Acute lung injury (ALI) is a critical manifestation of sepsis/septic shock. Heat shock protein A12B (HSPA12B), an endothelial cell-expressed heat shock protein, shows a negative regulation of lipopolysaccharide (LPS)-induced inflammation in myocardium and endothelial cells. However, it is unclear whether HSPA12B exerts protective effects against ALI during sepsis/septic shock. In this study, we treated HSPA12B transgenic mice (Tg) and wild type littermates (WT) with LPS for 6 h to induce endotoxemia. LPS treatment significantly caused pulmonary injuries as evidenced by microarchitecture destruction, vascular leakage and neutrophil recruitment in lungs of WT mice. However, the LPS-induced pulmonary injuries were significantly attenuated in Tg mice. Moreover, the LPS-induced activation of extracellular signal-regulated kinases (ERKs) and upregulation of intercellular adhesion molecule-1 (ICAM-1) and Cyclooxygenase-2 (Cox-2) were inhibited in Tg lungs compared with that in WT mice. Additionally, Tg lungs showed a significant lower level of vascular endothelial growth factor (VEGF) compared with WT mice. Our results demonstrate a pulmonary protective effect of HSPA12B against endotoxin challenge, which indicates management of HSPA12B expression could serve as a potential therapeutic target for ALI during sepsis/septic shock.

It is often difficult to discern true mycobacterial infection from colonization due to Mycobacterium gordonae (. M. gordonae) since this organism is ubiquitous and is commonly an innocuous saprophyte. This study reports a rare case of caseating hilar adenopathy and pulmonary disease caused by M. gordonae in a patient with chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis (RA) on maintenance steroids and methotrexate. Pathologic exam and cultures of lymph node excision biopsy and bronchoalveolar lavage (BAL) confirmed the diagnosis.Triple antimycobacterial therapy with azithromycin, ethambutol and rifabutin was administered. The patient had significant clinical and radiologic improvement and follow-up cultures confirmed microbiologic cure.Mycobacterium gordonae can be a rare cause of significant pulmonary infection, and positive sputum or BAL cultures for M. gordonae should not be automatically discarded and considered as nonpathogenic contaminants or colonizing organisms, especially in immunocompromised hosts with comorbidities. A detailed review of the case and relevant literature is provided.

Lung cancer patients generally experience high levels of physical and psychological distress and decreased quality of life (QOL). Sense of coherence (SOC) has been conceptualized as a personality orientation reflecting the degree to which an individual perceives their world as comprehensible, manageable and meaningful. The present study investigated the associations of SOC with QOL in lung cancer. It also examined potential psychological mediators by which SOC may exert its influences on QOL. Fifty-six participants with non-small cell lung cancer were administered self-report assessments of SOC, QOL and psychological distress. Results revealed that SOC was positively associated with QOL and this relationship may be mediated by depressive symptoms. The current study supports the notion that SOC may be a protective factor with regard to psychological adjustment and QOL in cancer survivors.

We have recently reported that antioxidant liposomes can be used as antidotes for mustard gas induced lung injury in guinea pigs. The maximum protection was achieved with a liposome composed of tocopherols (α, γ, δ) and N-acetylcysteine (NAC) when administered after 5 min of exposure of 2-chloroethyl ethyl sulfide (CEES), a half sulfur mustard gas. We also reported an association of mustard gas-induced lung injury with an activation of MAPK/AP-1 signaling pathway and cell proliferation. The objective of the present study was to investigate whether CEES-induced MAPKs/AP-1 signaling pathway is influenced by antioxidant liposome therapy. A single dose (200 μl) of the antioxidant liposome was administered intratracheally after 5 min of exposure of CEES (0.5 mg/kg). The animals were sacrificed after 1 h and 30 days of CEES exposure. Although the liposome treatment did not have any significant effect on the activation of the MAPKs family (ERK1/2, p38 and JNK1/2), it significantly counteracted the CEES-induced activation of AP-1 transcription factors and corresponding increase in the protein levels of Fos, ATF and Jun family members. The liposome treatment significantly blocked the CEES-induced increase in the protein levels of cyclin D1, a cell cycle protein and PCNA, a cell differentiation marker. Furthermore, it protected lung against CEES-induced inflammation and infiltration of neutrophils, eosinophils and erythrocytes in the alveolar space. This suggests that the protective effect of antioxidant liposome against CEES-induced lung damage is mediated via control of AP-1 signaling.

