne; Mamasoula, Chrysovalanto; Exley, Catherine; Wilkinson, Jennifer; Qian, Jessica; Watson, Gillian; Lewington, Oli; Chadwick, Thomas; McColl, Elaine; Pearce, Mark; Mann, Kay; McMeekin, Nicola; Vale, Luke; Tsui, Steven; Yonan, Nizar; Simon, Andre; Marczin, Nandor; Mascaro, Jorge; Dark, John

2016-11-01

Many patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use. The objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity. A multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs. Multicentre study involving all five UK officially designated NHS adult lung transplant centres. Patients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list. The study intervention was EVLP assessment of donor lungs before determining suitability for transplantation. The primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs. Lungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan-Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital stay was similar in both groups. There was a higher rate of very early grade 3 primary graft dysfunction (PGD) in the EVLP arm, but rates of PGD did not differ between groups after 72 hours. The requirement for extracorporeal membrane oxygenation (ECMO) support was higher in the EVLP arm (7/18, 38.8%) than in the standard arm (6/184, 3.2%). There were no major differences in rates of chest radiograph abnormalities, infection, lung function or rejection by 12 months. The cost of EVLP transplants is approximately £35,000 higher than the cost of standard transplants, as a result of the cost of the EVLP procedure, and the increased ECMO use and ITU stay. Predictors of cost were quality of life on joining the waiting list, type of transplant and number of lungs transplanted. An exploratory model comparing a NHS lung transplant service that includes EVLP and standard lung transplants with one including only standard lung transplants resulted in an incremental cost-effectiveness ratio of £73,000. Interviews showed that patients had a good understanding of the need for, and the processes of, EVLP. If EVLP can increase the number of usable donor lungs and reduce waiting, it is likely to be acceptable to those waiting for lung transplantation. Study limitations include small numbers in the EVLP arm, limiting analysis to descriptive statistics and the EVLP protocol change during the study. Overall, one-third of donor lungs subjected to EVLP were deemed suitable for transplant. Estimated survival over 12 months was lower than in the standard group, but the data were also consistent with no difference in survival between groups. Patients receiving these additional transplants experience a higher rate of early graft injury and need for unplanned ECMO support, at increased cost. The small number of participants in the EVLP arm because of early study termination limits the robustness of these conclusions. The reason for the increased PGD rates, high ECMO requirement and possible differences in lung injury between EVLP protocols needs evaluation. Current Controlled Trials ISRCTN44922411. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 20, No. 85. See the NIHR Journals Library website for further project information.

TU-CD-BRA-11: Application of Bone Suppression Technique to Inspiratory/expiratory Chest Radiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, R; Sanada, S; Sakuta, K

Purpose: The bone suppression technique based on advanced image processing can suppress the conspicuity of bones on chest radiographs, creating soft tissue images normally obtained by the dual-energy subtraction technique. This study was performed to investigate the usefulness of bone suppression technique in quantitative analysis of pulmonary function in inspiratory/expiratory chest radiography. Methods: Commercial bone suppression image processing software (ClearRead; Riverain Technologies) was applied to paired inspiratory/expiratory chest radiographs of 107 patients (normal, 33; abnormal, 74) to create corresponding bone suppression images. The abnormal subjects had been diagnosed with pulmonary diseases, such as pneumothorax, pneumonia, emphysema, asthma, and lung cancer.more » After recognition of the lung area, the vectors of respiratory displacement were measured in all local lung areas using a cross-correlation technique. The measured displacement in each area was visualized as displacement color maps. The distribution pattern of respiratory displacement was assessed by comparison with the findings of lung scintigraphy. Results: Respiratory displacement of pulmonary markings (soft tissues) was able to be quantified separately from the rib movements on bone suppression images. The resulting displacement map showed a left-right symmetric distribution increasing from the lung apex to the bottom region of the lung in many cases. However, patients with ventilatory impairments showed a nonuniform distribution caused by decreased displacement of pulmonary markings, which were confirmed to correspond to area with ventilatory impairments found on the lung scintigrams. Conclusion: The bone suppression technique was useful for quantitative analysis of respiratory displacement of pulmonary markings without any interruption of the rib shadows. Abnormal areas could be detected as decreased displacement of pulmonary markings. Inspiratory/expiratory chest radiography combined with the bone suppression technique has potential for predicting local lung function on the basis of dynamic analysis of pulmonary markings. This work was partially supported by Nakatani Foundation, Grant-in-aid for Scientific Research (C) of Ministry of Education, Culture, Sports, Science and Technology, JAPAN (Grant number : 24601007), and Nakatani Foundation, Mitsubishi Foundation, and the he Mitani Foundation for Research and Development. Yasushi Kishitani is a staff of TOYO corporation.« less

Polysaccharide K and Coriolus versicolor extracts for lung cancer: a systematic review.

PubMed

Fritz, Heidi; Kennedy, Deborah A; Ishii, Mami; Fergusson, Dean; Fernandes, Rochelle; Cooley, Kieran; Seely, Dugald

2015-05-01

Polysaccharide K, also known as PSK or Krestin, is derived from the Coriolus versicolor mushroom and is widely used in Japan as an adjuvant immunotherapy for a variety of cancer including lung cancer. Despite reported benefits, there has been no English language synthesis of PSK for lung cancer. To address this knowledge gap, we conducted a systematic review of PSK for the treatment of lung cancer. We searched PubMed, EMBASE, CINAHL, the Cochrane Library, AltHealth Watch, and the Library of Science and Technology from inception to August 2014 for clinical and preclinical evidence pertaining to the safety and efficacy of PSK or other Coriolus versicolor extracts for lung cancer. Thirty-one reports of 28 studies were included for full review and analysis. Six studies were randomized controlled trials, 5 were nonrandomized controlled trials, and 17 were preclinical studies. Nine of the reports were Japanese language publications. Fifteen of 17 preclinical studies supported anticancer effects for PSK through immunomodulation and potentiation of immune surveillance, as well as through direct tumor inhibiting actions in vivo that resulted in reduced tumor growth and antimetastatic effects. Nonrandomized controlled trials showed improvement of various survival measures including median survival and 1-, 2-, and 5-year survival. Randomized controlled trials showed benefits on a range of endpoints, including immune parameters and hematological function, performance status and body weight, tumor-related symptoms such as fatigue and anorexia, as well as survival. Although there were conflicting results for impact on some of the tumor-related symptoms and median survival, overall most randomized controlled trials supported a positive impact for PSK on these endpoints. PSK was safely administered following and in conjunction with standard radiation and chemotherapy. PSK may improve immune function, reduce tumor-associated symptoms, and extend survival in lung cancer patients. Larger, more rigorous randomized controlled trials for PSK in lung cancer patients are warranted. © The Author(s) 2015.

Genomic Medicine and Lung Diseases

PubMed Central

Center, David M.; Schwartz, David A.; Solway, Julian; Gail, Dorothy; Laposky, Aaron D.

2012-01-01

The recent explosion of genomic data and technology points to opportunities to redefine lung diseases at the molecular level; to apply integrated genomic approaches to elucidate mechanisms of lung pathophysiology; and to improve early detection, diagnosis, and treatment of lung diseases. Research is needed to translate genomic discoveries into clinical applications, such as detecting preclinical disease, predicting patient outcomes, guiding treatment choices, and most of all identifying potential therapeutic targets for lung diseases. The Division of Lung Diseases in the National Heart, Lung, and Blood Institute convened a workshop, “Genomic Medicine and Lung Diseases,” to discuss the potential for integrated genomics and systems approaches to advance 21st century pulmonary medicine and to evaluate the most promising opportunities for this next phase of genomics research to yield clinical benefit. Workshop sessions included (1) molecular phenotypes, molecular biomarkers, and therapeutics; (2) new technology and opportunity; (3) integrative genomics; (4) molecular anatomy of the lung; (5) novel data and information platforms; and (6) recommendations for exceptional research opportunities in lung genomics research. PMID:22652029

NHLBI workshop: respiratory medicine-related research training for adult and pediatric fellows.

PubMed

Choi, Augustine M K; Reynolds, Herbert Y; Colombini-Hatch, Sandra; Rothgeb, Ann; Blaisdell, Carol J; Gail, Dorothy B

2009-01-01

The pulmonary physician-scientist has a special niche to generate basic research findings and apply them to a clinical disease and perhaps impact its medical care. The availability of new high throughput-based scientific technologies in the "omics era" has made this an opportune time for physician scientists to prepare and embark on an academic career in respiratory disease research. However, maintaining an adequate flow through the research pipeline of physician-scientist investigators studying respiratory system diseases is currently a challenge. There may not be a sufficient workforce emerging to capitalize on current research opportunities. The National Heart, Lung, and Blood Institute (NHLBI) organized a workshop to assess ways to attract and properly train advanced fellows to pursue research careers in adult and pediatric lung diseases. Participants included representatives from the various pulmonary training programs, respiratory-related professional societies, and NHLBI staff. Deliberation centered on present barriers that might affect interest in pursuing research training, devising better incentives to attract more trainees, and how current research support offered by the NHLBI and the Professional Societies (in partnership with Industry and Patient Support groups) might be better coordinated and optimized to ensure a continued pipeline of pulmonary investigators. Major recommendations offered are: (1) Attract trainees to pulmonary/critical care medicine-based research careers by increasing research exposure and opportunities for high school, college, and medical students. (2) Increase awareness of the outstanding physician-scientist role models in the lung community for trainees. (3) Facilitate mechanisms by which the lung community (NHLBI, professional societies, and partners) can better support and bridge senior fellows as they transition from Institutional Training Grants (T32) to Career Series (K) awards in their early faculty career development.

Health effects research and regulation of diesel exhaust: an historical overview focused on lung cancer risk.

PubMed

Hesterberg, Thomas W; Long, Christopher M; Bunn, William B; Lapin, Charles A; McClellan, Roger O; Valberg, Peter A

2012-06-01

The mutagenicity of organic solvent extracts from diesel exhaust particulate (DEP), first noted more than 55 years ago, initiated an avalanche of diesel exhaust (DE) health effects research that now totals more than 6000 published studies. Despite an extensive body of results, scientific debate continues regarding the nature of the lung cancer risk posed by inhalation of occupational and environmental DE, with much of the debate focused on DEP. Decades of scientific scrutiny and increasingly stringent regulation have resulted in major advances in diesel engine technologies. The changed particulate matter (PM) emissions in "New Technology Diesel Exhaust (NTDE)" from today's modern low-emission, advanced-technology on-road heavy-duty diesel engines now resemble the PM emissions in contemporary gasoline engine exhaust (GEE) and compressed natural gas engine exhaust more than those in the "traditional diesel exhaust" (TDE) characteristic of older diesel engines. Even with the continued publication of epidemiologic analyses of TDE-exposed populations, this database remains characterized by findings of small increased lung cancer risks and inconsistent evidence of exposure-response trends, both within occupational cohorts and across occupational groups considered to have markedly different exposures (e.g. truckers versus railroad shopworkers versus underground miners). The recently published National Institute for Occupational Safety and Health (NIOSH)-National Cancer Institute (NCI) epidemiologic studies of miners provide some of the strongest findings to date regarding a DE-lung cancer association, but some inconsistent exposure-response findings and possible effects of bias and exposure misclassification raise questions regarding their interpretation. Laboratory animal studies are negative for lung tumors in all species, except for rats under lifetime TDE-exposure conditions with durations and concentrations that lead to "lung overload." The species specificity of the rat lung response to overload, and its occurrence with other particle types, is now well-understood. It is thus generally accepted that the rat bioassay for inhaled particles under conditions of lung overload is not predictive of human lung cancer hazard. Overall, despite an abundance of epidemiologic and experimental data, there remain questions as to whether TDE exposure causes increased lung cancers in humans. An abundance of emissions characterization data, as well as preliminary toxicological data, support NTDE as being toxicologically distinct from TDE. Currently, neither epidemiologic data nor animal bioassay data yet exist that directly bear on NTDE carcinogenic potential. A chronic bioassay of NTDE currently in progress will provide data on whether NTDE poses a carcinogenic hazard, but based on the significant reductions in PM mass emissions and the major changes in PM composition, it has been hypothesized that NTDE has a low carcinogenic potential. When the International Agency for Research on Cancer (IARC) reevaluates DE (along with GEE and nitroarenes) in June 2012, it will be the first authoritative body to assess DE carcinogenic health hazards since the emergence of NTDE and the accumulation of data differentiating NTDE from TDE.

Health effects research and regulation of diesel exhaust: an historical overview focused on lung cancer risk

PubMed Central

Hesterberg, Thomas W.; Long, Christopher M.; Bunn, William B.; Lapin, Charles A.; McClellan, Roger O.; Valberg, Peter A.

2012-01-01

The mutagenicity of organic solvent extracts from diesel exhaust particulate (DEP), first noted more than 55 years ago, initiated an avalanche of diesel exhaust (DE) health effects research that now totals more than 6000 published studies. Despite an extensive body of results, scientific debate continues regarding the nature of the lung cancer risk posed by inhalation of occupational and environmental DE, with much of the debate focused on DEP. Decades of scientific scrutiny and increasingly stringent regulation have resulted in major advances in diesel engine technologies. The changed particulate matter (PM) emissions in “New Technology Diesel Exhaust (NTDE)” from today's modern low-emission, advanced-technology on-road heavy-duty diesel engines now resemble the PM emissions in contemporary gasoline engine exhaust (GEE) and compressed natural gas engine exhaust more than those in the “traditional diesel exhaust” (TDE) characteristic of older diesel engines. Even with the continued publication of epidemiologic analyses of TDE-exposed populations, this database remains characterized by findings of small increased lung cancer risks and inconsistent evidence of exposure-response trends, both within occupational cohorts and across occupational groups considered to have markedly different exposures (e.g. truckers versus railroad shopworkers versus underground miners). The recently published National Institute for Occupational Safety and Health (NIOSH)-National Cancer Institute (NCI) epidemiologic studies of miners provide some of the strongest findings to date regarding a DE-lung cancer association, but some inconsistent exposure-response findings and possible effects of bias and exposure misclassification raise questions regarding their interpretation. Laboratory animal studies are negative for lung tumors in all species, except for rats under lifetime TDE-exposure conditions with durations and concentrations that lead to'lung overload."The species specificity of the rat lung response to overload, and its occurrence with other particle types, is now well-understood. It is thus generally accepted that the rat bioassay for inhaled particles under conditions of lung overload is not predictive of human lung cancer hazard. Overall, despite an abundance of epidemiologic and experimental data, there remain questions as to whether TDE exposure causes increased lung cancers in humans. An abundance of emissions characterization data, as well as preliminary toxicological data, support NTDE as being toxicologically distinct from TDE. Currently, neither epidemiologic data nor animal bioassay data yet exist that directly bear on NTDE carcinogenic potential. A chronic bioassay of NTDE currently in progress will provide data on whether NTDE poses a carcinogenic hazard, but based on the significant reductions in PM mass emissions and the major changes in PM composition, it has been hypothesized that NTDE has a low carcinogenic potential. When the International Agency for Research on Cancer (IARC) reevaluates DE (along with GEE and nitroarenes) in June 2012, it will be the first authoritative body to assess DE carcinogenic health hazards since the emergence of NTDE and the accumulation of data differentiating NTDE from TDE. PMID:22663144

Introduction to Nanotechnology for Defense Environment, Health & Safety (EHS) and Research Professionals in Support of the Acquisition Process

DTIC Science & Technology

2011-03-28

www.denix.osd.mil/MERIT Ultra fine particles ~50 1713- Ramazzini described black 197 4- First GMO lung disease mouse created by Jaenisch Diesel...exhaust Engineered NP _____ _,.? • GMO Technology 1985- Oberdorster described inhalation toxicity of Ti02 2003-lssue recognized by EPA, NIOSH...other agencies 2004- California pass broad ban on GMO products Growing Body of EHS Research Far-reaching implications or singular exceptions

Extracorporeal membrane oxygenation as a bridge to lung transplant: midterm outcomes.

PubMed

Bermudez, Christian A; Rocha, Rodolfo V; Zaldonis, Diana; Bhama, Jay K; Crespo, Maria M; Shigemura, Norihisa; Pilewski, Joseph M; Sappington, Penny L; Boujoukos, Arthur J; Toyoda, Yoshiya

2011-10-01

Extracorporeal membrane oxygenation (ECMO) is used occasionally as a bridge to lung transplantation. The impact on mid-term survival is unknown. We analyzed outcomes after lung transplant over a 19-year period in patients who received ECMO support. From March 1991 to October 2010, 1,305 lung transplants were performed at our institution. Seventeen patients (1.3%) were supported with ECMO before lung transplant. Diagnoses included retransplantation (n = 6), pulmonary fibrosis (n = 6), cystic fibrosis (n = 4), and chronic obstructive pulmonary disease (n = 1). Fifteen patients underwent double lung transplant, one patient had single left lung transplant and one patient had a heart-lung transplant. Venovenous and venoarterial ECMO were implanted in eight and nine cases, respectively. Median duration of support was 3.2 days (range, 1 to 49 days). Mean patient follow-up was 2.3 years. Thirty-day, 1-year, and 3-year survivals were 81%, 74%, and 65%, respectively, for the supported patients and 93%, 78%, and 62% in the control group (p = 0.56). Two-year survival was not affected by ECMO type, with survival of five out of nine patients supported by venoarterial ECMO vs seven out of eight patients supported by venovenous ECMO (p = 0.17). At 1- year follow-up, allograft function for the ECMO-supported patients did not differ from the control group (forced expiratory volume in one second, 2.35 L vs 2.09 L, p = 0.39) (forced vital capacity, 3.06 L vs 2.71 L, p = 0.34). Extracorporeal membrane oxygenation as a bridge to lung transplantation is associated with higher perioperative mortality but acceptable mid-term survival in carefully selected patients. Late allograft function did not differ in patients who received ECMO support before lung transplant from those who did not receive ECMO. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

[Application of medical imaging to general thoracic surgery].

PubMed

Oizumi, Hiroyuki

2014-07-01

Medical imaging technology is rapidly progressing. Positron emission tomography (PET) has played major role in the staging and choice of treatment modality in lung cancer patients. Magnetic resonance imaging (MRI) is now routinely used for mediastinal tumors and the use of diffusion-weighted images (DWI) may help in the diagnosis of malignancies including lung cancers. The benefits of medical imaging technology are not limited to diagnostics, and include simulation or navigation for complex lung resection and other procedures. Multidetector row computed tomography (MDCT) shortens imaging time to obtain detailed and precise volume data, which improves diagnosis of small-sized lung cancers. 3-dimensional reconstruction of the volume data allows the safe performance of thoracoscopic surgery. For lung lobectomy, identification of the branching structures, diameter, and length of the arteries is useful in selecting the procedure for blood vessel treatment. For lung segmentectomy, visualization of venous branches in the affected segments and intersegmental veins has facilitated the preoperative determination of the anatomical intersegmental plane. Therefore, the application of medical imaging technology is useful in general thoracic surgery.

Increasing radiology capacity within the lung cancer pathway: centralised work-based support for trainee chest X-ray reporting radiographers.

PubMed

Woznitza, Nick; Steele, Rebecca; Piper, Keith; Burke, Stephen; Rowe, Susan; Bhowmik, Angshu; Maughn, Sue; Springett, Kate

2018-05-27

Diagnostic capacity and time to diagnosis are frequently identified as a barrier to improving cancer patient outcomes. Maximising the contribution of the medical imaging workforce, including reporting radiographers, is one way to improve service delivery. An efficient and effective centralised model of workplace training support was designed for a cohort of trainee chest X-ray (CXR) reporting radiographers. A comprehensive schedule of tutorials was planned and aligned with the curriculum of a post-graduate certificate in CXR reporting. Trainees were supported via a hub and spoke model (centralised training model), with the majority of education provided by a core group of experienced CXR reporting radiographers. Trainee and departmental feedback on the model was obtained using an online survey. Fourteen trainees were recruited from eight National Health Service Trusts across London. Significant efficiencies of scale were possible with centralised support (48 h) compared to traditional workplace support (348 h). Trainee and manager feedback overall was positive. Trainees and managers both reported good trainee support, translation of learning to practice and increased confidence. Logistics, including trainee travel and release, were identified as areas for improvement. Centralised workplace training support is an effective and efficient method to create sustainable diagnostic capacity and support improvements in the lung cancer pathway. © 2018 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.

[Comparison of integration processing technology of origin and traditional cutting processing technology of Moslae Herba for lung-Yang deficiency rats].

PubMed

Sun, Dong-Yue; Wang, Xin-Ya; Wang, Xiao-Ting; Yan, Li; Liu, Xiao-Feng; Pang, Bo; Gao, Hui

2018-06-01

To compare the effect of integration processing technology of origin (IPTO) and traditional cutting processing technology (TCPT) of Moslae Herba for lung-Yang deficiency rats caused by complex factors, analyze the mechanism, and provide the modern pharmacology basis for the implementation of IPTO of Moslae Herba. The rat models of lung-Yang deficiency were established by smoking + swimming in ice water + drinking ice water. The model rats were randomly divided into different groups, and were treated with intragastric administration for 30 d. Then the general signs, anal temperature and autonomic activity of the rats were observed. The pathological morphology of lung tissues was observed, and the positive expression of tumor necrosis factor (TNF-α) was observed by immunohistochemical method, and the hematological indexes were determined. Enzyme linked immunosorbent assay (ELISA) method was used to detect serum nitric oxide (NO), immunoglobulin G (IGG), malondialdehyde (MDA), thromboxane B2 (TXB2) and interleukin-8 (IL-8) level, and the organ coefficients of heart, liver, spleen, lung, kidney and other organs were calculated. According to the results, Moslae Herba volatile oil and decoction could improve the general signs and autonomic activities of lung-Yang deficiency rats, improve the body weight, rectal temperature, and the content of IGG in serum of lung-Yang deficiency rats, reduce organ coefficients of heart, liver, spleen, lung and kidney, serum NO, MDA, TXB2, IL-8 contents, white blood cell and TNF-α mean optical density in the lung tissues of rats. witg statistically significant difference ( P <0.01 or P <0.05). The effects of IPTO volatile oil and water decoction were slightly higher. Therefore, Moslae Herba has therapeutic effect on lung-Yang deficiency rats, and ICPT has better effect, whose mechanism may be related to the intervention of TNF-α expression, improving the level of IGG, and inhibiting NO, MDA, IL-8, and TXB2 levels. Copyright© by the Chinese Pharmaceutical Association.

Airway Basal Cells. The “Smoking Gun” of Chronic Obstructive Pulmonary Disease

PubMed Central

2014-01-01

The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and ’omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the “smoking gun” of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders). PMID:25354273

Low-Flow Extracorporeal Carbon Dioxide Removal Using the Hemolung Respiratory Dialysis System® to Facilitate Lung-Protective Mechanical Ventilation in Acute Respiratory Distress Syndrome.

PubMed

Akkanti, Bindu; Rajagopal, Keshava; Patel, Kirti P; Aravind, Sangeeta; Nunez-Centanu, Emmanuel; Hussain, Rahat; Shabari, Farshad Raissi; Hofstetter, Wayne L; Vaporciyan, Ara A; Banjac, Igor S; Kar, Biswajit; Gregoric, Igor D; Loyalka, Pranav

2017-06-01

Extracorporeal carbon dioxide removal (ECCO 2 R) permits reductions in alveolar ventilation requirements that the lungs would otherwise have to provide. This concept was applied to a case of hypercapnia refractory to high-level invasive mechanical ventilator support. We present a case of an 18-year-old man who developed post-pneumonectomy acute respiratory distress syndrome (ARDS) after resection of a mediastinal germ cell tumor involving the left lung hilum. Hypercapnia and hypoxemia persisted despite ventilator support even at traumatic levels. ECCO 2 R using a miniaturized system was instituted and provided effective carbon dioxide elimination. This facilitated establishment of lung-protective ventilator settings and lung function recovery. Extracorporeal lung support increasingly is being applied to treat ARDS. However, conventional extracorporeal membrane oxygenation (ECMO) generally involves using large cannulae capable of carrying high flow rates. A subset of patients with ARDS has mixed hypercapnia and hypoxemia despite high-level ventilator support. In the absence of profound hypoxemia, ECCO 2 R may be used to reduce ventilator support requirements to lung-protective levels, while avoiding risks associated with conventional ECMO.

Lung cancer, caring for the caregivers. A qualitative study of providing pro-active social support targeted to the carers of patients with lung cancer.

PubMed

Ryan, P J; Howell, V; Jones, J; Hardy, E J

2008-04-01

Carers of patients with lung cancer often have a short time to access the support they require. The Macmillan Carers Project (MCP) was set up to provide non-clinical social support targeted in the community to the carers of patients with lung cancer and this study describes its evaluation. Prospective case study using interviews with the carers, project workers and health and social care professionals to obtain qualitative data for thematic analysis. 81 patients' carers received support from the MCP; 20 carers, 2 MCP workers and their manager and 10 other professionals (chest consultant physician, lung cancer clinical nurse specialist, GP, four Macmillan nurses, hospice social worker and two community social workers) were interviewed. Patients were predominantly male (62%), mean age 71 years and carers were predominantly female (70%) mean age 63 years. Carers identified the MCP as providing emotional support, more time, practical help, financial advice, information and back-up for a myriad of problems. Although there was some overlap with other services, the MCP was valued by carers and professionals as filling a gap in social care. The unique aspect of this study was support targeted to the carers of a single cancer site (lung) rather than generic cancer support. As lung cancer may progress rapidly, patients and their carers have a short time to gather new information, access services and adjust to their new circumstances and roles. By focusing on the needs of carers from the time of lung cancer diagnosis, we have shown that the MCP was a valued additional service, well received by carers, patients and professionals.

Quantitative proteomics analysis using 2D-PAGE to investigate the effects of cigarette smoke and aerosol of a prototypic modified risk tobacco product on the lung proteome in C57BL/6 mice.

PubMed

Elamin, Ashraf; Titz, Bjoern; Dijon, Sophie; Merg, Celine; Geertz, Marcel; Schneider, Thomas; Martin, Florian; Schlage, Walter K; Frentzel, Stefan; Talamo, Fabio; Phillips, Blaine; Veljkovic, Emilija; Ivanov, Nikolai V; Vanscheeuwijck, Patrick; Peitsch, Manuel C; Hoeng, Julia

2016-08-11

Smoking is associated with several serious diseases, such as lung cancer and chronic obstructive pulmonary disease (COPD). Within our systems toxicology framework, we are assessing whether potential modified risk tobacco products (MRTP) can reduce smoking-related health risks compared to conventional cigarettes. In this article, we evaluated to what extent 2D-PAGE/MALDI MS/MS (2D-PAGE) can complement the iTRAQ LC-MS/MS results from a previously reported mouse inhalation study, in which we assessed a prototypic MRTP (pMRTP). Selected differentially expressed proteins identified by both LC-MS/MS and 2D-PAGE approaches were further verified using reverse-phase protein microarrays. LC-MS/MS captured the effects of cigarette smoke (CS) on the lung proteome more comprehensively than 2D-PAGE. However, an integrated analysis of both proteomics data sets showed that 2D-PAGE data complement the LC-MS/MS results by supporting the overall trend of lower effects of pMRTP aerosol than CS on the lung proteome. Biological effects of CS exposure supported by both methods included increases in immune-related, surfactant metabolism, proteasome, and actin cytoskeleton protein clusters. Overall, while 2D-PAGE has its value, especially as a complementary method for the analysis of effects on intact proteins, LC-MS/MS approaches will likely be the method of choice for proteome analysis in systems toxicology investigations. Quantitative proteomics is anticipated to play a growing role within systems toxicology assessment frameworks in the future. To further understand how different proteomics technologies can contribute to toxicity assessment, we conducted a quantitative proteomics analysis using 2D-PAGE and isobaric tag-based LC-MS/MS approaches and compared the results produced from the 2 approaches. Using a prototypic modified risk tobacco product (pMRTP) as our test item, we show compared with cigarette smoke, how 2D-PAGE results can complement and support LC-MS/MS data, demonstrating the much lower effects of pMRTP aerosol than cigarette smoke on the mouse lung proteome. The combined analysis of 2D-PAGE and LC-MS/MS data identified an effect of cigarette smoke on the proteasome and actin cytoskeleton in the lung. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Discovery – Lung Cancer Screening Saves Lives: The NLST

Cancer.gov

NCI funded the National Lung Screening Trial, an eight-year study that used new technology to detect small, aggressive tumors early enough to surgically remove them. This approach reduced lung cancer deaths among participants by 20 percent.

Evidence supporting contemporary post-operative radiation therapy (PORT) using linear accelerators in N2 lung cancer.

PubMed

Patel, Suchit H; Ma, Yan; Wernicke, A Gabriella; Nori, Dattatreyudu; Chao, K S C; Parashar, Bhupesh

2014-05-01

Post-operative radiotherapy (PORT) treatment for lung cancer declined since a meta-analysis failed to show benefit in patients with N2 disease. Because several included studies employed outmoded radiation planning and delivery techniques, we sought to determine whether PORT with modern technology benefits patients with N2 disease. We conducted searches of the published literature. For inclusion, studies must have included patients with stage III-N2 lung cancer treated with PORT using only linear accelerators, used a control group that did not receive PORT, and reported outcome data for overall survival (OS). Prospective and retrospective analyses were included. Exclusion criteria were the use of cobalt devices or orthovoltage radiation. Data were evaluated with random-effects models. Three prospective and eight retrospective studies were included. The PORT and no-PORT groups included 1368 and 1360 patients, respectively. The PORT group had significantly improved OS over the no-PORT group (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.62-0.96, P = 0.020). Locoregional recurrence-free survival (LRFS) in 10 studies for which data was available was also improved in the PORT group (HR = 0.51, CI 0.41-0.65, P < 0.001). PORT was associated with significantly lower risk of death and locoregional recurrence in patients with N2 lung cancer. Our study was limited by lack of access to individual patient data, which would have enabled more detailed analyses. Regardless, data thus far suggest PORT may be associated with a survival benefit. Given a lack of large-scale prospective data, clinical trials evaluating PORT with modern technology are warranted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Proceedings of the Workshop on Acute Lung Injury and Pulmonary Edema Held in Aberdeen Proving Ground, Maryland on 4-5 May 1989

DTIC Science & Technology

1989-11-01

support of weapons development. Our mission is the development of medical countermeasures, pretreat-I ments, antidotes, and casualty treatment strategies...USAMRIID). The mission of USAMRICD can be broken down into three primary goals. The first is to maintain a technology base which comprises capabilities that...chemical agents themselves and for the proposed treatments and therapeutic agents. Another mission of our division is the management of a task area, the

A historical perspective on ventilator management.

PubMed

Shapiro, B A

1994-02-01

Paralysis via neuromuscular blockade in ICU patients requires mechanical ventilation. This review historically addresses the technological advances and scientific information upon which ventilatory management concepts are based, with special emphasis on the influence such concepts have had on the use of neuromuscular blocking agents. Specific reference is made to the scientific information and technological advances leading to the newer concepts of ventilatory management. Information from > 100 major studies in the peer-reviewed medical literature, along with the author's 25 yrs of clinical experience and academic involvement in acute respiratory care is presented. Nomenclature related to ventilatory management is specifically defined and consistently utilized to present and interpret the data. Pre-1970 ventilatory management is traced from the clinically unacceptable pressure-limited devices to the reliable performance of volume-limited ventilators. The scientific data and rationale that led to the concept of relatively large tidal volume delivery are reviewed in the light of today's concerns regarding alveolar overdistention, control-mode dyssynchrony, and auto-positive end-expiratory pressure. Also presented are the post-1970 scientific rationales for continuous positive airway pressure/positive end-expiratory pressure therapy, avoidance of alveolar hyperxia, and partial ventilatory support techniques (intermittent mandatory ventilation/synchronized intermittent mandatory ventilation). The development of pressure-support devices is discussed and the capability of pressure-control techniques is presented. The rationale for more recent concepts of total ventilatory support to avoid ventilator-induced lung injury is presented. The traditional techniques utilizing volume-preset ventilators with relatively large tidal volumes remain valid and desirable for the vast majority of patients requiring mechanical ventilation. Neuromuscular blockade is best avoided in these patients. However, adequate analgesia, amnesia, and sedation are required. For patients with severe lung disease, alveolar overdistention and hyperoxia should be avoided and may be best accomplished by total ventilatory support techniques, such as pressure control. Total ventilatory support requires neuromuscular blockade and may not provide eucapnic ventilation.

Technology for enhancing chest auscultation in clinical simulation.

PubMed

Ward, Jeffrey J; Wattier, Bryan A

2011-06-01

The ability to use an acoustic stethoscope to detect lung and/or heart sounds, and then to then communicate one's interpretation of those sounds is an essential skill for many medical professionals. Interpretation of lung and heart sounds, in the context of history and other examination findings, often aids the differential diagnosis. Bedside assessment of changing auscultation findings may also guide treatment. Learning lung and heart auscultation skills typically involves listening to pre-recorded normal and adventitious sounds, often followed by laboratory instruction to guide stethoscope placement, and finally correlating the sounds with the associated pathophysiology and pathology. Recently, medical simulation has become an important tool for teaching prior to clinical practice, and for evaluating bedside auscultation skills. When simulating cardiovascular or pulmonary problems, high-quality lung and heart sounds should be able to accurately corroborate other findings such as vital signs, arterial blood gas values, or imaging. Digital audio technology, the Internet, and high-fidelity simulators have increased opportunities for educators and learners. We review the application of these technologies and describe options for reproducing lung and heart sounds, as well as their advantages and potential limitations.

Interest in internet lung cancer support among rural cardiothoracic patients.

PubMed

Quin, Jacquelyn; Stams, Victor; Phelps, Beth; Boley, Theresa; Hazelrigg, Stephen

2010-05-01

The Internet may provide an alternative option for rural lung cancer patients who lack access to on-site cancer support; however, Internet access and use among rural patients is unknown. An anonymous waiting-room survey was administered to all outpatient cardiothoracic surgery patients over 3 mo. Survey questions included age, gender, and diagnosis, possession of a home computer and Internet service, estimated Internet use, and use of the Internet for health information. Patients with known or suspected lung cancer were asked to indicate their interest in on-site and Internet cancer support. There were 597 returned surveys (response rate 96%). The mean age was 64.6 y (SE 0.55), and 58% were men. Diagnoses included known or possible lung cancer (15.4%), lung disease (9.5%), heart disease (30.4%), other diagnoses (13.9%), and undetermined (30.6%). There were 343 patients (57.4%) with a home computer and 299 (50.1%) with home Internet service. Average Internet use was 8.5 h per wk (n = 298), and 225 patients used the Internet for health information. Of the 92 patients with lung cancer, 10 indicated interest in on-site support services while 37 expressed interest in Internet-based support. Based on survey results, a slight majority of rural patients have a home computer and Internet access. Internet use for health information appears relatively common. Overall interest for support services among lung cancer patients appears modest with a greater interest in Internet-based services compared with on-site support. Copyright 2010 Elsevier Inc. All rights reserved.

Relationship between resilience, social support as well as anxiety/depression of lung cancer patients: A cross-sectional observation study.

PubMed

Hu, Tingjie; Xiao, Jian; Peng, Juan; Kuang, Xiao; He, Bixiu

2018-01-01

The mood of patients with lung carcinoma would be greatly influenced by the diagnosing and treating processes. This study was aimed to explore the effects of resilience between social assistance and anxiety/depression of patients with lung cancer, which may assist in clinical intervention. A cross-sectional pilot study was conducted on lung cancer patients at Xiangya Hospital of Central South University, China. A total of 289 patients aged 25-81 years were included in this study. Correlational analyses revealed that anxiety/depression was negatively associated with psychological resilience and each dimension of social assistance, including subjective support, objective support along with the supports utilization (P < 0.01). Furthermore, psychological resilience was positively related to subjective support (P < 0.01), support utilization (P < 0.01) along with objective support (P < 0.05). Mediational analyses showed that, on the one hand, resilience could partially mediate the relation between anxiety and subjective support and totally mediate the relationship between support utilization and anxiety. On the other hand, resilience could totally mediate the relation between depression and subjective support and partially mediate the relation between support utilization and depression. However, resilience did not play an intermediary role between anxiety/depression and objective support. Lower psychological anxiety and depression would be experienced by lung cancer patients with higher resilience and social support. The level of anxiety and depression would be indirectly affected by social support through the mediation of resilience.

Trauma of lung due to impact load.

PubMed

Yen, R T; Fung, Y C; Liu, S Q

1988-01-01

A quantitative evaluation of lung injury due to impact loading is of general interest. Hemorrhage and edema are the usual sequelae to traumatic pulmonary impact. To gain some quantitative understanding of the phenomena, we perfused excised rabbit lung with Macrodex at isogravimetric condition and monitored lung weight continuously after impact. It is shown that a factor of importance is the rigidity of the surface on which the lung rests. The rate of lung weight increase is smaller if the lung was 'freely' supported on a soft cloth, more if it was supported on a rigid plate. This suggests the influence of stress wave reflection. The critical condition correlates with the initial velocity of impact at the surface of the lung, or with the maximum deflection. For a freely supported lung, the rate of lung weight increase was 22% of the initial total lung weight per h after impact when the impact velocity was 11.5 ms-1, 30% when the velocity was 13.2 ms-1, several 100% at 13.5 ms-1, signaling massive lung injury. Since the velocity of sound in rabbit lung is 33.3 ms-1 when the inflation (transpulmonary) pressure is 10 cm H2O, the critical velocity of 13.5 ms-1 corresponds to a Mach number of 0.4. The maximum surface displacement of the lung is almost linearly proportional to the initial velocity of impact. The exact cause of edema and hemorrhage is unknown; we hypothesize that it is due to tensile stress in the alveolar wall caused by the impact.

Aerosol delivery with two ventilation modes during mechanical ventilation: a randomized study.

PubMed

Dugernier, Jonathan; Reychler, Gregory; Wittebole, Xavier; Roeseler, Jean; Depoortere, Virginie; Sottiaux, Thierry; Michotte, Jean-Bernard; Vanbever, Rita; Dugernier, Thierry; Goffette, Pierre; Docquier, Marie-Agnes; Raftopoulos, Christian; Hantson, Philippe; Jamar, François; Laterre, Pierre-François

2016-12-01

Volume-controlled ventilation has been suggested to optimize lung deposition during nebulization although promoting spontaneous ventilation is targeted to avoid ventilator-induced diaphragmatic dysfunction. Comparing topographic aerosol lung deposition during volume-controlled ventilation and spontaneous ventilation in pressure support has never been performed. The aim of this study was to compare lung deposition of a radiolabeled aerosol generated with a vibrating-mesh nebulizer during invasive mechanical ventilation, with two modes: pressure support ventilation and volume-controlled ventilation. Seventeen postoperative neurosurgery patients without pulmonary disease were randomly ventilated in pressure support or volume-controlled ventilation. Diethylenetriaminepentaacetic acid labeled with technetium-99m (2 mCi/3 mL) was administrated using a vibrating-mesh nebulizer (Aerogen Solo(®), provided by Aerogen Ltd, Galway, Ireland) connected to the endotracheal tube. Pulmonary and extrapulmonary particles deposition was analyzed using planar scintigraphy. Lung deposition was 10.5 ± 3.0 and 15.1 ± 5.0 % of the nominal dose during pressure support and volume-controlled ventilation, respectively (p < 0.05). Higher endotracheal tube and tracheal deposition was observed during pressure support ventilation (27.4 ± 6.6 vs. 20.7 ± 6.0 %, p < 0.05). A similar penetration index was observed for the right (p = 0.210) and the left lung (p = 0.211) with both ventilation modes. A high intersubject variability of lung deposition was observed with both modes regarding lung doses, aerosol penetration and distribution between the right and the left lung. In the specific conditions of the study, volume-controlled ventilation was associated with higher lung deposition of nebulized particles as compared to pressure support ventilation. The clinical benefit of this effect warrants further studies. Clinical trial registration NCT01879488.

State-of-the-art MS technology applications in lung disease.

PubMed

Végvári, Ákos; Döme, Balázs

2011-12-01

Two frontline MS technologies, which have recently gained much attention, are discussed within the scope of this review. Besides a brief summary on the contemporary state of lung cancer and chronic obstructive pulmonary disease, the principles of multiple reaction monitoring and matrix assisted laser desorption ionization (MALDI) MS imaging are presented. A comprehensive overview of quantitative mass spectrometry applications is provided, covering multiple reaction monitoring assay developments for analysis of proteins (biomarkers) and low-molecular-weight compounds (drugs) with a special focus on the disease areas of lung cancer and chronic obstructive pulmonary disease. The MALDI-MS imaging applications are discussed similarly, providing references to studies conducted on lung tissues in order to localize drug compounds and protein biomarkers.

Stereotactic body radiotherapy for lung cancer: how much does it really cost?

PubMed

Lievens, Yolande; Obyn, Caroline; Mertens, Anne-Sophie; Van Halewyck, Dries; Hulstaert, Frank

2015-03-01

Despite the lack of randomized evidence, stereotactic body radiotherapy (SBRT) is being accepted as superior to conventional radiotherapy for patients with T1-2N0 non-small-cell lung cancer in the periphery of the lung and unfit or unwilling to undergo surgery. To introduce SBRT in a system of coverage with evidence development, a correct financing had to be determined. A time-driven activity-based costing model for radiotherapy was developed. Resource cost calculation of all radiotherapy treatments, standard and innovative, was conducted in 10 Belgian radiotherapy centers in the second half of 2012. The average cost of lung SBRT across the 10 centers (6221&OV0556;) is in the range of the average costs of standard fractionated 3D-conformal radiotherapy (5919&OV0556;) and intensity-modulated radiotherapy (7379&OV0556;) for lung cancer. Hypofractionated 3D-conformal radiotherapy and intensity-modulated radiotherapy schemes are less costly (3993&OV0556; respectively 4730&OV0556;). The SBRT cost increases with the number of fractions and is highly dependent of personnel and equipment use. SBRT cost varies more by centre than conventional radiotherapy cost, reflecting different technologies, stages in the learning curve and a lack of clear guidance in this field. Time-driven activity-based costing of radiotherapy is feasible in a multicentre setup, resulting in real-life resource costs that can form the basis for correct reimbursement schemes, supporting an early yet controlled introduction of innovative radiotherapy techniques in clinical practice.

Indoor Air Quality

MedlinePlus

... policy . Skip to main content ABOUT US OUR INITIATIVES LUNG HEALTH & DISEASES SUPPORT & COMMUNITY STOP SMOKING GET ... Supporters Careers Contact Us Corporate Ethics Reporting OUR INITIATIVES LUNG FORCE Saved By The Scan Research Healthy ...

Use of Electromagnetic Navigational Transthoracic Needle Aspiration (E-TTNA) for Sampling of Lung Nodules.

PubMed

Arias, Sixto; Lee, Hans; Semaan, Roy; Frimpong, Bernice; Ortiz, Ricardo; Feller-Kopman, David; Oakjones-Burgess, Karen; Yarmus, Lonny

2015-05-23

Lung nodule evaluation represents a clinical challenge especially in patients with intermediate risk for malignancy. Multiple technologies are presently available to sample nodules for pathological diagnosis. Those technologies can be divided into bronchoscopic and non-bronchoscopic interventions. Electromagnetic navigational bronchoscopy is being extensively used for the endobronchial approach to peripheral lung nodules but has been hindered by anatomic challenges resulting in a 70% diagnostic yield. Electromagnetic navigational guided transthoracic needle lung biopsy is novel non-bronchoscopic method that uses a percutaneous electromagnetic tip tracked needle to obtain core biopsy specimens. Electromagnetic navigational transthoracic needle aspiration complements bronchoscopic techniques potentially allowing the provider to maximize the diagnostic yield during one single procedure. This article describes a novel integrated diagnostic approach to pulmonary lung nodules. We propose the use of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging; radial EBUS, navigational bronchoscopy and E-TTNA during one single procedure to maximize diagnostic yield and minimize the number of invasive procedures needed to obtain a diagnosis. This manuscript describes in detail how the navigation transthoracic procedure is performed. Additional clinical studies are needed to determine the clinical utility of this novel technology.

Development of lung cancer CT screening operating support system

NASA Astrophysics Data System (ADS)

Ishigaki, Rikuta; Hanai, Kozou; Suzuki, Masahiro; Kawata, Yoshiki; Niki, Noboru; Eguchi, Kenji; Kakinuma, Ryutaro; Moriyama, Noriyuki

2009-02-01

In Japan, lung cancer death ranks first among men and third among women. Lung cancer death is increasing yearly, thus early detection and treatment are needed. For this reason, CT screening for lung cancer has been introduced. The CT screening services are roughly divided into three sections: office, radiology and diagnosis sections. These operations have been performed through paper-based or a combination of paper-based and an existing electronic health recording system. This paper describes an operating support system for lung cancer CT screening in order to make the screening services efficient. This operating support system is developed on the basis of 1) analysis of operating processes, 2) digitalization of operating information, and 3) visualization of operating information. The utilization of the system is evaluated through an actual application and users' survey questionnaire obtained from CT screening centers.

Comparison of the gas-liquid dual support fixation and Heitzman fixation techniques for preparing lung specimens

PubMed Central

Yu, Dongsheng; Qu, Weili; Xia, Haipeng; Li, Xiaofeng; Luan, Zhenfeng; Yan, Renjie; Lu, Xiaodong; Zhao, Peng

2017-01-01

The aim of the present study was to compare the gas-liquid dual support fixation and Heitzman fixation techniques for the preparation of lung specimens. A total of 40 fresh lung samples were surgically collected from 40 male patients with lung cancer by biopsy. Patients were recruited from the Affiliated Hospital of Qingdao University Medical College (Qingdao, China) between July 2007 and June 2014. Samples were prepared using either the gas-liquid dual support fixation method (group A; n=26) or the Heitzman fixation method (group B; n=14). High-resolution computed tomography (HRCT) scanning was performed prior to surgery and corresponding postoperative HRCT scanning was conducted for the lung specimens; the gross transverse specimen section, cord photography images and histological sections were evaluated. Morphological observations of lung specimens indicated that there were 22 cases in group A with grade I (84.6%) and 4 cases with grade II (15.4%), whereas, in group B, there were 5 cases with grade II (35.7%) and 9 cases with grade III (64.3%). Statistical analysis demonstrated that the grades of specimens between the two groups were significantly different (P<0.01). Results from imaging and histological studies found that the quality of lung specimens was superior in group A, compared with group B. In conclusion, the present study demonstrated that, compared with the Heitzman fixation method, gas-liquid dual support fixation may be a superior technique for the preparation of lung specimens. This finding may facilitate the improvement of lung HRCT and pathological studies. PMID:28673006

Comparison of the gas-liquid dual support fixation and Heitzman fixation techniques for preparing lung specimens.

PubMed

Yu, Dongsheng; Qu, Weili; Xia, Haipeng; Li, Xiaofeng; Luan, Zhenfeng; Yan, Renjie; Lu, Xiaodong; Zhao, Peng

2017-07-01

The aim of the present study was to compare the gas-liquid dual support fixation and Heitzman fixation techniques for the preparation of lung specimens. A total of 40 fresh lung samples were surgically collected from 40 male patients with lung cancer by biopsy. Patients were recruited from the Affiliated Hospital of Qingdao University Medical College (Qingdao, China) between July 2007 and June 2014. Samples were prepared using either the gas-liquid dual support fixation method (group A; n=26) or the Heitzman fixation method (group B; n=14). High-resolution computed tomography (HRCT) scanning was performed prior to surgery and corresponding postoperative HRCT scanning was conducted for the lung specimens; the gross transverse specimen section, cord photography images and histological sections were evaluated. Morphological observations of lung specimens indicated that there were 22 cases in group A with grade I (84.6%) and 4 cases with grade II (15.4%), whereas, in group B, there were 5 cases with grade II (35.7%) and 9 cases with grade III (64.3%). Statistical analysis demonstrated that the grades of specimens between the two groups were significantly different (P<0.01). Results from imaging and histological studies found that the quality of lung specimens was superior in group A, compared with group B. In conclusion, the present study demonstrated that, compared with the Heitzman fixation method, gas-liquid dual support fixation may be a superior technique for the preparation of lung specimens. This finding may facilitate the improvement of lung HRCT and pathological studies.

Computer aided detection system for Osteoporosis using low dose thoracic 3D CT images

NASA Astrophysics Data System (ADS)

Tsuji, Daisuke; Matsuhiro, Mikio; Suzuki, Hidenobu; Kawata, Yoshiki; Niki, Noboru; Nakano, Yasutaka; Harada, Masafumi; Kusumoto, Masahiko; Tsuchida, Takaaki; Eguchi, Kenji; Kaneko, Masahiro

2018-02-01

The patient of osteoporosis is about 13 million people in Japan and it is one of healthy life problems in the aging society. It is necessary to do early stage detection and treatment in order to prevent the osteoporosis. Multi-slice CT technology has been improving the three dimensional (3D) image analysis with higher resolution and shorter scan time. The 3D image analysis of thoracic vertebra can be used for supporting to diagnosis of osteoporosis. This analysis can be used for lung cancer detection at the same time. We develop method of shape analysis and CT values of spongy bone for the detection osteoporosis. Osteoporosis and lung cancer screening show high extraction rate by the thoracic vertebral evaluation CT images. In addition, we created standard pattern of CT value per thoracic vertebra for male age group using 298 low dose data.

Co-creation of an ICT-supported cancer rehabilitation application for resected lung cancer survivors: design and evaluation.

PubMed

Timmerman, Josien G; Tönis, Thijs M; Dekker-van Weering, Marit G H; Stuiver, Martijn M; Wouters, Michel W J M; van Harten, Wim H; Hermens, Hermie J; Vollenbroek-Hutten, Miriam M R

2016-04-27

Lung cancer (LC) patients experience high symptom burden and significant decline of physical fitness and quality of life following lung resection. Good quality of survivorship care post-surgery is essential to optimize recovery and prevent unscheduled healthcare use. The use of Information and Communication Technology (ICT) can improve post-surgery care, as it enables frequent monitoring of health status in daily life, provides timely and personalized feedback to patients and professionals, and improves accessibility to rehabilitation programs. Despite its promises, implementation of telehealthcare applications is challenging, often hampered by non-acceptance of the developed service by its end-users. A promising approach is to involve the end-users early and continuously during the developmental process through a so-called user-centred design approach. The aim of this article is to report on this process of co-creation and evaluation of a multimodal ICT-supported cancer rehabilitation program with and for lung cancer patients treated with lung resection and their healthcare professionals (HCPs). A user-centered design approach was used. Through semi-structured interviews (n = 10 LC patients and 6 HCPs), focus groups (n = 5 HCPs), and scenarios (n = 5 HCPs), user needs and requirements were elicited. Semi-structured interviews and the System Usability Scale (SUS) were used to evaluate usability of the telehealthcare application with 7 LC patients and 10 HCPs. The developed application consists of: 1) self-monitoring of symptoms and physical activity using on-body sensors and a smartphone, and 2) a web based physical exercise program. 71 % of LC patients and 78 % of HCPs were willing to use the application as part of lung cancer treatment. Accessibility of data via electronic patient records was essential for HCPs. LC patients regarded a positive attitude of the HCP towards the application essential. Overall, the usability (SUS median score = 70, range 35-95) was rated acceptable. A telehealthcare application that facilitates symptom monitoring and physical fitness training is considered a useful tool to further improve recovery following surgery of resected lung cancer (LC) patients. Involvement of end users in the design process appears to be necessary to optimize chances of adoption, compliance and implementation of telemedicine.

The iron lung: halfway technology or necessary step?

PubMed

Maxwell, J H

1986-01-01

The iron lung is often used to epitomize the costly halfway technologies of modern-day medicine that fail to cure and only prolong a seriously compromised existence. Historical evidence indicates that the iron lung was not a costly instrument of last resort; instead, it was a lifesaving device that played a critical role in the evolution of modern respirators and respiratory care. Contrary to the prevailing views of the biomedical research community, the creation of new devices and instruments is often as important a source of technical change in medicine as are advances in the biological sciences.

Health Effects of Ozone and Particle Pollution

MedlinePlus

... policy . Skip to main content ABOUT US OUR INITIATIVES LUNG HEALTH & DISEASES SUPPORT & COMMUNITY STOP SMOKING GET ... Supporters Careers Contact Us Corporate Ethics Reporting OUR INITIATIVES LUNG FORCE Saved By The Scan Research Healthy ...

Noninvasive detection of lung cancer using exhaled breath

PubMed Central

Fu, Xiao-An; Li, Mingxiao; Knipp, Ralph J; Nantz, Michael H; Bousamra, Michael

2014-01-01

Early detection of lung cancer is a key factor for increasing the survival rates of lung cancer patients. The analysis of exhaled breath is promising as a noninvasive diagnostic tool for diagnosis of lung cancer. We demonstrate the quantitative analysis of carbonyl volatile organic compounds (VOCs) and identification of lung cancer VOC markers in exhaled breath using unique silicon microreactor technology. The microreactor consists of thousands of micropillars coated with an ammonium aminooxy salt for capture of carbonyl VOCs in exhaled breath by means of oximation reactions. Captured aminooxy-VOC adducts are analyzed by nanoelectrospray Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometry (MS). The concentrations of 2-butanone, 2-hydroxyacetaldehyde, 3-hydroxy-2-butanone, and 4-hydroxyhexenal (4-HHE) in the exhaled breath of lung cancer patients (n = 97) were significantly higher than in the exhaled breath of healthy smoker and nonsmoker controls (n = 88) and patients with benign pulmonary nodules (n = 32). The concentration of 2-butanone in exhaled breath of patients (n = 51) with stages II though IV non–small cell lung cancer (NSCLC) was significantly higher than in exhaled breath of patients with stage I (n = 34). The carbonyl VOC profile in exhaled breath determined using this new silicon microreactor technology provides for the noninvasive detection of lung cancer. PMID:24402867

Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon.

PubMed

Ehmann, R; Boedeker, E; Friedrich, U; Sagert, J; Dippon, J; Friedel, G; Walles, T

2012-03-01

Patient prognosis in lung cancer largely depends on early diagnosis. The exhaled breath of patients may represent the ideal specimen for future lung cancer screening. However, the clinical applicability of current diagnostic sensor technologies based on signal pattern analysis remains incalculable due to their inability to identify a clear target. To test the robustness of the presence of a so far unknown volatile organic compound in the breath of patients with lung cancer, sniffer dogs were applied. Exhalation samples of 220 volunteers (healthy individuals, confirmed lung cancer or chronic obstructive pulmonary disease (COPD)) were presented to sniffer dogs following a rigid scientific protocol. Patient history, drug administration and clinicopathological data were analysed to identify potential bias or confounders. Lung cancer was identified with an overall sensitivity of 71% and a specificity of 93%. Lung cancer detection was independent from COPD and the presence of tobacco smoke and food odours. Logistic regression identified two drugs as potential confounders. It must be assumed that a robust and specific volatile organic compound (or pattern) is present in the breath of patients with lung cancer. Additional research efforts are required to overcome the current technical limitations of electronic sensor technologies to engineer a clinically applicable screening tool.

Prevention and management of lung cancer in China.

PubMed

Hong, Qun-Ying; Wu, Guo-Ming; Qian, Gui-Sheng; Hu, Cheng-Ping; Zhou, Jian-Ying; Chen, Liang-An; Li, Wei-Min; Li, Shi-Yue; Wang, Kai; Wang, Qi; Zhang, Xiao-Ju; Li, Jing; Gong, Xin; Bai, Chun-Xue

2015-09-01

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer. © 2015 American Cancer Society.

Taking Her Breath Away: The Rise of COPD in Women

MedlinePlus

... policy . Skip to main content ABOUT US OUR INITIATIVES LUNG HEALTH & DISEASES SUPPORT & COMMUNITY STOP SMOKING GET ... Supporters Careers Contact Us Corporate Ethics Reporting OUR INITIATIVES LUNG FORCE Saved By The Scan Research Healthy ...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

28 CFR 79.64 - Proof of primary lung cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.64... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... claimant. A conclusion that a claimant developed primary lung cancer must be supported by medical...

[Construction of 2-dimensional tumor microvascular architecture phenotype in non-small cell lung cancer].

PubMed

Liu, Jin-kang; Wang, Xiao-yi; Xiong, Zeng; Zhou, Hui; Zhou, Jian-hua; Fu, Chun-yan; Li, Bo

2008-08-01

To construct a technological platform of 2-dimensional tumor microvascular architecture phenotype (2D-TAMP) expression. Thirty samples of non-small cell lung cancer (NSCLC) were collected after surgery. The corresponding sections of tumor tissue specimens to the slice of CT perfusion imaging were selected. Immunohistochemical staining,Gomori methenamine silver stain, and electron microscope observation were performed to build a technological platform of 2D-TMAP expression by detecting the morphology and the integrity of basement membrane of microvasculature, microvascular density, various microvascular subtype, the degree of the maturity and lumenization of microvasculature, and the characteristics of immunogenetics of microvasculature. The technological platform of 2D-TMAP expression was constructed successfully. There was heterogeneity in 2D-TMAP expression of non-small cell lung cancer. The microvascular of NSCLC had certain characteristics. 2D-TMAP is a key technology that can be used to observe the overall state of micro-environment in tumor growth.

Gas Transfer in Cellularized Collagen-Membrane Gas Exchange Devices.

PubMed

Lo, Justin H; Bassett, Erik K; Penson, Elliot J N; Hoganson, David M; Vacanti, Joseph P

2015-08-01

Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m(2) of oxygen and ∼685 mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.

Help-seeking behaviour in newly diagnosed lung cancer patients: assessing the role of perceived stigma.

PubMed

Rose, Shiho; Boyes, Allison; Kelly, Brian; Cox, Martine; Palazzi, Kerrin; Paul, Christine

2018-05-26

This study explored help-seeking behaviours, group identification and perceived legitimacy of discrimination, and its potential relationship with perceived lung cancer stigma. Consecutive consenting adults (n=274) with a primary diagnosis of lung cancer within the previous four months were recruited at 31 outpatient clinics in Australia. A self-report survey assessed help-seeking, group identification, perceived legitimacy of discrimination and perceived lung cancer stigma. Services providing assistance from health professionals (69.5%) and informational support (68.5%) was more frequently used than emotional-based support. Only a small proportion (2.6%) of participants were unlikely to seek help from anyone, with the most popular sources of help being the general practitioner (91.0%), and oncologist/treating clinician (81.3%). One-fifth (21.1%) indicated they identified with being a lung cancer patient, and most did not perceive discrimination against lung cancer patients. Higher perceived lung cancer stigma was significantly associated with greater perceived legitimacy of discrimination (p<0.001), but not help-seeking behaviours or group identification. The relationship between lung cancer stigma and perceived legitimacy of discrimination may guide initiatives to reduce stigma for patients. It is encouraging that perceived stigma did not appear to inhibit help-seeking behaviours. However further research in this emerging field is needed to investigate patterns of perceived stigma and help-seeking over time to identify how and when to offer support services most appropriate to the needs of lung cancer patients. This article is protected by copyright. All rights reserved.

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.45 - Proof of primary lung cancer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of primary lung cancer. 79.45... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

28 CFR 79.54 - Proof of primary lung cancer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of primary lung cancer. 79.54... cancer. (a) In determining whether a claimant developed primary lung cancer following pertinent... conclusion that a claimant developed primary lung cancer must be supported by medical documentation. To prove...

A multicentre randomised controlled trial of reciprocal lung cancer peer review and supported quality improvement: results from the improving lung cancer outcomes project

PubMed Central

Russell, G K; Jimenez, S; Martin, L; Stanley, R; Peake, M D; Woolhouse, I

2014-01-01

Background: Results from the National Lung Cancer Audit demonstrate unexplained variation in outcomes. Peer review with supported quality improvement has been shown to reduce variation in other areas of health care but has not been formally tested in cancer multidisciplinary teams. The aim of the current study is to assess the impact of reciprocal peer-to-peer review visits with supported quality improvement and collaborative working on lung cancer process and outcome measures. Methods: English lung cancer teams were randomised to usual care or facilitated reciprocal peer review visits followed by 12 months of supported quality improvement. The primary outcome was change in the following national audit indicators; mulitdisciplinary team discussion, histological confirmation, active treatment, surgical resection, small-cell chemotherapy and specialist nurse review. Patient experience was measured using a new lung cancer patient questionnaire in the intervention group. Results: Thirty teams (31 trusts) entered the intervention group and 29 of these submitted a total of 67 quality improvement plans. Active treatment increased in the intervention group (n=31) by 5.2% compared with 1.2% in the control group (n=48, mean difference 4.1%, 95% CI −0.1 to 8.2%, P=0.055). The remaining audit indicators improved similarly in all groups. Mean patient experience scores in the intervention group did not change significantly during the study but a significant improvement was seen in the scores for the five teams with the worst baseline scores (0.86 to 0.22, P<0.001). Conclusions: Reciprocal peer review with supported quality improvement was feasible and effective in stimulating quality improvement activity but resulted in only modest improvements in lung cancer treatment rates and patient experience. PMID:24651386

Immunotherapy in lung cancer.

PubMed Central

Al-Moundhri, M.; O'Brien, M.; Souberbielle, B. E.

1998-01-01

More research and new treatment options are needed in all stages of lung cancer. To this end immunotherapy needs a revival in view of recent improved technologies and greater understanding of the underlying biology. In this review we discuss mechanisms of tumour immunotherapy, non-specific, specific and adoptive, with particular reference to a direct therapeutic action on all subtypes of lung cancer. PMID:9703271

Predictive role of computer simulation in assessing signaling pathways of crizotinib-treated A549 lung cancer cells.

PubMed

Xia, Pu; Mou, Fei-Fei; Wang, Li-Wei

2012-01-01

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer deaths worldwide. Crizotinib has been approved by the U.S. Food and Drug Administration for the treatment of patients with advanced NSCLC. However, understanding of mechanisms of action is still limited. In our studies, we confirmed crizotinib-induced apoptosis in A549 lung cancer cells. In order to assess mechanisms, small molecular docking technology was used as a preliminary simulation of signaling pathways. Interesting, our results of experiments were consistent with the results of computer simulation. This indicates that small molecular docking technology should find wide use for its reliability and convenience.

Liquid biopsies in lung cancer—time to implement research technologies in routine care?

PubMed Central

Köhn, Linda; Johansson, Mikael; Grankvist, Kjell

2017-01-01

Lung cancer is the leading cause of cancer mortality. A substantial progress in the understanding of lung cancer biology has resulted in several promising targeted therapies for advanced disease. Druggable targets today include point mutations such as EGFR, BRAF and re-arrangements in genes such as ALK and ROS1. Liquid biopsies collecting e.g., circulating tumor DNA (ctDNA) reflects overall tumor information and is not biased by analyzing of only a small fraction of the tumor and is always accessible in contrast to the lung cancer tissue. Technological advances in detection of low frequency mutation variants in ctDNA have made it the dominating liquid biopsy platform in terms of utility and sensitivity. Circulating DNA or RNA may possible be used to define populations with higher risk of developing lung cancer, thus reducing screening cohorts and increasing the positive predictive value of screening. Blood based-tests may also aid to identify genetic alterations several weeks prior to radiologically verified recurrence and may be of great value in the follow-up of lung cancer patients. Besides being an alternative to invasive biopsies in selected cases, liquid biopsies offer a unique possibility to monitor treatment response following medical treatment as well as treatment response and resistance development after targeted therapy, giving a possibility to modify the treatment after the genetic profile of the tumor. Ideally, genetic alterations found in ctDNA could be tracked in real-time discriminating between fast-growing life-threatening tumors from more indolent slow growing tumors or premalignant growth that are of no concern for the wellbeing of the patient. This review focuses on future perspectives of liquid biopsies in lung cancer care for different clinical settings and present current technological platforms for further discussion of possible strategies for implementation of liquid biopsies in lung cancer. PMID:28758104

Adaptive support ventilation may deliver unwanted respiratory rate-tidal volume combinations in patients with acute lung injury ventilated according to an open lung concept.

PubMed

Dongelmans, Dave A; Paulus, Frederique; Veelo, Denise P; Binnekade, Jan M; Vroom, Margreeth B; Schultz, Marcus J

2011-05-01

With adaptive support ventilation, respiratory rate and tidal volume (V(T)) are a function of the Otis least work of breathing formula. We hypothesized that adaptive support ventilation in an open lung ventilator strategy would deliver higher V(T)s to patients with acute lung injury. Patients with acute lung injury were ventilated according to a local guideline advising the use of lower V(T) (6-8 ml/kg predicted body weight), high concentrations of positive end-expiratory pressure, and recruitment maneuvers. Ventilation parameters were recorded when the ventilator was switched to adaptive support ventilation, and after recruitment maneuvers. If V(T) increased more than 8 ml/kg predicted body weight, airway pressure was limited to correct for the rise of V(T). Ten patients with a mean (±SD) Pao(2)/Fio(2) of 171 ± 86 mmHg were included. After a switch from pressure-controlled ventilation to adaptive support ventilation, respiratory rate declined (from 31 ± 5 to 21 ± 6 breaths/min; difference = 10 breaths/min, 95% CI 3-17 breaths/min, P = 0.008) and V(T) increased (from 6.5 ± 0.8 to 9.0 ± 1.6 ml/kg predicted body weight; difference = 2.5 ml, 95% CI 0.4-4.6 ml/kg predicted body weight, P = 0.02). Pressure limitation corrected for the rise of V(T), but minute ventilation declined, forcing the user to switch back to pressure-controlled ventilation. Adaptive support ventilation, compared with pressure-controlled ventilation in an open lung strategy setting, delivers a lower respiratory rate-higher V(T) combination. Pressure limitation does correct for the rise of V(T), but leads to a decline in minute ventilation.

