Littérature scientifique sur le sujet « Luns »

Recensión: Héctor Cajaraville Araújo, Os xogos de palabras na prensa gratuíta en galego: De Luns a Venres, Santiago de Compostela: Universidade de Santiago de Compostela, Servizo de Publicacións e Intercambio Científico, 2015, 216 páxinas.

BackgroundEvidence-based care pathways are required to support stroke patients and their carers in the longer term.AimsThe twofold aim of this programme of four interlinking projects was to enhance the care of stroke survivors and their carers in the first year after stroke and gain insights into the process of adjustment.Methods and resultsWe updated and further refined a purposely developed system of care (project 1) predicated on a patient-centred structured assessment designed to address areas of importance to patients and carers. The structured assessment is linked to evidence-based treatment algorithms, which we updated using a structured protocol: reviewing available guidelines, Cochrane reviews and randomised trials. A pragmatic cluster randomised controlled trial evaluation of the clinical effectiveness and cost-effectiveness of this system of care was undertaken in 29 community-based UK stroke care co-ordinator services (project 2). In total, 15 services provided the system of care and 14 continued with usual practice. The primary objective was to determine whether the intervention improved patient psychological outcomes (General Health Questionnaire-12) at 6 months; secondary objectives included functional outcomes for patients, outcomes for carers and cost-effectiveness, as measured through self-completed postal questionnaires at 6 and 12 months. A total of 800 patients and 208 carers were recruited; numbers of participants and their baseline characteristics were well balanced between intervention and control services. There was no evidence of statistically significant differences in primary or secondary end points or adverse events between the two groups, nor evidence of cost-effectiveness. Intervention compliance was high, indicating that this is an appropriate approach to implement evidence into clinical practice. A 22-item Longer-term Unmet Needs after Stroke (LUNS) questionnaire was developed and robustly tested (project 3). A pack including the LUNS questionnaire and outcome assessments of mood and social activity was posted to participants 3 or 6 months after stroke to assess acceptability and validity. The LUNS questionnaire was re-sent 1 week after return of the first pack to assess test–retest reliability. In total, 850 patients were recruited and the acceptability, validity and test–retest reliability of the LUNS questionnaire as a screening tool for post-stroke unmet need were confirmed. This tool is now available for clinical use. An in-depth qualitative investigation was undertaken with 22 patients (and carers) at least 1 year after stroke (project 4) to gain further insights into the experience of adjustment. This included initial semistructured interviews, limited observations and solicited diaries with a follow-up interview 3–4 months after the initial interview and highlighted a range of different trajectories for post-stroke recovery.ConclusionsThe programme has been completed as planned, including one of the largest ever stroke rehabilitation trials. This work highlights that successfully addressing the needs of a heterogeneous post-stroke population remains problematic. Future work could explore stratifying patients and targeting services towards patients (and carers) with specific needs, leading to a more specialised bespoke service. The newly developed LUNS questionnaire and the qualitative work will help inform such services.Trial registrationCurrent Controlled Trials ISRCTN67932305.FundingThe National Institute for Health Research (NIHR) Programme Grants for Applied Research programme. The Bradford Teaching Hospitals NHS Foundation Trust received additional funding for project 2 in the submitted work from the Stroke Association, reference number TSA 2006/15. The initial development work for the LUNS tool and the Longer-Term Stroke care (LoTS care) trial carried out before the start of the programme grant was funded by the Stroke Association, reference number TSADRC 2006/01.

Flash-based storage is replacing disk for an increasing number of data center applications, providing orders of magnitude higher throughput and lower average latency. However, applications also require predictable storage latency. Existing Flash devices fail to provide low tail read latency in the presence of write operations. We propose two novel techniques to address SSD read tail latency, including Redundant Array of Independent LUNs (RAIL) which avoids serialization of reads behind user writes as well as latency-aware hot-cold separation (HC) which improves write throughput while maintaining low tail latency. RAIL leverages the internal parallelism of modern Flash devices and allocates data and parity pages to avoid reads getting stuck behind writes. We implement RAIL in the Linux Kernel as part of the LightNVM Flash translation layer and show that it can reduce read tail latency by 7× at the 99.99th percentile, while reducing relative bandwidth by only 33%.

In order to survey arenaviruses in the Republic of Zambia, we captured 335 rodents from three cities between 2010 and 2011. Eighteen Luna virus (LUNV) and one lymphocytic choriomeningitis virus (LCMV)-related virus RNAs were detected by one-step RT-PCR from Mastomys natalensis and Mus minutoides, respectively. Four LUNV strains and one LCMV-related virus were isolated, and the whole genome nucleotide sequence was determined by pyrosequencing. Phylogenetic analyses revealed that the LUNV clade consists of two branches that are distinguished by geographical location and that the LCMV-related virus belongs to the LCMV clade, but diverges from the typical LCMVs. Comparison of nucleoprotein amino acid sequences indicated that the LCMV-related virus could be designated a novel arenavirus, which was tentatively named as the Lunk virus. Amino acid sequences of the GP, NP, Z and L proteins showed poor similarity among the three Zambian arenavirus strains, i.e. Luna, Lunk and Lujo virus.

Francien van Anrooij, De koloniale staat 1854-1942; Gids voor het archief van het ministerie van Koloniën; De Indonesische archipel. Jan Derix, Brengers van de Boodschap; Geschiedenis van de katholieke missionering vanuit Nederland van VOC tot Vaticanum II. Bert L.T. van der Linden, Nou… tabé dan!; De ‘bootreis’ naar Indië met de Rotterdamsche Lloyd en de ‘Nederland’ tussen 1899 en 1949. Harm Stevens, Jos Stoopman en Pauljac Verhoeven (red.), De laatste Batakkoning; Koloniale kroniek in documenten 1883-1911. Meta Knol, Remco Raben en Kitty Zijlmans (red.), Beyond the Dutch; Indonesië, Nederland en de beeldende kunsten van 1900 tot nu. Hans van Wessel (eindredactie), Indische sporen; Bronnen voor lerarenopleiders. Van Nederlandsch Indië tot Indonesië. Samenstelling Hans van den Berg. 2 dvd’s, 222’. Nederlands-Indië in de Tweede Wereldoorlog. Samenstelling René Kok. Strijd om Indië; Het Nederlands-Indonesische conflict 1945-1949. Samenstelling René Kok Sjahrir, een grondlegger van het onafhankelijke Indonesië; Soetan Sjahrir 1909-1966. Den Haag: Stichting Vrienden van Linggadjati. Rita Young en Zwaan de Vries, Oorlog en overleven buiten Japanse kampen; Drie generaties vertellen… Beatrijs van Agt, Florine Koning, Esther Tak en Esther Wils, Het verborgen verhaal; Indische Nederlanders in oorlogstijd 1942-1949. Florine Koning, De Pasar Malam van Tong Tong, een Indische onderneming. Piet Sanders, Herinneringen. Wouter Meijer, ‘Ze zijn gék geworden in Den Haag’; Willem Oltmans en de kwestie Nieuw-Guinea. Edwin Oden, De man van 8 miljoen; Vriend & vijand over het fantastische leven van Willem Oltmans 1925-2004. Albert Kersten, met medewerking van Frits Bergman, Luns, een politieke biografie. Jacob Vredenbregt, Terugzien en nakaarten; Zestig jaar ooggetuige in Indonesië. Melati van Java, Fernand. Met een inleiding van Vilan van de Loo. Annie Foore, Bogoriana; Roman uit Indië. Met een inleiding van Vilan van de Loo. Mina Kruseman, Een huwelijk in Indië. Met een inleiding van Vilan van de Loo.

BackgroundThe identification of novel therapeutic targets in lung cancer for the generation of targeted drugs is an urgent challenge. Lung-specific X (LunX) is a member of the palate, lung, and nasal epithelium clone (PLUNC) protein family. Some reports have suggested that the human PLUNC gene (also named LUNX) might be a potential marker for NSCLC, and PLUNC mRNA has been identified in peripheral blood and mediastinal lymph nodes from NSCLC patients.It is unclear whether LunX expression is associated with the pathological type and pathological severity in lung cancer patients. The utility of LunX as a potential therapeutic target in NSCLC is uncertain.MethodsClinically, 80% of lung cancers are non-small-cell lung cancers (NSCLCs). Here, we analyzed 158 NSCLC samples and detected LunX expression.ResultsIt showed that the expression of LunX were elevated in 90% (108/150) lung cancers by IHC staining, which accompanied with significantly lower rate of postsurgery survival. Further evaluation of LunX expression in invasive tumor cells in subclavicular lymph nodes, draining lymph nodes, hydrothorax of lung cancer patients, turned out that LunX is highly expressed in invasive lung cancer cells. These data indicated that LunX overexpresses in lung cancer and associates with tumorigenesis and tumor progression.Mechanistically, we discovered that LunX bound to 14-3-3 protein and facilitated their activation by maintaining these proteins in a dephosphorylated state, thereby contributing to the activation of pathways downstream of 14-3-3 protein, such as the Erk1/2 and JNK pathways. Thus, LunX promoted tumor growth and metastasis.Furthermore, we generated a therapeutic antibody specific for lung cancer, which not only inhibited lung cancer growth and reduced Ki67 staining and angiogenesis in xenograft model of subcutaneously transplanted tumor, but also blocked tumor metastasis and invasion, improved the survival of these mice. We also detected that antibody treatment induces LunX antigen-antibody complex endocytosis and the degradation of LunX protein.ConclusionsOur study suggests that LunX is a novel therapeutic target in lung cancer and that the LunX-targeted therapeutic antibody may have considerable clinical benefit.

