Mechanisms and Research Progress of Traditional Chinese Medicine Regulating NF-κB in the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

Acute lung injury(ALI)has multiple causes and can easily progress to acute respiratory distress syndrome(ARDS)if not properly treated.Nuclear factorκB(NF-κB)is a key pathway in the treatment of ALI/ARDS.By exploring the relevance of NF-κB and the pathogenesis of this disease,it was found that this disease was mainly associated with inflammation,dysfunction of the endothelial barrier,oxidative stress,impaired clearance of alveolar fluid,and coagulation disorders.Traditional Chinese medicine(TCM)has the characteristics of multitargeting,multipathway effects,and high safety,which can directly or indirectly affect the treatment of ALI/ARDS.This article summarizes the mechanism and treatment strategies of TCM in recent years through intervention in the NF-κB-related signaling pathways for treating ALI/ARDS.It provides an overview from the perspectives of Chinese herbal monomers,TCM couplet medicines,TCM injections,Chinese herbal compounds,and Chinese herbal preparations,offering insights into the prevention and treatment of ALI/ARDS with TCM.

Review:Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism,present strategies and future perspectives of therapies

Acute lung injury/acute respiratory distress syndrome （ALI/ARDS）, which manifests as non-cardiogcnic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.

Acute lung injury and acute respiratory distress syndrome： experimental and clinical investigations

Acute lung injury （ALl） or acute respiratory distress syndrome （ARDS） can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALl or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Effects of dynamic ventilatory factors on ventilatorinduced lung injury in acute respiratory distress syndrome dogs

BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries （VILI） and to explore its potential mechanisms.METHODS： Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope.RESULTS： IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-a ray degree of group B was significantly higher than that in the other groups （P〈0.01）, especially in group C （P〉0.05）. The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B.CONCLUSION： Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.

Ulinastatin for acute lung injury and acute respiratory distress syndrome: A systematic review and meta-analysis

AIM: To investigate the efficacy and safety of ulinastatin for patients with acute lung injury(ALI) and those with acute respiratory distress syndrome(ARDS).METHODS: A systematic review of randomized controlled trials(RCTs) of ulinastatin for ALI/ARDS was conducted. Oxygenation index, mortality rate [intensive care unit(ICU) mortality rate, 28-d mortality rate] and length of ICU stay were compared between ulinastatin group and conventional therapy group. Meta-analysis was performed by using Rev Man 5.1.RESULTS: Twenty-nine RCTs with 1726 participants were totally included, the basic conditions of which were similar. No studies discussed adverse effect. Oxygenation index was reported in twenty-six studies(1552 patients). Ulinastatin had a significant effect in improving oxygenation [standard mean difference(SMD) = 1.85, 95%CI: 1.42-2.29, P < 0.00001, I2 = 92%]. ICUmortality and 28-d mortality were respectively reported in eighteen studies(987 patients) and three studies(196 patients). We found that ulinastatin significantly decreased the ICU mortality [I2 = 0%, RR = 0.48, 95%CI: 0.38-0.59, number needed to treat(NNT) = 5.06, P < 0.00001], while the 28-d mortality was not significantly affected(I2 = 0%, RR = 0.78, 95%CI: 0.51-1.19, NNT = 12.66, P = 0.24). The length of ICU stay(six studies, 364 patients) in the ulinastatin group was significantly lower than that in the control group(SMD =-0.97, 95%CI:-1.20--0.75, P < 0.00001, I2 = 86%). CONCLUSION: Ulinastatin seems to be effective for ALI and ARDS though most trials included were of poor quality and no information on safety was provided.