[Supportive care during chemotherapy for lung cancer in daily practice].

PubMed

Müller, Veronika; Tamási, Lilla; Gálffy, Gabriella; Losonczy, György

2012-09-01

Active oncotherapy, combination chemotherapy of lung cancer is accompanied with many side effects which may impair patients' quality of life and compromise the effectiveness of chemotherapy. Most side effects of chemotherapy are preventable or treatable with optimal supportive care which enhances success in patient care and treatment. The aim of this review is to summarize the most important conditions that may be associated with combined chemotherapy of lung cancer from the practical point of view.

A Study to Determine the Evolution of Advances in Medical Technology Expected in the Next 25 Years and Possible Impacts on Coast Guard Operations and Support Programs. Appendix A. Medicine: The 20-Year Outlook.

DTIC Science & Technology

1980-05-01

increased risk of breast cancer . Diuretics usually are preferred because of fewer side effects and better patient compliance. Availability of sustained...exposing cancer cells to glutaraldehyde. Diagnosis Availa’e tests to detect earl7 cancer range from self-administered ( breast self-examination...gastrointestinal tuors, lung and breast cancer , and kidney 5"OncoloqT: 3lood Test for Ear17 Ca," Medical Wiorld News, Vol. 17, No. 4 (February 23, 1976), pp. 6

The Lung Microbiome After Lung Transplantation

PubMed Central

Becker, Julia B.; Poroyko, Valeriy

2014-01-01

Summary Lung transplantation survival remains significantly impacted by infections and the development of chronic rejection manifesting as bronchiolitis obliterans syndrome (BOS). Traditional microbiologic data has provided insight into the role of infections in BOS. Now, new non-culture-based techniques have been developed to characterize the entire population of microbes resident on the surfaces of the body, also known as the human microbiome. Early studies have identified that lung transplant patients have a different lung microbiome and have demonstrated the important finding that the transplant lung microbiome changes over time. Furthermore, both unique bacterial populations and longitudinal changes in the lung microbiome have now been suggested to play a role in the development of BOS. In the future, this technology will need to be combined with functional assays and assessment of the immune responses in the lung to help further explain the microbiome’s role in the failing lung allograft. PMID:24601662

Support Service Use and Interest in Support Services among Lung Cancer Patients

PubMed Central

Mosher, Catherine E.; Hanna, Nasser; Jalal, Shadia I.; Fakiris, Achilles J.; Einhorn, Lawrence H.; Birdas, Thomas J.; Kesler, Kenneth A.; Champion, Victoria L.

2013-01-01

Summary Objectives This study examined support service use and interest in support services among lung cancer patients (N = 165) at two comprehensive medical centers in the midwestern United States. Materials and Methods Patients completed an assessment of support service use (i.e., receipt of mental health services, complementary and alternative medicine [CAM], and help from a spiritual leader), interest in support services, and physical and psychological symptoms. Results Only 40% of patients with significant anxiety and depressive symptoms and 28% of the entire sample reported current mental health service use. However, nearly half (47%) of all patients were receiving support from a spiritual leader. Having late-stage lung cancer and a religious affiliation predicted receipt of spiritual support. Few patients who were not receiving mental health services or spiritual support were interested in these services (range = 4% to 18%). Conversely, although interest in CAM was expressed by a substantial minority of patients (27%) who were not using these services, rates of CAM use were relatively low (22%). Conclusion Findings suggest that distressed lung cancer patients underuse mental health services, but many patients receive help from spiritual leaders. Given the lack of interest in mental health services among patients who are not receiving them, efforts are needed to enhance palatability of services and identify and reduce barriers to evidence-based service use. PMID:23932457

77 FR 64818 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-23

... of Committee: National Heart, Lung, and Blood Institute Special Emphasis Panel; Virtual Reality Technologies for Research and Education in Obesity and Diabetes. Date: November 14, 2012. Time: 6:00 p.m. to 9...

Detection of early changes in lung-cell cytology by flow-systems analysis techniques. Progress report, January 1--June 30, 1976

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinkamp, J. A.; Hansen, K. M.; Wilson, J. S.

1976-08-01

This report summarizes results of preliminary experiments to develop cytological and biochemical indicators for estimating damage to respiratory epithelium exposed to toxic agents associated with the by-products of nonnuclear energy production using advanced flow-systems cell-analysis technologies. Since initiation of the program one year ago, progress has been made in obtaining adequate numbers of exfoliated lung cells from the Syrian hamster for flow analysis; cytological techniques developed on human exfoliated gynecological samples have been adapted to hamster lung epithelium for obtaining single-cell suspensions; and lung-cell samples have been initially characterized based on DNA content, total protein, nuclear and cytoplasmic size, andmore » multiangle light-scatter measurements. Preliminary results from measurements of the above parameters which recently became available are described in this report. As the flow-systems technology is adapted further to analysis of exfoliated lung cells, measurements of changes in physical and biochemical cellular properties as a function of exposure to toxic agents will be performed.« less

Microfluidic lung airway-on-a-chip with arrayable suspended gels for studying epithelial and smooth muscle cell interactions.

PubMed

Humayun, Mouhita; Chow, Chung-Wai; Young, Edmond W K

2018-05-01

Chronic lung diseases (CLDs) are regulated by complex interactions between many different cell types residing in lung airway tissues. Specifically, interactions between airway epithelial cells (ECs) and airway smooth muscle cells (SMCs) have been shown in part to play major roles in the pathogenesis of CLDs, but the underlying molecular mechanisms are not well understood. To advance our understanding of lung pathophysiology and accelerate drug development processes, new innovative in vitro tissue models are needed that can reconstitute the complex in vivo microenvironment of human lung tissues. Organ-on-a-chip technologies have recently made significant strides in recapitulating physiological properties of in vivo lung tissue microenvironments. However, novel advancements are still needed to enable the study of airway SMC-EC communication with matrix interactions, and to provide higher throughput capabilities and manufacturability. We have developed a thermoplastic-based microfluidic lung airway-on-a-chip model that mimics the lung airway tissue microenvironment, and in particular, the interactions between SMCs, ECs, and supporting extracellular matrix (ECM). The microdevice is fabricated from acrylic using micromilling and solvent bonding techniques, and consists of three vertically stacked microfluidic compartments with a bottom media reservoir for SMC culture, a middle thin hydrogel layer, and an upper microchamber for achieving air-liquid interface (ALI) culture of the epithelium. A unique aspect of the design lies in the suspended hydrogel with upper and lower interfaces for EC and SMC culture, respectively. A mixture of type I collagen and Matrigel was found to promote EC adhesion and monolayer formation, and SMC adhesion and alignment. Optimal culturing protocols were established that enabled EC-SMC coculture for more than 31 days. Epithelial monolayers displayed common morphological markers including ZO-1 tight junctions and F-actin cell cortices, while SMCs exhibited enhanced cell alignment and expression of α-SMA. The thermoplastic device construction facilitates mass manufacturing, allows EC-SMC coculture systems to be arrayed for increased throughput, and can be disassembled to allow extraction of the suspended gel for downstream analyses. This airway-on-a-chip device has potential to significantly advance our understanding of SMC-EC-matrix interactions, and their roles in the development of CLDs.

Malfolded Protein Structure and Proteostasis in Lung Diseases

PubMed Central

Balch, William E.; Sznajder, Jacob I.; Budinger, Scott; Finley, Daniel; Laposky, Aaron D.; Cuervo, Ana Maria; Benjamin, Ivor J.; Barreiro, Esther; Morimoto, Richard I.; Postow, Lisa; Weissman, Allan M.; Gail, Dorothy; Banks-Schlegel, Susan; Croxton, Thomas

2014-01-01

Recent discoveries indicate that disorders of protein folding and degradation play a particularly important role in the development of lung diseases and their associated complications. The overarching purpose of the National Heart, Lung, and Blood Institute workshop on “Malformed Protein Structure and Proteostasis in Lung Diseases” was to identify mechanistic and clinical research opportunities indicated by these recent discoveries in proteostasis science that will advance our molecular understanding of lung pathobiology and facilitate the development of new diagnostic and therapeutic strategies for the prevention and treatment of lung disease. The workshop's discussion focused on identifying gaps in scientific knowledge with respect to proteostasis and lung disease, discussing new research advances and opportunities in protein folding science, and highlighting novel technologies with potential therapeutic applications for diagnosis and treatment. PMID:24033344

Malfolded protein structure and proteostasis in lung diseases.

PubMed

Balch, William E; Sznajder, Jacob I; Budinger, Scott; Finley, Daniel; Laposky, Aaron D; Cuervo, Ana Maria; Benjamin, Ivor J; Barreiro, Esther; Morimoto, Richard I; Postow, Lisa; Weissman, Allan M; Gail, Dorothy; Banks-Schlegel, Susan; Croxton, Thomas; Gan, Weiniu

2014-01-01

Recent discoveries indicate that disorders of protein folding and degradation play a particularly important role in the development of lung diseases and their associated complications. The overarching purpose of the National Heart, Lung, and Blood Institute workshop on "Malformed Protein Structure and Proteostasis in Lung Diseases" was to identify mechanistic and clinical research opportunities indicated by these recent discoveries in proteostasis science that will advance our molecular understanding of lung pathobiology and facilitate the development of new diagnostic and therapeutic strategies for the prevention and treatment of lung disease. The workshop's discussion focused on identifying gaps in scientific knowledge with respect to proteostasis and lung disease, discussing new research advances and opportunities in protein folding science, and highlighting novel technologies with potential therapeutic applications for diagnosis and treatment.

Combining Cell Type-Restricted Adenoviral Targeting with Immunostaining and Flow Cytometry to Identify Cells-of-Origin of Lung Cancer.

PubMed

Best, Sarah A; Kersbergen, Ariena; Asselin-Labat, Marie-Liesse; Sutherland, Kate D

2018-01-01

Lung cancers display considerable intertumoral heterogeneity, leading to the classification of distinct tumor subtypes. Our understanding of the genetic aberrations that underlie tumor subtypes has been greatly enhanced by recent genomic sequencing studies and state-of-the-art gene targeting technologies, highlighting evidence that distinct lung cancer subtypes may be derived from different "cells-of-origin". Here, we describe the intra-tracheal delivery of cell type-restricted Ad5-Cre viruses into the lungs of adult mice, combined with immunohistochemical and flow cytometry strategies for the detection of lung cancer-initiating cells in vivo.

Data-driven decision support for radiologists: re-using the National Lung Screening Trial dataset for pulmonary nodule management.

PubMed

Morrison, James J; Hostetter, Jason; Wang, Kenneth; Siegel, Eliot L

2015-02-01

Real-time mining of large research trial datasets enables development of case-based clinical decision support tools. Several applicable research datasets exist including the National Lung Screening Trial (NLST), a dataset unparalleled in size and scope for studying population-based lung cancer screening. Using these data, a clinical decision support tool was developed which matches patient demographics and lung nodule characteristics to a cohort of similar patients. The NLST dataset was converted into Structured Query Language (SQL) tables hosted on a web server, and a web-based JavaScript application was developed which performs real-time queries. JavaScript is used for both the server-side and client-side language, allowing for rapid development of a robust client interface and server-side data layer. Real-time data mining of user-specified patient cohorts achieved a rapid return of cohort cancer statistics and lung nodule distribution information. This system demonstrates the potential of individualized real-time data mining using large high-quality clinical trial datasets to drive evidence-based clinical decision-making.

Beta-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice

USDA-ARS?s Scientific Manuscript database

Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer, but the data supporting this relationship are inconsistent. Here, we found that nicotine treatment not only induced emphysema but also increased both lung tumor multiplicity and volume in 4-nitrosa...

Are central institutional review boards the solution? The National Heart, Lung, and Blood Institute Working Group's report on optimizing the IRB process.

PubMed

Mascette, Alice M; Bernard, Gordon R; Dimichele, Donna; Goldner, Jesse A; Harrington, Robert; Harris, Paul A; Leeds, Hilary S; Pearson, Thomas A; Ramsey, Bonnie; Wagner, Todd H

2012-12-01

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened a working group in June 2011 to examine alternative institutional review board (IRB) models. The working group was held in response to proposed changes in the regulations for government-supported research and the proliferation of multicenter clinical trials where multiple individual reviews may be inefficient. Group members included experts in heart, lung, and blood research, research oversight, bioethics, health economics, regulations, and information technology (IT). The group discussed alternative IRB models, ethical concerns, metrics for evaluating IRBs, IT needs, and economic considerations. Participants noted research gaps in IRB best practices and in metrics. The group arrived at recommendations for process changes, such as defining specific IRB performance requirements in funding announcements, requiring funded researchers to use more efficient alternative IRB models, and developing IT systems to facilitate information sharing and collaboration among IRBs. Despite the success of the National Cancer Institute's central IRB (CIRB), the working group, concerned about the creation costs and unknown cost-efficiency of a new CIRB, and about the risk of shifting the burden of dealing with multiple IRBs from sponsors to research institutions, did not recommend the creation of an NHLBI-funded CIRB.

Auscultation of the lung: past lessons, future possibilities.

PubMed Central

Murphy, R L

1981-01-01

Review of the history of auscultation of the lung reveals few scientific investigations. The majority of these have led to inconclusive results. The mechanism of production of normal breath sounds remains uncertain. Hypotheses for the generation of adventitious sounds are unproven. Advances in instrumentation for lung sound recording and analysis have provided little of clinical value. There has been a recent resurgence of interest in lung sounds. Space-age technology has improved methodology for sonic analysis significantly. Lung sounds are complex signals that probably reflect regional lung pathophysiology. If they were understood more clearly important non-invasive diagnostic tools could be devised and the value of clinical auscultation could be improved. A multidisciplinary effort will be required to achieve this. PMID:7268687

Lung physiology during ECS resuscitation of DCD donors followed by in situ assessment of lung function.

PubMed

Reoma, Junewai L; Rojas, Alvaro; Krause, Eric M; Obeid, Nabeel R; Lafayette, Nathan G; Pohlmann, Joshua R; Padiyar, Niru P; Punch, Jeffery D; Cook, Keith E; Bartlett, Robert H

2009-01-01

Extracorporeal cardiopulmonary support (ECS) of donors after cardiac death (DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in vivo method to assess if lungs are suitable for transplantation from DCD donors after ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10 min of warm ischemia. Cannulae were placed into the right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90 min with lungs inflated, group 1 (n = 5) or deflated, group 2 (n = 3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-ventricular (bi-VAD) system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1-hr assessment period. The oxygenator was turned off, and ventilation was restarted. Flows, blood gases, PA and left atrial pressures, and compliance were recorded. In both the groups, LA pressure was <15 mm Hg during ECS. During the lung assessment period, PA flows were 1.4-2.2 L/min. PO2 was >300 mm Hg, with normal PCO2. Extracorporeal cardiopulmonary support resuscitation of DCD donors is feasible and allows for assessment of function before procurement. Extracorporeal cardiopulmonary support does not cause pulmonary congestion, and the lungs retain adequate function for transplantation. Compliance correlated with lung function.

A feasibility study of automatic lung nodule detection in chest digital tomosynthesis with machine learning based on support vector machine

NASA Astrophysics Data System (ADS)

Lee, Donghoon; Kim, Ye-seul; Choi, Sunghoon; Lee, Haenghwa; Jo, Byungdu; Choi, Seungyeon; Shin, Jungwook; Kim, Hee-Joung

2017-03-01

The chest digital tomosynthesis(CDT) is recently developed medical device that has several advantage for diagnosing lung disease. For example, CDT provides depth information with relatively low radiation dose compared to computed tomography (CT). However, a major problem with CDT is the image artifacts associated with data incompleteness resulting from limited angle data acquisition in CDT geometry. For this reason, the sensitivity of lung disease was not clear compared to CT. In this study, to improve sensitivity of lung disease detection in CDT, we developed computer aided diagnosis (CAD) systems based on machine learning. For design CAD systems, we used 100 cases of lung nodules cropped images and 100 cases of normal lesion cropped images acquired by lung man phantoms and proto type CDT. We used machine learning techniques based on support vector machine and Gabor filter. The Gabor filter was used for extracting characteristics of lung nodules and we compared performance of feature extraction of Gabor filter with various scale and orientation parameters. We used 3, 4, 5 scales and 4, 6, 8 orientations. After extracting features, support vector machine (SVM) was used for classifying feature of lesions. The linear, polynomial and Gaussian kernels of SVM were compared to decide the best SVM conditions for CDT reconstruction images. The results of CAD system with machine learning showed the capability of automatically lung lesion detection. Furthermore detection performance was the best when Gabor filter with 5 scale and 8 orientation and SVM with Gaussian kernel were used. In conclusion, our suggested CAD system showed improving sensitivity of lung lesion detection in CDT and decide Gabor filter and SVM conditions to achieve higher detection performance of our developed CAD system for CDT.

Genetic susceptibility to lung cancer—light at the end of the tunnel?

PubMed Central

Christiani, David C.

2013-01-01

Lung cancer is one of the most common and deadliest cancers in the world. The major socio-environmental risk factor involved in the development of lung cancer is cigarette smoking. Additionally, there are multiple genetic factors, which may also play a role in lung cancer risk. Early work focused on the presence of relatively prevalent but low-penetrance alterations in candidate genes leading to increased risk of lung cancer. Development of new technologies such as genomic profiling and genome-wide association studies has been helpful in the detection of new genetic variants likely involved in lung cancer risk. In this review, we discuss the role of multiple genetic variants and review their putative role in the risk of lung cancer. Identifying genetic biomarkers and patterns of genetic risk may be useful in the earlier detection and treatment of lung cancer patients. PMID:23349013

Lung Cancer Assistant: a hybrid clinical decision support application for lung cancer care.

PubMed

Sesen, M Berkan; Peake, Michael D; Banares-Alcantara, Rene; Tse, Donald; Kadir, Timor; Stanley, Roz; Gleeson, Fergus; Brady, Michael

2014-09-06

Multidisciplinary team (MDT) meetings are becoming the model of care for cancer patients worldwide. While MDTs have improved the quality of cancer care, the meetings impose substantial time pressure on the members, who generally attend several such MDTs. We describe Lung Cancer Assistant (LCA), a clinical decision support (CDS) prototype designed to assist the experts in the treatment selection decisions in the lung cancer MDTs. A novel feature of LCA is its ability to provide rule-based and probabilistic decision support within a single platform. The guideline-based CDS is based on clinical guideline rules, while the probabilistic CDS is based on a Bayesian network trained on the English Lung Cancer Audit Database (LUCADA). We assess rule-based and probabilistic recommendations based on their concordances with the treatments recorded in LUCADA. Our results reveal that the guideline rule-based recommendations perform well in simulating the recorded treatments with exact and partial concordance rates of 0.57 and 0.79, respectively. On the other hand, the exact and partial concordance rates achieved with probabilistic results are relatively poorer with 0.27 and 0.76. However, probabilistic decision support fulfils a complementary role in providing accurate survival estimations. Compared to recorded treatments, both CDS approaches promote higher resection rates and multimodality treatments.

Diagnosis by Volatile Organic Compounds in Exhaled Breath from Lung Cancer Patients Using Support Vector Machine Algorithm

PubMed Central

Sakumura, Yuichi; Koyama, Yutaro; Tokutake, Hiroaki; Hida, Toyoaki; Sato, Kazuo; Itoh, Toshio; Akamatsu, Takafumi; Shin, Woosuck

2017-01-01

Monitoring exhaled breath is a very attractive, noninvasive screening technique for early diagnosis of diseases, especially lung cancer. However, the technique provides insufficient accuracy because the exhaled air has many crucial volatile organic compounds (VOCs) at very low concentrations (ppb level). We analyzed the breath exhaled by lung cancer patients and healthy subjects (controls) using gas chromatography/mass spectrometry (GC/MS), and performed a subsequent statistical analysis to diagnose lung cancer based on the combination of multiple lung cancer-related VOCs. We detected 68 VOCs as marker species using GC/MS analysis. We reduced the number of VOCs and used support vector machine (SVM) algorithm to classify the samples. We observed that a combination of five VOCs (CHN, methanol, CH3CN, isoprene, 1-propanol) is sufficient for 89.0% screening accuracy, and hence, it can be used for the design and development of a desktop GC-sensor analysis system for lung cancer. PMID:28165388

Diagnosis by Volatile Organic Compounds in Exhaled Breath from Lung Cancer Patients Using Support Vector Machine Algorithm.

PubMed

Sakumura, Yuichi; Koyama, Yutaro; Tokutake, Hiroaki; Hida, Toyoaki; Sato, Kazuo; Itoh, Toshio; Akamatsu, Takafumi; Shin, Woosuck

2017-02-04

Monitoring exhaled breath is a very attractive, noninvasive screening technique for early diagnosis of diseases, especially lung cancer. However, the technique provides insufficient accuracy because the exhaled air has many crucial volatile organic compounds (VOCs) at very low concentrations (ppb level). We analyzed the breath exhaled by lung cancer patients and healthy subjects (controls) using gas chromatography/mass spectrometry (GC/MS), and performed a subsequent statistical analysis to diagnose lung cancer based on the combination of multiple lung cancer-related VOCs. We detected 68 VOCs as marker species using GC/MS analysis. We reduced the number of VOCs and used support vector machine (SVM) algorithm to classify the samples. We observed that a combination of five VOCs (CHN, methanol, CH₃CN, isoprene, 1-propanol) is sufficient for 89.0% screening accuracy, and hence, it can be used for the design and development of a desktop GC-sensor analysis system for lung cancer.

Functional genomics of chlorine-induced acute lung injury in mice.

PubMed

Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A; Dopico, Richard A; Di, Y Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J; Kaminski, Naftali; You, Ming; Prows, Daniel R

2010-07-01

Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury.

Should lung transplantation be performed for patients on mechanical respiratory support? The US experience.

PubMed

Mason, David P; Thuita, Lucy; Nowicki, Edward R; Murthy, Sudish C; Pettersson, Gösta B; Blackstone, Eugene H

2010-03-01

The study objectives were to (1) compare survival after lung transplantation in patients requiring pretransplant mechanical ventilation or extracorporeal membrane oxygenation with that of patients not requiring mechanical support and (2) identify risk factors for mortality. Data were obtained from the United Network for Organ Sharing for lung transplantation from October 1987 to January 2008. A total of 15,934 primary transplants were performed: 586 in patients on mechanical ventilation and 51 in patients on extracorporeal membrane oxygenation. Differences between nonsupport patients and those on mechanical ventilation or extracorporeal membrane oxygenation support were expressed as 2 propensity scores for use in comparing risk-adjusted survival. Unadjusted survival at 1, 6, 12, and 24 months was 83%, 67%, 62%, and 57% for mechanical ventilation, respectively; 72%, 53%, 50%, and 45% for extracorporeal membrane oxygenation, respectively; and 93%, 85%, 79%, and 70% for unsupported patients, respectively (P < .0001). Recipients on mechanical ventilation were younger, had lower forced vital capacity, and had diagnoses other than emphysema. Recipients on extracorporeal membrane oxygenation were also younger, had higher body mass index, and had diagnoses other than cystic fibrosis/bronchiectasis. Once these variables, transplant year, and propensity for mechanical support were accounted for, survival remained worse after lung transplantation for patients on mechanical ventilation and extracorporeal membrane oxygenation. Although survival after lung transplantation is markedly worse when preoperative mechanical support is necessary, it is not dismal. Thus, additional risk factors for mortality should be considered when selecting patients for lung transplantation to maximize survival. Reduced survival for this high-risk population raises the important issue of balancing maximal individual patient survival against benefit to the maximum number of patients. Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Predictors of lung transplant survival in eurotransplant.

PubMed

Smits, J M A; Mertens, B J A; Van Houwelingen, H C; Haverich, A; Persijn, G G; Laufer, G

2003-11-01

This study was undertaken to assess the influence of patient/donor and center factors on lung transplantation outcome. Outcomes of all consecutive first cadaveric lung transplants performed at 21 Eurotransplant centers in 1997-99 were analyzed. The risk-adjusted center effect on mortality was estimated. A Cox model was built including donor and recipient age and gender, primary disease, HLA mismatches, patient's residence, cold ischemic time, donor's cause of death, serum creatinine, type of lung transplant, respiratory support status, clinical condition and percentage predicted FEV1. The center effect was calculated (expressed as the standardized difference between the observed and expected survival rates), and empirical and full Bayes methods were applied to evaluate between-center differences. A total of 590 adults underwent lung transplantation. The primary disease (p=0.01), HLA-mismatches (p = 0.02), clinical condition(p < 0.0001) and the patient's respiratory support status (p = 0.05) were significantly associated with survival. After adjusting for case-mix, no between-center differences could be found. An in-depth empirical Bayes analysis showed the between-center variation to be zero. Similar results were obtained from the full Bayes analysis. Based on these data, there is no scientific basis to support a hypothesis of possible association between center volume and lung survival rates.

Web-Based Cancer Communication and Decision Making Systems: Connecting Patients, Caregivers, and Clinicians for Improved Health Outcomes

PubMed Central

DuBenske, Lori L.; Gustafson, David H.; Shaw, Bret R.; Cleary, James F.

2011-01-01

Over the cancer disease trajectory, from diagnosis and treatment to remission or end of life, patients and their families face difficult decisions. The provision of information and support when most relevant can optimize cancer decision making and coping. An interactive health communication system (IHCS) offers the potential to bridge the communication gaps that occur among patients, family, and clinicians and to empower each to actively engage in cancer care and shared decision making. This is a report of the authors' experience (with a discussion of relevant literature) in developing and testing a Web-based IHCS—the Comprehensive Health Enhancement Support System (CHESS)—for patients with advanced lung cancer and their family caregivers. CHESS provides information, communication, and coaching resources as well as a symptom tracking system that reports health status to the clinical team. Development of an IHCS includes a needs assessment of the target audience and applied theory informed by continued stakeholder involvement in early testing. Critical issues of IHCS implementation include 1) need for interventions that accommodate a variety of format preferences and technology comfort ranges; 2) IHCS user training, 3) clinician investment in IHCS promotion, and 4) IHCS integration with existing medical systems. In creating such comprehensive systems, development strategies need to be grounded in population needs with appropriate use of technology that serves the target users, including the patient/family, clinical team, and health care organization. Implementation strategies should address timing, personnel, and environmental factors to facilitate continued use and benefit from IHCS. An interactive health communication system (IHCS) offers one platform for providing the information, communication, and coaching resources that cancer patients and their families need to understand the disease, find support, and develop decision-making and coping skills. One such IHCS—the Comprehensive Health Enhancement Support System (CHESS)—has evolved over the past 20 years. Based on our recent experience creating and testing a new version of CHESS—“Coping with Lung Cancer: A Network of Support”—this article outlines the issues faced in developing and implementing such a system within the cancer context. PMID:21041539

Invadopodia formation in blood clots: Not so SLUGgish after all.

PubMed

Knowles, Lynn M; Maranchie, Jodi K; Pilch, Jan

2014-01-01

Blood clotting specifically supports the metastatic dissemination of malignant cells to the lung. We have recently demonstrated that 2 tumor types that are prone to form lung metastases, renal cell carcinoma and soft tissue sarcoma, share specific adhesive mechanisms that support the invasion and colonization of blood clots in the pulmonary vasculature.

Technology Experience of Solid Organ Transplant Patients and Their Overall Willingness to Use Interactive Health Technology.

PubMed

Vanhoof, Jasper M M; Vandenberghe, Bert; Geerts, David; Philippaerts, Pieter; De Mazière, Patrick; DeVito Dabbs, Annette; De Geest, Sabina; Dobbels, Fabienne

2018-03-01

The use of interactive health technology (IHT) is a promising pathway to tackle self-management problems experienced by many chronically ill patients, including solid organ transplant (Tx) patients. Yet, to ensure that the IHT is accepted and used, a human-centered design process is needed, actively involving end users in all steps of the development process. A first critical, predevelopment step involves understanding end users' characteristics. This study therefore aims to (a) select an IHT platform to deliver a self-management support intervention most closely related to Tx patients' current use of information and communication technologies (ICTs), (b) understand Tx patients' overall willingness to use IHT for self-management support, and investigate associations with relevant technology acceptance variables, and (c) explore Tx patients' views on potential IHT features. We performed a cross-sectional, descriptive study between October and December 2013, enrolling a convenience sample of adult heart, lung, liver, and kidney Tx patients from the University Hospitals Leuven, Belgium. Broad inclusion criteria were applied to ensure a representative patient sample. We used a 35-item newly designed interview questionnaire to measure Tx patients' use of ICTs, their overall willingness to use IHT, and their views on potential IHT features, as well as relevant technology acceptance variables derived from the Unified Theory of Acceptance and Use of Technology and a literature review. Descriptive statistics were used as appropriate, and an ordinal logistic regression model was built to determine the association between Tx patients' overall willingness to use IHT, the selected technology acceptance variables, and patient characteristics. Out of 139 patients, 122 agreed to participate (32 heart, 30 lung, 30 liver, and 30 kidney Tx patients; participation rate: 88%). Most patients were male (57.4%), married or living together (68%), and had a mean age of 55.9 ± 13.4 years. Only 27.9% of Tx patients possessed a smartphone, yet 72.1% owned at least one desktop or laptop PC with wireless Internet at home. On a 10-point numeric scale, asking patients whether they think IHT development is important to support them personally in their self-management, patients gave a median score of 7 (25th percentile 5 points; 75th percentile 10 points). Patients who were single or married or living together were more likely to give a higher rating than divorced or widowed patients; patients who completed only secondary education gave a higher rating than higher educated patients; and patients with prior ICT use gave a higher rating than patients without prior ICT use. Tx patients also had clear preferences regarding IHT features, such as automatic data transfer, as much as possible, visual aids (e.g., graphs) over text messages, and personally deciding when to access the IHT. By investigating Tx patients' possession and use of ICTs, we learned that computers and the Internet, and not smartphones, are the most suitable IHT platforms to deliver self-management interventions for our Tx patients. Moreover, Tx patients generally are open to using IHT, yet patient acceptance variables and their preferences for certain IHT features should be taken into account in the next steps of IHT development. Designers intending to develop or use existing IHTs should never overlook this critical first step in a human-centered design. Before considering using eHealth technology in clinical practice, professionals should always check whether patients are familiar with using information and communication technology, and whether they are willing to use technology for health-related purposes. © 2017 Sigma Theta Tau International.

National review of use of extracorporeal membrane oxygenation as respiratory support in thoracic surgery excluding lung transplantation.

PubMed

Rinieri, Philippe; Peillon, Christophe; Bessou, Jean-Paul; Veber, Benoît; Falcoz, Pierre-Emmanuel; Melki, Jean; Baste, Jean-Marc

2015-01-01

Extracorporeal membrane oxygenation (ECMO) for respiratory support is increasingly used in intensive care units (ICU), but rarely during thoracic surgical procedures outside the transplantation setting. ECMO can be an alternative to cardiopulmonary bypass for major trachea-bronchial surgery and single-lung procedures without in-field ventilation. Our aim was to evaluate the intraoperative use of ECMO as respiratory support in thoracic surgery: benefits, indications and complications. This was a multicentre retrospective study (questionnaire) of use of ECMO as respiratory support during the thoracic surgical procedure. Lung transplantation and lung resection for tumour invading the great vessels and/or the left atrium were excluded, because they concern respiratory and circulatory support. From March 2009 to September 2012, 17 of the 34 centres in France applied ECMO within veno-venous (VV) (n=20) or veno-arterial (VA) (n=16) indications in 36 patients. Ten VA ECMO were performed with peripheral cannulation and 6 with central cannulation; all VV ECMO were achieved through peripheral cannulation. Group 1 (total respiratory support) was composed of 28 patients without mechanical ventilation, involving 23 tracheo-bronchial and 5 single-lung procedures. Group 2 (partial respiratory support) was made up of 5 patients with respiratory insufficiency. Group 3 was made up of 3 patients who underwent thoracic surgery in a setting of acute respiratory distress syndrome (ARDS) with preoperative ECMO. Mortality at 30 days in Groups 1, 2 and 3 was 7, 40 and 67%, respectively (P<0.05). In Group 1, ECMO was weaned intraoperatively or within 24 h in 75% of patients. In Group 2, ECMO was weaned in ICU over several days. In Group 1, 2 patients with VA support were converted to VV support for chronic respiratory indications. Bleeding was the major complication with 17% of patients requiring return to theatre for haemostasis. There were two cannulation-related complications (6%). VV or VA ECMO is a satisfactory alternative to in-field ventilation in complex tracheo-bronchial surgery or in single-lung surgery. ECMO should be considered and used in precarious postoperative respiratory conditions. Full respiratory support can be achieved with VV ECMO. Indications for and results of ECMO during surgery in patients with ARDS warrant further careful investigation. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Measurement of lung function using Electrical Impedance Tomography (EIT) during mechanical ventilation

NASA Astrophysics Data System (ADS)

Nebuya, Satoru; Koike, Tomotaka; Imai, Hiroshi; Noshiro, Makoto; Brown, Brian H.; Soma, Kazui

2010-04-01

The consistency of regional lung density measurements as estimated by Electrical Impedance Tomography (EIT), in eleven patients supported by a mechanical ventilator, was validated to verify the feasibility of its use in intensive care medicine. There were significant differences in regional lung densities between the normal lung and diseased lungs associated with pneumonia, atelectasis and pleural effusion (Steel-Dwass test, p < 0.05). Temporal changes in regional lung density of patients with atelectasis were observed to be in good agreement with the results of clinical diagnosis. These results indicate that it is feasible to obtain a quantitative value for regional lung density using EIT.

The microbiome at the pulmonary alveolar niche and its role in Mycobacterium tuberculosis infection.

PubMed

Adami, Alexander J; Cervantes, Jorge L

2015-12-01

Advances in next generation sequencing (NGS) technology have provided the tools to comprehensively and accurately characterize the microbial community in the respiratory tract in health and disease. The presence of commensal and pathogenic bacteria has been found to have important effects on the lung immune system. Until relatively recently, the lung has received less attention compared to other body sites in terms of microbiome characterization, and its study carries special technological difficulties related to obtaining reliable samples as compared to other body niches. Additionally, the complexity of the alveolar immune system, and its interactions with the lung microbiome, are only just beginning to be understood. Amidst this complexity sits Mycobacterium tuberculosis (Mtb), one of humanity's oldest nemeses and a significant public health concern, with millions of individuals infected with Mtb worldwide. The intricate interactions between Mtb, the lung microbiome, and the alveolar immune system are beginning to be understood, and it is increasingly apparent that improved treatment of Mtb will only come through deep understanding of the interplay between these three forces. In this review, we summarize our current understanding of the lung microbiome, alveolar immunity, and the interaction of each with Mtb. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of electromagnetic navigational bronchoscopy in pulmonary nodule management

PubMed Central

Dahagam, Chanukya; Breen, David P.; Sarkar, Saiyad

2016-01-01

The incidence of pulmonary nodules and lung cancer is rising. Some of this increase in incidence is due to improved pick up by newer imaging modalities. However, the goal is to diagnose these lesion, many of which are located in the periphery, by safe and relatively non-invasive methods. This has led to the emergence of numerous techniques such as electromagnetic navigational bronchoscopy (ENB). Current evidence supports a role for these techniques in the diagnostic pathway. However, numerous factor influence the diagnostic accuracy. Thus despite significant advances, more research needs to be undertaken to further improve the currently available diagnostic technologies. PMID:27606080

Support and rehabilitation of patients with pulmonary expansion deficit by using game therapy.

PubMed

Chacon, P F S; Schon, C F; Furtado, V H L A; Signoretti, G L A M; Oliveira, J P P; Ribeiro, A G; Wanderley, C D V; Diniz, A A R; Soares, H B

2016-08-01

Patients suffering from hypoventilation and pulmonary expansion deficit are at increased risk of developing pulmonary complications such as atelectasis, pneumonia or pleural effusion. These complications can increase the length of stay and spending on health, and generate long-term functional impairment. This study aims to produce a therapeutic alternative to the traditional method of lung re-expansion through incentive spirometry (IS) using the game therapy to build an innovative system. This system makes use of infrared and Bluetooth communication technology to associate the game therapy to EI. At the end of the system implementation, we expect to obtain good adhesion of the patient and the physiotherapists.

Idiopathic pulmonary fibrosis

MedlinePlus

... a support group. Sharing with others who have common experiences and problems can help you not feel alone. These organizations are good resources for information on lung disease: American Lung ...

Early Lung Cancer Diagnosis by Biosensors

PubMed Central

Zhang, Yuqian; Yang, Dongliang; Weng, Lixing; Wang, Lianhui

2013-01-01

Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted. PMID:23892596

Ventilation in the patient with unilateral lung disease.

PubMed

Thomas, A R; Bryce, T L

1998-10-01

Severe ULD presents a challenge in ventilator management because of the marked asymmetry in the mechanics of the two lungs. The asymmetry may result from significant decreases or increases in the compliance of the involved lung. Traditional ventilator support may fail to produce adequate gas exchange in these situations and has the potential to cause further deterioration. Fortunately, conventional techniques can be safely and effectively applied in the majority of cases without having to resort to less familiar and potentially hazardous forms of support. In those circumstances when conventional ventilation is unsuccessful in restoring adequate gas exchange, lateral positioning and ILV have proved effective at improving and maintaining gas exchange. Controlled trials to guide clinical decision making are lacking. In patients who have processes associated with decreased compliance in the involved lung, lateral positioning may be a simple method of improving gas exchange but is associated with many practical limitations. ILV in these patients is frequently successful when differential PEEP is applied with the higher pressure to the involved lung. In patients in whom the pathology results in distribution of ventilation favoring the involved lung, particularly BPF, ILV can be used to supply adequate support while minimizing flow through the fistula and allowing it to close. The application of these techniques should be undertaken with an understanding of the pathophysiology of the underlying process; the reported experience with these techniques, including indications and successfully applied methods; and the potential problems encountered with their use. Fortunately, these modalities are infrequently required, but they provide a critical means of support when conventional techniques fail.

Combined application of extracorporeal membrane oxygenation and an artificial pacemaker in fulminant myocarditis in a child

PubMed Central

Ye, Sheng; Zhu, Lvchan; Ning, Botao; Zhang, Chenmei

2017-01-01

Fulminant myocarditis is severe and aggressive, but it is self-limited and usually has a favorable prognosis if the patients can survive the acute phase. When drug treatment is not effective, extracorporeal membrane oxygenation technology should be applied to support cardiopulmonary function. Extracorporeal membrane oxygenation can simultaneously support function of the left ventricle, right ventricle, and lungs, and provide stable blood circulation for patients with heart and respiratory failure, which allows sufficient time for the cardiopulmonary system to recover. Fulminant myocarditis affects cardiac systolic function, as well as the function of autorhythmic cells and the conduction system. If severe bradycardia or atrioventricular block appears, a pacemaker needs to be installed. We report a child with fulminant myocarditis who was treated with extracorporeal membrane oxygenation combined with an artificial pacemaker. PMID:28747842

Combined application of extracorporeal membrane oxygenation and an artificial pacemaker in fulminant myocarditis in a child.

PubMed

Ye, Sheng; Zhu, Lvchan; Ning, Botao; Zhang, Chenmei

2017-06-01

Fulminant myocarditis is severe and aggressive, but it is self-limited and usually has a favorable prognosis if the patients can survive the acute phase. When drug treatment is not effective, extracorporeal membrane oxygenation technology should be applied to support cardiopulmonary function. Extracorporeal membrane oxygenation can simultaneously support function of the left ventricle, right ventricle, and lungs, and provide stable blood circulation for patients with heart and respiratory failure, which allows sufficient time for the cardiopulmonary system to recover. Fulminant myocarditis affects cardiac systolic function, as well as the function of autorhythmic cells and the conduction system. If severe bradycardia or atrioventricular block appears, a pacemaker needs to be installed. We report a child with fulminant myocarditis who was treated with extracorporeal membrane oxygenation combined with an artificial pacemaker.

Mechanical Ventilation and Bronchopulmonary Dysplasia.

PubMed

Keszler, Martin; Sant'Anna, Guilherme

2015-12-01

Mechanical ventilation is an important potentially modifiable risk factor for the development of bronchopulmonary dysplasia. Effective use of noninvasive respiratory support reduces the risk of lung injury. Lung volume recruitment and avoidance of excessive tidal volume are key elements of lung-protective ventilation strategies. Avoidance of oxidative stress, less invasive methods of surfactant administration, and high-frequency ventilation are also important factors in lung injury prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Feasibility of an eight-week outpatient-based pulmonary rehabilitation program for advanced lung cancer patients undergoing cytotoxic chemotherapy in Korea.

PubMed

Park, Young Sik; Lee, Jinwoo; Keum, Bhumsuk; Oh, Byung-Mo

2018-06-22

The scientific evidence supporting pulmonary rehabilitation (PR) for lung cancer patients undergoing cytotoxic chemotherapy is accumulating; however, the feasibility of outpatient-based PR in these patients has not yet been evaluated in Korea. We conducted an eight-week outpatient-based PR feasibility study in a tertiary referral hospital setting. Patients with advanced lung cancer (non-small cell lung cancer IIIB-IV and small-cell lung cancer extensive disease) scheduled to undergo first-line cytotoxic chemotherapy underwent PR consisting of 60-minute sessions twice a week under the guidance and supervision of a physical therapist, for a total of eight weeks. Feasibility was assessed based on completion of the PR program. In total, 12 patients (median age 68 years) were enrolled; 11 (91.7%) were male with a history of smoking. Among these 12 patients, 9 (75%) completed the eight-week outpatient-based PR program. Three patients could not complete the PR program: two were unwilling and one died from complications of lung cancer. This study showed a 75% completion rate of an eight-week outpatient-based PR program for advanced lung cancer patients undergoing cytotoxic chemotherapy, which supports its feasibility. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Society of Behavioral Medicine supports implementation of high quality lung cancer screening in high-risk populations.

PubMed

Watson, Karriem S; Blok, Amanda C; Buscemi, Joanna; Molina, Yamile; Fitzgibbon, Marian; Simon, Melissa A; Williams, Lance; Matthews, Kameron; Studts, Jamie L; Lillie, Sarah E; Ostroff, Jamie S; Carter-Harris, Lisa; Winn, Robert A

2016-12-01

The Society of Behavioral Medicine (SBM) supports the United States Preventive Services Task Force (USPSTF) recommendation of low-dose computed tomography (LDCT) screening of the chest for eligible populations to reduce lung cancer mortality. Consistent with efforts to translate research findings into real-world settings, SBM encourages health-care providers and health-care systems to (1) integrate evidence-based tobacco treatment as an essential component of LDCT-based lung cancer screening, (2) examine the structural barriers that may impact screening uptake, and (3) incorporate shared decision-making as a clinical platform to facilitate consultations and engagement with individuals at high risk for lung cancer about the potential benefits and harms associated with participation in a lung cancer screening program. We advise policy makers and legislators to support screening in high-risk populations by continuing to (1) expand access to high quality LDCT-based screening among underserved high-risk populations, (2) enhance cost-effectiveness by integrating evidence-based tobacco treatments into screening in high-risk populations, and (3) increase funding for research that explores implementation science and increased public awareness and access of diverse populations to participate in clinical and translational research.

Application of a High Throughput Method of Biomarker Discovery to Improvement of the EarlyCDT®-Lung Test

PubMed Central

Macdonald, Isabel K.; Murray, Andrea; Healey, Graham F.; Parsy-Kowalska, Celine B.; Allen, Jared; McElveen, Jane; Robertson, Chris; Sewell, Herbert F.; Chapman, Caroline J.; Robertson, John F. R.

2012-01-01

Background The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung) to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT. Recent advances in high throughput (HTP) cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV)). Methods and Findings Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165). Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7). Conclusion This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT­-Lung test, and so further aid the early detection of lung cancer. PMID:23272083

WE-D-207-01: Background and Clinical Implementation of a Screening Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aberle, D.

2015-06-15

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancermore » Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in implementing Lung Cancer Screening protocols for CT, including utilizing resources such as the AAPM Protocols and the ACR Designated Lung Screening Center program. UCLA Department of Radiology has an Institutional research agreement with Siemens Healthcare; Dr. McNitt-Gray has been a recipient of Research Support from Siemens Healthcare in the past. Dr. Aberle has been a Member of Advisory Boards for the LUNGevity Foundation (2011-present) and Siemens Medical Solutions. (2013)« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancermore » Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in implementing Lung Cancer Screening protocols for CT, including utilizing resources such as the AAPM Protocols and the ACR Designated Lung Screening Center program. UCLA Department of Radiology has an Institutional research agreement with Siemens Healthcare; Dr. McNitt-Gray has been a recipient of Research Support from Siemens Healthcare in the past. Dr. Aberle has been a Member of Advisory Boards for the LUNGevity Foundation (2011-present) and Siemens Medical Solutions. (2013)« less

Optical medical imaging: from glass to man

NASA Astrophysics Data System (ADS)

Bradley, Mark

2016-11-01

A formidable challenge in modern respiratory healthcare is the accurate and timely diagnosis of lung infection and inflammation. The EPSRC Interdisciplinary Research Collaboration (IRC) `Proteus' seeks to address this challenge by developing an optical fibre based healthcare technology platform that combines physiological sensing with multiplexed optical molecular imaging. This technology will enable in situ measurements deep in the human lung allowing the assessment of tissue function and characterization of the unique signatures of pulmonary disease and is illustrated here with our in-man application of Optical Imaging SmartProbes and our first device Versicolour.

High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

PubMed

Ocak, S; Sos, M L; Thomas, R K; Massion, P P

2009-08-01

During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

Hyperpolarized 129Xe MRI of the Human Lung

PubMed Central

Mugler, John P.; Altes, Talissa A.

2012-01-01

By permitting direct visualization of the airspaces of the lung, MR imaging using hyperpolarized gases provides unique strategies for evaluating pulmonary structure and function. Although the vast majority of research in humans has been performed using hyperpolarized 3He, recent contraction in the supply of 3He and consequent increases in price have turned attention to the alternative agent, hyperpolarized 129Xe. Compared to 3He, 129Xe yields reduced signal due to its smaller magnetic moment. Nonetheless, taking advantage of advances in gas-polarization technology, recent studies in humans using techniques for measuring ventilation, diffusion, and partial pressure of oxygen have demonstrated results for hyperpolarized 129Xe comparable to those previously demonstrated using hyperpolarized 3He. In addition, xenon has the advantage of readily dissolving in lung tissue and blood following inhalation, which makes hyperpolarized 129Xe particularly attractive for exploring certain characteristics of lung function, such as gas exchange and uptake, which cannot be accessed using 3He. Preliminary results from methods for imaging 129Xe dissolved in the human lung suggest that these approaches will provide new opportunities for quantifying relationships among gas delivery, exchange, and transport, and thus show substantial potential to broaden our understanding of lung disease. Finally, recent changes in the commercial landscape of the hyperpolarized-gas field now make it possible for this innovative technology to move beyond the research lab. PMID:23355432

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Joe Y., E-mail: jychang@mdanderson.org; Jabbour, Salma K.; De Ruysscher, Dirk

Radiation dose escalation has been shown to improve local control and survival in patients with non–small cell lung cancer in some studies, but randomized data have not supported this premise, possibly owing to adverse effects. Because of the physical characteristics of the Bragg peak, proton therapy (PT) delivers minimal exit dose distal to the target volume, resulting in better sparing of normal tissues in comparison to photon-based radiation therapy. This is particularly important for lung cancer given the proximity of the lung, heart, esophagus, major airways, large blood vessels, and spinal cord. However, PT is associated with more uncertainty becausemore » of the finite range of the proton beam and motion for thoracic cancers. PT is more costly than traditional photon therapy but may reduce side effects and toxicity-related hospitalization, which has its own associated cost. The cost of PT is decreasing over time because of reduced prices for the building, machine, maintenance, and overhead, as well as newer, shorter treatment programs. PT is improving rapidly as more research is performed particularly with the implementation of 4-dimensional computed tomography–based motion management and intensity modulated PT. Given these controversies, there is much debate in the oncology community about which patients with lung cancer benefit significantly from PT. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group intends to address the issues of PT indications, advantages and limitations, cost-effectiveness, technology improvement, clinical trials, and future research directions. This consensus report can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions.« less

Bronchiectasis

MedlinePlus

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The roles of diol epoxide and o-quinone pathways in mouse lung tumorigenesis induced by benzo(a)pyrene: relevance to human lung carcinogenesis

EPA Science Inventory

There is sufficient epidemiological evidence supported by experimental data that some PAH-containing complex environmental mixtures pose risks to human health by increasing lung cancer incidence. The International Agency for Research on Cancer has determined that human respirator...

Acute Bronchitis

MedlinePlus

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Cystic Fibrosis

MedlinePlus

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Influence of quartz exposure on lung cancer types in cases of lymph node-only silicosis and lung silicosis in German uranium miners.

PubMed

Mielke, Stefan; Taeger, Dirk; Weitmann, Kerstin; Brüning, Thomas; Hoffmann, Wolfgang

2018-05-04

Inhaled crystalline quartz is a carcinogen. Analyses show differences in the distribution of lung cancer types depending on the status of silicosis. Using 2,524 lung tumor cases from the WISMUT autopsy repository database, silicosis was differentiated into cases without silicosis in lung parenchyma and its lymph nodes, with lymph node-only silicosis, or with lung silicosis including lymph node silicosis. The proportions of adenocarcinoma, squamous cell carcinoma, and small-cell lung carcinoma mortality for increasing quartz exposures were estimated in a multinomial logistic regression model. The relative proportions of the lung cancer subtypes in lymph node-only silicosis were more similar to lung silicosis than without any silicosis. The results support the hypothesis that quartz-related carcinogenesis in case of lymph node-only silicosis is more similar to that in lung silicosis than in without silicosis.

Work of breathing using different interfaces in spontaneous positive pressure ventilation: helmet, face-mask, and endotracheal tube.

PubMed

Oda, Shinya; Otaki, Kei; Yashima, Nozomi; Kurota, Misato; Matsushita, Sachiko; Kumasaka, Airi; Kurihara, Hutaba; Kawamae, Kaneyuki

2016-08-01

Noninvasive positive pressure ventilation (NPPV) using a helmet is expected to cause inspiratory trigger delay due to the large collapsible and compliant chamber. We compared the work of breathing (WOB) of NPPV using a helmet or a full face-mask with that of invasive ventilation by tracheal intubation. We used a lung model capable of simulating spontaneous breathing (LUNGOO; Air Water Inc., Japan). LUNGOO was set at compliance (C) = 50 mL/cmH2O and resistance (R) = 5 cmH2O/L/s for normal lung simulation, C = 20 mL/cmH2O and R = 5 cmH2O/L/s for restrictive lung, and C = 50 mL/cmH2O and R = 20 cmH2O/L/s for obstructive lung. Muscle pressure was fixed at 25 cmH2O and respiratory rate at 20 bpm. Pressure support ventilation and continuous positive airway pressure were performed with each interface placed on a dummy head made of reinforced plastic that was connected to LUNGOO. We tested the inspiratory WOB difference between the interfaces with various combinations of ventilator settings (positive end-expiratory pressure 5 cmH2O; pressure support 0, 5, and 10 cmH2O). In the normal lung and restrictive lung models, WOB decreased more with the face-mask than the helmet, especially when accompanied by the level of pressure support. In the obstructive lung model, WOB with the helmet decreased compared with the other two interfaces. In the mixed lung model, there were no significant differences in WOB between the three interfaces. NPPV using a helmet is more effective than the other interfaces for WOB in obstructive lung disease.

Bone Talk: Activated Osteoblasts Promote Lung Cancer Growth.

PubMed

Bružas, Emilis; Egeblad, Mikala

2018-03-01

Cancer cells can directly stimulate the generation and recruitment of tumor-supportive bone marrow-derived cells (BMDCs), including neutrophils, via secreted factors. A new study demonstrates that lung tumors also remotely activate bone-residing osteoblasts, which in turn promote neutrophil production. This is a multistep mechanism of establishing a supportive tumor microenvironment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comprehensive profiling and quantitation of oncogenic mutations in non-small cell lung carcinoma using single-molecule amplification and re-sequencing technology.

PubMed

Shi, Jian; Yuan, Meng; Wang, Zhan-Dong; Xu, Xiao-Li; Hong, Lei; Sun, Shenglin

2017-02-01

The carcinogenesis of non-small cell lung carcinoma has been found to associate with activating and resistant mutations in the tyrosine kinase domain of specific oncogenes. Here, we assessed the type, frequency, and abundance of epithelial growth factor receptor, KRAS, BRAF, and ALK mutations in 154 non-small cell lung carcinoma specimens using single-molecule amplification and re-sequencing technology. We found that epithelial growth factor receptor mutations were the most prevalent (44.2%), followed by KRAS (18.8%), ALK (7.8%), and BRAF (5.8%) mutations. The type and abundance of the mutations in tumor specimens appeared to be heterogeneous. Thus, we conclude that identification of clinically significant oncogenic mutations may improve the classification of patients and provide valuable information for determination of the therapeutic strategies.

WE-D-207-03: CT Protocols for Screening and the ACR Designated Lung Screening Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNitt-Gray, M.

2015-06-15

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancermore » Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. To understand the role of the medical physicist in implementing Lung Cancer Screening protocols for CT, including utilizing resources such as the AAPM Protocols and the ACR Designated Lung Screening Center program. UCLA Department of Radiology has an Institutional research agreement with Siemens Healthcare; Dr. McNitt-Gray has been a recipient of Research Support from Siemens Healthcare in the past. Dr. Aberle has been a Member of Advisory Boards for the LUNGevity Foundation (2011-present) and Siemens Medical Solutions. (2013)« less

Clinical applications of The Cancer Genome Atlas project (TCGA) for squamous cell lung carcinoma.

PubMed

Devarakonda, Siddhartha; Morgensztern, Daniel; Govindan, Ramaswamy

2013-09-01

Very little progress has been made in the treatment of patients with metastatic squamous cell lung cancer over the past 2 decades. Identification of novel molecular alterations for targeted therapies is necessary to improve outcomes. Advances in genomic technology have now made it possible to analyze the genomic landscape of tumor tissues comprehensively. We summarize here key findings from the comprehensive analysis of squamous cell lung cancer by The Cancer Genome Atlas group and discuss the clinical implications of these findings.

Mechanical ventilation strategies.

PubMed

Keszler, Martin

2017-08-01

Although only a small proportion of full term and late preterm infants require invasive respiratory support, they are not immune from ventilator-associated lung injury. The process of lung damage from mechanical ventilation is multifactorial and cannot be linked to any single variable. Atelectrauma and volutrauma have been identified as the most important and potentially preventable elements of lung injury. Respiratory support strategies for full term and late preterm infants have not been as thoroughly studied as those for preterm infants; consequently, a strong evidence base on which to make recommendations is lacking. The choice of modalities of support and ventilation strategies should be guided by the specific underlying pathophysiologic considerations and the ventilatory approach must be individualized for each patient based on the predominant pathophysiology at the time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Introduction to Pulmonary Fibrosis

MedlinePlus

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Perfluorodecalin lavage of a longstanding lung atelectasis in a child with spinal muscle atrophy.

PubMed

Henrichsen, Thore; Lindenskov, Paal H H; Shaffer, Thomas H; Loekke, Ruth J V; Fugelseth, Drude; Lindemann, Rolf

2012-04-01

Persistent lung atelectasis is difficult to treat and perfluorochemical (PFC) liquid may be an option for bronchioalveolar lavage (BAL). A 4-year-old girl with spinal muscle atrophy was admitted in respiratory failure. On admission, the X-ray confirmed the persistence of total right-sided lung atelectasis, which had been present for 14 months. She was endotracheally intubated and ventilated from the day of admission. BAL with normal saline was performed twice without improvement. Following failed extubation and being dependent on continuous respiratory support, a trial of BAL using PFC liquid (Perfluorodecalin HP) was carried out. The PFC was delivered through the endotracheal tube on three consecutive days. A loading dose of 3 ml/kg was administered, followed by a varying dose in order to more effectively lavage the lungs. She tolerated the procedure well the first 2 days, although there were no clinical signs of improvement in the atelectasis. Intentionally, higher inflation pressures were applied after PFC instillation on day 3. Chest X-ray then showed hazy infiltrates on her left lung and she required more ventilatory support. However, lung infiltrates cleared over the next 3 days. A tracheotomy was done 6 days after the last PFC instillation. She had a slow recovery and was successfully decanulated. Clinical improvement of lung function was seen including less need of BiPAP and oxygen. A chest CT scan showed then functional lung tissue appearing in the previous total atelectatic right lung. Lavage with PFC can safely be performed with a therapeutic effect in a child with unilateral total lung atelectasis. Copyright © 2011 Wiley Periodicals, Inc.

Bilateral versus single lung transplant for idiopathic pulmonary fibrosis.

PubMed

Lehmann, Sven; Uhlemann, Madlen; Leontyev, Sergey; Seeburger, Joerg; Garbade, Jens; Merk, Denis R; Bittner, Hartmuth B; Mohr, Friedrich W

2014-10-01

It is unknown if uni- or bilateral lung transplant is best for treatment of usual idiopathic pulmonary fibrosis. We reviewed our single-center experience comparing both treatments. Between 2002 and 2011, one hundred thirty-eight patients at our institution underwent a lung transplant. Of these, 58 patients presented with idiopathic pulmonary fibrosis (56.9%) and were the focus of this study. Thirty-nine patients received a single lung transplant and 19 patients a bilateral sequential lung transplant. The mean patient age was 54 ± 10 years, and 69% were male. The intraoperative course was uneventful, save for 7 patients who needed extracorporeal membrane oxygenation support. Three patients had respiratory failure before the lung transplant that required mechanical ventilation and was supported by extracorporeal membrane oxygenation. Elevated pulmonary artery pressure > 40 mm Hg was identified as an independent predictor of early mortality by uni- and multivariate analysis (P = .01; OR 9.7). Using a Cox regression analysis, postoperative extracorporeal membrane oxyge-nation therapy (P = .01; OR 10.2) and the need for > 10 red blood cell concentrate during the first 72 hours after lung transplant (P = .01; OR 5.6) were independent predictors of long-term survival. Actuarial survival at 1 and 5 years was 65.6% and 55.3%, with no significant between-group differences (70.6% and 54.3%). Lung transplant is a safe and curative treatment for idiopathic pulmonary fibrosis. According to our results, unilateral lung transplant for idiopathic pulmonary fibrosis is an alternative to bilateral lung transplant and may affect the allocation process.

Resource utilization and costs during the initial years of lung cancer screening with computed tomography in Canada.

PubMed

Cressman, Sonya; Lam, Stephen; Tammemagi, Martin C; Evans, William K; Leighl, Natasha B; Regier, Dean A; Bolbocean, Corneliu; Shepherd, Frances A; Tsao, Ming-Sound; Manos, Daria; Liu, Geoffrey; Atkar-Khattra, Sukhinder; Cromwell, Ian; Johnston, Michael R; Mayo, John R; McWilliams, Annette; Couture, Christian; English, John C; Goffin, John; Hwang, David M; Puksa, Serge; Roberts, Heidi; Tremblay, Alain; MacEachern, Paul; Burrowes, Paul; Bhatia, Rick; Finley, Richard J; Goss, Glenwood D; Nicholas, Garth; Seely, Jean M; Sekhon, Harmanjatinder S; Yee, John; Amjadi, Kayvan; Cutz, Jean-Claude; Ionescu, Diana N; Yasufuku, Kazuhiro; Martel, Simon; Soghrati, Kamyar; Sin, Don D; Tan, Wan C; Urbanski, Stefan; Xu, Zhaolin; Peacock, Stuart J

2014-10-01

It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer's perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. The average per-person cost for screening individuals with LDCT was $453 (95% confidence interval [CI], $400-$505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was $33,344 (95% CI, $31,553-$34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, ($47,792; 95% CI, $43,254-$52,200; p = 0.061). In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure.

Extracorporeal life support in lung and heart-lung transplantation for pulmonary hypertension in adults.

PubMed

Kortchinsky, Talna; Mussot, Sacha; Rezaiguia, Saïda; Artiguenave, Margaux; Fadel, Elie; Stephan, François

2016-09-01

After bilateral lung and heart-lung transplantation in adults with pulmonary hypertension, hemodynamic and oxygenation deficiencies are life-threatening complications that are increasingly managed with extracorporeal life support (ECLS). The primary aim of this retrospective study was to assess 30-day and 1-year survival rates in patients managed with vs without post-operative venoarterial ECLS in 2008-2013. The secondary endpoints were the occurrence rates of nosocomial infection, bleeding, and acute renal failure. Of the 93 patients with pulmonary hypertension who received heart-lung (n=29) or bilateral lung (n=64) transplants, 28 (30%) required ECLS a median of 0 [0-6] hours after surgery completion and for a median of 3.0 [2.0-8.5] days. Compared to ECLS patients, controls had higher survival at 30 days (95.0% vs 78.5%; P=.02) and 1 year (83% vs 64%; P=.005), fewer nosocomial infections (48% vs 79%; P=.0006), and fewer bleeding events (17% vs 43%; P=.008). The need for renal replacement therapy was not different between groups (11% vs 17%; P=.54). Venoarterial ECLS is effective in treating pulmonary graft dysfunction with hemodynamic failure after heart-lung or bilateral lung. However, ECLS use was associated with higher rates of infection and bleeding. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Post-mortem CT: Hounsfield unit profiles obtained in the lungs with respect to the cause of death assessment.

PubMed

Schober, Daniel; Schwendener, Nicole; Zech, Wolf-Dieter; Jackowski, Christian

2017-01-01

Segmentation of the lungs using post-mortem computed tomography (PMCT) data was so far not feasible due to post-mortem changes such as internal livores. Recently, an Osirix plug-in has been developed allowing automatically segmenting lungs also in PMCT data. The aim of this study was to investigate if the Hounsfield unit (HU) profiles obtained in PMCT data of the segmented lung tissue present with specific behaviour in relation to the cause of death. In 105 PMCT data sets of forensic cases, the entire lung volumes were segmented using the Mia Lite plug-in on Osirix. HU profiles of the lungs were generated and correlated to cause of death groups as assessed after forensic autopsy (cardiac death, fatal haemorrhage, craniocerebral injury, intoxication, drowning, hypothermia, hanging and suffocation). Especially cardiac death cases, intoxication cases, fatal haemorrhage cases and hypothermia cases showed very specific HU profiles. In drowning, the profiles showed two different behaviours representing wet and dry drowning. HU profiles rather varied in craniocerebral injury cases, hanging cases as well as in suffocation cases. HU profiles of the lungs segmented from PMCT data may support the cause of death diagnosis as they represent specific morphological changes in the lungs such as oedema, congestion or blood loss. Especially in cardiac death, intoxication, fatal haemorrhage, hypothermia and drowning cases, HU profiles may be very supportive for the forensic pathologist.

Beta-cryptoxanthin reduced lung tumor multiplicity and inhibited lung cancer cell motility by downregulating nicotinic acetylcholine receptor alpha7 signaling

USDA-ARS?s Scientific Manuscript database

Despite the consistent association between a higher intake of the provitamin A carotenoid beta-cryptoxanthin (BCX) and a lower risk of lung cancer among smokers, potential mechanisms supporting BCX as a chemopreventive agent are needed. We first examined the effects of BCX on 4-[methyl nitrosamino]-...

Advances in combination therapy of lung cancer: Rationales, delivery technologies and dosage regimens.

PubMed

Wu, Lan; Leng, Donglei; Cun, Dongmei; Foged, Camilla; Yang, Mingshi

2017-08-28

Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i.e. how administration routes, onsets, and durations of the combinations influence the therapeutic outcome. This is partly because combination therapy is challenged by distinct physicochemical properties and in vivo pharmacokinetics/pharmacodynamics of the individual pharmaceuticals, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Pulmonary adenocarcinoma: A renewed entity in 2011

PubMed Central

Kadara, Humam; Kabbout, Mohamed; Wistuba, Ignacio I.

