Treatment Of ARDS Research Articles

The tyrosine kinase inhibitor imatinib prevents lung injury and death after intravenous LPS in mice.

Severe sepsis and septic shock are frequent causes of the acute respiratory distress syndrome, and important sources of human mortality. Lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, plays a major role in the pathogenesis of severe sepsis and septic shock. LPS exposure induces the production of harmful reactive oxygen species, and the resultant oxidant injury has been implicated in the pathogenesis of both severe sepsis and ARDS. We previously showed that the tyrosine kinase inhibitor imatinib increases lung endothelial antioxidant enzymes and protects against pulmonary endothelial antioxidant injury. In the present study, we tested the hypothesis that imatinib would protect against lung injury and systemic inflammation caused by intravenous LPS in an intact mouse model of endotoxemia mimicking early sepsis. We found that intravenous LPS induced a significant increase in the activity of lung xanthine oxidoreductase (XOR), an enzyme which is a major source of reactive oxygen species and implicated in the pathogenesis of acute lung injury. Imatinib had no effect of LPS-induced XOR activity. However, pretreatment of mice with imatinib increased lung catalase activity and decreased intravenous LPS-induced lung oxidant injury as measured by γ-H2AX, a marker of oxidant-induced DNA damage, lung apoptosis, and pulmonary edema. Imatinib also attenuated systemic cytokine expression after intravenous LPS exposure. Finally, imatinib completely prevented mortality in an in vivo, intravenous LPS mouse model of endotoxemia and lung injury. These results support the testing of imatinib as a novel pharmacologic agent in the treatment of Gram-negative sepsis and sepsis-induced ARDS.

Is It Possible to Predict the Failure of Noninvasive Mechanical Ventilation for Acute Respiratory Failure Due to Pneumonia?

SESSION TITLE: Chest Infections Posters I SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: Non-invasive mechanical ventilation (NIMV) treatment in patients with acute hypoxemic respiratory failure due to pneumonia are controversial. The aim of this study is to determine the prognosis, failure rate of NIMV and risk factors for intubation in these patients. METHODS: Patients who were treated with NIMV for acute respiratory failure due to pneumonia in our intensive care unit (ICU) were assessed retrospectively. Demographic, clinical characteristics and laboratory results of patients were recorded. RESULTS: Eighty four patients (29 female, age 67 years, APACHE II score 17.5±7.0, median PaO2/FiO2 rate 222) were included in this study. NIMV was started on the first day after admission to ICU. The acute respiratory failure develpoed due to community, hospital acquired, healthcare associated pneumonia and pneumonia in immunocompromised patients (29.8%, 22.6%, 16.7%, 29.8%, respectively). 59.5% of patients were intubated on the second day because of failure of NIMV. In the patients of of whom the NIV failed, the baseline APACHE II score, respiratory rate and EPAP level were higher (p=0.008, p=0.001, p=0.002, respectively) and PaO2/FiO2 rate, hemoglobine, albumin levels were lower (p=0.001, p=0.001, p=0.001, respectively). The mortality rate due to acute respiratory failure was 58.3%. Hemoglobine level of <10 g/dl, existence of ARDS, absence of COPD and administration of vasopressor treatment were found to be independent risk factors for failure of NIMV (OR values were 11.09, 5.61, 6.17, 33.93 respectively) . CONCLUSIONS: NIMV can be applied to the patients who have acute hypoxemic respiratory failure due to pneumonia. However, there is a probability of failure of NIMV due to anemia, development of ARDS and baseline requirement for vasopressor treatment at baseline. CLINICAL IMPLICATIONS: NIMV can be used for the treatment of acute hypoxemic respiratory failure due to pneumonia. On the other hand, some factors such as aneima, existence of ARDS and vasopressor treatment at baseline may cause the failure of NIMV. Therefore, while applying NIMV in this group of patients, they should be monitored carefully. DISCLOSURE: The following authors have nothing to disclose: ALEV GURGUN, Imren Nesil, Pervin Korkmaz Ekren, Funda Elmas Uysal, Feza Bacakoglu No Product/Research Disclosure Information

Airway Pressure Release Ventilation and High-Frequency Oscillatory Ventilation: Potential Strategies to Treat Severe Hypoxemia and Prevent Ventilator-Induced Lung Injury.

