The latest medical research on Intensive Care Medicine
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Nasal Pneumococcal Density is Associated with Microaspiration and Heightened Human Alveolar Macrophage Responsiveness to Bacterial Pathogens.Resp Crit Care Med
Pneumococcal pneumonia remains a global health problem. Colonization of the nasopharynx with S.pneumoniae (Spn), although, a prerequisite of infection, is the main source of exposure and immunological boosting in children and adults. However, our knowledge of how nasal colonization impacts on the lung cells, especially on the predominant alveolar macrophage (AM) population, is limited.
Using a Controlled Human Infection Model to achieve nasal colonization with 6B serotype, we investigated the effect of Spn colonization on lung cells.
We collected bronchoalveolar lavages from healthy pneumococcal challenged participants aged 18-49 years. Confocal microscopy, molecular and classical microbiology were used to investigate microaspiration and pneumococcal presence in the lower airways. AM opsonophagocytic capacity was assessed by functional assays in vitro, whereas flow cytometry and transcriptomic analysis were used to assess further changes on the lung cellular populations.
AM from Spn-colonized exhibited increased opsonophagocytosis to pneumococcus (11.4% median increase) for four months after clearance of experimental pneumococcal colonization. AM had also increased responses against other bacterial pathogens. Pneumococcal DNA detected in the BAL samples of Spn-colonized were positively correlated with nasal pneumococcal density (r=0.71, p=0.029). Similarly, AM heightened opsonophagocytic capacity was correlated with nasopharyngeal pneumococcal density (r=0.61, p=0.025).
Our findings demonstrate that nasal colonization with pneumococcus and microaspiration prime AM, leading to brisker responsiveness to both pneumococcus and unrelated bacterial pathogens. The relative abundance of AM in the alveolar spaces, alongside with their potential for non-specific protection, render them an attractive target for novel vaccines. Clinical trial registration available at http://www.isrctn.com, ID: ISRCTN16993271.
Comparative Modelling of Tuberculosis Epidemiology and Policy Outcomes in California.Resp Crit Care Med
Rationale Mathematical modelling is used to understand disease dynamics, forecast trends, and inform public health prioritization. We conducted a c...
Targeting Proteases in Cystic Fibrosis Lung Disease: Paradigms, Progress, and Potential.Resp Crit Care Med
Cystic fibrosis (CF) is the most common life-limiting hereditary condition of Caucasian populations and is characterised by chronic airways inflamm...
Use of MIRUS™ for MAC-driven application of isoflurane, sevoflurane, and desflurane in postoperative ICU patients: a randomized controlled trial.Annals of Intensive Care
The MIRUS™ (TIM, Koblenz, Germany) is an electronical gas delivery system, which offers an automated MAC (minimal alveolar concentration)-driven application of isoflurane, sevoflurane, or desflurane, and can be used for sedation in the intensive care unit. We investigated its consumption of volatile anesthetics at 0.5 MAC (primary endpoint) and the corresponding costs. Secondary endpoints were the technical feasibility to reach and control the MAC automatically, the depth of sedation at 0.5 MAC, and awakening times. Mechanically ventilated and sedated patients after major surgery were enrolled. Upon arrival in the intensive care unit, patients obtained intravenous propofol sedation for at least 1 h to collect ventilation and blood gas parameters, before they were switched to inhalational sedation using MIRUS™ with isoflurane, sevoflurane, or desflurane. After a minimum of 2 h, inhalational sedation was stopped, and awakening times were recorded. A multivariate electroencephalogram and the Richmond Agitation Sedation Scale (RASS) were used to assess the depth of sedation. Vital signs, ventilation parameters, gas consumption, MAC, and expiratory gas concentrations were continuously recorded.
Thirty patients obtained inhalational sedation for 18:08 [14:46-21:34] [median 1st-3rd quartiles] hours. The MAC was 0.58 [0.50-0.64], resulting in a Narcotrend Index of 37.1 [30.9-42.4] and a RASS of - 3.0 [- 4.0 to (- 3.0)]. The median gas consumption was significantly lowest for isoflurane ([ml h-1]: isoflurane: 3.97 [3.61-5.70]; sevoflurane: 8.91 [6.32-13.76]; and desflurane: 25.88 [20.38-30.82]; p < 0.001). This corresponds to average costs of 0.39 € h-1 for isoflurane, 2.14 € h-1 for sevoflurane, and 7.54 € h-1 for desflurane. Awakening times (eye opening [min]: isoflurane: 9:48 [4:15-20:18]; sevoflurane: 3:45 [0:30-6:30]; desflurane: 2:00 [1:00-6:30]; p = 0.043) and time to extubation ([min]: isoflurane: 10:10 [8:00-20:30]; sevoflurane: 7:30 [4:37-14:22]; desflurane: 3:00 [3:00-6:00]; p = 0.007) were significantly shortest for desflurane.
