Bilateral Lung Injury Research Articles

Impact of airway closure and lung collapse on inhaled nitric oxide effect in acute lung injury: an experimental study

BackgroundEfficacy of inhaled therapy such as Nitric Oxide (iNO) during mechanical ventilation may depend on airway patency. We hypothesized that airway closure and lung collapse, countered by positive end-expiratory pressure (PEEP), influence iNO efficacy. This could support the role of an adequate PEEP titration for inhalation therapy. The main aim of this study was to assess the effect of iNO with PEEP set above or below the airway opening pressure (AOP) generated by airway closure, on hemodynamics and gas exchange in swine models of acute respiratory distress syndrome. Fourteen pigs randomly underwent either bilateral or asymmetrical two-hit model of lung injury. Airway closure and lung collapse were measured with electrical impedance tomography as well as ventilation/perfusion ratio (V/Q). After AOP detection, the effect of iNO (10ppm) was studied with PEEP set randomly above or below regional AOP. Respiratory mechanics, hemodynamics, and gas-exchange were recorded.ResultsAll pigs presented airway closure (AOP > 0.5cmH2O) after injury. In bilateral injury, iNO was associated with an improved mean pulmonary pressure from 49 ± 8 to 42 ± 7mmHg; (p = 0.003), and ventilation/perfusion matching, caused by a reduction in pixels with low V/Q and shunt from 16%[IQR:13–19] to 9%[IQR:4–12] (p = 0.03) only at PEEP set above AOP. iNO had no effect on hemodynamics or gas exchange for PEEP below AOP (low V/Q 25%[IQR:16–30] to 23%[IQR:14–27]; p = 0.68). In asymmetrical injury, iNO improved pulmonary hemodynamics and ventilation/perfusion matching independently from the PEEP set. iNO was associated with improved oxygenation in all cases.ConclusionsIn an animal model of bilateral lung injury, PEEP level relative to AOP markedly influences iNO efficacy on pulmonary hemodynamics and ventilation/perfusion match, independently of oxygenation.

Rapidly developing massive thromboembolism and death due to anticoagulant dose reduction in a patient with atrial fibrillation: case Report

Atrial fibrillation is one of the cardiac arrhythmias that can cause fatal complications. Patients diagnosed with atrial fibrillation face complications such as ischemic stroke, peripheral vascular embolism and pulmonary embolism if they are not under regular and strict treatment follow-up. In this case, in a 73-year-old woman with atrial fibrillation who was not receiving regular treatment, sudden onset of leg pain followed by rapid onset of dyspnea was clinically suggestive of acute peripheral arterial embolism followed by massive pulmonary embolism. The patient was tachypneic and confused at the time of presentation to the emergency department. After intubation with sedation and analgesia, radiologic imaging was obtained for possible complications secondary to atrial fibrillation. As a result, the patient had an embolus starting from the level of the abdominal aorta, extending to the right renal artery and spreading to the entire right iliac artery. The lung tissue showed bilateral acute lung injury without pulmonary embolism. In this case, we wanted to emphasize the importance of the subject by sharing the rapidly developing embolism and death process with the reduction of the anticoagulant dose used in the treatment of atrial fibrillation.

Waterproofing Spray-Associated Lung Injury Review: Differences between Cases of Early and Delayed Improvement of Waterproofing Spray-Associated Lung Injury

Waterproofing spray-associated lung injury (WALI) is an acute respiratory disorder characterized by bilateral diffuse lung injury on chest computed tomography (CT). In most cases, the symptoms and abnormal radiographic findings of WALI patients improve spontaneously over several days; however, some cases have persistent symptoms and abnormal shadows for >1 week. The distinctive features of each WALI are unknown. Herein, we present two new cases of WALI that we encountered in our hospital, and we previously reported two other cases of WALI. We examined the characteristics of WALI in our cases and 39 other cases of WALI definitively diagnosed and reported in PubMed and the Japan medical board with verifiable data during a 15-year period. We compared the clinical characteristics of the 22 cases in which the patients' symptoms were resolved within 1 week (early improvement) to those of the 21 cases in which the symptoms were resolved after >1 week (delayed improvement). The WALI cases with delayed improvement had significantly more shadowing that extended over the entire lung field and was not biased in intensity toward the upper or lower lung field. In addition, the serum white blood cell (WBC) counts and serum Krebs von den Lungen-6 (KL-6) levels differed significantly between the cases of early and delayed improvement of WALI.