Although lifesaving, mechanical ventilation can itself be responsible for damage to lung parenchyma. This ventilator-induced lung injury is especially observed in already injured lungs of patients with ARDS. New ventilatory approaches are needed to safely treat patients with ARDS, and recent studies have suggested the potential utility of open-lung strategies. Airway pressure release ventilation (APRV) and high-frequency oscillatory ventilation (HFOV) are 2 different open-lung strategies that have been proposed to treat refractory hypoxemic respiratory failure while preventing ventilator-induced lung injury. APRV provides increased airway pressure as a potential recruitment mechanism and allows spontaneous breathing, with the potential benefits of decreased sedation, shorter duration of mechanical ventilation, and improvement in cardiac performance. HFOV delivers very small tidal volumes, to prevent volutrauma, at a constant (relatively high) mean airway pressure, thus avoiding atelectrauma. Despite their theoretical benefits, the utility of APRV and HFOV remains unproven and controversial for the routine treatment of ARDS in adult patients. This review is focused on the theoretical and practical aspects of APRV and HFOV, provides an overview of the current evidence, and addresses their possible use in the treatment of ARDS.

PHARMACOLOGICAL AUGMENTATION OF LUNG RECRUITMENT EFFECTS LN THE THERAPY OF ACUTE RESPIRATORY DISTRESSSYNDROME AFTER CARDIAC SURGERY

The aim. To estimate efficacious of combined application of lung recruitment maneuver (LR) and surfactant administration for the treatment of ARDS after cardiac surgery. Materials and methods. 33 cardiac surgery patients with ARDS were included in to prospective, controlled non-randomized study. LR technique was used in 14 patients, who were included into the "LR" group. In 19 cases LR were combined with endobronchial administration of surfactant (Surfactant-BL, ”Biosurf” Russia), these patients were included into the "LR and surfactant" group. Results. Significant difference from baseline FiO 2 observed after 12 h in "LR and surfactant" group and after 24 h in "LR" group. Significant decrease from the baseline PEEP was observed after 48 h in "LR and surfactant" group and after 72 h in "LR" group. The duration of respiratory support was shorter in the "LR and surfactant" group: 87,5 ± 35,3 h vs 175,3 ± 52,5, p &lt;0,001. There was significant difference in the incidences of ventilator-associated pneumonia (VAP): 10.5% in the "LR and surfactant" group and 42.9% in the "LR" group, p &lt;0,05. Furthermore, we found significant difference in the ICU stay period between groups: 132,5 ± 42,2 h in the "LR and surfactant" group vs 282,5 ± 110,2 h in the "LR" group, p &lt;0,01. There was no significant difference between two groups In mortality rate: 3 (15.8%) in the "LR and surfactant" group and 3 (21.4%) in the "LR" group. Conclusions. The combination of LR and surfactant administration decrease the time of respiratory support and ICU stay, reduce the risk of VAP.

Is this the time to introduce ketamine in acute respiratory distress syndrome? A pilot study

Introduction Acute respiratory distress syndrome is regarded to be an acute, diffuse inflammation of the lung that leads to an increase in the permeability of the pulmonary vascular tissue. The relations between ARDS classes and the permeability of the pulmonary microvasculature as well as the water content of the pulmonary extravasculature remains to be clarified. The anti-inflammatory and the antioxidant properties of ketamine were observed in acute lung injury; ketamine promotes the attenuation of the expression of mediators of inflammation. The aim of the work The aim of this study was to test whether ketamine treatment by the inhaled route or the infusion route could be an efficient method of treatment for ARDS. Participants and methods Mechanically ventilated critically ill adult trauma patients admitted to the ICU with developing ARDS were eligible to participate in this study. Group A was treated by ketamine inhalation, group B was treated with ketamine infusion, and group C was treated by pulse steroid therapy. The serum interleukin-6 level was analyzed. Results Concerning group A (ketamine inhalation) and group B (ketamine infusion), there were significant correlations in both the groups starting from day 2 till day 5 of treatment with regard to the tidal volume and positive end-expiratory pressure and from day 3 of treatment with regard to the blood pressure and FiO 2 .

The Effect of Omega-3 Fatty Acids on ARDS: A Randomized Double-Blind Study.