A target-controlled, MAC-driven automated application of volatile anesthetics is technically feasible and enables an adequate depth of sedation. Gas consumption was highest for desflurane, which is also the most expensive volatile anesthetic. Although awakening times were shortest, the actual time saving of a few minutes might be negligible for most patients in the intensive care unit. Thus, using desflurane seems not rational from an economic perspective. Trial registration Clinical Trials Registry (ref.: NCT03860129). Registered 24 September 2018-Retrospectively registered.
Losartan Rescues Inflammation-Related Mucociliary Dysfunction in Relevant Models of Cystic Fibrosis.Resp Crit Care Med
Despite therapeutic progress in treating cystic fibrosis (CF) airway disease, airway inflammation with associated mucociliary dysfunction remains largely unaddressed. Inflammation reduces the activity of apically expressed large conductance, Ca2+-activated and voltage-dependent K+ channels (BK), critical for mucociliary function in the absence of CFTR.
Losartan's anti-inflammatory effectiveness to rescue BK activity and thereby mucociliary function was tested in vitro using primary, fully re-differentiated human airway epithelial cells homozygous for F508del and in vivo using a previously validated, now expanded pharmacological sheep model of CF- and inflammation-associated mucociliary dysfunction.
Nasal scrapings from CF patients showed that neutrophilic inflammation correlated with reduced expression of LRRC26, the γ subunit mandatory for BK function in the airways. TGF-β1, downstream of neutrophil elastase, decreased mucociliary parameters in vitro. These were rescued by losartan at concentrations achieved by nebulization in the airway and oral application in the bloodstream: BK dysfunction recovered acutely and over time (the latter via an increase in LRRC26 expression); ciliary beat frequency and airway surface liquid (ASL) volume improved; and mucus hyperconcentration and cellular inflammation decreased. These effects did not depend on angiotensin receptor blockade. Expanding on a validated and published nongenetic sheep model of CF, ewes inhaled CFTRinh172 and neutrophil elastase for three days, which resulted in prolonged tracheal mucus velocity reduction, mucus hyperconcentration and increased TGF-β1. Nebulized losartan rescued both mucus transport and mucus hyperconcentration and reduced TGF-β1.
Losartan effectively reversed CF- and inflammation-associated mucociliary dysfunction, independent of its angiotensin receptor blockade.
Improvements of right ventricular function and hemodynamics after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.Echocardiography
Right ventricular (RV) function is an important factor in the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH) in patients. In our study, we aimed to evaluate the timing and magnitude of regional RV function before and after balloon pulmonary angioplasty (BPA) using speckle tracking echocardiography (STE) and their relation to clinical and hemodynamic parameters in patients with CTEPH.
We enrolled 20 CTEPH patients and 19 healthy subjects in our study. Enrolled patients underwent echocardiography, right heart catheterization (RHC), and 6-minute walk distance (6MWD) test at baseline and after the BPA.
In hemodynamic RHC measurements and clinical evaluations, mean pulmonary artery pressure (median: 53.5 mm Hg vs 37.0 mm Hg, P = .001) and pulmonary vascular resistance (median: 12 Wood units [WU] vs 7 WU, P = .001) and pro-brain natriuretic peptide level decreased and 6MWD increased after BPA sessions. There was no statistically significant difference between before and after the BPA sessions in conventional echocardiographic measurements. In STE analysis, the electromechanical delay (EMD) between RV free wall (RVF) and LV lateral wall (LVL) (median: 65 ms vs 47.5 ms, P = .01) and RV peak systolic strain dispersion index (52 ms vs 29 ms, P = .001) were higher in patients with CTEPH than healthy controls before the BPA. Both these parameters decreased significantly after BPA.
Chronic thromboembolic pulmonary hypertension was associated with RV electromechanical delay and dispersion based on the STE analysis. Balloon pulmonary angioplasty might have an important impact on the improvement of both RV function and hemodynamics.
Biatrial and right ventricular deformation imaging: Implications of the recent EACVI consensus document in the clinics and beyond.Echocardiography
In this review, right ventricular (RV), right atrial (RA), and left atrial (LA) strain in some selected clinical situations has been discussed in l...
Pulmonary Alveolar Proteinosis (PAP)ATS ICU
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 8, Page P16-P17, October 15, 2019.
Erratum: XBP1S Regulates MUC5B in a Promoter Variant–Dependent Pathway in Idiopathic Pulmonary Fibrosis Airway EpitheliaATS ICU
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 8, Page 1074-1074, October 15, 2019.
Reply to Aubry and Veziris: Smear Microscopy Complements Xpert MTB/RIF When Considering Nontuberculous Mycobacterial InfectionsATS ICU
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 8, Page 1073-1074, October 15, 2019.
Smear Microscopy Complements Xpert MTB/RIF When Considering Nontuberculous Mycobacterial InfectionsATS ICU
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 8, Page 1072-1073, October 15, 2019.
Reply to Nalos and Robergs and to De Backer and VincentATS ICU
American Journal of Respiratory and Critical Care Medicine, Volume 200, Issue 8, Page 1071-1072, October 15, 2019.