Acute respiratory distress syndrome and lung injury: Pathogenetic mechanism and therapeutic implication

To review possible mechanisms and therapeutics for acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). ALI/ARDS causes high mortality. The risk factors include head injury, intracranial disorders, sepsis, infections and others. Investigations have indicated the detrimental role of nitric oxide(NO) through the inducible NO synthase(i NOS). The possible therapeutic regimen includes extracorporeal membrane oxygenation, prone position, fluid and hemodynamic management and permissive hypercapnic acidosis etc. Other pharmacological treatments are anti-inflammatory and/or antimicrobial agents, inhalation of NO, glucocorticoids, surfactant therapy and agents facilitating lung water resolution and ion transports. β-adrenergic agonists are able to accelerate lung fluid and ion removal and to stimulate surfactant secretion. In con-scious rats, regular exercise training alleviates the endotoxin-induced ALI. Propofol and N-acetylcysteine exert protective effect on the ALI induced by endotoxin. Insulin possesses anti-inflammatory effect. Pentobarbital is capable of reducing the endotoxin-induced ALI. In addition, nicotinamide or niacinamide abrogates the ALI caused by ischemia/reperfusion or endotoxemia. This review includes historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.

Basic and clinical research progress in acute lung injury/acute respiratory distress syndrome

Acute lung injury(ALI)/acute respiratory distress syndrome(ARDS) is an acute progressive respiratory failure caused by severe infection, trauma, shock, poisoning, inhaled harmful gas, acute pancreatitis, and pathological obstetrics. ALI and ARDS demonstrate similar pathophysiological changes. The severe stage of ALI is defined as ARDS. At present, a significant progress has been achieved in the study of the pathogenesis and pathophysiology of ALI/ARDS. Whether or not ALI/ARDS patients can recover depends on the degree of lung injury, extra-pulmonary organ damage, original primary disease of a patient, and adequacy in supportive care. Conservative infusion strategies and protective lung ventilation reduce ARDS disability and mortality. In this study, the pathogenesis of ALI/ARDS, lung injury, molecular mechanisms of lung repair, and conservative infusion strategies and pulmonary protective ventilation are reviewed comprehensively.

Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome

Endothelial cells(ECs)form a semi-permeable barrier between the interior space of blood vessels and the un-derlying tissues.Pulmonary endothelial barrier integrity is maintained through coordinated cellular processes involving receptors,signaling molecules,junctional complexes,and protein-regulated cytoskeletal reorganiza-tion.In acute lung injury(ALI)or its more severe form acute respiratory distress syndrome(ARDS),the loss of endothelial barrier integrity secondary to endothelial dysfunction caused by severe pulmonary inflamma-tion and/or infection leads to pulmonary edema and hypoxemia.Pro-inflammatory agonists such as histamine,thrombin,bradykinin,interleukin 1𝛽,tumor necrosis factor𝛼,vascular endothelial growth factor,angiopoietin-2,and platelet-activating factor,as well as bacterial toxins and reactive oxygen species,cause dynamic changes in cytoskeletal structure,adherens junction disorganization,and detachment of vascular endothelial cadherin(VE-cadherin)from the actin cytoskeleton,leading to an increase in endothelial permeability.Endothelial interactions with leukocytes,platelets,and coagulation enhance the inflammatory response.Moreover,inflammatory infil-tration and the associated generation of pro-inflammatory cytokines during infection cause EC death,resulting in further compromise of the structural integrity of lung endothelial barrier.Despite the use of potent antibiotics and aggressive intensive care support,the mortality of ALI is still high,because the mechanisms of pulmonary EC barrier disruption are not fully understood.In this review,we summarized recent advances in the studies of endothelial cytoskeletal reorganization,inter-endothelial junctions,endothelial inflammation,EC death,and endothelial repair in ALI and ARDS,intending to shed some light on the potential diagnostic and therapeutic targets in the clinical management of the disease.

