Severe Acute Pneumonia Research Articles

Design of Potential RNAi (miRNA and siRNA) Molecules for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Gene Silencing by Computational Method.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that manifests itself in viral infection with fever, cough, shortness of breath, renal failure and severe acute pneumonia, which often result in a fatal outcome. MERS-CoV has been shown to spread between people who are in close contact. Transmission from infected patients to healthcare personnel has also been observed and is irredeemable with present technology. Genetic studies on MERS-CoV have shown that ORF1ab encodes replicase polyproteins and play a foremost role in viral infection. Therefore, ORF1ab replicase polyprotein may be used as a suitable target for disease control. Viral activity can be controlled by RNA interference (RNAi) technology, a leading method for post transcriptional gene silencing in a sequence-specific manner. However, there is a genetic inconsistency in different viral isolates; it is a great challenge to design potential RNAi (miRNA and siRNA) molecules which can silence the respective target genes rather than any other viral gene simultaneously. In the current study, four effective miRNA and five siRNA molecules for silencing of nine different strains of MERS-CoV were rationally designed and corroborated using computational methods, which might lead to knockdown the activity of virus. siRNA and miRNA molecules were predicted against ORF1ab gene of different strains of MERS-CoV as effective candidate using computational methods. Thus, this method may provide an insight for the chemical synthesis of antiviral RNA molecule for the treatment of MERS-CoV, at genomic level.

Results of Surveillance of Influenza in Out-patients Influenza-like Illness (ILI), Inpatients Severe Acute Respiratory Illness (SARI) and Severe Pneumonia cases in Community Based Medical College Hospital, Bangladesh, Mymensingh during the period of May 2

Influenza is prevalent in Bangladesh among both adults and children. This observation is proved by recent population-based estimates. A hospital based surveillance study was conducted under the supervision of ICDDRB at Community Based Medical College Hospital, Bangladesh (CBMCH,B). To explore the epidemiology and seasonality of influenza throughout the Mymensingh region and all age groups, we analyzed the data collected during the period of May 2007 to May 2012 for a period of 5 years. The result revealed that out of 1014 patients, 140(14%) were influenza positive by real time RT-PCR. Among the sample-positive patients, 90(64%) were type A and 50(36%) type B. Hemagglutinin subtyping of type A virus detected 7(8%) A/H1 and 42(47%) A/H3, 41(46%) H1N1 pdm09 but no A/H5 or other novel influenza strains. The frequency of influenza cases was highest among children aged under 5 year 44%, while the laboratory confirmed cases were highest among patients aged under 1 year to 30 years 54%. We identified a distinct influenza peak during the rainy season (May to September), highest in July and August. There is a very low presence of influenza in the month of October, November and December (2, 1, 2 flu positive cases in 5 year period respectively). Our surveillance data confirms that influenza is prevalent throughout Mymensingh, affecting a wide range of ages and causing considerable morbidity and hospital care. A unimodal influenza seasonality may allow Mymensingh, Bangladesh to time annual influenza prevention messages and vaccination campaigns to reduce the national influenza burden. To scale-up such national interventions, we need to quantify the national rates of influenza and the economic burden associated this disease through further studies.
 CBMJ 2015 January: Vol. 04 No. 01 P: 03-12

Role of IL-22 in the protection against nontypeable Haemophilus influenza infection

Introduction Haemophilus influenzae infections are a major cause of disease exacerbation in inflammatory disorders including chronic obstructive pulmonary disease (COPD). During infection, IL-17 and IL-22 are essential for the control of both neutrophil inflammation and anti-microbial response. We observed a deficient IL-22 response during H. influenzae-induced exacerbations in COPD mice. Since the role of IL-22 is unknown, we investigate the function of this cytokine in the protection against nontypeable H. influenza (NTHI) in mice. Methods IL-22-deficient (IL-22-/−) and wild-type mice (C57BL/6) were exposed or not to sublethal dose of NTHI by intranasal route. The pro-Th1 (IL-2, IFN-γ and TNFα) and pro-Th17 (IL-1β, IL-6, IL-17 and IL-22) cytokines levels were measured by ELISA in blood, bronchoalveolar lavage (BAL) and lung tissues, 24 h and 48 h post-infection. Cytokine production was also evaluated in supernatants of spleen and lung cells after restimulation with specific Ag. Cellular profile, lung inflammation and tissue remodeling were evaluated by flow-cytometry and histological analysis, respectively. Results In WT mice, infection with NTHI strongly increased the levels of IL-17 and IL-22 in the lungs. Infected IL-22-/-mice revealed a higher bacterial load in the lung associated with an increased inflammatory reaction as shown by the levels of TNFα, IL6 in the BAL and IFNγ in the lung. In contrast, naive mice cleared the bacteria within 48 h. This defect in bacterial clearance is related with a lower production of IL-17 in the BAL and in Ag-stimulated lung cells. Histopathological and cytometric analysis confirmed that cellular infiltration with neutrophils and NK cells in the alveolar spaces and lung tissue was increased in IL-22-/-mice. IL-22-/-mice expressed a severe acute pneumonia with congestion of alveolar space at 48 h post-infection whereas WT mouse showed an acute alveolitis of moderate intensity. Conclusion These data show that a deficient production of IL-22 triggers a susceptibility to infections by H. influenzae and a more deleterious lung inflammatory reaction. Treatments favoring a Th17 response would be a potential therapeutic strategy in lung inflammatory disorders with exacerbation episodes.

