And/or Acute Respiratory Distress Syndrome Research Articles

Evaluation of feasibility phase of adaptive version of locally made bubble continuous positive airway pressure oxygen therapy for the treatment of COVID-19 positive and negative adults with severe pneumonia and hypoxaemia.

Bubble continuous positive airway pressure (bCPAP) oxygen therapy has been shown to be safe and effective in treating children with severe pneumonia and hypoxaemia in Bangladesh. Due to lack of adequate non-invasive ventilatory support during coronavirus disease 2019 (COVID-19) crisis, we aimed to evaluate whether bCPAP was safe and feasible when adapted for use in adults with similar indications. Adults (18-64 years) with severe pneumonia and moderate hypoxaemia (80 to <90% oxygen saturation (SpO2) in room air) were provided bCPAP via nasal cannula at a flow rate of 10 litres per minute (l/min) oxygen at 10 centimetres (cm) H2O pressure, in two tertiary hospitals in Dhaka, Bangladesh. Qualitative interviews and focus group discussions, using a descriptive phenomenological approach, were performed with patients and staff (n = 39) prior to and after the introduction (n = 12 and n = 27 respectively) to understand the operational challenges to the introduction of bCPAP. We enrolled 30 adults (median age 52, interquartile range (IQR) 40-60 years) with severe pneumonia and hypoxaemia and/or acute respiratory distress syndrome (ARDS) irrespective of coronavirus disease 2019 (COVID-19) test results to receive bCPAP. At baseline mean SpO2 on room air was 87% (±2) which increased to 98% (±2), after initiation of bCPAP. The mean duration of bCPAP oxygen therapy was 14.4 ± 24.8 hours. There were no adverse events of note, and no treatment failure or deaths. Operational challenges to the clinical introduction of bCPAP were lack of functioning pulse oximeters, difficult nasal interface fixation among those wearing nose pin, occasional auto bubbling or lack of bubbling in water-filled plastic bottle, lack of holder for water-filled plastic bottle, rapid turnover of trained clinicians at the hospitals, and limited routine care of patients by hospital clinicians particularly after official hours. If the tertiary hospitals in Bangladesh are supplied with well-functioning good quality pulse oximeters and enhanced training of the doctors and nurses on proper use of adapted version of bCPAP, in treating adults with severe pneumonia and hypoxaemia with or without ARDS, the bCPAP was found to be safe, well tolerated and not associated with treatment failure across all study participants. These observations increase the confidence level of the investigators to consider a future efficacy trial of adaptive bCPAP oxygen therapy compared to WHO standard low flow oxygen therapy in such patients. s Although bCPAP oxygen therapy was found to be safe and feasible in this pilot study, several challenges were identified that need to be taken into account when planning a definitive clinical trial.

Methylprednisolone use in children with severe pneumonia caused by severe acute respiratory syndrome coronavirus 2.

This study aimed to evaluate the effectiveness and optimal use of corticosteroids in children with severe coronavirus disease 2019 (COVID-19) pneumonia, for which effective treatment is still lacking with respect to this population. We conducted a retrospective study and included patients (aged < 18 years) with severe COVID-19 pneumonia and/or acute respiratory distress syndrome (ARDS) who received standard doses (2-4 mg/kg/day) and high doses (>250 mg/day) of methylprednisolone (MPZ). We adjusted for patients on steroid treatments with a propensity score and compared the side effects of different MPZ doses and patient survival. Fifty-nine patients were included: 61% were male, the median age was 8, interquartile range (IQR) 2-15) years. The overall survival was 84.4% in patients treated with standard-dose MPZ (n = 45, 76.3%) and 92.2% in patients treated with high-dose MPZ (n = 14, 23.7%; p = 0.67). The demographic, clinical, and laboratory data did not differ significantly after propensity score matching, apart from bradycardia, which was a prominent feature of the high-dose group. The clinical and radiological response rates on day 7 were higher and the need for invasive mechanical ventilation (IMV) was lower in the high-dose group. The patients with high-dose MPZ had better clinical and radiological responses than those with standard-dose MPZ, although the mortality rate did not differ between standard and high-dose regimens of MPZ.