2014-01-01

Lung cancer, of which non-small-cell lung cancer comprises the majority, is the leading cause of cancer-related deaths in the United States and worldwide. Lung adenocarcinomas are a major subtype of non-small-cell lung cancers, are increasing in incidence globally in both males and females and in smokers and non-smokers, and are the cause for almost 50% of deaths attributable to lung cancer. Lung adenocarcinoma is a tumour with complex biology that we have recently started to understand with the advent of various histological, transcriptomic, genomic and proteomic technologies. However, the histological and molecular pathogenesis of this malignancy is still largely unknown. This review will describe advances in the molecular pathology of lung adenocarcinoma with emphasis on genomics and DNA alterations of this disease. Moreover, the review will discuss recognized lung adenocarcinoma preneoplastic lesions and current concepts of the early pathogenesis and progression of the disease. We will also portray the field cancerization phenomenon and lineage-specific oncogene expression pattern in lung cancer and how both remerging concepts can be exploited to increase our understanding of lung adenocarcinoma pathogenesis for subsequent development of biomarkers for early detection of adenocarcinomas and possibly personalized prevention. PMID:22040022

Acute Respiratory Distress Syndrome (ARDS)

MedlinePlus

... Contact Us Corporate Ethics Reporting OUR INITIATIVES LUNG FORCE Saved By The Scan Research Healthy Air Tobacco ... Sponsors & Supporters Careers Contact Us OUR INITIATIVES LUNG FORCE Saved By The Scan Research Healthy Air Tobacco ...

Emphysema (image)

MedlinePlus

Emphysema is a lung disease involving damage to the air sacs (alveoli). There is progressive destruction of alveoli and the surrounding tissue that supports the alveoli. With more advanced disease, large air cysts develop where normal lung ...

76 FR 64360 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... Institute Special Emphasis Panel, Virtual Reality Technologies for Research and Education in Obesity and..., Virtual Reality Technologies for Research and Education in Obesity and Diabetes. Date: November 7, 2011...

Extracorporeal membrane oxygenation

MedlinePlus

ECMO; Heart-lung bypass - infants; Bypass - infants; Neonatal hypoxia - ECMO; PPHN - ECMO; Meconium aspiration - ECMO; MAS - ECMO ... back into the bloodstream of a very ill baby. This system provides heart-lung bypass support outside of the baby's body. ...

Developing Physiologic Models for Emergency Medical Procedures Under Microgravity

NASA Technical Reports Server (NTRS)

Parker, Nigel; O'Quinn, Veronica

2012-01-01

Several technological enhancements have been made to METI's commercial Emergency Care Simulator (ECS) with regard to how microgravity affects human physiology. The ECS uses both a software-only lung simulation, and an integrated mannequin lung that uses a physical lung bag for creating chest excursions, and a digital simulation of lung mechanics and gas exchange. METI s patient simulators incorporate models of human physiology that simulate lung and chest wall mechanics, as well as pulmonary gas exchange. Microgravity affects how O2 and CO2 are exchanged in the lungs. Procedures were also developed to take into affect the Glasgow Coma Scale for determining levels of consciousness by varying the ECS eye-blinking function to partially indicate the level of consciousness of the patient. In addition, the ECS was modified to provide various levels of pulses from weak and thready to hyper-dynamic to assist in assessing patient conditions from the femoral, carotid, brachial, and pedal pulse locations.

Developing Physiologic Models for Emergency Medical Procedures Under Microgravity

NASA Technical Reports Server (NTRS)

Parker, Nigel; OQuinn, Veronica

2012-01-01

Several technological enhancements have been made to METI's commercial Emergency Care Simulator (ECS) with regard to how microgravity affects human physiology. The ECS uses both a software-only lung simulation, and an integrated mannequin lung that uses a physical lung bag for creating chest excursions, and a digital simulation of lung mechanics and gas exchange. METI's patient simulators incorporate models of human physiology that simulate lung and chest wall mechanics, as well as pulmonary gas exchange. Microgravity affects how O2 and CO2 are exchanged in the lungs. Procedures were also developed to take into affect the Glasgow Coma Scale for determining levels of consciousness by varying the ECS eye-blinking function to partially indicate the level of consciousness of the patient. In addition, the ECS was modified to provide various levels of pulses from weak and thready to hyper-dynamic to assist in assessing patient conditions from the femoral, carotid, brachial, and pedal pulse locations.

Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology.

PubMed

Speck, Nicole E; Schuurmans, Macé M; Murer, Christian; Benden, Christian; Huber, Lars C

2016-06-21

Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

[Comparative study of protein markers in serum and bronchoalveolar lavage fluid from patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry].

PubMed

Zhou, Ji-hong; Liu, Guang-nan; Huang, Si-ming; Zhong, Xiao-ning; Su, Hong; Zhou, Yi

2011-04-01

To detect the protein markers in serum and bronchoalveolar lavage fluid (BALF) of the patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) technology, and to explore if they can be used as markers for the diagnosis of lung cancer. SELDI-TOF-MS technology and protein chips weak cation exchange (WCX-2 chip) were used to detect the protein mass spectrum in serum and BALF of 35 patients with lung cancer and 18 cases of benign pulmonary diseases. The different protein markers were analyzed by Biomarker Pattern Software and the initial diagnosis models were set up. The diagnosis models were verified further by blind screen to confirm the efficacy of diagnosis. Five protein peaks in the sera of the patients with lung cancer were significantly higher (P < 0.05). The protein peak with a mass/charge ratio (M/Z) of 5639 was selected to establish the classification tree model. The sensitivity of diagnosis was 80% (28/35) and the specificity was 78% (14/18). The results verified by blind screen showed a sensitivity of 85% (17/20), a specificity of 90% (9/10), a crude accuracy (CA) of 87% (26/30) and Youden's index (γ) of 0.7. Eight protein peaks in the BALF of the patients with lung cancer were significantly higher (P < 0.05). The different protein peaks with M/Z of 7976 and 11 809 respectively were selected to establish the classification tree model. The sensitivity of diagnosis was 86% (30/35) and the specificity was 72% (13/18). The results verified by blind screen showed a sensitivity of 90% (18/20), a specificity of 90% (9/10), a CA of 90% (27/30) and γ of 0.8. There was a complementary role in combination of differential proteins in serum and BALF and the sensitivity, specificity and accuracy of diagnosis for lung cancer were 100% by parallel test. The SELDI-TOF-MS technology can screen out the differential protein markers in serum and BALF of the patients with lung cancer, which show high sensitivity and specificity as tumor markers. The differential proteins in the BALF may be more promising for clinical application.

Computer-aided diagnosis for osteoporosis using chest 3D CT images

NASA Astrophysics Data System (ADS)

Yoneda, K.; Matsuhiro, M.; Suzuki, H.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

2016-03-01

The patients of osteoporosis comprised of about 13 million people in Japan and it is one of the problems the aging society has. In order to prevent the osteoporosis, it is necessary to do early detection and treatment. Multi-slice CT technology has been improving the three dimensional (3-D) image analysis with higher body axis resolution and shorter scan time. The 3-D image analysis using multi-slice CT images of thoracic vertebra can be used as a support to diagnose osteoporosis and at the same time can be used for lung cancer diagnosis which may lead to early detection. We develop automatic extraction and partitioning algorithm for spinal column by analyzing vertebral body structure, and the analysis algorithm of the vertebral body using shape analysis and a bone density measurement for the diagnosis of osteoporosis. Osteoporosis diagnosis support system obtained high extraction rate of the thoracic vertebral in both normal and low doses.

Stem cell therapy: the great promise in lung disease.

PubMed

Siniscalco, Dario; Sullo, Nikol; Maione, Sabatino; Rossi, Francesco; D'Agostino, Bruno

2008-06-01

Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions, or idiopathic pulmonary fibrosis characterized by excessive matrix deposition and destruction of the normal lung architecture, have essentially symptomatic treatments and their management is costly to the health care system.Regeneration of tissue by stem cells from endogenous, exogenous, and even genetically modified cells is a promising novel therapy. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension.Therefore, lung stem cell biology may provide novel approaches to therapy and could represent a great promise for the future of molecular medicine. In fact, several diseases can be slowed or even blocked by stem cell transplantation.

[Criteria of the molecular pathology testing of lung cancer].

PubMed

Tímár, József

2014-06-01

From the aspect of the contemporary pathologic diagnostics of lung cancer the tissue obtained is a key issue since small biopsies and cytology still play a major role. In the non-small cell lung cancer era cytology is considered equal to biopsy however, in recent years it is unable to provide quality diagnosis and must be replaced by biopsy. Various molecular techniques can handle various different tissue samples which must be considered during molecular pathology diagnosis. Moreover, tumor cell-normal cell ratio in the obtained tissue, as well as the absolute tumor cell number have great significance, which information must be provided in the primary lung cancer diagnosis. Last but not least, for continuous sustainable molecular diagnostics of lung cancer rational algorithms, affordable technology and appropriate reimbursement are equally necessary.

Minimal requirements for the molecular testing of lung cancer.

PubMed

Popper, Helmut H; Tímár, József; Ryska, Ales; Olszewski, Wlodzimierz

2014-10-01

From the aspect of the contemporary pathologic diagnostics of lung cancer, it is a key issue of the tissue obtained since small biopsies and cytology still play a major role. In the non-small cell lung cancer era, cytology considered equal to biopsy. However, in recent years it is unable to provide quality diagnosis and must be replaced by biopsy. Various molecular techniques can handle various different tissue samples which must be considered during molecular pathology diagnosis. Besides, tumor cell-normal cell ratio in the obtained tissue as well as the absolute tumor cell number have great significance whose information must be provided in the primary lung cancer diagnosis. Last but not least, for continuous sustainable molecular diagnostics of lung cancer rational algorythms, affordable technology and appropriate reimbursement are equally necessary.

Metachronous and Synchronous Presentation of Acute Myeloid Leukemia and Lung Cancer

PubMed Central

Varadarajan, Ramya; Ford, LaurieAnn; Sait, Sheila NJ; Block, AnneMarie W.; Barcos, Maurice; Wallace, Paul K.; Ramnath, Nithya; Wang, Eunice S.; Wetzler, Meir

2009-01-01

Smoking is associated with both acute myeloid leukemia (AML) and lung cancer. We therefore searched our database for concomitant presentation of AML and lung cancer. Among 775 AML cases and 5225 lung cancer cases presenting to Roswell Park Cancer Institute between the years January 1992 and May 2008 we found 12 (1.5% of AML cases; 0.23% of lung cancer cases) cases (seven metachronous and five synchronous) with AML and lung cancer. All but one patient were smokers. There were no unique characteristic of either AML or lung cancer in these patients. Nine patients succumbed to AML, one died from an unrelated cause while undergoing treatment for AML, one died of lung cancer and one patient is alive after allogeneic transplantation for AML. In summary, this study supports the need for effective smoking cessation programs. PMID:19181380

The role of the occupational therapist in the care of people living with lung cancer.

PubMed

White, Kahren M

2016-06-01

This paper aims to explore the vital role occupational therapists play in enabling people living with lung cancer to continue to actively live. Core assessments and interventions employed by occupational therapists are described in a case study. It will demonstrate how people living with lung cancer can continue to participate in meaningful and chosen life roles, even in the face of functional decline. Skilled management by the occupational therapist of the refractory symptoms of advanced lung cancer supports this participation.

Frontiers in planning optimization for lung SBRT.

PubMed

Giglioli, Francesca Romana; Clemente, Stefania; Esposito, Marco; Fiandra, Christian; Marino, Carmelo; Russo, Serenella; Strigari, Lidia; Villaggi, Elena; Stasi, Michele; Mancosu, Pietro

2017-12-01

Emerging data are showing the safety and the efficacy of Stereotactic Body Radiation therapy (SBRT) in lung cancer management. In this context, the very high doses delivered to the Planning Target Volume, make the planning phase essential for achieving high dose levels conformed to the shape of the target in order to have a good prognosis for tumor control and to avoid an overdose in relevant healthy adjacent tissue. In this non-systematic review we analyzed the technological and the physics aspects of SBRT planning for lung cancer. In particular, the aims of the study were: (i) to evaluate prescription strategies (homogeneous or inhomogeneous), (ii) to outline possible geometrical solutions by comparing the dosimetric results (iii) to describe the technological possibilities for a safe and effective treatment, (iv) to present the issues concerning radiobiological planning and the automation of the planning process. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

About the Lung and Upper Aerodigestive Cancer Research Group | Division of Cancer Prevention

Cancer.gov

The Lung and Upper Aerodigestive Cancer Research Group conducts and supports research on the prevention and early detection of lung and head and neck cancers, as well as new approaches to clinical prevention studies including cancer immunoprevention.Phase 0/I/II Cancer Prevention Clinical Trials ProgramThe group jointly administers the Phase 0/I/II Cancer Prevention Clinical

Comparative Effectiveness Research in Lung Diseases and Sleep Disorders

PubMed Central

Lieu, Tracy A.; Au, David; Krishnan, Jerry A.; Moss, Marc; Selker, Harry; Harabin, Andrea; Connors, Alfred

2011-01-01

The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed. PMID:21965016

LONG-TERM MECHANICAL CIRCULATORY SUPPORT (DESTINATION THERAPY): ON TRACK TO COMPETE WITH HEART TRANSPLANTATIO?

PubMed Central

Kirklin, James K.; Naftel, David C.; Pagani, Francis D.; Kormos, Robert L.; Stevenson, Lynne; Miller, Marissa; Young, James B.

2012-01-01

Objective(s) Average two-year survival following cardiac transplantation is approximately 80%. The evolution and subsequent approval of larger pulsatile and, more recently, continuous flow mechanical circulatory support (MCS) technology for destination therapy (DT) offers the potential for triage of some patients awaiting cardiac transplantation to DT. Methods The National Heart, Lung and Blood Institute Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a national multi-institutional study of chronic mechanical circulatory support. Between June 2006 and December 2011, 127 pulsatile and 1160 continuous flow pumps (24% of total primary LVADs) carried an initial strategy of DT therapy. Results By multivariable analysis, risk factors (p<0.05) for mortality following DT included older age, larger body mass index, history of cancer, history of cardiac surgery, INTERMACS level I (cardiogenic shock), dialysis, increased BUN, use of a pulsatile flow device and use of a RVAD. Among continuous flow LVAD patients who were not in cardiogenic shock, a particularly favorable survival was associated with no cancer, patients not in cardiogenic shock, and BUN < 50, resulting in one and two year survival of 88 and 80%. Conclusions 1) Evolution from pulsatile to continuous flow technology has dramatically improved one and two year survival; 2) Destination Therapy is not appropriate for patients with rapid hemodynamic deterioration; or severe right ventricular failure 4) Important subsets of continuous flow DT patients now enjoy survival which is competitive with heart transplantation out to about two years. PMID:22795459

Smart Technology in Lung Disease Clinical Trials.

PubMed

Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

2016-01-01

This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. Published by Elsevier Inc.

Extracellular matrix in lung development, homeostasis and disease

DOE PAGES

Zhou, Yong; Horowitz, Jeffrey C.; Naba, Alexandra; ...

2018-03-08

Here, the lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECMmore » in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.« less

Extracellular matrix in lung development, homeostasis and disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Yong; Horowitz, Jeffrey C.; Naba, Alexandra

Here, the lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this review, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECMmore » in normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. We identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.« less

Extracellular matrix in lung development, homeostasis and disease

DOE PAGES

Zhou, Yong; Horowitz, Jeffrey C.; Naba, Alexandra; ...

2018-03-08

The lung's unique extracellular matrix (ECM), while providing structural support for cells, is critical in the regulation of developmental organogenesis, homeostasis and injury-repair responses. The ECM, via biochemical or biomechanical cues, regulates diverse cell functions, fate and phenotype. The composition and function of lung ECM become markedly deranged in pathological tissue remodeling. ECM-based therapeutics and bioengineering approaches represent promising novel strategies for regeneration/repair of the lung and treatment of chronic lung diseases. In this paper, we assess the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM inmore » normal and aberrant lung development, adult lung diseases and autoimmunity; and ECM in the regulation of the stem cell niche. Finally, we identify opportunities to advance the field of lung ECM biology and provide a set recommendations for research priorities to advance knowledge that would inform novel approaches to the pathogenesis, diagnosis, and treatment of chronic lung diseases.« less

Impact of Transcriptomics on Our Understanding of Pulmonary Fibrosis

PubMed Central

Vukmirovic, Milica; Kaminski, Naftali

2018-01-01

Idiopathic pulmonary fibrosis (IPF) is a lethal fibrotic lung disease characterized by aberrant remodeling of the lung parenchyma with extensive changes to the phenotypes of all lung resident cells. The introduction of transcriptomics, genome scale profiling of thousands of RNA transcripts, caused a significant inversion in IPF research. Instead of generating hypotheses based on animal models of disease, or biological plausibility, with limited validation in humans, investigators were able to generate hypotheses based on unbiased molecular analysis of human samples and then use animal models of disease to test their hypotheses. In this review, we describe the insights made from transcriptomic analysis of human IPF samples. We describe how transcriptomic studies led to identification of novel genes and pathways involved in the human IPF lung such as: matrix metalloproteinases, WNT pathway, epithelial genes, role of microRNAs among others, as well as conceptual insights such as the involvement of developmental pathways and deep shifts in epithelial and fibroblast phenotypes. The impact of lung and transcriptomic studies on disease classification, endotype discovery, and reproducible biomarkers is also described in detail. Despite these impressive achievements, the impact of transcriptomic studies has been limited because they analyzed bulk tissue and did not address the cellular and spatial heterogeneity of the IPF lung. We discuss new emerging technologies and applications, such as single-cell RNAseq and microenvironment analysis that may address cellular and spatial heterogeneity. We end by making the point that most current tissue collections and resources are not amenable to analysis using the novel technologies. To take advantage of the new opportunities, we need new efforts of sample collections, this time focused on access to all the microenvironments and cells in the IPF lung. PMID:29670881

Lung Transplantation From Donors After Previous Cardiac Surgery: Ideal Graft in Marginal Donor?

PubMed

Palleschi, A; Mendogni, P; Tosi, D; Montoli, M; Carrinola, R; Mariolo, A V; Briganti, F; Nosotti, M

2017-05-01

Lung transplantation is a limited by donor pool shortage. Despite the efforts to extend the graft acceptability with recurrent donor criteria reformulations, previous cardiothoracic surgery is still considered a contraindication. A donor who underwent cardiac surgery could potentially provide an ideal lung but high intraoperative risks and intrinsic technical challenges are expected during the graft harvesting. The purpose of this study is to present our dedicated protocol and four clinical cases of successful lung procurements from donors who had a previous major cardiac surgery. One donor had ascending aortic root (AAR) substitution, another had mitral valve substitution, and two had coronary artery bypass surgery. The others' eligibility criteria for organ allocation, such as ABO compatibility, PaO 2 /FiO 2 ratio, absence of aspiration, or sepsis were respected. In one of the cases with previous coronary bypass grafting, the donor had a veno-arterial extracorporeal membrane oxygenation support. Consequently, the grafts required an ex vivo lung perfusion evaluation. We report the technical details of procurement and postoperative courses of recipients. All procurements were uneventful, without lung damage or waste of abdominal organs related to catastrophic intraoperative events. All recipients had a successful clinical outcome. We believe that successful transplantation is achievable even in a complicated setting, such as cases involving donors with previous cardiac surgery frequently are. Facing lung donor shortage, we strongly support any effort to avoid the loss of possible acceptable lungs. In particular, previous major cardiac surgery does not strictly imply a poor quality of lungs as well as unsustainable graft procurement. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative Biology of Decellularized Lung Matrix: Implications of Species Mismatch in Regenerative Medicine

PubMed Central

Balestrini, Jenna L.; Gard, Ashley L.; Gerhold, Kristin A.; Wilcox, Elise C.; Liu, Angela; Schwan, Jonas; Le, Andrew V.; Baevova, Pavlina; Dimitrievska, Sashka; Zhao, Liping; Sundaram, Sumati; Sun, Huanxing; Rittié, Laure; Dyal, Rachel; Broekelmann, Tom J.; Mecham, Robert P.; Schwartz, Martin A.; Niklason, Laura E.; White, Eric S.

2016-01-01

Lung engineering is a promising technology, relying on re-seeding of either human or xenographic decellularized matrices with patient-derived pulmonary cells. Little is known about the species-specificity of decellularization in various models of lung regeneration, or if species dependent cell-matrix interactions exist within these systems. Therefore decellularized scaffolds were produced from rat, pig, primate and human lungs, and assessed by measuring residual DNA, mechanical properties, and key matrix proteins (collagen, elastin, glycosaminoglycans). To study intrinsic matrix biologic cues, human endothelial cells were seeded onto acellular slices and analyzed for markers of cell health and inflammation. Despite similar levels of collagen after decellularization, human and primate lungs were stiffer, contained more elastin, and retained fewer glycosaminoglycans than pig or rat lung scaffolds. Human endothelial cells seeded onto human and primate lung tissue demonstrated less expression of vascular cell adhesion molecule and activation of nuclear factor-κB compared to those seeded onto rodent or porcine tissue. Adhesion of endothelial cells was markedly enhanced on human and primate tissues. Our work suggests that species-dependent biologic cues intrinsic to lung extracellular matrix could have profound effects on attempts at lung regeneration. PMID:27344365

Towards lung EIT image segmentation: automatic classification of lung tissue state from analysis of EIT monitored recruitment manoeuvres.

PubMed

Grychtol, Bartłomiej; Wolf, Gerhard K; Adler, Andy; Arnold, John H

2010-08-01

There is emerging evidence that the ventilation strategy used in acute lung injury (ALI) makes a significant difference in outcome and that an inappropriate ventilation strategy may produce ventilator-associated lung injury. Most harmful during mechanical ventilation are lung overdistension and lung collapse or atelectasis. Electrical impedance tomography (EIT) as a non-invasive imaging technology may be helpful to identify lung areas at risk. Currently, no automated method is routinely available to identify lung areas that are overdistended, collapsed or ventilated appropriately. We propose a fuzzy logic-based algorithm to analyse EIT images obtained during stepwise changes of mean airway pressures during mechanical ventilation. The algorithm is tested on data from two published studies of stepwise inflation-deflation manoeuvres in an animal model of ALI using conventional and high-frequency oscillatory ventilation. The timing of lung opening and collapsing on segmented images obtained using the algorithm during an inflation-deflation manoeuvre is in agreement with well-known effects of surfactant administration and changes in shunt fraction. While the performance of the algorithm has not been verified against a gold standard, we feel that it presents an important first step in tackling this challenging and important problem.

Occupational risk factors of lung cancer: a hospital based case-control study

PubMed Central

Droste, J. H.; Weyler, J. J.; Van Meerbeeck, J. P.; Vermeire, P. A.; van Sprundel, M. P.

1999-01-01

OBJECTIVES: To investigate the relation between lung cancer and exposure to occupational carcinogens in a highly industrialised region in western Europe. METHODS: In a case-control study 478 cases and 536 controls, recruited from 10 hospitals in the Antwerp region, were interviewed. Cases were male patients with histologically confirmed lung cancer; controls were male patients without cancer or primary lung diseases. Data were collected by questionnaires to obtain information on occupations, exposures, and smoking history. Job titles were coded with the Office of Populations, Censuses and Surveys industrial classification. Exposure was assessed by self report and by job-task exposure matrix. Exposure odds ratios were calculated with logistic regression analysis adjusted for age, smoking history, and marital and socio-economic status. RESULTS: A job history in the categories manufacturing of transport equipment other than automobiles (for example, shipyard workers), transport support services (for example, dockers), and manufacturing of metal goods (for example, welders) was significantly associated with lung cancer (odds ratios (ORs) 2.3, 1.6, and 1.6 respectively). These associations were independent of smoking, education, civil, and economic status. Self reported exposure to potential carcinogens did not show significant associations with lung cancer, probably due to nondifferential misclassification. When assessed by job-task exposure matrix, exposure to molybdenum, mineral oils, and chromium were significantly associated with lung cancer. A strong association existed between smoking and lung cancer: OR of ex- smokers 4.2, OR of current smokers 14.5 v non-smokers. However, smoking did not confound the relation between occupational exposure and lung cancer. CONCLUSIONS: The study has shown a significant excess risk of lung cancer among workers in manufacturing of metal goods, manufacturing of transport equipment (other than automobiles), and transport support services. Assessment of exposure to specific carcinogens resulted in significant associations of chromium, mineral oils, and molybdenum with lung cancer. This study is, to our knowledge, the first study reporting a significant association between occupational exposure to molybdenum and lung cancer.   PMID:10472306

An update on the role of advanced diagnostic bronchoscopy in the evaluation and staging of lung cancer

PubMed Central

Belanger, Adam R.; Akulian, Jason A.

2017-01-01

Lung cancer remains a common and deadly disease. Many modalities are available to the bronchoscopist to evaluate and stage lung cancer. We review the role of bronchoscopy in the staging of the mediastinum with convex endobronchial ultrasound (EBUS) and discuss emerging role of esophageal ultrasonography as a complementary modality. In addition, we discuss advances in scope technology and elastography. We review the bronchoscopic methods available for the diagnosis of peripheral lung nodules including radial EBUS and navigational bronchoscopy (NB) with a consideration of the basic methodologies and diagnostic accuracies. We conclude with a discussion of the comparison of the various methodologies. PMID:28470104

Fifty Years of Research in ARDS. Is Extracorporeal Circulation the Future of Acute Respiratory Distress Syndrome Management?

PubMed

Combes, Alain; Pesenti, Antonio; Ranieri, V Marco

2017-05-01

Mechanical ventilation (MV) remains the cornerstone of acute respiratory distress syndrome (ARDS) management. It guarantees sufficient alveolar ventilation, high Fi O 2 concentration, and high positive end-expiratory pressure levels. However, experimental and clinical studies have accumulated, demonstrating that MV also contributes to the high mortality observed in patients with ARDS by creating ventilator-induced lung injury. Under these circumstances, extracorporeal lung support (ECLS) may be beneficial in two distinct clinical settings: to rescue patients from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV, and to replace MV and minimize/abolish the harmful effects of ventilator-induced lung injury. High extracorporeal blood flow venovenous extracorporeal membrane oxygenation (ECMO) may therefore rescue the sickest patients with ARDS from the high risk for death associated with severe hypoxemia, hypercapnia, or both not responding to maximized conventional MV. Successful venovenous ECMO treatment in patients with extremely severe H1N1-associated ARDS and positive results of the CESAR trial have led to an exponential use of the technology in recent years. Alternatively, lower-flow extracorporeal CO 2 removal devices may be used to reduce the intensity of MV (by reducing Vt from 6 to 3-4 ml/kg) and to minimize or even abolish the harmful effects of ventilator-induced lung injury if used as an alternative to conventional MV in nonintubated, nonsedated, and spontaneously breathing patients. Although conceptually very attractive, the use of ECLS in patients with ARDS remains controversial, and high-quality research is needed to further advance our knowledge in the field.

Biomedical Investigations with Laser-Polarized Noble Gas Magnetic Resonance

NASA Technical Reports Server (NTRS)

Walsworth, Ronald L.

2003-01-01

We pursued advanced technology development of laser-polarized noble gas nuclear magnetic resonance (NMR) as a novel biomedical imaging tool for ground-based and eventually space-based application. This new multidisciplinary technology enables high-resolution gas-space magnetic resonance imaging (MRI)-e.g., of lung ventilation-as well as studies of tissue perfusion. In addition, laser-polarized noble gases (3He and 129Xe) do not require a large magnetic field for sensitive detection, opening the door to practical MRI at very low magnetic fields with an open, lightweight, and low-power device. We pursued two technology development specific aims: (1) development of low-field (less than 0.01 T) noble gas MRI of humans; and (2) development of functional MRI of the lung using laser-polarized noble gas and related techniques.

Respiratory system mechanics in acute respiratory distress syndrome.

PubMed

Kallet, Richard H; Katz, Jeffrey A

2003-09-01

Respiratory mechanics research is important to the advancement of ARDS management. Twenty-eight years ago, research on the effects of PEEP and VT indicated that the lungs of ARDS patients did not behave in a manner consistent with homogenously distributed lung injury. Both Suter and colleagues] and Katz and colleagues reported that oxygenation continued to improve as PEEP increased (suggesting lung recruitment), even though static Crs decreased and dead-space ventilation increased (suggesting concurrent lung overdistension). This research strongly suggested that without VT reduction, the favorable effects of PEEP on lung recruitment are offset by lung overdistension at end-inspiration. The implications of these studies were not fully appreciated at that time, in part because the concept of ventilator-associated lung injury was in its nascent state. Ten years later. Gattinoni and colleagues compared measurements of static pressure-volume curves with FRC and CT scans of the chest in ARDS. They found that although PEEP recruits collapsed (primarily dorsal) lung segments, it simultaneously causes overdistension of non-dependent, inflated lung regions. Furthermore, the specific compliance of the aerated, residually healthy lung tissue is essentially normal. The main implication of these findings is that traditional mechanical ventilation practice was injecting excessive volumes of gas into functionally small lungs. Therefore, the emblematic low static Crs measured in ARDS reflects not only surface tension phenomena and recruitment of collapsed airspaces but also overdistension of the remaining healthy lung. The studies reviewed in this article support the concept that lung injury in ARDS is heterogeneously distributed, with resulting disparate mechanical stresses, and indicate the additional complexity from alterations in chest wall mechanics. Most of these studies, however, were published before lung-protective ventilation. Therefore, further studies are needed to refine the understanding of the mechanical effects of lung-protective ventilation. Although low-VT ventilation is becoming a standard of care for ARDS patients, many issues remain unresolved; among them are the role of PEEP and recruitment maneuvers in either preventing or promoting lung injury and the effects of respiratory rate and graded VT reduction on mechanical stress in the lungs. The authors believe that advances in mechanical ventilation that may further improve patient outcomes are likely to come from more sophisticated monitoring capabilities (ie, the ability to measure P1 or perhaps Cslice) than from the creation of new modes of ventilatory support.

Spontaneously regulated vs. controlled ventilation of acute lung injury/acute respiratory distress syndrome.

PubMed

Marini, John J

2011-02-01

To present an updated discussion of those aspects of controlled positive pressure breathing and retained spontaneous regulation of breathing that impact the management of patients whose tissue oxygenation is compromised by acute lung injury. The recent introduction of ventilation techniques geared toward integrating natural breathing rhythms into even the earliest phase of acute respiratory distress syndrome support (e.g., airway pressure release, proportional assist ventilation, and neurally adjusted ventilatory assist), has stimulated a burst of new investigations. Optimizing gas exchange, avoiding lung injury, and preserving respiratory muscle strength and endurance are vital therapeutic objectives for managing acute lung injury. Accordingly, comparing the physiology and consequences of breathing patterns that preserve and eliminate breathing effort has been a theme of persisting investigative interest throughout the several decades over which it has been possible to sustain cardiopulmonary life support outside the operating theater.

Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases: An NHLBI Resource for the Gene Therapy Community

PubMed Central

Skarlatos, Sonia I.

2012-01-01

Abstract The goals of the National Heart, Lung, and Blood Institute (NHLBI) Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases are to conduct gene transfer studies in monkeys to evaluate safety and efficiency; and to provide NHLBI-supported investigators with expertise, resources, and services to actively pursue gene transfer approaches in monkeys in their research programs. NHLBI-supported projects span investigators throughout the United States and have addressed novel approaches to gene delivery; “proof-of-principle”; assessed whether findings in small-animal models could be demonstrated in a primate species; or were conducted to enable new grant or IND submissions. The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases successfully aids the gene therapy community in addressing regulatory barriers, and serves as an effective vehicle for advancing the field. PMID:22974119

Numerical simulation of volume-controlled mechanical ventilated respiratory system with 2 different lungs.

PubMed

Shi, Yan; Zhang, Bolun; Cai, Maolin; Zhang, Xiaohua Douglas

2017-09-01

Mechanical ventilation is a key therapy for patients who cannot breathe adequately by themselves, and dynamics of mechanical ventilation system is of great significance for life support of patients. Recently, models of mechanical ventilated respiratory system with 1 lung are used to simulate the respiratory system of patients. However, humans have 2 lungs. When the respiratory characteristics of 2 lungs are different, a single-lung model cannot reflect real respiratory system. In this paper, to illustrate dynamic characteristics of mechanical ventilated respiratory system with 2 different lungs, we propose a mathematical model of mechanical ventilated respiratory system with 2 different lungs and conduct experiments to verify the model. Furthermore, we study the dynamics of mechanical ventilated respiratory system with 2 different lungs. This research study can be used for improving the efficiency and safety of volume-controlled mechanical ventilation system. Copyright © 2016 John Wiley & Sons, Ltd.

Proceedings: Regenerative Medicine for Lung Diseases: A CIRM Workshop Report.

PubMed

Kadyk, Lisa C; DeWitt, Natalie D; Gomperts, Brigitte

2017-10-01

The mission of the California Institute of Regenerative Medicine (CIRM) is to accelerate treatments to patients with unmet medical needs. In September 2016, CIRM sponsored a workshop held at the University of California, Los Angeles, to discuss regenerative medicine approaches for treatment of lung diseases and to identify the challenges remaining for advancing such treatments to the clinic and market approval. Workshop participants discussed current preclinical and clinical approaches to regenerative medicine in the lung, as well as the biology of lung stem cells and the role of stem cells in the etiology of various lung diseases. The outcome of this effort was the recognition that whereas transient cell delivery approaches are leading the way in the clinic, recent advances in the understanding of lung stem cell biology, in vitro and in vivo disease modeling, gene editing and replacement methods, and cell engraftment approaches raise the prospect of developing cures for some lung diseases in the foreseeable future. In addition, advances in in vitro modeling using lung organoids and "lung on a chip" technology are setting the stage for high quality small molecule drug screening to develop treatments for lung diseases with complex biology. Stem Cells Translational Medicine 2017;6:1823-1828. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Indirect measurement of lung density and air volume from electrical impedance tomography (EIT) data.

PubMed

Nebuya, Satoru; Mills, Gary H; Milnes, Peter; Brown, Brian H

2011-12-01

This paper describes a method for estimating lung density, air volume and changes in fluid content from a non-invasive measurement of the electrical resistivity of the lungs. Resistivity in Ω m was found by fitting measured electrical impedance tomography (EIT) data to a finite difference model of the thorax. Lung density was determined by comparing the resistivity of the lungs, measured at a relatively high frequency, with values predicted from a published model of lung structure. Lung air volume can then be calculated if total lung weight is also known. Temporal changes in lung fluid content will produce proportional changes in lung density. The method was implemented on EIT data, collected using eight electrodes placed in a single plane around the thorax, from 46 adult male subjects and 36 adult female subjects. Mean lung densities (±SD) of 246 ± 67 and 239 ± 64 kg m(-3), respectively, were obtained. In seven adult male subjects estimates of 1.68 ± 0.30, 3.42 ± 0.49 and 4.40 ± 0.53 l in residual volume, functional residual capacity and vital capacity, respectively, were obtained. Sources of error are discussed. It is concluded that absolute differences in lung density of about 30% and changes over time of less than 30% should be detected using the current technology in normal subjects. These changes would result from approximately 300 ml increase in lung fluid. The method proposed could be used for non-invasive monitoring of total lung air and fluid content in normal subjects but needs to be assessed in patients with lung disease.

Right Ventricular Dysfunction in Chronic Lung Disease

PubMed Central

Kolb, Todd M.; Hassoun, Paul M.

2012-01-01

Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

Lung transplant recipients holding companion animals: impact on physical health and quality of life.

PubMed

Irani, S; Mahler, C; Goetzmann, L; Russi, E W; Boehler, A

2006-02-01

Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.

Single-Site Cannulation Venovenous Extracorporeal CO2 Removal as Bridge to Lung Volume Reduction Surgery in End-Stage Lung Emphysema.

PubMed

Redwan, Bassam; Ziegeler, Stephan; Semik, Michael; Fichter, Joachim; Dickgreber, Nicolas; Vieth, Volker; Ernst, Erik Christian; Fischer, Stefan

Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we first describe the application of low-flow venovenous extracorporeal CO2 removal (LFVV-ECCO2R) as bridge to LVRS in patients with end-stage lung emphysema experiencing severe hypercapnia caused by acute failure of the breathing pump. Between March and October 2015, n = 4 patients received single-site LFVV-ECCO2R as bridge to LVRS. Indication for extracorporeal lung support was severe hypercapnia with respiratory acidosis and acute breathing pump failure. Two patients required continuous mechanical ventilation over a temporary tracheostomy and were bed ridden. The other two patients were nearly immobile because of severe dyspnea at rest. Length of preoperative ECCO2R was 14 (1-42) days. All patients underwent unilateral LVRS. Anatomical resection of the right (n = 3) or left (n = 1) upper lobe was performed. Postoperatively, both patients with previous mechanical ventilatory support were successfully weaned. ECCO2R in patients with end-stage lung emphysema experiencing severe hypercapnia caused by acute breathing pump failure is a safe and effective bridging tool to LVRS. In such patients, radical surgery leads to a significant improvement of the performance status and furthermore facilitates respiratory weaning from mechanical ventilation.

Foot loading characteristics during three fencing-specific movements.

PubMed

Trautmann, Caroline; Martinelli, Nicolo; Rosenbaum, Dieter

2011-12-01

Plantar pressure characteristics during fencing movements may provide more specific information about the influence of foot loading on overload injury patterns. Twenty-nine experienced fencers participated in the study. Three fencing-specific movements (lunge, advance, retreat) and normal running were performed with three different shoe models: Ballestra (Nike, USA), Adistar Fencing Lo (Adidas, Germany), and the fencers' own shoes. The Pedar system (Novel, Munich, Germany) was used to collect plantar pressures at 50 Hz. Peak pressures, force-time integrals and contact times for five foot regions were compared between four athletic tasks in the lunge leg and supporting leg. Plantar pressure analysis revealed characteristic pressure distribution patterns for the fencing movements. For the lunge leg, during the lunge and advance movements the heel is predominantly loaded; during retreat, it is the hallux. For the supporting leg, during the lunge and advance movements the forefoot is predominantly loaded; during retreat, it is the hallux. Fencing-specific movements load the plantar surface in a distinct way compared with running. An effective cushioning in the heel and hallux region would help to minimize foot loading during fencing-specific movements.

Lung microenvironment promotes the metastasis of human hepatocellular carcinoma cells to the lungs.

PubMed

Jin, Yun; Ai, Junhua; Shi, Jun

2015-01-01

Cancer metastasis is a highly tissue-specific and organ-selective process. It has been shown that the affected tissues and/or organs play a major role in this complex process. The lung is the most common target organ of extrahepatic hepatocellular carcinoma (HCC) metastasis, but the precise molecular mechanism underlying this organ-specific metastasis remains unclear. We hypothesized that lung microenvironment was able to promote the metastasis of HCC cells to the lungs leading to distant metastases. In support of our hypothesis, we provided evidence from targeted metastasis in various types of cancer and contributing factors in the microenvironment of targeted tissues/organs. A better understanding of the steps involved in the interplay between HCC cells and lung microenvironment may offer new perspectives for the medical management of lung metastases of HCC.

Lung cancer in shipbuilding and related industries in Louisiana.

PubMed

Gottlieb, M S; Stedman, R B

1979-09-01

The relationship between shipbuilding and related industries and risk of fatal lung cancer (1960-1975) is described for selected Louisiana parishes. Deaths from lung cancer were matched to deaths not caused by cancer. Shipbuilders had a significantly increased risk (greater than twofold) of dying of lung cancer as compared with other causes. The risk of dying of lung cancer in related occupations (seamen and longshoremen) was also increased. Information on laterality of lung cancer was not supportive of particulate substances contributing to causality due to the large number of unspecified cases. The preponderance of deaths appears to be occurring in men with a greater number of years of exposure to this industry and in those aged 20 to 34 years in 1940. These common occupations in Louisiana could contribute to the high rate of lung cancer.

The Case for Lung Cancer Screening: What Nurses Need to Know.

PubMed

Sorrie, Kerrin; Cates, Lisa; Hill, Alethea

2016-06-01

Lung cancer screening with low-dose helical computed tomography (LDCT) can improve high-risk individuals' chances of being diagnosed at an earlier stage and increase survival. The aims of this article are to present the risk factors associated with the development of lung cancer, identify patients at high risk for lung cancer qualifying for LDCT screening, and understand the importance of early lung cancer detection through the use of LDCT screening. PubMed and CINAHL® databases were searched with key words lung cancer screening to identify full-text academic articles from 2004-2014. This resulted in 529 articles from PubMed and 195 from CINAHL. PubMed offered suggestions for additional relevant journal articles. The National Comprehensive Cancer Network guidelines also provided substantial evidence-based information. Nurses need to provide support, education, and resources for patients undergoing lung cancer screening.

Lung cancer induced in hamsters by low doses of alpha radiation from polonium-210.

PubMed

Little, J B; Kennedy, A R; McGandy, R B

1975-05-16

Lung cancers have been induced in 9 to 53 percent of hamsters given multiple intratracheal instillations of polonium-210 in amounts yielding lifetime exposures of 15 to 300 rads to the lungs. Cigarette smokers have previously been estimated to receive 20 rads to areas of the bronchial epithelium from deposited polonium-210. This finding thus supports the hypothesis that alpha radiation resulting from the polonium-210 or lead-210 present in cigarette smoke may be a significant causative factor in human lung cancer.

Nanotechnology applications in thoracic surgery

PubMed Central

Hofferberth, Sophie C.; Grinstaff, Mark W.; Colson, Yolonda L.

2016-01-01

Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of ‘theranostic’ multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future. PMID:26843431

Quantum-dot-based suspension microarray for multiplex detection of lung cancer markers: preclinical validation and comparison with the Luminex xMAP® system

NASA Astrophysics Data System (ADS)

Bilan, Regina; Ametzazurra, Amagoia; Brazhnik, Kristina; Escorza, Sergio; Fernández, David; Uríbarri, María; Nabiev, Igor; Sukhanova, Alyona

2017-03-01

A novel suspension multiplex immunoassay for the simultaneous specific detection of lung cancer markers in bronchoalveolar lavage fluid (BALF) clinical samples based on fluorescent microspheres having different size and spectrally encoded with quantum dots (QDEM) was developed. The designed suspension immunoassay was validated for the quantitative detection of three lung cancer markers in BALF samples from 42 lung cancer patients and 10 control subjects. Tumor markers were detected through simultaneous formation of specific immune complexes consisting of a capture molecule, the target antigen, and biotinylated recognition molecule on the surface of the different QDEM in a mixture. The immune complexes were visualized by fluorescently labeled streptavidin and simultaneously analyzed using a flow cytometer. Preclinical validation of the immunoassay was performed and results were compared with those obtained using an alternative 3-plex immunoassay based on Luminex xMAP® technology, developed on classical organic fluorophores. The comparison showed that the QDEM and xMAP® assays yielded almost identical results, with clear discrimination between control and clinical samples. Thus, developed QDEM technology can become a good alternative to xMAP® assays permitting analysis of multiple protein biomarkers using conventional flow cytometers.

Quantum-dot-based suspension microarray for multiplex detection of lung cancer markers: preclinical validation and comparison with the Luminex xMAP® system

PubMed Central

Bilan, Regina; Ametzazurra, Amagoia; Brazhnik, Kristina; Escorza, Sergio; Fernández, David; Uríbarri, María; Nabiev, Igor; Sukhanova, Alyona

2017-01-01

A novel suspension multiplex immunoassay for the simultaneous specific detection of lung cancer markers in bronchoalveolar lavage fluid (BALF) clinical samples based on fluorescent microspheres having different size and spectrally encoded with quantum dots (QDEM) was developed. The designed suspension immunoassay was validated for the quantitative detection of three lung cancer markers in BALF samples from 42 lung cancer patients and 10 control subjects. Tumor markers were detected through simultaneous formation of specific immune complexes consisting of a capture molecule, the target antigen, and biotinylated recognition molecule on the surface of the different QDEM in a mixture. The immune complexes were visualized by fluorescently labeled streptavidin and simultaneously analyzed using a flow cytometer. Preclinical validation of the immunoassay was performed and results were compared with those obtained using an alternative 3-plex immunoassay based on Luminex xMAP® technology, developed on classical organic fluorophores. The comparison showed that the QDEM and xMAP® assays yielded almost identical results, with clear discrimination between control and clinical samples. Thus, developed QDEM technology can become a good alternative to xMAP® assays permitting analysis of multiple protein biomarkers using conventional flow cytometers. PMID:28300171

Clinical Validation of Targeted Next Generation Sequencing for Colon and Lung Cancers

PubMed Central

D’Haene, Nicky; Le Mercier, Marie; De Nève, Nancy; Blanchard, Oriane; Delaunoy, Mélanie; El Housni, Hakim; Dessars, Barbara; Heimann, Pierre; Remmelink, Myriam; Demetter, Pieter; Tejpar, Sabine; Salmon, Isabelle

2015-01-01

Objective Recently, Next Generation Sequencing (NGS) has begun to supplant other technologies for gene mutation testing that is now required for targeted therapies. However, transfer of NGS technology to clinical daily practice requires validation. Methods We validated the Ion Torrent AmpliSeq Colon and Lung cancer panel interrogating 1850 hotspots in 22 genes using the Ion Torrent Personal Genome Machine. First, we used commercial reference standards that carry mutations at defined allelic frequency (AF). Then, 51 colorectal adenocarcinomas (CRC) and 39 non small cell lung carcinomas (NSCLC) were retrospectively analyzed. Results Sensitivity and accuracy for detecting variants at an AF >4% was 100% for commercial reference standards. Among the 90 cases, 89 (98.9%) were successfully sequenced. Among the 86 samples for which NGS and the reference test were both informative, 83 showed concordant results between NGS and the reference test; i.e. KRAS and BRAF for CRC and EGFR for NSCLC, with the 3 discordant cases each characterized by an AF <10%. Conclusions Overall, the AmpliSeq colon/lung cancer panel was specific and sensitive for mutation analysis of gene panels and can be incorporated into clinical daily practice. PMID:26366557

Association of emphysema-like lung on cardiac computed tomography and mortality in persons without airflow obstruction: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study

PubMed Central

Oelsner, Elizabeth C.; Hoffman, Eric A.; Folsom, Aaron R.; Carr, J. Jeffrey; Enright, Paul L.; Kawut, Steven M.; Kronmal, Richard; Lederer, David; Lima, Joao A. C.; Lovasi, Gina S.; Shea, Steven; Barr, R. Graham

2015-01-01

Background Whereas low lung function is known to predict mortality in the general population, the prognostic significance of emphysema on computed tomography (CT) in persons without chronic obstructive pulmonary disease (COPD) remains uncertain. Objective To determine whether greater emphysema-like lung on CT is associated with all-cause mortality among persons without airflow obstruction or COPD in the general population. Design Prospective cohort study. Setting Population-based, multiethnic sample from 6 US communities. Participants 2965 participants ages 45-84 years without airflow obstruction on spirometry. Measurements Emphysema-like lung was defined on cardiac CT as the number of lung voxels less than -950 Hounsfield Units, and was adjusted for the number of total imaged lung voxels. Results Among 2965 participants, 50.9% of whom never smoked, there were 186 deaths over a median of 6.2 years. Greater emphysema-like lung was independently associated with increased mortality (adjusted hazard ratio [HR]1.14 per one-half of the interquartile range, 95% CI 1.04-1.24, P=0.004), adjusting for potential confounders including cardiovascular risk factors and the forced expiratory volume in one second. Generalized additive models supported a linear association between emphysema-like lung and mortality without evidence for a threshold. The association was of greatest magnitude among smokers, although multiplicative interaction terms did not support effect modification by smoking status. Limitations Cardiac CT scans did not include lung apices. The number of deaths was limited among subgroup analyses. Conclusions Emphysema-like lung on CT was associated with all-cause mortality among persons without airflow obstruction or COPD in a general population sample, particularly among smokers. Recognition of the independent prognostic significance of emphysema on CT among patients without COPD on spirometry is warranted. Primary Funding Source NIH/NHLBI. PMID:25506855

Resource Utilization and Costs during the Initial Years of Lung Cancer Screening with Computed Tomography in Canada

PubMed Central

Lam, Stephen; Tammemagi, Martin C.; Evans, William K.; Leighl, Natasha B.; Regier, Dean A.; Bolbocean, Corneliu; Shepherd, Frances A.; Tsao, Ming-Sound; Manos, Daria; Liu, Geoffrey; Atkar-Khattra, Sukhinder; Cromwell, Ian; Johnston, Michael R.; Mayo, John R.; McWilliams, Annette; Couture, Christian; English, John C.; Goffin, John; Hwang, David M.; Puksa, Serge; Roberts, Heidi; Tremblay, Alain; MacEachern, Paul; Burrowes, Paul; Bhatia, Rick; Finley, Richard J.; Goss, Glenwood D.; Nicholas, Garth; Seely, Jean M.; Sekhon, Harmanjatinder S.; Yee, John; Amjadi, Kayvan; Cutz, Jean-Claude; Ionescu, Diana N.; Yasufuku, Kazuhiro; Martel, Simon; Soghrati, Kamyar; Sin, Don D.; Tan, Wan C.; Urbanski, Stefan; Xu, Zhaolin; Peacock, Stuart J.

2014-01-01

Background: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. Methods: Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer’s perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. Results: The average per-person cost for screening individuals with LDCT was $453 (95% confidence interval [CI], $400–$505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was $33,344 (95% CI, $31,553–$34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, ($47,792; 95% CI, $43,254–$52,200; p = 0.061). Conclusion: In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure. PMID:25105438

Protection of the lung from blast overpressure by stress wave decouplers, buffer plates or sandwich panels.

PubMed

Sedman, Andrew; Hepper, A

2018-03-19

This paper outlines aspects of UK Ministry of Defence's research and development of blast overpressure protection technologies appropriate for use in body armour, with the aim of both propagating new knowledge and updating existing information. Two simple models are introduced not only to focus the description of the mechanism by which the lungs can be protected, but also to provide a bridge between fields of research that may hold the key to further advances in protection technology and related body armour. Protection can be provided to the lungs by decoupling the stress wave transmission into the thorax by managing the blast energy imparted through the protection system. It is proposed that the utility of the existing 'simple decoupler' blast overpressure protection is reviewed in light of recent developments in the treatment of those sustaining both overpressure and fragment injuries. It is anticipated that further advances in protection technology may be generated by those working in other fields on the analogous technologies of 'buffer plates' and 'sandwich panels'. © Crown copyright (2018), Dstl. This material is licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@nationalarchives.gsi.gov.uk.

Role of the Lung Microbiome in the Pathogenesis of Chronic Obstructive Pulmonary Disease.

PubMed

Wang, Lei; Hao, Ke; Yang, Ting; Wang, Chen

2017-09-05

The development of culture-independent techniques for microbiological analysis shows that bronchial tree is not sterile in either healthy or chronic obstructive pulmonary disease (COPD) individuals. With the advance of sequencing technologies, lung microbiome has become a new frontier for pulmonary disease research, and such advance has led to better understanding of the lung microbiome in COPD. This review aimed to summarize the recent advances in lung microbiome, its relationships with COPD, and the possible mechanisms that microbiome contributed to COPD pathogenesis. Literature search was conducted using PubMed to collect all available studies concerning lung microbiome in COPD. The search terms were "microbiome" and "chronic obstructive pulmonary disease", or "microbiome" and "lung/pulmonary". The papers in English about lung microbiome or lung microbiome in COPD were selected, and the type of articles was not limited. The lung is a complex microbial ecosystem; the microbiome in lung is a collection of viable and nonviable microbiota (bacteria, viruses, and fungi) residing in the bronchial tree and parenchymal tissues, which is important for health. The following types of respiratory samples are often used to detect the lung microbiome: sputum, bronchial aspirate, bronchoalveolar lavage, and bronchial mucosa. Disordered bacterial microbiome is participated in pathogenesis of COPD; there are also dynamic changes in microbiota during COPD exacerbations. Lung microbiome may contribute to the pathogenesis of COPD by manipulating inflammatory and/or immune process. Normal lung microbiome could be useful for prophylactic or therapeutic management in COPD, and the changes of lung microbiome could also serve as biomarkers for the evaluation of COPD.

Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies.

PubMed

Morin, Jean-Paul; Baste, Jean-Marc; Gay, Arnaud; Crochemore, Clément; Corbière, Cécile; Monteil, Christelle

2013-01-01

1.We review the specific approaches for lung tissue slices preparation and incubation systems and the research application fields in which lung slices proved to be a very efficient alternative to animal experimentation for biomechanical, physiological, pharmacological and toxicological approaches. 2.Focus is made on air-liquid interface dynamic organ culture systems that allow direct tissue exposure to complex aerosol and that best mimic in vivo lung tissue physiology. 3.A compilation of research applications in the fields of vascular and airway reactivity, mucociliary transport, polyamine transport, xenobiotic biotransformation, chemicals toxicology and complex aerosols supports the concept that precision cut lung slices are a very efficient tool maintaining highly differentiated functions similar to in vivo lung organ when kept under dynamic organ culture. They also have been successfully used for lung gene transfer efficiency assessment, for lung viral infection efficiency assessment, for studies of tissue preservation media and tissue post-conditioning to optimize lung tissue viability before grafting. 4.Taken all together, the reviewed studies point to a great interest for precision cut lung slices as an efficient and valuable alternative to in vivo lung organ experimentation.

Real-time X-ray Imaging of Lung Fluid Volumes in Neonatal Mouse Lung.

PubMed

Van Avermaete, Ashley E; Trac, Phi T; Gauthier, Theresa W; Helms, My N

2016-07-18

At birth, the lung undergoes a profound phenotypic switch from secretion to absorption, which allows for adaptation to breathing independently. Promoting and sustaining this phenotype is critically important in normal alveolar growth and gas exchange throughout life. Several in vitro studies have characterized the role of key regulatory proteins, signaling molecules, and steroid hormones that can influence the rate of lung fluid clearance. However, in vivo examinations must be performed to evaluate whether these regulatory factors play important physiological roles in regulating perinatal lung liquid absorption. As such, the utilization of real time X-ray imaging to determine perinatal lung fluid clearance, or pulmonary edema, represents a technological advancement in the field. Herein, we explain and illustrate an approach to assess the rate of alveolar lung fluid clearance and alveolar flooding in C57BL/6 mice at post natal day 10 using X-ray imaging and analysis. Successful implementation of this protocol requires prior approval from institutional animal care and use committees (IACUC), an in vivo small animal X-ray imaging system, and compatible molecular imaging software.

Extracorporeal respiratory support in adult patients

PubMed Central

Romano, Thiago Gomes; Mendes, Pedro Vitale; Park, Marcelo; Costa, Eduardo Leite Vieira

2017-01-01

ABSTRACT In patients with severe respiratory failure, either hypoxemic or hypercapnic, life support with mechanical ventilation alone can be insufficient to meet their needs, especially if one tries to avoid ventilator settings that can cause injury to the lungs. In those patients, extracorporeal membrane oxygenation (ECMO), which is also very effective in removing carbon dioxide from the blood, can provide life support, allowing the application of protective lung ventilation. In this review article, we aim to explore some of the most relevant aspects of using ECMO for respiratory support. We discuss the history of respiratory support using ECMO in adults, as well as the clinical evidence; costs; indications; installation of the equipment; ventilator settings; daily care of the patient and the system; common troubleshooting; weaning; and discontinuation. PMID:28380189

Depression, social support, and clinical outcomes following lung transplantation: a single-center cohort study.

PubMed

Smith, Patrick J; Snyder, Laurie D; Palmer, Scott M; Hoffman, Benson M; Stonerock, Gregory L; Ingle, Krista K; Saulino, Caroline K; Blumenthal, James A

2018-05-01

Depressive symptoms are common among lung transplant candidates and have been associated with poorer clinical outcomes in some studies. Previous studies have been plagued by methodologic problems, including small sample sizes, few clinical events, and uncontrolled confounders, particularly perioperative complications. In addition, few studies have examined social support as a potential protective factor. We therefore examined the association between pretransplant depressive symptoms, social support, and mortality in a large sample of lung transplant recipients. As a secondary aim, we also examined the associations between psychosocial factors, perioperative outcomes [indexed by hospital length of stay (LOS)], and mortality. We hypothesized that depression would be associated with longer LOS and that the association between depression, social support, and mortality would be moderated by LOS. Participants included lung transplant recipients, transplanted at Duke University Medical Center from January 2009 to December 2014. Depressive symptoms were evaluated using the Beck Depression Inventory (BDI-II) and social support using the Perceived Social Support Scale (PSSS). Medical risk factors included forced vital capacity (FVC), partial pressure of carbon dioxide (PCO 2 ), donor age, acute rejection, and transplant type. Functional status was assessed using six-minute walk distance (6MWD). We also controlled for demographic factors, including age, gender, and native disease. Transplant hospitalization LOS was examined as a marker of perioperative clinical outcomes. Participants included 273 lung recipients (174 restrictive, 67 obstructive, 26 cystic fibrosis, and six "other"). Pretransplant depressive symptoms were common, with 56 participants (21%) exhibiting clinically elevated levels (BDI-II ≥ 14). Greater depressive symptoms were associated with longer LOS [adjusted b = 0.20 (2 days per 7-point higher BDI-II score), P < 0.01]. LOS moderated the associations between depressive symptoms (P = 0.019), social support (P < 0.001), and mortality, such that greater depressive symptoms and lower social support were associated with greater mortality only among individuals with longer LOS. For individuals with LOS ≥ 1 month, clinically elevated depressive symptoms (BDI-II ≥ 14) were associated with a threefold increased risk of mortality (HR = 2.97). Greater pretransplant depressive symptoms and lower social support may be associated with greater mortality among a subset of individuals with worse perioperative outcomes. © 2017 Steunstichting ESOT.

Continued family smoking after lung cancer diagnosis: the patient's perspective.

PubMed

Bottorff, Joan L; Robinson, Carole A; Sullivan, Kelli M; Smith, Michelle L

2009-05-01

To explore the influence of lung cancer diagnosis on interpersonal dynamics in families in which one or more members continue to smoke following diagnosis. Descriptive, qualitative. Three cancer care sites in western Canada. 16 participants from 8 family dyads. Patients with lung cancer receiving treatment and immediate family members were recruited to participate in individual or conjoint semistructured interviews. Thematic analysis was conducted on transcribed interviews. Intrafamily interaction patterns, smoking and smoking cessation, lung cancer diagnosis. Following diagnosis, patients with lung cancer experienced considerable distress as they struggled to understand family members' continued smoking. Patient orientations to family members who smoked included preserving relationships (maintaining harmony and connection with family members took priority over directly intervening with smokers) and risking relationships (patients repeatedly confronted family members about continued smoking to influence their cessation despite the impact on relationships). Neither pattern was successful in engaging relatives in smoking reduction or cessation, and the risking relationships approach resulted in conflict and strained family relationships. The findings provide additional support for examining family dynamics related to tobacco reduction and cessation as well as directions for future research. Nurses should encourage tobacco reduction as a supportive intervention for patients with lung cancer and their families to eliminate smoking-related distress.

Maternal lung cancer and testicular cancer risk in the offspring.

PubMed

Kaijser, Magnus; Akre, Olof; Cnattingius, Sven; Ekbom, Anders

2003-07-01

It has been hypothesized that smoking during pregnancy could increase the offspring's risk for testicular cancer. This hypothesis is indirectly supported by both ecological studies and studies of cancer aggregations within families. However, results from analytical epidemiological studies are not consistent, possibly due to methodological difficulties. To further study the association between smoking during pregnancy and testicular cancer, we did a population-based cohort study on cancer risk among offspring of women diagnosed with lung cancer. Through the use of the Swedish Cancer Register and the Swedish Second-Generation Register, we identified 8,430 women who developed lung cancer between 1958 and 1997 and delivered sons between 1941 and 1979. Cancer cases among the male offspring were then identified through the Swedish Cancer Register. Standardized incidence ratios were computed, using 95% confidence intervals. We identified 12,592 male offspring of mothers with a subsequent diagnosis of lung cancer, and there were 40 cases of testicular cancer (standardized incidence ratio, 1.90; 95% confidence interval, 1.35-2.58). The association was independent of maternal lung cancer subtype, and the risk of testicular cancer increased stepwise with decreasing time interval between birth and maternal lung cancer diagnosis. Our results support the hypothesis that exposure to cigarette smoking in utero increases the risk of testicular cancer.

Extracorporeal Membrane Oxygenation for Refractory Severe Respiratory Failure in Acute Interstitial Pneumonia.

PubMed

Gonçalves-Venade, Gabriela; Lacerda-Príncipe, Nuno; Roncon-Albuquerque, Roberto; Paiva, José Artur

2018-05-01

Acute interstitial pneumonia (AIP) is a rare idiopathic interstitial lung disease with rapid progressive respiratory failure and high mortality. In the present report, three cases of AIP complicated by refractory respiratory failure supported with extracorporeal membrane oxygenation (ECMO) are presented. One male and two female patients (ages 27-59) were included. Venovenous ECMO support was provided using miniaturized systems, with two-site femoro-jugular circuit configuration. Despite lung protective ventilation, prone position and neuromuscular blockade, refractory respiratory failure of unknown etiology supervened (ratio of arterial oxygen partial pressure to fractional inspired oxygen 46-130) and ECMO was initiated after 3-7 days of mechanical ventilation. AIP diagnosis was established after exclusion of infectious and noninfectious acute respiratory distress syndrome on the basis of clinical and analytical data, bronchoalveolar lavage analysis and lung imaging, with a confirmatory surgical lung biopsy revealing diffuse alveolar damage of unknown etiology. Immunosuppressive treatment consisted in high-dose corticosteroids and cyclophosphamide in one case. Two patients survived to hospital discharge. ECMO allowed AIP diagnosis and treatment in the presence of refractory respiratory failure, therefore reducing ventilator-induced lung injury and bridging lung recovery in two patients. ECMO referral should be considered in refractory respiratory failure if AIP is suspected. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD.

PubMed

Briend, Emmanuel; Ferguson, G John; Mori, Michiko; Damera, Gautam; Stephenson, Katherine; Karp, Natasha A; Sethi, Sanjay; Ward, Christine K; Sleeman, Matthew A; Erjefält, Jonas S; Finch, Donna K

2017-08-22

Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs. IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction. The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung. We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key regulator of IFNγ, are highly associated with such structures. Interleukin-1 family cytokines correlated with IFNγ in COPD sputum. We observed that the primary source of IL-18 in COPD lungs was myeloid cells within lymphoid aggregates and IL-18 was increased in severe disease. IL-18 released from infected epithelium or from activated myeloid cells, was more dominant in driving IFNγ when IL-18-producing and responder cells were in close proximity. Unlike tight regulation to control infection spread in lymphoid organs, this local interface between IL-18-expressing and responder cell is increasingly supported in lung as disease progresses, increasing its potential to increase tissue damage via IFNγ.

Integrated quantitative fractal polarimetric analysis of monolayer lung cancer cells

NASA Astrophysics Data System (ADS)

Shrestha, Suman; Zhang, Lin; Quang, Tri; Farrahi, Tannaz; Narayan, Chaya; Deshpande, Aditi; Na, Ying; Blinzler, Adam; Ma, Junyu; Liu, Bo; Giakos, George C.

2014-05-01

Digital diagnostic pathology has become one of the most valuable and convenient advancements in technology over the past years. It allows us to acquire, store and analyze pathological information from the images of histological and immunohistochemical glass slides which are scanned to create digital slides. In this study, efficient fractal, wavelet-based polarimetric techniques for histological analysis of monolayer lung cancer cells will be introduced and different monolayer cancer lines will be studied. The outcome of this study indicates that application of fractal, wavelet polarimetric principles towards the analysis of squamous carcinoma and adenocarcinoma cancer cell lines may be proved extremely useful in discriminating among healthy and lung cancer cells as well as differentiating among different lung cancer cells.

The 10 Pillars of Lung Cancer Screening: Rationale and Logistics of a Lung Cancer Screening Program.

PubMed

Fintelmann, Florian J; Bernheim, Adam; Digumarthy, Subba R; Lennes, Inga T; Kalra, Mannudeep K; Gilman, Matthew D; Sharma, Amita; Flores, Efren J; Muse, Victorine V; Shepard, Jo-Anne O

2015-01-01

On the basis of the National Lung Screening Trial data released in 2011, the U.S. Preventive Services Task Force made lung cancer screening (LCS) with low-dose computed tomography (CT) a public health recommendation in 2013. The Centers for Medicare and Medicaid Services (CMS) currently reimburse LCS for asymptomatic individuals aged 55-77 years who have a tobacco smoking history of at least 30 pack-years and who are either currently smoking or had quit less than 15 years earlier. Commercial insurers reimburse the cost of LCS for individuals aged 55-80 years with the same smoking history. Effective care for the millions of Americans who qualify for LCS requires an organized step-wise approach. The 10-pillar model reflects the elements required to support a successful LCS program: eligibility, education, examination ordering, image acquisition, image review, communication, referral network, quality improvement, reimbursement, and research frontiers. Examination ordering can be coupled with decision support to ensure that only eligible individuals undergo LCS. Communication of results revolves around the Lung Imaging Reporting and Data System (Lung-RADS) from the American College of Radiology. Lung-RADS is a structured decision-oriented reporting system designed to minimize the rate of false-positive screening examination results. With nodule size and morphology as discriminators, Lung-RADS links nodule management pathways to the variety of nodules present on LCS CT studies. Tracking of patient outcomes is facilitated by a CMS-approved national registry maintained by the American College of Radiology. Online supplemental material is available for this article. (©)RSNA, 2015.

Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.