Inhaled CO2 vs. Hypercapnia Obtained by Low Tidal Volume or Instrumental Dead Space in Unilateral Pulmonary Artery Ligation: Any Difference for Lung Protection?

BackgroundUnilateral ligation of the pulmonary artery (UPAL) induces bilateral lung injury in pigs undergoing controlled mechanical ventilation. Possible mechanisms include redistribution of ventilation toward the non-ligated lung and hypoperfusion of the ligated lung. The addition of 5% CO2 to the inspiratory gas (FiCO2) prevents the injury, but it is not clear whether lung protection is a direct effect of CO2 inhalation or it is mediated by plasmatic hypercapnia. This study aims to compare the effects and mechanisms of FiCO2 vs. hypercapnia induced by low tidal volume ventilation or instrumental dead space.MethodsHealthy pigs underwent left UPAL and were allocated for 48 h to the following: Volume-controlled ventilation (VCV) with VT 10 ml/kg (injury, n = 6); VCV plus 5% FiCO2 (FiCO2, n = 7); VCV with VT 6 ml/kg (low VT, n = 6); VCV plus additional circuit dead space (instrumental VD, n = 6). Histological score, regional compliance, wet-to-dry ratio, and inflammatory infiltrate were assessed to evaluate lung injury at the end of the study. To investigate the mechanisms of protection, we quantified the redistribution of ventilation to the non-ligated lung, as the ratio between the percentage of tidal volume to the right and to the left lung (VTRIGHT/LEFT), and the hypoperfusion of the ligated lung as the percentage of blood flow reaching the left lung (PerfusionLEFT).ResultsIn the left ligated lung, injury was prevented only in the FiCO2 group, as indicated by lower histological score, higher regional compliance, lower wet-to-dry ratio and lower density of inflammatory cells compared to other groups. For the right lung, the histological score was lower both in the FiCO2 and in the low VT groups, but the other measures of injury showed lower intensity only in the FiCO2 group. VTRIGHT/LEFT was lower and PerfusionLEFT was higher in the FiCO2 group compared to other groups.ConclusionIn a model of UPAL, inhaled CO2 but not hypercapnia grants bilateral lung protection. Mechanisms of protection include reduced overdistension of the non-ligated and increased perfusion of the ligated lung.

Addition of 5% CO2 to Inspiratory Gas Prevents Lung Injury in an Experimental Model of Pulmonary Artery Ligation.

Rationale: Unilateral ligation of the pulmonary artery may induce lung injury through multiple mechanisms, which might be dampened by inhaled CO2.Objectives: This study aims to characterize bilateral lung injury owing to unilateral ligation of the pulmonary artery in healthy swine undergoing controlled mechanical ventilation and its prevention by 5% CO2 inhalation and to investigate relevant pathophysiological mechanisms.Methods: Sixteen healthy pigs were allocated to surgical ligation of the left pulmonary artery (ligation group), seven to surgical ligation of the left pulmonary artery and inhalation of 5% CO2 (ligation + FiCO2 5%), and six to no intervention (no ligation). Then, all animals received mechanical ventilation with Vt 10 ml/kg, positive end-expiratory pressure 5 cm H2O, respiratory rate 25 breaths/min, and FiO2 50% (±FiCO2 5%) for 48 hours or until development of severe lung injury.Measurements and Main Results: Histological, physiological, and quantitative computed tomography scan data were compared between groups to characterize lung injury. Electrical impedance tomography and immunohistochemistry analysis were performed in a subset of animals to explore mechanisms of injury. Animals from the ligation group developed bilateral lung injury as assessed by significantly higher histological score, larger increase in lung weight, poorer oxygenation, and worse respiratory mechanics compared with the ligation + FiCO2 5% group. In the ligation group, the right lung received a larger fraction of Vt and inflammation was more represented, whereas CO2 dampened both processes.Conclusions: Mechanical ventilation induces bilateral lung injury within 48 hours in healthy pigs undergoing left pulmonary artery ligation. Inhalation of 5% CO2 prevents injury, likely through decreased stress to the right lung and antiinflammatory effects.