Background: Although several reports have shown an adverse cardiovascular and metabolic risk profile associated with childhood obesity, few reports have examined the effects of childhood obesity on pulmonary function. Objective: The purpose of this study was to examine the influence of obesity on pulmonary function in Navajo and Hopi children. Methods: Subjects included 256 (110 males, 16 females) Hopi children 6-12 years of age and 557 (274 males, 283 females) Navajo children 6-12 years of age (N=813). The body mass index was used to classify subjects as normal weight, overweight, or obese on the basis of international reference values. Forced vital capacity (FVC), forced expired volume in one second (FEVl), FEV1% (FEV1 to FVC ratio; FEV1/FVC), and forced expiratory flow between 25%-75% of vital capacity (FEF25-75) were determined according to the American Thoracic Society recommendations. Results: Approximately 26% of Navajo and Hopi children were defined as overweight (26.0% of boys and 25.6% of girls) and an additional 16% (14.6% of boys and 17.7% of girls) were defined as obese. In general, the patterns showed an increase in pulmonary function between normal weight and over-weight children and a decrease in pulmonary function of obese children. Significant differences among groups existed for FEV1% and FEF25-75 in boys and FVC and FEV1 in girls. Conclusions: The results indicate the pulmonary consequences of obesity in children and provide further evidence of the adverse consequences, of pediatric obesity among Native Americans.

We tested the hypothesis that oxytocin-induced labor augmented IL-1β-induced/-stimulated lung fluid absorption in preterm guinea pig fetuses. IL-1β was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. At day 3, oxytocin was administered, and fetuses were delivered by abdominal hysterotomy at 61 and by oxytocin-induced birth at 68 days gestation. Delivered fetuses were instilled with isosmolar 5% albumin into the lungs, and lung fluid movement was measured over 1 h by mass balance. Lung fluid absorption was induced in 61-day and stimulated in 68-day gestation lungs by IL-1β. Labor induction by oxytocin augmented IL-1β-induced/- stimulated lung fluid absorption. Metyrapone pretreatment did not affect oxytocin-induced/-stimulated lung fluid absorption, while completely blocking IL-1β-induced/-stimulated fluid absorption. Fetal lung fluid absorption, when present, was always propranolol and amiloride sensitive, suggesting that β-adrenoceptor stimulation and amiloride-sensitive sodium channels were critical for fluid absorption. Epithelial sodium channel and Na-K-ATPase subunit expressions were both increased by IL-1β, but not further by oxytocin. Our results indicate that IL-1β release into the maternal blood circulation positively affects lung maturation due to the IL-1β-induced release of cortisol and thus prepares the lungs for the epinephrine surge associated with labor.

No description available.

If Pulmonary Tuberculosis (PTB) is detected early in a patient, the greater the chances of treating and curing the disease. Early detection of PTB could result in an overall lower mortality rate. Detection of PTB is achieved in many ways, for instance, by using tests like the sputum culture test. The problem is that conducting tests like these can be a lengthy process and takes up precious time. The best and quickest PTB detection method is viewing the chest X-Ray image (CXR) of the patient. To make an accurate diagnosis requires a qualified professional Radiologist. Neural Networks have been around for several years but is only now making ground-breaking advancements in speech and image processing because of the increased processing power at our disposal. Artificial intelligence, especially Deep Learning Convolutional Neural Networks (DLCNN), has the potential to diagnose and detect the disease immediately. If DLCNN can be used in conjunction with the professional medical institutions, crucial time and effort can be saved. This project aims to determine and investigate proper methods to identify and detect Pulmonary Tuberculosis in the patient chest X-Ray images using DLCNN. Detection accuracy and success form a crucial part of the research. Simulations on an input dataset of infected and healthy patients are carried out. My research consists of firstly evaluating the colour depth and image resolution of the input images. The best resolution to use is found to be 64x64. Subsequently, a colour depth of 8 bit is found to be optimal for CXR images. Secondly, building upon the optimal resolution and colour depth, various image pre-processing techniques are evaluated. In further simulations, the pre-processed images with the best outcome are used. Thirdly the techniques evaluated are transfer learning, hyperparameter adjustment and data augmentation. Of these, the best results are obtained from data augmentation. Fourthly, a proposed hybrid approach. The hybrid method is a mixture of CAD and DLCNN using only the lung ROI images as training data. Finally, a combination of the proposed hybrid method, coupled with augmented data and specific hyperparameter adjustment, is evaluated. Overall, the best result is obtained from the proposed hybrid method combined with synthetic augmented data and specific hyperparameter adjustment. / Electrical and Mining Engineering