It's difficult to detect lung cancer and determine the severity of the disease without a CT scan of the lungs. The anonymity of nodules, as well as physical characteristics such as curvature and surrounding tissue, suggest that CT lung nodule segmentation has limitations. According to the study, a new, resource-efficient deep learning architecture dubbed U-INET is required. When a doctor orders a computed tomography (CT) scan for cancer diagnosis, precise and efficient lung nodule segmentation is required. Due to the nodules' hidden form, poor visual quality, and context, lung nodule segmentation is a challenging job. The U-INET model architecture is given in this article as a resource-efficient deep learning approach for dealing with the problem. To improve segmentation operations, it also includes the Mish non-linearity functions and mask class weights. Furthermore, the LUNA-16 dataset, which included 1200 lung nodules, was heavily utilized to train and evaluate the proposed model. The U-INET architecture outperforms the current U-INET model by 81.89 times and reaches human expert level accuracy.

The generation of oxygen free radicals by the cytosolic enzyme, xanthine oxidase (XO), has been implicated in post-ischemic or reperfusion damage in several organs. XO catalyzes the conversion of hypoxanthine to urate with the concomitant production of superoxide anion free radical (0₂̅˙) and hydrogen peroxide (H₂O₂). Oxygen free radical-mediated injury has also been demonstrated in inflammatory lung disease. The possible involvement of XO in oxidative injury in the lung has not yet been studied. Therefore, this research project was designed to determine whether XO is present in the lung and to investigate its characteristics in porcine, bovine, rat and human lung and other tissues. Immunochemical analysis of xanthine oxidase in the tissues employed on polyclonal antibody raised to bovine milk XO. Proteins were separated by SDS-polyacrylamide gel electrophoresis of tissue homogenates. Proteins were transfered from the gels to nitrocellulose filters by Western blotting. After incubating the filters with a antisera containing the antibody to the purified bovine XO. XO on the filter was detected by its reaction with an enzyme-conjugated second antibody. XO was immunologically detectable in bovine lung and milk. Rat lung, kidney and liver all showed XO reactivity. XO was detectable in porcine liver but not detectable in porcine lung or kidney. Thus, the antibody to bovine XO was cross-reactive with porcine and rat XO. XO protein was not immunologically detectable in human lung possibly because the antibody was not cross reactive with the bovine antibody. In vivo, xanthine oxidase exists predominantly as a dehydrogenase rather than an oxidase. In this form as xanthine dehydrogenase (XDH) the enxyme does not produce either 0₂̅˙ or H₂O₂. The activity of both XDH and XO was measured in several tissues using a fluorometric assay which uses an artifical substrate, pterin which is catalytically converted to the fluorescent product isoxanthopterin (IXP). XO activity in porcine liver was of 1.1 x 10⁻³ µg IXP/mg protein/min although XO activity was not detectable in porcine lung and kidney, in rat lung of 1.7 x 10⁻² µg IXP/mg protein/min, rat kidney of 1.5 x 10⁻² µg IXP/mg protein/min, and rat liver of 2.2 x 10⁻² µg IXP/mg protein/min. Seven human lung biopsy samples were obtained after lung resection and initially tested for viability by determination of NADH oxidase activity and then assayed for XO-XDH. Three of these samples showed NADH oxidase activity indicating tissue viability, but only one of these three showed measurable XO activity of 5.35 x 10⁻⁶ µg IXP/mg protein/min. Irreversible conversion of XDH to XO is thought to be the result of limited proteolysis by a Ca²⁺/calmodulin activated protease, whereas reversible conversion of the enzyme occurs by oxidation of critical thiol groups. Studies on the rate and nature of fluorescence assay to detect catalytic activities of both enzyme forms. Incubation of lung homogenates with trypsin for 60 min caused irreverisble conversion of 90% of the XDH to XO. In contrast, incubation of homogenates at 15°C for 10 hours caused conversion of 100% of the XDH to XO. This conversion was reversible to the extent of 80% by reduction of thiol groups with dithiothreitol (DTT). The effects of free Ca²⁺ on the conversion of XDH to X0 was examined by using EDTA, a chelator of Ca²⁺ and other divalent cations; and EGTA, a more specific chelator of Ca²⁺. The presence of these chelating agents during homogenization of either normoxic or ischemic rat lung tissue did not inhibit reversible enzyme conversion. Increased XO activity was reversible by DTT. In the normoxic rat lung, homogenates prepared with EDTA and EGTA showed a similar conversion of 95% of XDH to XO which was reversible to 70% with DTT. In the ischemic rat lung, samples prepared with EDTA and EGTA showed a'conversion of 80% and 95% XDH to XO which was similar to control samples. The extent of reversibility to XDH was 75% with DTT incubation. In addition, perfusion of rat lungs with EDTA and DTT via a pulmonary artery cannula prior to 60 min of ischemia and homogenization did not affect the extent of XDH to XO conversion. These results indicate that irreversible Ca²⁺-mediated proteolytic conversion of XDH to XO does not occur to a great extent in the rat lung during either normoxia or ischemia. However, reversible conversion of XDH to XO does occur, suggesting that reversible thiol dependent conversion may play a role in the lung under both physiological and pathophysiological states.
Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate

Infants with bronchopulmonary dysplasia (BPD), showed impaired body growth when compared to control infants. In terms of changes in the biochemical composition of the lung, BPD infants had higher DNA, soluble protein, collagen and desmosine contents as well as increased concentrations of DNA, collagen and desmosine in their lungs when compared to the growth patterns obtained for the lungs of control infants. Pathologically BPD was classified into 4 grades. Grade I BPD, was a phase of acute lung injury, grades II and III were proliferative phases. In grade IV BPD, lung structure returned towards normal. Evidence of fibrosis was seen by a significant increase in collagen concentration in grades II and III while desmosine concentration was seen to increase in grades III and IV suggesting that the increase in collagen and desmosine contents in the lungs of BPD infants may be controlled by two different mechanisms. Collagen type I/III ratio was seen to decrease progressively from grade II to grade IV BPD in comparison to age matched controls, indicating a higher proportion of type III collagen in the lungs of infants with BPD. From the clinical analysis and the results obtained from discriminant analysis procedure, it was seen that there was a high degree of correlation between the continuation of the disease and collagen accumulation in the lungs suggesting that pulmonary fibrosis with excessive collagen accumulation is an integral part of BPD. This fibrotic process seemed to correlate significantly with assisted ventilation and high oxygen supplementation received by the infants, but it was difficult to assess the individual contribution of the two treatments in the pathogenesis of BPD. Other variables such as severity of the initial disease and the length of survival of the infants, made the assessment of individual contribution much more difficult.
Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate

Introduction: CF (cystic fibrosis) and PCD (primary ciliary dyskinesia) are obstructive airway diseases characterised by frequent infections and neutrophilic inflammation. However, PCD has a much milder course than CF. Pilot data showed that in PCD (n=8) the relationship between LCI (lung clearance index) derived from multiple breath washout (MBW), and FEV1 (forced expiratory volume in 1 second) differed from the established correlation in CF. This thesis sought to identify the reasons. Materials and Methods: Larger PCD (n=38) and CF cohorts (n=125), a non-CF bronchiectasis comparator group (n=28), and healthy controls (n=44) were recruited. All performed LCI and spirometry, and subgroups had more complex MBW parameters (conventional and modified phase III analysis and curvilinearity) calculated and HRCT scans scored. Results: As in the pilot data, there was no relationship between LCI and FEV1 in PCD, unlike in CF. PCD patients had fewer structural abnormalities than CF despite similar or worse spirometry and LCI, and the relationship between HRCT and spirometry or LCI in PCD was again different from that seen in CF. MBW analyses showed that Scond* is near-normal in PCD, suggesting less flow asynchrony, compared with CF. Conclusions: There are differences in the nature of distal airway disease between PCD and CF. As the non-CF bronchiectasis patients were similar to CF (rather than PCD), this likely results from the primary mucociliary clearance defect in PCD compared with secondary impairment in the other two conditions. This may be important as care of PCD patients is extrapolated from that of CF patients, which may not be appropriate. It is important not to extrapolate outcome measures uncritically between different disease groups, both clinically and when planning randomised controlled trials. Finally, a better understanding of what causes the better prognosis in PCD may help identify future new treatment avenues in CF.