PubMed

Henry, Eric; Cores, Jhon; Hensley, M Taylor; Anthony, Shirena; Vandergriff, Adam; de Andrade, James B M; Allen, Tyler; Caranasos, Thomas G; Lobo, Leonard J; Cheng, Ke

2015-11-01

Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration. The results from the present study will lead to future human clinical trials using lung stem cell therapies to treat various incurable lung diseases, including pulmonary fibrosis. The data presented here also provide fundamental knowledge regarding how injected stem cells mediate lung repair in pulmonary fibrosis. ©AlphaMed Press.

New Strategies and Challenges in Lung Proteomics and Metabolomics. An Official American Thoracic Society Workshop Report.

PubMed

Bowler, Russell P; Wendt, Chris H; Fessler, Michael B; Foster, Matthew W; Kelly, Rachel S; Lasky-Su, Jessica; Rogers, Angela J; Stringer, Kathleen A; Winston, Brent W

2017-12-01

This document presents the proceedings from the workshop entitled, "New Strategies and Challenges in Lung Proteomics and Metabolomics" held February 4th-5th, 2016, in Denver, Colorado. It was sponsored by the National Heart Lung Blood Institute, the American Thoracic Society, the Colorado Biological Mass Spectrometry Society, and National Jewish Health. The goal of this workshop was to convene, for the first time, relevant experts in lung proteomics and metabolomics to discuss and overcome specific challenges in these fields that are unique to the lung. The main objectives of this workshop were to identify, review, and/or understand: (1) emerging technologies in metabolomics and proteomics as applied to the study of the lung; (2) the unique composition and challenges of lung-specific biological specimens for metabolomic and proteomic analysis; (3) the diverse informatics approaches and databases unique to metabolomics and proteomics, with special emphasis on the lung; (4) integrative platforms across genetic and genomic databases that can be applied to lung-related metabolomic and proteomic studies; and (5) the clinical applications of proteomics and metabolomics. The major findings and conclusions of this workshop are summarized at the end of the report, and outline the progress and challenges that face these rapidly advancing fields.

From mice and men to earth and space: joint NASA-NCI workshop on lung cancer risk resulting from space and terrestrial radiation.

PubMed

Shay, Jerry W; Cucinotta, Francis A; Sulzman, Frank M; Coleman, C Norman; Minna, John D

2011-11-15

On June 27-28, 2011, scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA, available data suggest that lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space, the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high-energy protons from solar flares and not from gamma radiation. In contrast, the NCI is endeavoring to estimate the increased lung cancer risk from the potential widespread implementation of computed tomographic (CT) screening in individuals at high risk for developing lung cancer based on the National Lung Cancer Screening Trial (NLST). For the latter, exposure will be X-rays from CT scans from the screening (which uses "low-dose" CT scans) and also from follow-up scans used to evaluate abnormalities found during initial screening. Topics discussed included the risk of lung cancer arising after HZE particle, proton, and low-dose exposure to Earth's radiation. The workshop examined preclinical models, epidemiology, molecular markers, "omics" technology, radiobiology issues, and lung stem cells that relate to the development of lung cancer. ©2011 AACR

Saudi lung cancer management guidelines 2017

PubMed Central

Jazieh, Abdul Rahman; Al Kattan, Khaled; Bamousa, Ahmed; Al Olayan, Ashwaq; Abdelwarith, Ahmed; Ansari, Jawaher; Al Twairqi, Abdullah; Al Fayea, Turki; Al Saleh, Khalid; Al Husaini, Hamed; Abdelhafiez, Nafisa; Mahrous, Mervat; Faris, Medhat; Al Omair, Ameen; Hebshi, Adnan; Al Shehri, Salem; Al Dayel, Foad; Bamefleh, Hanaa; Khalbuss, Walid; Al Ghanem, Sarah; Loutfi, Shukri; Khankan, Azzam; Al Rujaib, Meshael; Al Ghamdi, Majed; Ibrahim, Nagwa; Swied, Abdulmonem; Al Kayait, Mohammad; Datario, Marie

2017-01-01

BACKGROUND: Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care. METHODS: The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed. RESULTS: Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy. CONCLUSION: A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country. PMID:29118855

Saudi lung cancer management guidelines 2017.

PubMed

Jazieh, Abdul Rahman; Al Kattan, Khaled; Bamousa, Ahmed; Al Olayan, Ashwaq; Abdelwarith, Ahmed; Ansari, Jawaher; Al Twairqi, Abdullah; Al Fayea, Turki; Al Saleh, Khalid; Al Husaini, Hamed; Abdelhafiez, Nafisa; Mahrous, Mervat; Faris, Medhat; Al Omair, Ameen; Hebshi, Adnan; Al Shehri, Salem; Al Dayel, Foad; Bamefleh, Hanaa; Khalbuss, Walid; Al Ghanem, Sarah; Loutfi, Shukri; Khankan, Azzam; Al Rujaib, Meshael; Al Ghamdi, Majed; Ibrahim, Nagwa; Swied, Abdulmonem; Al Kayait, Mohammad; Datario, Marie

2017-01-01

Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care. The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed. Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy. A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country.

Successful Single-Lung Transplant for Severe Lung Graft-Versus-Host Disease Two Years After Sibling Allograft for Acute Lymphoblastic Leukemia: A Case Report.

PubMed

Irhimeh, M R; Musk, M; Cooney, J P

2016-11-01

Bone marrow transplantation (BMT) has been performed as a successful life-saving treatment for hematological and neoplastic diseases. Despite the predictable long-term survival rates in BMT, pulmonary complications reduce the survival rates significantly mainly because of chronic graft-versus-host disease (GVHD). This report briefly discusses a successful lung transplantation case for severe lung GVHD after allograft for acute lymphoblastic leukemia. This case report supports the scarce evidence in the literature for the importance of lung transplantation as a therapeutic option for patients who develop respiratory failure secondary to BMT. Copyright © 2016. Published by Elsevier Inc.

The liquid biopsy in lung cancer.

PubMed

Ansari, Junaid; Yun, Jungmi W; Kompelli, Anvesh R; Moufarrej, Youmna E; Alexander, Jonathan S; Herrera, Guillermo A; Shackelford, Rodney E

2016-11-01

The incidence of lung cancer has significantly increased over the last century, largely due to smoking, and remains the most common cause of cancer deaths worldwide. This is often due to lung cancer first presenting at late stages and a lack of curative therapeutic options at these later stages. Delayed diagnoses, inadequate tumor sampling, and lung cancer misdiagnoses are also not uncommon due to the limitations of the tissue biopsy. Our better understanding of the tumor microenvironment and the systemic actions of tumors, combined with the recent advent of the liquid biopsy, may allow molecular diagnostics to be done on circulating tumor markers, particularly circulating tumor DNA. Multiple liquid biopsy molecular methods are presently being examined to determine their efficacy as surrogates to the tumor tissue biopsy. This review will focus on new liquid biopsy technologies and how they may assist in lung cancer detection, diagnosis, and treatment.

Hippocampal-Sparing Whole-Brain Radiotherapy for Lung Cancer.

PubMed

Zhao, Ren; Kong, Wei; Shang, Jun; Zhe, Hong; Wang, Yan-Yang

2017-03-01

Brain metastases occur in 20% to 40% of lung cancer patients. Whole-brain radiotherapy (WBRT) has long been considered the treatment of choice for many patients with lung cancer, because of its wide availability, ease of delivery, and effectiveness in prolonging survival. However, WBRT is also associated with several side effects, such as decline in memory and other cognitive functions. There exists significant preclinical and clinical evidence that radiation-induced injury to the hippocampus correlates with neurocognitive decline of patients who receive WBRT. Technological advances in treatment planning and delivery facilitate the use of hippocampal-sparing (HS) WBRT as prophylactic cranial irradiation or the primary treatment modality for lung cancer patients with brain metastases. In this review, we provide a detailed and comprehensive discussion of the safety profile, techniques for hippocampus-sparing, and the clinical evidence of HS-WBRT for lung cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetically manipulated mouse models of lung disease: potential and pitfalls

PubMed Central

Choi, Alexander J. S.; Owen, Caroline A.; Choi, Augustine M. K.

2012-01-01

Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators. PMID:22198907

Preanalytics in lung cancer.

PubMed

Warth, Arne; Muley, Thomas; Meister, Michael; Weichert, Wilko

2015-01-01

Preanalytic sampling techniques and preparation of tissue specimens strongly influence analytical results in lung tissue diagnostics both on the morphological but also on the molecular level. However, in contrast to analytics where tremendous achievements in the last decade have led to a whole new portfolio of test methods, developments in preanalytics have been minimal. This is specifically unfortunate in lung cancer, where usually only small amounts of tissue are at hand and optimization in all processing steps is mandatory in order to increase the diagnostic yield. In the following, we provide a comprehensive overview on some aspects of preanalytics in lung cancer from the method of sampling over tissue processing to its impact on analytical test results. We specifically discuss the role of preanalytics in novel technologies like next-generation sequencing and in the state-of the-art cytology preparations. In addition, we point out specific problems in preanalytics which hamper further developments in the field of lung tissue diagnostics.

Non-invasive diagnostic platforms in management of non-small cell lung cancer: opportunities and challenges

PubMed Central

Pennell, Nathan A.

2017-01-01

Several non-invasive diagnostic platforms are already being incorporated in routine clinical practice in the work up and monitoring of patients with lung cancer. These approaches have great potential to improve patient selection and monitor patients while on therapy, however several challenges exist in clinical validation and standardization of such platforms. In this review, we summarize the current technologies available for non-invasive diagnostic evaluation from the blood of patients with non-small cell lung cancer (NSCLC), and discuss the technical and logistical challenges associated incorporating such testing in clinical practice. PMID:29057238

[Clinical laboratory tests supporting respiratory disease treatment--chairman's introductory remarks].

PubMed

Takai, Daiya

2014-12-01

The symposium consisted of four parts: history of lung function tests, nitric oxide for diagnosis and monitoring of bronchial asthma, radiological and functional changes of the lung in COPD, and combined pulmonary fibrosis and emphysema (CPFE) occasionally showing almost normal results in lung function tests. The history of lung function tests was presented by Dr. Naoko Tojo of the Tokyo Medical and Dental University. Nitric oxide tests in clinical use for diagnosis and monitoring of bronchial asthma were presented by Dr. Hiroyuki Nagase of Teikyo University. Radiological and functional changes of the lung in COPD were presented by Dr. Shigeo Muro of Kyoto University. Clinical features of combined pulmonary fibrosis and emphysema and their associated lung function were presented by Dr. Daiya Takai of the University of Tokyo. I hope that discussing the history of lung function tests until the present was useful for many medical technologists. (Review).

The Lung Microbiome, Immunity and the Pathogenesis of Chronic Lung Disease1

PubMed Central

O’Dwyer, David N.; Dickson, Robert P.; Moore, Bethany B.

2016-01-01

The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared to the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. PMID:27260767

Patient Recruitment 2.0: Become a Partner in the Patient Journey Using Digital Media

PubMed Central

Lindemann, Michael; Freeman, Tobe; Kilchenmann, Timothy; Harrison, Shuree; Chan, Margaret; Wygonik, Mark; Haines, Lea

2016-01-01

We describe a digital platform, Pioneering Healthcare, designed to inform and empower people who are impacted by lung cancer. The platform enables Roche to support an online conversation with patients and caregivers about lung cancer, and about the role of lung cancer clinical studies in the development of future treatment options. This conversation is live and ongoing on the platform. It provides insights about the views and motivations of patients, and about how to better support patients pursuing treatment for life-threatening illness. We discuss the strategies used to deploy Pioneering Healthcare, and the advantages of using digital platforms for raising disease awareness, increasing patient engagement and, ultimately, for boosting patient enrollment into clinical trials. PMID:26818938

Robotics in general thoracic surgery procedures.

PubMed

Latif, M Jawad; Park, Bernard J

2017-01-01

The use of robotic technology in general thoracic surgical practice continues to expand across various institutions and at this point many major common thoracic surgical procedures have been successfully performed by general thoracic surgeons using the robotic technology. These procedures include lung resections, excision of mediastinal masses, esophagectomy and reconstruction for malignant and benign esophageal pathologies. The success of robotic technology can be attributed to highly magnified 3-D visualization, dexterity afforded by 7 degrees of freedom that allow difficult dissections in narrow fields and the ease of reproducibility once the initial set up and instruments become familiar to the surgeon. As the application of robotic technology trickle downs from major academic centers to community hospitals, it becomes imperative that its role, limitations, learning curve and financial impact are understood by the novice robotic surgeon. In this article, we share our experience as it relates to the setup, common pitfalls and long term results for more commonly performed robotic assisted lung and thymic resections using the 4 arm da Vinci Xi robotic platform (Intuitive Surgical, Inc., Sunnyvale, CA, USA) to help guide those who are interested in adopting this technology.

Development of Laser-Polarized Noble Gas Magnetic Resonance Imaging (MRI) Technology

NASA Technical Reports Server (NTRS)

Walsworth, Ronald L.

2004-01-01

We are developing technology for laser-polarized noble gas nuclear magnetic resonance (NMR), with the aim of enabling it as a novel biomedical imaging tool for ground-based and eventually space-based application. This emerging multidisciplinary technology enables high-resolution gas-space magnetic resonance imaging (MRI)-e.g., of lung ventilation, perfusion, and gas-exchange. In addition, laser-polarized noble gases (3He and 1BXe) do not require a large magnetic field for sensitive NMR detection, opening the door to practical MRI with novel, open-access magnet designs at very low magnetic fields (and hence in confined spaces). We are pursuing two specific aims in this technology development program. The first aim is to develop an open-access, low-field (less than 0.01 T) instrument for MRI studies of human gas inhalation as a function of subject orientation, and the second aim is to develop functional imaging of the lung using laser-polarized He-3 and Xe-129.

Intersecting transcriptomic profiling technologies and long non-coding RNA function in lung adenocarcinoma: discovery, mechanisms, and therapeutic applications

PubMed Central

Castillo, Jonathan; Stueve, Theresa R.; Marconett, Crystal N.

2017-01-01

Previously thought of as junk transcripts and pseudogene remnants, long non-coding RNAs (lncRNAs) have come into their own over the last decade as an essential component of cellular activity, regulating a plethora of functions within multicellular organisms. lncRNAs are now known to participate in development, cellular homeostasis, immunological processes, and the development of disease. With the advent of next generation sequencing technology, hundreds of thousands of lncRNAs have been identified. However, movement beyond mere discovery to the understanding of molecular processes has been stymied by the complicated genomic structure, tissue-restricted expression, and diverse regulatory roles lncRNAs play. In this review, we will focus on lncRNAs involved in lung cancer, the most common cause of cancer-related death in the United States and worldwide. We will summarize their various methods of discovery, provide consensus rankings of deregulated lncRNAs in lung cancer, and describe in detail the limited functional analysis that has been undertaken so far. PMID:29113413

[Continuous lateral rotation or kinetic therapy: an update of knowledge].

PubMed

Calaf Tost, Carles; Comas Miquel, Emma

2005-01-01

Acute lung injury and, when extreme, acute respiratory distress syndrome, are thought to be expression of a diffuse and overwhelming inflammatory reaction of the pulmonary capillary membrane to a variety of causes. The ventilatory support is essential in this patients. In the last years we know the significance of the postural treatment in this type of patients through the prone positioning. The continuous lateral rotation therapy or kinetic therapy (KT) is the new manner by other positioning beside the technological advances. Lowly it's introducing in our setting. The follow article would respound the next questions: What's the KT? How must to make the KT? What recommendations have been offered by specialists from the complications? Which is it efectivity?

Mathematics of Ventilator-induced Lung Injury.

PubMed

Rahaman, Ubaidur

2017-08-01

Ventilator-induced lung injury (VILI) results from mechanical disruption of blood-gas barrier and consequent edema and releases of inflammatory mediators. A transpulmonary pressure (P L ) of 17 cmH 2 O increases baby lung volume to its anatomical limit, predisposing to VILI. Viscoelastic property of lung makes pulmonary mechanics time dependent so that stress (P L ) increases with respiratory rate. Alveolar inhomogeneity in acute respiratory distress syndrome acts as a stress riser, multiplying global stress at regional level experienced by baby lung. Limitation of stress (P L ) rather than strain (tidal volume [V T ]) is the safe strategy of mechanical ventilation to prevent VILI. Driving pressure is the noninvasive surrogate of lung strain, but its relations to P L is dependent on the chest wall compliance. Determinants of lung stress (V T , driving pressure, positive end-expiratory pressure, and inspiratory flow) can be quantified in terms of mechanical power, and a safe threshold can be determined, which can be used in decision-making between safe mechanical ventilation and extracorporeal lung support.

The theoretical foundation and research progress for WBRT combined with erlotinib for the treatment of multiple brain metastases in patients with lung adenocarcinoma.

PubMed

Zhuang, Hongqing; Wang, Jun; Zhao, Lujun; Yuan, Zhiyong; Wang, Ping

2013-11-15

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung adenocarcinoma, and a theoretical basis exists for utilising whole brain radiotherapy (WBRT) combined with erlotinib for the treatment for brain metastases in patients with lung adenocarcinoma. This therapeutic regimen has the potential to be a revolutionary treatment for which the most appropriate indication is lung adenocarcinoma. Currently, there is no difference in the treatment of brain metastasis, especially multiple brain metastases, in patients with lung adenocarcinoma of patients with other lung carcinomas. Furthermore, limited clinical trials that combine a TKI with WBRT to treat multiple lung adenocarcinoma metastases have been conducted, and many clinical questions remain unanswered. Lung adenocarcinoma has a high propensity to metastasize to the brain, and targeted therapy has been widely used; however, clinical trials are necessary to provide data to support the combination of erlotinib and WBRT. Copyright © 2013 UICC.

Double lung point in an 18-month-old child: a case report and literature review

PubMed Central

2015-01-01

Objective Double lung point is a rare sign of pneumothorax in clinical practice. In this report I presented an 18-month-old child who presented with bilateral pneumothorax. Data synthesis and case presentation Ultrasonography examination revealed conventional lung point sign on the right and double lung point on the left side. Thoracentesis was attempted and closed thoracic drainage was performed on the right side, but no gas was drawn on the left side. Clinical implication of double lung point sign found in chest ultrasonography is that the size of pneumothorax is limited and conservative treatment is enough. Conclusions To the best of our knowledge, this is the first case of double lung point identified with ultrasonography in child. The strength of the case is that the double lung point sign is supported by computed tomography (CT). Furthermore, we propose that the presence of double lung point indicates limited pneumothorax and conservative management may well be attempted. PMID:25922750

Development of phantom and methodology for 3D and 4D dose intercomparisons for advanced lung radiotherapy

NASA Astrophysics Data System (ADS)

Caloz, Misael; Kafrouni, Marilyne; Leturgie, Quentin; Corde, Stéphanie; Downes, Simon; Lehmann, Joerg; Thwaites, David

2015-01-01

There are few reported intercomparisons or audits of combinations of advanced radiotherapy methods, particularly for 4D treatments. As part of an evaluation of the implementation of advanced radiotherapy technology, a phantom and associated methods, initially developed for in-house commissioning and QA of 4D lung treatments, has been developed further with the aim of using it for end-to-end dose intercomparison of 4D treatment planning and delivery. The respiratory thorax phantom can house moving inserts with variable speed (breathing rate) and motion amplitude. In one set-up mode it contains a small ion chamber for point dose measurements, or alternatively it can hold strips of radiochromic film to measure dose distributions. Initial pilot and feasibility measurements have been carried out in one hospital to thoroughly test the methods and procedures before using it more widely across a range of hospitals and treatment systems. Overall, the results show good agreement between measured and calculated doses and distributions, supporting the use of the phantom and methodology for multi-centre intercomparisons. However, before wider use, refinements of the method and analysis are currently underway particularly for the film measurements.

Occupational pulmonary aluminosis: a case report.

PubMed

Smolková, Petra; Nakládalová, Marie; Tichý, Tomáš; Hampalová, Marie; Kolek, Vítězslav

2014-01-01

The authors present a case of occupational lung damage from exposure to dust containing aluminium. The first detected objective pathological finding was that of dispersed micronodules in the lungs seen in a chest radiograph. The final diagnosis of pulmonary aluminosis was established after three years of gradual exclusion of other interstitial lung diseases. The diagnosis was supported by the occupational history confirmed by hygiene assessment of the patient's workplace and especially by histological examination with elemental analysis of the lung tissue. The possibility of development of this rare condition should not be underestimated in workers at high-risk jobs.

Single lung transplantation from a brain-dead donor for a patient with idiopathic pulmonary fibrosis. A breakthrough after new legislation in Japan.

PubMed

Miyoshi, S; Minami, M; Ohta, M; Okumura, M; Takeda, S; Matsuda, H

2001-06-01

Two single lung transplants from a single cadaveric donor were successfully conducted at 2 institutions on March 29, 2000, the first such procedure in Japan under newly introduced legislation. Our patient was a 48-year-old woman with idiopathic pulmonary fibrosis who underwent left single-lung transplantation under cardiopulmonary support. The donor lung was preserved in 4 degrees C modified Euro-Collins solution. Total ischemic time was 5 hours and 37 minutes. The postoperative course was uneventful. The patient was discharged on postoperative day 62 with satisfactory respiratory function.

Why Do Patients and Caregivers Seek Answers From the Internet and Online Lung Specialists? A Qualitative Study

PubMed Central

Linssen, Cilia; Schramel, Franz MNH; Festen, Jan; Lammers, Ernst; Smit, Egbert F; Postmus, Pieter E; Westerman, Marjan J

2014-01-01

Background Since its launch in 2003, the Dutch Lung Cancer Information Center’s (DLIC) website has become increasingly popular. The most popular page of the website is the section “Ask the Physician”, where visitors can ask an online lung specialist questions anonymously and receive an answer quickly. Most questions were not only asked by lung cancer patients but also by their informal caregivers. Most questions concerned specific information about lung cancer. Objective Our goal was to explore the reasons why lung cancer patients and caregivers search the Internet for information and ask online lung specialists questions on the DLIC’s interactive page, “Ask the Physician”, rather than consulting with their own specialist. Methods This research consisted of a qualitative study with semistructured telephone interviews about medical information-seeking behavior (eg, information needs, reasons for querying online specialists). The sample comprised 5 lung cancer patients and 20 caregivers who posed a question on the interactive page of the DLIC website. Results Respondents used the Internet and the DLIC website to look for lung cancer–related information (general/specific to their personal situation) and to cope with cancer. They tried to achieve a better understanding of the information given by their own specialist and wanted to be prepared for the treatment trajectory and disease course. This mode of information supply helped them cope and gave them emotional support. The interactive webpage was also used as a second opinion. The absence of face-to-face contact made respondents feel freer to ask for any kind of information. By being able to pose a question instantly and receiving a relatively quick reply from the online specialist to urgent questions, respondents felt an easing of their anxiety as they did not have to wait until the next consultation with their own specialist. Conclusions The DLIC website with its interactive page is a valuable complementary mode of information supply and supportive care for lung cancer patients and caregivers. PMID:24496139

Lung Volume Reduction Surgery for Respiratory Failure in Infants With Bronchopulmonary Dysplasia.

PubMed

Sohn, Bongyeon; Park, Samina; Park, In Kyu; Kim, Young Tae; Park, June Dong; Park, Sung-Hye; Kang, Chang Hyun

2018-04-01

Lung volume reduction surgery (LVRS) can be performed in patients with severe emphysematous disease. However, LVRS in pediatric patients has not yet been reported. Here, we report our experience with 2 cases of pediatric LVRS. The first patient was a preterm infant girl with severe bronchopulmonary dysplasia, pulmonary hypertension, and hypothyroidism. The emphysematous portion of the right lung was removed via sternotomy and right hemiclamshell incision. The patient was discharged on full-time home ventilator support for 3 months after the surgery. Since then, her respiratory function has improved continuously. She no longer needs oxygen supplementation or ventilator care. Her T-cannula was removed recently. The second patient was also a preterm infant girl with bronchopulmonary dysplasia. She was born with pulmonary hypertension and multiple congenital anomalies, including an atrial septal defect. Despite receiving the best supportive care, she could not be taken off the mechanical ventilator because of severe hypercapnia. We performed LVRS on the right lung via thoracotomy. She was successfully weaned off the mechanical ventilator 1 month after the surgery. She was discharged without severe complications at 3 months after the operation. At present, she is growing well with the help of intermittent home ventilator support. She can now tolerate an oral diet. Our experience shows that LVRS can be considered as a treatment option for pediatric patients with severe emphysematous lung. It is especially helpful for discontinuing prolonged mechanical ventilator care for patients with respiratory failure. Copyright © 2018 by the American Academy of Pediatrics.

Ventilation distribution measured with EIT at varying levels of pressure support and Neurally Adjusted Ventilatory Assist in patients with ALI.

PubMed

Blankman, Paul; Hasan, Djo; van Mourik, Martijn S; Gommers, Diederik

2013-06-01

The purpose of this study was to compare the effect of varying levels of assist during pressure support (PSV) and Neurally Adjusted Ventilatory Assist (NAVA) on the aeration of the dependent and non-dependent lung regions by means of Electrical Impedance Tomography (EIT). We studied ten mechanically ventilated patients with Acute Lung Injury (ALI). Positive-End Expiratory Pressure (PEEP) and PSV levels were both 10 cm H₂O during the initial PSV step. Thereafter, we changed the inspiratory pressure to 15 and 5 cm H₂O during PSV. The electrical activity of the diaphragm (EAdi) during pressure support ten was used to define the initial NAVA gain (100 %). Thereafter, we changed NAVA gain to 150 and 50 %, respectively. After each step the assist level was switched back to PSV 10 cm H₂O or NAVA 100 % to get a new baseline. The EIT registration was performed continuously. Tidal impedance variation significantly decreased during descending PSV levels within patients, whereas not during NAVA. The dorsal-to-ventral impedance distribution, expressed according to the center of gravity index, was lower during PSV compared to NAVA. Ventilation contribution of the dependent lung region was equally in balance with the non-dependent lung region during PSV 5 cm H₂O, NAVA 50 and 100 %. Neurally Adjusted Ventilatory Assist ventilation had a beneficial effect on the ventilation of the dependent lung region and showed less over-assistance compared to PSV in patients with ALI.

[Advances in Liquid Biopsy and its Clinical Application in the Diagnosis 
and Treatment of Non-small Cell Lung Cancer].

PubMed

Zheng, Difan; Chen, Haiquan

2016-06-20

With the advances of technology, great progresses have been made in liquid biopsy in recent years. Liquid biopsy is currently playing a more and more important role in early diagnosis and treatment of cancer. Compared with traditional tissue biopsy, liquid biopsy is more popular in clinical practice due to its non-invasiveness, convenience and high repeatability. It has huge potential in the future. This review introduces circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) as the most important objects in liquid biopsy, mainly focusing on their history, biological characteristics, detection technologies, limitations and applications in non-small cell lung cancer.

Proteomic analysis of lung tissue by DIGE

USDA-ARS?s Scientific Manuscript database

Lungs perform an essential physiological function, mediated by a complex series of events that involve the coordination of multiple cell types to support not only gaseous exchange, but homeostasis and protection from infection. Guinea pigs are an important animal disease model for a number of infect...

Computerized analysis of cytology and fluorescence in situ hybridization (FISH) in induced sputum for lung cancer detection.

PubMed

Guber, Alexander; Greif, Joel; Rona, Roni; Fireman, Elizabeth; Madi, Lea; Kaplan, Tal; Yemini, Zipi; Gottfried, Maya; Katz, Ruth L; Daniely, Michal

2010-10-25

Lung cancer results from a multistep process, whereby genetic and epigenetic alterations lead to a malignant phenotype. Somatic mutations, deletions, and amplifications can be detected in the tumor itself, but they can also be found in histologically normal bronchial epithelium as a result of field cancerization. The present feasibility study describes a computer-assisted analysis of induced sputum employing morphology and fluorescence in situ hybridization (target-FISH), using 2 biomarkers located at chromosomes 3p22.1 and 10q22.3. Induced sputum samples were collected using a standardized protocol from 12 patients with lung cancer and from 15 healthy, nonsmoking controls. We used an automated scanning system that allows consecutive scans of morphology and FISH of the same slide. Cells derived for the lower airways were analyzed for the presence of genetic alterations in the 3p22.1 and 10q22.3 loci. The cutoff for a positive diagnosis was defined as >4% of cells showing genetic alterations. Eleven of 12 lung cancer patients and 12 of 15 controls were identified correctly, giving an overall sensitivity and specificity of 91.66% and 80%, respectively. This study describes a new technology for detecting lung cancer noninvasively in induced sputum via a combination of morphology and FISH analysis (target-FISH) using computer-assisted technology. This approach may potentially be utilized for mass screening of high-risk populations. © 2010 American Cancer Society.

Reciprocal peer review for quality improvement: an ethnographic case study of the Improving Lung Cancer Outcomes Project.

PubMed

Aveling, Emma-Louise; Martin, Graham; Jiménez García, Senai; Martin, Lisa; Herbert, Georgia; Armstrong, Natalie; Dixon-Woods, Mary; Woolhouse, Ian

2012-12-01

Peer review offers a promising way of promoting improvement in health systems, but the optimal model is not yet clear. We aimed to describe a specific peer review model-reciprocal peer-to-peer review (RP2PR)-to identify the features that appeared to support optimal functioning. We conducted an ethnographic study involving observations, interviews and documentary analysis of the Improving Lung Cancer Outcomes Project, which involved 30 paired multidisciplinary lung cancer teams participating in facilitated reciprocal site visits. Analysis was based on the constant comparative method. Fundamental features of the model include multidisciplinary participation, a focus on discussion and observation of teams in action, rather than paperwork; facilitated reflection and discussion on data and observations; support to develop focused improvement plans. Five key features were identified as important in optimising this model: peers and pairing methods; minimising logistic burden; structure of visits; independent facilitation; and credibility of the process. Facilitated RP2PR was generally a positive experience for participants, but implementing improvement plans was challenging and required substantial support. RP2PR appears to be optimised when it is well organised; a safe environment for learning is created; credibility is maximised; implementation and impact are supported. RP2PR is seen as credible and legitimate by lung cancer teams and can act as a powerful stimulus to produce focused quality improvement plans and to support implementation. Our findings have identified how RP2PR functioned and may be optimised to provide a constructive, open space for identifying opportunities for improvement and solutions.

The burden of lung cancer in Latin-America and challenges in the access to genomic profiling, immunotherapy and targeted treatments.

PubMed

Raez, Luis E; Cardona, Andrés F; Santos, Edgardo S; Catoe, Heath; Rolfo, Christian; Lopes, Gilberto; Barrios, Carlos; Mas, Luis A; Vallejos, Carlos; Zatarain-Barrón, Zyanya Lucia; Caglevic, Christian; Arrieta, Oscar

2018-05-01

Lung cancer is a public health problem worldwide and Latin America (LATAM) cannot escape this reality. This malignant disease has not only a high prevalence in the region, but is also the main cause of cancer related deaths, and in other emerging countries, the incidence rates are still on the rise. Interestingly in most LATAM countries, lung cancer mortality has been decreasing in men but not in women, reflecting smoking patterns in countries such as Chile, Bolivia, and Brazil. Despite the fact that these issues are well known to government agencies, physicians and patients in the region, current efforts still fall behind those needed in order to face this problem of epidemic proportions. Tobacco control and smoking cessation are the most important interventions against lung cancer, but even with their optimal implementation (which is far from reality at this time) the number of cases in the foreseeable future would still be significant. Beyond tobacco control, advances in our understanding of the molecular component of lung cancer have resulted in new targeted therapies and immune check point inhibitors, which have improved clinical outcomes but at a considerably higher financial cost. LATAM has not widely and speedily adopted these strategies, including new technology and approved novel drugs, due to a number of facts, and therefore only a dismal proportion of LATAḾs patient population have benefited from these new advances. A keen focus on a heterogeneous education system for caregivers in lung cancer treatment would likely help standardize care and improve future potential gains from domestic research. In this review we discuss the challenges of treatment implementation, focusing on new technologies. Copyright © 2018 Elsevier B.V. All rights reserved.

Diagnostic value of protein chips constructed by lung-cancer-associated markers selected by the T7 phage display library.

PubMed

Li, Hong-Mei; Guo, Kang; Yu, Zhuang; Feng, Rui; Xu, Ping

2015-07-01

Traditional diagnostic technology with tumor biomarkers is inefficient, expensive and requires a large number of serum samples. The purpose of this study was to construct human lung cancer protein chips with new lung cancer biomarkers screened by the T7-phage display library, and improve the early diagnosis rate of lung cancer. A T7-phage cDNA display library was constructed of fresh samples from 30 lung cancer patients. With biopanning and high-throughput screening, we gained the immunogenic phage clones from the cDNA library. The insert of selected phage was blasted at GeneBank for alignment to find the exact or the most similar known genes. Protein chips were then constructed and used to assay their expression level in lung cancer serum from 217 cases of lung cancer groups:80 cases of benign lung disease and 220 healthy controls. After four rounds of Biopanning and two rounds of enzyme-linked immunosorbent assay, 12 phage monoclonal samples were selected from 2880 phage monoclonal samples. After blasting at GeneBank, six similar genes were used to construct diagnostic protein chips. The protein chips were then used to assay expression level in lung cancer serum. The expression level of six genes in lung cancer groups was significantly higher than those in the other two groups (P < 0.05). In this study, we successfully constructed diagnostic protein chips with biomarkers selected from the lung cancer T7-phage cDNA library, which can be used for the early screening of lung cancer patients.

Short-term outcomes of cadaveric lung transplantation in ventilator-dependent patients

PubMed Central

2009-01-01

Introduction Survival after cadaveric lung transplantation (LTx) in respiratory failure recipients who were already dependent on ventilation support prior to transplantation is poor, with a relatively high rate of surgical mortality and morbidity. In this study, we sought to describe the short-term outcomes of bilateral sequential LTx (BSLTx) under extracorporeal membrane oxygenation (ECMO) support in a consecutive series of preoperative respiratory failure patients. Methods Between July 2006 and July 2008, we performed BSLTx under venoarterious (VA) ECMO support in 10 respiratory failure patients with various lung diseases. Prior to transplantation, 6 patients depended on invasive mechanical ventilation support and the others (40%) needed noninvasive positive pressure ventilation to maintain adequate gas exchange. Their mean age was 40.9 years and the mean observation period was 16.4 months. Results Except for 1 ECMO circuit that had been set up in the intensive care unit for pulmonary crisis 5 days prior to transplantation, most ECMO (90%) circuits were set up in the operating theater prior to pneumonectomy of native lung during transplantation. Patients were successfully weaned off ECMO circuits immediately after transplantation in 8 cases, and within 1 day (1/10 patients) and after 9 days (1/10 patients) due to severe reperfusion lung edema following transplantation. The mean duration of ECMO support in those successfully weaned off in the operating theater (n = 8) was 7.8 hours. The average duration of intensive care unit stay (n = 10) was 43.1 days (range, 35 to 162 days) and hospital stay (n = 10) was 70 days (range, 20 to 86 days). Although 4 patients (40%) had different degrees of complicated postoperative courses unrelated to ECMO, all patients were discharged home postoperatively. The mean forced vital capacity and the forced expiratory volume in 1 second both increased significantly postoperatively. The cumulative survival rates at 3 months and at 12 months post-transplantation were 100% and 90%. Conclusions Although BSLTx in this critical population has varied surgical complications and prolonged length of postoperative ICU and hospital stays, all the patients observed in this study could tolerate the transplant procedures under VA ECMO support with promising pulmonary function and satisfactory short-term outcome. PMID:19660110

Electromagnetic Navigational Bronchoscopy

PubMed Central

Port, Jeffrey; Harrison, Sebron

2013-01-01

Despite advances in technology and treatment options, lung cancer remains a deadly disease. National screening programs are being instituted in an attempt to discover lung cancer in high-risk individuals at an earlier stage. Such screening programs invariably discover small peripheral nodules that previously would not have been clinically apparent; the management of such lesions can be challenging. Current diagnostic options such as percutaneous biopsy are effective; however, they are hindered by their risk of morbidity such as pneumothorax. Electromagnetic bronchoscopy (ENB) is an emerging technology that allows the practitioner the ability to both sample and treat small peripheral pulmonary lesions. In experienced centers, ENB provides high rates of diagnostic yield for small lesions and a complication rate significantly lower than that of more conventional diagnostic modalities. Although there are current barriers to its widespread utilization (cost, specialized imaging, technical training), these obstacles will handled similarly to any other emerging technology and will likely not be long-term impediments to its use. PMID:24436528

Small Nodules Localization on CT Images of Lungs

NASA Astrophysics Data System (ADS)

Snezhko, E. V.; Kharuzhyk, S. A.; Tuzikov, A. V.; Kovalev, V. A.

2017-05-01

According to the World Health Organization (WHO) lung cancer remains the leading cause of death of men among all malignant tumors [1, 2]. One of the reasons of such a statistics is the fact that the lung cancer is hardly diagnosed on the yearly stages when it is almost asymptomatic. The purpose of this paper is to present a Computer-Aided Diagnosis (CAD) software developed for assistance of early detection of nodules in CT lung images including solitary pulmonary nodules (SPN) as well as multiple nodules. The efficiency of nodule localization was intended to be as high as the level of the best practice. The software developed supports several functions including lungs segmentation, selection of nodule candidates and nodule candidates filtering.

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

PubMed

Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

2017-12-01

Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

A review of the lung transplantation programme in Ireland 2005-2007.

PubMed

Bartosik, Waldemar; Egan, Jim J; Soo, Alan; Remund, Kaspar F; Nölke, Lars; McCarthy, James F; Wood, Alfred E

2009-05-01

Lung transplantation is a recognised surgical option for patients with end stage respiratory disease. We present data relating to the initiation of the Irish lung transplant programme in 2005. Seventeen patients: 7 male and 10 female have undergone lung transplantation. The indications for lung transplantation included COPD (n=8), idiopathic pulmonary fibrosis (n=5), bronchiolitis obliterans (n=2), lymphangioleiomyomatosis (n=1), and cystic fibrosis (n=1). Eleven single lungs transplants were completed, while six patients underwent double sequential lung transplantation. The immunosuppression regimen included basiliximab as induction therapy, with steroids, mycophenolate mofetil nd cyclosporine or tacrolimus. The operative mortality was zero. One patient died at 10 months post double lung transplantation secondary to bronchiolitis obliterans. Primary graft dysfunction was observed in two patients who required ventilatory support for 3 and 5 days respectively. Acute cellular rejection was observed in four patients (grade A2 n=3, grade A3 n=2). The cumulative 1-year survival was 94.1%, which compares favourably to an international standard of 78%. The initiation of a lung transplant programme in Ireland has been successfully undertaken and initially provided results comparable to established lung transplant programs.

Lung transplant of extrahospitalary donor after cardiac death.

PubMed

Mateos Rodríguez, Alonso A; Navalpotro Pascual, José Maria; del Río Gallegos, Francisco

2013-04-01

Non-heart-beating donors (NHBDs) have to meet the predefined criteria for organ donation including death from irreversible cessation of the beating heart. The Maastricht conference defined 4 NHBD categories to differentiate their viability and ethical-legal support. In Spain, NHBDs who originate from an out-of-hospital setting correspond to type II donors. These are patients who have had a cardiac arrest outside hospital and, after failed CPR attempts, are transferred with hemodynamic support measures to the hospital for organ donation. The Hospital Clínico San Carlos also has a lung donation program in collaboration with the Hospital Puerta de Hierro in Madrid and the Hospital Marques de Valdecilla in Santander. The objective of this study is to describe the results of lung transplantation of after cardiac death program, specifically the section regarding lung extraction donation. Twenty potential lung donors were obtained during the study. Most patients were male (19 cases), with a mean age of 42 years (36.5-49.5 years). A total of 33 lungs were donated (18 right and 15 left lungs). Most extractions were multiorganic (19 cases). One liver, 19 kidneys, 2 pancreas, and 19 corneas were obtained from these donors; bone tissue was obtained from all donors. The transplantation was bipulmonary in 13 cases and unipulmonary in 7. Thirty days after transplantation, 2 recipients died, 1 died of stroke associated with bilateral pneumonia and 1 died of hypovolemic shock resulting from hemothorax. The remaining 18 patients were progressing well at 30 days. Our data suggest that lung transplantation from patients after extrahospitalary cardiac death is feasible. Copyright © 2013 Elsevier Inc. All rights reserved.

Urgent Chemotherapy for Life-Threatening Complications Related to Solid Neoplasms.

PubMed

Zerbib, Yoann; Rabbat, Antoine; Fartoukh, Muriel; Bigé, Naïke; Andréjak, Claire; Mayaux, Julien; De Prost, Nicolas; Misset, Benoît; Lemiale, Virginie; Bruneel, Fabrice; Maizel, Julien; Ricome, Sylvie; Jacobs, Frédéric; Bornstain, Caroline; Dupont, Hervé; Baudin, François; Azoulay, Elie; Pène, Frédéric

2017-07-01

Solid neoplasms can be directly responsible for organ failures at the time of diagnosis or relapse. The management of such specific complications relies on urgent chemotherapy and eventual instrumental or surgical procedures, combined with advanced life support. We conducted a multicenter study to address the prognosis of this condition. A multicenter retrospective (2001-2015) chart review. Medical and respiratory ICUs. Adult patients who received urgent chemotherapy in the ICU for organ failure related to solid neoplasms were included. The modalities of chemotherapy, requirements of adjuvant instrumental or surgical procedures, and organ supports were collected. Endpoints were short- and long-term survival rates. None. One hundred thirty-six patients were included. Lung cancer was the most common malignancy distributed into small cell lung cancer (n = 57) and non-small cell lung cancer (n = 33). The main reason for ICU admission was acute respiratory failure in 111 patients (81.6%), of whom 89 required invasive mechanical ventilation. Compression and tissue infiltration by tumor cells were the leading mechanisms resulting in organ involvement in 78 (57.4%) and 47 (34.6%) patients. The overall in-ICU, in-hospital, 6-month, and 1-year mortality rates were 37%, 58%, 74%, and 88%, respectively. Small cell lung cancer was identified as an independent predictor of hospital survival. However, this gain in survival was not sustained since the 1-year survival rates of small cell lung cancer, non-small cell lung cancer, and non-lung cancer patients all dropped below 20%. Urgent chemotherapy along with aggressive management of organ failures in the ICU can be lifesaving in very selected cancer patients, most especially with small cell lung cancer, although the long-term survival is hardly sustainable.

Low-flow venovenous CO₂ removal in association with lung protective ventilation strategy in patients who develop severe progressive respiratory acidosis after lung transplantation.

PubMed

Ruberto, F; Bergantino, B; Testa, M C; D'Arena, C; Zullino, V; Congi, P; Paglialunga, S G; Diso, D; Venuta, F; Pugliese, F

2013-09-01

Primary graft dysfunction (PGD) might occur after lung transplantation. In some severe cases, conventional therapies like ventilatory support, administration of inhaled nitric oxide (iNO), and intravenous prostacyclins are not sufficient to provide an adequate gas exchange. The aim of our study was to evaluate the use of a lung protective ventilation strategy associated with a low-flow venovenous CO2 removal treatment to reduce ventilator-associated injury in patients that develop severe PGD after lung transplantation. From January 2009 to January 2011, 3 patients developed PGD within 24 hours after lung transplantation. In addition to conventional medical treatment, including hemodynamic support, iNO and prostaglandin E1 (PGE1), we initiated a ventilatory protective strategy associated with low-flow venovenous CO2 removal treatment (LFVVECCO2R). Hemodynamic and respiratory parameters were assessed at baseline as well as after 3, 12, 24, and 48 hours. No adverse events were registered. Despite decreased baseline elevated pulmonary positive pressures, application of a protective ventilation strategy with LFVVECCO2R reduced PaCO2 and pulmonary infiltrates as well as increased pH values and PaO2/FiO2 ratios. Every patient showed simultaneous improvement of clinical and hemodynamic conditions. They were weaned from mechanical ventilation and extubated after 24 hours after the use of the low-flow venovenous CO2 removal device. The use of LFVVECCO2R together with a protective lung ventilation strategy during the perioperative period of lung transplantation may be a valid clinical strategy for patients with PGD and severe respiratory acidosis occured despite adequate mechanical ventilation. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparative proteomic analysis of lung tissue from guinea pigs with Leptospiral Pulmonary Haemorrhage Syndrome (LPHS) reveals a decrease in abundance of host proteins involved in cytoskeletal and cellular organization

USDA-ARS?s Scientific Manuscript database

The recent completion of the complete genome sequence of the guinea pig (Cavia porcellus) provides innovative opportunities to apply proteomic technologies to an important animal model of disease. In this study, a 2-D guinea pig proteome lung map was used to investigate the pathogenic mechanisms of ...

Prophylactic Use of High-Frequency Percussive Ventilation in Patients with Inhalation Injury,

DTIC Science & Technology

1991-06-01

stabilizing such col- in burn wound management, infection control, lapsed diseased lung segments. 3- 2 In addition some in- and metabolic support increased the...confirmed in each patient by bronchoscopy and/or󈧥 Xe- 8. PCO2 < 50 mmHg but progressively increasing non ventilation-perfusion lung scan. The presence of...death for all patients admitted to the In- Inhalation injury documented by bronchoscopy or Xenon lung scan stitute of Surgical Research between January

Nanotechnology applications in thoracic surgery.

PubMed

Hofferberth, Sophie C; Grinstaff, Mark W; Colson, Yolonda L

2016-07-01

Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of 'theranostic' multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application.

PubMed

Alapati, Deepthi; Morrisey, Edward E

2017-03-01

Although our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis, and alpha-1 antitrypsin deficiency is extensive, treatment options are lacking. Because the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intratracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene-editing technology is a promising approach to repairing or inactivating disease-causing mutations. Recent reports have provided proof of concept by using CRISPR/Cas9 to successfully repair or inactivate mutations in animal models of monogenic human diseases. Potential pulmonary applications of CRISPR/Cas9 gene editing include gene correction of monogenic diseases in pre- or postnatal lungs and ex vivo gene editing of patient-specific airway stem cells followed by autologous cell transplant. Strategies to enhance gene-editing efficiency and eliminate off-target effects by targeting pulmonary stem/progenitor cells and the assessment of short-term and long-term effects of gene editing are important considerations as the field advances. If methods continue to advance rapidly, CRISPR/Cas9-mediated gene editing may provide a novel opportunity to correct monogenic diseases of the respiratory system.

Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL6 in non-small cell lung cancer in vivo

PubMed Central

Vicent, Silvestre; Sayles, Leanne C.; Vaka, Dedeepya; Khatri, Purvesh; Gevaert, Olivier; Chen, Ron; Zheng, Yanyan; Gillespie, Anna K.; Clarke, Nicole; Xu, Yue; Shrager, Joseph; Hoang, Chuong D.; Plevritis, Sylvia; Butte, Atul J.; Sweet-Cordero, E. Alejandro

2013-01-01

Cancer-associated fibroblasts (CAFs) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study the role of CAFs in NSCLC, a cross-species functional characterization of mouse and human lung CAFs was performed. CAFs supported the growth of lung cancer cells in vivo by secretion of soluble factors that directly stimulate the growth of tumor cells. Gene expression analysis comparing normal mouse lung fibroblasts (NFs) and mouse lung CAFs identified multiple genes that correlate with the CAF phenotype. A gene signature of secreted genes upregulated in CAFs was an independent marker of poor survival in NSCLC patients. This secreted gene signature was upregulated in NFs after long-term exposure to tumor cells, demonstrating that NFs are “educated” by tumor cells to acquire a CAF-like phenotype. Functional studies identified important roles for CLCF1-CNTFR and IL6-IL6R signaling, in promoting growth of NSCLC cells. This study identifies novel soluble factors contributing to the CAF protumorigenic phenotype in NSCLC and suggests new avenues for the development of therapeutic strategies. PMID:22962265

Clinical utility of circulating tumour cell detection in non-small-cell lung cancer.

PubMed

Fusi, Alberto; Metcalf, Robert; Krebs, Matthew; Dive, Caroline; Blackhall, Fiona

2013-12-01

Recent years have witnessed increased interest in the detection of circulating tumour cells (CTCs) for diagnosis, monitoring, and treatment decision making in patients with cancer. Factors that have led to accelerated research in this field include advances in technologies for examination of intact CTCs, personalised medicine with treatment selection according to molecular characteristics, and continued lack of understanding of the biology of treatment resistance and metastasis. CTCs offer promise as a surrogate for tissue where there is insufficient tissue for molecular analysis and where there is a requirement to serially monitor molecular changes in cancer cells through treatment or on progression. In patients with either small cell or non-small cell lung cancer (NSCLC), there is evidence that CTC number is prognostic and that CTCs counted before and after treatment mirror treatment response. In patients with molecularly defined subtypes of NSCLC, CTCs demonstrate the same molecular changes as the cancer cells of the tumour. However, CTCs are not quite ready for "primetime" in the lung cancer clinic. There are still more questions than answers with respect to the optimal technologies for their detection and analysis, their biological significance, and their clinical utility. Despite this the current pace of progress in CTC technology development seems set to make "liquid biopsies" a clinical reality within the next decade. For the everyday clinician and clinical trialist, it will be important to maintain knowledge of the strengths and weaknesses of the technologies and evolving evidence base for CTCs as a routinely used diagnostic tool.

The transcriptome of nitrofen-induced pulmonary hypoplasia in the rat model of congenital diaphragmatic hernia.

PubMed

Mahood, Thomas H; Johar, Dina R; Iwasiow, Barbara M; Xu, Wayne; Keijzer, Richard

2016-05-01

We currently do not know how the herbicide nitrofen induces lung hypoplasia and congenital diaphragmatic hernia in rats. Our aim was to compare the differentially expressed transcriptome of nitrofen-induced hypoplastic lungs to control lungs in embryonic day 13 rat embryos before the development of embryonic diaphragmatic defects. Using next-generation sequencing technology, we identified the expression profile of microRNA (miRNA) and mRNA genes. Once the dataset was validated by both RT-qPCR and digital-PCR, we conducted gene ontology, miRNA target analysis, and orthologous miRNA sequence matching for the deregulated miRNAs in silico. Our study identified 186 known mRNA and 100 miRNAs which were differentially expressed in nitrofen-induced hypoplastic lungs. Sixty-four rat miRNAs homologous to known human miRNAs were identified. A subset of these genes may promote lung hypoplasia in rat and/or human, and we discuss their associations. Potential miRNA pathways relevant to nitrofen-induced lung hypoplasia include PI3K, TGF-β, and cell cycle kinases. Nitrofen-induced hypoplastic lungs have an abnormal transcriptome that may lead to impaired development.

Lung cancer screening beyond low-dose computed tomography: the role of novel biomarkers.

PubMed

Hasan, Naveed; Kumar, Rohit; Kavuru, Mani S

2014-10-01

Lung cancer is the most common and lethal malignancy in the world. The landmark National lung screening trial (NLST) showed a 20% relative reduction in mortality in high-risk individuals with screening low-dose computed tomography. However, the poor specificity and low prevalence of lung cancer in the NLST provide major limitations to its widespread use. Furthermore, a lung nodule on CT scan requires a nuanced and individualized approach towards management. In this regard, advances in high through-put technology (molecular diagnostics, multi-gene chips, proteomics, and bronchoscopic techniques) have led to discovery of lung cancer biomarkers that have shown potential to complement the current screening standards. Early detection of lung cancer can be achieved by analysis of biomarkers from tissue samples within the respiratory tract such as sputum, saliva, nasal/bronchial airway epithelial cells and exhaled breath condensate or through peripheral biofluids such as blood, serum and urine. Autofluorescence bronchoscopy has been employed in research setting to identify pre-invasive lesions not identified on CT scan. Although these modalities are not yet commercially available in clinic setting, they will be available in the near future and clinicians who care for patients with lung cancer should be aware. In this review, we present up-to-date state of biomarker development, discuss their clinical relevance and predict their future role in lung cancer management.

From Mice and Men to Earth and Space: Joint NASA-NCI Workshop on Lung Cancer Risk Resulting from Space and Terrestrial Radiation

PubMed Central

Shay, Jerry W.; Cucinotta, Francis A.; Sulzman, Frank M.; Coleman, C. Norman; Minna, John D.

2011-01-01

On June 27–28, 2011 scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA – available data suggest lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high energy protons from solar flares and not from gamma radiation. By contrast the NCI is endeavoring to estimate the increased lung cancer risk from the potential wide-spread implementation of computed tomography (CT) screening in individuals at high risk for developing lung cancer based on the National Lung Cancer Screening Trial (NLST). For the latter, exposure will be x-rays from CT scans from the screening (which uses “low dose” CT scans) and also from follow-up scans used to evaluate abnormalities found during initial screening. Topics discussed included the risk of lung cancer arising after HZE particle, proton, and low dose Earth radiation exposure. The workshop examined preclinical models, epidemiology, molecular markers, “omics” technology, radiobiology issues, and lung stem cells (LSC) that relate to the development of lung cancer. PMID:21900398

78 FR 27243 - Proposed Collection; 60-Day Comment Request: Interactive Informed Consent for Pediatric Clinical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

... public comment on proposed data collection projects, the National Institute Heart, Lung, and Blood... projects to be submitted to the Office of Management and Budget (OMB) for review and approval. Written... other technological collection techniques or other forms of information technology. To Submit Comments...

Unraveling the Links Between the Initiation of Ventilation and Brain Injury in Preterm Infants

PubMed Central

Barton, Samantha K.; Tolcos, Mary; Miller, Suzie L.; Roehr, Charles C.; Schmölzer, Georg M.; Davis, Peter G.; Moss, Timothy J. M.; LaRosa, Domenic A.; Hooper, Stuart B.; Polglase, Graeme R.

2015-01-01

The initiation of ventilation in the delivery room is one of the most important but least controlled interventions a preterm infant will face. Tidal volumes (V T) used in the neonatal intensive care unit are carefully measured and adjusted. However, the V Ts that an infant receives during resuscitation are usually unmonitored and highly variable. Inappropriate V Ts delivered to preterm infants during respiratory support substantially increase the risk of injury and inflammation to the lungs and brain. These may cause cerebral blood flow instability and initiate a cerebral inflammatory cascade. The two pathways increase the risk of brain injury and potential life-long adverse neurodevelopmental outcomes. The employment of new technologies, including respiratory function monitors, can improve and guide the optimal delivery of V Ts and reduce confounders, such as leak. Better respiratory support in the delivery room has the potential to improve both respiratory and neurological outcomes in this vulnerable population. PMID:26618148

Hmga2 is required for canonical WNT signaling during lung development

PubMed Central

2014-01-01

Background The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. HMG proteins are present at high levels in various undifferentiated tissues during embryonic development and their levels are strongly reduced in the corresponding adult tissues, where they have been implicated in maintaining and activating stem/progenitor cells. Here we deciphered the role of the high-mobility-group AT-hook protein 2 (HMGA2) during lung development by analyzing the lung of Hmga2-deficient mice (Hmga2 −/− ). Results We found that Hmga2 is expressed in the mouse embryonic lung at the distal airways. Analysis of Hmga2 −/− mice showed that Hmga2 is required for proper cell proliferation and distal epithelium differentiation during embryonic lung development. Hmga2 knockout led to enhanced canonical WNT signaling due to an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as well as a reduction of the WNT signaling antagonizing proteins GATA-binding protein 6 and frizzled homolog 2. Analysis of siRNA-mediated loss-of-function experiments in embryonic lung explant culture confirmed the role of Hmga2 as a key regulator of distal lung epithelium differentiation and supported the causal involvement of enhanced canonical WNT signaling in mediating the effect of Hmga2-loss-of-fuction. Finally, we found that HMGA2 directly regulates Gata6 and thereby modulates Fzd2 expression. Conclusions Our results support that Hmga2 regulates canonical WNT signaling at different points of the pathway. Increased expression of the secreted WNT glycoproteins might explain a paracrine effect by which Hmga2-knockout enhanced cell proliferation in the mesenchyme of the developing lung. In addition, HMGA2-mediated direct regulation of Gata6 is crucial for fine-tuning the activity of WNT signaling in the airway epithelium. Our results are the starting point for future studies investigating the relevance of Hmga2-mediated regulation of WNT signaling in the adult lung within the context of proper balance between differentiation and self-renewal of lung stem/progenitor cells during lung regeneration in both homeostatic turnover and repair after injury. PMID:24661562

Anesthesiology Devices; Reclassification of Membrane Lung for Long-Term Pulmonary Support; Redesignation as Extracorporeal Circuit and Accessories for Long-Term Respiratory/Cardiopulmonary Failure. Final order.

PubMed

2016-02-12

The Food and Drug Administration (FDA) is issuing a final order to redesignate membrane lung devices for long-term pulmonary support, a preamendments class III device, as extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary failure, and to reclassify the device to class II (special controls) in patients with acute respiratory failure or acute cardiopulmonary failure where other available treatment options have failed, and continued clinical deterioration is expected or the risk of death is imminent. A membrane lung device for long-term pulmonary support (>6 hours) refers to the oxygenator in an extracorporeal circuit used during long-term procedures, commonly referred to as extracorporeal membrane oxygenation (ECMO). Because a number of other devices and accessories are used with the oxygenator in the circuit, the title and identification of the regulation are revised to include extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary failure. Although an individual device or accessory used in an ECMO circuit may already have its own classification regulation when the device or accessory is intended for short-term use (<=6 hours), such device or accessory will be subject to the same regulatory controls applied to the oxygenator (i.e., class II, special controls) when evaluated as part of the ECMO circuit for long-term use (>6 hours). On its own initiative, based on new information, FDA is revising the classification of the membrane lung device for long-term pulmonary support.

Alveolar and serum concentrations of imipenem in two lung transplant recipients supported with extracorporeal membrane oxygenation.

PubMed

Welsch, C; Augustin, P; Allyn, J; Massias, L; Montravers, P; Allou, N

2015-02-01

Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support. We report the cases of 2 patients supported with venovenous ECMO for refractory acute respiratory distress syndrome following single lung transplantation for pulmonary fibrosis, treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of Patient 2. Minimum inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L, respectively. Both patients were still alive on day 28. This is the first report, to our knowledge, of imipenem concentrations in lung transplantation patients supported with ECMO. This study confirms high variability in imipenem trough concentrations in patients on ECMO and with preserved renal function. An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended, where available. Population pharmacokinetic studies are indicated to develop evidence-based dosing guidelines for ECMO patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of long non-coding RNA in drug resistance in non-small cell lung cancer.

PubMed

Wang, Leirong; Ma, Leina; Xu, Fei; Zhai, Wenxin; Dong, Shenghua; Yin, Ling; Liu, Jia; Yu, Zhuang

2018-05-03

Lung cancer is the leading cause of cancer-associated death, and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. Many drugs have been used to treat NSCLC in order to improve patient prognosis. Platinum-based chemotherapy is the first-line treatment for locally advanced or metastatic patients. For patients with activating EGFR mutations, tyrosine kinase inhibitors are the best treatment choice. NSCLC initially exhibits an excellent response to treatment; however, acquired resistance has been observed in many patients, leading to ineffective treatment. Clinical resistance is an impediment in the treatment of patients with advanced NSCLC. Many sequencing technologies have shown that long non-coding RNA (lncRNA) is expressed differently between drug-resistant and drug-sensitive lung cancer cells. We review the literature on lncRNA in drug resistance of NSCLC. The aim of this review is to gain insight into the molecular mechanisms of drug resistance, mainly focusing on the role of lncRNA in NSCLC. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Current Status of Gene Therapy for Inherited Lung Diseases

PubMed Central

Driskell, Ryan R.; Engelhardt, John F.

2007-01-01

Gene therapy as a treatment modality for pulmonary disorders has attracted significant interest over the past decade. Since the initiation of the first clinical trials for cystic fibrosis lung disease using recombinant adenovirus in the early 1990s, the field has encountered numerous obstacles including vector inflammation, inefficient delivery, and vector production. Despite these obstacles, enthusiasm for lung gene therapy remains high. In part, this enthusiasm is fueled through the diligence of numerous researchers whose studies continue to reveal great potential of new gene transfer vectors that demonstrate increased tropism for airway epithelia. Several newly identified serotypes of adeno-associated virus have demonstrated substantial promise in animal models and will likely surface soon in clinical trials. Furthermore, an increased understanding of vector biology has also led to the development of new technologies to enhance the efficiency and selectivity of gene delivery to the lung. Although the promise of gene therapy to the lung has yet to be realized, the recent concentrated efforts in the field that focus on the basic virology of vector development will undoubtedly reap great rewards over the next decade in treating lung diseases. PMID:12524461

Genetic Contribution to Non-Squamous, Non-Small Cell Lung Cancer in Non-Smokers.

PubMed

Carr, Shamus R; Akerley, Wallace; Cannon-Albright, Lisa

2018-04-04

Lung carcinogenesis is strongly influenced by environmental and heritable factors. The genetic contribution to the different histologies is unknown. A population-based computerized genealogy resource linked to a statewide cancer registry of lung cancer cases (n=5408) was analyzed to evaluate the heritable contribution to lung cancer histology in smoking (n=1751) and non-smoking cases (n=818). Statistical methods were used to test for significant excess relatedness of lung cancer cases. Significant excess distant relatedness was observed for all lung cancer histology subgroups analyzed except the small cell lung cancer subset (p=0.213). When smoking and non-smoking histologic subsets of lung cancer were considered, excess relatedness was observed only in non-smoking NSCLC (n=653; p=0.026) and, particularly, in those non-smokers with non-squamous histology (n=561; p=0.036). Sixty one pedigrees were identified which demonstrated a significant excess risk of non-smoking, non-squamous lung cancer cases; and an excess of female cases was observed among the cases in these high-risk pedigrees. This analysis supports a genetic predisposition to lung cancer carcinogenesis in non-smoking, non-squamous NSCLC cases. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

National Heart, Lung, and Blood Institute

MedlinePlus

... of Intramural Research Research Resources Research Meeting Summaries Technology Transfer Clinical Trials What Are Clinical Trials? Children & Clinical Studies NHLBI Trials Clinical Trial Websites News & ...

Pulmonary cytomegalic inclusion-body disease in a diabetic

PubMed Central

Heard, Brian E.; Hassan, A. M.; Wilson, Stephanie M.

1962-01-01

Cytomegalic inclusion-body disease was found at necropsy in the lungs of a 57-year-old diabetic man. The characteristic large cells were found in all parts of the lungs. The alveolar walls showed no cellular infiltration, supporting Hamperl's suggestion that the cytomegalic virus alone may be incapable of causing pneumonitis. A small focus of aspergillosis was also found in one lung. The rarity of cytomegalic inclusion-body disease in adults was confirmed by re-examining histologically the lungs of 15 further cases of diabetes as well as 60 of other chronic diseases. No further example of pulmonary cytomegaly was found. Images PMID:13905763

CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation.

PubMed

Roux, Antoine; Mourin, Gisèle; Fastenackels, Solène; Almeida, Jorge R; Iglesias, Maria Candela; Boyd, Anders; Gostick, Emma; Larsen, Martin; Price, David A; Sacre, Karim; Douek, Daniel C; Autran, Brigitte; Picard, Clément; Miranda, Sandra de; Sauce, Delphine; Stern, Marc; Appay, Victor

2013-07-01

Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. Copyright © 2013 Elsevier Inc. All rights reserved.

The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease.

PubMed

O'Dwyer, David N; Dickson, Robert P; Moore, Bethany B

2016-06-15

The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. Copyright © 2016 by The American Association of Immunologists, Inc.

Special considerations in pediatric lung transplantation.

PubMed

Wells, Audrey; Faro, Albert

2006-10-01

More than 1300 lung or heart-lung transplants have been performed in children to date, resulting in many years of improved quality of life. Increasing experience has demonstrated that this therapy is unique and differs from adult lung transplantation in terms of indications, complications, pharmacokinetics, and monitoring. Unlike adult lung transplant recipients, cystic fibrosis and pulmonary vascular disease are very common indications. Complications such as graft dysfunction and bronchiolitis obliterans occur similarly in children as in adults, but others such as posttransplant lymphoproliferative disorders, growth retardation, respiratory tract infections, and medical nonadherence appear to be more common in pediatric lung transplant recipients. In addition, infants and adolescents are two very distinct populations that require special attention. Although the new lung allocation system grants some preference to children, donor shortage remains a limiting factor. Living donor lobar transplantation is an alternative for select candidates. Survival rates are similar between adult and pediatric transplant recipients. Support for collaborative studies is critical if we are to improve long-term outcomes for our young patients.