Contexte : Le cancer du poumon est le cancer le plus associé aux expositions professionnelles. Bien que l’amiante soit sans doute le facteur étiologique professionnel le plus connu, plusieurs éléments suggèrent également l’implication de facteurs modifiables d’origine environnementale ou professionnelle, beaucoup plus rarement étudiés, parmi lesquels les agents biologiques. Si les endotoxines - toxines situées dans la membrane externe des bacilles Gram négatif - sont fréquemment associées à une réduction du risque de cancer du poumon, les infections à papillomavirus humains sont suspectées d’augmenter ce risque. Les résultats des études épidémiologiques sur le sujet sont divergents et sont régulièrement limités par de nombreuses faiblesses méthodologiques incluant entre autres la non prise en compte du tabagisme et de l’exposition à l’amiante.Objectifs : L’objectif de cette thèse est d’étudier le rôle des agents biologiques présents sur les lieux de travail dans la survenue des cancers broncho-pulmonaires. Plus spécifiquement, les objectifs de ce travail sont : (1) d’étudier le rôle de l’exposition professionnelle aux endotoxines sur le risque de cancer du poumon, d’évaluer les aspects de la relation dose-effet ainsi que les interactions possibles avec les antécédents des maladies respiratoires; (2) de s’intéresser plus particulièrement à l’industrie textile, source de fortes expositions aux endotoxines, en étudiant le risque de cancer du poumon associé à l’exposition professionnelle aux poussières textiles ; (3) d’étudier le risque de cancer du poumon dans l’industrie de la viande en testant, notamment l’hypothèse d’une exposition à un agent viral.Population et méthodes : Ce travail s’est appuyé sur les données de l’étude cas-témoins en population générale ICARE. Les cas de cancer du poumon ont été identifiés dans 10 départements français abritant un registre général de cancer. Au total, 2276 cas de cancer du poumon et 2780 témoins hommes ont été inclus ainsi que 650 cas de cancers du poumon et 775 témoins femmes. Les descriptions détaillées de l’histoire professionnelle complète recueillies par des questionnaires standardisés ont permis de coder les professions et les secteurs d’activités de chaque emploi selon les classifications CITP 1968 et NAF 2000.Résultats : Nous avons trouvé une association inverse entre les expositions professionnelles aux endotoxines et le risque de cancer du poumon particulièrement plus marquée chez les travailleurs de l’élevage (tous types) et de la collecte et traitements des déchets. Les odds ratios de cancer du poumon diminuent avec la durée et l’indice cumulé d’exposition aux endotoxines. Nos résultats ne soutiennent pas l'existence d'une forte association entre l'exposition professionnelle aux poussières textiles et le cancer du poumon, néanmoins, ils montrent une diminution significative de 30% du risque de cancer du poumon chez les travailleurs du coton avec OR= 0,7 ; IC 95% [0,5-0,9]. Par ailleurs, nous observons une association positive significative avec le risque de cancer du poumon chez les travailleurs de l’industrie de la viande (OR= 1,46 [1,0-2,1]). Cependant, les antécédents de verrues de la main ne semblent pas avoir d’effet modificateur dans l’association entre le travail dans l’industrie de la viande et le risque de cancer du poumon.Conclusion : Nos résultats soutiennent le rôle important des expositions professionnelles comme déterminants du risque de cancer du poumon. Ils confirment les associations inverses entre les expositions aux endotoxines et le risque de cancer du poumon suggérant fortement l’hypothèse d’un effet anti-tumoral des endotoxines vis-à-vis du poumon. Par ailleurs, ils semblent indiquer que le travail dans l’industrie de la viande est une situation d’exposition à risque de cancer du poumon sans toutefois conclure formellement quant à l’implication des infections à papillomavirus humains. / Background: Lung cancer is the most common cancer associated with occupational exposures. Although asbestos is the best known occupational etiologic factor, several hypotheses suggest the involvement of some environmental or occupational modifiable factors, much more rarely studied, including biological agents. Endotoxins-toxins being part of the outer membrane of Gram-negative bacilli- are commonly associated with reduced risk of lung cancer, while human papillomavirus infections are suspected of increasing the risk. However, the majority of published studies had small numbers of cases and some methodological issues such as inadequate adjustment for tobacco smoking and occupational exposure to asbestos.Objectives: The aim of the present work is to study the role of biological agents found in the workplace on lung cancer risk and more specifically: (1) to investigate the role of occupational exposure to endotoxins on lung cancer risk, to assess dose-response relationship aspects and possible interactions with history of respiratory disease; (2) to focus on the textile industry, which is a source of high exposure to endotoxins, by examining the risk of lung cancer associated with occupational exposure to textile dust; (3) to study the risk of lung cancer in the meat industry by testing the hypothesis of an exposure to a viral agent.Population and methods: This work was based on a large population-based case-control study, ICARE. Cases and controls were recruited from 10 French departments. Incident cases were identified through French cancer registries. A total of 2,926 lung cancer cases (2,276 men and 650 women) and 3,555 controls (2,780 men and 775 women) were included. Detailed information on lifetime occupation was collected through standardized questionnaires. Jobs and sectors were coded according to the ISCO 1968 and the NAF 2000 classifications.Results: Our results showed an inverse association between exposure to endotoxins and lung cancer risk particularly among livestock (all types) and waste collection and treatment workers. Negative trends were shown with duration and cumulative exposure. Furthermore, our findings do not the existence of strong association between occupational exposure to textile dust and lung cancer. A decreased risk was suggested for distant exposures and for work with cotton fibres (OR = 0.7; 95% CI [0.5-0.9]). On the other hand, we observe a significantly increased risk among meat workers OR = 1.46 [1.1-2.1]). However, the history of hand warts does not seem to have any modifying effect on the association between work in the meat industry and the risk of lung cancer.Conclusion: Our findings support the important role of occupational exposures as a determinant of lung cancer risk. This confirms the inverse associations between endotoxin exposures and the risk of lung cancer strongly suggesting an anti-tumor effect of endotoxins towards the lung. This also seems to indicate that working in the meat industry is a risky situation for lung cancer without, however, formally concluding about the involvement of human papillomavirus infections.