Impacto de la rehabilitación pulmonar en pacientes con enfermedad pulmonar restrictiva

IntroductionRestrictive lung diseases present alterations in thoracic-pulmonary mechanics, reduced functional capacity and lung function. Intrinsic and extrinsic alterations can be found where the interstitium, thoracic expandability and even lung parenchymal conditions are altered. Pulmonary rehabilitation could benefit patients with the restrictive condition and improve their functional condition. ObjectiveEstablish the impact of pulmonary rehabilitation in patients with intrinsic and extrinsic restrictive respiratory compromise on dyspnea, functional capacity, anxiety/depression and health-related quality of life. MethodsLongitudinal descriptive study with 50 patients with restrictive lung disease who performed pulmonary rehabilitation in a clinic in the city of Cali, Colombia. The participants linked to the study were separated into two groups, the first with intrapulmonary restrictive disease (IRD) and the second group with extrapulmonary restrictive disease (ERD). ResultsThe mean age of the patients was 53.3years. Among the restrictive intrapulmonary diseases there were: diffuse interstitial lung disease (ILD), post-condition pneumonia and/or acute respiratory distress syndrome (ARDS) and sequelae of pulmonary tuberculosis. Extrapulmonary respiratory diseases: lung resection, pulmonary lobe resection, and wedge resection. At the end of pulmonary rehabilitation, the IRD group presented statistically significant improvements in distance covered, estimated oxygen consumption (VO2e), dyspnea, anxiety, and quality of life. The ERD group presented a significant increase in the distance traveled and VO2e. ConclusionPatients with restrictive lung disease improve the distance traveled, VO2e, dyspnea, anxiety and quality of life; patients with extrapulmonary respiratory disease show improvements in functional capacity.

Convalescent Plasma Therapy in Critically Ill COVID-19 Patients: An Open Label Trial.

ObjectivesThe novel severe acute respiratory syndrome coronavirus 2 pandemic continues to spread globally without an effective treatment. In search of the cure, convalescent plasma (CP) containing protective antibodies from survivors of coronavirus disease 2019 (COVID-19) infection has shown potential benefit in a non-intensive care unit setting. We sought to evaluate the effectiveness of CP therapy for patients with COVID-19 on mechanical ventilation (MV) and/or acute respiratory distress syndrome (ARDS).MethodsWe conducted an open-label trial in a single center, Royal Hospital, in Oman. The study was conducted from 17 April to 20 June 2020. The trial included 94 participants with laboratory-confirmed COVID-19. The primary outcomes included extubation rates, discharges from the hospital and overall mortality, while secondary outcomes were the length of stay and improvement in respiratory and laboratory parameters. Analyses were performed using univariate statistics.ResultsThe overall mean age of the cohort was 50.0±15.0 years, and 90.4% (n = 85) were males. A total of 77.7% (n = 73) of patients received CP. Those on CP were associated with a higher extubation rate (35.6% vs. 76.2%; p < 0.001), higher extubation/home discharges rate (64.4% vs. 23.8%; p =0.001), and tendency towards lower overall mortality (19.2% vs. 28.6%; p =0.354; study power = 11.0%) when compared to COVID-19 patients that did not receive CP.ConclusionsCP was associated with higher extubation/home discharges and a tendency towards lower overall mortality when compared to those that did not receive CP in COVID-19 patients on MV or in those with ARDS. Further studies are warranted to corroborate our findings.

BMSC-derived exosomes ameliorate sulfur mustard-induced acute lung injury by regulating the GPRC5A-YAP axis.