Effectiveness and safety of Qidong Huoxue decoction(芪冬活血饮)in treatment of acute lung injury and acute respiratory distress syndrome:a randomized,controlled trial

OBJECTIVE:To evaluate the efficacy of Qidong Huoxue decoction(芪冬活血饮,QDHX)in treating acute lung injury and acute respiratory distress syndrome(ALI/ARDS)when used as an adjunctive treatment.METHODS:ALI/ARDS patients admitted to our medical intensive care unit were randomly allocated to the control group or the QDHX group and received standard therapy.The QDHX group received QDHX(50 mL per day for 14 d)orally or via a gastric tube.The primary outcome was measured according to Traditional Chinese Medicine(TCM)syndrome scores,with partial pressure of oxygen/fraction of inspired oxygen(PaO_(2)/FiO_(2))levels as the secondary outcome.RESULTS:A total of 73 patients completed the study(36 in the TCM and 37 in the conventional group),and their records were analyzed.After 14-d treatment,the TCM group showed a significant decrease in TCM syndrome scores(P<0.05)and increased PaO_(2)/FiO_(2) levels(P<0.05).The therapeutic effect of integrated Chinese and western medicine was more significant than that of Western Medicine alone.No serious side effects were observed.CONCLUSIONS:Our study results show that QDHX in combination with conventional drug therapy can significantly reduce some clinical symptoms in patients with ALI/ARDS.

Outpatient insulin use in type 2 diabetes mellitus and acute respiratory distress syndrome outcomes:A retrospective cohort study

BACKGROUND The impact of type 2 diabetes mellitus(T2DM)on acute respiratory distress syndrome(ARDS)is debatable.T2DM was suspected to reduce the risk and complications of ARDS.However,during coronavirus disease 2019(COVID-19),T2DM predisposed patients to ARDS,especially those who were on insulin at home.AIMTo evaluate the impact of outpatient insulin use in T2DM patients on non-COVID-19 ARDS outcomes.METHODS We conducted a retrospective cohort analysis using the Nationwide Inpatient Sample database.Adult patients diagnosed with ARDS were stratified into insulin-dependent diabetes mellitus(DM)(IDDM)and non-insulindependent DM(NIDDM)groups.After applying exclusion criteria and matching over 20 variables,we compared cohorts for mortality,duration of mechanical ventilation,incidence of acute kidney injury(AKI),length of stay(LOS),hospitalization costs,and other clinical outcomes.RESULTS Following 1:1 propensity score matching,the analysis included 274 patients in each group.Notably,no statistically significant differences emerged between the IDDM and NIDDM groups in terms of mortality rates(32.8%vs 31.0%,P=0.520),median hospital LOS(10 d,P=0.537),requirement for mechanical ventilation,incidence rates of sepsis,pneumonia or AKI,median total hospitalization costs,or patient disposition upon discharge.CONCLUSION Compared to alternative anti-diabetic medications,outpatient insulin treatment does not appear to exert an independent influence on in-hospital morbidity or mortality in diabetic patients with non-COVID-19 ARDS.

Effect of High Frequency Oscillatory Ventilation on EVLW and Lung Capillary Permeability of Piglets with Acute Respiratory Distress Syndrome Caused by Pulmonary and Extrapulmonary Insults

The effect of high frequency oscillatory ventilation（HFOV） at early stage on hemodynamic parameters, extravascular lung water（EVLW）, lung capillary permeability, CC16 and s ICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome（ARDS） was explored. Central vein pressure（CVP） and pulse indicator continuous cardiac output（Pi CCO） were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS（ARDSp） and extrapulmonary ARDS（ARDSexp） models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index（EVLWI）, EVLW/intratroracic blood volume（ITBV） and pulmonary vascular permeability index（PVPI） were measured before and after modeling（T0 and T1）, and T2（1 h）, T3（2 h）, T4（3 h） and T5（4 h） after HFOV. CC16 and s ICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group（P〈0.05）. The EVLWI in ARDSp group was increased at T1（P=0.008）, and sustained continuously within 2 h（P=0.679, P=0.216）, but decreased at T4（P=0.007） and T5（P=0.037）. The EVLWI in ARDSexp group was also increased at T1（P=0.003）, but significantly decreased at T3（P=0.002） and T4（P=0.019）. PVPI was increased after modeling in both two groups（P=0.004, P=0.012）, but there was no significant change within 4 h（T5） under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI（P=0.13）, ΔPVPI（P=0.28） and ΔEVLW/ITBV between the two groups（P=0.63）. The significant decreases in both CC16 and s ICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV.