Polycyclic aromatic hydrocarbons (PAHs) comprise an important class of environmental pollutants that are known to cause lung cancer in animals and suspected lung carcinogens in humans. PAHs are also known to cause cancer in offspring when provided to a pregnant mouse. Some evidence from cell-based studies points to PAHs as modulators of the epigenome, that is modifications to DNA structure that control the expression of genes. Inappropriate changes to the epigenome and consequently expression of cancer-critical genes are often characteristic of cancer cells. The objective of this thesis research was to determine the impact of transplacental exposure to two model PAHs on the epigenome of fetal and adult lung tissues in offspring. Specifically, we measured patterns of methylation of DNA, a type of epigenetic mark, in different types of lung tissue to assess changes in the epigenome associated with development of lung cancer. Two strategies were employed: 1) a targeted approach using ultra-deep bisulfite sequencing to precisely measure the specific pattern of methylated sites in the promoter regulatory region for several tumor suppressor genes, including Cdkn2a, Rarb, Dapk1 and Mgmt; and 2) a broad, genome-wide approach using a microarray covering all regulatory promoter regions in the entire mouse genome. Our first approach did not yield any marked differences in methylation patterns for any of the target genes for lung tissues obtained at birth or at various ages up to 45 weeks, nor according to the type of tissue (normal, pre-neoplastic, tumor). However, the genome-wide approach did yield specific patterns of methylation in lung tumors, including distinct profiles associated with lung tumor tissue from PAH-exposed animals that were substantially different from normal lung tissue in control animals. Altogether, the research presented here identified several new target genes of interest for future studies investigating the epigenetics of PAHinitiated lung cancer. This work also provided new knowledge that exposure to PAHs can lead to distinct DNA methylation profiles in lung tumors in adult offspring.