Gene Expression-Based Survival Prediction in Lung Adenocarcinoma: A Multi-Site, Blinded Validation Study

PubMed Central

Shedden, Kerby; Taylor, Jeremy M.G.; Enkemann, Steve A.; Tsao, Ming S.; Yeatman, Timothy J.; Gerald, William L.; Eschrich, Steve; Jurisica, Igor; Venkatraman, Seshan E.; Meyerson, Matthew; Kuick, Rork; Dobbin, Kevin K.; Lively, Tracy; Jacobson, James W.; Beer, David G.; Giordano, Thomas J.; Misek, David E.; Chang, Andrew C.; Zhu, Chang Qi; Strumpf, Dan; Hanash, Samir; Shepherd, Francis A.; Ding, Kuyue; Seymour, Lesley; Naoki, Katsuhiko; Pennell, Nathan; Weir, Barbara; Verhaak, Roel; Ladd-Acosta, Christine; Golub, Todd; Gruidl, Mike; Szoke, Janos; Zakowski, Maureen; Rusch, Valerie; Kris, Mark; Viale, Agnes; Motoi, Noriko; Travis, William; Sharma, Anupama

2009-01-01

Although prognostic gene expression signatures for survival in early stage lung cancer have been proposed, for clinical application it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) can be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas. PMID:18641660

Through the Looking Glass: Real-Time Video Using 'Smart' Technology Provides Enhanced Intraoperative Logistics.

PubMed

Baldwin, Andrew C W; Mallidi, Hari R; Baldwin, John C; Sandoval, Elena; Cohn, William E; Frazier, O H; Singh, Steve K

2016-01-01

In the setting of increasingly complex medical therapies and limited physician resources, the recent emergence of 'smart' technology offers tremendous potential for improved logistics, efficiency, and communication between medical team members. In an effort to harness these capabilities, we sought to evaluate the utility of this technology in surgical practice through the employment of a wearable camera device during cardiothoracic organ recovery. A single procurement surgeon was trained for use of an Explorer Edition Google Glass (Google Inc., Mountain View, CA) during the recovery process. Live video feed of each procedure was securely broadcast to allow for members of the home transplant team to remotely participate in organ assessment. Primary outcomes involved demonstration of technological feasibility and validation of quality assurance through group assessment. The device was employed for the recovery of four organs: a right single lung, a left single lung, and two bilateral lung harvests. Live video of the visualization process was remotely accessed by the home transplant team, and supplemented final verification of organ quality. In each case, the organs were accepted for transplant without disruption of standard procurement protocols. Media files generated during the procedures were stored in a secure drive for future documentation, evaluation, and education purposes without preservation of patient identifiers. Live video streaming can improve quality assurance measures by allowing off-site members of the transplant team to participate in the final assessment of donor organ quality. While further studies are needed, this project suggests that the application of mobile 'smart' technology offers not just immediate value, but the potential to transform our approach to the practice of medicine.

GC-MS/MS Analyses of Biological Samples in Support of Developmental Toxic Effects on Percutaneous Exposure of Rats to VX

DTIC Science & Technology

2016-07-01

of blood, tissues, and organs (heart, lung, liver, kidney , brain, eye, diaphragm, and skin) that were obtained from rats (postnatal days 42 and 70...of blood, tissues, and organs (heart, lung, liver, kidney , brain, eye, and diaphragm) that were used to quantify the amounts of free and regenerated...Biosamples (brain, diaphragm, eye, heart, lung, liver, and kidney ) were collected at time of death or 48 h post-exposure for survivors. All

SU-E-J-113: Effects of Deformable Registration On First-Order Texture Maps Calculated From Thoracic Lung CT Scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, C; Cunliffe, A; Al-Hallaq, H

Purpose: To determine the stability of eight first-order texture features following the deformable registration of serial computed tomography (CT) scans. Methods: CT scans at two different time points from 10 patients deemed to have no lung abnormalities by a radiologist were collected. Following lung segmentation using an in-house program, texture maps were calculated from 32×32-pixel regions of interest centered at every pixel in the lungs. The texture feature value of the ROI was assigned to the center pixel of the ROI in the corresponding location of the texture map. Pixels in the square ROI not contained within the segmented lungmore » were not included in the calculation. To quantify the agreement between ROI texture features in corresponding pixels of the baseline and follow-up texture maps, the Fraunhofer MEVIS EMPIRE10 deformable registration algorithm was used to register the baseline and follow-up scans. Bland-Altman analysis was used to compare registered scan pairs by computing normalized bias (nBias), defined as the feature value change normalized to the mean feature value, and normalized range of agreement (nRoA), defined as the range spanned by the 95% limits of agreement normalized to the mean feature value. Results: Each patient’s scans contained between 6.8–15.4 million ROIs. All of the first-order features investigated were found to have an nBias value less than 0.04% and an nRoA less than 19%, indicating that the variability introduced by deformable registration was low. Conclusion: The eight first-order features investigated were found to be registration stable. Changes in CT texture maps could allow for temporal-spatial evaluation of the evolution of lung abnormalities relating to a variety of diseases on a patient-by-patient basis. SGA and HA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology. Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number R25GM109439.« less

Infection rate and tissue localization of murine IL-12p40-producing monocyte-derived CD103(+) lung dendritic cells during pulmonary tuberculosis.

PubMed

Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus

2013-01-01

Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naïve donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103(+) dendritic cells (αE-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that αE-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of αE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of αE-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that αE-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung αE-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that αE-DC contain the highest frequency of IL-12p40(+) cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive αE-DC phenotype.

Infection Rate and Tissue Localization of Murine IL-12p40-Producing Monocyte-Derived CD103+ Lung Dendritic Cells during Pulmonary Tuberculosis

PubMed Central

Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D.; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus

2013-01-01

Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naïve donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103+ dendritic cells (αE-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that αE-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of αE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of αE-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that αE-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung αE-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that αE-DC contain the highest frequency of IL-12p40+ cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive αE-DC phenotype. PMID:23861965

Extracorporeal membrane oxygenation as a bridge to lung transplantation: A single-center experience in the present era.

PubMed

Todd, Emily M; Biswas Roy, Sreeja; Hashimi, A Samad; Serrone, Rosemarie; Panchanathan, Roshan; Kang, Paul; Varsch, Katherine E; Steinbock, Barry E; Huang, Jasmine; Omar, Ashraf; Patel, Vipul; Walia, Rajat; Smith, Michael A; Bremner, Ross M

2017-11-01

Extracorporeal membrane oxygenation has been used as a bridge to lung transplantation in patients with rapid pulmonary function deterioration. The reported success of this modality and perioperative and functional outcomes are varied. We retrospectively reviewed all patients who underwent lung transplantation at our institution over 1 year (January 1, 2015, to December 31, 2015). Patients were divided into 2 groups depending on whether they required extracorporeal membrane oxygenation support as a bridge to transplant; preoperative characteristics, lung transplantation outcomes, and survival were compared between groups. Of the 93 patients, 12 (13%) received bridge to transplant, and 81 (87%) did not. Patients receiving bridge to transplant were younger, had higher lung allocation scores, had lower functional status, and were more often on mechanical ventilation at listing. Most patients who received bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant extracorporeal membrane oxygenation support was 103.6 hours in duration (range, 16-395 hours). All patients who received bridge to transplant were decannulated immediately after lung transplantation but were more likely to return to the operating room for secondary chest closure or rethoracotomy. Grade 3 primary graft dysfunction within 72 hours was similar between groups. Lung transplantation success and hospital discharge were 100% in the bridge to transplant group; however, these patients experienced longer hospital stays and higher rates of discharge to acute rehabilitation. The 1-year survival was 100% in the bridge to transplant group and 91% in the non-bridge to transplant group (log-rank, P = .24). The 1-year functional status was excellent in both groups. Extracorporeal membrane oxygenation can be used to safely bridge high-acuity patients with end-stage lung disease to lung transplantation with good 30-day, 90-day, and 1-year survival and excellent 1-year functional status. Long-term outcomes are being studied. Copyright © 2017. Published by Elsevier Inc.

Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma.

PubMed

Bunyavanich, S; Boyce, J A; Raby, B A; Weiss, S T

2012-02-01

Distinct receptors likely exist for leukotriene (LT)E(4), a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE(4)-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Nineteen single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n = 1266). Using family based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Five SNPs in P2RY12 were associated with multiple lung function measures (P-values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P-values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P-values 0.0028–0.040). The P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.

Exploiting unsupervised and supervised classification for segmentation of the pathological lung in CT

NASA Astrophysics Data System (ADS)

Korfiatis, P.; Kalogeropoulou, C.; Daoussis, D.; Petsas, T.; Adonopoulos, A.; Costaridou, L.

2009-07-01

Delineation of lung fields in presence of diffuse lung diseases (DLPDs), such as interstitial pneumonias (IP), challenges segmentation algorithms. To deal with IP patterns affecting the lung border an automated image texture classification scheme is proposed. The proposed segmentation scheme is based on supervised texture classification between lung tissue (normal and abnormal) and surrounding tissue (pleura and thoracic wall) in the lung border region. This region is coarsely defined around an initial estimate of lung border, provided by means of Markov Radom Field modeling and morphological operations. Subsequently, a support vector machine classifier was trained to distinguish between the above two classes of tissue, using textural feature of gray scale and wavelet domains. 17 patients diagnosed with IP, secondary to connective tissue diseases were examined. Segmentation performance in terms of overlap was 0.924±0.021, and for shape differentiation mean, rms and maximum distance were 1.663±0.816, 2.334±1.574 and 8.0515±6.549 mm, respectively. An accurate, automated scheme is proposed for segmenting abnormal lung fields in HRC affected by IP

New insights into saccular development and vascular formation in lung allografts under the renal capsule

PubMed Central

Vu, Thiennu H.; Alemayehu, Yemisrach; Werb, Zena

2009-01-01

The study of distal lung morphogenesis and vascular development would be greatly facilitated by an in vitro or ex vivo experimental model. In this study we show that the growth of mouse embryonic day 12.5 lung rudiments implanted underneath the kidney capsules of syngeneic or immunodeficient hosts follows closely lung development in utero. The epithelium develops extensively with both proximal and distal differentiation to the saccular stage. The vasculature also develops extensively. Large blood vessels accompany large airways and capillaries develop within the saccular walls. Interestingly, vessels in the lung grafts develop from endothelial progenitor cells endogenous to the explants and host vessels do not vascularize the grafts independently. This suggests that embryonic lungs possess mechanisms to prevent the inappropriate ingrowth of surrounding vessels. However, vessels in the lung grafts do connect to host vessels, showing that embryonic lungs have the ability to stimulate host angiogenesis and recruit host vessel connections. These data support the hypothesis that the lung vasculature develops by both vasculogenic and angiogenic processes: a vascular network develops in situ in lung mesenchyme, which is then connected to angiogenic processes from central vessels. The lung renal capsule allograft is thus an excellent model to study the development of the pulmonary vasculature and of late fetal lung development that requires a functional blood supply. PMID:12591600

OMARC: An online multimedia application for training health care providers in the assessment of respiratory conditions.

PubMed

Meruvia-Pastor, Oscar; Patra, Pranjal; Andres, Karen; Twomey, Creina; Peña-Castillo, Lourdes

2016-05-01

OMARC, a multimedia application designed to support the training of health care providers for the identification of common lung sounds heard in a patient's thorax as part of a health assessment, is described and its positive contribution to user learning is assessed. The main goal of OMARC is to effectively help health-care students become familiar with lung sounds as part of the assessment of respiratory conditions. In addition, the application must be easy to use and accessible to students and practitioners over the internet. OMARC was developed using an online platform to facilitate access to users in remote locations. OMARC's unique contribution as an educational software tool is that it presents a narrative about normal and abnormal lung sounds using interactive multimedia and sample case studies designed by professional health-care providers and educators. Its interface consists of two distinct components: a sounds glossary and a rich multimedia interface which presents clinical case studies and provides access to lung sounds placed on a model of a human torso. OMARC's contents can be extended through the addition of sounds and case studies designed by health-care educators and professionals. To validate OMARC and determine its efficacy in improving learning and capture user perceptions about it, we performed a pilot study with ten nursing students. Participants' performance was measured through an evaluation of their ability to identify several normal and adventitious/abnormal sounds prior and after exposure to OMARC. Results indicate that participants are able to better identify different lung sounds, going from an average of 63% (S.D. 18.3%) in the pre-test evaluation to an average of 90% (S.D. of 11.5%) after practising with OMARC. Furthermore, participants indicated in a user satisfaction questionnaire that they found the application helpful, easy to use and that they would recommend it to other persons in their field. OMARC is an online multimedia application for training health care students in the assessment of respiratory conditions. The software integrates multimedia technology and health-care education concepts to facilitate learning, while being useful and easy to use. Results from a pilot study indicate that OMARC significantly helps to improve the capacity of the users to correctly identify lung sounds for different respiratory conditions. In addition, participants' opinions about OMARC were quite positive: users were likely to recommend the application to other persons in their field and found the application easy to use and helpful to better identify lung sounds. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Patients' experiences of information and support during the first six months after heart or lung transplantation.

PubMed

Ivarsson, Bodil; Ekmehag, Björn; Sjöberg, Trygve

2013-08-01

Heart or lung recipients are taught about a new lifestyle, risk factors, medication, food restrictions and exercise so they can take an active role and responsibility for disease management after transplantation. However, little is known about patients' experiences of information and support in these situations. The aim of the study was to illuminate how patients, six months after a heart or lung transplantation, experienced the information and support they received in connection with the transplantation. Sixteen patients were included in the study, and interviews were analysed using a qualitative content analysis method. The findings are presented in three themes: Alternating between gratitude and satisfaction and resignation, Striving to follow treatment strategies and Returning to a relatively normal life. The patients expressed gratitude when their health improved markedly but resignation when complications or side effects occurred due to the lack of information and support they received. Healthcare professionals can make specific improvements in the information they provide to patients to increase their preparedness. Information and support should be provided regularly so as to avoid non-adherence to essential guidelines. To return to a normal life, patients need support from healthcare organizations, families, employers and society in general. These findings should be taken into account in the clinical management of transplant patients, particularly those with dependent children or failing social networks.

Pulmonary drug delivery. Part II: The role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications

PubMed Central

Labiris, N R; Dolovich, M B

2003-01-01

Research in the area of pulmonary drug delivery has gathered momentum in the last several years, with increased interest in using the lung as a means of delivering drugs systemically. Advances in device technology have led to the development of more efficient delivery systems capable of delivering larger doses and finer particles into the lung. As more efficient pulmonary delivery devices and sophisticated formulations become available, physicians and health professionals will have a choice of a wide variety of device and formulation combinations that will target specific cells or regions of the lung, avoid the lung's clearance mechanisms and be retained within the lung for longer periods. It is now recognized that it is not enough just to have inhalation therapy available for prescribing; physicians and other healthcare providers need a basic understanding of aerosol science, inhaled formulations, delivery devices, and bioequivalence of products to prescribe these therapies optimally. PMID:14616419

Computer-aided auscultation learning system for nursing technique instruction.

PubMed

Hou, Chun-Ju; Chen, Yen-Ting; Hu, Ling-Chen; Chuang, Chih-Chieh; Chiu, Yu-Hsien; Tsai, Ming-Shih

2008-01-01

Pulmonary auscultation is a physical assessment skill learned by nursing students for examining the respiratory system. Generally, a sound simulator equipped mannequin is used to group teach auscultation techniques via classroom demonstration. However, nursing students cannot readily duplicate this learning environment for self-study. The advancement of electronic and digital signal processing technologies facilitates simulating this learning environment. This study aims to develop a computer-aided auscultation learning system for assisting teachers and nursing students in auscultation teaching and learning. This system provides teachers with signal recording and processing of lung sounds and immediate playback of lung sounds for students. A graphical user interface allows teachers to control the measuring device, draw lung sound waveforms, highlight lung sound segments of interest, and include descriptive text. Effects on learning lung sound auscultation were evaluated for verifying the feasibility of the system. Fifteen nursing students voluntarily participated in the repeated experiment. The results of a paired t test showed that auscultative abilities of the students were significantly improved by using the computer-aided auscultation learning system.

Residential radon exposure and risk of lung cancer in Missouri.

PubMed Central

Alavanja, M C; Lubin, J H; Mahaffey, J A; Brownson, R C

1999-01-01

OBJECTIVES: This study investigated residential radon exposure and lung cancer risk, using both standard radon dosimetry and a new radon monitoring technology that, evidence suggests, is a better measure of cumulative radon exposure. METHODS: Missouri women (aged 30 to 84 years) newly diagnosed with primary lung cancer during the period January 1, 1993, to January 31, 1994, were invited to participate in this population-based case-control study. Both indoor air radon detectors and CR-39 alpha-particle detectors (surface monitors) were used. RESULTS: When surface monitors were used, a significant trend in lung cancer odds ratios was observed for 20-year time-weighted-average radon concentrations. CONCLUSIONS: When surface monitors were used, but not when standard radon dosimetry was used, a significant lung cancer risk was found for radon concentrations at and above the action level for mitigation of houses currently used in the United States (148 Bqm-3). The risk was below the action level used in Canada (750 Bqm-3) and many European countries (200-400 Bqm-3). PMID:10394313

[Lung protective ventilation - pathophysiology and diagnostics].

PubMed

Uhlig, Stefan; Frerichs, Inéz

2008-06-01

Mechanical ventilation may lead to lung injury depending on the ventilatory settings (e.g. pressure amplitudes, endexpiratory pressures, frequency) and the length of mechanical ventilation. Particularly in the inhomogeneously injured lungs of ARDS patients, alveolar overextension results in volutrauma, cyclic opening and closure of alveolar units in atelectrauma. Particularly important appears to be the fact that these processes may also cause biotrauma, i.e. the ventilator-induced hyperactivation of inflammatory responses in the lung. These side effects are reduced, but not eliminated with the currently recommended ventilation strategy with a tidal volume of 6 ml/kg idealized body weight. It is our hope that in the future optimization of ventilator settings will be facilated by bedside monitoring of novel indices of respiratory mechanics such as the stress index or the Slice technique, and by innovative real-time imaging technologies such as electrical impedance tomography.

[Possible Significance of Bronchoalveolar Lavage Cytology at Initial Diagnosis and Follow-up of Lung Cancer].

PubMed

Grünewaldt, A; Hügel, C; Hermann, E; Wagner, T O F

2017-02-01

Bronchoalveolar lavage [BAL] is an important procedure in the diagnosis of a variety of lung diseases. While it has enormous value in the diagnostics of inflammatory parenchymal diseases, its significance in lung cancer is unclear. Keeping in mind that immune therapy (e. g. application of checkpoint inhibitors) is gaining importance in the management of lung carcinoma, it is important to know if there are typical cellular patterns in BAL of lung cancer patients. Methods  In a retrospective proof of principle-study, we analyzed 38 patients who underwent BAL at the initial diagnosis of lung cancer. Results  We observed an elevated level of CD25 lymphocytes as well as an increased expression of DR antigen, both signaling lymphocyte activation. We could not find a typical cytologic pattern of inflammatory cells in lung carcinoma patients. Sensitivity of BAL to malignant cells was rare, thus confirming earlier analysis. Conclusion  We could not demonstrate typical cellular patterns in BAL of lung cancer patients. Evaluation of specific microRNA patterns might play a supporting role in the initial diagnosis as well as follow-up of lung cancer patients. © Georg Thieme Verlag KG Stuttgart · New York.

Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

PubMed

Shafaghi, Shadi; Abbasi Dezfuli, Azizollah; Ansari Aval, Zahra; Sheikhy, Kambiz; Farzanegan, Behrooz; Mortaz, Esmaeil; Emami, Habib; Aigner, Clemens; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

2017-02-01

Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

Bronchoscopy in the investigation of outpatients with hemoptysis at a lung cancer clinic.

PubMed

Arooj, Parniya; Bredin, Emily; Henry, Michael T; Khan, Kashif A; Plant, Barry J; Murphy, Desmond M; Kennedy, Marcus P

2018-06-01

In the investigation of lung cancer, current practice in many healthcare systems would support bronchoscopy regardless of CT findings in patients with hemoptysis. We sought to identify the cause, the diagnostic yield of CT and bronchoscopy and the requirement for bronchoscopy in at risk patients with hemoptysis with a normal CT scan through our rapid access lung cancer clinic (RALC). Initially, a chart review was performed on all patients with hemoptysis (2011-2012) and thereafter a prospective analysis was performed (2013-2016). Our analysis represents the largest study to date in outpatients with hemoptysis. In our retrospective study, 155 patients reported hemoptysis. Causes were lower respiratory tract infections (RTIs) (47%) and lung cancer (16%). Our prospective study included 182 patients. The causes of hemoptysis were RTIs (50%) and lung cancer (18%). There were no false negative CT-scans for lung cancer. 47/57 present with lung cancer underwent bronchoscopy and 43/47 were positive for lung cancer (92%). Patients with hemoptysis and lung cancer have a higher stage of malignancy with a predominance of squamous cell lung carcinoma. Smoking status, the duration of hemoptysis or description of hemoptysis were not predictive of lung cancer however lung cancer was not identified in patients age <50. One sixth of patients presenting with hemoptysis to our lung cancer clinic had lung cancer. No patient identified with cancer related haemoptysis had a CT negative for lung cancer and a combination of bronchoscopy plus endobronchial ultrasound trans-bronchial needle aspiration (EBUS-TBNA) in those patients with a CT suspicious of lung cancer is 92% sensitive for lung cancer causing hemoptysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

NOTE: An innovative phantom for quantitative and qualitative investigation of advanced x-ray imaging technologies

NASA Astrophysics Data System (ADS)

Chiarot, C. B.; Siewerdsen, J. H.; Haycocks, T.; Moseley, D. J.; Jaffray, D. A.

2005-11-01

Development, characterization, and quality assurance of advanced x-ray imaging technologies require phantoms that are quantitative and well suited to such modalities. This note reports on the design, construction, and use of an innovative phantom developed for advanced imaging technologies (e.g., multi-detector CT and the numerous applications of flat-panel detectors in dual-energy imaging, tomosynthesis, and cone-beam CT) in diagnostic and image-guided procedures. The design addresses shortcomings of existing phantoms by incorporating criteria satisfied by no other single phantom: (1) inserts are fully 3D—spherically symmetric rather than cylindrical; (2) modules are quantitative, presenting objects of known size and contrast for quality assurance and image quality investigation; (3) features are incorporated in ideal and semi-realistic (anthropomorphic) contexts; and (4) the phantom allows devices to be inserted and manipulated in an accessible module (right lung). The phantom consists of five primary modules: (1) head, featuring contrast-detail spheres approximate to brain lesions; (2) left lung, featuring contrast-detail spheres approximate to lung modules; (3) right lung, an accessible hull in which devices may be placed and manipulated; (4) liver, featuring conrast-detail spheres approximate to metastases; and (5) abdomen/pelvis, featuring simulated kidneys, colon, rectum, bladder, and prostate. The phantom represents a two-fold evolution in design philosophy—from 2D (cylindrically symmetric) to fully 3D, and from exclusively qualitative or quantitative to a design accommodating quantitative study within an anatomical context. It has proven a valuable tool in investigations throughout our institution, including low-dose CT, dual-energy radiography, and cone-beam CT for image-guided radiation therapy and surgery.

Caplan syndrome

MedlinePlus

... not clear how RP develops. There are two theories: When people breathe in inorganic dust, it affects ... than treating any lung and joint disease. Support Groups Attending a support group with people who have ...

Exposure to diesel and gasoline engine emissions and the risk of lung cancer.

PubMed

Parent, Marie-Elise; Rousseau, Marie-Claude; Boffetta, Paolo; Cohen, Aaron; Siemiatycki, Jack

2007-01-01

Pollution from motor vehicles constitutes a major environmental health problem. The present paper describes associations between diesel and gasoline engine emissions and lung cancer, as evidenced in a 1979-1985 population-based case-control study in Montreal, Canada. Cases were 857 male lung cancer patients. Controls were 533 population controls and 1,349 patients with other cancer types. Subjects were interviewed to obtain a detailed lifetime job history and relevant data on potential confounders. Industrial hygienists translated each job description into indices of exposure to several agents, including engine emissions. There was no evidence of excess risks of lung cancer with exposure to gasoline exhaust. For diesel engine emissions, results differed by control group. When cancer controls were considered, there was no excess risk. When population controls were studied, the odds ratios, after adjustments for potential confounders, were 1.2 (95% confidence interval: 0.8, 1.8) for any exposure and 1.6 (95% confidence interval: 0.9, 2.8) for substantial exposure. Confidence intervals between risk estimates derived from the two control groups overlapped considerably. These results provide some limited support for the hypothesis of an excess lung cancer risk due to diesel exhaust but no support for an increase in risk due to gasoline exhaust.

Clinical challenges in mechanical ventilation.

PubMed

Goligher, Ewan C; Ferguson, Niall D; Brochard, Laurent J

2016-04-30

Mechanical ventilation supports gas exchange and alleviates the work of breathing when the respiratory muscles are overwhelmed by an acute pulmonary or systemic insult. Although mechanical ventilation is not generally considered a treatment for acute respiratory failure per se, ventilator management warrants close attention because inappropriate ventilation can result in injury to the lungs or respiratory muscles and worsen morbidity and mortality. Key clinical challenges include averting intubation in patients with respiratory failure with non-invasive techniques for respiratory support; delivering lung-protective ventilation to prevent ventilator-induced lung injury; maintaining adequate gas exchange in severely hypoxaemic patients; avoiding the development of ventilator-induced diaphragm dysfunction; and diagnosing and treating the many pathophysiological mechanisms that impair liberation from mechanical ventilation. Personalisation of mechanical ventilation based on individual physiological characteristics and responses to therapy can further improve outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Current questions in HIV-associated lung cancer.

PubMed

Shcherba, Marina; Shuter, Jonathan; Haigentz, Missak

2013-09-01

In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

Automatic Solitary Lung Nodule Detection in Computed Tomography Images Slices

NASA Astrophysics Data System (ADS)

Sentana, I. W. B.; Jawas, N.; Asri, S. A.

2018-01-01

Lung nodule is an early indicator of some lung diseases, including lung cancer. In Computed Tomography (CT) based image, nodule is known as a shape that appears brighter than lung surrounding. This research aim to develop an application that automatically detect lung nodule in CT images. There are some steps in algorithm such as image acquisition and conversion, image binarization, lung segmentation, blob detection, and classification. Data acquisition is a step to taking image slice by slice from the original *.dicom format and then each image slices is converted into *.tif image format. Binarization that tailoring Otsu algorithm, than separated the background and foreground part of each image slices. After removing the background part, the next step is to segment part of the lung only so the nodule can localized easier. Once again Otsu algorithm is use to detect nodule blob in localized lung area. The final step is tailoring Support Vector Machine (SVM) to classify the nodule. The application has succeed detecting near round nodule with a certain threshold of size. Those detecting result shows drawback in part of thresholding size and shape of nodule that need to enhance in the next part of the research. The algorithm also cannot detect nodule that attached to wall and Lung Chanel, since it depend the searching only on colour differences.

Correlation of lung surface area to apoptosis and proliferation in human emphysema.

PubMed

Imai, K; Mercer, B A; Schulman, L L; Sonett, J R; D'Armiento, J M

2005-02-01

Pulmonary emphysema is associated with alterations in matrix proteins and protease activity. These alterations may be linked to programmed cell death by apoptosis, potentially influencing lung architecture and lung function. To evaluate apoptosis in emphysema, lung tissue was analysed from 10 emphysema patients and six individuals without emphysema (normal). Morphological analysis revealed alveolar cells in emphysematous lungs with convoluted nuclei characteristic of apoptosis. DNA fragmentation was detected using terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL) and gel electrophoresis. TUNEL revealed higher apoptosis in emphysematous than normal lungs. Markers of apoptosis, including active caspase-3, proteolytic fragment of poly (ADP-ribose) polymerase, Bax and Bad, were detected in emphysematous lungs. Linear regression showed that apoptosis was inversely correlated with surface area. Emphysematous lungs demonstrated lower surface areas and increased cell proliferation. There was no correlation between apoptosis and proliferation, suggesting that, although both events increase during emphysema, they are not in equilibrium, potentially contributing to reduced lung surface area. In summary, cell-based mechanisms associated with emphysematous parenchymal damage include increased apoptosis and cell proliferation. Apoptosis correlated with airspace enlargement, supporting epidemiological evidence of the progressive nature of emphysema. These data extend the understanding of cell dynamics and structural changes within the lung during emphysema pathogenesis.

Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.

PubMed

Klar, Joakim; Blomstrand, Peter; Brunmark, Charlott; Badhai, Jitendra; Håkansson, Hanna Falk; Brange, Charlotte Sollie; Bergendal, Birgitta; Dahl, Niklas

2011-10-01

Genetic factors influencing lung function may predispose to chronic obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10) signalling pathway is critical for lung development and lung epithelial renewal. The hypothesis behind this study was that constitutive FGF10 insufficiency may lead to pulmonary disorder. Therefore investigation of the pulmonary functions of patients heterozygous for loss of function mutations in the FGF10 gene was performed. The spirometric measures of lung function from patients and non-carrier siblings were compared and both groups were related to matched reference data for normal human lung function. The patients show a significant decrease in lung function parameters when compared to control values. The average FEV1/IVC quota (FEV1%) for the patients is 0.65 (80% of predicted) and reversibility test using Terbutalin resulted in a 3.7% increase in FEV1. Patients with FGF10 haploinsufficiency have lung function parameters indicating COPD. A modest response to Terbutalin confirms an irreversible obstructive lung disease. These findings support the idea that genetic variants affecting the FGF10 signalling pathway are important determinants of lung function that may ultimately contribute to COPD. Specifically, the results show that FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD.

Use of a Doppler pulmonary artery catheter for continuous measurement of right ventricular pump function and contractility during single lung transplantation.

PubMed

Heerdt, P M; Pond, C G; Kussman, M K; Triantafillou, A N

1993-01-01

Despite numerous technologic advances in intraoperative monitoring, the only methods routinely available for assessment of right ventricular function in lung transplant recipients are continuous measurement of right heart pressures and intermittent thermodilution determination of cardiac output and ejection fraction. Additional data may now be obtained with transesophageal echocardiography, although this technology is expensive and not widely available and requires diverting attention from a potentially unstable patient for data acquisition and analysis. Recently, a Doppler pulmonary artery catheter was introduced that measures beat-to-beat pulmonary artery blood flow-velocity, cross sectional area, and volume flow. Because of data indicating that acceleration of blood in the pulmonary artery (measured as the first derivative of either the velocity or flow waveform) is a sensitive indicator of right ventricular contractility, we have used waveforms obtained with the catheter for assessment of right ventricular pump function (stroke volume and peak pulmonary artery flow rate) and contractility in heart surgery patients. We report here our experience with this method in two patients undergoing left single lung transplantation.

Pulmonary parenchyma segmentation in thin CT image sequences with spectral clustering and geodesic active contour model based on similarity

NASA Astrophysics Data System (ADS)

He, Nana; Zhang, Xiaolong; Zhao, Juanjuan; Zhao, Huilan; Qiang, Yan

2017-07-01

While the popular thin layer scanning technology of spiral CT has helped to improve diagnoses of lung diseases, the large volumes of scanning images produced by the technology also dramatically increase the load of physicians in lesion detection. Computer-aided diagnosis techniques like lesions segmentation in thin CT sequences have been developed to address this issue, but it remains a challenge to achieve high segmentation efficiency and accuracy without much involvement of human manual intervention. In this paper, we present our research on automated segmentation of lung parenchyma with an improved geodesic active contour model that is geodesic active contour model based on similarity (GACBS). Combining spectral clustering algorithm based on Nystrom (SCN) with GACBS, this algorithm first extracts key image slices, then uses these slices to generate an initial contour of pulmonary parenchyma of un-segmented slices with an interpolation algorithm, and finally segments lung parenchyma of un-segmented slices. Experimental results show that the segmentation results generated by our method are close to what manual segmentation can produce, with an average volume overlap ratio of 91.48%.

Ectopic lobe of right lung with abscess formation in children: a visual diagnosis case.

PubMed

Wu, Chyi-Sen; Wan, Kong-Sang

2013-08-01

We report a 9-year-old boy who had chest pain of 3 weeks' duration caused by ectopic lobe of the right lung with abscess formation. The diagnosis was supported by chest computed tomography and video-assisted thoracoscopy. The child responded well to the operation and fully recovered.

IL-1α is Critical for Resistance Against Highly Virulent Aspergillus fumigatus Isolates.

PubMed

Caffrey-Carr, Alayna K; Kowalski, Caitlin H; Beattie, Sarah R; Blaseg, Nathan A; Upshaw, Chanell R; Thammahong, Arsa; Lust, Hannah E; Tang, Yi-Wei; Hohl, Tobias M; Cramer, Robert A; Obar, Joshua J

2017-09-25

Heterogeneity amongst Aspergillus fumigatus isolates results in unique virulence potential and inflammatory responses. How these isolates drive specific immune responses and how this affects fungal-induced lung damage and disease outcome is unresolved. We demonstrate that the highly virulent CEA10 strain is able to rapidly germinate within the immune competent lung environment inducing greater lung damage, vascular leakage, and IL-1α release compared to the low virulent Af293 strain that germinates with lower frequency in this environment. Importantly, clearance of CEA10 was consequently dependent on IL-1α in contrast to Af293. Release of IL-1α occurred in a caspase 1/11- and P2XR7-independent mechanism, but was dependent on calpain activity. Our finding that early fungal conidia germination drives greater lung damage and IL-1α dependent inflammation is supported by three independent experimental lines. First, pre-germination of Af293 prior to in vivo challenge drives lung damage and an IL-1α dependent neutrophil response. Second, the virulent EVOL20 strain, derived from Af293, is able to germinate in the airways, leading to enhanced lung damage and IL-1α dependent inflammation and fungal clearance. Third, primary environmental A. fumigatus isolates that rapidly germinate in the airway conditions follow the same trend toward IL-1α dependency. Our data support the hypothesis that A. fumigatus phenotypic variation significantly contributes to disease outcomes. Copyright © 2017 American Society for Microbiology.

Impact of endotracheal tube shortening on work of breathing in neonatal and pediatric in vitro lung models.

PubMed

Mohr, Rebecca; Thomas, Jörg; Cannizzaro, Vincenzo; Weiss, Markus; Schmidt, Alexander R

2017-09-01

Work of breathing accounts for a significant proportion of total oxygen consumption in neonates and infants. Endotracheal tube inner diameter and length significantly affect airflow resistance and thus work of breathing. While endotracheal tube shortening reduces endotracheal tube resistance, the impact on work of breathing in mechanically ventilated neonates and infants remains unknown. The objective of this in vitro study was to quantify the effect of endotracheal tube shortening on work of breathing in simulated pediatric lung settings. We hypothesized that endotracheal tube shortening significantly reduces work of breathing. We used the Active-Servo-Lung 5000 to simulate different clinical scenarios in mechanically ventilated infants and neonates under spontaneous breathing with and without pressure support. Endotracheal tube size, lung resistance, and compliance, as well as respiratory settings such as respiratory rate and tidal volume were weight and age adapted for each lung model. Work of breathing was measured before and after maximal endotracheal tube shortening and the reduction of the daily energy demand calculated. Tube shortening with and without pressure support decreased work of breathing to a maximum of 10.1% and 8.1%, respectively. As a result, the calculated reduction of total daily energy demand by endotracheal tube shortening was between 0.002% and 0.02%. In this in vitro lung model, endotracheal tube shortening had minimal effects on work of breathing. Moreover, the calculated percentage reduction of the total daily energy demand after endotracheal tube shortening was minimal. © 2017 John Wiley & Sons Ltd.

Enhanced pulmonary absorption of a macromolecule through coupling to a sequence-specific phage display-derived peptide.

PubMed

Morris, Christopher J; Smith, Mathew W; Griffiths, Peter C; McKeown, Neil B; Gumbleton, Mark

2011-04-10

With the aim of identifying a peptide sequence that promotes pulmonary epithelial transport of macromolecule cargo we used a stringent peptide-phage display library screening protocol against rat lung alveolar epithelial primary cell cultures. We identified a peptide-phage clone (LTP-1) displaying the disulphide-constrained 7-mer peptide sequence, C-TSGTHPR-C, that showed significant pulmonary epithelial translocation across highly restrictive polarised cell monolayers. Cell biological data supported a differential alveolar epithelial cell interaction of the LTP-1 peptide-phage clone and the corresponding free synthetic LTP-1 peptide. Delivering select phage-clones to the intact pulmonary barrier of an isolated perfused rat lung (IPRL) resulted in 8.7% of lung deposited LTP-1 peptide-phage clone transported from the IPRL airways to the vasculature compared (p<0.05) to the cumulative transport of less than 0.004% for control phage-clone groups. To characterise phage-independent activity of LTP-1 peptide, the LTP-1 peptide was conjugated to a 53kDa anionic PAMAM dendrimer. Compared to respective peptide-dendrimer control conjugates, the LTP-1-PAMAM conjugate displayed a two-fold (bioavailability up to 31%) greater extent of absorption in the IPRL. The LTP-1 peptide-mediated enhancement of transport, when LTP-1 was either attached to the phage clone or conjugated to dendrimer, was sequence-dependent and could be competitively inhibited by co-instillation of excess synthetic free LTP-1 peptide. The specific nature of the target receptor or mechanism involved in LTP-1 lung transport remains unclear although the enhanced transport is enabled through a mechanism that is non-disruptive with respect to the pulmonary transport of hydrophilic permeability probes. This study shows proof-of principle that array technologies can be effectively exploited to identify peptides mediating enhanced transmucosal delivery of macromolecule therapeutics across an intact organ. Copyright © 2010 Elsevier B.V. All rights reserved.

Clinical trial design and rationale of the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) investigational device exemption clinical study protocol.

PubMed

Heatley, Gerald; Sood, Poornima; Goldstein, Daniel; Uriel, Nir; Cleveland, Joseph; Middlebrook, Don; Mehra, Mandeep R

2016-04-01

The HeartMate 3 left ventricular assist system (LVAS; St. Jude Medical, Inc., formerly Thoratec Corporation, Pleasanton, CA) was recently introduced into clinical trials for durable circulatory support in patients with medically refractory advanced-stage heart failure. This centrifugal, fully magnetically levitated, continuous-flow pump is engineered with the intent to enhance hemocompatibility and reduce shear stress on blood elements, while also possessing intrinsic pulsatility. Although bridge-to-transplant (BTT) and destination therapy (DT) are established dichotomous indications for durable left ventricular assist device (LVAD) support, clinical practice has challenged the appropriateness of these designations. The introduction of novel LVAD technology allows for the development of clinical trial designs to keep pace with current practices. The prospective, randomized Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) clinical trial aims to evaluate the safety and effectiveness of the HeartMate 3 LVAS by demonstrating non-inferiority to the HeartMate II LVAS (also St. Jude Medical, Inc.). The innovative trial design includes patients enrolled under a single inclusion and exclusion criteria , regardless of the intended use of the device, with outcomes ascertained in the short term (ST, at 6 months) and long term (LT, at 2 years). This adaptive trial design includes a pre-specified safety phase (n = 30) analysis. The ST cohort includes the first 294 patients and the LT cohort includes the first 366 patients for evaluation of the composite primary end-point of survival to transplant, recovery or LVAD support free of debilitating stroke (modified Rankin score >3), or re-operation to replace the pump. As part of the adaptive design, an analysis by an independent statistician will determine whether sample size adjustment is required at pre-specified times during the study. A further 662 patients will be enrolled to reach a total of 1,028 patients for evaluation of the secondary end-point of pump replacement at 2 years. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury

PubMed Central

Acosta-Herrera, Marialbert; Lorenzo-Diaz, Fabian; Pino-Yanes, Maria; Corrales, Almudena; Valladares, Francisco; Klassert, Tilman E.; Valladares, Basilio; Slevogt, Hortense; Ma, Shwu-Fan

2015-01-01

Acute lung injury (ALI) is a severe inflammatory process of the lung. The only proven life-saving support is mechanical ventilation (MV) using low tidal volumes (LVT) plus moderate to high levels of positive end-expiratory pressure (PEEP). However, it is currently unknown how they exert the protective effects. To identify the molecular mechanisms modulated by protective MV, this study reports transcriptomic analyses based on microarray and microRNA sequencing in lung tissues from a clinically relevant animal model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP) in male Sprague-Dawley rats. At 24 hours post-CLP, septic animals were randomized to three ventilatory strategies: spontaneous breathing, LVT (6 ml/kg) plus 10 cmH2O PEEP and high tidal volume (HVT, 20 ml/kg) plus 2 cmH2O PEEP. Healthy, non-septic, non-ventilated animals served as controls. After 4 hours of ventilation, lung samples were obtained for histological examination and gene expression analysis using microarray and microRNA sequencing. Validations were assessed using parallel analyses on existing publicly available genome-wide association study findings and transcriptomic human data. The catalogue of deregulated processes differed among experimental groups. The ‘response to microorganisms’ was the most prominent biological process in septic, non-ventilated and in HVT animals. Unexpectedly, the ‘neuron projection morphogenesis’ process was one of the most significantly deregulated in LVT. Further support for the key role of the latter process was obtained by microRNA studies, as four species targeting many of its genes (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) were found deregulated. Additional analyses revealed 'VEGF signaling' as a central underlying response mechanism to all the septic groups (spontaneously breathing or mechanically ventilated). Based on this data, we conclude that a co-deregulation of 'VEGF signaling' along with 'neuron projection morphogenesis', which have been never anticipated in ALI pathogenesis, promotes lung-protective effects of LVT with high levels of PEEP. PMID:26147972

Compton scatter imaging: A promising modality for image guidance in lung stereotactic body radiation therapy

PubMed Central

Redler, Gage; Jones, Kevin C.; Templeton, Alistair; Bernard, Damian; Turian, Julius; Chu, James C. H.

2018-01-01

Purpose Lung stereotactic body radiation therapy (SBRT) requires delivering large radiation doses with millimeter accuracy, making image guidance essential. An approach to forming images of patient anatomy from Compton-scattered photons during lung SBRT is presented. Methods To investigate the potential of scatter imaging, a pinhole collimator and flat-panel detector are used for spatial localization and detection of photons scattered during external beam therapy using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software is used to develop a model to simulate scatter images. This model is validated by comparing experimental and simulated phantom images. Patient scatter images are then simulated from 4DCT data. Results Experimental lung tumor phantom images have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU (0.5 s temporal resolution). The relative signal intensity from objects of different composition as well as lung tumor contrast for simulated phantom images agree quantitatively with experimental images, thus validating the Monte Carlo model. Scatter images are shown to display high contrast between different materials (lung, water, bone). Simulated patient images show superior (~double) tumor contrast compared to MV transmission images. Conclusions Compton scatter imaging is a promising modality for directly imaging patient anatomy during treatment without additional radiation, and it has the potential to complement existing technologies and aid tumor tracking and lung SBRT image guidance. PMID:29360151

Developments for Personalized Medicine of Lung Cancer Subtypes: Mass Spectrometry-Based Clinical Proteogenomic Analysis of Oncogenic Mutations.

PubMed

Nishimura, Toshihide; Nakamura, Haruhiko

2016-01-01

Molecular therapies targeting lung cancers with mutated epidermal growth factor receptor (EGFR) by EGFR-tyrosin kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, changed the treatment system of lung cancer. It was revealed that drug efficacy differs by race (e.g., Caucasians vs. Asians) due to oncogenic driver mutations specific to each race, exemplified by gefitinib / erlotinib. The molecular target drugs for lung cancer with anaplastic lymphoma kinase (ALK) gene translocation (the fusion gene, EML4-ALK) was approved, and those targeting lung cancers addicted ROS1, RET, and HER2 have been under development. Both identification and quantification of gatekeeper mutations need to be performed using lung cancer tissue specimens obtained from patients to improve the treatment for lung cancer patients: (1) identification and quantitation data of targeted mutated proteins, including investigation of mutation heterogeneity within a tissue; (2) exploratory mass spectrometry (MS)-based clinical proteogenomic analysis of mutated proteins; and also importantly (3) analysis of dynamic protein-protein interaction (PPI) networks of proteins significantly related to a subgroup of patients with lung cancer not only with good efficacy but also with acquired resistance. MS-based proteogenomics is a promising approach to directly capture mutated and fusion proteins expressed in a clinical sample. Technological developments are further expected, which will provide a powerful solution for the stratification of patients and drug discovery (Precision Medicine).

Compton scatter imaging: A promising modality for image guidance in lung stereotactic body radiation therapy.

PubMed

Redler, Gage; Jones, Kevin C; Templeton, Alistair; Bernard, Damian; Turian, Julius; Chu, James C H

2018-03-01

Lung stereotactic body radiation therapy (SBRT) requires delivering large radiation doses with millimeter accuracy, making image guidance essential. An approach to forming images of patient anatomy from Compton-scattered photons during lung SBRT is presented. To investigate the potential of scatter imaging, a pinhole collimator and flat-panel detector are used for spatial localization and detection of photons scattered during external beam therapy using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software is used to develop a model to simulate scatter images. This model is validated by comparing experimental and simulated phantom images. Patient scatter images are then simulated from 4DCT data. Experimental lung tumor phantom images have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU (0.5 s temporal resolution). The relative signal intensity from objects of different composition as well as lung tumor contrast for simulated phantom images agree quantitatively with experimental images, thus validating the Monte Carlo model. Scatter images are shown to display high contrast between different materials (lung, water, bone). Simulated patient images show superior (~double) tumor contrast compared to MV transmission images. Compton scatter imaging is a promising modality for directly imaging patient anatomy during treatment without additional radiation, and it has the potential to complement existing technologies and aid tumor tracking and lung SBRT image guidance. © 2018 American Association of Physicists in Medicine.

Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase.

PubMed

Aguayo, S M; Schuyler, W E; Murtagh, J J; Roman, J

1994-06-01

The expression of bombesin-like peptides (BLPs) by pulmonary neuroendocrine cells is transiently upregulated during lung development. A functional role for BLPs is supported by their ability to stimulate lung growth and maturation both in vitro and in vivo during the late stages of lung development. In addition, the cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP), which inactivates BLPs and other regulatory peptides, is also expressed by developing lungs and modulates the stimulatory effects of BLPs on lung growth and maturation. We hypothesized that, in addition to expressing BLPs and CD10/NEP, embryonic lungs must express BLP receptors, and that BLPs may also regulate processes that occur during early lung development such as branching morphogenesis. Using reverse transcriptase-polymerase chain reaction and oligonucleotide primers designed for amplifying a BLP receptor originally isolated from Swiss 3T3 mouse fibroblasts, we found that embryonic mouse lungs express a similar BLP receptor mRNA during the pseudoglandular stage of lung development when branching morphogenesis take place. Subsequently, we evaluated the effects of ligands for this BLP receptor using embryonic mouse lungs in an in vitro model of lung branching morphogenesis. We found that, in comparison with control lungs, treatment with bombesin (1 to 100 nM) resulted in a modest increase in clefts or branching points. In contrast, embryonic mouse lungs treated with the BLP analog [Leu13-psi(CH2NH)Leu14]bombesin (1 microM), which also binds to this BLP receptor but has predominantly antagonistic effects, demonstrated fewer branching points.(ABSTRACT TRUNCATED AT 250 WORDS)

MO-E-BRB-00: PANEL DISCUSSION: SBRT/SRS Case Studies - Lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

In this interactive session, lung SBRT patient cases will be presented to highlight real-world considerations for ensuring safe and accurate treatment delivery. An expert panel of speakers will discuss challenges specific to lung SBRT including patient selection, patient immobilization techniques, 4D CT simulation and respiratory motion management, target delineation for treatment planning, online treatment alignment, and established prescription regimens and OAR dose limits. Practical examples of cases, including the patient flow thought the clinical process are presented and audience participation will be encouraged. This panel session is designed to provide case demonstration and review for lung SBRT in terms ofmore » (1) clinical appropriateness in patient selection, (2) strategies for simulation, including 4D and respiratory motion management, and (3) applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent, and (4) image guidance in treatment delivery. Learning Objectives: Understand the established requirements for patient selection in lung SBRT Become familiar with the various immobilization strategies for lung SBRT, including technology for respiratory motion management Understand the benefits and pitfalls of applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent determination for lung SBRT Understand established prescription regimes and OAR dose limits.« less

Lung and Heart Sounds Analysis: State-of-the-Art and Future Trends.

PubMed

Padilla-Ortiz, Ana L; Ibarra, David

2018-01-01

Lung sounds, which include all sounds that are produced during the mechanism of respiration, may be classified into normal breath sounds and adventitious sounds. Normal breath sounds occur when no respiratory problems exist, whereas adventitious lung sounds (wheeze, rhonchi, crackle, etc.) are usually associated with certain pulmonary pathologies. Heart and lung sounds that are heard using a stethoscope are the result of mechanical interactions that indicate operation of cardiac and respiratory systems, respectively. In this article, we review the research conducted during the last six years on lung and heart sounds, instrumentation and data sources (sensors and databases), technological advances, and perspectives in processing and data analysis. Our review suggests that chronic obstructive pulmonary disease (COPD) and asthma are the most common respiratory diseases reported on in the literature; related diseases that are less analyzed include chronic bronchitis, idiopathic pulmonary fibrosis, congestive heart failure, and parenchymal pathology. Some new findings regarding the methodologies associated with advances in the electronic stethoscope have been presented for the auscultatory heart sound signaling process, including analysis and clarification of resulting sounds to create a diagnosis based on a quantifiable medical assessment. The availability of automatic interpretation of high precision of heart and lung sounds opens interesting possibilities for cardiovascular diagnosis as well as potential for intelligent diagnosis of heart and lung diseases.

Transcriptome profile and unique genetic evolution of positively selected genes in yak lungs.

PubMed

Lan, DaoLiang; Xiong, XianRong; Ji, WenHui; Li, Jian; Mipam, Tserang-Donko; Ai, Yi; Chai, ZhiXin

2018-04-01

The yak (Bos grunniens), which is a unique bovine breed that is distributed mainly in the Qinghai-Tibetan Plateau, is considered a good model for studying plateau adaptability in mammals. The lungs are important functional organs that enable animals to adapt to their external environment. However, the genetic mechanism underlying the adaptability of yak lungs to harsh plateau environments remains unknown. To explore the unique evolutionary process and genetic mechanism of yak adaptation to plateau environments, we performed transcriptome sequencing of yak and cattle (Bos taurus) lungs using RNA-Seq technology and a subsequent comparison analysis to identify the positively selected genes in the yak. After deep sequencing, a normal transcriptome profile of yak lung that containing a total of 16,815 expressed genes was obtained, and the characteristics of yak lungs transcriptome was described by functional analysis. Furthermore, Ka/Ks comparison statistics result showed that 39 strong positively selected genes are identified from yak lungs. Further GO and KEGG analysis was conducted for the functional annotation of these genes. The results of this study provide valuable data for further explorations of the unique evolutionary process of high-altitude hypoxia adaptation in yaks in the Tibetan Plateau and the genetic mechanism at the molecular level.

Conservative fluid management prevents age-associated ventilator induced mortality.

PubMed

Herbert, Joseph A; Valentine, Michael S; Saravanan, Nivi; Schneck, Matthew B; Pidaparti, Ramana; Fowler, Alpha A; Reynolds, Angela M; Heise, Rebecca L

2016-08-01

Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hospital mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality. 2month old and 20month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4h with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non-ventilated mice were used as controls. At 4h, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1h in advanced age HVT subjects. In 4h ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in older subjects. Our study demonstrates that conservative fluid alone can attenuate the age associated increase in ventilator associated mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Conservative Fluid Management Prevents Age-Associated Ventilator Induced Mortality

PubMed Central

Herbert, Joseph A.; Valentine, Michael S.; Saravanan, Nivi; Schneck, Matthew B.; Pidaparti, Ramana; Fowler, Alpha A.; Reynolds, Angela M.; Heise, Rebecca L.

2017-01-01

Background Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hosptial mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality. Methods 2 month old and 20 month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4 hours with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non-ventilated mice were used as controls. Results At 4hrs, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1hr in advanced age HVT subjects. In 4hr ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in older subjects. Conclusion Our study demonstrates that conservative fluid alone can attenuate the age associated increase in ventilator associated mortality. PMID:27188767

Ultrasonography evaluation during the weaning process: the heart, the diaphragm, the pleura and the lung.

PubMed

Mayo, P; Volpicelli, G; Lerolle, N; Schreiber, A; Doelken, P; Vieillard-Baron, A

2016-07-01

On a regular basis, the intensivist encounters the patient who is difficult to wean from mechanical ventilatory support. The causes for failure to wean from mechanical ventilatory support are often multifactorial and involve a complex interplay between cardiac and pulmonary dysfunction. A potential application of point of care ultrasonography relates to its utility in the process of weaning the patient from mechanical ventilatory support. This article reviews some applications of ultrasonography that may be relevant to the process of weaning from mechanical ventilatory support. The authors have divided these applications of ultrasonography into four separate categories: the assessment of cardiac, diaphragmatic, and lung function; and the identification of pleural effusion; which can all be evaluated with ultrasonography during a dynamic process in which the intensivist is uniquely positioned to use ultrasonography at the point of care. Ultrasonography may have useful application during the weaning process from mechanical ventilatory support.

Buccal Epithelium, Cigarette Smoking, and Lung Cancer: Review of the Literature.

PubMed

Saba, Raya; Halytskyy, Oleksandr; Saleem, Nasir; Oliff, Ira A

2017-01-01

Lung cancer is currently the leading cause of cancer-related mortality among men and women in the United States, and optimal screening methods are still lacking. The field effect is a well-supported phenomenon wherein a noxious stimulus triggers genetic, epigenetic and molecular changes that are widespread throughout the entire exposed organ system. The buccal epithelium is an easily accessible part of the respiratory tree that has good potential of yielding a surrogate marker for the field effect in cigarette smokers, and thus, a noninvasive, reliable lung cancer screening method. Herein, we review the literature on the relationship between the buccal epithelium, cigarette smoking, and lung cancer. © 2017 S. Karger AG, Basel.

In their own words: A qualitative study of the psychosocial concerns of posttreatment and long-term lung cancer survivors.

PubMed

Rohan, Elizabeth A; Boehm, Jennifer; Allen, Kristine Gabuten; Poehlman, Jon

2016-01-01

Although lung cancer is the deadliest type of cancer, survival rates are improving. To address the dearth of literature about the concerns of lung cancer survivors, the authors conducted 21 in-depth interviews with lung cancer survivors that focused on experiences during diagnosis, treatment, and long-term survivorship. Emergent themes included feeling blamed for having caused their cancer, being stigmatized as throwaways, and long-term survivors' experiencing surprise that they are still alive, given poor overall survival rates. Survivors also desired increased public support. It is imperative for healthcare and public health professionals to learn more about needs of this population.

In their own words: A qualitative study of the psychosocial concerns of posttreatment and long-term lung cancer survivors

PubMed Central

Rohan, Elizabeth A.; Boehm, Jennifer; Allen, Kristine Gabuten; Poehlman, Jon

2017-01-01

Although lung cancer is the deadliest type of cancer, survival rates are improving. To address the dearth of literature about the concerns of lung cancer survivors, the authors conducted 21 in-depth interviews with lung cancer survivors that focused on experiences during diagnosis, treatment, and long-term survivorship. Emergent themes included feeling blamed for having caused their cancer, being stigmatized as throwaways, and long-term survivors’ experiencing surprise that they are still alive, given poor overall survival rates. Survivors also desired increased public support. It is imperative for healthcare and public health professionals to learn more about needs of this population. PMID:26764569

Detection of early changes in lung cell cytology by flow-systems analysis techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinkamp, J.A.; Hansen, K.M.; Wilson, J.S.

1976-12-01

This report summarizes results of continuing experiments to develop cytological and biochemical indicators for estimating damage to respiratory cells in test animals exposed by inhalation to toxic agents associated with nonnuclear energy production, the specific goal being the application of advanced multiparameter flow-systems technologies to the detection of early atypical cellular changes in lung epithelium. Normal Syrian hamster lung cell samples composed of macrophages, leukocytes, ciliated columnar cells, and epithelial cells were stained with fluorescent dyes specific for different biochemical parameters and were analyzed in liquid suspension as they flowed through a chamber intersecting a laser beam of exciting light.more » Multiple sensors measured the total or two-color fluorescence and light scatter on a cell-by-cell basis. Cellular parameters proportional to optical measurements (i.e., cell size, DNA content, total protein, nonspecific esterase activity, nuclear and cytoplasmic diameters) were displayed as frequency distribution histograms. Lung cell samples were also separated according to various cytological parameters and identified microscopically. The basic operating features of the methodology are discussed briefly, along with specific examples of preliminary results illustrating the initial characterization of exfoliated pulmonary cells from normal hamsters. As the flow technology is adapted further to the analysis of respiratory cells, measurements of changes in physical and biochemical properties as a function of exposure to toxic agents will be performed.« less

Treatment of Lung Cancer in Medically Compromised Patients.

PubMed

Crawford, Jeffrey; Wheatley-Price, Paul; Feliciano, Josephine Louella

2016-01-01

Outcomes for patients with lung cancer have been improved substantially through the integration of surgery, radiation, and systemic therapy for patients with early-stage disease. Meanwhile, advances in our understanding of molecular mechanisms have substantially advanced our treatment of patients with advanced lung cancer through the introduction of targeted therapies, immune approaches, improvements in chemotherapy, and better supportive care. However, the majority of these advances have occurred among patients with good functional status, normal organ function, and with the social and economic support systems to be able to benefit most from these treatments. The aim of this article is to bring greater attention to management of lung cancer in patients who are medically compromised, which remains a major barrier to care delivery. Impaired performance status is associated with poor outcomes and correlates with the high prevalence of cachexia among patients with advanced lung cancer. CT imaging is emerging as a research tool to quantify muscle loss in patients with cancer, and new therapeutics are on the horizon that may provide important adjunctive therapy in the future. The benefits of cancer therapy for patients with organ failure are poorly understood because of their exclusion from clinical trials. The availability of targeted therapy and immunotherapy may provide alternatives that may be easier to deliver in this population, but clinical trials of these new agents in this population are vital. Patients with lower socioeconomic status are disproportionately affected by lung cancer because of higher rates of tobacco addiction and the impact of socioeconomic status on delay in diagnosis, treatment, and outcomes. For all patients who are medically compromised with lung cancer, multidisciplinary approaches are particularly needed to evaluate these patients and to incorporate rapidly changing therapeutics to improve outcomes.

Tidal volume in acute respiratory distress syndrome: how best to select it.

PubMed

Umbrello, Michele; Marino, Antonella; Chiumello, Davide

2017-07-01

Mechanical ventilation is the type of organ support most widely provided in the intensive care unit. However, this form of support does not constitute a cure for acute respiratory distress syndrome (ARDS), as it mainly works by buying time for the lungs to heal while contributing to the maintenance of vital gas exchange. Moreover, it can further damage the lung, leading to the development of a particular form of lung injury named ventilator-induced lung injury (VILI). Experimental evidence accumulated over the last 30 years highlighted the factors associated with an injurious form of mechanical ventilation. The present paper illustrates the physiological effects of delivering a tidal volume to the lungs of patients with ARDS, and suggests an approach to tidal volume selection. The relationship between tidal volume and the development of VILI, the so called volotrauma, will be reviewed. The still actual suggestion of a lung-protective ventilatory strategy based on the use of low tidal volumes scaled to the predicted body weight (PBW) will be presented, together with newer strategies such as the use of airway driving pressure as a surrogate for the amount of ventilatable lung tissue or the concept of strain, i.e., the ratio between the tidal volume delivered relative to the resting condition, that is the functional residual capacity (FRC). An ultra-low tidal volume strategy with the use of extracorporeal carbon dioxide removal (ECCO 2 R) will be presented and discussed. Eventually, the role of other ventilator-related parameters in the generation of VILI will be considered (namely, plateau pressure, airway driving pressure, respiratory rate (RR), inspiratory flow), and the promising unifying framework of mechanical power will be presented.

Tidal volume in acute respiratory distress syndrome: how best to select it

PubMed Central

Umbrello, Michele; Marino, Antonella

2017-01-01

Mechanical ventilation is the type of organ support most widely provided in the intensive care unit. However, this form of support does not constitute a cure for acute respiratory distress syndrome (ARDS), as it mainly works by buying time for the lungs to heal while contributing to the maintenance of vital gas exchange. Moreover, it can further damage the lung, leading to the development of a particular form of lung injury named ventilator-induced lung injury (VILI). Experimental evidence accumulated over the last 30 years highlighted the factors associated with an injurious form of mechanical ventilation. The present paper illustrates the physiological effects of delivering a tidal volume to the lungs of patients with ARDS, and suggests an approach to tidal volume selection. The relationship between tidal volume and the development of VILI, the so called volotrauma, will be reviewed. The still actual suggestion of a lung-protective ventilatory strategy based on the use of low tidal volumes scaled to the predicted body weight (PBW) will be presented, together with newer strategies such as the use of airway driving pressure as a surrogate for the amount of ventilatable lung tissue or the concept of strain, i.e., the ratio between the tidal volume delivered relative to the resting condition, that is the functional residual capacity (FRC). An ultra-low tidal volume strategy with the use of extracorporeal carbon dioxide removal (ECCO2R) will be presented and discussed. Eventually, the role of other ventilator-related parameters in the generation of VILI will be considered (namely, plateau pressure, airway driving pressure, respiratory rate (RR), inspiratory flow), and the promising unifying framework of mechanical power will be presented. PMID:28828362

Simulation of late inspiratory rise in airway pressure during pressure support ventilation.

PubMed

Yu, Chun-Hsiang; Su, Po-Lan; Lin, Wei-Chieh; Lin, Sheng-Hsiang; Chen, Chang-Wen

2015-02-01

Late inspiratory rise in airway pressure (LIRAP, Paw/ΔT) caused by inspiratory muscle relaxation or expiratory muscle contraction is frequently seen during pressure support ventilation (PSV), although the modulating factors are unknown. We investigated the effects of respiratory mechanics (normal, obstructive, restrictive, or mixed), inspiratory effort (-2, -8, or -15 cm H2O), flow cycle criteria (5-40% peak inspiratory flow), and duration of inspiratory muscle relaxation (0.18-0.3 s) on LIRAP during PSV using a lung simulator and 4 types of ventilators. LIRAP occurred with all lung models when inspiratory effort was medium to high and duration of inspiratory muscle relaxation was short. The normal lung model was associated with the fastest LIRAP, whereas the obstructive lung model was associated with the slowest. Unless lung mechanics were normal or mixed, LIRAP was unlikely to occur when inspiratory effort was low. Different ventilators were also associated with differences in LIRAP speed. Except for within the restrictive lung model, changes in flow cycle level did not abolish LIRAP if inspiratory effort was medium to high. Increased duration of inspiratory relaxation also led to the elimination of LIRAP. Simulation of expiratory muscle contraction revealed that LIRAP occurred only when expiratory muscle contraction occurred sometime after the beginning of inspiration. Our simulation study reveals that both respiratory resistance and compliance may affect LIRAP. Except for under restrictive lung conditions, LIRAP is unlikely to be abolished by simply lowering flow cycle criteria when inspiratory effort is strong and relaxation time is rapid. LIRAP may be caused by expiratory muscle contraction when it occurs during inspiration. Copyright © 2015 by Daedalus Enterprises.

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung

PubMed Central

Willinger, Tim; Rongvaux, Anthony; Takizawa, Hitoshi; Yancopoulos, George D.; Valenzuela, David M.; Murphy, Andrew J.; Auerbach, Wojtek; Eynon, Elizabeth E.; Stevens, Sean; Manz, Markus G.; Flavell, Richard A.

2011-01-01

Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and function of human myeloid cells and the absence of human immune responses at mucosal surfaces, such as the lung. To overcome this, we generated human IL-3/GM-CSF knock-in (hIL-3/GM-CSF KI) mice. These mice faithfully expressed human GM-CSF and IL-3 and developed pulmonary alveolar proteinosis because of elimination of mouse GM-CSF. We demonstrate that hIL-3/GM-CSF KI mice engrafted with human CD34+ hematopoietic cells had improved human myeloid cell reconstitution in the lung. In particular, hIL-3/GM-CSF KI mice supported the development of human alveolar macrophages that partially rescued the pulmonary alveolar proteinosis syndrome. Moreover, human alveolar macrophages mounted correlates of a human innate immune response against influenza virus. The hIL-3/GM-CSF KI mice represent a unique mouse model that permits the study of human mucosal immune responses to lung pathogens. PMID:21262803

Proteomic biomarkers in lung cancer.

PubMed

Pastor, M D; Nogal, A; Molina-Pinelo, S; Carnero, A; Paz-Ares, L

2013-09-01

The correct understanding of tumour development relies on the comprehensive study of proteins. They are the main orchestrators of vital processes, such as signalling pathways, which drive the carcinogenic process. Proteomic technologies can be applied to cancer research to detect differential protein expression and to assess different responses to treatment. Lung cancer is the number one cause of cancer-related death in the world. Mostly diagnosed at late stages of the disease, lung cancer has one of the lowest 5-year survival rates at 15 %. The use of different proteomic techniques such as two-dimensional gel electrophoresis (2D-PAGE), isotope labelling (ICAT, SILAC, iTRAQ) and mass spectrometry may yield new knowledge on the underlying biology of lung cancer and also allow the development of new early detection tests and the identification of changes in the cancer protein network that are associated with prognosis and drug resistance.

Outcome of long-term mechanical ventilation support in children.