Lung recruitment maneuver effects on respiratory mechanics and extravascular lung water index in patients with acute respiratory distress syndrome

BACKGROUND：Animal experiments showed that recruitment maneuver （RM） and protective ventilation strategy of the lung could improve oxygenation and reduce extravascular lung water. This study was to investigate the effects of RM on respiratory mechanics and extravascular lung water index （EVLWI） in patients with acute respiratory distress syndrome （ARDS）. METHODS：Thirty patients with ARDS were randomized into a RM group and a non-RM group. In the RM group, after basic mechanical ventilation stabilized for 30 minutes, RM was performed and repeated once every 12 hours for 3 days. In the non-RM group, lung protective strategy was conducted without RM. Oxygenation index （PaO2/FiO2）, peak inspiratory pressure （PIP）, Plateau pressure （Pplat）, static pulmonary compliance （Cst） and EVLWI of patients before treatment and at 12, 24, 48, 72 hours after the treatment were measured and compared between the groups. Hemodynamic changes were observed before and after RM. One-way ANOVA, Student＇s t test and Fisher＇s exact test were used to process the data. RESULTS：The levels of PaO2/FiO2 and Cst increased after treatment in the two groups, but they were higher in the RM group than in the non-RM group （P〈0.05）. The PIP and Pplat decreased after treatment in the two groups, but they were lower in the RM group than in the non-RM group （P〈0.05）. The EVLWI in the two groups showed downward trend after treatment （P〈0.05）, and the differences were signifcant at all time points （P〈0.01）; the EVLWI in the RM group was lower than that in the non-RM group at 12, 24, 48 and 72 hours （P〈0.05 or P〈0.01）. Compared with pre-RM, hemodynamics changes during RM were significantly different （P〈0.01）; compared with pre-RM, the changes were not significantly different at 120 seconds after the end of RM （P〉0.05）. CONCLUSIONS： RM could reduce EVLWI, increase oxygenation and lung compliance. The effect of RM on hemodynamics was transient.

Mitofusion 2 Overexpression Decreased Proliferation of Human Embryonic Lung Fibroblasts in Acute Respiratory Distress Syndrome through Inhibiting RAS-RAF-1-ERK1/2 Pathway

Acute respiratory distress syndrome(ARDS)is one of the most fatal diseases worldwide.Pulmonary fibrosis occurs early in ARDS,and its severity plays a crucial role in ARDS mortality rate.Some studies suggested that fibroproliferation is an essential mechanism in ARDS.Mitofusion2(Mfn2)overexpression plays a role in inhibiting cell proliferation.However,the role and potential mechanism of Mfn2 on the proliferation of fibroblasts is still unknown.In this study,we aimed at exploring the effect of Mfn2 on the human embryonic lung fibroblasts(HELF)and discussed its related mechanism.The HELF were treated with the Mfn2 overexpressing lentivirus(adv-Mfn2).The cell cycle was detected by flow cytometry.MTT,PCR and Western blotting were used to investigate the effect of Mfn2 on the proliferation of the HELF,collagen expression,the RAS-RAF-1-ERK1/2 pathway and the expression of cycle-related proteins(p21,p27,Rb,Raf-1,p-Raf-1,Erk1/2 and p-Erk1/2).The co-immunoprecipitation assay was used to explore the interaction between Mfn2 and Ras.The results showed that the overexpression of Mfn2 inhibited the proliferation of the HELF and induced the cell cycle arrest at the G0/G1 phase.Meanwhile,Mfn2 also inhibited the expression of collagen I,p-Erk and p-Raf-1.In addition,an interaction between Mfn2 and Ras existed in the HELF.This study suggests that the overexpression of Mfn2 can decrease the proliferation of HELF in ARDS,which was associated with the inhibition of the RAS-RAF-1-ERK1/2 pathway.The results may offer a potential therapeutic intervention for patients with ARDS.