Risk of Acute Lung Injury after Esophagectomy

To develop a new approach for identifying acute lung injury (ALI) in surgical ward setting and to assess incidence rate, clinical outcomes, and risk factors for ALI cases after esophagectomy. We also compare the degree of lung injury between operative and non-operative sides. Consecutive esophageal cancer patients (n=1022) who underwent esophagectomy from Dec 2012 to Nov 2018 in our hospital were studied. An approach for identifying ALI was proposed that integrated radiographic assessment of lung edema (RALE) score to quantify degree of lung edema. Stepwise logistic regression identified risk factors for postoperative ALI incidence. The degree of bilateral lung injury was compared using the RALE score. The approach for identifying ALI in surgical ward setting was defined as acute onset, PaO2/FiO2≤300 mmHg, bilateral opacities on bedside chest radiograph with a RALE score≥16, and exclusion of cardiogenic pulmonary edema. Incidence rate of ALI was estimated to be 9.7%. ALI diagnosis was associated with multiple clinical complications, prolonged hospital stay, higher medical bills, and higher perioperative mortality. Nine risk factors including BMI, ASA class, DLCO%, duration of surgery, neutrophil percentage, high-density lipoprotein, and electrolyte disorders were identified. The RALE score of the lung lobes of the operative side was higher than the non-operative side. A new approach for identifying ALI in esophageal cancer patients receiving esophagectomy was proposed and several risk factors were identified. ALI is common and has severe outcomes. The lung lobes on the operative side are more likely to be affected than the non-operative side.

Case of a placental site trophoblastic tumor that manifested a pulmonary hemorrhage

Placental site trophoblastic tumor (PSTT) is the 3rd most frequently encountered gestational trophoblastic tumor after destructive cystic mole and choriocarcinoma. Currently, according to the literature, just over 600 cases are described in the world. The low incidence of this tumor, the non-specific clinical picture and the lack of changes in the overall clinical analysis pose significant challenges for clinicians in terms of reliable preoperative diagnosis. Clinical observation is made of a 34-year-old patient with PSTT manifested by hemoptysis due to bilateral metastatic lung injury. The diagnosis was verified histologically using immunohistochemical methods of investigation after an open biopsy of pulmonary tissue (lung resection). Then the patient underwent courses of adjuvant chemotherapy, surgical intervention on the opposite lung to remove the remaining tumor deposits Chemotherapy after the second surgery was continued. The patient at the time of writing (within 1 year and 6 months after the first lung operation) is alive, hysterectomy was not performed, clinical and radiological signs of tumor progression are absent.