The aim of this study was to evaluate the effect of an enteral nutrition diet, enriched with omega-3 fatty acids because of its anti-inflammatory effects on treatment of patients with mild to moderate ARDS. This randomized clinical trial was performed in two ICUs of Tabriz University of Medical Sciences from Jun 2011 until Sep 2013 in north west of Iran. Fifty-eight patients with mild to moderate ARDS were enroled in this clinical trial. All patients received standard treatment for ARDS based on ARDS network trial. In intervention group, patients received 6 soft-gels of omega-3/day in addition to the standard treatment. Tidal volume, PEEP, pH, PaO2/FiO2 , SaO2, P platue and PaCO2 on the 7(th) and 14(th) days didn't have significant difference between two groups. Indices of lung mechanics (Resistance, Compliance) had significant difference between the groups on the 14(th) day. Pao2 had significant difference between two groups on both 7(th) and 14(th) days. Trend of PaO2 changes during the study period in two groups were significant. We showed that adjusted mortality rate did not have significant difference between two groups. It seems that adding omega-3 fatty acids to enteral diet of patients with ARDS has positive results in term of ventilator free days, oxygenation, lung mechanic indices; however, we need more multi center trials with large sample size and different doses of omega-3 fatty acids for their routine usage as an adjuant for ARDS treatment.

Preventing ARDS: Progress, Promise, and Pitfalls

Advances in critical care practice have led to a substantial decline in the incidence of ARDS over the past several years. Low tidal volume ventilation, timely resuscitation and antimicrobial administration, restrictive transfusion practices, and primary prevention of aspiration and nosocomial pneumonia have likely contributed to this reduction. Despite decades of research, there is no proven pharmacologic treatment of ARDS, and mortality from ARDS remains high. Consequently, recent initiatives have broadened the scope of lung injury research to include targeted prevention of ARDS. Prediction scores have been developed to identify patients at risk for ARDS, and clinical trials testing aspirin and inhaled budesonide/formoterol for ARDS prevention are ongoing. Future trials aimed at preventing ARDS face several key challenges. ARDS has not been validated as an end point for pivotal clinical trials, and caution is needed when testing toxic therapies that may prevent ARDS yet potentially increase mortality.

Gas Transfer of an Implatable Artificial Lung

The water flow characteristics in the implantable artificial lung (IAL) were evaluated by in vitro experiments. The 50-fiber modules were of different lengths but contained well-spaced fibers; and the 300-fiber module had a volume fraction of 0.9. A lower number of tired hollow fibers produce a higher water-side film coefficient of oxygen transfer at a constant velocity of water-side flow. The area of the water flow decreases with increasing hollow fiber packing density, thus if water is induced to flow uniformly in the IAL module, the oxygen transfer rate should monotonously increase with the packing density. The water flow in the IAL is not uniform and depends on the hollow fiber packing density. The stagnation of the water flow occurs in the bundle of the hollow fibers at the water inlet. Intravascular oxygenation represents an attractive, alternative support modality for patients with ARDS. The concept of intravascular oxygenation as an alternative ARDS therapy originated with Mortensen (7), who developed an intravenous oxygenator (IVOX) consisting of a bundle of crimped hollow fiber positioned in the vena cava. In phase I clinical trials, the IVOX provided an average of 28% of basal gas exchange requirements for patients with severe ARDS (8-14). The clinical study, however, concluded that more gas exchange was needed for intravascular oxygenation to be clinically effective in ARDS treatment. We are developing an intravenous membrane oxygenator (IMO) with a design goal of 50% of basal oxygen and carbon dioxide exchange requirements for end-stage ARDS patients. Like the IVOX, the IMO consists of a bundle of manifolded hollow fiber, and is intended for intravenous placement within the superior and inferior vena cava. The target level of gas exchange in the IVOX, and consequently, the IMO, incorporates a polyurethane balloon concentric with the fiber bundle, which rhythmically inflates and deflates to provide active blood mixing, and thus enhances gas exchange. Our current efforts focus on device improvements intended to provide the target levels of gas exchange, given the constraints imposed by intravenous placement on fiber bundle size and hence fiber area for gas exchange. Although critical care techniques have been improved, the high mortality of severe ARDS has not significantly changed (10-15). In an implantable artificial lung (IAL), the greater part of the oxygen transfer resistance is located in the blood-side laminar film (16), and various methods have been attempted to make the laminar film thin and improve the oxygen transfer rate (17, 18). In the present study, the water flow characteristics in the IAL were evaluated by in vitro experiments. The effect of hollow fiber packing fraction on water flow condition was evaluated to produce effective constant of water with the hollow fibers. Oxygen transfer rates were evaluated, and the optimum hollow fiber packing fraction was determined at an outside diameter of hollow fibers of 380 μm. II. THEORYT The Reynolds number (NRe =Lv/υ) characterizes the flow regime and is the ratio of inertial force to viscous force. The Schmidt number (NSc=υ/D), analogous to the Prandtl number in heat transfer, characterizes the fluid properties and is the ratio of momentum transport to diffusive transport. The Peclet number (NPe=Lv/D), which is the product of NRe, characterizes the relative importance of convective and diffusive processes and is the ratio of bulk mass transport to diffusive mass transport. The Sherwood number (NSh=KL/D), also known as the mass transfer Nusselt number, likewise characterizes the relative importance of convective and diffusive transport; it is the ratio of total transport to diffusive transport. The mass transfer Stanton number (NSt=K/v) is proportional to the ratio of the actual mass flux to the mass flux capacity of the flow, i.e. the amount of mass potentially transferable per unit time and cross-sectional area.