Sociodemographic, Epidemiological, and Clinical Risk Factors for Childhood Pulmonary Tuberculosis in Severely Malnourished Children Presenting With Pneumonia: Observation in an Urban Hospital in Bangladesh.

We aimed to evaluate sociodemographic, epidemiological, and clinical risk factors for pulmonary tuberculosis (PTB) in children presenting with severe acute malnutrition (SAM) and pneumonia. Children aged 0 to 59 months with SAM and radiologic pneumonia from April 2011 to July 2012 were studied in Bangladesh. Children with confirmed PTB (by culture and/or X-pert MTB/RIF) (cases = 27) and without PTB (controls = 81; randomly selected from 378 children) were compared. The cases more often had the history of contact with active PTB patient (P < .01) and exposure to cigarette smoke (P = .04) compared with the controls. In logistic regression analysis, after adjusting for potential confounders, the cases were independently associated with working mother (P = .05) and positive tuberculin skin test (TST; P = .02). Thus, pneumonia in SAM children is a common presentation of PTB and further highlights the importance of the use of simple TST and/or history of contact with active TB patients in diagnosing PTB in such children, especially in resource-limited settings.

Post-Legionellosis Proliferative Glomerulonephritis

To the Editor: Today in developed countries, infection-related glomerulonephritides are incommon and often associated with debilitating diseases. Legionnaires’ disease (LD) is one of the most common causes of severe community-acquired acute pneumonia in Europe and in up to 40% of cases of hospital-acquired pneumonia. The acute kidney injury (AKI) in LD is a well described complication but the renal morphology has only been reported in a few cases. The Tubulointerstitial Nephritis (TIN) is the most diagnosed histological change; instead, there [...]

Design of potential RNAi (miRNA and siRNA) molecules for Middle East respiratory syndrome coronavirus (MERS-CoV) gene silencing by computational method.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that manifests itself in viral infection with fever, cough, shortness of breath, renal failure and severe acute pneumonia, which often result in a fatal outcome. MERS-CoV has been shown to spread between people who are in close contact. Transmission from infected patients to healthcare personnel has also been observed and is irredeemable with present technology. Genetic studies on MERS-CoV have shown that ORF 1ab encodes replicase polyproteins and play a foremost role in viral infection. Therefore, ORF 1ab replicase polyprotein may be used as suitable target for disease control. Viral activity can be controlled by RNA interference (RNAi) technology, a leading method for post transcriptional gene silencing in a sequence specific manner. However, there is a genetic inconsistency in different viral isolates; it is a great challenge to design potential RNAi (miRNA and siRNA) molecules which can silence the respective target genes rather than any other viral gene simultaneously. In current study four effective miRNA and five siRNA molecules for silencing of nine different strains of MERS-CoV were rationally designed and corroborated using computational methods, which might lead to knockdown the activity of virus. siRNA and miRNA molecules were predicted against ORF1ab gene of different strains of MERS-CoV as effective candidate using computational methods. Thus, this method may provide an insight for the chemical synthesis of antiviral RNA molecule for the treatment of MERS-CoV, at genomic level.

