Recruitment maneuver in pulmonary and extrapulmonary experimental acute lung injury

Objective. The aim of this study is to test the hypothesis that recruitment maneuvers (RMs) might act differently in models of pulmonary (p) and extrapulmonary (exp) acute lung injury (ALI) with similar transpulmonary pressure changes. Design: Prospective, randomized, controlled experimental study. Setting. University research laboratory. Subjects: Wistar rats were randomly divided into four groups. In control groups, sterile saline solution was intratracheally (0.1 mL, Cp) or intraperitoneally (1 mL, Cexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (100 jig, ALIp) or intraperitoneally (1 mg, ALIexp). After 24 hrs, animals were mechanically ventilated (tidal volume, 6 mL/kg; positive end-expiratory pressure, 5 cm H2O) and three RMs (pressure inflations to 40 cm H2O for 40 secs, 1 min apart) applied. Measurements and Main Results. Pao(2), lung resistive and viscoelastic pressures, static elastance, lung histology (light and electron microscopy), and type III procollagen messenger RNA expression in pulmonary tissue were measured before RMs and at the end of 1 hr of mechanical ventilation. Mechanical variables, gas exchange, and the fraction of area of alveolar collapse were similar in both ALI groups. After RMs, lung resistive and viscoelastic pressures and static elastance decreased more in ALIexp (255%,180%, and 118%, respectively) than in ALIp (103%, 59%, and 89%, respectively). The amount of atelectasis decreased more in ALIexp than in ALIp (from 58% to 19% and from 59% to 33%, respectively). RMs augmented type III procollagen messenger RNA expression only in the ALIp group (19%), associated with worsening in alveolar epithelium injury but no capillary endothelium lesion, whereas the ALIexp group showed a minor detachment of the alveolar capillary membrane. Conclusions. Given the same transpulmonary pressures, RMs are more effective at opening collapsed alveoli in ALIexp than in ALIp, thus improving lung mechanics and oxygenation with limited damage to alveolar epithelium.

Hantavirus Pulmonary Syndrome: Report of the first three cases in São Paulo, Brazil

The hantavirus pulmonary syndrome was first recognized in cases that occurred in the U.S. in 1993, which served as an alert not only for American physicians but also for physicians in other countries for the identification of the disease. In the city of São Paulo, Brazil, 3 cases of the syndrome were recorded in 1993. The patients were young brothers residing in the Mata Atlântica (Atlantic Forest) region submitted to recent deforestation. Two of the patients died of acute respiratory insufficiency and the third recovered without sequelae. In the surviving patient the diagnosis was established by a laboratory criterion based on the detection of specific IgM and IgG class antibodies by indirect immunofluorescence. In the two patients who died, the diagnosis was confirmed by laboratory tests using immunoperoxidase technique for hantavirus in tissue, in histological lung and heart sections in one case, and by clinical and epidemiological data in the other

Hantavirus pulmonary syndrome in Brazil: clinical aspects of three new cases

Hantavirus pulmonary syndrome (HPS) has been recognized recently in Brazil, where 28 cases have been reported as of September 1999. We report here the clinical and laboratory findings of three cases whose diagnoses were confirmed serologically. All the patients were adults who presented a febrile illness with respiratory symptoms that progressed to respiratory failure that required artificial ventilation in two of them. Laboratory findings were most of the time consistent with those reported in the United States in patients infected with the Sin Nombre virus, and included elevated hematocrit and thrombocytopenia; presence of atypical lymphocytes was observed in one patient. The chest radiological findings observed in all the patients were bilateral, diffuse, reticulonodular infiltrates. Two patients died. Histopathological examination of the lungs of these patients revealed interstitial and alveolar edema, alveolar hemorrhage, and mild interstitial pneumonia characterized by infiltrate of immunoblasts and mononuclear cells. In the epidemiologic investigation of one of the cases, serologic (ELISA) tests were positive in 3 (25%) out of 12 individuals who shared the same environmental exposure. HPS should be included in the differential diagnosis of interstitial pneumonia progressing to acute respiratory failure.