Update on the diagnosis and treatment of ARDS

Update on the diagnosis and treatment of ARDS

Successful Treatment of Adenovirus-Induced ARDS With Cidofovir and IVIG

Successful Treatment of Adenovirus-Induced ARDS With Cidofovir and IVIG

CrossTalk opposing view: There is not added benefit to providing permissive hypercapnia in the treatment of ARDS

CrossTalk opposing view: There is not added benefit to providing permissive hypercapnia in the treatment of ARDS

Hyperoxia-induced alterations in the pulmonary proteome of juvenile rats

ABSTRACTHigh inspired concentrations of oxygen (hyperoxia) are often necessary to counteract tissue hypoxia during the treatment of ARDS. Reactive oxygen species generated by hyperoxic therapy may influence the expression of the pulmonary proteome and the application of discovery proteomics to the hyperoxic lung has the potential to divulge mechanisms regulating the expression of specific proteins integral to lung injury and repair. The present study examined the proteome derived from 30-day-old Sprague-Dawley rats exposed to room air (RA) and 95% O2 (Ox) for 24–72 hours using 2-dimensional difference in-gel electrophoresis (2D-DIGE) coupled with MALDI-ToF/ToF mass spectrometry. A total of 870 protein spots were visualized by 2D-DIGE across all gels. Mass spectral analysis identified 51 proteins representing 187 of the 214 significantly altered spots. Molecular and cellular function analysis grouped the identified proteins into free radical scavenging, cell death, cell-to-cell signaling, and cellular movement categories. The majority of the differences in the protein spots between RA and Ox occurred at 72 hours, with albumin, annexin A6 (AnxA6), and transferrin being increased, and mitochondrial Lon peptidase 1 being decreased by at least 20%. In Ox animals, AnxA6 protein expression increased three-fold without an increase in mRNA expression. Bioinformatic analysis of the AnxA6 transcript revealed the presence of a putative internal ribosome entry site within the 5′-untranslated region. These findings indicate that hyperoxia induces significant alterations in the pulmonary proteome which are temporally related. In addition, hyperoxia selectively enhances the expression of some proteins whose transcripts contain sequence motifs, which impart translational regulation.

ARDS: Who Needs to be Pronated?

Acute Distress Respiratory Syndrome (ARDS) is defined as a severe respiratory failure characterized by marked hypoxemia, bilateral infiltrates on the chest X-ray and the absence of signs of cardiogenic pulmonary edema. ARDS treatment remains primarily supportive and the use of mechanical ventilation with positive and expiratory pressure is required to maintain adequate gas exchange. Lung-protective mechanical ventilation strategy decreases mortality and increases ventilator free days. Prone positioning is considered a rescue therapy despite it improves gas exchange through resolution of dorsal atelectases with lung recruitment, better distribution of pulmonary perfusion and reduction of lung stress and strain. Nevertheless, several randomized controlled trials failed to demonstrate a reduction in mortality in pronated ARDS patients. Recent meta-analysis instead demonstrated a significant reduction of mortality in patients with most severe ARDS (PaO2/FiO2 ratio < 200) ventilated in prone position. These data were confirmed by the results of the PROSEVA study, published in June 2013 that reports a 16% reduction of mortality rate. The results of several meta-analysis and this large clinical trial suggest that prone positioning is a useful strategy that saves lives in more severely ill ARDS patients, when applied earlier and for at least 16 hours/day.