Sulfur mustard (SM) is a highly toxic chemical warfare agent that causes acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). There are no effective therapeutic treatments or antidotes available currently to counteract its toxic effects. Our previous study shows that bone marrow-derived mesenchymal stromal cells (BMSCs) could exert therapeutic effects against SM-induced lung injury. In this study, we explored the therapeutic potential of BMSC-derived exosomes (BMSC-Exs) against ALI and the underlying mechanisms. ALI was induced in mice by injection of SM (30 mg/kg, sc) at their medial and dorsal surfaces. BMSC-Exs (20 μg/kg in 200 μL PBS, iv) were injected for a 5-day period after SM exposure. We showed that BMSC-Exs administration caused a protective effect against pulmonary edema. Using a lung epithelial cell barrier model, BMSC-Exs (10, 20, 40 μg) dose-dependently inhibited SM-induced cell apoptosis and promoted the recovery of epithelial barrier function by facilitating the expression and relocalization of junction proteins (E-cadherin, claudin-1, occludin, and ZO-1). We further demonstrated that BMSC-Exs protected against apoptosis and promoted the restoration of barrier function against SM through upregulating G protein-coupled receptor family C group 5 type A (GPRC5A), a retinoic acid target gene predominately expressed in the epithelial cells of the lung. Knockdown of GPRC5A reduced the antiapoptotic and barrier regeneration abilities of BMSC-Exs and diminished their therapeutic effects in vitro and in vivo. BMSC-Exs-caused upregulation of GPRC5A promoted the expression of Bcl-2 and junction proteins via regulating the YAP pathway. In summary, BMSC-Exs treatment exerts protective effects against SM-induced ALI by promoting alveolar epithelialbarrier repair and maybe an alternative approach to stem cell-based therapy.

In silico Analysis Revealed Potential Anti-SARS-CoV-2 Main Protease Activity by the Zonulin Inhibitor Larazotide Acetate

The most severe outcome of COVID-19 infection is the development of interstitial pneumonia causing acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS), both responsible for the infected patients' mortality. ALI and ARDS are characterized by a leakage of plasma components into the lungs, compromising their ability to expand and optimally engage in gas exchange with blood, resulting in respiratory failure. We have previously reported that zonulin, a protein dictating epithelial and endothelial permeability in several districts, including the airways, is involved in ALI pathogenesis in mouse models, and that its peptide inhibitor Larazotide acetate (also called AT1001) ameliorated ALI and subsequent mortality by decreasing mucosal permeability to fluid and extravasation of neutrophils into the lungs. With the recent crystallographic resolution of the SARS-CoV-2 main protease (Mpro), an enzyme fundamental in the viral lifecycle, bound to peptidomimetic inhibitors N3 and 13b, we were able to perform molecular modeling investigation showing that AT1001 presents structural motifs similar to co-crystallized ligands. Specifically, molecular docking, MM-GBSA-based predictions and molecular dynamics showed that AT1001 docks extremely well in the Mpro catalytic domain through a global turn conformational arrangement without any unfavorable steric hindrance. Finally, we have observed that AT1001 can be superimposed onto the crystallized structures of N3 and 13b, establishing a higher number of interactions and accordingly a tighter binding. In vitro studies confirmed AT1001 anti-Mpro and preliminary investigation indicted an anti-viral activity. Combined, these studies suggest that AT1001, besides its well-demonstrated effect in ameliorating mucosal permeability in ALI/ARDS, may also exert a direct anti-SARS-CoV-2 effect by blocking the Mpro. AT1001 has been used extensively in a variety of animal models of ALI demonstrating robust safety and efficacy; it is currently in phase 3 trials in celiac subjects showing strong safety and efficacy profiles. We therefore propose its use as a specific anti-SARS-CoV-2 multitargeting treatment for the current pandemic.

Oferta energética e proteica para pacientes críticos submetidos à oxigenação por membrana extracorpórea venovenosa (ECMO-VV): revisão sistemática

Objective: Identify the energy and protein supply for critical patients with severe respiratory failure and/or acute respiratory distress syndrome (ARDS) undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO). Methods: Systematic review with search performed on the Cochrane, Embase and MEDLINE via PubMed databases. Observational studies (cross-sectional, cohort and case-control) were included, targeting adult patients with severe respiratory failure and/or ARDS, undergoing VV-ECMO. Results: Among the 11 articles analyzed, the energy supply, when estimated using weight-based equations, ranged from 20 to 30 kcal/kg/day. When measured by indirect calorimetry, ranged from 1703 to 2013 kcal/day and from 13 to 18 kcal/kg/day. The protein supply, when estimated using weight-based equations, ranged from 1.2 to 2.5 g/kg/day; when measured by nitrogen balance, ranged from 1.8 to 2.5 g/kg/day. Conclusion: Studies to date show a great variability in the caloric-protein supply for critically ill patients in ECMO-VV. Given the importance of nutritional support, it is evident the need for further studies with better methodological design to determine the most adequate energy and protein supply for these patients.