ĐẶC ĐIỂM LÂM SÀNG, NGUYÊN NHÂN, PHÂN LOẠI SUY HÔ HẤP CẤP Ở TRẺ EM THEO KHÍ MÁU

SUMMARY
 THE CLINICAL FEATURE, CAUSES AND CLASSIFICATION OF PEDIATRIC ACUTE RESPIRATORY FAILURE THROUGH ARTERIAL BLOOD GAS
 Pham Thi Que, Pham Van Thang
 Ha Noi Medical University
 
 Objectives: The study to describe clinical feature, causes and classification of acute respiratory failure in children through arterial blood gas in the Intensive Care Unit of Vietnam National Children's Hospital.
 Subjects and Methods: Aprospective descriptive study on 96 patients with acute respiratory failure in the Intensive Care Unit in Vietnam of National Children's Hospital from 10/2016 to 10/2017.
 Results: Type 2 acute respiratory failure was 55,2%, followed by type 1 with 25% and type 3 with 19,8%. Total patients with type 1 respiratory failure had tachypnea, cyanosis and SpO2 ˂ 90% and bilateral parenchymal lung injury. Type 2 acute respiratory failure can have symptoms like brachypnea, acynosis, SpO2 ≥ 90%. Wheezing is most common; emphysema and atelectasis with 37,2%. Bronchopneumonia is the most common cause of acute respiratory failure, including 61,1% type 2 acute respiratory failure.
 Conclusion: Based on the clinical feature of acute respiratory failure as a basis for assessing severe condition and appropriate treatment interventions.
 Key words: classification of acute respiratory failure, arterial blood gas.

The Effect of Compartmental Asymmetry on the Monitoring of Pulmonary Mechanics and Lung Volumes.

Esophageal pressure measurement for computation of transpulmonary pressure (Ptp) has begun to be incorporated into clinical use for evaluating forces across the lungs. Gaps exist in our understanding of how esophageal pressure (and therefore Ptp), a value measured at a single site, responds when respiratory system compartments are asymmetrically affected by whole-lung atelectasis or unilateral injury as well as changes in chest wall compliance. We reasoned that Ptp would track with aerated volume changes as estimated by functional residual capacity (FRC) and tidal volume. We examined this hypothesis in the setting of asymmetric lungs and changes in intra-abdominal pressure. This study was conducted in the animal laboratory of a university-affiliated hospital. Models of unilateral atelectasis and unilateral and bilateral lung injury exposed to intra-abdominal hypertension (IAH) in 10 deeply sedated mechanically ventilated swine. Atelectasis was created by balloon occlusion of the left main bronchus. Unilateral lung injury was induced by saline lavage of isolated right lung. Diffuse lung injury was induced by saline lavage of both lungs. The peritoneum was insufflated with air to create a model of pressure-regulated IAH. We measured esophageal pressures, airway pressures, FRC by gas dilution, and oxygenation. FRC was reduced by IAH in normal lungs (P < .001) and both asymmetric lung pathologies (P < .001). Ptp at end-expiration was decreased by IAH in bilateral (P = .001) and unilateral lung injury (P = .003) as well as unilateral atelectasis (P = .019). In the setting of both lung injury models, end-expiratory Ptp showed a moderate correlation in tracking with FRC. Ptp tracks with aerated lung volume in the setting of thoracic asymmetry and changes in intra-abdominal pressure. However, used alone, it cannot distinguish the relative contributions of air-space distention and recruitment of lung units.

2016 Influenza epidemics: clinical and epidemiological features and current abilities for effective treatment (according to data from the Clinical Infectious Diseases Hospital No. 1, Moscow)