Design of potential RNAi (miRNA and siRNA) molecules for Middle East respiratory syndrome coronavirus (MERS-CoV) gene silencing by computational method.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that manifests itself in viral infection with fever, cough, shortness of breath, renal failure and severe acute pneumonia, which often result in a fatal outcome. MERS-CoV has been shown to spread between people who are in close contact. Transmission from infected patients to healthcare personnel has also been observed and is irredeemable with present technology. Genetic studies on MERS-CoV have shown that ORF 1ab encodes replicase polyproteins and play a foremost role in viral infection. Therefore, ORF 1ab replicase polyprotein may be used as suitable target for disease control. Viral activity can be controlled by RNA interference (RNAi) technology, a leading method for post transcriptional gene silencing in a sequence specific manner. However, there is a genetic inconsistency in different viral isolates; it is a great challenge to design potential RNAi (miRNA and siRNA) molecules which can silence the respective target genes rather than any other viral gene simultaneously. In current study four effective miRNA and five siRNA molecules for silencing of nine different strains of MERS-CoV were rationally designed and corroborated using computational methods, which might lead to knockdown the activity of virus. siRNA and miRNA molecules were predicted against ORF1ab gene of different strains of MERS-CoV as effective candidate using computational methods. Thus, this method may provide an insight for the chemical synthesis of antiviral RNA molecule for the treatment of MERS-CoV, at genomic level.

Crystal structure of the papain-like protease of MERS coronavirus reveals unusual, potentially druggable active-site features

The Middle-East Respiratory Syndrome coronavirus (MERS-CoV) causes severe acute pneumonia and renal failure. The MERS-CoV papain-like protease (PLpro) is a potential target for the development of antiviral drugs. To facilitate these efforts, we determined the three-dimensional structure of the enzyme by X-ray crystallography. The molecule consists of a ubiquitin-like domain and a catalytic core domain. The catalytic domain displays an extended right-hand fold with a zinc ribbon and embraces a solvent-exposed substrate-binding region. The overall structure of the MERS-CoV PLpro is similar to that of the corresponding SARS-CoV enzyme, but the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites differ from the latter. These differences are the likely reason for reduced in vitro peptide hydrolysis and deubiquitinating activities of the MERS-CoV PLpro, compared to the homologous enzyme from the SARS coronavirus. Introduction of a side-chain capable of oxyanion stabilization through the Leu106Trp mutation greatly enhances the in vitro catalytic activity of the MERS-CoV PLpro. The unique features observed in the crystal structure of the MERS-CoV PLpro should allow the design of antivirals that would not interfere with host ubiquitin-specific proteases.

Restrictive parenteral fluid therapy in infants and children presenting with acute severe viral pneumonia in the PICU: a single-center experience

Acute viral (RSV and non-RSV) pneumonia is one of the most common causes of lower respiratory tract infection in infants and children. Although only 2 to 3% of infants with bronchiolitis require hospitalized management based on published literature, in recent years we see more children requiring hospitalization in high-dependency units. Most of these children require intravenous fluid therapy and some form of oxygen supplementation. As there is no standardized evidence-based parenteral fluid therapy protocol specific for acute severe viral pneumonia available, we decided to retrospectively analyze the result of our restrictive fluid therapy protocol.

The Role of Oxidative Stress Markers in Acute Respiratory Distress Syndrome

Abstract Introduction. Patients in the intensive care unit (ICU) are likely to suffer from acute respiratory failure (ARF) with a risk of developing acute lung injury (ALI) and its more severe condition, acute respiratory distress syndrome (ARDS) with 30 - 50% mortality. Evidence shows, that important role in ARDS pathophysiology may play an imbalance between oxidant and antioxidant species. Oxidative stress is well established in adult critical illnesses characterized by systemic inflammatory response. Aim of the study was to investigate the influence of oxidative stress species on developing of acute respiratory distress syndrome in patients at risk. Materials and methods. The study was conducted in Pauls Stradins Clinical University Hospital ICU during 6 months in 2013 and approved by ethics committee. There were included 15 ARDS risk patients over 18 years of age with mechanical lung ventilation (MLV) over 24 hours and massive blood component transfusions, acute severe pancreatitis, pneumonia or sepsis. Blood samples were taken three times during observational period- first sample were taken just exactly after inclusion, second sample- on 4th and the last sample- on 7th day after inclusion. The developing of ARDS were diagnosed using revised diagnostic criteria according to the Berlin definition. Reactive oxygen species were measured in plasma using manual or automatic spectrophotometry. Results. Among included patients 82.4 % were males with the mean age 49.3 years, for female 67 years. The most popular diagnosis was acute severe pneumonia (n= 5; 33.3 %), followed by patients with sepsis (n= 4; 26.7%) and acute severe pancreatitis (n= 4; 26.7%). The most informative marker of oxidative stress among all ARDS risk patients is GPx, which correlates with PaO2/ FiO2 and oxidation index (R= -0.52; p= 0.045 and R= 0.57; p= 0.027) at the 1st day of observation. At the 4th day of observation GPx shows statistically significant relation with the level of PEEP (R= 0.57; p= 0.033). Among ARDS patients we have found correlation between PaO2/FiO2 ratio and MDA+ HNE plasma levels (R= 0.69; p= 0.026) at the 1st day of observation. Conclusion. Reactive oxygen substances causing oxidative stress shows a dynamic changes in ARDS patients. The changes of some oxidative markers are related to the increased level of hypoxemia and PEEP used in treatment of ARDS patients.