PubMed

Hsia, Shao-Hsuan; Lin, Jainn-Jim; Huang, I-Anne; Wu, Chang-Teng

2012-10-01

Improved technology and care in recent years have significantly improved the prognosis and quality of life for patients on long-term mechanical ventilation. This study examined the status of children on long-term mechanical ventilation (MV) support in Taiwan. The medical records of patients between January 1998 and December 2006 were retrospectively reviewed, and the clinical factors were systematically reviewed. One hundred and thirty-nine (139) patients aged 3 months to 18 years, with 53 (38.1%) girls and 86 (61.9%) boys, were enrolled. The common underlying disorders included neurologic/neuromuscular diseases (n=100, 71.9%) and airway/lung dysfunction (n=19, 13.7%). After instituting MV, the children returned to the medical center mainly for infection (n=157, 47.7%) and elective surgery or procedures (n=46, 13.9%). After long-term follow-up, 37 (26.6%) died, 81 (58.3%) were transferred to respiratory care wards in local hospitals, and 21 (15.1%) received home care support. There are now more children on long-term MV support in Taiwan and most are in respiratory care wards in local hospitals. The shift in underlying diagnoses from pulmonary disease to neurogenic respiratory insufficiency affects hospitalization. The main cause of respiratory insufficiency is neurologic insult. Copyright © 2012. Published by Elsevier B.V.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larner, J.

In this interactive session, lung SBRT patient cases will be presented to highlight real-world considerations for ensuring safe and accurate treatment delivery. An expert panel of speakers will discuss challenges specific to lung SBRT including patient selection, patient immobilization techniques, 4D CT simulation and respiratory motion management, target delineation for treatment planning, online treatment alignment, and established prescription regimens and OAR dose limits. Practical examples of cases, including the patient flow thought the clinical process are presented and audience participation will be encouraged. This panel session is designed to provide case demonstration and review for lung SBRT in terms ofmore » (1) clinical appropriateness in patient selection, (2) strategies for simulation, including 4D and respiratory motion management, and (3) applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent, and (4) image guidance in treatment delivery. Learning Objectives: Understand the established requirements for patient selection in lung SBRT Become familiar with the various immobilization strategies for lung SBRT, including technology for respiratory motion management Understand the benefits and pitfalls of applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent determination for lung SBRT Understand established prescription regimes and OAR dose limits.« less

SU-E-J-251: Incorporation of Pre-Therapy 18F-FDG Uptake with CT Texture Features in a Predictive Model for Radiation Pneumonitis Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anthony, G; Cunliffe, A; Armato, S

2015-06-15

Purpose: To determine whether the addition of standardized uptake value (SUV) statistical variables to CT lung texture features can improve a predictive model of radiation pneumonitis (RP) development in patients undergoing radiation therapy. Methods: Anonymized data from 96 esophageal cancer patients (18 RP-positive cases of Grade ≥ 2) were retrospectively collected including pre-therapy PET/CT scans, pre-/posttherapy diagnostic CT scans and RP status. Twenty texture features (firstorder, fractal, Laws’ filter and gray-level co-occurrence matrix) were calculated from diagnostic CT scans and compared in anatomically matched regions of the lung. The mean, maximum, standard deviation, and 50th–95th percentiles of the SUV valuesmore » for all lung voxels in the corresponding PET scans were acquired. For each texture feature, a logistic regression-based classifier consisting of (1) the average change in that texture feature value between the pre- and post-therapy CT scans and (2) the pre-therapy SUV standard deviation (SUV{sub SD}) was created. The RP-classification performance of each logistic regression model was compared to the performance of its texture feature alone by computing areas under the receiver operating characteristic curves (AUCs). T-tests were performed to determine whether the mean AUC across texture features changed significantly when SUV{sub SD} was added to the classifier. Results: The AUC for single-texturefeature classifiers ranged from 0.58–0.81 in high-dose (≥ 30 Gy) regions of the lungs and from 0.53–0.71 in low-dose (< 10 Gy) regions. Adding SUVSD in a logistic regression model using a 50/50 data partition for training and testing significantly increased the mean AUC by 0.08, 0.06 and 0.04 in the low-, medium- and high-dose regions, respectively. Conclusion: Addition of SUVSD from a pre-therapy PET scan to a single CT-based texture feature improves RP-classification performance on average. These findings demonstrate the potential for more accurate prediction of RP using information from multiple imaging modalities. Supported, in part, by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under grant number T32 EB002103; SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology. HA receives royalties through the University of Chicago for computer-aided diagnosis technology.« less

Concomitant weekly cisplatin and thoracic radiotherapy for Pancoast tumors of the lung: pilot experience of the San Antonio Cancer Institute.

PubMed

Barnes, Jonathan B; Johnson, Scott B; Dahiya, Rajiv S; Temes, R Thomas; Herman, Terence S; Thomas, Charles R

2002-02-01

Pancoast (superior sulcus tumors) comprise a subset of non-small-cell lung cancers that have a unique clinical presentation by virtue of the locoregional pattern of disease progression. We herein report a brief report on our group's pilot experience in managing these challenging lung neoplasms with an aggressive concomitant modality approach. These results and those of the recent Southwest Oncology-lead Intergroup prospective phase 2 trial (SWOG-9416/INT-0160) support the use of concomitant chemoradiation followed by an attempt at surgical resection.

Diagnostic Imaging and Newer Modalities for Thoracic Diseases: PET/Computed Tomographic Imaging and Endobronchial Ultrasound for Staging and Its Implication for Lung Cancer.

PubMed

Counts, Sarah J; Kim, Anthony W

2017-08-01

Modalities to detect and characterize lung cancer are generally divided into those that are invasive [endobronchial ultrasound (EBUS), esophageal ultrasound (EUS), and electromagnetic navigational bronchoscopy (ENMB)] versus noninvasive [chest radiography (CXR), computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI)]. This chapter describes these modalities, the literature supporting their use, and delineates what tests to use to best evaluate the patient with lung cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Three cases of donor-derived pulmonary tuberculosis in lung transplant recipients and review of 12 previously reported cases: opportunities for early diagnosis and prevention.

PubMed

Mortensen, E; Hellinger, W; Keller, C; Cowan, L S; Shaw, T; Hwang, S; Pegues, D; Ahmedov, S; Salfinger, M; Bower, W A

2014-02-01

Solid organ transplant recipients have a higher frequency of tuberculosis (TB) than the general population, with mortality rates of approximately 30%. Although donor-derived TB is reported to account for <5% of TB in solid organ transplants, the source of Mycobacterium tuberculosis infection is infrequently determined. We report 3 new cases of pulmonary TB in lung transplant recipients attributed to donor infection, and review the 12 previously reported cases to assess whether cases could have been prevented and whether any cases that might occur in the future could be detected and investigated more quickly. Specifically, we evaluate whether opportunities existed to determine TB risk on the basis of routine donor history, to expedite diagnosis through routine mycobacterial smears and cultures of respiratory specimens early post transplant, and to utilize molecular tools to investigate infection sources epidemiologically. On review, donor TB risk was present among 7 cases. Routine smears and cultures diagnosed 4 asymptomatic cases. Genotyping was used to support epidemiologic findings in 6 cases. Validated screening protocols, including microbiological testing and newer technologies (e.g., interferon-gamma release assays) to identify unrecognized M. tuberculosis infection in deceased donors, are warranted. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Alveolar ventilation and recruitment under lung protective ventilation].

PubMed

Putensen, Christian; Muders, Thomas; Kreyer, Stefan; Wrigge, Hermann

2008-11-01

Goal of mechanical ventilation is to improve gas exchange and reduce work of breathing without contributing to further lung injury. Besides providing adequate EELV and thereby arterial oxygenation PEEP in addition to a reduction in tidal volume is required to prevent cyclic alveolar collapse and tidal recruitment and hence protective mechanical ventilation. Currently, there is no consensus if and if yes at which price alveolar recruitment with high airway pressures should be intended ("open up the lung"), or if it is more important to reduce the mechanical stress and strain to the lungs as much as possible ("keep the lung closed"). Potential of alveolar recruitment differs from patient to patient but also between lung regions. Potential for recruitment depends probably more on regional lung mechanics - especially on lung elastance - than on the underlying disease. Based on available data neither high PEEP nor other methods used for alveolar recruitment could demonstrate a survival benefit in patients with ARDS. These results may support an individualized titration of PEEP or other manoeuvres used for recruitment taking into consideration the regional effects. Bedside imaging techniques allowing titration of PEEP or other manoeuvres to prevent end-expiratory alveolar collapse (tidal recruitment) and inspiratory overinflation may be a promising development.

Single-breath CO2 analysis as a predictor of lung volume in a healthy animal model during controlled ventilation.

PubMed

Stenz, R I; Grenier, B; Thompson, J E; Arnold, J H

1998-08-01

To examine the utility of single-breath CO2 analysis as a measure of lung volume. A prospective, animal cohort study comparing 21 parameters derived from single-breath CO2 analysis with lung volume measurements determined by nitrogen washout in animals during controlled ventilation. An animal laboratory in a university-affiliated medical center. Seven healthy lambs. The single-breath CO2 analysis station consists of a mainstream capnometer, a variable orifice pneumotachometer, a signal processor and computer software with capability for both on- and off-line data analysis. Twenty-one derived components of the CO2 expirogram were evaluated as predictors of lung volume. Lung volume was manipulated by 3 cm H2O incremental increases in positive end-expiratory pressure from 0 to 21 cm H2O, and ranged between 147 and 942 mL. Fifty-five measurements of lung volume were available for comparison with derived variables from the CO2 expirogam. Stepwise linear regression identified four variables that were most predictive of lung volume: a) dynamic lung compliance; b) the slope of phase 3; c) the slope of phase 2 divided by the mixed expired CO2 tension; and d) airway deadspace. The multivariate equation was highly statistically significant and explained 94% of the variance (adjusted r2 =.94, p < .0001). The bias and precision of the calculated lung volume was .00 and 51, respectively. The mean percent difference for the lung volume estimate derived from the single-breath CO2 analysis station was 0.79%. Our data indicate that analysis of the CO2 expirogram can yield accurate information about lung volume. Specifically, four variables derived from a plot of expired CO2 concentration vs. expired volume predict changes in lung volume in healthy lambs with an adjusted coefficient of determination of .94. Prospective application of this technology in the setting of lung injury and rapidly changing physiology is essential in determining the clinical usefulness of the technique.

Emerging indications for extracorporeal membrane oxygenation in adults with respiratory failure.

PubMed

Abrams, Darryl; Brodie, Daniel

2013-08-01

Recent advances in technology have spurred the increasing use of extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure. However, this accounts for only a small percentage of patients with respiratory failure. We envision the application of ECMO in many other forms of respiratory failure in the coming years. Patients with less severe forms of acute respiratory distress syndrome, for instance, may benefit from enhanced lung-protective ventilation with the very low tidal volumes made possible by direct carbon dioxide removal from the blood. For those in whom hypercapnia predominates, extracorporeal support will allow for the elimination of invasive mechanical ventilation in some cases. The potential benefits of ECMO may be further enhanced by improved techniques, which facilitate active mobilization. Although ECMO for these and other expanded applications is under active investigation, it has yet to be proven beneficial in these settings in rigorous controlled trials. Ultimately, with upcoming and future technological advances, there is the promise of true destination therapy, which could lead to a major paradigm shift in the management of respiratory failure.

Innovations in health information technologies for chronic pulmonary diseases.

PubMed

Himes, Blanca E; Weitzman, Elissa R

2016-04-05

Asthma and chronic obstructive pulmonary disease (COPD) are common chronic obstructive lung disorders in the US that affect over 49 million people. There is no cure for asthma or COPD, but clinical guidelines exist for controlling symptoms that are successful in most patients that adhere to their treatment plan. Health information technologies (HITs) are revolutionizing healthcare by becoming mainstream tools to assist patients in self-monitoring and decision-making, and subsequently, driving a shift toward a care model increasingly centered on personal adoption and use of digital and web-based tools. While the number of chronic pulmonary disease HITs is rapidly increasing, most have not been validated as clinically effective tools for the management of disease. Online communities for asthma and COPD patients are becoming sources of empowerment and support, as well as facilitators of patient-centered research efforts. In addition to empowering patients and facilitating disease self-management, HITs offer promise to aid researchers in identifying chronic pulmonary disease endotypes and personalized treatments based on patient-specific profiles that integrate symptom occurrence and medication usage with environmental and genomic data.

The Telemetric and Holter ECG Warehouse Initiative (THEW): a Data Repository for the Design, Implementation and Validation of ECG-related Technologies

PubMed Central

Couderc, Jean-Philippe

2011-01-01

We present an initiative supported by the National Heart Lung, and Blood Institute and the Food and Drug Administration for the development of a repository containing continuous electrocardiographic information to be shared with the worldwide scientific community. We believe that sharing data reinforces open scientific inquiry. It encourages diversity of analysis and opinion while promoting new research and facilitating the education of new researchers. In this paper, we present the resources available in this initiative for the scientific community. We describe the set of ECG signals currently hosted and we briefly discuss the associated clinical information (medical history. Disease and study-specific endpoints) and software tools we propose. Currently, the repository contains more than 250GB of data from eight clinical studies including healthy individuals and cardiac patients. This data is available for the development, implementation and validation of technologies related to body-surface ECGs. To conclude, the Telemetric and Holter ECG Warehouse (THEW) is an initiative developed to benefit the scientific community and to advance the field of quantitative electrocardiography and cardiac safety. PMID:21097349

Mechanical Ventilation–associated Lung Fibrosis in Acute Respiratory Distress Syndrome A Significant Contributor to Poor Outcome

PubMed Central

Cabrera-Benitez, Nuria E.; Laffey, John G.; Parotto, Matteo; Spieth, Peter M.; Villar, Jesús; Zhang, Haibo; Slutsky, Arthur S.

2016-01-01

One of the most challenging problems in critical care medicine is the management of patients with the acute respiratory distress syndrome. Increasing evidence from experimental and clinical studies suggests that mechanical ventilation, which is necessary for life support in patients with acute respiratory distress syndrome, can cause lung fibrosis, which may significantly contribute to morbidity and mortality. The role of mechanical stress as an inciting factor for lung fibrosis versus its role in lung homeostasis and the restoration of normal pulmonary parenchymal architecture is poorly understood. In this review, the authors explore recent advances in the field of pulmonary fibrosis in the context of acute respiratory distress syndrome, concentrating on its relevance to the practice of mechanical ventilation, as commonly applied by anesthetists and intensivists. The authors focus the discussion on the thesis that mechanical ventilation—or more specifically, that ventilator-induced lung injury—may be a major contributor to lung fibrosis. The authors critically appraise possible mechanisms underlying the mechanical stress–induced lung fibrosis and highlight potential therapeutic strategies to mitigate this fibrosis. PMID:24732023

Mechanical ventilation-associated lung fibrosis in acute respiratory distress syndrome: a significant contributor to poor outcome.

PubMed

Cabrera-Benitez, Nuria E; Laffey, John G; Parotto, Matteo; Spieth, Peter M; Villar, Jesús; Zhang, Haibo; Slutsky, Arthur S

2014-07-01

One of the most challenging problems in critical care medicine is the management of patients with the acute respiratory distress syndrome. Increasing evidence from experimental and clinical studies suggests that mechanical ventilation, which is necessary for life support in patients with acute respiratory distress syndrome, can cause lung fibrosis, which may significantly contribute to morbidity and mortality. The role of mechanical stress as an inciting factor for lung fibrosis versus its role in lung homeostasis and the restoration of normal pulmonary parenchymal architecture is poorly understood. In this review, the authors explore recent advances in the field of pulmonary fibrosis in the context of acute respiratory distress syndrome, concentrating on its relevance to the practice of mechanical ventilation, as commonly applied by anesthetists and intensivists. The authors focus the discussion on the thesis that mechanical ventilation-or more specifically, that ventilator-induced lung injury-may be a major contributor to lung fibrosis. The authors critically appraise possible mechanisms underlying the mechanical stress-induced lung fibrosis and highlight potential therapeutic strategies to mitigate this fibrosis.

Sharing news of a lung cancer diagnosis with adult family members and friends: a qualitative study to inform a supportive intervention.

PubMed

Ewing, Gail; Ngwenya, Nothando; Benson, John; Gilligan, David; Bailey, Susan; Seymour, Jane; Farquhar, Morag

2016-03-01

Extensive research exists on breaking bad news by clinicians. This study examines perspectives of patients and those accompanying them at diagnosis-giving of subsequently sharing news of lung cancer with adult family/friends, and views of healthcare professionals, to inform development of a supportive intervention. Qualitative interviews with 20 patients, 17 accompanying persons; focus groups and interviews with 27 healthcare professionals from four Thoracic Oncology Units. Intervention development workshops with 24 healthcare professionals and six service users with experience of sharing a cancer diagnosis. Framework thematic analysis. Patients and accompanying persons shared news of lung cancer whilst coming to terms with the diagnosis. They recalled general support from healthcare professionals but not support with sharing bad news. Six elements were identified providing a framework for a potential intervention: 1-people to be told, 2-information to be shared, 3-timing of sharing, 4-responsibility for sharing, 5-methods of telling others and 6-reactions of those told. This study identifies the challenge of sharing bad news and a potential framework to guide delivery of a supportive intervention tailored to individual needs of patients. The identified framework could extend the portfolio of guidance on communication in cancer and potentially in other life-limiting conditions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Inflammation and angiogenesis in fibrotic lung disease.

PubMed

Keane, Michael P; Strieter, Robert M; Lynch, Joseph P; Belperio, John A

2006-12-01

The pathogenesis of pulmonary fibrosis is poorly understood. Although inflammation has been presumed to have an important role in the development of fibrosis this has been questioned recently, particularly with regard to idiopathic pulmonary fibrosis (IPF). It is, however, increasingly recognized that the polarization of the inflammatory response toward a type 2 phenotype supports fibroproliferation. Increased attention has been on the role of noninflammatory structural cells such as the fibroblast, myofibroblast, epithelial cell, and endothelial cells. Furthermore, the origin of these cells appears to be multifactorial and includes resident cells, bone marrow-derived cells, and epithelial to mesenchymal transition. Increasing evidence supports the presence of vascular remodeling in fibrotic lung disease, although the precise role in the pathogenesis of fibrosis remains to be determined. Therefore, the pathogenesis of pulmonary fibrosis is complex and involves the interaction of multiple cell types and compartments within the lung.

Respiratory mechanics in brain injury: A review.

PubMed

Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

2016-02-04

Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.

Lung Allocation Score: A Single-Center Simulation.

PubMed

Rosso, L; Palleschi, A; Tosi, D; Mendogni, P; Righi, I; Carrinola, R; Montoli, M; Damarco, F; Rossetti, V; Morlacchi, L C; Nosotti, M

2016-03-01

The lung allocation score (LAS) was introduced in the United States in May 2005 with the main goal of reducing the waiting list mortality of patients with end-stage lung diseases, but also to enhance the lung transplant benefit and improve the management of urgent candidates. Several papers have reported that LAS resulted in a reduction of the waiting list mortality but no significant survival benefit was noted. We evaluate the usefulness of LAS as a predictor for lung transplantation outcome in 123 patients listed for lung transplantation in an Italian center. Primary endpoints were waiting list mortality and posttransplant mortality at 1 year; secondary endpoints included perioperative circulatory support, cardiopulmonary bypass, primary graft dysfunction, and long-term survival after transplantation. We observed the absence of correlation between LAS and waiting list mortality. The LAS did not affect the long-term survival in our population. High LAS was predictive of primary graft dysfunction of grade 3 in the first 72 hours after transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Rapamycin prevents the development and progression of mutant epidermal growth factor receptor lung tumors with the acquired resistance mutation T790M.

PubMed

Kawabata, Shigeru; Mercado-Matos, José R; Hollander, M Christine; Donahue, Danielle; Wilson, Willie; Regales, Lucia; Butaney, Mohit; Pao, William; Wong, Kwok-Kin; Jänne, Pasi A; Dennis, Phillip A

2014-06-26

Lung cancer in never-smokers is an important disease often characterized by mutations in epidermal growth factor receptor (EGFR), yet risk reduction measures and effective chemopreventive strategies have not been established. We identify mammalian target of rapamycin (mTOR) as potentially valuable target for EGFR mutant lung cancer. mTOR is activated in human lung cancers with EGFR mutations, and this increases with acquisition of T790M mutation. In a mouse model of EGFR mutant lung cancer, mTOR activation is an early event. As a single agent, the mTOR inhibitor rapamycin prevents tumor development, prolongs overall survival, and improves outcomes after treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI). These studies support clinical testing of mTOR inhibitors in order to prevent the development and progression of EGFR mutant lung cancers. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Psychosocial and financial aspects of lung transplantation.

PubMed

Smolin, T L; Aguiar, L J

1996-09-01

This article summarizes the many psychosocial phases a patient will encounter during his or her transplantation experience and the ways the social worker can assist during this time. These include supportive services such as facilitating support groups and orientation programs, counseling, and crisis intervention. Also of importance is the financing of lung transplantation and its many associated costs, such as immunosuppressive medications and temporary housing. With the rise in managed care, the role of the transplant financial coordinator is of increasing importance from both a fiscal perspective and customer service standpoint for both the patient and the institution.

Lung cancer risk among construction workers in California, 1988-2007.

PubMed

Calvert, Geoffrey M; Luckhaupt, Sara; Lee, Soo-Jeong; Cress, Rosemary; Schumacher, Pam; Shen, Rui; Tak, SangWoo; Deapen, Dennis

2012-05-01

Although lung cancer risks can vary by race/ethnicity and by construction occupation, these risks have not been examined extensively. This study analyzed 110,937 lung cancer cases identified from the California Cancer Registry between 1988 and 2007. Mean age at diagnosis, proportion diagnosed at an advanced stage, and proportion with 3-year survival were calculated for lung cancer cases employed in the construction industry. Case-control methodology was also used to assess the risk of lung cancer. Morbidity odds ratios (MORs) were estimated by conditional logistic regression. Construction workers were found to have a significantly elevated risk for all lung cancer combined (MOR = 1.57) and for each lung cancer histologic subtype examined. All construction occupations, except managers/engineers and supervisors, had a significantly elevated risk for all lung cancer combined. Roofers and welders had the highest risks for total lung cancer and for each of the histologic subtypes. Construction workers in each of the four race/ethnicity groups also had significantly increased lung cancer risks. Compared to non-construction workers, construction workers were diagnosed at an earlier age, at a more advanced stage, and had significantly lower 3-year survival, though differences were modest. These findings justify additional reductions in carcinogenic exposures in construction, and increased support for smoking cessation programs at construction sites. Copyright © 2012 Wiley Periodicals, Inc.

WNTLESS IS REQUIRED FOR PERIPHERAL LUNG DIFFERENTIATION AND PULMONARY VASCULAR DEVELOPMENT

PubMed Central

Cornett, Bridget; Snowball, John; Varisco, Brian M.; Lang, Richard; Whitsett, Jeffrey; Sinner, Debora

2013-01-01

Wntless (Wls), a gene highly conserved across the animal kingdom, encodes for a transmembrane protein that mediates Wnt ligand secretion. Wls is expressed in developing lung, wherein Wnt signaling is necessary for pulmonary morphogenesis. We hypothesize that Wls plays a critical role in modulating Wnt signaling during lung development and therefore affects processes critical for pulmonary morphogenesis. We generated conditional Wls mutant mice utilizing Shh-Cre and Dermo1-Cre mice to delete Wls in the embryonic respiratory epithelium and mesenchyme, respectively. Epithelial deletion of Wls disrupted lung branching morphogenesis, peripheral lung development and pulmonary endothelial differentiation. Epithelial Wls mutant mice died at birth due to respiratory failure caused by lung hypoplasia and pulmonary hemorrhage. In the lungs of these mice, VEGF and Tie2-angiopoietin signaling pathways, which mediate vascular development, were downregulated from early stages of development. In contrast, deletion of Wls in mesenchymal cells of the developing lung did not alter branching morphogenesis or early mesenchymal differentiation. In vitro assays support the concept that Wls acts in part via Wnt5a to regulate pulmonary vascular development. We conclude that epithelial Wls modulates Wnt ligand activities critical for pulmonary vascular differentiation and peripheral lung morphogenesis. These studies provide a new framework for understanding the molecular mechanisms underlying normal pulmonary vasculature formation and the dysmorphic pulmonary vasculature development associated with congenital lung disease. PMID:23523683

Wntless is required for peripheral lung differentiation and pulmonary vascular development.

PubMed

Cornett, Bridget; Snowball, John; Varisco, Brian M; Lang, Richard; Whitsett, Jeffrey; Sinner, Debora

2013-07-01

Wntless (Wls), a gene highly conserved across the animal kingdom, encodes for a transmembrane protein that mediates Wnt ligand secretion. Wls is expressed in developing lung, wherein Wnt signaling is necessary for pulmonary morphogenesis. We hypothesize that Wls plays a critical role in modulating Wnt signaling during lung development and therefore affects processes critical for pulmonary morphogenesis. We generated conditional Wls mutant mice utilizing Shh-Cre and Dermo1-Cre mice to delete Wls in the embryonic respiratory epithelium and mesenchyme, respectively. Epithelial deletion of Wls disrupted lung branching morphogenesis, peripheral lung development and pulmonary endothelial differentiation. Epithelial Wls mutant mice died at birth due to respiratory failure caused by lung hypoplasia and pulmonary hemorrhage. In the lungs of these mice, VEGF and Tie2-angiopoietin signaling pathways, which mediate vascular development, were downregulated from early stages of development. In contrast, deletion of Wls in mesenchymal cells of the developing lung did not alter branching morphogenesis or early mesenchymal differentiation. In vitro assays support the concept that Wls acts in part via Wnt5a to regulate pulmonary vascular development. We conclude that epithelial Wls modulates Wnt ligand activities critical for pulmonary vascular differentiation and peripheral lung morphogenesis. These studies provide a new framework for understanding the molecular mechanisms underlying normal pulmonary vasculature formation and the dysmorphic pulmonary vasculature development associated with congenital lung disease. Copyright © 2013 Elsevier Inc. All rights reserved.

The measurement of lung volumes using body plethysmography and helium dilution methods in COPD patients: a correlation and diagnosis analysis.

PubMed

Tang, Yongjiang; Zhang, Mingke; Feng, Yulin; Liang, Binmiao

2016-11-23

Chronic obstructive pulmonary disease (COPD) is a chronic airway disease characterized by persistent airflow limitation. Moreover, lung hyperinflation evaluated by lung volumes is also the key pathophysiologic process during COPD progression. Nevertheless, there is still no preferred method to evaluate lung volumes. For this study, we recruited 170 patients with stable COPD to assess lung volumes stratified by airflow limitation severity. Lung volumes including residual volume (RV) and total lung capacity (TLC) were determined by both body plethysmography and helium dilution methods. The discrepancies between these two methods were recorded as ΔRV%pred, ΔTLC%pred, and ΔRV/TLC. We found that ΔRV%pred, ΔTLC%pred, and ΔRV/TLC increased significantly with the severity of COPD. The differences of lung capacity between these two methods were negatively correlated with FEV 1 %pred, and diffusing capacity for carbon monoxide (D L CO%pred). Moreover, the receiver operating characteristic (ROC) for ΔTLC%pred to distinguish severe COPD from non-severe COPD had an area under curve (AUC) of 0.886. The differences of lung volume parameters measured by body plethysmography and helium dilution methods were associated with airflow limitation and can effectively differentiate COPD severity, which may be a supportive method to assess the lung function of stable COPD patients.

β-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice.

PubMed

Iskandar, Anita R; Liu, Chun; Smith, Donald E; Hu, Kang-Quan; Choi, Sang-Woon; Ausman, Lynne M; Wang, Xiang-Dong

2013-04-01

Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer, but the data supporting this relationship are inconsistent. Here, we found that nicotine treatment not only induced emphysema but also increased both lung tumor multiplicity and volume in 4-nitrosamino-1-(3-pyridyl)-1-butanone (NNK)-initiated lung cancer in A/J mice. This tumor-promoting effect of nicotine was accompanied by significant reductions in survival probability and lung Sirtuin 1 (SIRT1) expression, which has been proposed as a tumor suppressor. The decreased level of SIRT1 was associated with increased levels of AKT phosphorylation and interleukin (il)-6 mRNA but decreased tumor suppressor p53 and retinoic acid receptor (RAR)-β mRNA levels in the lungs. Using this mouse model, we then determined whether β-cryptoxanthin (BCX), a xanthophyll that is strongly associated with a reduced risk of lung cancer in several cohort studies, can inhibit nicotine-induced emphysema and lung tumorigenesis. We found that BCX supplementation at two different doses was associated with reductions of the nicotine-promoted lung tumor multiplicity and volume, as well as emphysema in mice treated with both NNK and nicotine. Moreover, BCX supplementation restored the nicotine-suppressed expression of lung SIRT1, p53, and RAR-β to that of the control group, increased survival probability, and decreased the levels of lung il-6 mRNA and phosphorylation of AKT. The present study indicates that BCX is a preventive agent against emphysema and lung cancer with SIRT1 as a potential target. In addition, our study establishes a relevant animal lung cancer model for studying tumor growth within emphysematous microenvironments.

Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies.

PubMed

Dinh, Phuong-Uyen C; Cores, Jhon; Hensley, M Taylor; Vandergriff, Adam C; Tang, Junnan; Allen, Tyler A; Caranasos, Thomas G; Adler, Kenneth B; Lobo, Leonard J; Cheng, Ke

2017-06-30

Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality. In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery. From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days. Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

Bronchoalveolar lavage fluid of lung cancer patients: mapping the uncharted waters using proteomics technology.

PubMed

Oumeraci, Tonio; Schmidt, Bernd; Wolf, Thomas; Zapatka, Marc; Pich, Andreas; Brors, Benedikt; Eils, Roland; Fleischhacker, Michael; Schlegelberger, Brigitte; von Neuhoff, Nils

2011-04-01

The search for proteome-level markers of non-small cell lung cancer (NSCLC) has been mainly limited to serum or cell line screening approaches up to this point. We would like to demonstrate by this proof-of-principle study investigating bronchoalveolar lavage fluid samples from a cohort of NSCLC and control patients, that this readily available biofluid might be a more suitable source for discovering clinically usable NSCLC biomarkers. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Advances in diagnostic interventional pulmonology

PubMed Central

Al-Zubaidi, Nassar; Soubani, Ayman O.

2015-01-01

The recent advances in diagnostic pulmonary procedures have revolutionized the evaluation of abnormal thoracic findings including lung nodules and masses, mediastinal lymphadenopathy, and pleural diseases. Bronchoscopies with endobronchial ultrasonography and electromagnetic navigation are examples of new technology that has significantly improved the specificity and sensitivity of these procedures in diagnosis and staging of lung cancer without the need for more invasive procedures. This report describes the different diagnostic pulmonary interventions providing a description of the procedures, their indications, diagnostic yield and drawback. PMID:26229756

A549 Cells: Lung Carcinoma Cell Line for Adenovirus | NCI Technology Transfer Center | TTC

Cancer.gov

Scientists at the National Cancer Institute have developed a cell line designated A549 that was derived from explanted cultures of human lung cancer tissue. The A549 cell line has been tested under the guidance of the United States Food and Drug Administration (FDA) so, under current Good Manufacturing Practices (GMP), these cells may be suitable for use in manufacturing constructs for use in clinical trials. The National Cancer Institute seeks parties to non-exclusively license this research material.

Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure.

PubMed

Park, Robert M; Stayner, Leslie T; Petersen, Martin R; Finley-Couch, Melissa; Hornung, Richard; Rice, Carol

2012-05-01

Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940-2002), a revised cadmium (Cd) exposure matrix and improved work history information. Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure-response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m(3) Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20-25 years. These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 μg/m(3) Cd.

Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure

PubMed Central

Park, Robert M; Stayner, Leslie T; Petersen, Martin R; Finley-Couch, Melissa; Hornung, Richard; Rice, Carol

2015-01-01

Objectives Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. Methods A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940–2002), a revised cadmium (Cd) exposure matrix and improved work history information. Results Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure–response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m3 Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20–25 years. Conclusions These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 μg/m3 Cd. PMID:22271639

Curbing the burden of lung cancer.

PubMed

Urman, Alexandra; Hosgood, H Dean

2016-06-01

Lung cancer contributes substantially to the global burden of disease and healthcare costs. New screening modalities using low-dose computerized tomography are promising tools for early detection leading to curative surgery. However, the screening and follow-up diagnostic procedures of these techniques may be costly. Focusing on prevention is an important factor to reduce the burden of screening, treatment, and lung cancer deaths. The International Agency for Research on Cancer has identified several lung carcinogens, which we believe can be considered actionable when developing prevention strategies. To curb the societal burden of lung cancer, healthcare resources need to be focused on early detection and screening and on mitigating exposure(s) of a person to known lung carcinogens, such as active tobacco smoking, household air pollution (HAP), and outdoor air pollution. Evidence has also suggested that these known lung carcinogens may be associated with genetic predispositions, supporting the hypothesis that lung cancers attributed to differing exposures may have developed from unique underlying genetic mechanisms attributed to the exposure of interest. For instance, smokingattributed lung cancer involves novel genetic markers of risk compared with HAP-attributed lung cancer. Therefore, genetic risk markers may be used in risk stratification to identify subpopulations that are at a higher risk for developing lung cancer attributed to a given exposure. Such targeted prevention strategies suggest that precision prevention strategies may be possible in the future; however, much work is needed to determine whether these strategies will be viable.

Gene expression analysis in hypoplastic lungs in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Burgos, Carmen Mesas; Uggla, Andreas Ringman; Fagerström-Billai, Fredrik; Eklöf, Ann-Christine; Frenckner, Björn; Nord, Magnus

2010-07-01

Pulmonary hypoplasia and persistent pulmonary hypertension are the main causes of mortality and morbidity in newborns with congenital diaphragmatic hernia (CDH). Nitrofen is well known to induce CDH and lung hypoplasia in a rat model, but the mechanism remains unknown. To increase the understanding of the underlying pathogenesis of CDH, we performed a global gene expression analysis using microarray technology. Pregnant rats were given 100 mg nitrofen on gestational day 9.5 to create CDH. On day 21, fetuses after nitrofen administration and control fetuses were removed; and lungs were harvested. Global gene expression analysis was performed using Affymetrix Platform and the RAE 230 set arrays. For validation of microarray data, we performed real-time polymerase chain reaction and Western blot analysis. Significantly decreased genes after nitrofen administration included several growth factors and growth factors receptors involved in lung development, transcription factors, water and ion channels, and genes involved in angiogenesis and extracellular matrix. These results could be confirmed with real-time polymerase chain reaction and protein expression studies. The pathogenesis of lung hypoplasia and CDH in the nitrofen model includes alteration at a molecular level of several pathways involved in lung development. The complexity of the nitrofen mechanism of action reminds of human CDH; and the picture is consistent with lung hypoplasia and vascular disease, both important contributors to the high mortality and morbidity in CDH. Increased understanding of the molecular mechanisms that control lung growth may be the key to develop novel therapeutic techniques to stimulate pre- and postnatal lung growth. Copyright 2010 Elsevier Inc. All rights reserved.

Study on traditional Chinese medicine theory of lung being connected with large intestine.

PubMed

Liu, Ping; Wang, Ping; Tian, Daizhi; Liu, Junfeng; Chen, Gang; Liu, Songlin

2012-09-01

The theory of lung being connected with large intestine, which is a major topic in Traditional Chinese Medicine (TCM), has guided clinical practice for thousands of years in China. In this study, we analyzed the history, main contents, clinical application, and material basis of the theory, to attempt to improve the potential clinical significance of "lung being connected with large intestine" in China. The lung being connected with large intestine was first described in "Huang Di Nei Jing", and formed one of the basic theories of TCM. For thousands of years, the majority of TCM practitioners explored this theory continuously, leading to its development and use as an important theory in the guidance of TCM clinics In the last decade, researchers in the field of integrated TCM and Western medicine have studied clinical applications and biomedical mechanisms with experimental methods to explore the implications of the theory. With the further development of science and technology, research concerning the theory of lung being connected with large intestine will be greatly stimulated and contribute to the modernization of TCM.

Detection of early changes in lung cell cytology by flow-systems analysis techniques, July 1--December 31, 1975

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinkamp, J.A.; Ingram, M.; Hansen, K.M.

1976-03-01

This report summarizes results of preliminary experiments to demonstrate the feasibility of using automated flow-systems analysis in detecting early changes of respiratory epithelium exposed to physical and chemical agents associated with the by-products of nonnuclear energy production. The Syrian hamster was selected as the experimental test animal to begin investigation of the effects of toxic agents to cells of the respiratory tract. Since initiation of the program approximately six months ago, the goals have been acquisition of adequate numbers of exfoliated cells from the lung; adaptation of cytological techniques developed on human exfoliated gynecological samples to hamster lung epithelium formore » obtaining single-cell suspensions; utilization of existing cell staining methods to measure DNA content in lung cells; and analysis of DNA content and cell size. As the flow-system cell analysis technology is adapted to the measurement of exfoliated lung cells, rapid and quantitative determination of early changes in the physical and biochemical cellular properties will be attempted as a function of exposure to the toxic agents. (auth)« less

Lung Cancer Brain Metastases.

PubMed

Goldberg, Sarah B; Contessa, Joseph N; Omay, Sacit B; Chiang, Veronica

2015-01-01

Brain metastases are common among patients with lung cancer and have been associated with significant morbidity and limited survival. However, the treatment of brain metastases has evolved as the field has advanced in terms of central nervous system imaging, surgical technique, and radiotherapy technology. This has allowed patients to receive improved treatment with less toxicity and more durable benefit. In addition, there have been significant advances in systemic therapy for lung cancer in recent years, and several treatments including chemotherapy, targeted therapy, and immunotherapy exhibit activity in the central nervous system. Utilizing systemic therapy for treating brain metastases can avoid or delay local therapy and often allows patients to receive effective treatment for both intracranial and extracranial disease. Determining the appropriate treatment for patients with lung cancer brain metastases therefore requires a clear understanding of intracranial disease burden, tumor histology, molecular characteristics, and overall cancer prognosis. This review provides updates on the current state of surgery and radiotherapy for the treatment of brain metastases, as well as an overview of systemic therapy options that may be effective in select patients with intracranial metastases from lung cancer.

[Comparative studies on toxicity of various dielectrics, petroleum derivatives, used in electroerosion technology. IV. Morphological and cytoenzymatic changes in the lungs and acid-base imbalance in rats chronically exposed to petroleum hydrocarbons].

PubMed

Starek, A; Kamiński, M

1981-01-01

In rats exposed to odourless kerosene of 75 and 300 mg/m3 concentration, for 14 weeks, morphologic and cytoenzymatic examinations of lungs have been carried out and acid-base equilibrium indices in blood have been determined. Passive congestion of lung parenchyma, subpleural blood extravasation, atelectasis foci, thickened interalveolar septa with infiltrates from neutrophils, lymphocytes, eosinophils and macrophages have been found. In addition a decrease in succinic dehydrogenase activity, NADPH -- tetrazolium reductase, and Mg++-ATP-ase and increase in acid phosphatase activity have been revealed. Those have been focal changes, involving, apart from bronchial tree (low exposure -- 75 mg/m3), the remaining lung parenchyma segments (high exposure -- 300 mg/m3). In addition, disturbances in acid-base equilibrium in form of compensated metabolic alkalosis (75 mg/m3) and compensated metabolic acidosis (300 mg/m3) have occurred. The obtained results demonstrate toxic effects of kerosene hydrocarbons on the function and structure of lungs.

Automated system for lung nodules classification based on wavelet feature descriptor and support vector machine.

PubMed

Madero Orozco, Hiram; Vergara Villegas, Osslan Osiris; Cruz Sánchez, Vianey Guadalupe; Ochoa Domínguez, Humberto de Jesús; Nandayapa Alfaro, Manuel de Jesús

2015-02-12

Lung cancer is a leading cause of death worldwide; it refers to the uncontrolled growth of abnormal cells in the lung. A computed tomography (CT) scan of the thorax is the most sensitive method for detecting cancerous lung nodules. A lung nodule is a round lesion which can be either non-cancerous or cancerous. In the CT, the lung cancer is observed as round white shadow nodules. The possibility to obtain a manually accurate interpretation from CT scans demands a big effort by the radiologist and might be a fatiguing process. Therefore, the design of a computer-aided diagnosis (CADx) system would be helpful as a second opinion tool. The stages of the proposed CADx are: a supervised extraction of the region of interest to eliminate the shape differences among CT images. The Daubechies db1, db2, and db4 wavelet transforms are computed with one and two levels of decomposition. After that, 19 features are computed from each wavelet sub-band. Then, the sub-band and attribute selection is performed. As a result, 11 features are selected and combined in pairs as inputs to the support vector machine (SVM), which is used to distinguish CT images containing cancerous nodules from those not containing nodules. The clinical data set used for experiments consists of 45 CT scans from ELCAP and LIDC. For the training stage 61 CT images were used (36 with cancerous lung nodules and 25 without lung nodules). The system performance was tested with 45 CT scans (23 CT scans with lung nodules and 22 without nodules), different from that used for training. The results obtained show that the methodology successfully classifies cancerous nodules with a diameter from 2 mm to 30 mm. The total preciseness obtained was 82%; the sensitivity was 90.90%, whereas the specificity was 73.91%. The CADx system presented is competitive with other literature systems in terms of sensitivity. The system reduces the complexity of classification by not performing the typical segmentation stage of most CADx systems. Additionally, the novelty of the algorithm is the use of a wavelet feature descriptor.

Raman microimaging of murine lungs: insight into the vitamin A content.

PubMed

Marzec, K M; Kochan, K; Fedorowicz, A; Jasztal, A; Chruszcz-Lipska, K; Dobrowolski, J Cz; Chlopicki, S; Baranska, M

2015-04-07

The composition of the lung tissue of mice was investigated using Raman confocal microscopy at 532 nm excitation wavelength and was supported with various staining techniques as well as DFT calculations. This combination of experimental and theoretical techniques allows for the study of the distribution of lung lipofibroblasts (LIFs), rich in vitamin A, as well as the chemical structure of vitamin A. The comparison of the Raman spectra derived from LIFs with the experimental and theoretical spectra of standard retinoids showed the ability of LIFs to store all-trans retinol, which is partially oxidized to all-trans retinal and retinoic acid. Moreover, we were able to visualize the distribution of other lung tissue components including the surfactant and selected enzymes (lipoxygenase/glucose oxidase).

[Ventilatory strategy for ARDS].

PubMed

Yoshida, Takeshi; Takegawa, Ryousuke; Ogura, Hiroshi

2016-02-01

Fifteen years have passed since lung protective strategy to the patients with acute respiratory distress syndrome (ARDS) established. Recently, the new Berlin Definition of ARDS has been developed and this classified ARDS into three stages (mild, moderate, and severe ARDS), depending on the PaO2/FiO2. After this new definition of ARDS, each treatment to the patients with ARDS should be considered, depending on the severity of lung injury, such as prone position to the patients with severe ARDS, muscle paralysis to the patients with severe ARDS. In this review article, we review the history of lung protective strategy and ARDS definition, discuss the novel physiological approaches to minimizing ventilator-induced lung injury, and highlight a numbers of experimental/clinical studies to support these concepts.

Protocol for a Randomized Controlled Trial of Proactive Web-Based Versus Telephone-Based Information and Support: Can Electronic Platforms Deliver Effective Care for Lung Cancer Patients?

PubMed

Paul, Christine L; Boyes, Allison W; O'Brien, Lorna; Baker, Amanda L; Henskens, Frans A; Roos, Ian; Clinton-McHarg, Tara; Bellamy, Douglas; Colburn, Glenda; Rose, Shiho; Cox, Martine E; Fradgley, Elizabeth A; Baird, Hannah; Barker, Daniel

2016-10-26

Community-based services such as telephone support lines can provide valuable informational, emotional, and practical support for cancer patients via telephone- or Web-based (live chat or email) platforms. However, very little rigorous research has examined the efficacy of such services in improving patient outcomes. This study will determine whether: proactive telephone or Web-delivered support produces outcomes superior to printed information; and Web-delivered support produces outcomes comparable to telephone support. A consecutive sample of 501 lung cancer outpatients will be recruited from 50 Australian health services to participate in a patient-randomized controlled trial (RCT). Eligible individuals must: be 18 years or older; have received a lung cancer diagnosis (including mesothelioma) within the previous 4 months; have an approximate life expectancy of at least 6 months; and have Internet access. Participants will be randomly allocated to receive: (1) an information booklet, (2) proactive telephone support, or (3) proactive Web support, chat, and/or email. The primary patient outcomes will be measured by the General Health Questionnaire (GHQ-12) and Health Education and Impact Questionnaire (heiQ) at 3 and 6 months post recruitment. The acceptability of proactive recruitment strategies will also be assessed. It is hypothesized that participants receiving telephone or Web support will report reduced distress (GHQ-12 scores that are 0.3 standard deviations (SD) lower) and greater self-efficacy (heiQ scores that are 0.3 SDs higher) than participants receiving booklets. Individuals receiving Web support will report heiQ scores within 0.29 SDs of individuals receiving telephone support. If proven effective, electronic approaches such as live-chat and email have the potential to increase the accessibility and continuity of supportive care delivered by community-based services. This evidence may also inform the redesigning of helpline-style services to be effective and responsive to patient needs.

Nutritional state and lung disease in cystic fibrosis.

PubMed

Bakker, W

1992-10-01

The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the severity and progress of the pulmonary involvement associated with the disease. Many data support the view that malnutrition and deterioration of lung function are closely interrelated and interdependent, with each affecting the other, leading to a spiral decline in both. The occurrence of malnutrition appears to be associated with poor lung function and poor survival, and conversely prevention of malnutrition appears to be associated with better lung function and improved survival. Nutritional intervention may lead to an improvement in body weight, lung function and exercise tolerance, provided that the intervention is combined with exercise training in order to increase both respiratory and other muscle mass. These improvements can be preserved when patients have the stamina to continue with a high-energy, high-fat diet and daily exercise training at home.

Directional Multi-scale Modeling of High-Resolution Computed Tomography (HRCT) Lung Images for Diffuse Lung Disease Classification

NASA Astrophysics Data System (ADS)

Vo, Kiet T.; Sowmya, Arcot

A directional multi-scale modeling scheme based on wavelet and contourlet transforms is employed to describe HRCT lung image textures for classifying four diffuse lung disease patterns: normal, emphysema, ground glass opacity (GGO) and honey-combing. Generalized Gaussian density parameters are used to represent the detail sub-band features obtained by wavelet and contourlet transforms. In addition, support vector machines (SVMs) with excellent performance in a variety of pattern classification problems are used as classifier. The method is tested on a collection of 89 slices from 38 patients, each slice of size 512x512, 16 bits/pixel in DICOM format. The dataset contains 70,000 ROIs of those slices marked by experienced radiologists. We employ this technique at different wavelet and contourlet transform scales for diffuse lung disease classification. The technique presented here has best overall sensitivity 93.40% and specificity 98.40%.

Lived Experience among Patients Newly Diagnosed with Lung Adenocarcinoma Stage IV within One Year.

PubMed

Shih, Whei-Mei Jean; Hsu, Hsiu-Chin; Jiang, Ru-Shang; Lin, Mei-Hsiang

2015-01-01

lung cancer (LC) is the fifth of the 10 leading causes of death in the world. LC is in first place for cancer-related mortality for both males and females in Taiwan. It is one of the most difficult cancers to treat and is often diagnosed at a late stage. Patients with stage IV are often unprepared for the diagnosis. To explore lived experience among patients newly diagnosed with lung adenocarcinoma stage IV within one year. Twelve participants were recruited in this study. Content analysis of the interviews revealed four themes: (1) emotional roller coaster, (2) trying to find out causes, (3) adjusting my lifestyle, and (4) cancer fighter. This study provides new insight into the experiences of lung cancer patients y with newly diagnosed lung adenocarcinoma stage 4. These results will inform future supportive care service development and intervention research for patients with advanced stage cancer.

Measurement of absolute lung volumes by imaging techniques.

PubMed

Clausen, J

1997-10-01

In this paper, the techniques available for estimating total lung capacities from standard chest radiographs in children and infants as well as adults are reviewed. These techniques include manual measurements using ellipsoid and planimetry techniques as well as computerized systems. Techniques are also available for making radiographic lung volume measurements from portable chest radiographs. There are inadequate data in the literature to support recommending one specific technique over another. Though measurements of lung volumes by radiographic, plethysmographic, gas dilution or washout techniques result in remarkably similar mean results when groups of normal subjects are tested, in patients with disease, the results of these different basic measurement techniques can differ significantly. Computed tomographic and magnetic resonance techniques can also be used to measure absolute lung volumes and offer the theoretical advantages that the results in individual subjects are less affected by variances of thoracic shape than are measurements made using conventional chest radiographs.

The first patient treatment of electromagnetic-guided real time adaptive radiotherapy using MLC tracking for lung SABR.

PubMed

Booth, Jeremy T; Caillet, Vincent; Hardcastle, Nicholas; O'Brien, Ricky; Szymura, Kathryn; Crasta, Charlene; Harris, Benjamin; Haddad, Carol; Eade, Thomas; Keall, Paul J

2016-10-01

Real time adaptive radiotherapy that enables smaller irradiated volumes may reduce pulmonary toxicity. We report on the first patient treatment of electromagnetic-guided real time adaptive radiotherapy delivered with MLC tracking for lung stereotactic ablative body radiotherapy. A clinical trial was developed to investigate the safety and feasibility of MLC tracking in lung. The first patient was an 80-year old man with a single left lower lobe lung metastasis to be treated with SABR to 48Gy in 4 fractions. In-house software was integrated with a standard linear accelerator to adapt the treatment beam shape and position based on electromagnetic transponders implanted in the lung. MLC tracking plans were compared against standard ITV-based treatment planning. MLC tracking plan delivery was reconstructed in the patient to confirm safe delivery. Real time adaptive radiotherapy delivered with MLC tracking compared to standard ITV-based planning reduced the PTV by 41% (18.7-11cm 3 ) and the mean lung dose by 30% (202-140cGy), V20 by 35% (2.6-1.5%) and V5 by 9% (8.9-8%). An emerging technology, MLC tracking, has been translated into the clinic and used to treat lung SABR patients for the first time. This milestone represents an important first step for clinical real-time adaptive radiotherapy that could reduce pulmonary toxicity in lung radiotherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In Vivo Detection of Hyperoxia-Induced Pulmonary Endothelial Cell Death Using 99mTc-Duramycin

PubMed Central

Audi, Said H.; Jacobs, Elizabeth R.; Zhao, Ming; Roerig, David L.; Haworth, Steven T.; Clough, Anne V.

2014-01-01

Introduction: 99mTc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury. Methods: Rats were exposed to room air (normoxic) or >98% O2 for 48 or 60 hours. DU was injected i.v. in anesthetized rats, scintigraphy images were acquired at steady-state, and lung DU uptake was quantified from the images. Post-mortem, the lungs were removed for histological studies. Sequential lung sections were immunostained for caspase activation and endothelial and epithelial cells. Results: Lung DU uptake increased significantly (p < 0.001) by 39% and 146% in 48-hr and 60-hr exposed rats, respectively, compared to normoxic rats. There was strong correlation (r2 = 0.82, p = 0.005) between lung DU uptake and the number of cleaved caspase 3 (CC3) positive cells, and endothelial cells accounted for more than 50% of CC3 positive cells in the hyperoxic lungs. Histology revealed preserved lung morphology through 48 hours. By 60 hours there was evidence of edema, and modest neutrophilic infiltrate. Conclusions: Rat lung DU uptake in vivo increased after just 48 hours of >98% O2 exposure, prior to the onset of any substantial evidence of lung injury. These results suggest that apoptotic endothelial cells are the primary contributors to the enhanced DU lung uptake, and support the utility of DU imaging for detecting early endothelial cell death in vivo. PMID:25218023

New era of radiotherapy: an update in radiation-induced lung disease

PubMed Central

Benveniste, M. F. K.; Welsh, J.; Godoy, M. C. B.; Betancourt, S. L.; Mawlawi, O. R; Munden, R. F.

2014-01-01

Over the last few decades, advances in radiotherapy (RT) technology have improved delivery of radiation therapy dramatically. Advances in treatment planning with the development of image-guided radiotherapy and in techniques such as proton therapy, allows the radiation therapist to direct high doses of radiation to the tumour. These advancements result in improved local regional control while reducing potentially damaging dosage to surrounding normal tissues. It is important for radiologists to be aware of the radiological findings from these advances in order to differentiate expected radiation-induced lung injury (RILD) from recurrence, infection, and other lung diseases. In order to understand these changes and correlate them with imaging, the radiologist should have access to the radiation therapy treatment plans. PMID:23473474

Electromagnetic Tracking Navigation to Guide Radiofrequency Ablation (RFA) of a Lung Tumor

PubMed Central

Amalou, Hayet; Wood, Bradford J.

2013-01-01

Radiofrequency ablation (RFA) may be an option for patients with lung tumors who have unresectable disease and are not suitable for available palliative modalities. RFA electrode positioning may take several attempts, necessitating multiple imaging acquisitions or continuous use of CT (Computed Tomography). Electromagnetic tracking utilizes miniature sensors integrated with RFA equipment to guide tools in real-time, while referencing to pre-procedure imaging. This technology was demonstrated successfully during a lung tumor ablation, and was more accurate at targeting the tumor, compared to traditional freehand needle insertion. It is possible, although speculative and anecdotal, that more accuracy could prevent unnecessary repositioning punctures and decrease radiation exposure. Electromagnetic tracking has theoretical potential to benefit minimally invasive interventions. PMID:23207535

Successful prolonged ex vivo lung perfusion for graft preservation in rats.

PubMed

Noda, Kentaro; Shigemura, Norihisa; Tanaka, Yugo; Bhama, Jay K; D'Cunha, Jonathan; Luketich, James D; Bermudez, Christian A

2014-03-01

Ex vivo lung perfusion (EVLP) strategies represent a new frontier in lung transplantation technology, and there have been many clinical studies of EVLP in lung transplantation. The establishment of a reliable EVLP model in small animals is crucial to facilitating translational research using an EVLP strategy. The main objective of this study was to develop a reproducible rat EVLP (R-EVLP) model that enables prolonged evaluation of the explanted lung during EVLP and successful transplantation after EVLP. The donor heart-lung blocks were procured with cold low-potassium dextran solution and immersed in the solution for 1 h at 4 °C. And then, the heart-lung blocks were flushed retrogradely and warmed up to 37 °C in a circuit perfused antegradely with acellular perfusate. The perfusate was deoxygenated with a gas mixture (6% O2, 8% CO2, 86% N2). The perfusion flow was maintained at 20% of the entire cardiac output. At 37 °C, the lungs were mechanically ventilated and perfusion continued for 4 h. Every hour, the perfused lung was evaluated for gas exchange, dynamic lung compliance (Cdyn) and pulmonary vascular resistance (PVR). R-EVLP was performed for 4 h. Pulmonary oxygenation ability (pO2/pCO2) was stable for 4 h during EVLP. It was noted that Cdyn and PVR were also stable. After 4 h of EVLP, pO2 was 303 ± 19 mmHg, pCO2 was 39.6 ± 1.2 mmHg, PVR was 1.75 ± 0.10 mmHg/ml/min and Cdyn was 0.37 ± 0.03 ml/cmH2O. Lungs that were transplanted after 2 h of R-EVLP resulted in significantly better post-transplant oxygenation and compliance when compared with those after standard cold static preservation. Our R-EVLP model maintained stable lung oxygenation, compliance and vascular resistance for up to 4 h of perfusion duration. This reliable model should facilitate further advancement of experimental work using EVLP.

Mechanical ventilation during extracorporeal membrane oxygenation.

PubMed

Schmidt, Matthieu; Pellegrino, Vincent; Combes, Alain; Scheinkestel, Carlos; Cooper, D Jamie; Hodgson, Carol

2014-01-21

The timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes.

Mechanical ventilation during extracorporeal membrane oxygenation

PubMed Central

2014-01-01

The timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes. PMID:24447458

Radiotherapeutic Management of Non-Small Cell Lung Cancer in the Minimal Resource Setting.

PubMed

Rodin, Danielle; Grover, Surbhi; Xu, Melody J; Hanna, Timothy P; Olson, Robert; Schreiner, L John; Munshi, Anusheel; Mornex, Francoise; Palma, David; Gaspar, Laurie E

2016-01-01

Lung cancer is the most common cancer worldwide and the fifth most common cause of death globally. Its incidence continues to increase, especially within low- and middle-income countries (LMICs), which have limited capacity to address the growing need for treatment. The standard of care for lung cancer treatment often involves radiation therapy (RT), which plays an important therapeutic role in curative-intent treatment of early-stage to locally advanced disease, as well as in palliation. The infrastructure, equipment, and human resources required for RT may be limited in LMICs. However, this narrative review discusses the scope of the problem of lung cancer in LMICs, the role of RT technologies in lung cancer treatment, and RT capacity in developing countries. Strategies are presented for maximizing the availability and impact of RT in settings with minimal resource availability, and areas for potential future innovation are identified. Priorities for LMICs involve increasing access to RT equipment and trained health care professionals, ensuring quality of care, providing guidance on priority setting with limited resources, and encouraging innovation to increase the economic efficiency of RT delivery. Several international initiatives are currently under way and represent important first steps toward scaling up RT in LMICs to treat lung cancer. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment.

PubMed

Winkler-Heil, R; Hussain, M; Hofmann, W

2015-05-01

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM(-1). If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas.

Inhalation of gas metal arc-stainless steel welding fume promotes lung tumorigenesis in A/J mice.

PubMed

Falcone, Lauryn M; Erdely, Aaron; Meighan, Terence G; Battelli, Lori A; Salmen, Rebecca; McKinney, Walter; Stone, Samuel; Cumpston, Amy; Cumpston, Jared; Andrews, Ronnee N; Kashon, Michael; Antonini, James M; Zeidler-Erdely, Patti C

2017-08-01

Epidemiologic studies suggest an increased risk of lung cancer with exposure to welding fumes, but controlled animal studies are needed to support this association. Oropharyngeal aspiration of collected "aged" gas metal arc-stainless steel (GMA-SS) welding fume has been shown by our laboratory to promote lung tumor formation in vivo using a two-stage initiation-promotion model. Our objective in this study was to determine whether inhalation of freshly generated GMA-SS welding fume also acts as a lung tumor promoter in lung tumor-susceptible mice. Male A/J mice received intraperitoneal (IP) injections of corn oil or the chemical initiator 3-methylcholanthrene (MCA; 10 µg/g) and 1 week later were exposed by whole-body inhalation to air or GMA-SS welding aerosols for 4 h/d × 4 d/w × 9 w at a target concentration of 40 mg/m 3 . Lung nodules were enumerated at 30 weeks post-initiation. GMA-SS fume significantly promoted lung tumor multiplicity in A/J mice initiated with MCA (16.11 ± 1.18) compared to MCA/air-exposed mice (7.93 ± 0.82). Histopathological analysis found that the increased number of lung nodules in the MCA/GMA-SS group were hyperplasias and adenomas, which was consistent with developing lung tumorigenesis. Metal deposition analysis in the lung revealed a lower deposited dose, approximately fivefold compared to our previous aspiration study, still elicited a significant lung tumorigenic response. In conclusion, this study demonstrates that inhaling GMA-SS welding fume promotes lung tumorigenesis in vivo which is consistent with the epidemiologic studies that show welders may be at an increased risk for lung cancer.

Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice

PubMed Central

Martin, Timothy M.; Concel, Vincent J.; Upadhyay, Swapna; Bein, Kiflai; Brant, Kelly A.; George, Leema; Mitra, Ankita; Thimraj, Tania A.; Fabisiak, James P.; Vuga, Louis J.; Fattman, Cheryl; Kaminski, Naftali; Schulz, Holger; Leikauf, George D.

2014-01-01

Secreted phosphoprotein 1 (Spp1) is located within quantitative trait loci associated with lung function that was previously identified by contrasting C3H/HeJ and JF1/Msf mouse strains that have extremely divergent lung function. JF1/Msf mice with diminished lung function had reduced lung SPP1 transcript and protein during the peak stage of alveologenesis (postnatal day [P]14–P28) as compared with C3H/HeJ mice. In addition to a previously identified genetic variant that altered runt-related transcription factor 2 (RUNX2) binding in the Spp1 promoter, we identified another promoter variant in a putative RUNX2 binding site that increased the DNA protein binding. SPP1 induced dose-dependent mouse lung epithelial-15 cell proliferation. Spp1(−/−) mice have decreased specific total lung capacity/body weight, higher specific compliance, and increased mean airspace chord length (Lm) compared with Spp1(+/+) mice. Microarray analysis revealed enriched gene ontogeny categories, with numerous genes associated with lung development and/or respiratory disease. Insulin-like growth factor 1, Hedgehog-interacting protein, wingless-related mouse mammary tumor virus integration site 5A, and NOTCH1 transcripts decreased in the lung of P14 Spp1(−/−) mice as determined by quantitative RT-PCR analysis. SPP1 promotes pneumocyte growth, and mice lacking SPP1 have smaller, more compliant lungs with enlarged airspace (i.e., increased Lm). Microarray analysis suggests a dysregulation of key lung developmental transcripts in gene-targeted Spp1(−/−) mice, particularly during the peak phase of alveologenesis. In addition to its known roles in lung disease, this study supports SPP1 as a determinant of lung development in mice. PMID:24816281

Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

PubMed

Rotta, A T; Gunnarsson, B; Fuhrman, B P; Hernan, L J; Steinhorn, D M

2001-11-01

To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. A prospective, randomized, controlled, in vivo animal laboratory study. Animal research facility of a health sciences university. Forty-six New Zealand White rabbits. Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and decreased lung damage. However, in this small-animal model of acute lung injury, an open lung strategy with deliberate hypercapnia was associated with significant hemodynamic instability.

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update.

PubMed

Sweet, David G; Carnielli, Virgilio; Greisen, Gorm; Hallman, Mikko; Ozek, Eren; Plavka, Richard; Saugstad, Ola Didrik; Simeoni, Umberto; Speer, Christian P; Vento, Máximo; Visser, Gerard H A; Halliday, Henry L

2017-01-01

Advances in the management of respiratory distress syndrome (RDS) ensure that clinicians must continue to revise current practice. We report the third update of the European Guidelines for the Management of RDS by a European panel of expert neonatologists including input from an expert perinatal obstetrician based on available literature up to the beginning of 2016. Optimizing the outcome for babies with RDS includes consideration of when to use antenatal steroids, and good obstetric practice includes methods of predicting the risk of preterm delivery and also consideration of whether transfer to a perinatal centre is necessary and safe. Methods for optimal delivery room management have become more evidence based, and protocols for lung protection, including initiation of continuous positive airway pressure and titration of oxygen, should be implemented from soon after birth. Surfactant replacement therapy is a crucial part of the management of RDS, and newer protocols for surfactant administration are aimed at avoiding exposure to mechanical ventilation, and there is more evidence of differences among various surfactants in clinical use. Newer methods of maintaining babies on non-invasive respiratory support have been developed and offer potential for greater comfort and less chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease although minimizing the time spent on mechanical ventilation using caffeine and if necessary postnatal steroids are also important considerations. Protocols for optimizing the general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome. © 2016 S. Karger AG, Basel.

In Vivo Imaging of Influenza Virus Infection in Immunized Mice

PubMed Central

Czakó, Rita; Vogel, Leatrice; Lamirande, Elaine W.; Bock, Kevin W.; Moore, Ian N.; Ellebedy, Ali H.; Ahmed, Rafi

2017-01-01

ABSTRACT Immunization is the cornerstone of seasonal influenza control and represents an important component of pandemic preparedness strategies. Using a bioluminescent reporter virus, we demonstrate the application of noninvasive in vivo imaging system (IVIS) technology to evaluate the preclinical efficacy of candidate vaccines and immunotherapy in a mouse model of influenza. Sequential imaging revealed distinct spatiotemporal kinetics of bioluminescence in groups of mice passively or actively immunized by various strategies that accelerated the clearance of the challenge virus at different rates and by distinct mechanisms. Imaging findings were consistent with conclusions derived from virus titers in the lungs and, notably, were more informative than conventional efficacy endpoints in some cases. Our findings demonstrate the reliability of IVIS as a qualitative approach to support preclinical evaluation of candidate medical countermeasures for influenza in mice. PMID:28559489

Global perspectives of emerging occupational and environmental lung diseases.

PubMed

Moitra, Subhabrata; Puri, Rajan; Paul, Devon; Huang, Yuh-Chin T

2015-03-01

New technologies continue to be introduced into the workplace and the environment. These novel technologies also bring in new hazards leading to evolving patterns of established occupational and environmental diseases, as well as novel conditions never before encountered. Many of these emerging conditions have appeared in media outlets or in the literature as case reports. These sentinel cases often serve as a warning sign for subsequent outbreaks. This review will discuss environmental and occupational lung diseases and exposures from a global perspective. These diseases and exposures include environmental exposure to asbestos and lung diseases, accelerated silicosis in sandblasting jean workers, coal worker's pneumoconiosis in surface coal miners, health effects of indoor air pollution from burning of biomass fuels and exposures to heavy metals and potential health effects from hydraulic fracturing (fracking). Other emerging conditions are also discussed, including smog in developing countries, sand storms in Asia and the Middle East and respiratory illnesses from nanoparticles and man-made fibres. Clinicians must remain vigilant for potential occupational and environmental exposures, especially when evaluating patients with unusual and unique presentation, so that occupational and environmental risk factors may be identified, and monitoring and preventive measures can be implemented early.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saccomanno, G.