The aim of this study was to monitor in-hospital influenza virus infection during 2015 – 2016 epidemic flu season. Methods. Influenza virus was searched in patients hospitalized to a clinical infectious diseases hospital with acute respiratory viral infection during 2015 – 2016 influenza seasonal growth period using real-time RT-PCR method. Influenza virus was isolated from nasal swabs and autopsy material using canine kidney cell line. Other laboratory methods used included complete blood count, blood chemistry, blood gas analysis, urinalysis, and chest X-ray examination. Results. We examined 1,491 patients (375 adults, 546 children, 570 pregnant women with early gestational age). The proportion of hospitalized patients with confirmed A / H1N1pdm09 influenza in January – February, 2016, was 91.3%. A / H3N2 influenza virus was diagnosed in 5.7%, influenza B virus was isolated in 1.2% of patients. Totally, influenza virus was detected in 35.2% of samples, of which 30.1% of samples were obtained from adults, 33.7% of samples were obtained from children, and 39.8% of samples were obtained from pregnant women. The prevalent patient’s age was 15 to 60 years (76.1%) in adults and 3 to 6 years in children. Moderate course of influenza with a high rate of hospital admission was seen more often and was similar to that of 2009 – 2010 epidemic season. Proportion of patients with flu complicated by pneumonia was higher than that in 2014 – 2015 epidemic season. Bilateral lung injury was diagnosed in 48.4% of patients. High mortality in ICU (46.4%) was due to delayed start of antiviral treatment and late admission to a hospital. Conclusion. In 2015 – 2016 epidemic flu season, higher morbidity, complications and poor outcomes were related to predominant infection of A – H1N1pdm09 influenza virus. Risk factors of complications and death were delayed care seeking, lack of modern antiviral medications and comorbidity.

初療室でECMOを導入し，救命し得た重症多発外傷の2症例(Two case of polytrauma patients with extracorporeal membrane oxygenation introduced in ER)

要旨平成22年人口動態統計によると，外傷死亡者の傷病部位として胸部外傷は頭部外傷に次いで多い 。胸部外傷を伴う多発外傷患者が，大量輸液・輸血や凝固障害により，他部位の止血処置中に著しい低酸素血症に陥ることは，重症例では稀ではない。これまで，胸部外傷によるsecondary ARDSに対するextracorporeal membrane oxygenation（以下，ECMO）導入の報告は散見されるが，病院到着から数時間以内の超急性期に初療室でECMOを導入することで，良好な経過をたどった2症例を経験したため報告する。症例1は，重症肺挫傷に対する下葉切除中の低酸素血症，低換気に対して術中にECMOを導入した。症例2は，重症骨盤骨折，腸管損傷に肺挫傷を合併し，腹部骨盤手術中に喀血し呼吸不全に陥ったため，ECMO実施下に止血を行った。2症例とも肺実質内に造影剤の血管外漏出像を認め，さらに他部位に複数箇所の止血を要する多発外傷例であり，ECMO導入により止血まで十分な酸素化が得られた。外傷症例に対して，来院から数時間以内に初療室においてECMO導入を速やかに行い，呼吸を担保しつつ止血術を行うことで救命し得た。外傷は，止血が得られれば引き続く集学的治療で十分可逆的な病態もあるため，救命手段の一つとして初療室でのECMO導入は有用な可能性がある。

The molecular fingerprint of lung inflammation after blunt chest trauma.

BackgroundAfter severe blunt chest trauma, the development of an acute lung injury (ALI) is often associated with severe or even lethal complications. Especially in multiple injured patients after blunt chest trauma ALI/ARDS [acute respiratory distress syndrome (ARDS)] is frequent. However, in the initial posttraumatic phase, inflammatory clinical signs are often not apparent and underlying changes in gene-expression profile are unknown.MethodsTherefore, inflammation in lung tissue following blunt chest trauma was characterized in a well-defined bilateral lung injury model. Using DNA microarrays representing 9240 genes, the temporal sequence of blunt chest trauma-induced gene-expression patterns in lung tissue was examined.ResultsThe results suggest an activation of a highly complex transcriptional program in response to chest trauma. Chest trauma led to elevated expression levels of inflammatory and coagulatory proteins (such as TNFα receptor, IL-1α, IL-1β, C3, NF-κB and plasminogen activator). However, upregulation of proteins was found, usually incoherent of exerting effects in blunt thoracic trauma (pendrin, resistin, metallothionein and glucocorticoid-induced leucine zipper). Furthermore, significant downregulation was observed as early as 10 min after trauma for cytokines and complement factors (LCR-1, C4) as well as for intracellular signaling molecules (inhibitory protein phosphatase) and ion-channels (voltage-dependent Ca2+ channel).ConclusionsTaken together, the provided global perspective of the inflammatory response following blunt chest trauma could provide a molecular framework for future research in trauma pathophysiology.