Halogen Inhalation-Induced Lung Injury and Acute Respiratory Distress Syndrome

Objective：Exposure to halogens,such as chlorine or bromine,results in environmental and occupational hazard to the lung and other organs.Chlorine is highly toxic by inhalation,leading to dyspnea,hypoxemia,airway obstruction,pneumonitis,pulmonary edema,and acute respiratory distress syndrome （ARDS）.Although bromine is less reactive and oxidative than chlorine,inhalation also results in bronchospasm,airway hyperresponsiveness,ARDS,and even death.Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well.There is no specific antidote for these injuries since the mechanisms are largely unknown.Data Sources：This review was based on articles published in PubMed databases up to January,2018,with the following keywords：＂chlorine,＂ ＂bromine,＂ ＂lung injury,＂ and ＂ARDS.＂Study Selection：The original articles and reviews including the topics were the primary references.Results：Based on animal studies,it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity;thus,potential treatments will target the oxidative stress and inflammation induced by chlorine.Antioxidants,cAMP-elevating agents,anti-inflammatory agents,nitric oxide-modulating agents,and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury.Elevated free heme level is involved in acute lung injury caused by bromine inhalation.Hemopexin,a heme-scavenging protein,when administered postexposure,decreases lung injury and improves survival.Conclusions：At present,there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs.

Is Chinese Medicine Injection Applicable for Treating Acute Lung Injury and Acute Respiratory Distress Syndrome?A Systematic Review and Meta-analysis of Randomized Controlled Trials

Objective To assess the efficacy and safety of Chinese medicine injection(CMI)for treating acute lung injury/acute respiratory distress syndrome(ALI/ARDS).Methods Randomized controlled trials(RCTs)were identified by searching 3 English databases and 4 Chinese databases from their inceptions until February 2019.The Cochrane Handbook was used to evaluate risk of bias in the included studies.Data analysis was conducted using RevMan 5.3.3 software.Results A total of 19 eligible RCTs involving 1,334 participants was included in this systematic review and meta-analysis.The main meta-analysis showed that CMI combined with conventional therapy(CT)was more effective than CT alone in reducing the acute physiology and chronic health evaluation(APACHE)H score[mean difference(MD):−1.74 points,95%confidence interval(CI):−2.77 to−0.71,I^2=0]and increasing the total effective rate[relative risk(RR):1.35,95%CI:1.17 to 1.56,I^2=37%].Compared with CT,CMI combined with CT showed improvements in the arterial partial pressure of oxygen(PaO2,MD:9.25 mm Hg,95%CI:0.87 to 17.63,I^2=98%)and oxygenation index[arterial partial pressure of oxygen(PaO2)/fraction of inspired oxygen(FiO2),MD:50.75 mm Hg,95%CI:35.18 to 66.31,I^2=94%].CMI plus CT was superior to CT in reducing the systemic inflammatory response syndrome(SIRS)score(MD:−0.84 points,95%CI:−1.26 to−0.42,I^2=65%),length of hospital stay(MD:−4.22 days,95%CI:−6.49 to−1.95,I^2=92%),and duration of mechanical ventilation(MD:−2.94 days,95%CI:−4.68 to−1.21,I^2=89%).Only 1 study reported adverse events.Conclusions CMI as an adjuvant therapy showed great potential benefits for the treatment of ALI/ARDS.However,we could not make a definite conclusion due to low quality of included studies and uncertain security.Future studies should focus on improving research design,especially in blindness and placebo.The reporting of adverse events was also needed.

Pro-resolution of inflammation： a potential strategy for treatment of acute lung injury/acute respiratory distress syndrome

Acute lung injury （ALI） and its more severe form acute respiratory distress syndrome （ARDS） are acute clinical complications,which cause significant morbidity and mortality.1 Despite recent advances in our understanding of the pathophysiology and diagnosis of ALI and ARDS,the clinical strategies are restricted to mechanical ventilation and supportive treatments,such as fluid conservative management and glucocorticoids （GCs）.Mechanical ventilation is a common and life-saving strategy for the patients with ARDS.Lung protective ventilation strategy with lower tidal volumes can improve hypoxia and reduce the mortality in patients with ARDS.