Protocol Failure Detection: The Conflation of Acute Respiratory Distress Syndrome, SARS-CoV-2 Pneumonia and Respiratory Dysfunction.

In medicine, protocols are applied to assure the provision of the treatment with the greatest probability of success. However, the development of protocols is based on the determination of the best intervention for the group. If the group is heterogeneous, there will always be a subset of patients for which the protocol will fail. Furthermore, over time, heterogeneity of the group may not be stable, so the percentage of patients for which a given protocol may fail may change depending on the dynamic patient mix in the group. This was thrown into stark focus during the severe acute respiratory syndrome-2 coronavirus (SARS-CoV-2) pandemic. When a COVID-19 patient presented meeting SIRS or the Berlin Criteria, these patients met the criteria for entry into the sepsis protocol and/or acute respiratory distress syndrome (ARDS) protocol, respectively and were treated accordingly. This was perceived to be the correct response because these patients met the criteria for the “group” definitions of sepsis and/or ARDS. However, the application of these protocols to patients with SARS-CoV-2 infection had never been studied. Initially, poor outcomes were blamed on protocol noncompliance or some unknown patient factor. This initial perception is not surprising as these protocols are standards and were perceived as comprising the best possible evidence-based care. While the academic response to the pandemic was robust, recognition that existing protocols were failing might have been detected sooner if protocol failure detection had been integrated with the protocols themselves. In this review, we propose that, while protocols are necessary to ensure that minimum standards of care are met, protocols need an additional feature, integrated protocol failure detection, which provides an output responsive to protocol failure in real time so other treatment options can be considered and research efforts rapidly focused.

Inflammation, Thrombosis, and Destruction: The Three-Headed Cerberus of Trauma- and SARS-CoV-2-Induced ARDS.

Physical trauma can be considered an unrecognized “pandemic” because it can occur anywhere and affect anyone and represents a global burden. Following severe tissue trauma, patients frequently develop acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) despite modern surgical and intensive care concepts. The underlying complex pathophysiology of life-threatening ALI/ARDS has been intensively studied in experimental and clinical settings. However, currently, the coronavirus family has become the focus of ALI/ARDS research because it represents an emerging global public health threat. The clinical presentation of the infection is highly heterogeneous, varying from a lack of symptoms to multiple organ dysfunction and mortality. In a particular subset of patients, the primary infection progresses rapidly to ALI and ARDS. The pathophysiological mechanisms triggering and driving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced ALI/ARDS are still poorly understood. Although it is also generally unknown whether insights from trauma-induced ARDS may be readily translated to SARS-CoV-2-associated ARDS, it was still recommended to treat coronavirus-positive patients with ALI/ARDS with standard protocols for ALI/ARDS. However, this strategy was questioned by clinical scientists, because it was documented that some severely hypoxic SARS-CoV-2-infected patients exhibited a normal respiratory system compliance, a phenomenon rarely observed in ARDS patients with another underlying etiology. Therefore, coronavirus-induced ARDS was defined as a specific ARDS phenotype, which accordingly requires an adjusted therapeutic approach. These suggestions reflect previous attempts of classifying ARDS into different phenotypes that might overall facilitate ARDS diagnosis and treatment. Based on the clinical data from ARDS patients, two major phenotypes have been proposed: hyper- and hypo-inflammatory. Here, we provide a comparative review of the pathophysiological pathway of trauma-/hemorrhagic shock-induced ARDS and coronavirus-induced ARDS, with an emphasis on the crucial key points in the pathogenesis of both these ARDS forms. Therefore, the manifold available data on trauma-/hemorrhagic shock-induced ARDS may help to better understand coronavirus-induced ARDS.

Awake prone positioning for COVID-19 hypoxemic respiratory failure: A rapid review.