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Introduction: The hallmark of severe ARDS, defined as PaO2/FiO2 ratio (P/F)? 100, is severe hypoxemia, which is associated with high mortality rates (45-83% in recent studies). In the Berlin ARDS definition validation, mortality increased in both clinical & physiologic databases between mild (P/F 201-300: 27%, 20%), moderate (P/F 101-200: 32%, 41%), & severe ARDS (P/F? 100: 45%, 52%). Hypothesis: An evidence-based ARDS treatment algorithm, including rescue strategies, is associated with reduced mortality. Methods: Prospective cohort study (6 years, 7/2005-6/2011). ARDS patients (n=240) treated with an evidence-based algorithm combining low tidal volume lung protective ventilation & rescue strategies [inhaled nitric oxide, prone positioning, high frequency oscillatory ventilation (HFOV), & ECMO]. Data were collected prospectively by a single APACHE Data Coordinator & analyzed by Berlin definition ARDS severity. Results: Hypoxemia severity was associated with increased mortality: mild (mean P/F=251.6 ± 28.4, n=7; 1 death, 14%), moderate (mean P/F=137.1 ± 30.0, n=50; 10 deaths, 20%), & severe (mean P/F=67.5 ± 15.7, n=183; 58 deaths, 32%). Severe group mortality was less than in the Berlin validation data (32% vs. 45%/52%, p=0.0011/0.02). Mortality etiology was multi-system organ failure (mild: 1, moderate: 8, severe: 48) & hypoxemia (moderate: 2, severe: 10). ICU LOS increased with ARDS severity (mild: 7.6d±8.5, moderate: 15.9d±17.8, severe: 21.1d±25.4). HFOV & ECMO were used more in the severe (67, 47) than in moderate group (4, 2).SAPS II & APACHE III scores were 54.1 ± 30.4/60.7 ± 28.0 (mild), 67.5 ± 20.8/71.8 ± 22.4 (moderate), & 66.0 ± 23.1/68.8 ± 23.7 (severe). Lower scores in severe ARDS document underestimation of illness severity by not accounting for PEEP & rescue therapies. Standardized mortality ratios (SMR, actual vs. APACHE national predicted, based on primary ICU diagnoses which were not uniform) were 0.74 in mild, 0.60 in moderate, & 0.99 in severe ARDS. Conclusions: In this largest single-center study of 183 severe ARDS patients, mortality was significantly reduced with use of an evidence-based treatment algorithm compared to national multicenter data. Critical care of severe ARDS patients should be regionalized.

Lungenersatzverfahren – Welche Therapie für welchen Patienten? Wahl der Beatmungsstrategie im akuten Lungenversagen

Ventilator-induced lung injury (VILI) contributes to the high mortality of ALI/ARDS. Lung protective ventilation with a tidal volume of 6 ml / kgIBW (Ideal Body Weight) and a plateau pressure <30 cm H2O has shown to reduce mortality and was thus selected as one of ten quality indicators for critical care in Germany. The optimal level of PEEP is currently unclear; however, patients with severe disorders of gas exchange seem to benefit from higher PEEP levels.Adjusting the respirator settings to the mechanical properties of the individual patient will change the treatment of ARDS in the next few years. Measurements of transpulmonary pressure by an oesophageal probe or electrical impedance tomography (EIT) are promising approaches, but still need to proof their superiority. Until then, every clinician must aim to translate the recommendations of lung protective ventilation into daily practice.

Treatment of Sepsis and ARDS With Extracorporeal Membrane Oxygenation and Interventional Lung Assist Membrane Ventilator in a Patient With Acute Lymphoblastic Leukemia

We report an 18-year-old ice skater with acute lymphoblast leukemia. She developed Staphylococcus epidermidis bacteremia, severe sepsis, septic shock, and ARDS following chemotherapy-induced severe bone marrow failure. She was successfully treated with extraordinary life support measures, which included extracorporeal membrane oxygenation, double lumen lung ventilation for management of hemoptysis, and lung assist membrane ventilation. After 57 days of ICU treatment and a year of rehabilitation, the patient has fully regained her functional status, is now finishing high school, and is ice skating again.

