Inspiratory Effort and Respiratory Mechanics in Patients with Acute Exacerbation of Idiopathic Pulmonary fibrosis: A Preliminary Matched Control Study.

BACKGROUND: Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking. METHODS: Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive non-invasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔPes) and respiratory mechanics before and after 2 hours of NIV were collected as primary outcome. The correlation between positive end-expiratory pressure (PEEP) levels and changes of in dynamic compliance (dynCRS) and PaO2/FiO2 ratio was assessed. Further, an exploratory comparison with a historical cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO2/FiO2 level was performed. RESULTS: At baseline, AE-IPF patients presented a high respiratory drive activation with ΔPes = 27 (21-34) cmH2O, respiratory rate (RR) = 34 (30-39) bpm and minute ventilation (VE) = 21 (20-26) L/min. Two hours after NIV application, ΔPes, RR and VE values showed a significant reduction (16 [14-24] cmH2O, p<0.0001, 27 [25-30] bpm, p=0.001, and 18 [17-20] L/min, p=0.003, respectively) while no significant change was found in dynamic transpulmonary pressure, expiratory tidal volume (Vte), dynCRS and dynamic mechanical power. PEEP levels negatively correlated with PaO2/FiO2 ratio and dynCRS (r=-0.67, p=0.03 and r=-0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔPes, RR, VE and dynamic mechanical power. Differently from AE-IPF, in ARDS both Vte and dynCRS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO2/FiO2 ratio and dynCRS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively). CONCLUSIONS: In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without a significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS patients of similar severity.

Prevalence and development of chronic critical illness in acute patients admitted to a respiratory intensive care setting.

INTRODUCTION: Chronic Critical Illness (chronic CI) is a condition associated to patients surviving an episode of acute respiratory failure (ARF). The prevalence and the factors associated with the development of chronic CI in the population admitted to a Respiratory Intensive Care Unit (RICU) have not yet been clarified. METHODS: An observational prospective cohort study was undertaken at the RICU of the University Hospital of Modena (Italy). Patients mechanically ventilated with ARF in RICU were enrolled. Demographics, severity scores (APACHEII, SOFA, SAPSII), and clinical condition (septic shock, pneumonia, ARDS) were recorded on admission. Respiratory mechanics and inflammatory-metabolic blood parameters were measured both on admission and over the first week of stay. All variables were tested as predictors of chronic CI through univariate and multivariate analysis. RESULTS: Chronic CI occurred in 33 out of 100 patients observed. Higher APACHEII, the presence of septic shock, diaphragmatic dysfunction (DD) at sonography, multidrug-resistant (MDR) bacterial infection, the occurrence of a second infection during stay, and a C-reactive protein (CRP) serum level inceasing 7 days over admission were associated with chronic CI. Septic shock was the strongest predictor of chronic CI (AUC = 0.92 p < 0.0001). CONCLUSIONS: Chronic CI is frequent in patients admitted to RICU and mechanically ventilated due to ARF. Infection-related factors seem to play a major role as predictors of this syndrome.

Efficacy and cost effectiveness of rapid on site examination (ROSE) in management of patients with mediastinal lymphadenopathies.

BACKGROUND: The diagnostic and staging approach for the mediastinal lymphadenopathies, with or whithout pulmonary lesions endoscopically visible, is based on transbronchial needle aspiration (TBNA) during fiberoptic bronchoscopy and on mediastinoscopy. One important factor impacting on TBNA sensitivity is the rapid on site cytological examination (ROSE). AIM: The aim of this study was to evaluate the economic impact of TBNA and TBNA + ROSE, in the diagnosis of these lesions. PATIENTS AND METHODS: 120 patients, affected by mediastinal lymphadenopathies suspected for lung cancer, underwent TBNA during fiberoptic bronchoscopy: 60 patients without ROSE (group A) and other 60 with ROSE (group B). Whenever needle aspirations failed to provide diagnosis, the patient underwent mediastinoscopy. The economic impact of the diagnostic process was performed. RESULTS: In group A, 39 patients (65%) obtained a diagnosis with TBNA while 21 patients (35%) required mediastinoscopy. In group B, 48 patients (80%) obtained a diagnosis with TBNA + ROSE, while 12 patients (20%) required mediastinoscopy. With regards to the costs of the procedures performed in the diagnostic process, the use of TBNA with ROSE as first diagnostic approach has saved a considerable amount of euros (19,413) compared to the use of TBNA without ROSE and the combined procedure increased (p < 0.02; chi square test) the sensitivity of TBNA by 15%. CONCLUSIONS: ROSE significantly impacts on the diagnostic yield, as well as on the overall management costs of patients with mediastinal lymphadenopathy, suspected for lung cancer.