Abstract Background Infection with SARS-CoV-2 can result in Coronavirus Disease–19 (COVID-19) [1, 2]. While the majority of patients are asymptomatic or have mild disease [3], approximately 14% develop more severe disease including hypoxemic respiratory failure and/or Acute Respiratory Distress Syndrome (ARDS) [3]. Prone positioning is a life-saving intervention for mechanically ventilated patients with moderate-severe ARDS [4]. Based on this, the World Health Organization (WHO) guidelines recommend these patients be considered for a trial of prone positioning [5]. Recently the use of prone positioning in awake non-intubated COVID-19 patients has been recommended by several notable organizations with the goal of preventing intubation and potentially improving patient-oriented outcomes [6, 7]. In contrast to prone positioning for intubated mechanically ventilated patients with ARDS, there have been no randomized control trials examining the role of awake prone positioning for non-intubated patients with hypoxemic respiratory failure. To further explore this question we used rapid review methodology (Tricco et al., 2015 [8]) to quickly identify and synthesize studies examining the effect of awake prone positioning on patients with hypoxemic respiratory failure (including those with ARDS and/or COVID-19). Methods We have elected to use “rapid review” methodology rather than “systematic review” methodology primarily due to the speed and efficiency through which we are able to conduct this review, as previously described [8]. In the absence of an EQUATOR guidance document, we used PRISMA guidelines where applicable [9]. Studies were included if they met the following criteria 1) population – non-intubated patients with hypoxemic respiratory failure, 2) intervention – prone positioning, 3) comparator – usual management, 4) outcomes – intubation, survival, change in respiratory parameters, adverse events, 5) setting – hospitalized patients 6) study design – observational or randomized control trial. Studies were not limited to ARDS or COVID-19 patients. The search strategy was developed by a critical care physician (KP), a critical care epidemiologist (KF) and a medical librarian (NL) (See search details in Online Supplement). Briefly, the search strategy involved combinations of keywords and subject headings relating to the concepts of, 1) SARS-Cov-2 or COVID-19 or coronavirus, 2) awake prone positioning, and 3) hypoxemic respiratory failure, including but not limited to ARDS and other potentially relevant conditions. The search was conducted on May 19, 2020 and was updated on August 7, 2020 with no restrictions on publication language or date. Databases and grey literature sources searched included: MEDLINE (Ovid), PubMed, Trip PRO, Cochrane Library, LitCOVID, WHO COVID-19 Research Database, Centre for Evidence-Based Medicine (CEBM), National Institute for Health and Care Excellence (NICE), medRxiv, BMJ Best Practice, Cambridge Coronavirus Free Access Collection, and Google Scholar. Titles and abstracts were reviewed independently and in duplicate (KP and JW) for selection for full text review. Disagreements were resolved through discussion or with a third reviewer (KS). Full text review and data abstraction was conducted independently and in duplicate (KP, KS, JW). Data abstracted included study characteristics, participant demographics, and outcomes.

Emodin alleviates LPS-induced inflammatory response in lung injury rat by affecting the function of granulocytes

BackgroundAcute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are critical life-threatening syndromes characterized by the infiltration of a large number of granulocytes (mainly neutrophils) that lead to an excessive inflammatory response. Emodin (Emo) is a naturally occurring anthraquinone derivative and an active ingredient of Chinese medicine. It is believed to have anti-inflammatory effects. In this study, we examined the impact of Emo on the pulmonary inflammatory response and the granulocytes function in a rat model of lipopolysaccharide (LPS)-induced ALI.ResultsTreatment with Emo protected rat against LPS-induced ALI. Compared to untreated rat, Emo-treated rat exhibited significantly ameliorated lung pathological changes and decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). However, Emo has no protective effect on the rat model of acute lung injury with granulocyte deficiency. In addition, treatment with Emo enhanced the bactericidal capacity of LPS-induced granulocytes via the up-regulation of the ability of granulocytes to phagocytize bacteria and generate neutrophil extracellular traps (NETs). Emo also downregulated the respiratory burst and the expression of reactive oxygen species (ROS) in LPS-stimulated granulocytes, alleviating the damage of granulocytes to surrounding tissues. Finally, Emo can accelerate the resolution of inflammation by promoting apoptosis of granulocytes.ConclusionOur results provide the evidence that Emo could ameliorates LPS-induced ALI via its anti-inflammatory action by modulating the function of granulocytes. Emo may be a promising preventive and therapeutic agent in the treatment of ALI.