This study examined the effects of epinephrine, norepinephrine, AVP and ACh on fluid movement by the lungs of the late-term guinea pig fetus. Catecholamines and AVP are secreted in high amounts by the fetus during delivery, and could be important with respect to fetal lung fluid removal; this event is vital at the time of birth. The lungs were supported in vitro for a duration of three hours, and production rates were measured using a dye-dilution technique. The average resting production rate in terms of ml/kg‧h declined with gestational age (54-67 days gestation; n=171). There was a lesser decline in the average resting production rate in terms of ml/h. The average production rate of untreated preparations in the first hour was 1.60 ± 0.26 ml/kg body weight per hour, and rates did not change significantly during the remaining two hours of experimentation (n=30). This rate is comparable to those reported from chronically catheterized fetal sheep. Treatment was administered during the second hour of experimentation, following an ABA design. Lungs (n=36) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of epinephrine: (a) 10‾⁵ M; (b) 10‾⁶ M; (c) 10‾⁷ M; (d) 5 x 10‾⁸ M; (e) 10‾⁸ M; and (f) 10‾⁹ M. With the exception of the top dose, epinephrine treatment caused an immediate reduction in fluid secretion, or fluid reabsorption. Sodium followed the movement of water in all cases. The effect of epinephrine at 10‾⁷ M was maximal, and the threshold dose for epinephrine was calculated at 1.78 x 10‾¹¹ M. Phentolamine and propranolol had no effect in control preparations. However, phentolamine completely blocked the effect of epinephrine, whereas propranolol was ineffective. Isoproterenol had no effect on pulmonary fluid production. Alpha-adrenergic receptors apparently mediate the effect of epinephrine on pulmonary fluid movement in the fetal guinea pig lung. This conclusion is different from that obtained in fetal sheep, in which beta-adrenergic receptors are utilized. A possible synergism between epinephrine and AVP was examined. Lungs (n=12) were transferred to fresh Krebs-Henseleit saline containing either (a) 0.6 mU/ml AVP, or b) 0.6 mU/ml AVP combined with epinephrine at 10‾⁷ M. Treatment with AVP caused a slow, prolonged reduction in fluid production. Treatment with AVP together with epinephrine did not demonstrate synergism. The effect of norepinephrine (NE) was examined. Lungs (n=36) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of NE: (a) 1.24 x 10‾⁵ M; (b) 1.24 x 10‾⁶ M; (c) 1.24 x 10‾⁷ M; (d) 5.24 x 10‾⁸ M; (e) 1.24 x 10‾⁸ M; and (f) 1.24 x 10‾⁹ M. In all preparations, treatment with NE resulted in an immediate reduction in fluid production, and reabsorptions were observed at the higher doses. Sodium followed the movement of water in every case. The threshold dose was calculated at 3.16 x 10‾¹⁰ M. Phentolamine blocked the effect of NE, reinforcing the importance of pulmonary alpha-adrenergic receptors in the fetal guinea pig. There was no relationship between age and degree of response with treatment of either epinephrine or NE, but fetuses under 78.0 g did not respond to NE. The effect of ACh was examined. Lungs (n=24) were transferred to fresh Krebs-Henseleit saline containing one of the following concentrations of ACh: (a) 10‾⁴ M; (b) 10‾⁵ M; (c) 10‾⁶ M; and (d) 10‾⁸ M. At the three top doses, immediate and powerful reabsorptions of pulmonary fluid were observed in older fetuses (60 days gestation and above); significant falls were observed in the younger fetuses. This result was unexpected, as it was hypothesized that ACh would stimulate fluid production. The threshold dose for ACh was between 10‾⁶ M and 10‾⁸ M. Phentolamine blocked the effect of ACh. This result suggested that reabsorption is a result of an indirect effect of ACh acting through pulmonary alpha receptors. The results in this study show that epinephrine, NE, AVP and ACh are all important promoters of fetal pulmonary fluid removal in the fetal guinea pig. Pulmonary alpha-adrenergic receptors mediate the effects of epinephrine, NE and ACh (indirectly). The conclusions drawn from this study emphasize the importance of species' comparison in fetal research. LIST OF ABBREVIATIONS AVP Arginine Vasopressin NE Norepinephrine DOPA dihydroxyphenylalanine PNMT Phenylethanolamine n-methyltransferase ACh Acetylcholine
Science, Faculty of
Zoology, Department of
Graduate

This study was designed to gain an understanding of the family experience when an adult member has chronic obstructive pulmonary disease (COPD). It is recognized that illness within the family affects the well-being of the family unit and the health of all members. To understand the impact of COPD upon the family, however, the literature provides only knowledge of the experience of the individual who has COPD and the spouse, not that of the family unit. Thus, the purpose of this study was to describe and explain the COPD experience from the perspective of the family unit. A qualitative method, phenomenology, was chosen for this investigation. Data were collected through semi-structured interviews with eight families who shared their experiences. From the content analysis of these data, three themes that were common throughout the families' accounts were identified and developed to describe and explain family life with COPD. The first theme, disease-dictated family life, describes four aspects of a common lifestyle that is imposed on the family by the characteristics of COPD. The second theme, isolation, describes the isolation that accompanies the illness experience, for the family group and the individual members within the group. The final theme, family work, describes the four primary challenges the families face and the coping strategies they use to deal with them. These findings revealed that COPD acts as an intense stressor within the family, requiring extensive family work to cope with COPD in a way that maintains the well-being of the family unit. Furthermore, it was found that living with COPD in many ways inhibits the resources within the family and those external sources of support that foster the family's ability to manage the stress associated with living with COPD. The implications for nursing practice and nursing research were delineated in light of the research findings.
Applied Science, Faculty of
Nursing, School of
Graduate

The aim of this thesis is a data transfer protocol implementation for a mobile control unit for transporting lungs. Apart from this thesis the data transfer protocol is used in AlveoPic project. The introductory part is focused on an anatomical and physiological background of a human respiratory system. Consequently it describes the i-Lung module and the mobile circulation module (MCM). It deals with the healthcare informatics interoperability standards with an emphasis to the ISO/IEEE 11073 standard. The subsequent part is represented by MCM’s simulator realization and design of a monitoring application. The final part aims at an analysis of the test cases for a monitoring application’s and a protocol framework’s control.