Evaluation of Serologic and Antigenic Relationships Between Middle Eastern Respiratory Syndrome Coronavirus and Other Coronaviruses to Develop Vaccine Platforms for the Rapid Response to Emerging Coronaviruses

Background. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing severe acute respiratory disease and pneumonia, with 44% mortality among 136 cases to date. Design of vaccines to limit the virus spread or diagnostic tests to track newly emerging strains requires knowledge of antigenic and serologic relationships between MERS-CoV and other CoVs. Methods. Using synthetic genomics and Venezuelan equine encephalitis virus replicons (VRPs) expressing spike and nucleocapsid proteins from MERS-CoV and other human and bat CoVs, we characterize the antigenic responses (using Western blot and enzyme-linked immunosorbent assay) and serologic responses (using neutralization assays) against 2 MERS-CoV isolates in comparison with those of other human and bat CoVs. Results. Serologic and neutralization responses against the spike glycoprotein were primarily strain specific, with a very low level of cross-reactivity within or across subgroups. CoV N proteins within but not across subgroups share cross-reactive epitopes with MERS-CoV isolates. Our findings were validated using a convalescent-phase serum specimen from a patient infected with MERS-CoV (NA 01) and human antiserum against SARS-CoV, human CoV NL63, and human CoV OC43. Conclusions. Vaccine design for emerging CoVs should involve chimeric spike protein containing neutralizing epitopes from multiple virus strains across subgroups to reduce immune pathology, and a diagnostic platform should include a panel of nucleocapsid and spike proteins from phylogenetically distinct CoVs.

Influenza A Virus Impairs Control of Mycobacterium tuberculosis Coinfection Through a Type I Interferon Receptor–Dependent Pathway

Influenza followed by severe acute bacterial pneumonia is a major cause of mortality worldwide. Several mechanisms account for this enhanced susceptibility, including increased production of type I interferon (IFN). In individuals infected with Mycobacterium tuberculosis, the influence of acute viral infections on tuberculosis progression is unclear. We show that prior exposure of mice to influenza A virus, followed by M. tuberculosis infection, leads to enhanced mycobacterial growth and decreased survival. Following M. tuberculosis/influenza virus coinfection, mycobacterial growth is enhanced by a type I IFN signaling pathway. Our findings highlight the detrimental influence influenza virus infection can have before or during M. tuberculosis infection.

Noninvasive ventilation for acute respiratory failure: state of the art (I part)

Background: In the last years Non-Invasive Ventilation (NIV) has been playing an important role in the treatment of Acute Respiratory Failure (ARF). A lot of trials have shown improvements in clinical features (respiratory rate, neurological score), pH and arterial blood gases. Methods: In particular clinical conditions, such as Acute Cardiogenic Pulmonary Edema (ACPE) and acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD), systematic reviews and meta-analysis show a reduction in the need for intubation and in-hospital mortality compared to standard medical treatment. In other clinical conditions, such as acute asthma, Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS) and severe pneumonia, NIV does not show significant improvements in term of avoided intubations or mortality rate. Although the first important data on NIV comes from studies performed in Intensive Care Units (ICUs), subsequently these methodologies of ventilation have been used with increasing frequency in Emergency Departments (ED) and medical wards. Results: Studies developed in ICU sometimes report slightly worse outcomes compared to studies performed in general wards due to the need to treat more severe patients in ICU. Aetiology remains one of the most important factor determining prognosis: different pathological mechanisms substain different clinical conditions and not in all cases the application of positive pressures to the airways is useful. NIV for ARF due to COPD and ACPE is feasible, safe and effective also in a general medical ward if selection of patients, staff training and monitoring are appropriate: its early application improves clinical parameters, arterial blood gases, prevents endotracheal intubation, decreases mortality and hospitalisation. This should encourage the diffusion of NIV in this specific setting.