Hantavirus pulmonary syndrome in Anajatuba, Maranhão, Brazil

The authors report a confirmed case of hantavirus pulmonary syndrome in the rural area of the municipality of Anajatuba, state of Maranhão. Two other suspected cases from the same region are also described. The confirmed case involved a previously healthy young woman who died with signs and symptoms of acute respiratory insufficiency 5 days after presenting fever, myalgia and a dry cough. The patient was a student who was helping her parents with work in the fields; it was a habit of the family to store rice inside the house. The suspected cases involved two first-degree relatives working as field hands who died of acute respiratory insufficiency 24 and 48 hours, respectively, after presenting fever, myalgia and a dry cough. Both stored rice and corn inside their home. People living in the region reported massive infestations with rats in the woods and fields.

Acute Eosinophilic and Neutrophilic Pneumonia following Transarterial Chemoembolization with Drug-Eluting Beads Loaded with Doxorubicin for Hepatocellular Carcinoma: A Case Report.

At an intermediate or advanced stage, i.e. stage B or C, based on the Barcelona Clinic Liver Cancer classification of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) may be offered as a treatment of palliative intent. We report the case of a patient suffering from acute respiratory distress syndrome after TACE with drug-eluting beads loaded with doxorubicin for HCC. To our knowledge, this is the first case described where a bronchoalveolar lavage was performed, and where significant levels of alveolar eosinophilia and neutrophilia were evident, attributed to a pulmonary toxicity of doxorubicin following liver chemoembolization. © 2014 S. Karger AG, Basel.

Un projet multicentrique suisse pour améliorer la prévention et la récidive après un syndrome coronarien aigu [A Swiss multicentric project to improve the prevention of cardiovascular event recurrence after acute coronary syndromes].

Recurrence of cardiovascular events and mortality remain high after acute coronary syndromes. A Swiss multicentric study, "Inflammation and acute coronary syndromes (ACS)--Novel strategies for prevention and clinical managements", is currently underway with the support of the Swiss National Science Foundation. The study includes a clinical research subproject of which the aim is to assess the impact of the ELIPS program (multi-dimEnsionaL prevention Program after acute coronary Syndrome) on the recurrence of cardiovascular events after an ACS. The basic research sub-projects aim to investigate novel cardiovascular risk biomarkers and genetic determinants of recurrence and to study the role of stem cells after an ACS. Another sub-project will evaluate intracoronary imaging techniques and the efficacy of different types of stents.

Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients.

Background: Lung transplant recipients are frequently exposed to respiratory viruses and are particularly at risk for severe complications. The aim of this study was to assess the association among the presence of a respiratory virus detected by molecular assays in bronchoalveolar lavage (BAL) fluid, respiratory symptoms, and acute rejection in adult lung transplant recipients. Methods: Upper (nasopharyngeal swab) and lower (BAL) respiratory tract specimens from 77 lung transplant recipients enrolled in a cohort study and undergoing bronchoscopy with BAL and transbronchial biopsies were screened using 17 different polymerase chain reaction-based assays. Result: BAL fluid and biopsy specimens from 343 bronchoscopic procedures performed in 77 patients were analyzed. We also compared paired nasopharyngeal and BAL fluid specimens collected in a subgroup of 283 cases. The overall viral positivity rate was 29.3% in the upper respiratory tract specimens and 17.2% in the BAL samples (). We observed a significant association P < .001 between the presence of respiratory symptoms and positive viral detection in the lower respiratory tract (Pp. 012). Conversely, acute rejection was not associated with the presence of viral infection (odds ratio, 0.41; 95% confidence interval, 0.20-0.88). The recovery of lung function was significantly slower when acute rejection and viral infection were both present. Conclusions: A temporal relationship exists between acute respiratory symptoms and positive viral nucleic acid detection in BAL fluid from lung transplant recipients. We provide evidence suggesting that respiratory viruses are not associated with acute graft rejection during the acute phase of infection.

Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung injury

Acute lung injury is characterized by a severe disruption of alveolo-capillary structures and includes a variety of changes in lung cell populations. Evidence suggests the occurrence of rupture of the basement membranes and interstitial matrix remodeling during acute lung injury. The dynamic equilibrium of the extracellular matrix (ECM) under physiological conditions is a consequence of the balance between the regulation of synthesis and degradation of ECM components. Matrix metalloproteinases (MMPs) represent a group of enzymes involved in the degradation of most of the components of the ECM and therefore participate in tissue remodeling associated with pathological situations such as acute lung injury. MMP activity is regulated by proteolytic activation of the latent secreted proenzyme and by interaction with specific tissue inhibitors of metalloproteinases. This review details our knowledge of the involvement of MMPs, namely MMP-2 and MMP-9, in acute lung injury and acute respiratory distress syndrome.

Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. The objective of this study was to examine the major determinants of coronary disease severity, including those coronary risk factors associated with metabolic syndrome, during the early period after an acute coronary episode. We tested the hypothesis that inflammatory markers, especially highly sensitive C-reactive protein (hsCRP), are related to coronary atherosclerosis, in addition to traditional coronary risk factors. Subjects of both genders aged 30 to 75 years (N = 116) were prospectively included if they had suffered a recent acute coronary syndrome (acute myocardial infarction or unstable angina pectoris requiring hospitalization) and if they had metabolic syndrome diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III. Patients were submitted to a coronary angiography and the burden of atherosclerosis was estimated by the Gensini score. The severity of coronary disease was correlated (Spearman’s or Pearson’s coefficient) with gender (r = 0.291, P = 0.008), age (r = 0.218, P = 0.048), hsCRP (r = 0.256, P = 0.020), ApoB/ApoA ratio (r = 0.233, P = 0.041), and carotid intima-media thickness (r = 0.236, P = 0.041). After multiple linear regression, only male gender (P = 0.046) and hsCRP (P = 0.012) remained independently associated with the Gensini score. In this high-risk population, male gender and high levels of hsCRP, two variables that can be easily obtained, were associated with more extensive coronary disease, identifying patients with the highest potential of developing new coronary events.

Syndrome de détresse respiratoire aiguë (SDRA) : étude de mécanismes impliqués dans la phase exsudative

Le syndrome de détresse respiratoire aiguë (SDRA) se développe suite à une atteinte pulmonaire lésionnelle, induisant un œdème et une inflammation excessive, généralement suivis d’une réparation atypique menant à la fibrose. Malgré de signifiants progrès dans les traitements, la mortalité reste élevée : ~ 40 %. Mon hypothèse de travail est que l’atténuation de l’œdème ou de la réponse inflammatoire pourrait freiner le développement ou la sévérité de la phase exsudative. Nous avons évalué cette hypothèse à l’aide d’un modèle de phase exsudative du SDRA, i.e. instillation intra-trachéale de bléomycine, chez les souris.  La modulation des fluides alvéolaires est étudiée avec des souris transgénique (Tg) pour le canal ENaC, qui sont sensibles à la formation d’un œdème. Cependant, ces souris Tg ne sont pas plus sensibles au développement de la phase exsudative en condition lésionnelle (bléomycine). Nous avons déterminé par une étude électrophysiologique des cellules épithéliales alvéolaires de type II (AT II) que ce n’est pas lié à une inhibition par la bléomycine de la fonction du canal ENaC.  Le traitement de la réponse inflammatoire associée au SDRA par des glucocorticoïdes est une thérapie potentielle mais controversée. Les glucocorticoïdes dans notre modèle murin ne réduisent pas la sévérité des lésions. Nous avons pu déterminé lors d’expériences in vitro que ce serait dû à une réduction de la capacité de réparation des AT II. En résumé :  La modulation du canal ENaC ne modifie pas le développement de la phase exsudative, suggérant que la régulation de l’œdème n’est pas suffisante pour modifier l’évolution du SDRA.  La modulation de l’inflammation par les glucocorticoïdes est ineffective, possiblement à cause d’une altération de la réparation. Mon étude suggère que le traitement de la phase exsudative du SDRA est complexe. En effet, la régulation de l’œdème ou de l’inflammation de façon isolée ne peut pas modifier l’évolution du SDRA. L'hétérogénéité des sources du SDRA et la redondance des mécanismes cellulaires impliqués dans l’évolution des lésions pulmonaires suggèrent que le traitement nécessitera une approche visant plusieurs cibles mécanistiques afin d’en accélérer la résolution.