Impact of Chest Wall Modifications and Lung Injury on the Correspondence Between Airway and Transpulmonary Driving Pressures.

Recent interest has arisen in airway driving pressure (DP(AW)), the quotient of tidal volume (V(T)), and respiratory system compliance (C(RS)), which could serve as a direct and easily measured marker for ventilator-induced lung injury risk. We aimed to test the correspondence between DP(AW) and transpulmonary driving pressure (DP(TP))-the quotient of V(T) and lung compliance (C(L)), in response to intra-abdominal hypertension and changes in positive end-expiratory pressure during different models of lung pathology. Well-controlled experimental setting that allowed reversible modification of chest wall compliance (C(CW)) in a variety of models of lung pathology. Large animal laboratory of a university-affiliated hospital. Ten deeply anesthetized swine. Application of intra-abdominal pressures of 0 and 20 cm H2O at positive end-expiratory pressure of 1 and 10 cm H2O, under volume-controlled mechanical ventilation in the settings of normal lungs (baseline), unilateral whole-lung atelectasis, and unilateral and bilateral lung injuries caused by saline lavage. Pulmonary mechanics including esophageal pressure and calculations of DP(AW), DP(TP), C(RS), C(L), and C(CW). When compared with normal intra-abdominal pressures, intra-abdominal hypertension increased DP(AW), during both "normal lung conditions" (p < 0.0001) and "unilateral atelectasis" (p = 0.0026). In contrast, DP(TP) remained virtually unaffected by changes in positive end-expiratory pressure or intra-abdominal pressures in both conditions. During unilateral lung injury, both DPA(W) and DP(TP) were increased by the presence of intra-abdominal hypertension (p < 0.0001 and p = 0.0222, respectively). During bilateral lung injury, intra-abdominal hypertension increased both DP(AW) (at positive end-expiratory pressure of 1 cm H2O, p < 0.0001; and at positive end-expiratory pressure of 10 cm H2O, p = 0.0091) and DP(TP) (at positive end-expiratory pressure of 1 cm H2O, p = 0.0510; and at positive end-expiratory pressure of 10 cm H2O, p = 0.0335). Our data indicate that DP(AW) is influenced by reductions in chest wall compliance and by underlying lung properties. As with other measures of pulmonary mechanics that are based on unmodified P(AW), caution is advised in attempting to attribute hazard or safety to any specific absolute value of DP(AW).

Clinical analysis of chronic lung injury in patients with non-Hodgkin lymphoma after CHOP chemotherapy.

We conducted a preliminarily study on the clinical characteristics of chronic lung injury (CLI) in patients with non-Hodgkin lymphoma (NHL) after CHOP chemotherapy and observed the effects of this injury on CHOP treatment efficacy. Sixty patients who were diagnosed as NHL and received CHOP chemotherapy in hospital were enrolled for this clinical trial. CLI was assessed by clinical symptoms and computed tomography (CT) scan conducted before and after chemotherapy. The effect of CLI on the efficacy of CHOP chemotherapy in patients with NHL was evaluated by comparing treatment response and recurrence rate to patients with no signs of lung injury. Our CT scans revealed multiple signs of CLI in 35 patients (56.67%), such as pulmonary diffuse, limited infiltration shadow or ground glass-like changes. Among them, 23 patients (38.33%) showed bilateral diffuse lung injury and 12 (20.00%) showed topical lung injury. Most patients suffering from 6 to 12months delayed recurrence exhibited signs of CLI. The inflammatory response of CLI may increase the risk of disease progression and recurrence. Therefore, early diagnosis and intervention, which play a positive role in the clinical treatment and the long-term efficacy, are critical for patients with NHL.