Effect of nitric oxide inhalation on gas exchange in acute severe pneumonia

Inhaled nitric oxide (NO) causes selective pulmonary vasodilatation and may improve gas exchange. The study was aimed to evaluate the acute effects of inhaled NO on pulmonary gas exchange in severe unilateral pneumonia, where hypoxemia results from increased intrapulmonary shunt. We studied 8 patients without preexisting lung disease (59±18 yr; 4M/4F) with early unilateral severe pneumonia and respiratory failure. Pulmonary and systemic hemodynamics and gas exchange, including ventilation–perfusion (V;A/Q;) distributions, were measured at baseline and while breathing 5 and 40 parts per million (ppm) of NO. Inhaled NO caused a dose-dependent fall in pulmonary vascular resistance (by 12% and 21%, with 5 and 40ppm, respectively; p<0.01, each) and improvement of PaO2 (by 25% and 23%; p<0.05, each), owing to the reduction of intrapulmonary shunt (by 23% and 27%; p<0.05, each), without changes in the amount of perfusion to low V;A/Q; ratio alveolar units. Patients with greater baseline intrapulmonary shunt exhibited greater improvement in arterial oxygenation (r2=0.55, p<0.05). We conclude that low doses of inhaled NO improve pulmonary gas exchange in acute severe pneumonia.

Efficient Replication of the Novel Human Betacoronavirus EMC on Primary Human Epithelium Highlights Its Zoonotic Potential

ABSTRACTThe recent emergence of a novel human coronavirus (HCoV-EMC) in the Middle East raised considerable concerns, as it is associated with severe acute pneumonia, renal failure, and fatal outcome and thus resembles the clinical presentation of severe acute respiratory syndrome (SARS) observed in 2002 and 2003. Like SARS-CoV, HCoV-EMC is of zoonotic origin and closely related to bat coronaviruses. The human airway epithelium (HAE) represents the entry point and primary target tissue for respiratory viruses and is highly relevant for assessing the zoonotic potential of emerging respiratory viruses, such as HCoV-EMC. Here, we show that pseudostratified HAE cultures derived from different donors are highly permissive to HCoV-EMC infection, and by using reverse transcription (RT)-PCR and RNAseq data, we experimentally determined the identity of seven HCoV-EMC subgenomic mRNAs. Although the HAE cells were readily responsive to type I and type III interferon (IFN), we observed neither a pronounced inflammatory cytokine nor any detectable IFN responses following HCoV-EMC, SARS-CoV, or HCoV-229E infection, suggesting that innate immune evasion mechanisms and putative IFN antagonists of HCoV-EMC are operational in the new host. Importantly, however, we demonstrate that both type I and type III IFN can efficiently reduce HCoV-EMC replication in HAE cultures, providing a possible treatment option in cases of suspected HCoV-EMC infection.

Infection of the Upper Respiratory Tract with Seasonal Influenza A(H3N2) Virus Induces Protective Immunity in Ferrets against Infection with A(H1N1)pdm09 Virus after Intranasal, but Not Intratracheal, Inoculation

The clinical symptoms caused by infection with influenza A virus vary widely and depend on the strain causing the infection, the dose and route of inoculation, and the presence of preexisting immunity. In most cases, seasonal influenza A viruses cause relatively mild upper respiratory tract disease, while sometimes patients develop an acute severe pneumonia. Heterosubtypic immunity induced by previous infections with influenza A viruses may dampen the development of clinical symptoms caused by infection with influenza A viruses of another subtype, as is the case during influenza pandemics. Here we show that ferrets acquire protective immunity after infection of the upper respiratory tract with a seasonal influenza A(H3N2) virus against subsequent infection with influenza A(H1N1)pdm09 virus inoculated by the intranasal route. However, protective heterosubtypic immunity was afforded locally, since the prior infection with the A(H3N2) virus did not provide protection against the development of pneumonia induced after intratracheal inoculation with the A(H1N1)pdm09 virus. Interestingly, some of these animals developed more severe disease than that observed in naïve control animals. These findings are of interest in light of the development of so-called universal influenza vaccines that aim at the induction of cross-reactive T cell responses.

