Methionine supplementation for multi-organ dysfunction in MetRS-related pulmonary alveolar proteinosis.

INTRODUCTION: Pulmonary alveolar proteinosis related to mutations in the methionine tRNA synthetase (MARS1) gene is a severe, early-onset disease that results in death before the age of 2 years in one-third of patients. It is associated with a liver disease, growth failure and systemic inflammation. As methionine supplementation in yeast models restored normal enzymatic activity of the synthetase, we studied the tolerance, safety and efficacy of daily oral methionine supplementation in patients with severe and early disease. METHODS: Four patients received methionine supplementation and were followed for respiratory, hepatic, growth and inflammation-related outcomes. Their course was compared to those of historical controls. Reactive oxygen species production by patient monocytes before and after methionine supplementation was also studied. RESULTS: Methionine supplementation was associated with respiratory improvement, clearance of the extracellular lipoproteinaceous material and discontinuation of whole-lung lavage in all patients. The three patients who required oxygen or noninvasive ventilation could be weaned off within 60 days. In addition, liver dysfunction, inflammation and growth delay improved or resolved. At a cellular level, methionine supplementation normalised the production of reactive oxygen species by peripheral monocytes. CONCLUSION: Methionine supplementation was associated with important improvements in children with pulmonary alveolar proteinosis related to mutations in the MARS1 gene. This study paves the way for similar strategies for other tRNA synthetase deficiencies.

Effect of early whole lung lavage at different time-points for promoting the removal of depleted uranium from the lung.

PURPOSE: This study compared the effect of whole lung lavage (WLL) at different time-points early after exposure of the respiratory system to insoluble radioactive particles. MATERIALS AND METHODS: Forty adult beagles were randomized into a control group and the 3-h, 8-h, 24-h, and 48-h lavage groups (n = 8). A canine model of acute lung injury was established by spraying a depleted uranium (DU) suspension using a superfine fiber bronchoscope, at a dose of 20 mg/kg. The lavage groups were subjected to WLL at 3 h, 8 h, 24 h, and 48 h post-DU exposure, while the control group received no treatment after exposure. Measurement of U in serum was performed using inductively coupled plasma mass spectrometry; measurements in the lavage fluid and left lung tissue were performed using inductively coupled plasma atomic emission spectrometry. The color of the lavage fluid was analyzed using colorimetry, and shadow changes in the lung were observed using chest computed tomography (CT). RESULTS: The lavage groups showed similarly increasing trends for serum U levels from DU exposure to 3 and 7 days after exposure; however, these values were significantly lower than those in the control group (p < .01). The U content in the lavage fluid was significantly higher in the 3-h group than in the 8-h, 24-h, and 48-h groups (p < .01), while that in the 8-h group was markedly higher than those in the 24-h and 48-h groups (p < .05). The average clearance rate of DU in the lungs varied in the range of 0.63‒7.06%. The U content in the left lung tissue of each lavage group was significantly lower than that in the control group (p < .01), while the content in the 8-h, 24-h, and 48-h groups was significantly higher than that in the 3-h group (p < .05). The colorimetric score of the lavage fluid in the 3-h group was significantly lower than those in the 8-h, 24-h, and 48-h groups (p < .05). Chest CT showed different degrees of consolidation and ground glass shadow changes in all groups. The score of the left lung shadow volume in the 3-h group was significantly lower than in the control, 8-h, 24-h, and 48-h groups (p < .01), while the score in the 8-h group was significantly higher than those in the 48-h and control groups (p < .05). CONCLUSIONS: The best effect of WLL after exposure of the respiratory system to insoluble radioactive particles was achieved at 3 h, followed by 8 h; there was no difference in the effectiveness of lung lavage at 24 h and 48 h.

Detection of Carbapenemase and CTX-M Encoding Genes Directly from Bronchoalveolar Lavage Using the CRE and ESBL ELITe MGB Assays: Toward Early and Optimal Antibiotic Therapy Management of Critically Ill Patients with Pneumonia.