Dissertation (PhD)--University of Stellenbosch, 2003.
ENGLISH ABSTRACT: Background to the study OLA can give rise to certain problems: 1. A significant decrease in lung volume is reported to occur in the dependent lung during OLA in the LDP. This decrease in lung volume can result in an acute increase in opposition to RV ejection. The potential problem is that the right ventricle is a thin walled structure that can generate considerably less work than the thicker walled LV. It possesses little reserve to deal with an acute rise in afterload as may occur during acute lung injury or after lung resection. Therefore, this increase in afterload during OLA may potentially impair RV-PA coupling. Albeit this potential problem exists, the changes in RV afterload and how the right ventricle performs during OLA have not been well studied. 2. Arterial hypoxemia, due mainly to venous blood being shunted via the non-ventilated lung, may present a clinical problem during one lung ventilation. a. The relative resistances of the pulmonary vascular beds of the dependent ventilated and nondependent non-ventilated lungs are an important factor governing shunting and thus arterial oxygenation during one lung anesthesia. A high non-ventilated lung PVR and low ventilated lung PVR will facilitate good arterial oxygenation during OLA. An increase in non-ventilated lung PVR is governed predominantly by hypoxic pulmonary vasoconstriction. A low opposition to pulmonary blood flow in the dependent lung is facilitated predominantly by a high alveolar oxygen tension and normal lung volume, albeit other factors also play a role in this regard. b. The saturation and oxygen content of mixed venous blood will contribute significantly to the arterial oxygenation in the presence of a large shunt as occurs during OLA. i. On the one hand, venous desaturation as a cause of hypoxemia during one lung anesthesia has not as yet been systematically addressed in the literature. ii. On the other hand, if RV afterload increases to such a degree that it leads poor RV performance, this may cause impairment of global circulatory efficiency and lead to mixed venous desaturation. The question that has been raised is whether inotrope infusions could improve RV and LV performance, cardiac output, and thereby the efficiency of the circulation. Increases in the efficiency of the circulation will result in an improvement in mixed venous and arterial oxygenation in the presence of a large shunt. Nonetheless, the administration of inotrope infusions in the presence of a shunt and during OLA has been reported to aggravate hypoxemia. Thus at the time of conducting the study, conflicting reports of whether increasing cardiac output and thereby mixed venous oxygenation would increase or decrease arterial oxygenation during OLA In the light of the above, the researcher thus investigated RV afterload, RV performance and coupling to its load during OLA. The study also addressed the question whether different levels of inotrope infusion or PEEP hadbeneficial or deleterious effects on RV afterload, RV performance and coupling to its load during OLA. Furthermore, if cardiac output increased during OLA secondary to the infusion of inotropes, would this improve the efficiency of the circulation, mixed venous oxygenation and thus the arterial oxygenation during OLA, or would it worsen shunt and arterial oxygenation during OLA? Control group: OLA and the opposition to pulmonary flow Pulmonary arterial elastance increased by between 18 to 36% during OLA and mean PAP rose by 32% after initiation of OLA This increase in mean PAP on initiation of OLA is greater than that observed by certain investigators but similar to that seen previously in patients with damaged lungs. The question arose as to why pulmonary artery pressure rises during OLA? From consideration of Ohm’s law, pressure may be regarded as the product of flow and resistance (Mark, Slaughter et al. 2000). The increase in mean PAP during OLA is due to two reasons. 1. Firstly, the pressure versus flow curve is likely to be steeper during OLA. This is because pulmonary vascular recruitment and dilatation (pulmonary vascular reserve) is more limited in scope in these patients than is usual and most likely accounts for the increase in pulmonary artery pressure during OLA. The reasons for the limited pulmonary vascular reserve in the DL during OLA include: a. The pulmonary vascular bed of patients subjected to OLA is frequently abnormal because of its underlying pathology, b. During OLA in the lateral decubitus position, lung volume decreases to a greater degree than during two-lung anesthesia (Klingstedt, Hedenstierna et al. 1990). c. This decrease in lung volume will be further aggravated by DLT malpositions, secretions and blood, and absorption atelectasis due to the use of high concentrations of oxygen (Hedenstierna 1998; Krucylak, Naunheim et al. 1996). d. Excessive amounts of extrinsic or intrinsic PEEP during OLA can compress the intra-alveolar capillaries and deleteriously affect the pulmonary vascular resistance (Ducros, Moutafis et al. 1999; Inomata, Nishikawa et al. 1997; Bardoczky, Yernault et al. 1996; Yokota, Toriumi et al. 1996). 2. Secondly, there is greater flow through this vascular bed that possesses a higher resistance. It is noteworthy that the increase in mean PAP did not exceed a value of 25 mm Hg during OLA, even though cardiac output increased by 30%. However, in studies conducted in patients with “damaged lungs”, greater increases in PA pressure (accompanied by a decrease in RVEF) have been reported to occur on PA ligation. A question arises as to why differences exist between PA clamping and OLA? The answer may well be that the observed plateau in the rise of PA pressure during OLA is as a result of progressive diversion of flow to the NDL as PA pressure rises. Support for such a suggestion comes from the observation that concomitant with increases in PA pressure during OLA, HPV is progressively inhibited and shunt fraction progressively rises. This increase in shunt fraction that has been observed to occur as PA pressure rises, reflects an increase in diversion of pulmonary blood flow to the NDL. The impact of diversion of this blood to the NDL is that it possibly acts as a safety mechanism limiting increases in PA pressure and other indices of opposition to pulmonary flow during OLA. This “blow-off effect” will protect the RV until PA clamping occurs.Control group: OLA and RV function The current study represented the opportunity to investigate the significance of the abovementioned increases in PA pressures and elastance on RV performance during OLA. The current study indicates that at the moderate (30%) increases in PAP that accompanied the initiation of OLA, RV performance, as judged by stroke volume, cardiac index, RVEF and RVSWI, did not deteriorate compared to the baseline awake status. In fact, cardiac output increased following surgical incision: this was probably due to sympathetic nervous system stimulation. This observation also fits in with other studies in which RV performance usually only begins to deteriorate when indices of opposition to RV ejection reach 200 to 250% of baseline. Furthermore, a constant preload, as indicated by unchanged central venous and pulmonary artery wedge pressures, and right ventricular end-diastolic volumes were observed throughout the study period. In other words, this increase in RV afyterlad did not cuse the RV to dilate durign OLA. The relationship between stroke work and afterload will vary, depending on the contractile reserve of the ventricle. In this regard, it could be concluded that under the conditions operative in the current study, the RV was operating on the upslope of the RVSWI versus Ea relationship. This supports the observation that RV function is well preserved during OLA. In conclusion, regarding the indices of opposition to pulmonary flow and RV performance during OLA, it can be concluded that: 1. Opposition to RV ejection increases. This is evidenced by a 30% rise in mean PAP and 18 to 36% increase in pulmonary arterial elastance. 2. Right ventricular performance as indicated by RVSWI, RVEF and stroke volume does not decrease during OLA compared with when the patients awake or subjected to two-lung anesthesia. 3. Furthermore, coupling between the RV and its load is well preserved during OLA. This would imply that the RV operates at close to maximal efficiency during OLA and that RV stroke work reserve is present during OLA. It is likely that the RV, which continues operating as a flow pump as it does in normal life, easily copes with the small increases in RV afterload during OLA. Dobutamine during OLA: opposition to pulmonary flow and RV performance The effects of dobutamine infusions on RV performance during OLA can be summarised as follows: 1. Low rates of dobutamine infusion (3 ug.kg-1.min-1) increased cardiac output, stroke volume, and RVSWI. The administration of dobutamine 3 ug.kg-1.min-1 was not accompanied by increases in RV afterload. Therefore, low infusion rates of dobutamine did benefit RV-PA coupling during OLA. 2. However, administration of higher dosages of dobutamine (5 and 7 ug.kg-1.min-1) during OLA was associated with increases in certain indices of opposition to pulmonary blood flow. For example, PA elastance, mean PA pressure, and PVR increased by 30% to 40% compared to both when the patients were awake and when both lungs were being ventilated. Furthermore, PA compliance decreased by up to 61% when dobutamine 5 and 7 ug.kg-1.min-1 were infused compared to the OLA step when dobutaminewas not administered. The increases in mean PAP and PVR are considered to be of limited clinical significance. However, the decrease in PA compliance during the infusion of the highest dosage of dobutamine is clinically significant. PA compliance represents one of the factors determining vascular impedance in the Windkessel model of the circulation. The increases in opposition to pulmonary flow and lack of progressive increase in indices of RV performance are in contrast to what is expected to occur on administration of increasing dosages of the inotrope and pulmonary vasodilator, dobutamine. The reasons for the increase in opposition to pulmonary flow include exhaustion of the pulmonary vascular reserve during OLA at the high cardiac indices of 5 to 5.5 l.min-1.m-2. This aspect overshadowed the expected pulmonary vasodilator effects of dobutamine. Moreover, it is probable that the increase in RV afterload was significant enough to prevent right ventricular performance increasing as would be expected with the administration of progressively higher dosages of inotrope. While dobutamine was being administered during OLA, mean PAP increased to a maximum of 24.9 ± 6.2 mm Hg at a cardiac index of 5.5 ± 1.2 l.min-1.m-2. However during OLA, in the control group, mean PAP was 24.0 ± 7.7 mm Hg at the maximum cardiac index of 4.4 ± 1.1 l.min-1.m-2. This represented a relatively limited rise in PA pressure compared with administration of dobutamine alone. The most likely reason why there may have been a limited increase in mean PAP while dobutamine was being administered is that the “blow off” effect of the NDL vasculature limited the rise in PA pressure. Oxygenation during OLA With regard to oxygen flux, venous and arterial oxygenation during OLA in the control group, the following was observed: 1. Induction of anesthesia and the approximately 1O Celsius decrease in temperature induced an approximately 40% decrease in VO2 that continued during OLA. 2. Initiation of OLA resulted in an increase in cardiac output compared to baseline OLA and awake states. 3. The consequence was an increase in S􀀀��������O2 from 75% and P􀀀��������O2 from 5.4 kPa when the patients were awake to a P􀀀��������O2 of 9.0 ± 1.7 kPa and S􀀀��������O2 of 90.6 ± 4.7% during one-lung anesthesia. 4. During OLA, the significant increase in venous oxygenation resulted in an increase in arterial oxygenation compared to the awake state in spite of the approximately 37% shunt occuring during OLA. 5. Under conditions in the present study, dobutamine administration during OLA did not improve, but maintained the already high venous and arterial oxygenation compared with OLA alone. Therefore, the study hypothesis, that dobutamine would induce improvement in RVF and the increase in cardiac output during OLA would improve arterial oxygenation, does not hold in the current study. The hypothesis that dobutamine administration and improving cardiac output during OLA would increase arterial oxygenation was therefore rejected. However, the rejection of the hypothesis means that the findings of the current study are in contrast to the findings of Mathru et al, and Nomoto and Kawamura. These authors demonstrated that inotrope administration resulted in an increase in arterial oxygenation. Nonetheless, the different results are not at odds with each other. In fact, these differences help to clarify the effect of increases in cardiac output on arterial oxygenation in the presence of asignificant shunt. The differences between the studies can be explained in the following way. Conditions in the current study resulted in a favourable DO2/VO2 ratio and a high starting P􀀀��������O2 even before dobutamine administration was commenced. Therefore the venous saturations were on the flat part of the oxygen dissociation curve and also on the flat part of the relationship between cardiac output and arterial oxygen content originally described by Kelman, Nunn and colleagues. Further increases in cardiac output and the DO2/VO2 ratio would not be expected to, and did not, increase P􀀀��������O2, S􀀀��������O2, or C􀀀��������O2. Thus, arterial oxygenation content and saturation did not change subsequent to the increase in cardiac output associated with the administration of dobutamine in the current study. In contrast, in the Mathru study, the low starting venous saturations and tensions were improved by increases in the DO2/VO2 ratio. As the starting venous saturation was “low,” significant benefit in arterial oxygenation was obtained on increasing cardiac output in that study. One significant concern for the clinician regarding the administration of the inotrope dobutamine during OLA is that it may increase shunt fraction (Qs/Qt) and thereby decrease arterial oxygenation during one lung ventilation. The influence of dobutamine on arterial oxygenation during OLA may theoretically be related to the balance of the following divergent effects: 1. By improving the relationship between oxygen delivery and consumption, dobutamine increases P􀀀��������O2. This increase will benefit arterial oxygenation in the presence of a large shunt, 2. The above has to be weighed against possible increases in VO2 induced by dobutamine, the consequence of which will be a decrease in P􀀀��������O2. Such increases in VO2 were not seen on administration of dobutamine in the current study, 3. An increase in PA pressure accompanying the increased cardiac output will oppose HPV and increase shunt in both the dependent and non-dependent lungs, 4. Direct inhibition of HPV by dobutamine and, 5. The influence of P􀀀��������O2 on HPV (i.e. high levels of venous oxygenation will inhibit whereas low levels will potentiate HPV). Nonetheless, in spite of the concerns (risk) of hypoxemia on administering dobutamine during OLA, dobutamine administration did not decrease PaO2 or arterial oxygen saturation, and neither did it increase the cost of oxygenation compared to when OLA was conducted in the absence of dobutamine infusions. In addition, the findings of studies conducted by Mathru and colleagues, Nomoto and Kawamura and the current study indicate that under usual clinical conditions present during OLA in the LDP, the administration of low dosages of dobutamine do not increase shunt fraction. In fact, the beneficial effect of the increase in cardiac output on venous oxygenation resulted in an increase in arterial oxygenation in the study by Mathru and colleagues; similar mechanisms were most likely operative in the study conducted by Nomoto and Kawamura. Therefore, there is currently no evidence that the administration of dobutamine in dosages of up to 7 ug.kg-1.min-1 increases shunt and worsens arterial oxygenation in humans subjected to OLA in the LDP. It is apparent that the vasodilatory effects of dobutamine resulting in a possible increase in shunt fraction (Qs/Qt) is therefore not the only factor to consider when studying its effects on arterial oxygenation. What is also of great relevance whenconsidering the effects of an inotrope on arterial oxygenation is the effect of inotropic drugs on the venous oxygen content. It is possible that Qs/Qt could be increased by the administration of inotrope. Nonetheless, if venous oxygenation is favourably affected by the administration of dobutamine, then a depressant effect on arterial oxygenation by an increase in the amount of blood passing via the shunt may be negated. If the increase in venous oxygenation is very significant, there may even be benefits in terms of arterial oxygenation, as was the case in the current study. This approach to how the quality of the blood passing via the shunt affects arterial oxygenation shifts the emphasis on prevention and treatment of hypoxemia during OLA from the lung to the efficacy of the circulation. In other words, the emphasis is shifted from what predominantly happens to the non-ventilated lung (HPV) to primarily the efficacy of oxygen flux during OLA. Extrinsic and intrinsic PEEP and OLA The effects of PEEP on hemodynamics and oxygenation observed during OLA in the current study may be summarised as follows. When PEEP5 was applied to the DL during OLA in the current study: 1. Neither right ventricular function, hemodynamics, oxygen flux nor arterial oxygenation was affected by the application of PEEP5 compared to the step when no external PEEP was applied. 2. Significant amounts of intrinsic PEEP were present during OLA in the control group patients. The degree of intrinsic PEEP was weakly related to the degree of obstructive airways disease present on preoperative LFT’s. 3. The most likely reason why PEEP5 did not make a difference to oxygenation or hemodynamics was the existence of similar amounts of intrinsic PEEP during OLA. These findings confirm Myles’s contention that low levels of intrinsic PEEP may have salutary effects on oxygenation during OLA. When PEEP10 was applied to the DL during OLA in the current study, it led to a decrease in stroke volume. This decrease is predominantly due to a decrease in preload, as PVR does not increase to levels that are known to impair RV performance. The decrease in the DO2/VO2 ratio that was induced by PEEP10 predictably decreases P􀀀��������O2 and can potentially lead to impairment of arterial oxygenation. It can therefore be concluded that greater (excessive) amounts of PEEP under more unfavourable circulatory conditions than were observed in the current study, may have deleterious cardio-respiratory effects. In summary, optimising DL volume plays an important role in determining arterial oxygenation. However, the therapeutic index for PEEP is narrow and the anesthesiologist needs to know firstly when the lung volume of the DL approaches FRC and secondly, how to avoid dynamic hyperinflation of that lung. One significant problem is that the best method of monitoring FRC during OLA is not clear at present.