The New Age of Virus Discovery: Genomic Analysis of a Novel Human Betacoronavirus Isolated from a Fatal Case of Pneumonia

ABSTRACTA new human betacoronavirus in lineage c, tentatively called HCoV-EMC, was isolated from a patient from the Kingdom of Saudi Arabia who died from acute severe pneumonia and renal failure. The viral RNA has been detected in eight additional cases. Sequencing and bioinformatic analysis of the viral genomic RNA showed that it is a novel virus not previously detected in any other species and that its closest relatives are two Asian bat coronaviruses. HCoV-EMC may represent a sporadic spillover to humans from an unknown animal reservoir. In a recent article, van Boheemen et al. demonstrated how state-of-the-art sequencing technology and bioinformatic analysis can quickly provide critical insight into the viral genome sequence, phylogeny, replication strategy, and potential drug and vaccine targets and generate tools to evaluate the possible epidemic risk associated with this novel human virus.

The role of atypical microorganisms and viruses in severe acute community-acquired pneumonia

RésuméL’attention des réanimateurs n’est guère attirée par les bactéries atypiques ou les virus dans le cadre des pneumonies communautaires sévères. Seules classiquement, Legionella pneumophila et les virus influenza, du fait de la pandémie grippale récente H1N1, restent présents dans la réflexion diagnostique. Pourtant, les pneumonies bactériennes atypiques ne sont pas rares, représentant jusqu’à 44 % des pneumonies communautaires. Considérées comme moins sévères que les pneumonies à bactéries pyogènes « typiques », 25 % d’entre elles justifient une hospitalisation, et 15 % présentent des critères de sepsis sévères. Si Legionella pneumophila est plus fréquemment en cause dans les formes graves, Mycoplasma pneumoniae peut être responsable de véritables défaillances multiviscérales. Les outils diagnostiques sont aujourd’hui performants (antigénurie légionelle et recherche en polymerase chain reaction [PCR] de mycoplasme en particulier) et permettent un diagnostic rapide et précoce. Le traitement est bien codifié et repose sur les macrolides ou les fluoroquinolones, en association dans les formes graves de légionellose. Le rôle des virus au cours des pneumonies communautaires sévères, seuls ou associés à des bactéries, devient de plus en plus établi grâce aux méthodes de diagnostic rapide de biologie moléculaire. Ces techniques ont permis la mise en évidence dans ces pneumonies de nombreux et nouveaux virus. Toute la question est désormais à l’imputabilité clinique de ces résultats biologiques très performants et donc à la décision d’instaurer ou non un traitement antiviral dont l’efficacité dans les formes sévères reste discutable.

Arginase 1: An Unexpected Mediator of Pulmonary Capillary Barrier Dysfunction in Models of Acute Lung Injury

The integrity of epithelial and endothelial barriers in the lower airspaces of the lungs has to be tightly regulated, in order to prevent leakage and to assure efficient gas exchange between the alveoli and capillaries. Both G− and G+ bacterial toxins, such as lipopolysaccharide and pneumolysin, respectively, can be released in high concentrations within the pulmonary compartments upon antibiotic treatment of patients suffering from acute respiratory distress syndrome (ARDS) or severe pneumonia. These toxins are able to impair endothelial barrier function, either directly, or indirectly, by induction of pro-inflammatory mediators and neutrophil sequestration. Toxin-induced endothelial hyperpermeability can involve myosin light chain phosphorylation and/or microtubule rearrangement. Endothelial nitric oxide synthase (eNOS) was proposed to be a guardian of basal barrier function, since eNOS knock-out mice display an impaired expression of inter-endothelial junction proteins and as such an increased vascular permeability, as compared to wild type mice. The enzyme arginase, the activity of which can be regulated by the redox status of the cell, exists in two isoforms – arginase 1 (cytosolic) and arginase 2 (mitochondrial) – both of which can be expressed in lung microvascular endothelial cells. Upon activation, arginase competes with eNOS for the substrate l-arginine, as such impairing eNOS-dependent NO generation and promoting reactive oxygen species generation by the enzyme. This mini-review will discuss recent findings regarding the interaction between bacterial toxins and arginase during acute lung injury and will as such address the role of arginase in bacterial toxin-induced pulmonary endothelial barrier dysfunction.

Acute Eosinophilic Pneumonia

Acute eosinophilic pneumonia is a severe and rapidly progressive lung disease that can cause fatal respiratory failure. Since this disease exhibits totally different clinical features to other eosinophilic lung diseases (ELD), it is not difficult to distinguish it among other ELDs. However, this can be similar to other diseases causing acute respiratory distress syndrome or severe community-acquired pneumonia, so the diagnosis can be delayed. The cause of this disease in the majority of patients is unknown, even though some cases may be caused by smoke, other patients inhaled dust or drugs. The diagnosis is established by bronchoalveolar lavage. Treatment with corticosteroids shows a rapid and dramatic positive response without recurrence.