Análise de perfil epidemiológico e parâmetros ventilatórios de puérperas submetidas à ventilação mecânica por meio da tomografia por impedância elétrica

Introdução: As doenças relacionadas à gravidez tem agravado o quadro de puérperas, que acabam fazendo uso de Ventilação Mecânica (VM) quando internadas em Unidades de Terapia Intensiva (UTI). A VM, apesar de trazer benefícios, está associada a efeitos deletérios que podem ser minimizados com o uso da Tomografia por Impedância Elétrica (TIE). Objetivo: Analisar o perfil epidemiológico e parâmetros ventilatórios de puérperas que evoluíram com Síndrome HELLP, Sepse e/ou Síndrome do Desconforto Respiratório Agudo (SDRA), sob VM e monitoradas com a TIE. Métodos: Estudo observacional, transversal retrospectivo e prospectivo, realizado entre março e setembro de 2018, por meio de fichas de coletas preenchidas a partir de banco de dados/prontuários sociodemográficos, obstétricos e ventilatórios de puérperas internadas em UTI. Resultados: Amostra composta por 13 puérperas, oito com Sepse (61,5%), sete com Síndrome HELLP (53,8%) e quatro com SDRA (30,8%), demonstrando que cinco (38,5%) pacientes evoluíram com mais de uma dessas patologias. Acerca dos parâmetros ventilatórios avaliados, observou-se VT 378.9 (± 103.9) e que valores médios encontrados para PEEP 9.8 (±1.9) e driving pressure 11.1 (±1.4) estão abaixo dos preconizados pela literatura, predizendo menores índices de mortalidade e morbidade. Conclusão: Demonstrou-se relevância da avaliação de driving pressure no cenário da VM, parâmetro avaliado por meio da TIE e diretamente relacionado à Cst, PEEP, VT e otimização da ventilação pulmonar regional. Destaca-se a necessidade de pesquisas futuras que apresentem maiores significâncias clínicas voltadas ao perfil de puérperas em relação às doenças cada vez mais frequentes nesta população.

RvD1 ameliorates LPS-induced acute lung injury via the suppression of neutrophil infiltration by reducing CXCL2 expression and release from resident alveolar macrophages

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are life-threatening critical syndromes characterized by the infiltration of a large number of inflammatory cells that lead to an excessive inflammatory response. Resolvin D1 (RvD1), an endogenous lipid mediator, is believed to have anti-inflammatory and proresolving effects. In the present study, we examined the impact of RvD1 on the pulmonary inflammatory response, neutrophil influx, and lung damage in a murine model of lipopolysaccharide (LPS)-induced ALI. Treatment with RvD1 protected mice against LPS-induced ALI, and compared to untreated mice, RvD1-treated mice exhibited significantly ameliorated lung pathological changes, decreased tumor necrosis factor-α (TNF-α) concentrations and attenuated neutrophil infiltration. In addition, treatment with RvD1 attenuated LPS-induced neutrophil infiltration via the downregulation of CXCL2 expression on resident alveolar macrophages. Finally, BOC-2, which inhibits the RvD1 receptor lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2), reversed the protective effects of RvD1. These data demonstrate that RvD1 ameliorates LPS-induced ALI via the suppression of neutrophil infiltration by an ALX/FPR2-dependent reduction in CXCL2 expression on resident alveolar macrophages.

Recombinant chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) protects against LPS-induced lung injury in mice

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are clinical conditions caused by trauma, lung infection or sepsis. ALI/ARDS is associated with massive recruitment of neutrophils into the lung with release of reactive oxygen species and excessive inflammatory response that damage alveolar tissue. Here we report the successful use of a potent recombinant chemotaxis inhibitory protein (rCHIPS) derived from Staphylococcus aureus in reducing the severity of ALI/ARDS. Treatment with rCHIPS reduces pulmonary inflammation and permeability in mice after intranasal administration of lipopolysaccharide (LPS). rCHIPS treatment significantly reduces lung myeloperoxidase (MPO) activity, pro-inflammatory cytokines, broncho-alveolar lavage (BAL) fluid protein content as well as histopathological changes. In addition, treatment with rCHIPS significantly diminishes neutrophils and leukocytes recruitment into lung tissue after LPS administration and hence protects mice from reactive oxygen species mediated lung injury. Our finding reveals potential therapeutic benefits of using rCHIPS for the treatment of ALI/ARDS.