Single Lung Acute Respiratory Distress Syndrome

Hydatid disease or echinococcosis is a zoonotic parasitic disease. The lungs are the second most commonly affected organ after the liver. Intrathoracic and extrapulmonary hydatid disease can affect the pleura, mediastinum, heart, diaphragm, and chest wall. The unusual location or complications of thoracic hydatid disease can present both a diagnostic problem and a therapeutic and surgical problem. We present results of a case of multilocular thoracic hydatid disease complicated by aortic wall erosion and cystic fistula in a 23-year-old patient who developed acute respiratory distress syndrome (ARDS) on the 4th day after emergency pneumonectomy. The surgery was carried out under the conditions of the auxiliary artificial circulation. This case represented a serious clinical situation with the highest risk to life. The need for immediate respiratory support was due to the development of severe respiratory failure, and the presence of direct and indirect harmful factors of ARDS. The correct choice of modes and techniques of mechanical ventilation resulted in significant and sustained improvement in gas exchange parameters without hemodynamic disorders with a further favorable outcome.

Changes in intestinal microflora in rats with acute respiratory distress syndrome

AIM: To implement high-throughput 16S rDNA sequencing to study microbial diversity in the fecal matter of rats with acute lung injury/acute respiratory distress syndrome (ALI/ARDS).

Intestinal bacterial overgrowth in the early stage of severe acute pancreatitis is associated with acute respiratory distress syndrome

BACKGROUND In the early stage of acute pancreatitis(AP),a large number of cytokines induced by local pancreatic inflammation seriously damage the intestinal barrier function,and intestinal bacteria and endotoxins enter the blood,causing inflammatory storm,resulting in multiple organ failure,infectious complications,and other disorders,eventually leading to death.Intestinal failure occurs early in the course of AP,accelerating its development.As an alternative method to detect small intestinal bacterial overgrowth,the hydrogen breath test is safe,noninvasive,and convenient,reflecting the number of intestinal bacteria in AP indirectly.This study aimed to investigate the changes in intestinal bacteria measured using the hydrogen breath test in the early stage of AP to clarify the relationship between intestinal bacteria and acute lung injury(ALI)/acute respiratory distress syndrome(ARDS).Early clinical intervention and maintenance of intestinal barrier function would be highly beneficial in controlling the development of severe acute pancreatitis(SAP).AIM To analyze the relationship between intestinal bacteria change and ALI/ARDS in the early stage of SAP.METHODS A total of 149 patients with AP admitted to the intensive care unit of the Digestive Department,Xuanwu Hospital,Capital Medical University from 2016 to 2019 were finally enrolled,following compliance with the inclusion and exclusion criteria.The results of the hydrogen breath test within 1 wk of admission were collected,and the hydrogen production rates at admission,72 h,and 96 h were calculated.The higher the hydrogen production rates the more bacteria in the small intestine.First,according to the improved Marshall scoring system in the 2012 Atlanta Consensus on New Standards for Classification of Acute Pancreatitis,66 patients with a PaO2/FiO2 score≤1 were included in the mild AP(MAP)group,18 patients with a PaO2/FiO2 score≥2 and duration<48 h were included in the moderately SAP(MSAP)group,and 65 patients with a PaO2/FiO2 score≥2 and duration>48 h were included in the SAP group,to analyze the correlation between intestinal bacterial overgrowth and organ failure in AP.Second,ALI(PaO2/FiO2=2)and ARDS(PaO2/FiO2>2)were defined according to the simplified diagnostic criteria proposed by the 1994 European Union Conference.The MSAP group was divided into two groups according to the PaO2/FiO2 score:15 patients with PaO2/FiO2 score=2 were included in group A,and three patients with score>2 were included in group B.Similarly,the SAP group was divided into two groups:28 patients with score=2 were included in group C,and 37 patients with score>2 were included in group D,to analyze the correlation between intestinal bacterial overgrowth and ALI/ARDS in AP.RESULTS A total of 149 patients were included:66 patients in the MAP group,of whom 53 patients were male(80.3%)and 13 patients were female(19.7%);18 patients in the MSAP group,of whom 13 patients were male(72.2%)and 5 patients were female(27.8%);65 patients in the SAP group,of whom 48 patients were male(73.8%)and 17 patients were female(26.2%).There was no significant difference in interleukin-6 and procalcitonin among the MAP,MSAP,and SAP groups(P=0.445 and P=0.399,respectively).There was no significant difference in the growth of intestinal bacteria among the MAP,MSAP,and SAP groups(P=0.649).There was no significant difference in the growth of small intestinal bacteria between group A and group B(P=0.353).There was a significant difference in the growth of small intestinal bacteria between group C and group D(P=0.038).CONCLUSION Intestinal bacterial overgrowth in the early stage of SAP is correlated with ARDS.