This work, supported by the United States Department of Energy, continues to add data on the health effects of cigarette smoking and radon exposure. Since the beginning of this contract, 473 sputum samples have been collected from 286 uranium workers who are routinely screened in an effort to identify cell changes that could signal possible progression to lung cancer; seven new lung cancer cases have been identified during this period. At this time, there are 426 lung cancer cases in the uranium miner tumor registry with diagnostic slides from surgery and/or autopsy; an additional 40 cases have been diagnosed withmore » sputum cytology only.« less

Lung cancer diagnosis with quantitative DIC microscopy and support vector machine

NASA Astrophysics Data System (ADS)

Zheng, Longfei; Cai, Shuangshuang; Zeng, Bixin; Xu, Min

2017-01-01

We report the study of lung squamous cell carcinoma diagnosis using the TI-DIC microscopy and the scattering-phase theorem. The spatially resolved optical properties of tissue are computed from the 2D phase map via the scattering-phase theorem. The scattering coefficient, the reduced scattering coefficient, and the anisotropy factor are all found to increase with the grade of lung cancer. The retrieved optical parameters are shown to distinguish cancer cases from the normal cases with high accuracy. This label-free microscopic approach applicable to fresh tissues may be promising for in situ rapid cancer diagnosis.

[Analysis of EML4-ALK gene fusion mutation in patients 
with non-small cell lung cancer].

PubMed

Wang, Xuzhou; Chen, Weisheng; Yu, Yinghao

2015-02-01

Non-small cell lung cancer (NSCLC) is the main type of lung cancer, and the related locus mutation detection research has become a hot direction of molecular targeted therapy, studying on gene mutation status of echinodem microtubule associated protein like 4-Anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR), detecting the sensitivity of EML4-ALK gene fusion and gene mutation of EGFR. EML4-ALK gene fusion in 85 cases of paraffin embedded tumor tissue and adjacent lung tissue was detected with the application of immunohistochemistry (IHC), Scorpions amplification refractory mutation system (Scorpions ARMS) fluorescence quantitative PCR and fluorescence in situ hybridization (FISH) technology, and EGFR gene in 18, 19, 20 and 21 exon mutation status was detected with the application of ARMS method. In 115 cases of NSCLC, IHC showed 32 cases with ALK (D5F3) expression, the expression rate was 27.8%; ARMS showed 27 cases with EML4-ALK fusion gene mutation, the mutation detection rate was 23.5%; 53 cases were detected with EGFR mutation, the mutation rate was 46%. While FISH showed 23 cases with EML4-ALK fusion gene mutation, the detection rate was 20%, slightly lower than the ARMS detection results, suggesting that ARMS more sensitive. The application of IHC, ARMS fluorescence quantitative PCR and FISH technology can make a rapid and accurate evaluation of EML4-ALK gene fusion.

National Center on Sleep Disorders Research

MedlinePlus

... for Updates The National Center on Sleep Disorders Research (NCSDR) Located within the National Heart, Lung, and ... key functions: research, training, technology transfer, and coordination. Research Sleep disorders span many medical fields, requiring multidisciplinary ...

Hybridization-Induced Aggregation Technology for Practical Clinical Testing: KRAS Mutation Detection in Lung and Colorectal Tumors.

PubMed

Sloane, Hillary S; Landers, James P; Kelly, Kimberly A

2016-07-01

KRAS mutations have emerged as powerful predictors of response to targeted therapies in the treatment of lung and colorectal cancers; thus, prospective KRAS genotyping is essential for appropriate treatment stratification. Conventional mutation testing technologies are not ideal for routine clinical screening, as they often involve complex, time-consuming processes and/or costly instrumentation. In response, we recently introduced a unique analytical strategy for revealing KRAS mutations, based on the allele-specific hybridization-induced aggregation (HIA) of oligonucleotide probe-conjugated microbeads. Using simple, inexpensive instrumentation, this approach allows for the detection of any common KRAS mutation in <10 minutes after PCR. Here, we evaluate the clinical utility of the HIA method for mutation detection (HIAMD). In the analysis of 20 lung and colon tumor pathology specimens, we observed a 100% correlation between the KRAS mutation statuses determined by HIAMD and sequencing. In addition, we were able to detect KRAS mutations in a background of 75% wild-type DNA-a finding consistent with that reported for sequencing. With this, we show that HIAMD allows for the rapid and cost-effective detection of KRAS mutations, without compromising analytical performance. These results indicate the validity of HIAMD as a mutation-testing technology suitable for practical clinical testing. Further expansion of this platform may involve the detection of mutations in other key oncogenic pathways. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Nurse's perceptions and experiences of using of a mobile-phone-based Advanced Symptom Management System (ASyMS) to monitor and manage chemotherapy-related toxicity.

PubMed

Maguire, R; McCann, L; Miller, M; Kearney, N

2008-09-01

Many people diagnosed with cancer will receive chemotherapy as a core component of their care. Recent changes in the delivery of cancer services mean that patients frequently receive care on an out-patient basis and are therefore often required to manage related side effects at home without direct support from oncology health professionals. The use of information and communications technology may be seen as a means of supporting patients receiving chemotherapy in the home care setting. This mixed methods study, reports on the perceptions of nurses (n=35) who participated in a randomised controlled trial of a mobile phone based, Advanced Symptom Management System (ASyMS), in the management of chemotherapy-related toxicity in patients with breast, lung and colorectal cancer. Nurses' perceptions of ASyMS were evaluated at the start and the end of the study. Overall, they could see the benefits of ASyMS in the remote monitoring of chemotherapy toxicity and its role in facilitating early intervention and subsequent management, demonstrating the potential utility of the system within clinical practice.

Welding and Lung Cancer in a Pooled Analysis of Case-Control Studies

PubMed Central

Kendzia, Benjamin; Behrens, Thomas; Jöckel, Karl-Heinz; Siemiatycki, Jack; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Van Gelder, Rainer; Olsson, Ann; Brüske, Irene; Wichmann, H.-Erich; Stücker, Isabelle; Guida, Florence; Tardón, Adonina; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Pohlabeln, Hermann; Ahrens, Wolfgang; Landi, Maria Teresa; Caporaso, Neil; Consonni, Dario; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Gustavsson, Per; Marcus, Michael; Fabianova, Eleonora; ‘t Mannetje, Andrea; Pearce, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Rudnai, Peter; Bencko, Vladimir; Janout, Vladimir; Mates, Dana; Foretova, Lenka; Forastiere, Francesco; McLaughlin, John; Demers, Paul; Bueno-de-Mesquita, Bas; Boffetta, Paolo; Schüz, Joachim; Straif, Kurt; Pesch, Beate; Brüning, Thomas

2013-01-01

Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer. PMID:24052544

Welding and lung cancer in a pooled analysis of case-control studies.

PubMed

Kendzia, Benjamin; Behrens, Thomas; Jöckel, Karl-Heinz; Siemiatycki, Jack; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Van Gelder, Rainer; Olsson, Ann; Brüske, Irene; Wichmann, H-Erich; Stücker, Isabelle; Guida, Florence; Tardón, Adonina; Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo; Pohlabeln, Hermann; Ahrens, Wolfgang; Landi, Maria Teresa; Caporaso, Neil; Consonni, Dario; Zaridze, David; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Gustavsson, Per; Marcus, Michael; Fabianova, Eleonora; 't Mannetje, Andrea; Pearce, Neil; Tse, Lap Ah; Yu, Ignatius Tak-Sun; Rudnai, Peter; Bencko, Vladimir; Janout, Vladimir; Mates, Dana; Foretova, Lenka; Forastiere, Francesco; McLaughlin, John; Demers, Paul; Bueno-de-Mesquita, Bas; Boffetta, Paolo; Schüz, Joachim; Straif, Kurt; Pesch, Beate; Brüning, Thomas

2013-11-15

Several epidemiologic studies have indicated an increased risk of lung cancer among welders. We used the SYNERGY project database to assess welding as a risk factor for developing lung cancer. The database includes data on 15,483 male lung cancer cases and 18,388 male controls from 16 studies in Europe, Canada, China, and New Zealand conducted between 1985 and 2010. Odds ratios and 95% confidence intervals between regular or occasional welding and lung cancer were estimated, with adjustment for smoking, age, study center, and employment in other occupations associated with lung cancer risk. Overall, 568 cases and 427 controls had ever worked as welders and had an odds ratio of developing lung cancer of 1.44 (95% confidence interval: 1.25, 1.67) with the odds ratio increasing for longer duration of welding. In never and light smokers, the odds ratio was 1.96 (95% confidence interval: 1.37, 2.79). The odds ratios were somewhat higher for squamous and small cell lung cancers than for adenocarcinoma. Another 1,994 cases and 1,930 controls had ever worked in occupations with occasional welding. Work in any of these occupations was associated with some elevation of risk, though not as much as observed in regular welders. Our findings lend further support to the hypothesis that welding is associated with an increased risk of lung cancer.

Lung cancer in patients with idiopathic pulmonary fibrosis.

PubMed

Karampitsakos, Theodoros; Tzilas, Vasilios; Tringidou, Rodoula; Steiropoulos, Paschalis; Aidinis, Vasilis; Papiris, Spyros A; Bouros, Demosthenes; Tzouvelekis, Argyris

2017-08-01

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease of unknown etiology. With a gradually increasing worldwide prevalence and a mortality rate exceeding that of many cancers, IPF diagnosis and management are critically important and require a comprehensive multidisciplinary approach. This approach also involves assessment of comorbid conditions, such as lung cancer, that exerts a dramatic impact on disease survival. Emerging evidence suggests that progressive lung scarring in the context of IPF represents a risk factor for lung carcinogenesis. Both disease entities present with major similarities in terms of pathogenetic pathways, as well as potential causative factors, such as smoking and viral infections. Besides disease pathogenesis, anti-cancer agents, including nintedanib, have been successfully applied in the treatment of patients with IPF while an oncologic approach with a cocktail of several pleiotropic anti-fibrotic agents is currently in the therapeutic pipeline of IPF. Nevertheless, epidemiologic association between IPF and lung cancer does not prove causality. Currently there is significant lack of knowledge supporting a direct association between lung fibrosis and cancer reflecting to disappointing therapeutic algorithms. An optimal therapeutic strategy for patients with both IPF and lung cancer represents an amenable need. This review article synthesizes the current state of knowledge regarding pathogenetic commonalities between IPF and lung cancer and focuses on clinical and therapeutic data that involve both disease entities. Copyright © 2017. Published by Elsevier Ltd.

Viral colonization in exhaled breath condensate of lung cancer patients: Possible role of EBV and CMV.

PubMed

Carpagnano, Giovanna E; Lacedonia, Donato; Natalicchio, Maria Iole; Cotugno, Grazia; Zoppo, Luigi; Martinelli, Domenico; Antonetti, Raffaele; Foschino-Barbaro, Maria Pia

2018-02-01

Today, an increasing interest is being addressed to the viral etiology of lung tumors. As a consequence, research efforts are currently being directed to the identification of the new viruses involved in lung carcinogenesis toward which the screening programs could be directed. The aim of this study was to investigate the airways colonization by the Epstein-Barr virus (EBV) and Citomegalovirus (CMV) in patients affected by lung cancer using, as a respiratory non-invasive sample, the exhaled breath condensate (EBC). About 70 lung-cancer patients and 40 controls were enrolled. All subjects underwent bronchial brushing and EBC collection. EBV-DNA and CMV-DNA were evaluated in both samples by real-time PCR assay. They were able to detect EBV and CMV in the EBC. An increase of the EBV positivity in non-small cell lung cancer (NSCLC) patients compared with controls and of the CMV in advanced stages of lung cancer were observed. The association of the positivity of the cytology and the CMV test (in EBC or brushing) slightly increased the sensitivity of malignant diagnosis. EBV and CMV resulted detectable in the EBC. In consideration of the potential involvement of these viruses in lung cancer, which was confirmed in this study, future studies in this direction were supported. © 2016 John Wiley & Sons Ltd.

Aerosol-administered alpha-tocopherol attenuates lung inflammation in rats given lipopolysaccharide intratracheally.

PubMed

Hybertson, Brooks M; Chung, Jin H; Fini, Mehdi A; Lee, Young M; Allard, Jenny D; Hansen, Brian N; Cho, Okyong J; Shibao, Gayle N; Repine, John E

2005-04-01

Intrapulmonary administration of bacterial lipopolysaccharide (LPS) induces a well-characterized lung inflammatory response involving alveolar macrophage activation, proinflammatory cytokine elaboration, and neutrophil influx. Vitamin E, a lipophilic antioxidant consisting of a family that includes tocopherols and tocotrienols, has previously been shown to have a variety of anti-inflammatory effects, raising interest in its possible uses in disease prevention or therapy. Because aerosol delivery is a specific and rapid way to administer agents to the lungs, the authors undertook to determine whether inhaled vitamin E aerosols would have an anti-inflammatory effect in the lungs. Using a rat model of acute lung inflammation caused by intratracheally administered LPS (10 microg Pseudomonas aeruginosa LPS), the authors examined the effect of aerosol-administered vitamin E, in this case alpha-tocopherol, on several indices of lung inflammation which are increased by LPS treatment. It was found that inhaled alpha-tocopherol aerosol, but not inhaled alpha-tocopherol acetate aerosol, decreased tumor necrosis factor alpha (TNFalpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA levels in lung tissue, TNFalpha and CINC-1 immunoreactive protein levels in lung lavage, and the number of neutrophils recoverable by lung lavage from rats given LPS intratracheally. These results contribute to the increasing body of work describing immunomodulatory functions of alpha-tocopherol, and support the idea that direct aerosol administration of alpha-tocopherol may play a beneficial role in strategies to control inflammatory lung illnesses.

Validation of a Plasma-Based Comprehensive Cancer Genotyping Assay Utilizing Orthogonal Tissue- and Plasma-Based Methodologies.

PubMed

Odegaard, Justin I; Vincent, John J; Mortimer, Stefanie; Vowles, James V; Ulrich, Bryan C; Banks, Kimberly C; Fairclough, Stephen R; Zill, Oliver A; Sikora, Marcin; Mokhtari, Reza; Abdueva, Diana; Nagy, Rebecca J; Lee, Christine E; Kiedrowski, Lesli A; Paweletz, Cloud P; Eltoukhy, Helmy; Lanman, Richard B; Chudova, Darya I; Talasaz, AmirAli

2018-04-24

Purpose: To analytically and clinically validate a circulating cell-free tumor DNA sequencing test for comprehensive tumor genotyping and demonstrate its clinical feasibility. Experimental Design: Analytic validation was conducted according to established principles and guidelines. Blood-to-blood clinical validation comprised blinded external comparison with clinical droplet digital PCR across 222 consecutive biomarker-positive clinical samples. Blood-to-tissue clinical validation comprised comparison of digital sequencing calls to those documented in the medical record of 543 consecutive lung cancer patients. Clinical experience was reported from 10,593 consecutive clinical samples. Results: Digital sequencing technology enabled variant detection down to 0.02% to 0.04% allelic fraction/2.12 copies with ≤0.3%/2.24-2.76 copies 95% limits of detection while maintaining high specificity [prevalence-adjusted positive predictive values (PPV) >98%]. Clinical validation using orthogonal plasma- and tissue-based clinical genotyping across >750 patients demonstrated high accuracy and specificity [positive percent agreement (PPAs) and negative percent agreement (NPAs) >99% and PPVs 92%-100%]. Clinical use in 10,593 advanced adult solid tumor patients demonstrated high feasibility (>99.6% technical success rate) and clinical sensitivity (85.9%), with high potential actionability (16.7% with FDA-approved on-label treatment options; 72.0% with treatment or trial recommendations), particularly in non-small cell lung cancer, where 34.5% of patient samples comprised a directly targetable standard-of-care biomarker. Conclusions: High concordance with orthogonal clinical plasma- and tissue-based genotyping methods supports the clinical accuracy of digital sequencing across all four types of targetable genomic alterations. Digital sequencing's clinical applicability is further supported by high rates of technical success and biomarker target discovery. Clin Cancer Res; 1-11. ©2018 AACR. ©2018 American Association for Cancer Research.

Current and new challenges in occupational lung diseases.

PubMed

De Matteis, Sara; Heederik, Dick; Burdorf, Alex; Colosio, Claudio; Cullinan, Paul; Henneberger, Paul K; Olsson, Ann; Raynal, Anne; Rooijackers, Jos; Santonen, Tiina; Sastre, Joaquin; Schlünssen, Vivi; van Tongeren, Martie; Sigsgaard, Torben

2017-12-31

Occupational lung diseases are an important public health issue and are avoidable through preventive interventions in the workplace. Up-to-date knowledge about changes in exposure to occupational hazards as a result of technological and industrial developments is essential to the design and implementation of efficient and effective workplace preventive measures. New occupational agents with unknown respiratory health effects are constantly introduced to the market and require periodic health surveillance among exposed workers to detect early signs of adverse respiratory effects. In addition, the ageing workforce, many of whom have pre-existing respiratory conditions, poses new challenges in terms of the diagnosis and management of occupational lung diseases. Primary preventive interventions aimed to reduce exposure levels in the workplace remain pivotal for elimination of the occupational lung disease burden. To achieve this goal there is still a clear need for setting standard occupational exposure limits based on transparent evidence-based methodology, in particular for carcinogens and sensitising agents that expose large working populations to risk. The present overview, focused on the occupational lung disease burden in Europe, proposes directions for all parties involved in the prevention of occupational lung disease, from researchers and occupational and respiratory health professionals to workers and employers. The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2017.

MO-E-BRB-03: Panel Member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salter, B.

2016-06-15

In this interactive session, lung SBRT patient cases will be presented to highlight real-world considerations for ensuring safe and accurate treatment delivery. An expert panel of speakers will discuss challenges specific to lung SBRT including patient selection, patient immobilization techniques, 4D CT simulation and respiratory motion management, target delineation for treatment planning, online treatment alignment, and established prescription regimens and OAR dose limits. Practical examples of cases, including the patient flow thought the clinical process are presented and audience participation will be encouraged. This panel session is designed to provide case demonstration and review for lung SBRT in terms ofmore » (1) clinical appropriateness in patient selection, (2) strategies for simulation, including 4D and respiratory motion management, and (3) applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent, and (4) image guidance in treatment delivery. Learning Objectives: Understand the established requirements for patient selection in lung SBRT Become familiar with the various immobilization strategies for lung SBRT, including technology for respiratory motion management Understand the benefits and pitfalls of applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent determination for lung SBRT Understand established prescription regimes and OAR dose limits.« less

MO-E-BRB-01: Panel Member

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benedict, S.

2016-06-15

In this interactive session, lung SBRT patient cases will be presented to highlight real-world considerations for ensuring safe and accurate treatment delivery. An expert panel of speakers will discuss challenges specific to lung SBRT including patient selection, patient immobilization techniques, 4D CT simulation and respiratory motion management, target delineation for treatment planning, online treatment alignment, and established prescription regimens and OAR dose limits. Practical examples of cases, including the patient flow thought the clinical process are presented and audience participation will be encouraged. This panel session is designed to provide case demonstration and review for lung SBRT in terms ofmore » (1) clinical appropriateness in patient selection, (2) strategies for simulation, including 4D and respiratory motion management, and (3) applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent, and (4) image guidance in treatment delivery. Learning Objectives: Understand the established requirements for patient selection in lung SBRT Become familiar with the various immobilization strategies for lung SBRT, including technology for respiratory motion management Understand the benefits and pitfalls of applying multi imaging modality (4D CT imaging, MRI, PET) for tumor volume delineation and motion extent determination for lung SBRT Understand established prescription regimes and OAR dose limits.« less

Noninvasive imaging of experimental lung fibrosis.

PubMed

Zhou, Yong; Chen, Huaping; Ambalavanan, Namasivayam; Liu, Gang; Antony, Veena B; Ding, Qiang; Nath, Hrudaya; Eary, Janet F; Thannickal, Victor J

2015-07-01

Small animal models of lung fibrosis are essential for unraveling the molecular mechanisms underlying human fibrotic lung diseases; additionally, they are useful for preclinical testing of candidate antifibrotic agents. The current end-point measures of experimental lung fibrosis involve labor-intensive histological and biochemical analyses. These measures fail to account for dynamic changes in the disease process in individual animals and are limited by the need for large numbers of animals for longitudinal studies. The emergence of noninvasive imaging technologies provides exciting opportunities to image lung fibrosis in live animals as often as needed and to longitudinally track the efficacy of novel antifibrotic compounds. Data obtained by noninvasive imaging provide complementary information to histological and biochemical measurements. In addition, the use of noninvasive imaging in animal studies reduces animal usage, thus satisfying animal welfare concerns. In this article, we review these new imaging modalities with the potential for evaluation of lung fibrosis in small animal models. Such techniques include micro-computed tomography (micro-CT), magnetic resonance imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and multimodal imaging systems including PET/CT and SPECT/CT. It is anticipated that noninvasive imaging will be increasingly used in animal models of fibrosis to gain insights into disease pathogenesis and as preclinical tools to assess drug efficacy.

[Use of bronchial blocker in emergent thoracotomy in presence of upper airway hemorrhage, and cervical spine fracture: a difficult decision].

PubMed

Almeida, Carlos; Freitas, Maria João; Brandão, Diogo; Assunção, José Pedro

2018-01-13

Female, 85 y.o., weighting 60kg, multiple trauma patient. After an initial laparotomy, an emergent thoracotomy was performed using a bronchial blocker for lung isolation (initial active suction was applied). During surgery, bronchial cuff was deflated, causing a self-limited tracheal blood flooding. A second lung isolation was attempted but it was not as effective as initially. Probably, a lung collapse with the same bronchial blocker was impaired in the second attempt because of the obstruction of bronchial blocker lumen by intraoperative endobronchial hemorrhage. Bronchial blocker active suction may contribute to obtain or accelerate lung collapse, particularly in patients that do not tolerate ventilator disconnection technique or lung surgical compression. The use of bronchial blockers technology was a valuable alternative to double lumen tubes in this case of emergent thoracotomy in the context of a patient having thoracic, abdominal trauma, severe laceration of tongue and apophysis odontoid fracture associated to massive hemorrhage, despite several pitfalls that could compromise its use. The authors intend to discuss the advantages and disadvantages of bronchial blockers comparing to double-lumen tubes for lung isolation, and the risks of our approach, in this complex multitrauma case. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

The detection of pleural effusion using a parametric EIT technique.

PubMed

Arad, M; Zlochiver, S; Davidson, T; Shoenfeld, Y; Adunsky, A; Abboud, S

2009-04-01

The bioimpedance technique provides a safe, low-cost and non-invasive alternative for routine monitoring of lung fluid levels in patients. In this study we have investigated the feasibility of bioimpedance measurements to monitor pleural effusion (PE) patients. The measurement system (eight-electrode thoracic belt, opposite sequential current injections, 3 mA, 20 kHz) employed a parametric reconstruction algorithm to assess the left and right lung resistivity values. Bioimpedance measurements were taken before and after the removal of pleural fluids, while the patient was sitting at rest during tidal respiration in order to minimize movements of the thoracic cavity. The mean resistivity difference between the lung on the side with PE and the lung on the other side was -48 Omega cm. A high correlation was found between the mean lung resistivity value before the removal of the fluids and the volume of pleural fluids removed, with a sensitivity of -0.17 Omega cm ml(-1) (linear regression, R=0.53). The present study further supports the feasibility and applicability of the bioimpedance technique, and specifically the approach of parametric left and right lung resistivity reconstruction, in monitoring lung patients.

Overview of ultrasound-induced lung hemorrhage

NASA Astrophysics Data System (ADS)

O'Brien, William D.; Simpson, Douglas G.; Frizzell, Leon A.; Oelze, Michael L.; Zachary, James F.

2003-10-01

It is well documented that ultrasound-induced lung hemorrhage can occur in mice, rats, rabbits, pigs, and monkeys. Our own experimental studies have focused on mice, rats, and pigs as animal models. The characteristics of the lesions produced in mice, rats and pigs were similar to those described in studies by our research group and others, suggesting a common pathogenesis for the initiation and propagation of the lesions at the macroscopic and microscopic levels. Five experimental in vivo studies have been conducted to evaluate whether cavitation is responsible for ultrasound-induced lung hemorrhage. The studies evaluated the dependencies of hydrostatic pressure, frequency, pulse polarity, contrast agents and lung inflation, and the results of each study appeared inconsistent with the hypothesis that the mechanism for the production of a lung hemorrhage was inertial cavitation. Other dependencies evaluated included beam width, pulse repetition frequency, pulse duration, exposure duration, and animal species and age. The thresholds for producing ultrasound-induced lung hemorrhage, in general, were less than the FDA's regulatory limit of a Mechanical Index (MI) of 1.9. Further, the MI does not appear to provide a risk-based index for lung hemorrhage. [Work supported by NIH Grant No. R01EB02641.

EFFECT OF THE LESION DUE TO INFLUENZA VIRUS ON THE RESISTANCE OF MICE TO INHALED PNEUMOCOCCI

PubMed Central

Harford, Carl G.; Leidler, Virginia; Hara, Mary

1949-01-01

1. The normal lung of the mouse possesses the power of reducing markedly its content of Type I pneumococci within 3 hours after inhalation of the organisms in the form of fine droplets. 2. Lungs with fully developed influenza viral pneumonia not only fail to reduce the pulmonary content of pneumococci administered in this manner but, on the contrary, support their growth. 3. After intrabronchial inoculation into mice, influenza virus multiplies rapidly in the lung within 24 hours. 4. Criteria have been established for distinction between true viral lesions of the lung and changes due to the inoculation of diluents as vehicles for the virus. 5. 24 hours after inoculation of virus, there are no macroscopic lesions in the lung and the microscopic changes are due to the diluent. 6. Presence and multiplication of the virus in the lung 24 hours after inoculation have no apparent effect on the power of the lung to reduce rapidly its content of inhaled pneumococci. 7. The effect of the virus in lowering resistance to secondary bacterial infection appears to be due to the presence of the lesion produced by the virus. PMID:18099165

Serum metabolic profiling study of lung cancer using ultra high performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

PubMed

Li, Yanjie; Song, Xue; Zhao, Xinjie; Zou, Lijuan; Xu, Guowang

2014-09-01

Lung cancer is currently the leading cause of cancer-related mortality worldwide. It is, therefore, important to enhance understanding and add a new auxiliary detection tool of lung cancer. In this work, serum metabolic characteristics of lung cancer were investigated with a non-targeted metabolomics method. The metabolic profiling of 23 patients with lung cancer and 23 healthy controls were analyzed using ultra high performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS). Partial least squares discriminant analysis (PLS-DA) model of the metabolic data allowed the clear separation of the lung cancer patients from the healthy controls. In total, 27 differential metabolites were identified, which were mostly related to the perturbation of lipid metabolism, including choline, free fatty acids, lysophosphatidylcholines, etc. Choline and linoleic acid were defined as one combinational biomarker using binary logistic regression, which was supported by the validation with a smaller sample-set (9 patients and 9 healthy controls). These findings show that LC/MS-based serum metabolic profiling has potential application in complementary identification of lung cancer patients, and could be a powerful tool for cancer research. Copyright © 2014 Elsevier B.V. All rights reserved.

Adult bone marrow-derived stem cells for the lung: implications for pediatric lung diseases.

PubMed

van Haaften, Timothy; Thébaud, Bernard

2006-04-01

Bronchopulmonary dysplasia (BPD) and cystic fibrosis (CF) are two common serious chronic respiratory disorders without specific treatments affecting children. BPD is characterized by an arrest in alveolar growth in premature infants requiring respiratory support. CF is the most common fatal inherited genetic disorder characterized by abnormally thick mucus secretions, recurrent infection and ultimately lung destruction. One commonality between these two diseases is the promise of utilizing stem cells therapeutically. Indeed, the use of exogenous cells to supplement the natural repair mechanisms or the possibility of genetic manipulation in vitro before administration are appealing therapeutic options for these diseases. Increasing attention has been focused on the use of adult bone marrow-derived stem cells (BMSC) to regenerate damaged organs such as the heart, the brain, and the liver. However, due to the lung's complexity as well as the low rate of cellular turnover within the lung, progress has been slower in this area compared with the skin or liver. Initial work suggests that BMSC can engraft and differentiate into a variety of lung cells, but these findings have been challenged recently. This article critically reviews the current advances on the therapeutic use of stem cells for lung regeneration.

Transbronchial biopsies safely diagnose amyloid lung disease

PubMed Central

Govender, Praveen; Keyes, Colleen M.; Hankinson, Elizabeth A.; O’Hara, Carl J.; Sanchorawala, Vaishali; Berk, John L.

2018-01-01

Background Autopsy identifies lung involvement in 58–92% of patients with the most prevalent forms of systemic amyloidoses. In the absence of lung biopsies, amyloid lung disease often goes unrecognized. Report of a death following transbronchial biopsies in a patient with systemic amyloidosis cautioned against the procedure in this patient cohort. We reviewed our experience with transbronchial biopsies in patients with amyloidosis to determine the safety and utility of bronchoscopic lung biopsies. Methods We identified patients referred to the Amyloidosis Center at Boston Medical Center with lung amyloidosis diagnosed by transbronchial lung biopsies (TBBX). Amyloid typing was determined by immunohistochemistry or mass spectrometry. Standard end organ assessments, including pulmonary function test (PFT) and chest tomography (CT) imaging, and extra-thoracic biopsies established the extent of disease. Results Twenty-five (21.7%) of 115 patients with lung amyloidosis were diagnosed by TBBX. PFT classified 33.3% with restrictive physiology, 28.6% with obstructive disease, and 9.5% mixed physiology; 9.5% exhibited isolated diffusion defects while 19% had normal pulmonary testing. Two view chest or CT imaging identified focal opacities in 52% of cases and diffuse interstitial disease in 48%. Amyloid type and disease extent included 68% systemic AL disease, 16% localized (lung limited) AL disease, 12% ATTR disease, and 4% AA amyloidosis. Fluoroscopy was not used during biopsy. No procedure complications were reported. Conclusions Our case series of 25 patients supports the use of bronchoscopic transbronchial biopsies for diagnosis of parenchymal lung amyloidosis. Normal PFTs do not rule out the histologic presence of amyloid lung disease. PMID:28393574

Survival after extreme left atrial hypertension and pulmonary hemorrhage in an infant supported with extracorporeal membrane oxygenation for refractory atrial flutter.

PubMed

Cisco, Michael J; Asija, Ritu; Dubin, Anne M; Perry, Stanton B; Hanley, Frank L; Roth, Stephen J

2011-05-01

We report here the survival of an infant who developed extreme left atrial hypertension and severe pulmonary hemorrhage while supported with extracorporeal membrane oxygenation for refractory atrial flutter. The patient recovered after decompression of the left heart and catheter ablation of the atrioventricular node. Lucile Packard Children's Hospital (Stanford, CA). Chart review. Recovery of lung function is possible despite systemic-level left atrial pressure resulting in pulmonary hemorrhage and complete solidification of lung parenchyma on gross inspection. Resolution of pulmonary hemorrhage despite anticoagulation while on extracorporeal membrane oxygenation can occur after relief of left atrial hypertension.

Experience with the first 50 ex vivo lung perfusions in clinical transplantation.

PubMed

Cypel, Marcelo; Yeung, Jonathan C; Machuca, Tiago; Chen, Manyin; Singer, Lianne G; Yasufuku, Kazuhiro; de Perrot, Marc; Pierre, Andrew; Waddell, Thomas K; Keshavjee, Shaf

2012-11-01

Normothermic ex vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our experience with 50 consecutive transplants after ex vivo lung perfusion. A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pao(2)/Fio(2) <300 mm Hg or lungs with radiographic or clinical findings of pulmonary edema) and lungs from cardiac death donors were subjected to 4 to 6 hours of ex vivo lung perfusion. Lungs that achieved stable airway and vascular pressures and Pao(2)/Fio(2) greater than 400 mm Hg during ex vivo lung perfusion were transplanted. The primary end point was the incidence of primary graft dysfunction grade 3 at 72 hours after transplantation. End points were compared with lung transplants not treated with ex vivo lung perfusion (controls). A total of 317 lung transplants were performed during the study period (39 months). Fifty-eight ex vivo lung perfusion procedures were performed, resulting in 50 transplants (86% use). Of these, 22 were from cardiac death donors and 28 were from brain death donors. The mean donor Pao(2)/Fio(2) was 334 mm Hg in the ex vivo lung perfusion group and 452 mm Hg in the control group (P = .0001). The incidence of primary graft dysfunction grade 3 at 72 hours was 2% in the ex vivo lung perfusion group and 8.5% in the control group (P = .14). One patient (2%) in the ex vivo lung perfusion group and 7 patients (2.7%) in the control group required extracorporeal lung support for primary graft dysfunction (P = 1.00). The median time to extubation, intensive care unit stay, and hospital length of stay were 2, 4, and 20 days, respectively, in the ex vivo lung perfusion group and 2, 4, and 23 days, respectively, in the control group (P > .05). Thirty-day mortality (4% in the ex vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the ex vivo lung perfusion group and 86% in the control group, P = 1.00) were similar in both groups. Transplantation of high-risk donor lungs after 4 to 6 hours of ex vivo lung perfusion is safe, and outcomes are similar to those of conventional transplants. Ex vivo lung perfusion improved our center use of donor lungs, accounting for 20% of our current lung transplant activity. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Production and Assessment of Decellularized Pig and Human Lung Scaffolds

PubMed Central

Niles, Jean; Riddle, Michael; Vargas, Gracie; Schilagard, Tuya; Ma, Liang; Edward, Kert; La Francesca, Saverio; Sakamoto, Jason; Vega, Stephanie; Ogadegbe, Marie; Mlcak, Ronald; Deyo, Donald; Woodson, Lee; McQuitty, Christopher; Lick, Scott; Beckles, Daniel; Melo, Esther; Cortiella, Joaquin

2013-01-01

The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production. PMID:23638920

Production and assessment of decellularized pig and human lung scaffolds.

PubMed

Nichols, Joan E; Niles, Jean; Riddle, Michael; Vargas, Gracie; Schilagard, Tuya; Ma, Liang; Edward, Kert; La Francesca, Saverio; Sakamoto, Jason; Vega, Stephanie; Ogadegbe, Marie; Mlcak, Ronald; Deyo, Donald; Woodson, Lee; McQuitty, Christopher; Lick, Scott; Beckles, Daniel; Melo, Esther; Cortiella, Joaquin

2013-09-01

The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production.

The use of lung ultrasound images for the differential diagnosis of pulmonary and cardiac interstitial pathology.

PubMed

Soldati, Gino; Demi, Marcello

2017-06-01

In recent years, great advances have been made in the use of lung ultrasound to detect pulmonary edema and interstitial changes in the lung. However, it is clear that B-lines oversimplify the description of the physical phenomena associated with their presence. The artifactual images that ultrasounds provide in interstitial pulmonary pathology are merely the ultimate outcome of the complex interaction of a specific acoustic wave with a specific three-dimensional biological structure. This interaction lacks a solid physical interpretation of the acoustic signs to support it. The aim of this paper was to describe the differences between the sonographic interstitial syndrome related to lung diseases and that related to cardiogenic edema in the light of current knowledge regarding the pleural plane's response to ultrasound waves.

Obesity: “Priming” the Lung for Injury

PubMed Central

Konter, Jason; Baez, Elizabeth; Summer, Ross S

2012-01-01

Acute lung injury (ALI) is a severe inflammatory condition that develops in response to local and systemic lung challenges. To date, specific risk factors for development of ALI remain poorly defined. Recent epidemiological studies have reported obesity as an important predisposing factor in the development of this condition. Although the pathogenic mechanisms linking obesity and ALI have not been well-elucidated, emerging scientific evidence has described factors secreted by adipose tissue that have important biological activities in lung and has suggested that altered secretion of these factors during obesity contributes to increased ALI susceptibility. The objective of this manuscript is to highlight recent clinical evidence supporting the association between obesity and ALI and to discuss the posited role for adipose tissue-derived factors in the pathogenesis of this condition. PMID:22449512

Time-series analysis of lung texture on bone-suppressed dynamic chest radiograph for the evaluation of pulmonary function: a preliminary study

NASA Astrophysics Data System (ADS)

Tanaka, Rie; Matsuda, Hiroaki; Sanada, Shigeru

2017-03-01

The density of lung tissue changes as demonstrated on imagery is dependent on the relative increases and decreases in the volume of air and lung vessels per unit volume of lung. Therefore, a time-series analysis of lung texture can be used to evaluate relative pulmonary function. This study was performed to assess a time-series analysis of lung texture on dynamic chest radiographs during respiration, and to demonstrate its usefulness in the diagnosis of pulmonary impairments. Sequential chest radiographs of 30 patients were obtained using a dynamic flat-panel detector (FPD; 100 kV, 0.2 mAs/pulse, 15 frames/s, SID = 2.0 m; Prototype, Konica Minolta). Imaging was performed during respiration, and 210 images were obtained over 14 seconds. Commercial bone suppression image-processing software (Clear Read Bone Suppression; Riverain Technologies, Miamisburg, Ohio, USA) was applied to the sequential chest radiographs to create corresponding bone suppression images. Average pixel values, standard deviation (SD), kurtosis, and skewness were calculated based on a density histogram analysis in lung regions. Regions of interest (ROIs) were manually located in the lungs, and the same ROIs were traced by the template matching technique during respiration. Average pixel value effectively differentiated regions with ventilatory defects and normal lung tissue. The average pixel values in normal areas changed dynamically in synchronization with the respiratory phase, whereas those in regions of ventilatory defects indicated reduced variations in pixel value. There were no significant differences between ventilatory defects and normal lung tissue in the other parameters. We confirmed that time-series analysis of lung texture was useful for the evaluation of pulmonary function in dynamic chest radiography during respiration. Pulmonary impairments were detected as reduced changes in pixel value. This technique is a simple, cost-effective diagnostic tool for the evaluation of regional pulmonary function.

Particle characteristics and lung deposition patterns in a human airway replica of a dry powder formulation of polylactic acid produced using supercritical fluid technology.

PubMed

Cheng, Y S; Yazzie, D; Gao, J; Muggli, D; Etter, J; Rosenthal, G J

2003-01-01

Polylactic acid (PLA) powders have been used as vector particles to carry pharmaceutical material. Drugs incorporated in the PLA powder can be retained in the lung for a longer period and may be more effective than free-form drugs. A new formulation of L-PLA dry powder, which was easy to disperse in the air, was produced by using a supercritical technology. The L-PLA powder was characterized in terms of physical particle size and aerodynamic size as generated with a Turbuhaler dry powder inhaler (DPI). Electron microscopy analysis of the particles indicated that they were individual particles in bulk form and became aggregate particles after generation by the Turbuhaler. Aerodynamic particle size analysis using both an Aerodynamic Particle Sizer (APS) aerosol spectrometer and Andersen impactor showed that the aerodynamic size decreased as the flow rate in the Turbuhaler increased from 28.3 to 90 L min(-1). Deposition patterns in the human respiratory tract were estimated using a realistic physical replica of human airways. Deposition of the L-PLA was high (80.8%) in the oral airway at 28.3 L min(-1) and an average of 73.4% at flow rates of 60 and 90 L min(-1). In the lung region, the deposition totaled 7.2% at 28.3 L min(-1), 18.3% at 60 L min(-1), and 17.6% at 90 L min(-1). These deposition patterns were consistent with aerodynamic size measurement, which showed 76 to 86% deposition in the USP/EP (US Pharmacopoeia/European Pharmacopoeia) induction port. As the flow rate increased, fewer aggregates were formed resulting in the smaller aerodynamic particles. As a result, more particles penetrated the oral airways and were available for deposition in the lung. Our results showed that L-PLA particles as manufactured by the supercritical technology could be used in a DPI that does not require the use of carrier particles to facilitate aerosol delivery.

Effects of Cardiopulmonary Support With a Novel Pediatric Pump-Lung in a 30-Day Ovine Animal Model.

PubMed

Liu, Yang; Sanchez, Pablo G; Wei, Xufeng; Watkins, Amelia C; Niu, Shuqiong; Wu, Zhongjun J; Griffith, Bartley P

2015-12-01

The scarcity of donor organs has led to the development of devices that provide optimal long-term respiratory or cardiopulmonary support to bridge recipients as they wait for lung and/or heart transplantation. This study was designed to evaluate the 30-day in vivo performance of the newly developed pediatric pump-lung (PediPL) for cardiopulmonary support using a juvenile sheep model. The PediPL device was placed surgically between the right atrium and descending aorta in eight sheep (25.4-31.2 kg) and evaluated for 30 days. Anticoagulation was maintained with continuous heparin infusion (activated clotting time 150-200 s). The flow rate was measured continually, and gas transfer was measured daily. Plasma free hemoglobin, platelet activation, hematologic data, and blood biochemistry were assessed twice a week. Sheep were euthanized after 30 days. The explanted devices were examined for gross thrombosis. Six sheep survived for 30-32 days. During the study, the oxygen transfer rate of the devices was 54.9 ± 13.2 mL/min at a mean flow rate of 1.14 ± 0.46 L/min with blood oxygen saturation of 95.4% ± 1.7%. Plasma free hemoglobin was 8.2 ± 3.7 mg/dL. Platelet activation was 5.35 ± 2.65%. The animals had normal organ chemistries except for surgery-related transient alterations in kidney and liver function. Although we found some scattered thrombi on the membrane surfaces of some explanted devices during the necropsy, the device function and performance did not degrade. The PediPL device was capable of providing cardiopulmonary support with long-term reliability and good biocompatibility over the 30-day duration and offers the potential option for bridging pediatric patients with end-stage heart or lung disease to heart and/or lung transplantation. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

In vivo detection of hyperoxia-induced pulmonary endothelial cell death using (99m)Tc-duramycin.

PubMed

Audi, Said H; Jacobs, Elizabeth R; Zhao, Ming; Roerig, David L; Haworth, Steven T; Clough, Anne V

2015-01-01

(99m)Tc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury. Rats were exposed to room air (normoxic) or >98% O2 for 48 or 60 hours. DU was injected i.v. in anesthetized rats, scintigraphy images were acquired at steady-state, and lung DU uptake was quantified from the images. Post-mortem, the lungs were removed for histological studies. Sequential lung sections were immunostained for caspase activation and endothelial and epithelial cells. Lung DU uptake increased significantly (p<0.001) by 39% and 146% in 48-hr and 60-hr exposed rats, respectively, compared to normoxic rats. There was strong correlation (r(2)=0.82, p=0.005) between lung DU uptake and the number of cleaved caspase 3 (CC3) positive cells, and endothelial cells accounted for more than 50% of CC3 positive cells in the hyperoxic lungs. Histology revealed preserved lung morphology through 48 hours. By 60 hours there was evidence of edema, and modest neutrophilic infiltrate. Rat lung DU uptake in vivo increased after just 48 hours of >98% O2 exposure, prior to the onset of any substantial evidence of lung injury. These results suggest that apoptotic endothelial cells are the primary contributors to the enhanced DU lung uptake, and support the utility of DU imaging for detecting early endothelial cell death in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

Feasibility of using 'lung density' values estimated from EIT images for clinical diagnosis of lung abnormalities in mechanically ventilated ICU patients.

PubMed

Nebuya, Satoru; Koike, Tomotaka; Imai, Hiroshi; Iwashita, Yoshiaki; Brown, Brian H; Soma, Kazui

2015-06-01

This paper reports on the results of a study which compares lung density values obtained from electrical impedance tomography (EIT), clinical diagnosis and CT values (HU) within a region of interest in the lung. The purpose was to assess the clinical use of lung density estimation using EIT data. In 11 patients supported by a mechanical ventilator, the consistency of regional lung density measurements as estimated by EIT was validated to assess the feasibility of its use in intensive care medicine. There were significant differences in regional lung densities recorded in the supine position between normal lungs and diseased lungs associated with pneumonia, atelectasis and pleural effusion (normal; 240 ± 71.7 kg m(-3), pneumonia; 306 ± 38.6 kg m(-3), atelectasis; 497 ± 130 kg m(-3), pleural effusion; 467 ± 113 kg m(-3): Steel-Dwass test, p < 0.05). In addition, in order to compare lung density with CT image pixels, the image resolution of CT images, which was originally 512 × 512 pixels, was changed to 16 × 16 pixels to match that of the EIT images. The results of CT and EIT images from five patients in an intensive care unit showed a correlation coefficient of 0.66 ± 0.13 between the CT values (HU) and the lung density values (kg m(-3)) obtained from EIT. These results indicate that it may be possible to obtain a quantitative value for regional lung density using EIT.

Foraging behavior of humpback whales: kinematic and respiratory patterns suggest a high cost for a lunge.

PubMed

Goldbogen, Jeremy A; Calambokidis, John; Croll, Donald A; Harvey, James T; Newton, Kelly M; Oleson, Erin M; Schorr, Greg; Shadwick, Robert E

2008-12-01

Lunge feeding in rorqual whales is a drag-based feeding mechanism that is thought to entail a high energetic cost and consequently limit the maximum dive time of these extraordinarily large predators. Although the kinematics of lunge feeding in fin whales supports this hypothesis, it is unclear whether respiratory compensation occurs as a consequence of lunge-feeding activity. We used high-resolution digital tags on foraging humpback whales (Megaptera novaengliae) to determine the number of lunges executed per dive as well as respiratory frequency between dives. Data from two whales are reported, which together performed 58 foraging dives and 451 lunges. During one study, we tracked one tagged whale for approximately 2 h and examined the spatial distribution of prey using a digital echosounder. These data were integrated with the dive profile to reveal that lunges are directed toward the upper boundary of dense krill aggregations. Foraging dives were characterized by a gliding descent, up to 15 lunges at depth, and an ascent powered by steady swimming. Longer dives were required to perform more lunges at depth and these extended apneas were followed by an increase in the number of breaths taken after a dive. Maximum dive durations during foraging were approximately half of those previously reported for singing (i.e. non-feeding) humpback whales. At the highest lunge frequencies (10 to 15 lunges per dive), respiratory rate was at least threefold higher than that of singing humpback whales that underwent a similar degree of apnea. These data suggest that the high energetic cost associated with lunge feeding in blue and fin whales also occurs in intermediate sized rorquals.

Emerging science and therapies in non-small-cell lung cancer: targeting the MET pathway.

PubMed

Kris, Mark G; Arenberg, Douglas A; Herbst, Roy S; Riely, Gregory J

2014-11-01

During this enduring, learner-driven, interactive CME webseries, lung cancer specialists will address the science and targeted therapies for the MET pathway in non-small cell lung cancer. Over the past decade, research has evolved in the science of identifying targeted biological changes in DNA and individual cancer cells. Along with the advanced understanding of lung cancer mutations, has come the development of specific targeted therapies that improve patient outcomes. The first step in treating a patient with lung cancer is proper diagnosis and staging, applying to the principles of personalize medicine. Our current understanding of lung cancer is that of a collection of diseases individualized through specific mutations. This CME activity reviews the role of the pulmonologist and pathologist in proper tissue acquisition and analysis. This new era of personalized medicine and clinical research advances has changed the way clinicians evaluate and treat patients with lung cancer. The data on lung cancer cell mutations and newer targeted therapies have improved the progression free survival and quality of life of lung cancer patients. This CME activity is designed to present a practical overview of recent evidenced based data of MET targeted therapies for patients with lung cancer. As research continues to evolve, we continue to advance our understanding in the science of lung cancers involving the MET pathway. Evidenced based data supporting newer targeted therapeutics provides insight on applying treatment for optimal outcomes. This CME activity will focus on the individualized treatment strategies using practical decision making for patients with MET expression. This activity has been designed to meet the educational needs of medical oncologists, pathologists, radiation oncologists, surgeons, pulmonologists, internists, and other healthcare clinicians responsible for the care of patients with lung cancer. Online access:http://www.elseviercme.com/516/.

Is Survival for Patients with Resectable Lung Metastatic Colorectal Cancer Comparable to Those with Resectable Liver Disease? Results from the South Australian Metastatic Colorectal Registry.

PubMed

Patel, Dainik; Townsend, Amanda R; Karapetis, Christos; Beeke, Carol; Padbury, Rob; Roy, Amitesh; Maddern, Guy; Roder, David; Price, Timothy J

2016-10-01

Hepatic resection for colorectal (CRC) metastasis is considered a standard of care. Resection of metastasis isolated to lung also is considered potentially curable, although there is still some variation in recommendations. We explore outcomes for patients undergoing lung resection for mCRC, with the liver resection group as the comparator. South Australian (SA) metastatic CRC registry data were analysed to assess patient characteristics and survival outcomes for patients suitable for lung or liver resection. A total of 3241 patients are registered on the database to December 2014. One hundred two (3.1 %) patients were able to undergo a lung resection compared with 420 (12.9 %) who had a liver resection. Of the lung resection patients, 62 (61 %) presented with lung disease only, 21 % initially presented with liver disease only, 11 % had both lung and liver, and 7 % had brain or pelvic disease resection. Of these patients, 79 % went straight to surgery without any neoadjuvant treatment and 34 % had lung resection as the only intervention. Chemotherapy for metastatic disease was given more often to liver resection patients: 76.9 versus 53.9 %, p = 0.17. Median overall survival is 5.6 years for liver resection and has not been reached for lung resection (hazard ratio 0.82, 95 % confidence interval 0.54-1.24, p = 0.33). Lung resection was undertaken in 3.1 % of patients with mCRC in our registry. These data provide further support for long-term survival after lung resection in mCRC, survival that is at least comparable to those who undergo resection for liver metastasis in mCRC.

Severe transfusion-related acute lung injury managed with extracorporeal membrane oxygenation (ECMO) in an obstetric patient.

PubMed

Lee, Allison J; Koyyalamudi, Pushpa L; Martinez-Ruiz, Ricardo

2008-11-01

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality in the United States. Management is usually supportive, including supplemental oxygen, intravenous fluids, and mechanical ventilation if necessary. Most patients recover within 72 hours. We present a nearly fatal case of TRALI in an obstetric patient, which was successfully managed with extracorporeal membrane oxygenation (ECMO).

The Cell-CT 3D Cell Imaging Technology Platform Enables the Detection of Lung Cancer Using the Non-Invasive LuCED Sputum Test

PubMed Central

Meyer, Michael G.; Hayenga, Jon; Neumann, Thomas; Katdare, Rahul; Presley, Chris; Steinhauer, David; Bell, Timothy; Lancaster, Christy; Nelson, Alan C.

2015-01-01

The war against cancer has yielded important advances in the early diagnosis and treatment of certain cancer types, but the poor detection rate and 5-year survival rate for lung cancer remains little changed over the past 40 years. Early detection through emerging lung cancer screening programs promises the most reliable means of improving mortality. Sputum cytology has been tried without success because sputum contains few malignant cells that are difficult for cytologists to detect. However, research has shown that sputum contains diagnostic malignant cells and could serve as a means of lung cancer detection if those cells could be detected and correctly characterized. Recently, the National Lung Cancer Screening Trial reported that screening by three consecutive low-dose X-ray CT scans provides a 20% reduction in lung cancer mortality compared to chest X-ray. This reduction in mortality, however, comes with an unacceptable false positive rate that increases patient risks and the overall cost of lung cancer screening. This article reviews the LuCED® test for detecting early lung cancer. LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell-CT®, which images cells in three dimensions with sub-micron resolution. Algorithms are applied to the 3D cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist's manual review. LuCED promotes accurate cell classification which could enable cost effective detection of lung cancer. PMID:26148817

[Extracorporeal membrane oxygenation in primary graft dysfunction in a paediatric double lung transplant: presentation of a case].

PubMed

López-Cantero, M; Grisolía, A L; Vicente, R; Moreno, I; Ramos, F; Porta, J; Torregrosa, S

2014-04-01

Primary graft dysfunction is a leading cause of morbimortality in the immediate postoperative period of patients undergoing lung transplantation. Among the treatment options are: lung protective ventilatory strategies, nitric oxide, lung surfactant therapy, and supportive treatment with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery of lung function or re-transplant. We report the case of a 9-year-old girl affected by cystic fibrosis who underwent double-lung transplantation complicated with a severe primary graft dysfunction in the immediate postoperative period and refractory to standard therapies. Due to development of multiple organ failure, it was decided to insert arteriovenous ECMO catheters (pulmonary artery-right atrium). The postoperative course was satisfactory, allowing withdrawal of ECMO on the 5th post-surgical day. Currently the patient survives free of rejection and with an excellent quality of life after 600 days of follow up. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Magnetic Resonance Microscopy of the Lung

NASA Astrophysics Data System (ADS)

Johnson, G. Allan

1999-11-01

The lung presents both challenges and opportunities for study by magnetic resonance imaging (MRI). The technical challenges arise from respiratory and cardiac motion, limited signal from the tissues, and unique physical structure of the lung. These challenges are heightened in magnetic resonance microscopy (MRM) where the spatial resolution may be up to a million times higher than that of conventional MRI. The development of successful techniques for MRM of the lung present enormous opportunities for basic studies of lung structure and function, toxicology, environmental stress, and drug discovery by permitting investigators to study this most essential organ nondestructively in the live animal. Over the last 15 years, scientists at the Duke Center for In Vivo Microscopy have developed techniques for MRM in the live animal through an interdisciplinary program of biology, physics, chemistry, electrical engineering, and computer science. This talk will focus on the development of specialized radiofrequency coils for lung imaging, projection encoding methods to limit susceptibility losses, specialized support structures to control and monitor physiologic motion, and the most recent development of hyperpolarized gas imaging with ^3He and ^129Xe.

Lung capillary injury and repair in left heart disease: a new target for therapy?

PubMed

Azarbar, Sayena; Dupuis, Jocelyn

2014-07-01

The lungs are the primary organs affected in LHD (left heart disease). Increased left atrial pressure leads to pulmonary alveolar-capillary stress failure, resulting in cycles of alveolar wall injury and repair. The reparative process causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. Although the resultant reduction in vascular permeability is initially protective against pulmonary oedema, the process becomes maladaptive causing a restrictive lung syndrome with impaired gas exchange. This pathological process may also contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have specifically evaluated lung structural remodelling and the effect of related therapies in LHD. Currently approved treatment for chronic HF (heart failure) may have direct beneficial effects on lung structural remodelling. In the future, novel therapies specifically targeting the remodelling processes may potentially be utilized. In the present review, we summarize data supporting the clinical importance and pathophysiological mechanisms of lung structural remodelling in LHD and propose that this pathophysiological process should be explored further in pre-clinical studies and future therapeutic trials.

Lung Cancer Screening Participation: Developing a Conceptual Model to Guide Research

PubMed Central

Carter-Harris, Lisa; Davis, Lorie L.; Rawl, Susan M.

2017-01-01

Purpose To describe the development of a conceptual model to guide research focused on lung cancer screening participation from the perspective of the individual in the decision-making process. Methods Based on a comprehensive review of empirical and theoretical literature, a conceptual model was developed linking key psychological variables (stigma, medical mistrust, fatalism, worry, and fear) to the health belief model and precaution adoption process model. Results Proposed model concepts have been examined in prior research of either lung or other cancer screening behavior. To date, a few studies have explored a limited number of variables that influence screening behavior in lung cancer specifically. Therefore, relationships among concepts in the model have been proposed and future research directions presented. Conclusion This proposed model is an initial step to support theoretically based research. As lung cancer screening becomes more widely implemented, it is critical to theoretically guide research to understand variables that may be associated with lung cancer screening participation. Findings from future research guided by the proposed conceptual model can be used to refine the model and inform tailored intervention development. PMID:28304262

Lung Cancer Screening Participation: Developing a Conceptual Model to Guide Research.

PubMed

Carter-Harris, Lisa; Davis, Lorie L; Rawl, Susan M

2016-11-01

To describe the development of a conceptual model to guide research focused on lung cancer screening participation from the perspective of the individual in the decision-making process. Based on a comprehensive review of empirical and theoretical literature, a conceptual model was developed linking key psychological variables (stigma, medical mistrust, fatalism, worry, and fear) to the health belief model and precaution adoption process model. Proposed model concepts have been examined in prior research of either lung or other cancer screening behavior. To date, a few studies have explored a limited number of variables that influence screening behavior in lung cancer specifically. Therefore, relationships among concepts in the model have been proposed and future research directions presented. This proposed model is an initial step to support theoretically based research. As lung cancer screening becomes more widely implemented, it is critical to theoretically guide research to understand variables that may be associated with lung cancer screening participation. Findings from future research guided by the proposed conceptual model can be used to refine the model and inform tailored intervention development.

Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis.

PubMed

Wielpütz, Mark O; von Stackelberg, Oyunbileg; Stahl, Mirjam; Jobst, Bertram J; Eichinger, Monika; Puderbach, Michael U; Nährlich, Lutz; Barth, Sandra; Schneider, Christian; Kopp, Matthias V; Ricklefs, Isabell; Buchholz, Michael; Tümmler, Burkhard; Dopfer, Christian; Vogel-Claussen, Jens; Kauczor, Hans-Ulrich; Mall, Marcus A

2018-05-24

A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. A standardised chest 1.5 T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2 ± 1.5 years, range 0-6 years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3 ± 5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r = 0.43-0.50, p < 0.01). Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Attitudes and Beliefs of Primary Care Providers in New Mexico About Lung Cancer Screening Using Low-Dose Computed Tomography

PubMed Central

Hoffman, Richard M.; Sussman, Andrew L.; Getrich, Christina M.; Rhyne, Robert L.; Crowell, Richard E.; Taylor, Kathryn L.; Reifler, Ellen J.; Wescott, Pamela H.; Murrietta, Ambroshia M.; Saeed, Ali I.

2015-01-01

Introduction On the basis of results from the National Lung Screening Trial (NLST), national guidelines now recommend using low-dose computed tomography (LDCT) to screen high-risk smokers for lung cancer. Our study objective was to characterize the knowledge, attitudes, and beliefs of primary care providers about implementing LDCT screening. Methods We conducted semistructured interviews with primary care providers practicing in New Mexico clinics for underserved minority populations. The interviews, conducted from February through September 2014, focused on providers’ tobacco cessation efforts, lung cancer screening practices, perceptions of NLST and screening guidelines, and attitudes about informed decision making for cancer screening. Investigators iteratively reviewed transcripts to create a coding structure. Results We reached thematic saturation after interviewing 10 providers practicing in 6 urban and 4 rural settings; 8 practiced at federally qualified health centers. All 10 providers promoted smoking cessation, some screened with chest x-rays, and none screened with LDCT. Not all were aware of NLST results or current guideline recommendations. Providers viewed study results skeptically, particularly the 95% false-positive rate, the need to screen 320 patients to prevent 1 lung cancer death, and the small proportion of minority participants. Providers were uncertain whether New Mexico had the necessary infrastructure to support high-quality screening, and worried about access barriers and financial burdens for rural, underinsured populations. Providers noted the complexity of discussing benefits and harms of screening and surveillance with their patient population. Conclusion Providers have several concerns about the feasibility and appropriateness of implementing LDCT screening. Effective lung cancer screening programs will need to educate providers and patients to support informed decision making and to ensure that high-quality screening can be efficiently delivered in community practice. PMID:26160294

Patient Perspectives on Low-Dose Computed Tomography for Lung Cancer Screening, New Mexico, 2014

PubMed Central

Sussman, Andrew L.; Murrietta, Ambroshia M.; Getrich, Christina M.; Rhyne, Robert; Crowell, Richard E.; Taylor, Kathryn L.; Reifler, Ellen J.; Wescott, Pamela H.; Saeed, Ali I.; Hoffman, Richard M.

2016-01-01

Introduction National guidelines call for annual lung cancer screening for high-risk smokers using low-dose computed tomography (LDCT). The objective of our study was to characterize patient knowledge and attitudes about lung cancer screening, smoking cessation, and shared decision making by patient and health care provider. Methods We conducted semistructured qualitative interviews with patients with histories of heavy smoking who received care at a Federally Qualified Health Center (FQHC Clinic) and at a comprehensive cancer center-affiliated chest clinic (Chest Clinic) in Albuquerque, New Mexico. The interviews, conducted from February through September 2014, focused on perceptions about health screening, knowledge and attitudes about LDCT screening, and preferences regarding decision aids. We used a systematic iterative analytic process to identify preliminary and emergent themes and to create a coding structure. Results We reached thematic saturation after 22 interviews (10 at the FQHC Clinic, 12 at the Chest Clinic). Most patients were unaware of LDCT screening for lung cancer but were receptive to the test. Some smokers said they would consider quitting smoking if their screening result were positive. Concerns regarding screening were cost, radiation exposure, and transportation issues. To support decision making, most patients said they preferred one-on-one discussions with a provider. They also valued decision support tools (print materials, videos), but raised concerns about readability and Internet access. Conclusion Implementing lung cancer screening in sociodemographically diverse populations poses significant challenges. The value of tobacco cessation counseling cannot be overemphasized. Effective interventions for shared decision making to undergo lung cancer screening will need the active engagement of health care providers and will require the use of accessible decision aids designed for people with low health literacy. PMID:27536900

Segmentation and Image Analysis of Abnormal Lungs at CT: Current Approaches, Challenges, and Future Trends

PubMed Central

Mansoor, Awais; Foster, Brent; Xu, Ziyue; Papadakis, Georgios Z.; Folio, Les R.; Udupa, Jayaram K.; Mollura, Daniel J.

2015-01-01

The computer-based process of identifying the boundaries of lung from surrounding thoracic tissue on computed tomographic (CT) images, which is called segmentation, is a vital first step in radiologic pulmonary image analysis. Many algorithms and software platforms provide image segmentation routines for quantification of lung abnormalities; however, nearly all of the current image segmentation approaches apply well only if the lungs exhibit minimal or no pathologic conditions. When moderate to high amounts of disease or abnormalities with a challenging shape or appearance exist in the lungs, computer-aided detection systems may be highly likely to fail to depict those abnormal regions because of inaccurate segmentation methods. In particular, abnormalities such as pleural effusions, consolidations, and masses often cause inaccurate lung segmentation, which greatly limits the use of image processing methods in clinical and research contexts. In this review, a critical summary of the current methods for lung segmentation on CT images is provided, with special emphasis on the accuracy and performance of the methods in cases with abnormalities and cases with exemplary pathologic findings. The currently available segmentation methods can be divided into five major classes: (a) thresholding-based, (b) region-based, (c) shape-based, (d) neighboring anatomy–guided, and (e) machine learning–based methods. The feasibility of each class and its shortcomings are explained and illustrated with the most common lung abnormalities observed on CT images. In an overview, practical applications and evolving technologies combining the presented approaches for the practicing radiologist are detailed. ©RSNA, 2015 PMID:26172351

Perioperative detection of circulating tumour cells in patients with lung cancer.

PubMed

Chudasama, Dimple; Burnside, Nathan; Beeson, Julie; Karteris, Emmanouil; Rice, Alexandra; Anikin, Vladimir

2017-08-01

Lung cancer is a leading cause of mortality and despite surgical resection a proportion of patients may develop metastatic spread. The detection of circulating tumour cells (CTCs) may allow for improved prediction of metastatic spread and survival. The current study evaluates the efficacy of the ScreenCell® filtration device, to capture, isolate and propagate CTCs in patients with primary lung cancer. Prior to assessment of CTCs, the present study detected cancer cells in a proof-of-principle- experiment using A549 human lung carcinoma cells as a model. Ten patients (five males and five females) with pathologically diagnosed primary non-small cell lung cancer undergoing surgical resection, had their blood tested for CTCs. Samples were taken from a peripheral vessel at the baseline, from the pulmonary vein draining the lobe containing the tumour immediately prior to division, a further central sample was taken following completion of the resection, and a final peripheral sample was taken three days post-resection. A significant increase in CTCs was observed from baseline levels following lung manipulation. No association was able to be made between increased levels of circulating tumour cells and survival or the development of metastatic deposits. Manipulation of the lung during surgical resection for non-small cell lung carcinoma results in a temporarily increased level of CTCs; however, no clinical impact for this increase was observed. Overall, the study suggests the ScreenCell® device has the potential to be used as a CTC isolation tool, following further work, adaptations and improvements to the technology and validation of results.

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis.