Effects of Inhaled Nitric Oxide on Oxidative Stress and Histopathological and Inflammatory Lung Injury in a Saline-Lavaged Rabbit Model of Acute Lung Injury

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differences in Evolution of Children with Non-severe Acute Lower Respiratory Tract Infection With and Without Radiographically Diagnosed Pneumonia

Objective: To identify differences in the evolution of children with non-severe acute lower respiratory tract infection between those with and without radiographically diagnosed pneumonia. Design: Prospective cohort study. Setting: A public university pediatric hospital in Salvador, Northeast Brazil. Patients: Children aged 2-59 months. Methods: By active surveillance, the pneumonia cases were prospectively identified in a 2-year period. Each case was followed-up for changes in various clinical symptoms and signs. Demographic, clinical and radiographic data were recorded in standardized forms. Exclusion was due to antibiotic use in the previous 48 hours, signs of severe disease, refusal to give informed consent, underlying chronic illness, hospitalization in the previous 7 days or amoxicillin allergy. Chest X-ray (CXR) was later read by at least 2 independent pediatric radiologists. Main Outcome Measures: Radiographic diagnosed pneumonia based on agreed detection of pulmonary infiltrate or pleural effusion in 2 assessments. Results: A total of 382 patients receiving amoxicillin were studied, of whom, 372 (97.4%) had concordant radiographic diagnosis which was pneumonia (52%), normal CXR (41%). and others (7%). By multivariate analysis, age (OR=1.03; 95% CI: 1.02-1.05), disease >= 5days (OR = 1.04; 95% CI: 1.001-1.08), reduced pulmonary expansion (OR = 3.3; 95% CI: 1.4-8.0), absence of wheezing (OR = 0.5; 95% CI: 0.3-0.9), crackles on admission (OR = 2.0; 95% CI: 1.2-3.5), inability to drink on day 1 (OR = 4.2; 95% CI: 1.05-17.3), consolidation percussion sign (OR = 7.0; 95% CI: 1.5-32.3), tachypnea (OR = 2.0; 95% CI: 1.09-3.6) and fever (OR = 3.6; 95% CI: 1.4-9.4) on day 2 were independently associated with pneumonia. The highest positive predictive value was at the 2nd day of evolution for tachypnea (71.0%) and fever (81.1%). Conclusion: Persistence of fever or tachypnea up to the second day of amoxicillin treatment is predictive of radiographically diagnosed pneumonia among children with non-severe lower respiratory tract diseases.

[MRI-based diagnosis of an acute bilateral compartment syndrome]

The acute compartment syndrome describes a posttraumatic or inflammatory edema, which leads to a painful constraint of muscular movement and paresthesia. An increase in pressure in the anatomical compartment is postulated. The main symptoms include local swelling, sensory loss, local muscle weakness as well as late livid discoloration. Therapy of choice is an early fasciotomy with decompression to avoid serious complications like muscle necrosis. Here we report a 22 year old patient who postoperatively suffered from a bilateral paresis of the foot jack. Further examinations by electromyography and magnetic resonance imaging (MRI) led to the diagnosis of an acute bilateral compartment syndrome.

TONOMETRY REVISITED: PERFUSION-RELATED, METABOLIC, AND RESPIRATORY COMPONENTS OF GASTRIC MUCOSAL ACIDOSIS IN ACUTE CARDIORESPIRATORY FAILURE

Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial Pco2 gradient, DeltaPco2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial Pco2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63 +/- 2 [mean +/- SEM]; Acute Physiology and Chronic Health Evaluation II score, 20 +/- 1; Sequential Organ Failure Assessment score, 8 +/- 0). pHi, and the effects of bicarbonate and arterial and mucosal Pco2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27 +/- 0.01) due to low arterial bicarbonate and increased DeltaPco2. Low pHi (<7.32) at admission (n = 58; mortality, 29% vs. 13% in those with pHi >/=7.32 at admission; P = 0.061) was associated with an increased DeltaPco2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltaPco2; P = 0.0003). An increased versus normal DeltaPco2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; P < 0.0001; n = 39) and at 6 h (34% vs. 13%; P = 0.016; n = 45). A delayed normalization or persistently low pHi (n = 47) or high DeltaPco2 (n = 25) was associated with high mortality (low pHi [34%] vs. high DeltaPco2 [60%]; P = 0.046). In nonsurvivors, hypocapnia increased pHi at baseline, 6, and 24 h (all P