Effect of protective lung ventilation strategy combined with lung recruitment maneuver in patients with acute respiratory distress syndrome (ARDS)

Objective:To evaluate the efficacy and safety of protective lung ventilation strategy combined with lung recruitment maneuver (RM) in the treatment patients with acute respiratory distress syndrome (ARDS).Methods:Totally 74 patients with ARDS admitted to the Department of Intensive Care Unit, Changshu Second People's Hospital in Jiangsu Province between September 2010 and June 2013 were selected and randomly divided into lung recruitment group and non-lung recruitment group, and the initial ventilation solution for both groups was synchronized intermittent mandatory ventilation (SIMV). For RM, SIMV mode (pressure control and pressure support) was adopted. Positive end expiratory pressure (PEEP) was increased by 5 cm H2O every time and maintained for 40-50 s before entering the next increasing period, and the peak airway pressure was kept below 45 cm H2O. After PEEP reached the maximum value, it was gradually reduced by 5 cm H2O every time and finally maintained at 15 cm H2O for 10 min.Results:A total of 74 patients with mean age of (49.0±18.6) years old were enrolled, 36 patients were enrolled in lung recruitment maneuver (RM) group and 38 patients were enrolled into non-lung recruitment maneuver (non-RM) group. 44 were male and accounted for 59.5% of all the patients. For the indicators such as PEEP, pressure support (PS), plateau airway pressure (Pplat), peak airway pressure (Ppeak), vital capacity (VC) and fraction of inspired oxygen (FiO2), no statistical differences in the indicators were found between the RM group and non-RM group on D1, D3 and D7 (P>0.05), except that only FiO2 of RM group on D7 was significantly lower than that of non-RM group (47.2±10.0) vs. (52.2±10.5),P<0.05]. For the indicators of blood gas analysis, including pH, arterial oxygen pressure (PaO2), arterial carbon dioxide pressure (PaCO2) and oxygenation index (PaO2/FiO2), PaO2 and PaO2/FiO2 of RM group were significantly higher than those of non-RM group on D7, and the values were [(90.2±16.1) mmHg vs. (76.4±11.3) mmHg,P<0.05] and [(196.5±40.7) mmHg vs. (151.7±37.3) mmHg,P<0.05] respectively. There was no statistical difference in heart rate (HR), cardiac index (CI), central venous pressure (CVP) or mean arterial pressure (MAP) between RM group and non-RM group on D1, D3 and D7 (P>0.05). 28-day mortality, ICU mortality and in-hospital mortality were 25% vs. 28.9%, 25% vs. 26.3% and 36.1% vs. 39.5% respectively between RM group and non-RM group (allP>0.05).Conclusion:Protective lung ventilation strategy combined with lung recruitment maneuver can improve the indicators such as PaO2, FiO2 and PaO2/FiO2 on D7, but failed to improve the final outcomes such as 28-day mortality, ICU mortality and in-hospital mortality.