Improving survival in decompensated cirrhosis.

Mortality in cirrhosis is consequent of decompensation, only treatment being timely liver transplantation. Organ allocation is prioritized for the sickest patients based on Model for End Stage Liver Disease (MELD) score. In order to improve survival in patients with high MELD score it is imperative to preserve them in suitable condition till transplantation. Here we examine means to prolong life in high MELD score patients till a suitable liver is available. We specially emphasize protection of airways by avoidance of sedatives, avoidance of Bilevel Positive Airway Pressure, elective intubation in grade III or higher encephalopathy, maintaining a low threshold for intubation with lesser grades of encephalopathy when undergoing upper endoscopy or colonoscopy as pre transplant evaluation or transferring patient to a transplant center. Consider post-pyloric tube feeding in encephalopathy to maintain muscle mass and minimize risk of aspiration. In non intubated and well controlled encephalopathy, frequent physical mobility by active and passive exercises are recommended. When renal replacement therapy is needed, night-time Continuous Veno-Venous Hemodialysis may be useful in keeping the daytime free for mobility. Sparing and judicious use of steroids needs to be borne in mind in treatment of ARDS and acute hepatitis from alcohol or autoimmune process.

What Is the Acute Respiratory Distress Syndrome?

It has been known for decades that shock and sepsis can cause a syndrome of acute respiratory failure with characteristics of non-cardiogenic pulmonary edema. Over the years, this syndrome has been given a number of names, including congestive atelectasis, traumatic wet lung, and shock lung. In 1967 the modern counterpart to this syndrome was described and subsequently called the "acute respiratory distress syndrome" (ARDS). This syndrome results from lung injury and inflammation. As with inflammation elsewhere, ARDS is accompanied by many cellular and molecular processes, some of them specific to the syndrome, others perpetuating the syndrome, and others inactivating the by-products of inflammation. Since no specific clinical sign or diagnostic test has yet been described that identifies ARDS, its diagnosis is based on a constellation of clinical, hemodynamic, and oxygenation criteria. Current ARDS treatment is mainly supportive, since these patients frequently have coexisting conditions. Although in 1994 a new standard ARDS definition was accepted, that definition failed to standardize the measurement of the oxygenation defect and does not recognize different severities of pulmonary dysfunction. Based on current evidence there is a need for a better definition and classification system that could help us to identify ARDS patients who would be most responsive to supportive therapies and those unlikely to benefit because of the severity of their disease process. This paper examines our current understanding of ARDS and discusses why the current definition may not be the most appropriate for research and clinical practice.

Research progress on the role of TGF-β signal pathway in acute lung injury fibrosis

Background Acute lung injury is a common clinical Intensive. The studies showed that TGF -β signaling pathway played an important role in the developmentof this disease. Objective This paper was to summarize the literatures which includedthe correlation and mechanisms of TGF-β signaling pathway in the lung injury and fibrosis. Content This article described the biological properties, activation, and the possible mechanisms of TGF-β in lung fibrosis; The cross-talk of Samds-dependent TGF-β signaling with other pathways; and the role of caveolin-1 in pulmonary fibrosis and the transduction of TGF-β signaling pathway;TGF signaling pathway-targeted treatment. Trend TGF-β/Smads signaling pathway plays an important role in the occurrence and development of acute lung injury fibrosis. TGF-β and Smad protein expression in a variety of time positioning, the significance of the different smad proteins, the feedback regnlation mechanism, the interactionof cytokine network, the possible link between signaling pathways need to be gradually revealed. The regulation of TGF-β and its signaling transduction protein may be a new and effective target for the treatment of ARDS in the future. Key words: Acute lung injury ; Transforming growth factor-β ; Smads proteins ; Caveolin-1 ; Target treatment ;

Year in review 2010: Interstitial lung diseases, acute lung injury, sleep, physiology, imaging, bronchoscopic intervention and lung cancer

Year in review 2010: Interstitial lung diseases, acute lung injury, sleep, physiology, imaging, bronchoscopic intervention and lung cancer