AFRIKAANSE OPSOMMING: Agtergrond tot die studie Eenlongnarkose mag tot sekere probleme aanleiding gee. ’n Betekenisvolle afname in volume van die onderlong vind in die laterale decubitus posisie tydens eenlongnarkose plaas. Hierdie afname in longvolume mag egter ’n akute verhoging in regter ventrikulêre nalading tot stand bring. Die probleem is egter dat die regter ventrikel ’n dunwandige struktuur is wat potensieel baie minder werk as die dikwandige linker ventrikel kan genereer. Die regter ventrikel het min reserwe om ’n akute verhoging in nalading te weerstaan soos wat gebeur met akute longbesering of na longreseksie. Dus die verhoging in nalading wat gepaard gaan met eenlongnarkose mag die koppeling tussen die regter ventrikel en die pulmonale arterie belemmer. Alhoewel hierdie potensiële probleem bestaan, is die verandering albei in regter ventrikulêre nalading en hoe die regter ventrikel funksioneer tydens eenlongnarkose nog nie goed bestudeer nie. 1. Arteriële hipoksemie, hoofsaaklik te wyte aan die groot aftakking via die long wat nie geventileer word nie, mag kliniese probleme tydens eenlongnarkose teweegbring. 2. Die weerstand wat die pulmonale vaskulêre beddens van die geventileerde en nie-geventileerde longe bied teen bloedvloei is belangrike faktore wat aftakking en dus arteriële oksigenasie tydens eenlongnarkose beheer. ’n Hoë weerstand van die nie-geventileerde long en ’n lae weerstand van die geventileerde long se pulmonale vaskulêre beddens sal bevredigende arteriële oksigenasie tydens eenlongnarkose fasiliteer. ’n Verhoging in die pulmonale vaskulêre weerstand van die nie-geventileerde long is hoofsaaklik te wyte aan hipoksiese pulmonale vasokonstriksie. ’n Lae pulmonale vaskulêre weerstand in die geventileerde onderlong is hoofsaaklik gefasiliteer deur ’n hoë alveolêre suurstofspanning en ’n normale long volume, alhoewel alle faktore ook ’n rol in hierdie verband speel. 3. In die teenwoordigheid van die groot aftakking wat bestaan tydens eenlongnarkose, sal die saturasie en suurstof inhoud van gemeng veneuse bloed ’n betekenisvolle bydrae aan arteriële oksigenasie maak. a. Veneuse saturasie as ’n oorsaak van hipoksemie tydens eenlongnarkose, is nog nie sistematies in die literatuur ondersoek nie. b. Indien regter ventrikulêre nalading tot so ’n mate verhoog dat dit tot swak ventrikulêre uitwerp lei, mag dit ’n oorsaak wees van ontoereikendheid van die globale bloedsomloop en tot gemeng veneuse desaturasie lei. Die vraag is dus of verhoging van die kardiale omset deur inotrope ondersteuning die toereikendheid van die sirkulasie kan verbeter. Verbeterde sirkulasie toereikendheid sal tot ’n verhoging in gemeng veneuse en arteriële oksigenasie lei in die teenwoordigheid van ’n groot aftakking. Nietemin, die toediening van inotrope in die teenwoordigheid van ’n groot aftakking tydens eenlongnarkose gerapporteer om hipoksemie te vererger tydens eenlongnarkose. Dus ten tye van die uitvoer van dié studie, is daar uitdrukking gegee tot teenstrydige opinies in die literatuur oftewel verhoging in kardiale omset arteriële oksigenasie sal verbeter of versleg tydens eenlongnarkose.In die lig van die agtergrond hierbo, het die navorser dus regter ventrikulêre nalading, regter ventrikulêre funksie en koppeling van die regter ventrikel met sy lading tydens eenlongnarkose ondersoek. Die studie het ook die vraag benader of inotroop infusies of PEEP goeie of slegte gevolge sou hê op regter ventrikulêre nalading, regter ventrikulêre funksie en koppeling van die regter ventrikel aan sy lading tydens eenlongnarkose. Sou die kardiale omset en die toereikendheid van die sirkulasie sou verbeter sekondêr tot die toediening van inotrope tydens eenlongnarkose, gemeng veneuse oksigenasie en dus arteriële oksigenasie tydens eenlongnarkose verbeter, of sou dit aftakking en arteriële oksigenasie versleg tydens eenlongnarkose? Kontrole groep Pulmonêre elastansie het tussen 18 en 36% verhoog en gemene pulmonale arterie druk het met 32% tydens eenlongnarkose vermeerder. Die verhoging in gemene pulmonale arterie druk met die aanvang van eenlongnarkose is groter as die waardes gesien deur sekere navorsers maar gelyk met waardes gevind in pasiënte met beskadigde longe. Die vraag ontstaan dan hoekom styg pulmonale arterie druk tydens eenlongnarkose? volgens Ohm se Wet, mag druk as die veelvoud van vloei en weerstand beskou word. Die verhoging in gemene pulmonale arterie druk tydens eenlongnarkose is daarvolgens hoofsaaklik te wyte aan twee redes. 1. Eerstens, die kurwe van druk teenoor vloei is waarskynlik styler tydens eenlongnarkose. Hierdie is omdat pulmonale vaskulêre werwing en verwyding (pulmonale vaskulêre reserwe) is meer beperk as nornaal in pasiënte met longsiekte. Hierdie is die waarskynlikste rede hoekom pulmonale arterie druk tydens eenlongnarkose verhoog. Die redes hoekom die pulmonale vaskulêre reserwe in die onderste long tydens eenlongnarkose beperk is sluit in die volgende: 1.1 Die pulmonale vaskulêre bed van pasiënte onderwerp aan eenlongnarkose mag abnormaal wees weens die onderliggende long patologie, 1.2 Tydens eenlongnarkose in die laterale decubitus posisie, is long volume in hoë mate verminder as tydens tweelongnarkose, 1.3 Die voorafgenoemde vermindering in longvolume sal verder verminder word deur wanposisies van die dubbellumenbuis, sekresies en bloed, en absorpsie atelektase. 1.4 Te hoë vlakke van PEEP, oftewel intrinsiek of ekstrensiek van oorsprong, sal die intraalveolêre vate toedruk en so die pulmonale vaskulêre weerstand verhoog. 2. Tweedens, is daar groter vloei deur hierdie vaskulêre bed wat ‘n hoër weerstand bevat. Dit is opmerkingswaardig dat die verhoging in gemene pulmonale arterie druk ‘n waarde van 25 mmHg nie oorskry het nie tydens eenlongnarkose, alhoewel kardiale omset met 30% verhoog het. In pasiënte met beskadigde longe, het vorige studies egter bewys dat groter verhoging in PA druk gebeur tydens afbinding van die pulmonale arterie. Die vraag ontstaan dus hoekom daar verskille bestaan tussen wat gebeur tydens afbind van die pulmonale arterie en eenlongnarkose? Die antwoord mag wees dat die beperking in die styging in PA druk tydens eenlongnarkose as gevolg van ‘n progressiewe afleiding van bloedvloei na die nie-geventileerde long gebeur sodra pulmonale arterie druk styg tydens eenlongnarkose. Die implikasie van die afleiding van bloed na die nie geventileerde long is dat dit as ‘n veiligheids meganisme optree en verdere styging in pulmonale arterie druk beperk tydens eenlongnarkose. Hierdie afblaas meganisme sal die regter ventrikel beskerm tot en met PA afbind.Kontrole groep: eenlongnarkose en regter ventrikulêre funksie Die huidige studie bied die geleentheid om die betekenis van die voorafgenoemde verhoging in PA drukke en elastansie op regter ventrikulêre funksie tydens eenlongnarkose te ondersoek. Die huidige studie dui aan dat die 30% verhoging in pulmonale arterie druk wat met die aanvang van eenlongnarkose plaasvind, glad nie regter ventrikulêre funksie belemmer nie indien dit vergelyk word met die basislyn wakker staat. In teendeel, kardiale omset het verhoog na chirurgiese insnyding: hierdie verhoging is waarskynlik te wyte aan simpatiese senuwee stimulasie na die chirurgiese insnyding. Hierdie waarnemings pas in ook met ander studies waartydens regter ventrikulêre ejeksie alleenlik begin om af te neem indien die indekse van opposisie tot regter ventrikulêre ejeksie 200 tot 250% van basislyn bereik. Verder, die induksie van voorlading, naamlik sentrale veneuse druk, pulmonale arterie wigdruk en regter ventrikulêre einddiastoliese volumes is onveranderd tydens die huidige studie; dit beteken die ventrikel het nie gedilateer het nie tydens die verhoging in regter ventrikulêre nalading. Die verband tussen slagwerk en nalading sal varieer, afhanklik van die kontraktiele status van die ventrikel. In hierdie opsig, kon ons aflei dat die regter ventrikel, onder omstandighede wat tydens diė studie plaasgevind het, gefunksioneer het op die stygende been van die verband tussen regter ventrikulêre slagwerk en pulmonale arterie elastansie. Hierdie waarneming ondersteun die argument in die vorige paragraaf dat die regter ventrikel funksie behoue is tydens eenlongnarkose. Ter opsomming omtrent die indekse van opposisie tot pulmonale vloei en regter ventrikulêre funksie tydens eenlongnarkose: 1. Opposisie tot regter ventrikulêre uitwerp verhoog. Die bewys hiervoor is ’n 30% verhoging in gemene pulmonale arterie druk en ’n 36% verhoging in pulmonale arterie elastansie. 2. Ten spyte van die verhoging in weerstand teen RV uitwerping, het regter ventrikulêre funksie (soos bepaal deur regter ventrikulêre slagwerk indeks, regter ventrikulêre ejeksie fraksie en slag volume), nie verminder tydens eenlongnarkose in vergelyking met die waardes verkry wanneer die pasiënte wakker is of aan tweelongnarkose onderwerp is. 3. Ons kon ook aflei dat die koppeling tussen die regter ventrikel en sy lading goed behoue is tydens eenlongnarkose. Die implikasie hiervan is dat regter ventrikulêre slagwerk reserwe teenwoordig is tydens eenlongnarkose. Tydens eenlongnarkose funksioneer die regter ventrikel as ’n vloeipomp, net soos in normale lewe; dit beteken dat en die klein verhoging in regter ventrikulêre nalading wat ondervind word tydens eenlongnarkose maklik getolereer word. Dobutamien tydens eenlongnarkose: opposisie tot pulmonale vloei en regter ventrikulêre funksie Die uitwerking van dobutamien op regter ventrikulêre funksie tydens eenlongnarkose kan as volg opgesom word: 1. Lae dosisse dobutamien (3 μg.kg-1.min-1) verhoog kardiale omset, slagvolume en regter ventrikulêre slagwerkindeks. Die toediening van dobutamien 3 μg.kg-1.min-1 het nie saamgegaan met ‘n verhoging in regter ventrikulêre nalading nie. Dus, lae dosisse van dobutamien het wel die koppeling tussen die regter ventrikel en die pulmonale vaskulatuur tydens eenlongnarkose verbeter.2. Nietemin, albei die hoër dosisse van dobutamien (5 en 7 μg.kg-1.min-1) tydens eenlongnarkose het verhogings in die opposisie tot pulmonale bloedvloei teweeggebring. Byvoorbeeld, PA elastansie, gemene PA druk en pulmonale vaskulêre weerstand het met 30 tot 40% verhoog in vergelyking met die waardes gekry toe die pasiënte wakker was en toe albei longe geventileer is. ’n Belangrike opmerking in hierdie opsig is dat pulmonale arterie vervormbaarheid tydens eenlongnarkose met 61% verminder het tydens albei dobutamien 5 en 7 μg.kg-1.min-1. Die verhogings in gemene pulmonale arterie druk en pulmonale vaskulêre weerstand is, volgens mening, nie van kliniese of statistiese betekenis nie, alhoewel die vermindering in PA vervormbaarheid tydens die dobutamien 7 μg.kg-1.min-1 infusie wel van kliniese betekenis is. PA vervormbaarheid weerspieël een van die faktore wat vaskulêre impedansie in die 3- element Windkessel model van sirkulasie het. Die verhoging in opposisie tot pulmonale vloei en die afwesigheid van progressiewe verhogings in indekse van regter ventrikulêre funksie is nie wat verwag word indien die dosisse van die inotroop en pulmonale vasodilator dobutamien, progressief verhoog word. Die redes hoekom die opposisie tot pulmonale vloei verhoog tydens die toediening van dobutamien sluit in die uitwissing van die pulmonale vaskulêre reserwe tydens eenlongnarkose. Tydens die hoë kardiale indekse van 5 tot 5.5 μg.kg-1.min-1. is die pulmonale vaskulêre reserwe uitgeput en die meganisme het die verwagte pulmonale vaskulêre vasodilatasie van dobutamien oorskadu. Bowendien is dit waarskynlik dat die verhoging in regter ventrikulêre nalading betekenisvol genoeg was om te verhoed dat regter ventrikulêre funksie progressief verhoog soos sou verwag word met die administrasie van hoër dosisse inotroop. Die administrasie van dobutamien tydens eenlongnarkose het gemene pulmonale arterie druk verhoog tot ’n maksimum van 24,9 ± 6.2 mm Hg teen ’n kardiale indeks van 5.5 ± 1.2 l.min-1.m2. Nietemin is gemene pulmonale arterie druk 24.0 ± 7.7 mm Hg teen die maksimum kardiale indeks in die kontrole groep van 4.4 ± 1.1 l.min-1.m-2 tydens eenlongnarkose in die kontrole groep. Hierdie weerspieël dus ’n relatief beperkte verhoging in pulmonale arterie druk in vergelyking met die verhoging in pulmonale arterie druk wat gebeur het tydens die administrasie van dobutamien. Die waarskynlikste rede hoekom daar ’n beperkte verhoging in pulmonale arterie druk sou gewees het tydens die infusie van dobutamien is die afblaas effek van die nie-geventileerde long wat die verhoging in PA druk beperk het. Oksigenasie tydens eenlongnarkose Die volgende waarnemings is gemaak in verband met suurstof vloed, veneuse en arteriële oksigenasie tydens eenlongnarkose in die kontrole groep: 1. Die kombinasie van Induksie van narkose en die 1ºC vermindering in temperatuur het saamgegaan met ’n 40% vermindering in suurstof verbruik tydens twee long narkose. Hierdie vermindering in suurstof verbruik het voortgegaan tydens eenlongnarkose. 2. Die aanvang van eenlongnarkose is geassosieerd met ’n verhoging in kardiale omset in vergelyking met albei die basislyn eenlongnarkose en wakker state. 3. Die gevolge van punte 1 en 2 hierbo is dat die gemengde veneuse suurstof saturasie vanaf 75% en die gemeng veneuse suurstof spanning vanaf 5.4 kPa (toe die pasiënte wakker was) gestyg het tydens4. Tydens eenlongnarkose het die betekenisvolle verhoging in veneuse oksigenasie veroorsaak dat daar ’n verhoging in arteriële oksigenasie was in vergelyking met wanneer die pasiënte wakker was. Hierdie styging in arteriele oksigenasie was ten spyte van die 37% aftakking wat teenwoordig was tydens eenlongnarkose. 5. Onder toestande in die huidige studie, het dobutamien tydens eenlongnarkose nog arteriële nog veneuse oksigenasie verbeter nie, maar die arteriele oksigenasie het konstant gebly. ’n Belangrike observasie wat daarmee saamgaan is dat dobutamien toediening nie met ’n daling in arteriële suurstof spanning geassosieer is nie. Vervolgens, die hipotese dat die verhoging in kardiale omset geassosieer met dobutamien toediening tydens eenlongnarkose ’n verhoging in arteriële oksigenasie beweeg bring, is dus verwerp. Die verwerping van die hipotese van die deel van die studie beteken dat die bevindinge die teenoorgestelde is van die studies gepubliseer deur Mathru en sy kollegas en Nomoto en Kawamura. Hierdie outeurs het gedemonstreer dat die toediening van inotrope ’n verhoging in arteriële oksigenasie teweeg gebring het. Nietemin is die teenoorgestelde gevolgtrekkinge nie teenstrydig met mekaar nie. Inteendeel hierdie verskille help ons om die effek van ’n verhoging in kardiale omset of arteriële oksigenasie in die teenwoordigheid van ’n betekenisvolle aftakking duidelik te maak. Die verskille tussen die studies kan op die volgende manier verduidelik word. Toestande wat in die huidige studie teenwoordig was het veroorsaak dat die verband tussen suurstof lewering en verbruik baie hoog was en dat die gemeng veneuse suurstof spanning baie hoog was om mee te begin alvorens dobutamien geinfuseer is. Dus is die veneuse saturasies op die plat deel van albei die suurstof dissosiasie kurwe en ook van die verband tussen kardiale omset en arteriële suurstof inhoud oorspronklik deur Kelman, Nunn en kollegas beskryf. Verdere verhogings in kardiale omset sou dus nie verwag word, en het nie, verhogings in gemeng veneuse suurstof spanning, gemeng veneuse suurstof saturasie of gemeng veneuse suurstof inhoud teweeg gebring. Dus, arteriële suurstof inhoud en saturasie het nie verander na die verhoging in kardiale omset wat teweeg gebring is deur die toediening van dobutamien in die huidige studie. Inteendeel, in die studie deur Mathru en kollegas, is die lae aanvanklike veneuse saturasie en spanning verbeter deur verhogings in die verband tussen suurstoflewering en suurstofverbruik. Omdat die veneuse saturasie aan die begin van die Mathru studie laag was, is betekenisvolle voordeel in arterieël oksigenasie teweeg gebring deur om die kardiale omset te verhoog. ’n Groot bekommernis vir die klinikus is dat die aftakking mag verhoog met die toediening van die inotroop dobutamien tydens eenlongnarkose en, op die manier, arteriële oksigenasie mag verminder. Die invloed van dobutamien op arteriële oksigenasie tydens eenlongnarkose mag teoreties te wyte wees aan die balans van die volgende uiteenlopende faktore: 1. Deur om die verband tussen suurstof lewering en verbruik te verbeter, sal dobutamien gemeng veneuse suurstof spanning verhoog. Hierdie verhoging sal arteriële oksigenasie verbeter in die teenwoordigheid van ’n groot aftakking, 2. Die bogenoemde moet teenoor potensiële verhogings in suurstofverbruik deur dobutamien oorweeg word. Die gevolge hiervan sou potensieel ’n vermindering in gemeng veneuse suurstof spanning wees. Sulke verhogings in suurstof verbruik is nie tydens die huidige studie gesien nie,3. ’n Verhoging in pulmonale arterie druk wat saamgaan met die verhoogde kardiale omset sal hipoksiese pulmonale vasokonstriksie teenwerk wat die aftakking in albei die geventileerde en nie geventileerde longe sal verhoog, 4. Direkte inhibisie van hipoksiese pulmonale vasokonstriksie deur dobutamien en, 5. Die invloed van gemeng veneuse suurstof spanning op hipoksiese pulmonale vasokonstriksie moet ook oorweeg word (d.i. hoe gemeng veneuse suurstof parsiele druk sal hipoksiese pulmonale vasokonstriksie inhibeer). Nietemin, ten spyte van die bekommernisse rondom hipoksemie tydens die toediening van dobutamien tydens eenlongnarkose, het dobutamien toediening nie ’n verlaging in arteriële suurstof spanning teweeg gebring nie, en ook het dit nie die koste van oksigenasie verhoog nie. Verder, die bevindinge van studies tydens eenlongnarkose in die laterale decubitus posisie deur Mathru en sy kollegas, Nomota en Kawamura en ook die huidige studie, dui aan dat die toediening van lae dosisse van dobutamien nie toe ’n verhoging in aftakking lei nie. Inteendeel, die voordelige effekte van die verhoging in kardiale omset op veneuse saturasie het veroorsaak dat daar ’n verhoging in arteriële saturasie is in die studie deur Mathru en sy kollegas soortgelyke meganismes is waarskynlik ook van toepassing in die studie wat gedoen is deur Nomoto en Kawamura. Dus, dwars deur die literatuur, is daar geen huidiglike bewys dat die toediening van dobutamien tot en met dosisse van 7μg.kg-1.min-1 aftakking verhoog of arteriële oksigenasie versleg in mense onderworpe aan eenlongnarkose in die laterale decubitus posisie. Dit is duidelik dat die vasodilatoriese effekte van dobutamien wat moontlik ’n verhoging in aftakking fraksie teweeg kan bring, nie die enigste faktore is om te oorweeg wanneer die middel se invloed op arteriële oksigenasie bestudeer word nie. Dit is ook van kliniese belang om die invloed van inotrope middels op veneuse suurstof inhoud te oorweeg. Dit is moontlik dat ’n aftakking verhoog kan word deur die toediening van ’n inotroop. Nietemin, mag die negatiewe effek wat die toediening van ’n inotroop sal inhou op arteriële oksigenasie deur middel van sy verhoging in aftakking, negeer word indien veneuse oksigenasie voordelig beïnvloed is. Verder, indien die verhoging in veneuse oksigenasie wat teweeggebring word deur die toediening van inotrope baie betekenisvol is, mag die gevolg hiervan wees dat arteriële oksigenasie voordelig beïnvloed word soos die geval in die huidige studie was. Die huidige benadering waar die kwaliteit van die bloed wat deur die aftakking vloei die arteriële oksigenasie beïnvloed, skuif die klem van voorkoming en behandeling van hipoksemie tydens eenlongnarkose van die long na die toereikendheid van die sirkulasie. Met ander woorde, die klem is geskuif van wat gebeur in die nie-geventileerde long (hipoksie pulmonale vasokonstriksie) tot primêr die toereikendheid van suurstof flux tydens eenlongnarkose. Ekstrinsieke en intrinsieke PEEP tydens eenlongnarkose Die invloed van PEEP op hemodinamika en oksigenasie tydens eenlongnarkose in die huidige studie mag as volg opgesom word. Toe PEEP5 tydens eenlongnarkose toegedien is: 1. Nie regter ventrikulêre funksie, hemodinamika, suurstof flux nog arteriële oksigenasie is beïnvloed deur die toediening van PEEP5 in vergelyking met die stap wanneer geen eksterne PEEP toegedien is nie. 2. Betekenisvolle hoeveelhede intrinsieke PEEP is teenwoordig tydens eenlongnarkose in die kontrole groep.Die hoeveelheid intrinsieke PEEP wat teenwoordig was, is swak maar betekenisvol verwant aan die graad obstruktiewe lugwegsiekte wat teenwoordig was gemeet deur pre-operatiewe longfunksie toetse. 3. Die waarskynlikste rede hoekom PEEP5 nie ’n verskil gemaak het aan oksigenasie of hemodinamika nie is die teenwoordigheid van soortgelyke hoeveelhede intrinsieke PEEP tydens eenlongnarkose. Hierdie bevinding bevestig Myle’s se beweringe dat lae vlakke intrinsieke PEEP voordelige effekte op oksigenasie tydens eenlongnarkose mag hê. PEEP10 toediening aan die onderlong tydens eenlongnarkose in die huidige studie het tot ’n vermindering in slagvolume gelei. Hierdie vermindering is primêr veroorsaak deur ’n vermindering in voorlading en nie die gevolg van ’n verhoging in pulmonale vaskulêre weerstand nie. Die gevolgtrekking is gemaak omdat regerventrikulere enddiastoliese volume verlaag het maar pulmonale vaskulêre weerstand het nie verhoog tot vlakke wat bekend is om regter ventrikulêre funksie te belemmer nie. Die vermindering in die verhouding tussen suurstof lewering en suurstof verbruik wat geïnduseer is deur PEEP10 het (voorspelbaar) gemeng veneuse suurstof spanning verminder en kon potensieël gelei het tot belemmering in arteriële oksigenasie. Indien minder voordelige sirkulatoriese toestande geheers het tydens die huidige studie, sou groter (oorbodige) hoeveelhede PEEP slegter kardiorespiratoriese gevolge tot gevolg gehad het. Ter opsomming, optimalisering van die volume van die onderlong tydens eenlongnarkose speel ’n belangrike rol in die bepaling van arteriële oksigenasie. Nietemin, die terapeutiese indeks vir PEEP is nou en die narkotiseur het die behoefte om te weet wanneer die volume van die onderlong optimaal is. In die opsig, is ’n betekenisvolle probleem tydens eenlongnarkose dat meting van funksionele residuele kapasiteit nie huidiglik maklik is nie