PubMed

Takahashi, Youhei; Saito, Atsushi; Chiba, Hirofumi; Kuronuma, Koji; Ikeda, Kimiyuki; Kobayashi, Tomofumi; Ariki, Shigeru; Takahashi, Motoko; Sasaki, Yasushi; Takahashi, Hiroki

2018-02-27

Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. Although IPF has not been thought to be associated with bacterial communities, recent papers reported the possible role of microbiome composition in IPF. The roles of microbiomes in respiratory functions and as clinical biomarkers for IPF remain unknown. In this study, we aim to identify the relationship between the microbial environment in the lung and clinical findings. Thirty-four subjects diagnosed with IPF were included in this analysis. The 16S rDNA was purified from bronchoalveolar lavage fluid obtained at the time of diagnosis and analyzed using next-generation sequencing techniques to characterize the bacterial communities. Furthermore, microbiomes from mice with bleomycin-induced lung fibrosis were analyzed. The most prevalent lung phyla were Firmicutes, Proteobacteria and Bacteroidetes. Decreased microbial diversity was found in patients with low forced vital capacity (FVC) and early mortality. Additionally, the diversity and relative abundance of Firmicutes, Streptococcaceae, and Veillonellaceae were significantly associated with FVC, 6-min walk distance, and serum surfactant protein D. Bleomycin-induced lung fibrosis resulted in decrease of diversity and alteration of microbiota in PCoA analysis. These results support the observations in human specimens. This study identified relationships between specific taxa in BALF and clinical findings, which were also supported by experiments in a mouse model. Our data suggest the possibility that loss of microbial diversity is associated with disease activities of IPF.

Symbolic rule-based classification of lung cancer stages from free-text pathology reports.

PubMed

Nguyen, Anthony N; Lawley, Michael J; Hansen, David P; Bowman, Rayleen V; Clarke, Belinda E; Duhig, Edwina E; Colquist, Shoni

2010-01-01

To classify automatically lung tumor-node-metastases (TNM) cancer stages from free-text pathology reports using symbolic rule-based classification. By exploiting report substructure and the symbolic manipulation of systematized nomenclature of medicine-clinical terms (SNOMED CT) concepts in reports, statements in free text can be evaluated for relevance against factors relating to the staging guidelines. Post-coordinated SNOMED CT expressions based on templates were defined and populated by concepts in reports, and tested for subsumption by staging factors. The subsumption results were used to build logic according to the staging guidelines to calculate the TNM stage. The accuracy measure and confusion matrices were used to evaluate the TNM stages classified by the symbolic rule-based system. The system was evaluated against a database of multidisciplinary team staging decisions and a machine learning-based text classification system using support vector machines. Overall accuracy on a corpus of pathology reports for 718 lung cancer patients against a database of pathological TNM staging decisions were 72%, 78%, and 94% for T, N, and M staging, respectively. The system's performance was also comparable to support vector machine classification approaches. A system to classify lung TNM stages from free-text pathology reports was developed, and it was verified that the symbolic rule-based approach using SNOMED CT can be used for the extraction of key lung cancer characteristics from free-text reports. Future work will investigate the applicability of using the proposed methodology for extracting other cancer characteristics and types.

Efficacy of prone position in acute respiratory distress syndrome patients: A pathophysiology-based review

PubMed Central

Koulouras, Vasilios; Papathanakos, Georgios; Papathanasiou, Athanasios; Nakos, Georgios

2016-01-01

Acute respiratory distress syndrome (ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mortality. The mainstay of treatment for ARDS is lung protective ventilation with low tidal volumes and positive end-expiratory pressure sufficient for alveolar recruitment. Prone positioning is a supplementary strategy available in managing patients with ARDS. It was first described 40 years ago and it proves to be in alignment with two major ARDS pathophysiological lung models; the “sponge lung” - and the “shape matching” -model. Current evidence strongly supports that prone positioning has beneficial effects on gas exchange, respiratory mechanics, lung protection and hemodynamics as it redistributes transpulmonary pressure, stress and strain throughout the lung and unloads the right ventricle. The factors that individually influence the time course of alveolar recruitment and the improvement in oxygenation during prone positioning have not been well characterized. Although patients’ response to prone positioning is quite variable and hard to predict, large randomized trials and recent meta-analyses show that prone position in conjunction with a lung-protective strategy, when performed early and in sufficient duration, may improve survival in patients with ARDS. This pathophysiology-based review and recent clinical evidence strongly support the use of prone positioning in the early management of severe ARDS systematically and not as a rescue maneuver or a last-ditch effort. PMID:27152255

Biomolecular and clinical practice in malignant pleural mesothelioma and lung cancer: what thoracic surgeons should know†

PubMed Central

Opitz, Isabelle; Bueno, Raphael; Lim, Eric; Pass, Harvey; Pastorino, Ugo; Boeri, Mattia; Rocco, Gaetano

2014-01-01

Today, molecular-profile-directed therapy is a guiding principle of modern thoracic oncology. The knowledge of new biomolecular technology applied to the diagnosis, prognosis, and treatment of lung cancer and mesothelioma should be part of the 21st century thoracic surgeons' professional competence. The European Society of Thoracic Surgeons (ESTS) Biology Club aims at providing a comprehensive insight into the basic biology of the diseases we are treating. During the 2013 ESTS Annual Meeting, different experts of the field presented the current knowledge about diagnostic and prognostic biomarkers in malignant pleural mesothelioma including new perspectives as well as the role and potential application of microRNA and genomic sequencing for lung cancer, which are summarized in the present article. PMID:24623168

The dawn of a revolution in personalized lung cancer prevention.

PubMed

Khuri, Fadlo R

2011-07-01

Lung cancer prevention and early detection, which have fallen on hard times for more than the past 20 years, seem to have turned a corner toward better times ahead. Exciting new results of randomized controlled trials that targeted the arachidonic acid pathway, including a celecoxib trial reported by Mao and colleagues in this issue of the journal (beginning on page 984) and a trial of the prostacyclin analog iloprost, complement recently reported 20%-30% lung cancer mortality reductions, either with aspirin in targeting the arachidonic acid pathway or with computed tomography screening. The new results show encouraging activity personalized to former smokers and/or people expressing predictive biomarkers. These trials and technological advances in molecular profiling and imaging herald substantial clinical advances on the horizon of this field.

Auscultation of the respiratory system

PubMed Central

Sarkar, Malay; Madabhavi, Irappa; Niranjan, Narasimhalu; Dogra, Megha

2015-01-01

Auscultation of the lung is an important part of the respiratory examination and is helpful in diagnosing various respiratory disorders. Auscultation assesses airflow through the trachea-bronchial tree. It is important to distinguish normal respiratory sounds from abnormal ones for example crackles, wheezes, and pleural rub in order to make correct diagnosis. It is necessary to understand the underlying pathophysiology of various lung sounds generation for better understanding of disease processes. Bedside teaching should be strengthened in order to avoid erosion in this age old procedure in the era of technological explosion. PMID:26229557

[Progress of treatments in non-small cell lung cancer with brain metastases].

PubMed

Ma, Chunhua; Jiang, Rong

2012-05-01

Brain metastases is one of the most common complications of non-small cell lung cancer, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), surgery and chemotherapy are standard methods in the treatment of brain metastases. But the effect of those treatments are still sad. Comprehensive treatment can prolong the survival and improve the quality of life. Recently, the improvement of technology, targeted therapy, survival time and the quality of life are in increasingly concerned. The paper make a summary of current situation and progress for comprehensive therapy of brain metastases.

SU-F-R-31: Identification of Robust Normal Lung CT Texture Features for the Prediction of Radiation-Induced Lung Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, W; Riyahi, S; Lu, W

Purpose: Normal lung CT texture features have been used for the prediction of radiation-induced lung disease (radiation pneumonitis and radiation fibrosis). For these features to be clinically useful, they need to be relatively invariant (robust) to tumor size and not correlated with normal lung volume. Methods: The free-breathing CTs of 14 lung SBRT patients were studied. Different sizes of GTVs were simulated with spheres placed at the upper lobe and lower lobe respectively in the normal lung (contralateral to tumor). 27 texture features (9 from intensity histogram, 8 from grey-level co-occurrence matrix [GLCM] and 10 from grey-level run-length matrix [GLRM])more » were extracted from [normal lung-GTV]. To measure the variability of a feature F, the relative difference D=|Fref -Fsim|/Fref*100% was calculated, where Fref was for the entire normal lung and Fsim was for [normal lung-GTV]. A feature was considered as robust if the largest non-outlier (Q3+1.5*IQR) D was less than 5%, and considered as not correlated with normal lung volume when their Pearson correlation was lower than 0.50. Results: Only 11 features were robust. All first-order intensity-histogram features (mean, max, etc.) were robust, while most higher-order features (skewness, kurtosis, etc.) were unrobust. Only two of the GLCM and four of the GLRM features were robust. Larger GTV resulted greater feature variation, this was particularly true for unrobust features. All robust features were not correlated with normal lung volume while three unrobust features showed high correlation. Excessive variations were observed in two low grey-level run features and were later identified to be from one patient with local lung diseases (atelectasis) in the normal lung. There was no dependence on GTV location. Conclusion: We identified 11 robust normal lung CT texture features that can be further examined for the prediction of radiation-induced lung disease. Interestingly, low grey-level run features identified normal lung diseases. This work was supported in part by the National Cancer Institute Grants R01CA172638.« less

Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lingappan, Krithika, E-mail: lingappa@bcm.edu; Jiang, Weiwu; Wang, Lihua

Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expressionmore » in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.« less

What can imaging tell us about physiology? Lung growth and regional mechanical strain.

PubMed

Hsia, Connie C W; Tawhai, Merryn H

2012-09-01

The interplay of mechanical forces transduces diverse physico-biochemical processes to influence lung morphogenesis, growth, maturation, remodeling and repair. Because tissue stress is difficult to measure in vivo, mechano-sensitive responses are commonly inferred from global changes in lung volume, shape, or compliance and correlated with structural changes in tissue blocks sampled from postmortem-fixed lungs. Recent advances in noninvasive volumetric imaging technology, nonrigid image registration, and deformation analysis provide valuable tools for the quantitative analysis of in vivo regional anatomy and air and tissue-blood distributions and when combined with transpulmonary pressure measurements, allow characterization of regional mechanical function, e.g., displacement, strain, shear, within and among intact lobes, as well as between the lung and the components of its container-rib cage, diaphragm, and mediastinum-thereby yielding new insights into the inter-related metrics of mechanical stress-strain and growth/remodeling. Here, we review the state-of-the-art imaging applications for mapping asymmetric heterogeneous physical interactions within the thorax and how these interactions permit as well as constrain lung growth, remodeling, and compensation during development and following pneumonectomy to illustrate how advanced imaging could facilitate the understanding of physiology and pathophysiology. Functional imaging promises to facilitate the formulation of realistic computational models of lung growth that integrate mechano-sensitive events over multiple spatial and temporal scales to accurately describe in vivo physiology and pathophysiology. Improved computational models in turn could enhance our ability to predict regional as well as global responses to experimental and therapeutic interventions.

Novel algorithm to identify and differentiate specific digital signature of breath sound in patients with diffuse parenchymal lung disease.

PubMed

Bhattacharyya, Parthasarathi; Mondal, Ashok; Dey, Rana; Saha, Dipanjan; Saha, Goutam

2015-05-01

Auscultation is an important part of the clinical examination of different lung diseases. Objective analysis of lung sounds based on underlying characteristics and its subsequent automatic interpretations may help a clinical practice. We collected the breath sounds from 8 normal subjects and 20 diffuse parenchymal lung disease (DPLD) patients using a newly developed instrument and then filtered off the heart sounds using a novel technology. The collected sounds were thereafter analysed digitally on several characteristics as dynamical complexity, texture information and regularity index to find and define their unique digital signatures for differentiating normality and abnormality. For convenience of testing, these characteristic signatures of normal and DPLD lung sounds were transformed into coloured visual representations. The predictive power of these images has been validated by six independent observers that include three physicians. The proposed method gives a classification accuracy of 100% for composite features for both the normal as well as lung sound signals from DPLD patients. When tested by independent observers on the visually transformed images, the positive predictive value to diagnose the normality and DPLD remained 100%. The lung sounds from the normal and DPLD subjects could be differentiated and expressed according to their digital signatures. On visual transformation to coloured images, they retain 100% predictive power. This technique may assist physicians to diagnose DPLD from visual images bearing the digital signature of the condition. © 2015 Asian Pacific Society of Respirology.

Early detection of lung cancer from CT images: nodule segmentation and classification using deep learning

NASA Astrophysics Data System (ADS)

Sharma, Manu; Bhatt, Jignesh S.; Joshi, Manjunath V.

2018-04-01

Lung cancer is one of the most abundant causes of the cancerous deaths worldwide. It has low survival rate mainly due to the late diagnosis. With the hardware advancements in computed tomography (CT) technology, it is now possible to capture the high resolution images of lung region. However, it needs to be augmented by efficient algorithms to detect the lung cancer in the earlier stages using the acquired CT images. To this end, we propose a two-step algorithm for early detection of lung cancer. Given the CT image, we first extract the patch from the center location of the nodule and segment the lung nodule region. We propose to use Otsu method followed by morphological operations for the segmentation. This step enables accurate segmentation due to the use of data-driven threshold. Unlike other methods, we perform the segmentation without using the complete contour information of the nodule. In the second step, a deep convolutional neural network (CNN) is used for the better classification (malignant or benign) of the nodule present in the segmented patch. Accurate segmentation of even a tiny nodule followed by better classification using deep CNN enables the early detection of lung cancer. Experiments have been conducted using 6306 CT images of LIDC-IDRI database. We achieved the test accuracy of 84.13%, with the sensitivity and specificity of 91.69% and 73.16%, respectively, clearly outperforming the state-of-the-art algorithms.

Influence of vascular network design on gas transfer in lung assist device technology.

PubMed

Bassett, Erik K; Hoganson, David M; Lo, Justin H; Penson, Elliot J N; Vacanti, Joseph P

2011-01-01

Blood oxygenators are vital for the critically ill, but their use is limited to the hospital setting. A portable blood oxygenator or a lung assist device for ambulatory or long-term use would greatly benefit patients with chronic lung disease. In this work, a biomimetic blood oxygenator system was developed which consisted of a microfluidic vascular network covered by a gas permeable silicone membrane. This system was used to determine the influence of key microfluidic parameters-channel size, oxygen exposure length, and blood shear rate-on blood oxygenation and carbon dioxide removal. Total gas transfer increased linearly with flow rate, independent of channel size and oxygen exposure length. On average, CO(2) transfer was 4.3 times higher than oxygen transfer. Blood oxygen saturation was also found to depend on the flow rate per channel but in an inverse manner; oxygenation decreased and approached an asymptote as the flow rate per channel increased. These relationships can be used to optimize future biomimetic vascular networks for specific lung applications: gas transfer for carbon dioxide removal in patients with chronic obstructive pulmonary disease or oxygenation for premature infants requiring complete lung replacement therapy.

Shotgun glycomics of pig lung identifies natural endogenous receptors for influenza viruses.

PubMed

Byrd-Leotis, Lauren; Liu, Renpeng; Bradley, Konrad C; Lasanajak, Yi; Cummings, Sandra F; Song, Xuezheng; Heimburg-Molinaro, Jamie; Galloway, Summer E; Culhane, Marie R; Smith, David F; Steinhauer, David A; Cummings, Richard D

2014-06-03

Influenza viruses bind to host cell surface glycans containing terminal sialic acids, but as studies on influenza binding become more sophisticated, it is becoming evident that although sialic acid may be necessary, it is not sufficient for productive binding. To better define endogenous glycans that serve as viral receptors, we have explored glycan recognition in the pig lung, because influenza is broadly disseminated in swine, and swine have been postulated as an intermediary host for the emergence of pandemic strains. For these studies, we used the technology of "shotgun glycomics" to identify natural receptor glycans. The total released N- and O-glycans from pig lung glycoproteins and glycolipid-derived glycans were fluorescently tagged and separated by multidimensional HPLC, and individual glycans were covalently printed to generate pig lung shotgun glycan microarrays. All viruses tested interacted with one or more sialylated N-glycans but not O-glycans or glycolipid-derived glycans, and each virus demonstrated novel and unexpected differences in endogenous N-glycan recognition. The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis.

AISLE: an automatic volumetric segmentation method for the study of lung allometry.

PubMed

Ren, Hongliang; Kazanzides, Peter

2011-01-01

We developed a fully automatic segmentation method for volumetric CT (computer tomography) datasets to support construction of a statistical atlas for the study of allometric laws of the lung. The proposed segmentation method, AISLE (Automated ITK-Snap based on Level-set), is based on the level-set implementation from an existing semi-automatic segmentation program, ITK-Snap. AISLE can segment the lung field without human interaction and provide intermediate graphical results as desired. The preliminary experimental results show that the proposed method can achieve accurate segmentation, in terms of volumetric overlap metric, by comparing with the ground-truth segmentation performed by a radiologist.

History of Mechanical Ventilation. From Vesalius to Ventilator-induced Lung Injury.

PubMed

Slutsky, Arthur S

2015-05-15

Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure.

[A case of fat embolism syndrome associated with pathological femoral fracture caused by metastatic adenocarcinoma of the lung].

PubMed

Sato, Takashi; Soejima, Kenzo; Nakayama, Sohei; Satomi, Ryosuke; Sayama, Koichi; Asano, Koichiro

2010-10-01

A 76-year-old woman with multiple bone metastases from lung adenocarcinoma was admitted due to a pathological femoral fracture. On the night after admission, her consciousness deteriorated rapidly and she developed progressive respiratory failure. Computed tomography of the chest revealed diffuse ground glass opacities in both lungs, and magnetic resonance imaging of the brain showed multiple acute infarctions. Her condition improved after several days of supportive treatment with oxygen, corticosteroids and diuretics. Fat embolism syndrome should be considered as a differential diagnosis if consciousness disturbance and respiratory failure occur in patients with metastatic bone carcinoma and pathological long bone fractures.

Linking lung function to structural damage of alveolar epithelium in ventilator-induced lung injury.

PubMed

Hamlington, Katharine L; Smith, Bradford J; Dunn, Celia M; Charlebois, Chantel M; Roy, Gregory S; Bates, Jason H T

2018-05-06

Understanding how the mechanisms of ventilator-induced lung injury (VILI), namely atelectrauma and volutrauma, contribute to the failure of the blood-gas barrier and subsequent intrusion of edematous fluid into the airspace is essential for the design of mechanical ventilation strategies that minimize VILI. We ventilated mice with different combinations of tidal volume and positive end-expiratory pressure (PEEP) and linked degradation in lung function measurements to injury of the alveolar epithelium observed via scanning electron microscopy. Ventilating with both high inspiratory plateau pressure and zero PEEP was necessary to cause derangements in lung function as well as visually apparent physical damage to the alveolar epithelium of initially healthy mice. In particular, the epithelial injury was tightly associated with indicators of alveolar collapse. These results support the hypothesis that mechanical damage to the epithelium during VILI is at least partially attributed to atelectrauma-induced damage of alveolar type I epithelial cells. Copyright © 2018. Published by Elsevier B.V.

Deformation of a flexible disk bonded to an elastic half space-application to the lung.

PubMed

Lai-Fook, S J; Hajji, M A; Wilson, T A

1980-08-01

An analysis is presented of the deformation of a homogeneous, isotropic, elastic half space subjected to a constant radial strain in a circular area on the boundary. Explicit analytic expressions for the normal and radial displacements and the shear stress on the boundary are used to interpret experiments performed on inflated pig lungs. The boundary strain was induced by inflating or deflating the lung after bonding a flexible disk to the lung surface. The prediction that the surface bulges outward for positive boundary strain and inward for negative strain was observed in the experiments. Poisson's ratio at two transpulmonary pressures was measured, by use of the normal displacement equation evaluated at the surface. A direct estimate of Poisson's ratio was possible because the normal displacement of the surface depended uniquely on the compressibility of the material. Qualitative comparisons between theory and experiment support the use of continuum analyses in evaluating the behavior of the lung parenchyma when subjected to small local distortions.

Intraoperative mechanical ventilation for the pediatric patient.

PubMed

Kneyber, Martin C J

2015-09-01

Invasive mechanical ventilation is required when children undergo general anesthesia for any procedure. It is remarkable that one of the most practiced interventions such as pediatric mechanical ventilation is hardly supported by any scientific evidence but rather based on personal experience and data from adults, especially as ventilation itself is increasingly recognized as a harmful intervention that causes ventilator-induced lung injury. The use of low tidal volume and higher levels of positive end-expiratory pressure became an integral part of lung-protective ventilation following the outcomes of clinical trials in critically ill adults. This approach has been readily adopted in pediatric ventilation. However, a clear association between tidal volume and mortality has not been ascertained in pediatrics. In fact, experimental studies have suggested that young children might be less susceptible to ventilator-induced lung injury. As such, no recommendations on optimal lung-protective ventilation strategy in children with or without lung injury can be made. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gene expression analysis of microtubule affinity-regulating kinase 2 in non-small cell lung cancer.

PubMed

Marshall, Erin A; Ng, Kevin W; Anderson, Christine; Hubaux, Roland; Thu, Kelsie L; Lam, Wan L; Martinez, Victor D

2015-12-01

Lung cancer is the leading cause of cancer death worldwide, and has a five-year survival rate of 18% [1]. MARK2 is a serine/threonine-protein kinase, and is a key component in the phosphorylation of microtubule-associated proteins [2], [3]. A recent study published by Hubaux et al. found that microtubule affinity-regulating kinase 2 (MARK2) showed highly frequent DNA and RNA level disruption in lung cancer cell lines and independent non-small cell lung cancer (NSCLC) cohorts [4]. These alterations result in the acquisition of oncogenic properties in cell lines, such as increased viability and anchorage-independent growth. Furthermore, a microarray-based transcriptome analysis of three short hairpin RNA (shRNA)-mediated MARK2 knockdown lung adenocarcinoma cell lines (GEO#: GSE57966) revealed an association between MARK2 gene expression and cell cycle activation and DNA damage response. Here, we present a detailed description of transcriptome analysis to support the described role of MARK2 in promoting a malignant phenotype.

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer

NASA Astrophysics Data System (ADS)

Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

2016-06-01

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity.

Intercostal muscle flap to protect the bronchial stump in pediatric lobectomy for lung abscess.

PubMed

Lisi, Gabriele; Lauriti, Giuseppe; Cascini, Valentina; Lococo, Achille; Chiesa, Pierluigi Lelli

2013-01-01

Lung suppurative diseases in children are usually responsive to medical treatment or percutaneous drainage. Rarely, pulmonary resection is required for lung abscess in childhood, particularly in presence of co-morbidities. In these cases, a lobectomy is usually performed through an open thoracotomy, with a reported incidence of bronco-pleural fistula up to 9.1% of pediatric series. This consequence is mainly due to the inflammatory condition; however the lack of knowledge of pediatric and thoracic surgeons with this rare condition in childhood can also play a role. In adults with lung cancer, the buttressing of bronchial stump with the additional support of an intercostal muscle (ICM) flap has proved to prevent this complication, as well as to reduce post-operative pain. We report the first pediatric experience of ICM flap used in 2 immunocompetent children requiring lobectomy for suppurative lung conditions. Our preliminary experience confirms the feasibility of protecting the bronchial stump after lobectomy in children, especially in conditions at risk for bronco-pleural fistula development.

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer

PubMed Central

Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

2016-01-01

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity. PMID:27279498

Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer.

PubMed

Praveen, Paurush; Hülsmann, Helen; Sültmann, Holger; Kuner, Ruprecht; Fröhlich, Holger

2016-06-09

Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity.

Spirometry: a predictor of lung cancer among asbestos workers.

PubMed

Świątkowska, Beata; Szeszenia-Dąbrowska, Neonila

2017-01-01

The significance of lung function as an independent risk factor for lung cancer remains unclear. The objective of the study is to answer the question if spirometry can identify patients at risk for lung cancer among people occupationally exposed to asbestos dust in the past. In order to identify a group of individuals with the highest risk of lung cancer incidence based on lung function levels of FEV 1 % predicted value, we examined 6882 subjects enrolled in the health surveillance program for asbestos related diseases over the years 2000-2014. We found a total of 110 cases confirmed as primary lung cancer. Using Cox's proportional hazards model after adjustment for age, gender, number of cigarettes, duration of smoking and cumulative asbestos exposure, we estimated that compared with the subjects with FEV 1 ≥90% pred, the HR of lung cancer was 1.40 (95%CI: 0.94-2.08) for the subjects with FEV 1 less than 90% and 1.95 (HR = 1.86; 95%CI: 1.12-3.08) for those with FEV 1 less than 70%. In addition, probability of the occurrence of lung cancer for FEV 1 <90% of the predicted value was HR = 2.19 (95%CI: 1.04-4.61) in the subjects whose time since spirometry and cancer diagnosis was three years or less. The results strongly support the hypothesis that spirometry can identify patients at a risk of lung cancer development. Regular spirometry should be offered to all patients with a history of asbestos exposure, at least once every three years.

Predicting the response of the injured lung to the mechanical breath profile

PubMed Central

Smith, Bradford J.; Lundblad, Lennart K. A.; Kollisch-Singule, Michaela; Satalin, Joshua; Nieman, Gary; Habashi, Nader

2015-01-01

Mechanical ventilation is a crucial component of the supportive care provided to patients with acute respiratory distress syndrome. Current practice stipulates the use of a low tidal volume (Vt) of 6 ml/kg ideal body weight, the presumptive notion being that this limits overdistension of the tissues and thus reduces volutrauma. We have recently found, however, that airway pressure release ventilation (APRV) is efficacious at preventing ventilator-induced lung injury, yet APRV has a very different mechanical breath profile compared with conventional low-Vt ventilation. To gain insight into the relative merits of these two ventilation modes, we measured lung mechanics and derecruitability in rats before and following Tween lavage. We fit to these lung mechanics measurements a computational model of the lung that accounts for both the degree of tissue distension of the open lung and the amount of lung derecruitment that takes place as a function of time. Using this model, we predicted how tissue distension, open lung fraction, and intratidal recruitment vary as a function of ventilator settings both for conventional low-Vt ventilation and for APRV. Our predictions indicate that APRV is more effective at recruiting the lung than low-Vt ventilation, but without causing more overdistension of the tissues. On the other hand, low-Vt ventilation generally produces less intratidal recruitment than APRV. Predictions such as these may be useful for deciding on the relative benefits of different ventilation modes and thus may serve as a means for determining how to ventilate a given lung in the least injurious fashion. PMID:25635004

Deletion of Pten Expands Lung Epithelial Progenitor Pools and Confers Resistance to Airway Injury

PubMed Central

Tiozzo, Caterina; De Langhe, Stijn; Yu, Mingke; Londhe, Vedang A.; Carraro, Gianni; Li, Min; Li, Changgong; Xing, Yiming; Anderson, Stewart; Borok, Zea; Bellusci, Saverio; Minoo, Parviz

2009-01-01

Rationale: Pten is a tumor-suppressor gene involved in stem cell homeostasis and tumorigenesis. In mouse, Pten expression is ubiquitous and begins as early as 7 days of gestation. Pten−/− mouse embryos die early during gestation indicating a critical role for Pten in embryonic development. Objectives: To test the role of Pten in lung development and injury. Methods: We conditionally deleted Pten throughout the lung epithelium by crossing Ptenflox/flox with Nkx2.1-cre driver mice. The resulting PtenNkx2.1-cre mutants were analyzed for lung defects and response to injury. Measurements and Main Results: PtenNkx2.1-cre embryonic lungs showed airway epithelial hyperplasia with no branching abnormalities. In adult mice, PtenNkx2.1-cre lungs exhibit increased progenitor cell pools composed of basal cells in the trachea, CGRP/CC10 double-positive neuroendocrine cells in the bronchi, and CC10/SPC double-positive cells at the bronchioalveolar duct junctions. Pten deletion affected differentiation of various lung epithelial cell lineages, with a decreased number of terminally differentiated cells. Over time, PtenNxk2.1-cre epithelial cells residing in the bronchioalveolar duct junctions underwent proliferation and formed uniform masses, supporting the concept that the cells residing in this distal niche may also be the source of procarcinogenic stem cells. Finally, increased progenitor cells in all the lung compartments conferred an overall selective advantage to naphthalene injury compared with wild-type control mice. Conclusions: Pten has a pivotal role in lung stem cell homeostasis, cell differentiation, and consequently resistance to lung injury. PMID:19574443

Initial in vitro evaluation of a pediatric vortex-mixing membrane lung.

PubMed

Peacock, J A; Bellhouse, B J; Abel, K; Bellhouse, E L; Bellhouse, F H; Jeffree, M A; Sykes, M K; Gardaz, J P

1983-05-01

A new design for a pediatric membrane lung is described in this paper. The lung consists of eight blood compartments, each having six U-shaped blood channels, with microporous PTFE membranes supported on rigid plates in such a way that the membranes form furrowed blood channels. Two rolling diaphragm pumps are attached to the open ends of the U-shaped blood channels; these pumps are operated in antiphase. Mean flow is provided by a roller pump placed at the inlet end of the membrane lung. Pulsatile blood flow within the blood channels produces successive vortex formation and ejection, leading to good blood mixing and high efficiency in gas transport. The design of the rolling diaphragm piston pumps ensures that the blood prime volume is low (280 ml), and the grouping of the pumps at one end of the oxygenator allows the driving mechanism to be simple and compact. The relatively wide blood channels (minimum width 0.5 mm) and vortex mixing make priming the membrane lung particularly easy. The membrane area is 0.39 m2. Preliminary performance testing of the pediatric membrane lung was undertaken by pumping blood around a circuit containing a roller pump, the membrane lung, and a bubble oxygenator (to adjust the blood gases at the inlet to the membrane lung). In five such experiments it was shown that the membrane lung transferred 80 ml O2/min and 120 ml CO2/min at a blood flow rate of 1.5 L/min.

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion

PubMed Central

Andreasson, Anders S.I.; Karamanou, Danai M.; Gillespie, Colin S.; Özalp, Faruk; Butt, Tanveer; Hill, Paul; Jiwa, Kasim; Walden, Hannah R.; Green, Nicola J.; Borthwick, Lee A.; Clark, Stephen C.; Pauli, Henning; Gould, Kate F.; Corris, Paul A.; Ali, Simi; Dark, John H.

2017-01-01

Abstract OBJECTIVES: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. METHODS: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. RESULTS: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. CONCLUSIONS: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study. PMID:28082471

Manganese Superoxide Dismutase Gene-Modified Mesenchymal Stem Cells Attenuate Acute Radiation-Induced Lung Injury.

PubMed

Chen, Hai-Xu; Xiang, Hang; Xu, Wen-Huan; Li, Ming; Yuan, Jie; Liu, Juan; Sun, Wan-Jun; Zhang, Rong; Li, Jun; Ren, Zhao-Qi; Zhang, Xiao-Mei; Du, Bin; Wan, Jun; Wu, Ben-Yan; Zeng, Qiang; He, Kun-Lun; Yang, Chao

2017-06-01

Radiation-induced lung injury (RILI) is a major clinical complication for radiotherapy in thoracic tumors. An immediate effect of lung irradiation is the generation of reactive oxygen that can produce oxidative damage to DNA, lipids, and proteins resulting in lung cell injury or death. Currently, the medical management of RILI remains supportive. Therefore, there is an urgent need for the development of countermeasures. The present study aimed to evaluate the protective effect of manganese superoxide dismutase (MnSOD) gene-modified mesenchymal stem cells (MSCs) to facilitate the improved recovery of RILI. Here, nonobese diabetic/severe combined immunodeficiency mice received a 13 Gy dose of whole-thorax irradiation, and were then transfused intravenously with MnSOD-MSCs and monitored for 30 days. Lung histopathologic analysis, plasma levels of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-10, and tumor necrosis factor-α), profibrotic factor transforming growth factor-β1, and the oxidative stress factor (hydroxyproline) were evaluated after MnSOD-MSC transplant. Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated nick-end labeling immunohistochemical method. Colonization and differentiation of MnSOD-MSCs in the irradiated lung were analyzed by immunofluorescence staining. Consequently, systemic administration of MnSOD-MSCs significantly attenuated lung inflammation, ameliorated lung damage, and protected the lung cells from apoptosis. MnSOD-MSCs could differentiate into epithelial-like cells in vivo. MnSOD-MSCs were effective in modulating RILI in mice and had great potential for accelerating from bench to bedside.

Esophageal Manometry and Regional Transpulmonary Pressure in Lung Injury.

PubMed

Yoshida, Takeshi; Amato, Marcelo B P; Grieco, Domenico Luca; Chen, Lu; Lima, Cristhiano A S; Roldan, Rollin; Morais, Caio C A; Gomes, Susimeire; Costa, Eduardo L V; Cardoso, Paulo F G; Charbonney, Emmanuel; Richard, Jean-Christophe M; Brochard, Laurent; Kavanagh, Brian P

2018-04-15

Esophageal manometry is the clinically available method to estimate pleural pressure, thus enabling calculation of transpulmonary pressure (Pl). However, many concerns make it uncertain in which lung region esophageal manometry reflects local Pl. To determine the accuracy of esophageal pressure (Pes) and in which regions esophageal manometry reflects pleural pressure (Ppl) and Pl; to assess whether lung stress in nondependent regions can be estimated at end-inspiration from Pl. In lung-injured pigs (n = 6) and human cadavers (n = 3), Pes was measured across a range of positive end-expiratory pressure, together with directly measured Ppl in nondependent and dependent pleural regions. All measurements were obtained with minimal nonstressed volumes in the pleural sensors and esophageal balloons. Expiratory and inspiratory Pl was calculated by subtracting local Ppl or Pes from airway pressure; inspiratory Pl was also estimated by subtracting Ppl (calculated from chest wall and respiratory system elastance) from the airway plateau pressure. In pigs and human cadavers, expiratory and inspiratory Pl using Pes closely reflected values in dependent to middle lung (adjacent to the esophagus). Inspiratory Pl estimated from elastance ratio reflected the directly measured nondependent values. These data support the use of esophageal manometry in acute respiratory distress syndrome. Assuming correct calibration, expiratory Pl derived from Pes reflects Pl in dependent to middle lung, where atelectasis usually predominates; inspiratory Pl estimated from elastance ratio may indicate the highest level of lung stress in nondependent "baby" lung, where it is vulnerable to ventilator-induced lung injury.

Quantification of Age-Related Lung Tissue Mechanics under Mechanical Ventilation.

PubMed

Kim, JongWon; Heise, Rebecca L; Reynolds, Angela M; Pidaparti, Ramana M

2017-09-29

Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator-induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator-induced lung injuries. Two age-related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50-year-old (normal) and second is for an 80-year old (aged) model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s) decreased by about 40% in the alveolar sac (G23) and 27% in the bronchiole (G20), respectively, for the 80-year-old as compared to the 50-year-old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain) over G20 and G23 for the 80-year-old decreased by about 64% (three-fold) and 80% (four-fold), respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold) in lung compliance for the 80-year-old in comparison to the 50-year-old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study.

Palliative and end-of-life care in lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

PubMed

Ford, Dee Walker; Koch, Kathryn A; Ray, Daniel E; Selecky, Paul A

2013-05-01

In the United States, lung cancer is a major health problem that is associated with significant patient distress and often limited survival, with some exceptions. The purpose of this article is to address the role of palliative and end-of-life care in the management of patients with lung cancer and to address the need for good communication skills to provide support to patients and families. This article is based on an extensive review of the medical literature up to April 2012, with some articles as recent as August 2012. The authors used the PubMed and Cochrane databases, as well as EBESCO Host search, for articles addressing palliative care, supportive care, lung neoplasm, and quality of life in cancer or neoplasm, with no limitation on dates. The research was limited to human studies and the English language. There was no "definitive" work in this area, most of it being concurrence based rather than evidence based. Several randomized controlled trials were identified, which are reviewed in the text. The article focuses on the assessment and treatment of suffering in patients with lung cancer, as well as the importance of communication in the care of these patients over the course of the disease. The aim of medical care for patients with terminal lung cancer is to decrease symptom burden, enhance the quality of remaining life, and increase survival benefit. A second objective is to emphasize the importance of good communication skills when addressing the needs of the patient and his or her family, starting at the time of diagnosis, which in itself is a life-changing event. Too often we do it poorly, but by using patient-centered communication skills, the outcome can be more satisfactory. Finally, the article addresses the importance of advance care planning for patients with lung cancer, from the time of diagnosis until the last phase of the illness, and it is designed to enhance the physician's role in facilitating this planning process. This article provides guidance on how to reduce patient distress and avoid nonbeneficial treatment in patients with lung cancer. The goal is to decrease symptom burden, enhance quality of life, and increase survival benefit. Good communication and advance care planning are vital to the process.

Effects of Cardiopulmonary Support with a Novel Pediatric Pump-Lung (PediPL) in a Thirty-Day Ovine Animal Model

PubMed Central

Liu, Yang; Sanchez, Pablo G; Wei, Xufeng; Watkins, Amelia C; Niu, Shuqiong; Wu, Zhongjun J; Griffith, Bartley P

2016-01-01

The scarcity of donor organs has led to the development of devices that provide optimal long-term respiratory or cardiopulmonary support to bridge recipients as they wait for lung and/or heart transplantation. This study was designed to evaluate the 30-day in-vivo performance of the newly developed pediatric pump-lung (PediPL) for cardiopulmonary support using a juvenile sheep model. The PediPL device was placed surgically between the right atrium and descending aorta in eight sheep (25.4 to 31.2kg) and evaluated for 30 days. Anticoagulation was maintained with continuous heparin infusion (ACT 150–200 sec). The flow rate was measured continually and gas transfer was measured daily. Plasma free hemoglobin, platelet activation, hematologic data, and blood biochemistry were assessed twice a week. Sheep were euthanized after 30 days. The explanted devices were examined for gross thrombosis. Six sheep survived for 30 to 32 days. During the study, the oxygen transfer rate of the devices was 54.9 ± 13.2mL/min at a mean flow rate of 1.14 ± 0.46 L/min with blood oxygen saturation of 95.4% ± 1.7%. Plasma free hemoglobin was 8.2 ± 3.7 mg/dL. Platelet activation was 5.35 ± 2.65%. The animals had normal organ chemistries except for surgery-related transient alterations in kidney and liver function. Although we found some scattered thrombi on the membrane surfaces of some explanted devices during the necropsy, the device function and performance did not degrade. The PediPL device was capable of providing cardiopulmonary with long-term reliability and good biocompatibility over the 30 day duration and offering the potential option for bridging to heart and/or lung transplant pediatric patients with end-stage heart or lung disease. PMID:25921361

Central versus peripheral cannulation of extracorporeal membrane oxygenation support during double lung transplant for pulmonary hypertension.

PubMed

Glorion, Matthieu; Mercier, Olaf; Mitilian, Delphine; De Lemos, Alexandra; Lamrani, Lilia; Feuillet, Séverine; Pradere, Pauline; Lepavec, Jérôme; Lehouerou, Daniel; Stephan, François; Savale, Laurent; Fabre, Dominique; Mussot, Sacha; Fadel, Elie

2018-03-08

Extracorporeal membrane oxygenation (ECMO) has become the standard of cardiopulmonary support during a sequential double lung transplant for pulmonary hypertension. Whether central or peripheral cannulation is the best strategy for these patients remains unknown. Our goal was to determine which is the best strategy by comparing 2 populations of patients. We performed a single-centre retrospective study based on an institutional prospective lung transplant database. Between January 2011 and November 2016, 103 patients underwent double lung transplant for pulmonary hypertension. We compared 54 patients who had central ECMO (cECMO group) to 49 patients who had peripheral ECMO (pECMO group). The pECMO group had significantly more bridged patients who received emergency transplants (31% vs 6%, P = 0.001). The incidence of Grade 3 primary graft dysfunction requiring ECMO (14% vs 11%, P = not significant) and of in-hospital mortality (11% vs 14%, P = not significant) was similar between the groups. Groin infections (16% vs 4%, P = 0.031), deep vein thrombosis (27% vs 11%, P = 0.044) and lower limb ischaemia (12% vs 2%, P = 0.031) occurred significantly more often in the pECMO group. The number of chest reopenings for bleeding or infection was similar between the groups. The 3-month, 1-year and 5-year survival rates did not differ between the groups (P = 0.94). Central or peripheral ECMO produced similar results during double lung transplant for pulmonary hypertension in terms of in-hospital deaths and long-term survival rates. Central ECMO provided satisfactory results without major bleeding provided the patient was weaned from ECMO at the end of the procedure. Despite the rate of groin and lower limb complications, peripheral cannulation remained the preferred solution to bridge the patient to transplant or for postoperative support.

Acute respiratory distress syndrome and acute lung injury.

PubMed

Dushianthan, A; Grocott, M P W; Postle, A D; Cusack, R

2011-09-01

Acute respiratory distress syndrome (ARDS) is a life threatening respiratory failure due to lung injury from a variety of precipitants. Pathologically ARDS is characterised by diffuse alveolar damage, alveolar capillary leakage, and protein rich pulmonary oedema leading to the clinical manifestation of poor lung compliance, severe hypoxaemia, and bilateral infiltrates on chest radiograph. Several aetiological factors associated with the development of ARDS are identified with sepsis, pneumonia, and trauma with multiple transfusions accounting for most cases. Despite the absence of a robust diagnostic definition, extensive epidemiological investigations suggest ARDS remains a significant health burden with substantial morbidity and mortality. Improvements in outcome following ARDS over the past decade are in part due to improved strategies of mechanical ventilation and advanced support of other failing organs. Optimal treatment involves judicious fluid management, protective lung ventilation with low tidal volumes and moderate positive end expiratory pressure, multi-organ support, and treatment where possible of the underlying cause. Moreover, advances in general supportive measures such as appropriate antimicrobial therapy, early enteral nutrition, prophylaxis against venous thromboembolism and gastrointestinal ulceration are likely contributory reasons for the improved outcomes. Although therapies such as corticosteroids, nitric oxide, prostacyclins, exogenous surfactants, ketoconazole and antioxidants have shown promising clinical effects in animal models, these have failed to translate positively in human studies. Most recently, clinical trials with β2 agonists aiding alveolar fluid clearance and immunonutrition with omega-3 fatty acids have also provided disappointing results. Despite these negative studies, mortality seems to be in decline due to advances in overall patient care. Future directions of research are likely to concentrate on identifying potential biomarkers or genetic markers to facilitate diagnosis, with phenotyping of patients to predict outcome and treatment response. Pharmacotherapies remain experimental and recent advances in the modulation of inflammation and novel cellular based therapies, such as mesenchymal stem cells, may reduce lung injury and facilitate repair.

A NOVEL WEARABLE PUMP-LUNG DEVICE: IN-VITRO AND ACUTE IN-VIVO STUDY

PubMed Central

Zhang, Tao; Wei, Xufeng; Bianchi, Giacomo; Wong, Philip M.; Biancucci, Brian; Griffith, Bartley P.; Wu, Zhongjun J.

2011-01-01

Background To provide long-term ambulatory cardiopulmonary and respiratory support for adult patients, a novel wearable artificial pump-lung device has been developed. The design features, in-vitro and acute in-vivo performance of this device are reported in this paper. Methods This device features a uniquely designed hollow fiber membrane bundle integrated with a magnetically levitated impeller together to form one ultra-compact pump-lung device, which can be placed like current paracorporeal ventricular assist devices to allow ambulatory support. The device is 117 mm in length and 89 mm in diameter and has a priming volume of 115 ml. In-vitro hydrodynamic, gas transfer and biocompatibility experiments were carried out in mock flow loops using ovine blood. Acute in-vivo characterization was conducted in ovine by surgically implanting the device between right atrium and pulmonary artery. Results The in-vitro results showed that the device with a membrane surface area of 0.8 m2 was capable of pumping blood from 1 to 4 L/min against a wide range of pressures and transferring oxygen at a rate of up to 180 ml/min at a blood flow of 3.5 L/min. Standard hemolysis tests demonstrated low hemolysis at the targeted operating condition. The acute in-vivo results also confirmed that the device can provide sufficient oxygen transfer with excellent biocompatibility. Conclusions Base on the in-vitro and acute in-vivo study, this highly integrated wearable pump-lung device can provide efficient respiratory support with good biocompatibility and it is ready for long-term evaluation. PMID:22014451

Lung parenchyma at maturity is influenced by postnatal growth but not by moderate preterm birth in sheep.

PubMed

Maritz, Gert; Probyn, Megan; De Matteo, Robert; Snibson, Ken; Harding, Richard

2008-01-01

We have recently shown that moderate preterm birth, in the absence of respiratory support, altered the structure of lung parenchyma in young lambs, but the long-term effects are unknown. To determine whether structural changes persist to maturity, and whether postnatal growth affects lung structure at maturity in sheep. At approximately 1.2 years after birth, lung parenchyma of sheep born 14 days before term (n = 7) was stereologically compared with that of controls born at term (n = 8, term approx. 146 days). Preterm birth per se had no significant effect on lung volume, alveolar number and size, and thicknesses of the alveolar walls and blood-gas barrier. After combining the preterm and term groups, we examined the effects of postnatal growth rates on lung parenchyma. Slower-growing sheep (SG; n = 7: 4 preterm, 3 term) were compared with faster-growing sheep (FG; n = 8: 3 preterm, 5 term). At approximately 1.2 years, the right lung volume, relative to body weight, was significantly lower in SG than FG sheep (p < 0.05) and alveolar number was significantly lower by approximately 44%. The total alveolar internal surface area of the right lung of SG sheep was 38% smaller than in FG sheep; it was also significantly lower when related to both lung and body weight. Our data suggest that moderate preterm birth does not cause persistent alterations in lung parenchyma. However, slow postnatal growth in low-birth-weight sheep results in smaller lungs with fewer alveoli and a lower alveolar surface area relative to body weight. Copyright (c) 2007 S. Karger AG, Basel.

Exponential analysis of the lung pressure-volume curve in patients with chronic pigeon-breeder's lung.

PubMed

Sansores, R; Perez-Padilla, R; Paré, P D; Selman, M

1992-05-01

Pigeon-breeder's lung (PBL) is extremely common in Mexico City and often progresses to irreversible pulmonary fibrosis. The exponential analysis of the lung pressure-volume (PV) curve (V = A - Be-kp) has been suggested as a method to separate the lung restriction caused by inflammation from that caused by pulmonary fibrosis; a significantly decreased value for the exponential constant, k, suggests a change in the mechanical properties of the functioning lung parenchyma, while a normal value accompanied by restriction suggests subtraction of lung units without a change in the mechanical properties of the functioning units. We measured lung volumes and static PV curves in 29 patients who had persistent lung restriction following a biopsy-proven diagnosis of PBL. Mean values in the 29 subjects were as follows: age, 43 +/- 13 years; TLC, 61 +/- 15 percent of predicted; VC, 46 +/- 19 percent of predicted; and k, 55 +/- 17 percent of predicted. Twenty-four of the 29 patients had values for k that were below the 95 percent confidence level, and five had "normal" values. There was no difference in TLC and VC (percent of predicted) between those with or without a decreased value for k. Four of five patients with a normal value for k improved subsequent to diagnosis, while only one of 21 patients with a decreased k improved. We conclude that increased lung elasticity manifested by a low value for k is common in patients with chronic PBL. These results support the observation of frequent irreversible lung fibrosis in these patients. Measurements of k could prove a good prognostic indicator at the time of initial diagnosis.

Regulation of mouse lung development by the extracellular calcium-sensing receptor, CaR

PubMed Central

Finney, Brenda A; del Moral, Pierre M; Wilkinson, William J; Cayzac, Sebastien; Cole, Martin; Warburton, David; Kemp, Paul J; Riccardi, Daniela

2008-01-01

Postnatal lung function is critically dependent upon optimal embryonic lung development. As the free ionized plasma calcium concentration ([Ca2+]o) of the fetus is higher than that of the adult, the process of lung development occurs in a hypercalcaemic environment. In the adult, [Ca2+]o is monitored by the G-protein coupled, extracellular calcium-sensing receptor (CaR), but neither its ontogeny nor its potential role in lung development are known. Here, we demonstrate that CaR is expressed in the mouse lung epithelium, and that its expression is developmentally regulated, with a peak of expression at embryonic day 12.5 (E12.5) and a subsequent decrease by E18, after which the receptor is absent. Experiments carried out using the lung explant culture model in vitro show that lung branching morphogenesis is sensitive to [Ca2+]o, being maximal at physiological adult [Ca2+]o (i.e. 1.0–1.3 mm) and lowest at the higher, fetal (i.e. 1.7 mm) [Ca2+]o. Administration of the specific CaR positive allosteric modulator, the calcimimetic R-568, mimics the suppressive effects of high [Ca2+]o on branching morphogenesis while both phospholipase C and PI3 kinase inhibition reverse these effects. CaR activation suppresses cell proliferation while it enhances intracellular calcium signalling, lung distension and fluid secretion. Conditions which are restrictive either to branching or to secretion can be rescued by manipulating [Ca2+]o in the culture medium. In conclusion, fetal Cao2+, acting through a developmentally regulated CaR, is an important extrinsic factor that modulates the intrinsic lung developmental programme. Our observations support a novel role for the CaR in preventing hyperplastic lung disease in utero. PMID:18955379

Spatiotemporal Aeration and Lung Injury Patterns Are Influenced by the First Inflation Strategy at Birth.

PubMed

Tingay, David G; Rajapaksa, Anushi; Zonneveld, C Elroy; Black, Don; Perkins, Elizabeth J; Adler, Andy; Grychtol, Bartłomiej; Lavizzari, Anna; Frerichs, Inéz; Zahra, Valerie A; Davis, Peter G

2016-02-01

Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.

Indoor air pollution from solid fuel use, chronic lung diseases and lung cancer in Harbin, Northeast China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galeone, C.; Pelucchi, C.; La Vecchia, C.

In some areas of China, indoor air pollution (IAP) originating principally from the combustion of solid fuels has a relevant role in lung cancer. Most previous studies focused on the female population and only a few on both the sexes. We analyzed the relationship between IAP from solid fuel use and selected chronic lung diseases and lung cancer risk in Harbin, Northeast China, an area with a very high base line risk of lung cancer for both the sexes. We used data from a case-control study conducted between 1987 and 1990, including 218 patients with incident, histologically confirmed lung cancermore » and 436 controls admitted to the same hospitals as cases. We calculated an index of IAP from solid fuel use exposure using data on heating type, cooking fuel used, and house measurements. Cases reported more frequently than controls on exposure to coal fuel for house heating and/or cooking, and the odds ratio (OR) for ever versus never exposed was 2.19 (95% confidence interval (CI): 1.08-4.46). The ORs of lung cancer according to subsequent tertiles of IAP exposure index were 1.82 (95% CI: 1.14-2.89) and 1.99 (95% CI: 1.26-3.15) as compared with the lowest tertile. The ORs of lung cancer for participants with a history of chronic bronchitis and tuberculosis were 3.79 (95% CI: 2.38-6.02) and 3.82 (95% CI: 1.97-7.41), respectively. This study gives further support and quantification of the positive association between IAP, history of selected nonmalignant lung diseases, and lung cancer risk for both the sexes.« less

Silicosis and coal workers' pneumoconiosis.

PubMed Central

Castranova, V; Vallyathan, V

2000-01-01

Exposure to coal mine dust and/or crystalline silica results in pneumoconiosis with initiation and progression of pulmonary fibrosis. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:10931786

Malondialdehyde-acetaldehyde (MAA) adducted protein inhalation causes lung injury

PubMed Central

Wyatt, T. A.; Kharbanda, K. K.; McCaskill, M. L.; Tuma, D. J.; Yanov, D.; DeVasure, J.; Sisson, J. H.

2011-01-01

In addition to cigarette smoking, alcohol exposure is also associated with increased lung infections and decreased mucociliary clearance. However, little research has been conducted on the combination effects of alcohol and cigarette smoke on lungs. Previously, we have demonstrated in a mouse model that the combination of cigarette smoke and alcohol exposure results in the formation of a very stable hybrid malondialdehyde-acetaldehyde (MAA)-adducted protein in the lung. In in vitro studies, MAA-adducted protein stimulates bronchial epithelial cell interleukin-8 via the activation of protein kinase C epsilon (PKCε). We hypothesized that direct MAA-adducted protein exposure in the lungs would mimic such a combination of smoke and alcohol exposure leading to airway inflammation. To test this hypothesis, C57BL/6J female mice were intranasally instilled with either saline, 30 µL of 50 µg/mL BSA-MAA, or unadducted BSA for up to 3 wk. Likewise, human lung surfactant proteins A and D (SPA, SPD) were purified from human pulmonary proteinosis lung lavage fluid and successfully MAA-adducted in vitro. Similar to BSA-MAA, SPD-MAA was instilled into mouse lungs. Lungs were necropsied and assayed for histopathology, PKCε activation, and lung lavage chemokines. In control mice instilled with saline, normal lungs had few inflammatory cells. No significant effects were observed in un-adducted BSA- or SPD-instilled mice. However, when mice were instilled with BSA-MAA or SPD-MAA for 3 wk, a significant peribronchiolar localization of inflammatory cells was observed. Both BSA-MAA and SPD-MAA stimulated increased lung lavage neutrophils and caused a significant elevation in the chemokine, KC, which is a functional homologue to human interleukin-8. Likewise, MAA-adducted protein stimulated the activation of airway and lung slice PKCε. These data support that MAA-adducted protein induces a pro-inflammatory response in the lungs and that lung surfactant protein is a biologically relevant target for malondialdehyde and acetaldehyde adduction. These data further implicate MAA-adduct formation as a potential mechanism for smoke and alcohol induced lung injury. PMID:21958604

Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood

PubMed Central

Harris, Donald G.; Quinn, Kevin J.; French, Beth M.; Schwartz, Evan; Kang, Elizabeth; Dahi, Siamak; Phelps, Carol J.; Ayares, David L.; Burdorf, Lars; Azimzadeh, Agnes M.; Pierson, Richard N.

2014-01-01

Background Genetically modified pigs are a promising potential source of lung xenografts. Ex-vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series. Methods Data from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had 1 genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 hours of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype. Results Each increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 hours generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO-1, hCD55 or hEPCR were associated with improved survival. hTBM, HLA-E, and hCD39 were associated with no significant effect on the primary outcome. Conclusion This meta-analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression and pathway-specific injury, and explore why some genes apparently exhibit neutral (hTBM, HLA-E) or inconclusive (CD39) effects, GalTKO, hCD46, HO-1, hCD55, and hEPCR modifications were associated with significant lung xenograft protection. This analysis supports the hypothesis that multiple genetic modifications targeting different known mechanisms of xenograft injury will be required to optimize lung xenograft survival. PMID:25470239

The Transient Receptor Potential Vanilloid 1 Antagonist Capsazepine Improves the Impaired Lung Mechanics during Endotoxemia.

PubMed

Cabral, Layla D M; Giusti-Paiva, Alexandre

2016-11-01

Acute lung injury (ALI) caused by systemic inflammatory response remains a leading cause of morbidity and mortality in critically ill patients. Management of patients with sepsis is largely limited to supportive therapies, reflecting an incomplete understanding of the underlying pathophysiology. Furthermore, there have been limited advances in the treatments for ALI. In this study, lung function and a histological analysis were performed to evaluate the impact of transient receptor potential vanilloid-1 receptor (TRPV1) antagonist (capsazepine; CPZ) on the lipopolysaccharide (LPS)-induced lung injury in mice. For this, adult mice pre-treated with CPZ or vehicle received intraperitoneal injections of LPS or saline and 24 hr after, the mice were anaesthetized, and lung mechanics was evaluated. The LPS-challenged mice exhibited substantial mechanical impairment, characterized by increases in respiratory system resistance, respiratory system elastance, tissue damping and tissue elastance. The pre-treatment with CPZ prevented the increase in respiratory system resistance and decreased the increase in tissue damping during endotoxemia. In addition, mice pre-treated with CPZ had an attenuated lung injury evidenced by reduction on collapsed area of the lung parenchyma induced by LPS. This suggests that the TRPV1 antagonist capsazepine has a protective effect on lung mechanics in ALI during endotoxemia and that it may be a target for enhanced therapeutic efficacy in ALI. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Expression of microRNA-133 inhibits epithelial-mesenchymal transition in lung cancer cells by directly targeting FOXQ1.

PubMed

Xiao, Bo; Liu, Huazhen; Gu, Zeyun; Ji, Cheng

2016-10-01

MicroRNA (miR) was implicated in the tumorigenesis of many types of cancer, but no study was conducted on the exact role of miR-133 in lung cancer. We have identified miR-133 as a putative regulator of FOXQ1 expression, and investigated the potential involvement of miR-133 in the migration and invasion of lung cancer cells, as well as the underlying molecular mechanism. MiR-133 directly targeted and down-regulated FOXQ1 expression, which in turn reduced TGF-β level. MiR-133 was down-regulated in lung cancer cell lines A549 and HCC827, and its re-expression significantly inhibited the migration and invasion of the lung cancer cells. Further investigation revealed that this inhibition was caused by reversing the epithelial-mesenchymal transition, evidenced by miR-133 induced elevation of epithelial marker E-cadherin, and reduction of mesenchymal marker Vimentin. Our study is the first to identify miR-133 as a biomarker for lung cancer. It functions to down-regulate FOXQ1, and inhibit epithelial-mesenchymal transition, which antagonizes lung cancer tumorigenesis. Therefore our data support the role of miR-133 as a potential molecular therapeutic tool in treating lung cancer. Copyright © 2015 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Pressure Dynamic Characteristics of Pressure Controlled Ventilation System of a Lung Simulator

PubMed Central

Shi, Yan; Ren, Shuai; Cai, Maolin; Xu, Weiqing; Deng, Qiyou

2014-01-01

Mechanical ventilation is an important life support treatment of critically ill patients, and air pressure dynamics of human lung affect ventilation treatment effects. In this paper, in order to obtain the influences of seven key parameters of mechanical ventilation system on the pressure dynamics of human lung, firstly, mechanical ventilation system was considered as a pure pneumatic system, and then its mathematical model was set up. Furthermore, to verify the mathematical model, a prototype mechanical ventilation system of a lung simulator was proposed for experimental study. Last, simulation and experimental studies on the air flow dynamic of the mechanical ventilation system were done, and then the pressure dynamic characteristics of the mechanical system were obtained. The study can be referred to in the pulmonary diagnostics, treatment, and design of various medical devices or diagnostic systems. PMID:25197318

Computer and mobile technology interventions for self-management in chronic obstructive pulmonary disease.

PubMed

McCabe, Catherine; McCann, Margaret; Brady, Anne Marie

2017-05-23

Chronic obstructive pulmonary disease (COPD) is characterised by airflow obstruction due to an abnormal inflammatory response of the lungs to noxious particles or gases, for example, cigarette smoke. The pattern of care for people with moderate to very severe COPD often involves regular lengthy hospital admissions, which result in high healthcare costs and an undesirable effect on quality of life. Research over the past decade has focused on innovative methods for developing enabling and assistive technologies that facilitate patient self-management. To evaluate the effectiveness of interventions delivered by computer and by mobile technology versus face-to-face or hard copy/digital documentary-delivered interventions, or both, in facilitating, supporting, and sustaining self-management among people with COPD. In November 2016, we searched the Cochrane Airways Group Specialised Register (CAGR), which contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and PsycINFO, and we handsearched respiratory journals and meeting abstracts. We included randomised controlled trials that measured effects of remote and Web 2.0-based interventions defined as technologies including personal computers (PCs) and applications (apps) for mobile technology, such as iPad, Android tablets, smart phones, and Skype, on behavioural change towards self-management of COPD. Comparator interventions included face-to-face and/or hard copy/digital documentary educational/self-management support. Two review authors (CMcC and MMcC) independently screened titles, abstracts, and full-text study reports for inclusion. Two review authors (CMcC and AMB) independently assessed study quality and extracted data. We expressed continuous data as mean differences (MDs) and standardised mean differences (SMDs) for studies using different outcome measurement scales. We included in our review three studies (Moy 2015; Tabak 2013; Voncken-Brewster 2015) with a total of 1580 randomised participants. From Voncken-Brewster 2015, we included the subgroup of individuals with a diagnosis of COPD (284 participants) and excluded those at risk of COPD who had not received a diagnosis (1023 participants). As a result, the total population available for analysis included 557 participants; 319 received smart technology to support self-management and 238 received face-to-face verbal/written or digital information and education about self-management. The average age of participants was 64 years. We included more men than women because the sample from one of the studies consisted of war veterans, most of whom were men. These studies measured five of our nine defined outcomes. None of these studies included outcomes such as self-efficacy, cost-effectiveness, functional capacity, lung function, or anxiety and depression.All three studies included our primary outcome - health-related quality of life (HRQoL) as measured by the Clinical COPD Questionnaire (CCQ) or St George's Respiratory Questionnaire (SGRQ). One study reported our other primary outcomes - hospital admissions and acute exacerbations. Two studies included our secondary outcome of physical activity as measured by daily step counts. One study addressed smoking by providing a narrative analysis. Only one study reported adverse events and noted significant differences between groups, with 43 events noted in the intervention group and eight events in the control group (P = 0.001). For studies that measured outcomes at week four, month four, and month six, the effect of smart technology on self-management and subsequent HRQoL in terms of symptoms and health status was significantly better than when participants received face-to-face/digital and/or written support for self-management of COPD (SMD -0.22, 95% confidence interval (CI) -0.40 to -0.03; P = 0.02). The single study that reported HRQoL at 12 months described no significant between-group differences (MD 1.1, 95% CI -2.2 to 4.5; P = 0.50). Also, hospitalisations (logistic regression odds ratio (OR) 1.6, 95% CI 0.8 to 3.2; P = 0.19) and exacerbations (logistic regression OR 1.4, 95% CI 0.7 to 2.8; P = 0.33) did not differ between groups in the single study that reported these outcomes at 12 months. The activity level of people with COPD at week four, month four, and month six was significantly higher when smart technology was used than when face-to-face/digital and/or written support was provided (MD 864.06 daily steps between groups, 95% CI 369.66 to 1358.46; P = 0.0006). The only study that measured activity levels at 12 months reported no significant differences between groups (mean -108, 95% CI -720 to 505; P = 0.73). Participant engagement in this study was not sustained between four and 12 months. The only study that included smoking cessation found no significant treatment effect (OR 1.06, 95%CI 0.43 to 2.66; P = 0.895). Meta-analyses showed no significant heterogeneity between studies (Chi² = 0.39, P = 0.82; I² = 0% and Chi² = 0.01, P = 0.91; I² = 0%, respectively). Although our review suggests that interventions aimed at facilitating, supporting, and sustaining self-managment in people with COPD and delivered via smart technology significantly improved HRQoL and levels of activity up to six months compared with interventions given through face-to-face/digital and/or written support, no firm conclusions can be drawn. This improvement may not be sustained over a long duration. The only included study that measured outcomes up to 12 months highlighted the need to ensure sustained engagement with the technology over time. Limited evidence suggests that using computer and mobile technology for self-management for people with COPD is not harmful and may be more beneficial for some people than for others, for example, those with an interest in using technology may derive greater benefit.The evidence, provided by three studies at high risk of bias, is of poor quality and is insufficient for advising healthcare professionals, service providers, and members of the public with COPD about the health benefits of using smart technology as an effective means of supporting, encouraging, and sustaining self-management. Further research that focuses on outcomes relevant to different stages of COPD is needed. Researchers should provide clear information on how self-management is assessed and should include longitudinal measures that allow comment on behavioural change.

Cerium oxide nanoparticles protect rodent lungs from hypobaric hypoxia-induced oxidative stress and inflammation.

PubMed

Arya, Aditya; Sethy, Niroj Kumar; Singh, Sushil Kumar; Das, Mainak; Bhargava, Kalpana

2013-01-01

Cerium oxide nanoparticles (nanoceria) are effective at quenching reactive oxygen species (ROS) in cell culture and animal models. Although nanoceria reportedly deposit in lungs, their efficacy in conferring lung protection during oxidative stress remains unexplored. Thus, the study evaluated the protective efficacy of nanoceria in rat lung tissue during hypobaric hypoxia. A total of 48 animals were randomly divided into four equal groups (control [C], nanoceria treated [T], hypoxia [H], and nanoceria treated plus hypoxia [T+H]). Animals were injected intraperitoneally with either a dose of 0.5 μg/kg body weight/week of nanoceria (T and T+H groups) or vehicle (C and H groups) for 5 weeks. After the final dose, H and T+H animals were challenged with hypobaric hypoxia, while C and T animals were maintained at normoxia. Lungs were isolated and homogenate was obtained for analysis of ROS, lipid peroxidation, glutathione, protein carbonylation, and 4-hydroxynonenal-adduct formation. Plasma was used for estimating major inflammatory cytokines using enzyme-linked immunosorbent assay. Intact lung tissues were fixed and both transmission electron microscopy and histopathological examinations were carried out separately for detecting internalization of nanoparticles as well as altered lung morphology. Spherical nanoceria of 7-10 nm diameter were synthesized using a microemulsion method, and the lung protective efficacy of the nanoceria evaluated during hypobaric hypoxia. With repeated intraperitoneal injections of low micromole concentration, we successfully localized the nanoceria in rodent lung without any inflammatory response. The lung-deposited nanoceria limited ROS formation, lipid peroxidation, and glutathione oxidation, and prevented oxidative protein modifications like nitration and carbonyl formation during hypobaric hypoxia. We also observed reduced lung inflammation in the nanoceria-injected lungs, supporting the anti-inflammatory properties of nanoceria. Cumulatively, these results suggest nanoceria deposit in lungs, confer protection by quenching noxious free radicals during hypobaric hypoxia, and do not evoke any inflammatory response.