Protective Lung Ventilation and Morbidity After Pulmonary Resection: A Propensity Score-Matched Analysis.

Protective lung ventilation (PLV) during one-lung ventilation (OLV) for thoracic surgery is frequently recommended to reduce pulmonary complications. However, limited outcome data exist on whether PLV use during OLV is associated with less clinically relevant pulmonary morbidity after lung resection. Intraoperative data were prospectively collected in 1080 patients undergoing pulmonary resection with OLV, intentional crystalloid restriction, and mechanical ventilation to maintain inspiratory peak airway pressure <30 cm H2O. Other ventilator settings and all aspects of anesthetic management were at the discretion of the anesthesia care team. We defined PLV and non-PLV as <8 or ≥8 mL/kg (predicted body weight) mean tidal volume. The primary outcome was the occurrence of pneumonia and/or acute respiratory distress syndrome (ARDS). Propensity score matching was used to generate PLV and non-PLV groups with comparable characteristics. Associations between outcomes and PLV status were analyzed by exact logistic regression, with matching as cluster in the anatomic and nonanatomic lung resection cohorts. In the propensity score-matched analysis, the incidence of pneumonia and/or ARDS among patients who had an anatomic lung resection was 9/172 (5.2%) in the non-PLV compared to the PLV group 7/172 (4.1%; odds ratio, 1.29; 95% confidence interval, 0.48-3.45, P= .62). The incidence of pneumonia and/or ARDS in patients who underwent nonanatomic resection was 3/118 (2.5%) in the non-PLV compared to the PLV group, 1/118 (0.9%; odds ratio, 3.00; 95% confidence interval, 0.31-28.84, P= .34). In this prospective observational study, we found no differences in the incidence of pneumonia and/or ARDS between patients undergoing lung resection with tidal volumes <8 or ≥8 mL/kg. Our data suggest that when fluid restriction and peak airway pressures are limited, the clinical impact of PLV in this patient population is small. Future randomized trials are needed to better understand the benefits of a small tidal volume strategy during OLV on clinically important outcomes.

Effect of nebulized budesonide on respiratory mechanics and oxygenation in acute lung injury/acute respiratory distress syndrome: Randomized controlled study.

Background:We tested the hypothesis that nebulized budesonide would improve lung mechanics and oxygenation in patients with early acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) during protective mechanical ventilation strategy without adversely affecting systemic hemodynamics.Methods:Patients with ALI/ARDS were included and assigned into two groups; budesonide group (30 cases) in whom 1 mg–2 ml budesonide suspension was nebulized through the endotracheal tube and control group (30 cases) in whom 2 ml saline (placebo) were nebulized instead of budesonide. This regimen was repeated every 12 h for three successive days alongside with constant ventilator settings in both groups. Hemodynamics, airway pressures, and PaO2/FiO2 were measured throughout the study period (72 h) with either nebulized budesonide or saline. Furthermore, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) were analyzed serologically as markers of inflammation at pre- and post-nebulization sessions.Results:We found a significant difference between the two groups regarding PaO2/FiO2 (P = 0.023), peak (P = 0.021), and plateau (P = 0.032) airway pressures. Furthermore, TNF-α, IL-1β, and IL-6 were significantly reduced after budesonide nebulizations. No significant difference was found between the two groups regarding hemodynamic variables.Conclusion:Nebulized budesonide improved oxygenation, peak, and plateau airway pressures and significantly reduced inflammatory markers (TNF-α, IL-1β and IL-6) without affecting hemodynamics.Trial Registry:Australian New Zealand Clinical Trial Registry (ANZCTR) at the number: ACTRN12615000373572.

An Inhaled Inhibitor of Myristoylated Alanine-Rich C Kinase Substrate Reverses LPS-Induced Acute Lung Injury in Mice.