Comparative proteome analysis of laboratory grown Brucella abortus 2308 and Brucella melitensis 16M.

Brucella species are pathogenic agents that cause brucellosis, a debilitating zoonotic disease that affects a large variety of domesticated animals and humans. Brucella melitensis and Brucella abortus are considered major health threats because of their highly infectious nature and worldwide occurrence. The availability of the annotated genomes for these two species has allowed a comparative proteomics study of laboratory grown B. melitensis 16M and B. abortus 2308 by two-dimensional (2-D) gel electrophoresis and peptide mass fingerprinting. Computer-assisted analysis of the different 2-D gel images of strains 16M and 2308 revealed significant quantitative and qualitative differences in their protein expression patterns. Proteins involved in membrane transport, particularly the high affinity amino acids binding proteins, and those involved in Sec-dependent secretion systems related to type IV and type V secretion systems, were differentially expressed. Differential expression of these proteins may be responsible for conferring specific host preference in the two strains 2308 and 16M.

Comparative secretome analyses of three Bacillus anthracis strains with variant plasmid contents.

Bacillus anthracis, the causative agent of anthrax, secretes numerous proteins into the extracellular environment during infection. A comparative proteomic approach was employed to elucidate the differences among the extracellular proteomes (secretomes) of three isogenic strains of B. anthracis that differed solely in their plasmid contents. The strains utilized were the wild-type virulent B. anthracis RA3 (pXO1(+) pXO2(+)) and its two nonpathogenic derivative strains: the toxigenic, nonencapsulated RA3R (pXO1(+) pXO2(-)) and the totally cured, nontoxigenic, nonencapsulated RA3:00 (pXO1(-) pXO2(-)). Comparative proteomics using two-dimensional gel electrophoresis followed by computer-assisted gel image analysis was performed to reveal unique, up-regulated, or down-regulated secretome proteins among the strains. In total, 57 protein spots, representing 26 different proteins encoded on the chromosome or pXO1, were identified by peptide mass fingerprinting. S-layer-derived proteins, such as Sap and EA1, were most frequently observed. Many sporulation-associated enzymes were found to be overexpressed in strains containing pXO1(+). This study also provides evidence that pXO2 is necessary for the maximal expression of the pXO1-encoded toxins lethal factor (LF), edema factor (EF), and protective antigen (PA). Several newly identified putative virulence factors were observed; these include enolase, a high-affinity zinc uptake transporter, the peroxide stress-related alkyl hydroperoxide reductase, isocitrate lyase, and the cell surface protein A.

Epithelial cells respond to proteolytic and non-proteolytic detachment by enhancing interleukin-6 responses.

Intestinal inflammatory disease or infection often results in the loss of the epithelial layer as a result mainly of the action of proteases, including the leucocyte serine proteinases (neutrophil elastase), lysosomal cathepsins and the matrix metalloproteinases from recruited inflammatory cells. Previous studies have shown that bronchial or intestinal epithelial cells (IEC) can respond to proteolytic attack by producing cytokines. In this study, we have determined the effect of protease treatment on interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production by IEC lines. Both neutrophil elastase and trypsin treatment induced elevated levels of mRNA for IL-6 in rat IEC-6 cells. Non-proteolytic detachment of the IEC-6 cells also induced elevated levels of IL-6 mRNA, suggesting that the effect was not caused by a specific protease or degradation product, but probably by an effect on cell shape or cell detachment. Similar results were seen with the IEC-18 cell line. Trypsin treatment of the IEC-6 cells also enhanced unstimulated and IL-1 beta costimulated IL-6 secretion, but not MCP-1 secretion or mRNA levels. Finally, nuclear levels of the CCAAT/enhancer binding protein-beta (C/EBP-beta) were rapidly enhanced after proteolytic detachment of the IEC-6 cells, suggesting a mechanism for the enhancement of IL-6 mRNA responses. These data indicate that epithelial cells can respond to proteolytic attack or cell detachment by producing IL-6, a cytokine with several anti-inflammatory and antiprotease effects, which may be important in moderating the loss of the epithelial layer by its effects on nearby epithelial or inflammatory cells.