COMMUNITY-ACQUIRED PNEUMONIA: RISK FACTORS OF DEATH

The objective of this study was to analyze risk factors of death in patients with community-acquired pneumonia (CAP). This was a retrospective analysis of medical records of 62 patients dead from CAP within a year in hospitals at Kazan city. We described clinical course of CAP leading to a patient's death. Predictors of fatal outcome of CAP were social status, delayed admission to a hospital, smoking history, alcohol abuse, mental and nutritive disorders, bilateral lung injury, pleural effusion, respiratory failure and haemodynamic instability.

Character features of community-acquired pneumonia during the pandemic influenza A / N1N1 / 2009

Summary. Course and complications of community-acquired pneumonia (CAP) during the pandemic influenza A / N1N1 / 2009 were studied based on clinical, laboratory and radiology data. The study involved 250 patients, of them 57 patients with uncomplicated CAP (the 1st group), 124 patients with CAP and the systemic inflammatory response syndrome (SIRS) (the 2nd group), 53 patients with CAP and severe sepsis (the 3rd group), and 16 patients with CAP and septic shock (the 4th group). All patients received antiviral, antibacterial and symptomatic therapy; 193 (77.2 %) patients needed supplemental oxygen, 108 (56 %) were admitted to ICU, 15.6 % of patients needed mechanical ventilation. Bilateral lung injury was diagnosed in 225 patients (90.0 %). Overall mortality was 10.4 %, mortality in obese patients was 30.0 %.

Morphological and structural variants of cellular and stromal interaction in a focus of destruction in acute lung abscess and lung gangrene in term of formation and stabilisation of fibrin-associated processes

Purulent and destructive lung diseases are often complicated by loss of anatomic structure of lung tissue, development of lung cirrhosis with subsequent respiratory and heart failure. We performed pathomorphological examination of operational and post mortem lung tissue specimens from 116 inpatients of 25 to 78 years of age with acute lung abscess or lung gangrene who was treated at a pulmonology center from 1999 to 2005. Acute lung inflammation tending to suppuration was characterized by pronounced cell reaction with no "fibrin blockage" and resulted in extended histolysis and abscess formation. "Young" fibrin was often found. Microvessels were fully passable, full-blooded with no fibrin into lumen. At subacute stage, fibrin was "maturing" with subsequent organization and growth of granulated tissue. Clinically, there were sequestered lung abscesses. Massive deposits of "young" and "maturing" fibrin formed "fibrin cocoon" with macrophages and neutrophils bricked up inside. Cell reaction was weak. There were swelling and desquamation of endothelium of microvessels, massive fibrin deposits into vessel lumen and prominent perivascular impregnation with fibrin. This pathological variant could lead to formation of abscess or pulmonary fibrosis with carnification. In cases of massive subtotal or total, often bilateral lung injury with weak delimiting of purulent and destructive process massive destructive zones with resting lung parenchyma faintly impregnated with fibrin were seen. There were no features of fibrin deposition inside microvessels. Functional activity of neutrophils and macrophages was greatly decreased. Therefore, the most favourable pathohistological variant appears to be formation of fibrin blockage consisted of "young" fibrin deposits; prominent cell reaction and absence of microcirculatory block. Structural changes of cells and stroma should be considered during pathological examination in order to provide optimal treatment strategy.