Intratracheal instillation of bacterial LPS is a well-established model of acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Because the myristoylated alanine-rich C kinase substrate (MARCKS) protein is involved in neutrophil migration and proinflammatory cytokine production, we examined whether an aerosolized peptide that inhibits MARCKS function could attenuate LPS-induced lung injury in mice. The peptide, BIO-11006, was delivered at 50 μM via inhalation either just before intratracheal instillation of 5 μg of LPS into Balb/C mice, or 4, 12, 24, or 36 hours after LPS instillation. Effects of BIO-11006 were evaluated via analysis of mouse disease-related behavior, lung histology, bronchoalveolar lavage fluid total protein, neutrophil counts and percentages, cytokine (KC [CXCl1, mouse IL-8 equivalent] and TNF-α) expression, and activation of NF-κB in lung tissue. Treatment with aerosolized BIO-11006 at 0, 4, 12, 24, and even 36 hours after LPS instillation reversed the disease process: mouse behavior returned to normal after two treatments 12 hours apart with the inhaled peptide after LPS injury, whereas control LPS-instilled animals treated with PBS only remained moribund. Histological appearance of inflammation, bronchoalveolar lavage fluid protein levels, leukocyte and neutrophil numbers, KC and TNF-α gene and protein expression, and NF-κB activation were all significantly attenuated by inhaled BIO-11006 at all time points. These results implicate MARCKS protein in the pathogenesis of ALI/ARDS and suggest that MARCKS-inhibitory peptide(s), delivered by inhalation, could represent a new and potent therapeutic treatment for ALI/ARDS, even if administered well after the disease process has begun.

A systematic review of one-lung ventilation during thoracic surgery comparing the safety and efficacy of high and low tidal volumes

Lung isolation, a technique largely used to facilitate access during thoracic surgery, can create some difficulty in maintaining a patient's blood gas balance. Strategies have been used to overcome the ventilation-perfusion mismatch associated with one-lung ventilation (OLV). However, such strategies may induce volutrauma, barotrauma and atelectotrauma in the ventilated lung, leading to acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Different ventilatory parameters have been used to improve the safety and efficacy of OLV, with the use of high or low tidal volumes (VT) being the most contentious.

A systematic review of one - lung ventilation during thoracic surgery comparing the safety and efficacy of high and low tidal volumes

Background/Introduction Lung isolation, a technique largely used to facilitate access during thoracic surgery, can create some difficulty in maintaining a patient’s blood gas balance. Strategies have been used to overcome the ventilation-perfusion mismatch associated with one-lung ventilation (OLV). However, such strategies may induce volutrauma, barotrauma and atelectotrauma in the ventilated lung, leading to acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Different ventilatory parameters have been used to improve the safety and efficacy of OLV, with the use of high or low tidal volumes (VT) being the most contentious.

Lung recruitment maneuver with and without nebulized albuterol for acute lung injury: a randomized, controlled study

Background β2-Adrenoceptor agonists accelerate the resolution of pulmonary edema in experimental and clinical studies. We tested the hypothesis that combining nebulized albuterol with lung recruitment maneuver (RM) during mechanical ventilation would improve oxygenation and accelerate the resolution of pulmonary edema more than would RM alone in patients with acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Materials and methods In this randomized, controlled, single-blinded study, 60 patients admitted to the ICU of Qena University Hospitals and suffering from ALI and/or ARDS were recruited. All patients were subjected to the lung RM. They were assigned to two equal groups: the albuterol group (30 patients), in which patients were medicated with nebulized albuterol 1 mg diluted in 10 ml saline; and the control group (30 patients), in which patients were given 10 ml nebulized saline instead of albuterol. This regimen was repeated every 8 h for 3 days. Alveolar fluid samples were withdrawn before and 1 h after the lung recruitment for protein concentration measurement in the alveolar fluid. Results We found a significant difference between the two groups regarding PaO2 ( P = 0.003) and PaO2/FiO2 ( P = 0.023) before and after RM ± albuterol. No significant difference between the two groups was found regarding alveolar fluid clearance and alveolar protein concentration. Conclusion RM with nebulized albuterol improved oxygenation but the addition of albuterol was not beneficial regarding alveolar fluid clearance in terms of lowering alveolar protein concentration in ALI/ARDS patients. Trial registration The study was registered in the Australian Newzealand clinical trial registry (ANZCTR), with the number, ACTRN12613000836730, and website, http://www.ANZCTR.org.au/ACTRN12613000836730.aspx .