Abstract Lung donation is the most risky transplant procedures. With low survival rates, and poor acceptance of donated lungs, those in need of a lung transplant are at high risk of dying. One reason for poor outcomes is the lack of optimal match between donor and recipient when it comes to lung size and shape. Lungs that do not properly fit in the recipient’s chest cavity can fail to inflate fully and quickly start to deteriorate. In such patients, lung contusions can form, edema occurs in healthy lung tissue, and overall lung function declines. To improve patient outcomes after lung transplant, we describe here a developed a computational pipeline which enables donor lungs to be properly matched to recipients. This tool uses CT scans from both the donor and potential recipients to calculate how anatomically different the sets of lungs are, and therefore provide improved matches in both size and shape for the donor lungs.

The mechanics of lung deformation is traditionally assessed at a whole-lung or lobar level. We submit that key aspects of lung mechanics maybe better understood by studying regional patterns of lung deformation by leveraging recent developments in tomographic imaging and image processing techniques. Our group has developed an inverse consistent registration technique for estimating local displacement distributions from paired lung CT volumes [1,2]. This facilitates the estimation of strain distributions and consequently, the regional patterns in volume change and its preferential directionalities (anisotropy in deformation). In this study, we use this novel method to compare regional deformation in the lungs between static and dynamic inflations in an adult sheep. Much of our research has focused on registration of static lung images at different positive end-expiratory pressures (PEEP). More recently, respiratory-gated CT scans of supine, positive-pressure inflated sheep lungs have been gathered in order to compare the displacement fields of a dynamically inflating lung to the static lung scans. The theory is that scanning a dynamically inflating lung will more accurately reflect natural deformation during breathing by realizing time-dependent mechanical properties (viscoelasticity). The downside to human dynamic lung imaging is the increased radiation dose necessary to acquire the image data across the respiratory cycle, though low-dose CT scans are an option [3]. This experiment observed the difference in strain distribution between dynamically inflated lungs versus static apneic lungs using the inverse consistent image registration developed in our lab.