The detection of carbapenemase extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (EB) has become a major issue among critically ill patients, especially due to their impact on appropriate antimicrobial therapy. This study aimed at evaluating the potential contribution of molecular assays to early optimization of empirical antibiotic therapy among critically ill patients with carbapenemase- and/or CTX-M-producing EB pneumonia. The CRE and ESBL ELITe MGB® assays were evaluated directly on 197 bronchoalveolar lavage (BAL) samples obtained from 120 patients. Molecular results were then compared to routine culture-based diagnostic results, and a retrospective analysis of the therapeutic antimicrobial management was performed. Among the 197 clinical specimens, blaKPC-like and blaCTX-M-like were detected in 20 (10.2%) and 12 (6.1%) specimens belonging to 15 and 11 patients, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of the CRE ELITe MGB Kit were 85% [95% confidence interval [CI]: 64.9-94.6] and 100%, respectively. PPV and NPV of the ESBL ELITe MGB Kit were 75% [95% CI: 49.4-90.2] and 100%, respectively. Retrospective analysis of the therapeutic antimicrobial management at the time of BAL collection showed that in ∼50% of patients with carbapenemase- and CTX-M-producing EB pneumonia empirical antibiotic therapy could have been optimized at least 48-72 hr earlier if positive molecular data had been used. The CRE and ESBL ELITe MGB assays might be an interesting tool for expediting optimization of empirical antibiotic therapy in critically ill patients with pneumonia, depending on local epidemiology of antibiotic resistance, patient risk stratification for EB infection, and availability of an antimicrobial stewardship team.

Of onions and men: Report of cavitary community acquired pneumonia due to Burkholderia cepacia complex in an immunocompetent patient and review of the literature.

Burkholderia cepacia complex consists of highly antibiotic resistant gram negative bacilli that are plant symbionts and also potential agents of human infection.  This bacterial family's claim to fame in clinical medicine is as the scourge of cystic fibrosis patients, in whom it is a notorious respiratory pathogen.  Outside of cystic fibrosis, it rarely comes to mind as an etiology of community acquired pneumonia with or without lung cavitation in immunocompetent hosts.  We describe a case of an otherwise healthy, community-dwelling man who presented with subacute cavitary lung disease, the causative organism of which turned out to be Burkholderia cepacia complex.  Our report is accompanied by a review of the literature, which identified an additional eleven cases in the same category.  We analyze all of the available cases for the emergence of any identifiable patterns or peculiarities.

[THE UTILITY OF BRONCHOSCOPY IN INTENSIVE CARE UNIT PATIENTS WITH VENTILATOR ASSOCIATED PNEUMONIA].

BACKGROUND: Ventilator associated pneumonia (VAPI is a common complication leading to lengthier hospitalizations and higher mortality. Prompt adequate initial antibiotic coverage is the crucial issue affecting survival. Currently, there is no gold standard diagnostic test. No conclusive data regarding the benefit of bronchoscopy exists in the literature reviewed. AIM: This study aims to evaluate the change of prognosis for patients who developed VAP, following a positive culture from bronchoalveolar lavage (BAL). DESIGN: This is a retrospective cohort study. SETTING: General intensive care unit in a tertiary university healthcare center. PARTICIPANTS: All patients who were admitted to Surgical ICU and developed VAP and who then underwent diagnostic bronchoscopy with BAL between the period 01/02/2007 - 31/02/2011. MEASUREMENTS AND RESULTS: A total of 66 patients who were admitted to the ICU, developed VAP and underwent bronchoscopy while ventilated; 30 patients were excluded. The positive BAL culture group was compared to the negative BAL culture group; there was no difference between demographic and clinical characteristics, mortality rates (for 30 days) or therapy change between the two groups. No complications were reported regarding the bronchoscopy procedure. CONCLUSIONS: Our findings demonstrate that performing y a diagnostic bronchoscopy with BAL does not improve the prognosis of patients with VAP. Furthermore, expanded prospective studies will be needed to conclude regarding its benefit in diagnosis and subsequent rectifying of therapy.

Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice.

Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to demarcate between cancerous and normal cells thereby causing severe form of systemic toxicity. Among which pulmonary toxicity is a dreadful complication developed in cancer patients upon cyclophosphamide (CP) therapy. Oxidative stress, fibrosis, and apoptosis are the major patho-mechanisms involved in CP-induced pulmonary toxicity. In the present study, we have synthesized Nano-Se, nanotechnology-based new form of elemental selenium which has significantly lower toxicity and acceptable bioavailability. In order to meet the need of effective drugs against CP-induced adverse effects, nano selenium (Nano-Se) was tested for its possible protective efficacy on CP-induced pulmonary toxicity and bone marrow toxicity. CP intoxication resulted in structural and functional lung impairment which was revealed by massive histopathological changes. Lung injury was associated with oxidative stress/lipid peroxidation as evident by increased in reactive oxygen species, nitric oxide level, and malondialdehyde (MDA) formation with decreased in level of antioxidants such as reduced glutathione, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase, and catalase. Furthermore, CP at a dose of 25 mg/kg b.w. increased pulmonary DNA damage ('comet tail') and triggered DNA fragmentation and apoptosis in mouse bone marrow cells. On the other hand, Nano-Se at a dose of 2 mg Se/kg b.w., significantly inhibited CP-induced DNA damage in bronchoalveolar lavage cells, and decreased the apoptosis and percentage of DNA fragmentation in bone marrow cells and also antagonized the reduction of the activities of antioxidant enzymes and the increase level of MDA. Thus, our results suggest that Nano-Se in pre- and co-administration may serve as a promising preventive strategy against CP-induced pulmonary toxicity.

Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid.

Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

[Successful risk management in flexible bronchoscopy]. / Erfolgreiches Risikomanagement bei der flexiblen Bronchoskopie.

Flexible bronchoscopy is one of the most important diagnostic procedures in respiratory medicine. The investigator operates in a vital organ and therefore must face a broad range of potential complications. This article provides an overview of all important complications associated with flexible bronchoscopy. It is further discussed how this risk can be minimized. A skillfull team, close monitoring and readily available resuscitation facilities are mandatory to avoid and to deal with major complications.

Grave afectación laringotraqueal secundaria a rinoescleroma por Klebsiella pneumoniae ssp. ozaenae / No disponible

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Whole lung lavage in the treatment of pulmonary alveolar proteinosis.

Although a rare condition, pulmonary alveolar proteinosis (PAP) can be a very devastating diagnosis with life-altering consequences. This case study follows the path of a young woman who is currently undergoing whole lung lavage as treatment for pulmonary alveolar proteinosis. The entire concept of flooding a lung with large quantities of saline as a treatment for lung disease is contrary to normal respiratory care. Caring for the patient with PAP provides many challenges for the perianesthesia nurse. Management of the postanesthesia airway, oxygen administration and maintenance of oxygen saturation, and pain relief skills are all of high importance to the patient with PAP. These skills plus the emotional support provided by the experienced perianesthesia nurse can ensure a safe recovery from this unusual procedure.

The role of soluble components in ambient fine particles-induced changes in human lungs and blood.

Normal individuals developed pulmonary neutrophilic inflammation and increased blood fibrinogen following inhalation of concentrated ambient particles (CAPS). In this study, we sought to determine how soluble components in CAPS contributed to these changes. We expanded and reanalyzed data from 37 young healthy volunteers from a previous study (Ghio et al., 2000) who were exposed to either filtered air or CAPS. Postexposure bronchoalveolar lavage (BAL) as well as pre- and postexposure venous blood samples was analyzed for cellular and acute inflammatory endpoints. Nine most abundant components in the water-soluble fraction of CAPS were correlated with these endpoints using principal component analysis. We found that a sulfate/Fe/Se factor was associated with increased BAL percentage of neutrophils and a Cu/Zn/V factor with increased blood fibrinogen. The concentrations of sulfate, Fe, and Se correlated highly with PM mass (R > 0.75) while the correlations between PM and Cu/Zn/V were modest (R = 0.2-0.6). These results from controlled human exposure linked specific PM components to pulmonary neutrolphil influx and blood fibrinogen increase, and indicated the soluble components of pollutant particles may differentially affect pulmonary and hematological systems in humans exposed to PM.

Pediatric bronchoscopy.

Diagnostic flexible endoscopy for pediatric respiratory diseases is performed in many centers. Technical advances have resulted in performance of interventional bronchoscopies, and new diagnostic indications are being explored. Indications with documented clinical benefit include congenital or acquired progressive or unexplained airway obstruction. Pulmonary infections in immunodeficient children who do not respond to empirical antibiotic treatment may be diagnosed by bronchoscopy and bronchoalveolar lavage (BAL). The potential usefulness of bronchoscopy and BAL for managing chronic cough, wheeze, or selected cases with asthma or cystic fibrosis requires further study. The use of transbronchial biopsies (TBB) is established in pediatric lung transplantation. The role of TBB in the diagnosis of chronic interstitial lung disease in children remains to be determined. For a number of interventional applications, rigid endoscopy is required, and pediatric bronchoscopists should be trained in its use. Complications in pediatric bronchoscopy are rare, but severe nosocomial infection or overdosing with local anesthetics has occurred. The issues of quality control, video documentation, interobserver variability of findings, and educational standards will have to be addressed in the future as bronchoscopy use becomes less restricted to only large pediatric pulmonary units.