THE ROLE OF C5A IN THE INNATE IMMUNE RESPONSE AFTER EXPERIMENTAL BLUNT CHEST TRAUMA

The inflammatory response after severe blunt chest trauma often leads to acute lung injury and acute respiratory distress syndrome which are associated with high mortality rates. Whereas the role of innate immunity in acute lung injury has been broadly investigated, the immune response after blunt chest trauma is still poorly understood. Therefore, the role of complement and neutrophils was determined in bilateral lung injury induced by a single blast wave. The following time-points were investigated posttrauma: sham, 1, 6, 12, and 24 h. There was a time-dependent systemic activation of complement as determined by CH-50 and presence of C5a-dependent chemotactic plasma activity. Moreover, factor H, a complement regulatory protein, was increased systemically and locally after injury. Anti-C5a treatment immediately after trauma ameliorated these peaks. After an initial systemic leukopenic phase, a marked leukocytosis occurred. The latter was normalized by C5a blockade. In parallel, white blood cell count in bronchioalveolar lavage fluids was increased as a function of time and was significantly decreased by anti-C5a treatment. Trauma-induced lung injury was also associated with dramatic changes in neutrophil function, namely early enhanced chemotaxis and phagocytosis, followed by prolonged functional defects-all of which were ameliorated by anti-C5a treatment. Furthermore, blockade of C5a ameliorated the buildup of the proinflammatory cytokine TNF-alpha, diminished the increase of cytokine-induced neutrophil chemoattractant 1, and altered the levels of the anti-inflammatory cytokine IL-10. These data suggest that blunt chest trauma leads to systemic activation of complement and robust C5a generation, which causes perturbations in defensive functions of neutrophils. Thus, C5a might represent a potential target for therapeutic immunomodulation to prevent immune dysfunctions post-trauma and thereby, perhaps, the progression to acute respiratory distress syndrome.

THE ROLE OF C5A IN EXPERIMENTAL BLUNT CHEST TRAUMA

The inflammatory response following severe blunt chest trauma often leads to ARDS, which is associated with a high mortality rate. The systemic immune response of ARDS is still poorly understood. Therefore, the role of complement and neutrophils was determined in bilateral lung injury, induced by a single blast wave. There was a time-dependent systemic activation of complement as determined by reduction in CH-50 and presence of C5a-dependent chemotactic serum activity. Post trauma, there was an initial systemic leukopenic phase, followed by a marked leukocytotic phase, both of which were normalized by C5a-blockade. Trauma-induced lung injury was also associated with dramatic changes in neutrophil function, namely enhanced chemotactic and phagocytic rates in blood neutrophils, followed by prolonged functional defects, all of which were prevented by anti-C5a treatment. Furthermore, there was a C5a-dependent increase in serum and BAL fluids of the complement regulatory protein, factor H. These data suggest that blunt chest trauma leads to systemic C5a generation, which causes perturbations in innate immune defensive functions of neutrophils. Thus, C5a might represent a potential target for therapeutic immune modulation to prevent the development of neutrophil defects and, perhaps, the progression to ARDS.

Molecular Profiling of Experimental Blunt Chest Trauma

Trauma to the chest still causes approximately a quarter of all trauma-related deaths and pulmonary contusion itself has an age-dependent mortality up to 42%. Here we explore the diverse transcriptional programs activated after blunt thoracic trauma, which is still poorly understood. Bilateral lung injury was induced in rats by a single blast wave, followed by RNA-isolation and microarray analysis at various time points after trauma (0–24h post-trauma). To determine the protective effects of a systemic C5a-blockade in the 3h post trauma window, either pre-immune IgG or anti-C5a IgG was applied intravenously. During the early post-traumatic phase, proteins of the intracellular PIP3-kinase pathway were significantly downregulated, while various cytokines and their receptors were upregulated. Proteins encoding for the coagulation system were massively upregulated. Whereas the expression of the complement split product C4a was consistently reduced, C3 was upregulated 12h post injury. In the late post-traumatic phase, MAP-kinase and ion-channels were also affected and down-regulated. While various important complement players, MAP-kinase and the bradykinin-receptor were down-regulated 3h post injury in IgG-treated animals, systemic C5a blockade after trauma led to a more transcriptional balance program similar to the sham treated group. These data might lead to a better understanding of the molecular signature after severe trauma and reveal new therapeutic targets to prevent the severe consequences of blunt chest trauma. This work was supported by NIH Grants No. GM-61656, GM-29507 and HL-31963.