Lung cancer causes more than 1 million deaths worldwide annually [1]. In a recent study by the American Cancer Society in 2011, more than 221,000 new cases of lung cancers were reported [2]. Out of these, the mortality rate was found in roughly 70% of the cases [2]. Lung cancer is divided into two major categories: small cell and non-small cell. In the United States, non-small cell lung cancer accounts for 85% of all lung cancers and is considered the most common type of lung cancer [2]. It is usually resistant to chemotherapy, therefore making it extremely difficult to treat [3]. Furthermore adenocarcinomas, a type of non-small cell lung cancer, occur towards the periphery of the lungs and are the most common type accounting for 40–45% of all lung cancer cases [3]. Epithelial cells in the healthy lungs undergo stresses during inhalation and expiration of normal breathing. In addition to the forces of normal breathing, lung cancer cells may also experience abnormal mechanical forces due to pre-existing lung diseases such as asthma, bronchitis and chronic obstructive pulmonary disease or other tumor associated structural changes. These conditions can significantly alter the structure of the lungs and cell phenotype [4]. The change in the structure of the lungs affects the mechanical environment of the cells. Changes in extracellular (ECM) stiffness, cell stretch, and shear stress influence tumorigenesis and metastasis [5]. One mechanism through which the cells sense and respond to the cellular mechanical environment is through the primary cilia [6–7]. Primary cilia are non-motile, solitary structures formed from the cellular microtubules and protrude out of each cell. They have also been shown to play an important role in facilitating common cancer signaling pathways such as Sonic Hedgehog and Wnt/β-catenin signaling [8–9]. The objective of this study was to test the hypothesis that lung cancer cells respond to mechanical stimuli with the formation of primary cilia that are necessary for 3 hallmarks of tumor progression: proliferation, epithelial mesenchymal-transition, and migration.

The flexible bronchoscope, used both to directly visualize and biopsy lesions, is an important tool for diagnosing lung cancer [1]. Presented here is a conceptual design for a device that increases the depth to which the scope can be fed into the lungs. This allows doctors to find and accurately diagnose more cases of lung cancer first occurring deeper in the lungs.

We introduce in this paper a method for reliable automatic extraction of lung area from CT chest images with a wide variety of lungs image shapes by using Connected Components Labeling (CCL) technique with some morphological operations. The paper introduces also a method using the CCL technique with distance measure based classification for the efficient detection of lungs nodules from extracted lung area. We further tested our complete detection and extraction approach using a performance consistency check by applying it to lungs CT images of healthy persons (contain no nodules). The experimental results have shown that the performance of the method in all stages is high.

A patient-specific non-uniform pressure outlet boundary condition was developed and used in unsteady simulations of cyclic breathing in a large-scale model of the lung airway from the oronasal opening to the terminal bronchioles. The computational domain is a reduced-geometry model, in which some airway branches in each generation were truncated, and only selected paths were retained to the terminal generation. To characterize pressure change through airway tree extending from the truncated outlets to pulmonary zone, virtual airways represented by extended volume mesh zones were constructed in order to apply a zero-dimensional airway resistance model. The airway resistances were prescribed based on a precursor steady simulation under constant ventilation condition. The virtual airways accommodate the use of patient-specific alveolar pressure conditions. Furthermore, the time-dependent alveolar pressure profile was composed with the physiologically accurate pleural pressure predicted by the whole-body simulation software HumMod, and the transpulmonary pressure evaluated based on lung compliance and local air volume change. To investigate airway flow patterns of healthy and diseased lungs, unsteady breathing simulations were conducted with varying lung compliances accounting for healthy lungs, and lungs with emphysema or interstitial fibrosis. Results show that the simulations using this patient-specific pressure boundary condition are capable of reproducing physiologically realistic flow patterns corresponding to abnormal pulmonary compliance in diseased lungs, such as the hyperventilation in lungs with emphysema, and the demand of more mechanic work for breathing in lungs with fibrosis.

Pediatric patients or newborns admitted to Neonatal Intensive Care Units (NICU) receive life support care due to various conditions and pathologies. The physiotherapist controls and applies medicinal gases, institutes and monitors invasive and non-invasive mechanical ventilation, as well as performs weaning, among others. Learning ventilatory management must be appropriate for the age and, therefore, consider different lungs for the proper simulations of compliance and resistance. Although the insertion of physical therapists is relatively recent, there are several postgraduate courses and training in this area. The creation of a mechanical lungthat covers, separately, neonatal and pediatric patients will be a fundamental tool for the learning and training of future professionals who will work in the area. To develop two neonatal and pediatric mechanical lungs, as well as to simulate different elastic and resistive behaviors inherent in clinical practice. Experimental study, bench, divided into two stages: creation of mechanical lungs and evaluation of mechanical characteristics. The lungs will be made on a two-story metallic base: on the upper floor, the pediatric lung and the lower floor, the neonatal. In the second stage, the mechanical lung will be connected to a mechanical ventilator, using its own ventilatory parameters used in both types of patients. For the neonatal, respiratory rate of 35rpm, inspiratory time of 0.45 and endotracheal tube of 3.0 mm. The pediatric lung will be ventilated with a volume between 100-120mL, 20-25 compliance and a 4.5mm orotracheal tube. The construction of the neonatal and pediatric mechanical lung will strongly add the teaching of the Neonatal and Pediatric Intensive Physical Therapy specialty in the Undergraduate and Graduate settings, adding value to the teaching and training of professionals.

Introduction: Currently, the problem of chemical defeats at work continues to be relevant. According to the Federal Center for Hygiene and Epidemiology of Rospotrebnadzor, diseases (intoxication) caused by chemical factors exposure averaged 5.74–6.39% of occupational diseases per year all registered cases. As result of toxic substances inhalation, direct damage to lungs occurs with the further development of acute respiratory distress syndrome (ARDS). According to the national intensive care guide in the treatment of ARDS, the following main areas are distinguished - respiratory therapy and drug treatment. The latter includes infusion therapy, the use of glucocorticoids, surfactant preparations, narcotic analgesics and diuretics. Respiratory support consists in the use of mechanical ventilation (MV), and if the latter is not effective, extracorporeal membrane oxygenation (ECMO). Methods: literature data analyzes of acute chemical lung lesions treatment, as well as data on types, methods of liquid ventilation lung use. Results: It was found that the use of lungs both partial and total liquid ventilation using perfluorocarbon (PFC) compounds not only improved gas exchange in the lungs, but reduced the severity of the inflammatory response also. It was shown that the method of lung liquid ventilation (LVL) is promising. In turn, the increase in oxygenation we received, the increase in partial blood pressure during the alveolar phase of oedema, shows the advantage of liquid ventilation over existing ventilation regimes MV, thereby reflecting the potential of LAVL as a new method of respiratory support in acute lung lesions.

Certain serious illnesses, including pneumonia and the acute respiratory distress syndrome (ARDS), can lead to fluid accumulation in the lung and obstruction of the small pulmonary airways. Fluid in the lungs inhibits gas exchange and patients may require mechanical ventilation, which can expose the lung to mechanical stresses that exacerbate the existing injury and result in additional fluid accumulation. Recent improvements in ventilation protocols (e.g. low lung volume ventilation) have improved ARDS treatment, but mortality rates remain high (30–40%).

The distribution of inhaled air throughout human lungs is determined by the pressure losses in lung airways. These losses are reflections of patient health; alterations in measured pressure drops can indicate the presence of respiratory disease [1]. Pressure losses also have implications for the effective treatment of such diseases, as they affect how effectively inhaled medication can be distributed throughout the lung.

Review question / Objective: To identify the risk of lung cancer in FHRC patients compared to the general population. Condition being studied: The incidence rate of lung cancer in women is obviously increasing over the past decade and previous evidence have indicated the significant relationship between disturbances in hormone levels and the risk of lung cancer. Therefore, we hypothesized female hormone-related cancer (FHRC), including the breast, endometrial, cervix, and ovary cancer, patients may experience a higher risk of developing subsequent lung cancer.

Review question / Objective: This systematic review aims to provide an overview of the immunotherapy resistance mechanisms and identify potential biomarkers associated with immunotherapy response in NSCLC, as well as examine new treatment options to overcome this hurdle. Condition being studied: Lung Cancer (LC) remains one of the leading cancers worldwide. In 2020, were globally estimated 2 206 771 new cases and 1 796 144 deaths, representing the uttermost frequent cause of cancer death. LC is classified histologically into small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), being the last one the most common, representing 80 to 85% of all LC. The three predominantly subtypes of NSCLC are lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and large cell carcinoma (LCLC). NSCLC is usually diagnosed in advanced-staged disease due to ambiguous and delayed severe symptoms.