Since the beginning of the 21st century, the severe respiratory infectious diseases worldwide [such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza A H1N1 and novel coronavirus infection have attracted wide attention from all walks of life due to their superior pathogenicity and transmissibility. Aerosols-carrying pathogens are the main transmission route of many severe respiratory infectious diseases, which can lead to severe respiratory failure and even acute respiratory distress syndrome (ARDS) in infected individuals. Mechanical ventilation is the primary treatment for ARDS, and the small tidal volume, appropriate level of positive end-expiratory pressure based lung protective ventilation strategy can effectively reduce the incidence of ventilator-induced lung injury (VILI). However, in the process of clinical treatment, it is sometimes necessary to briefly disconnect the connection between the artificial airway and the ventilator circuit, which will not only cause the residual aerosol in the respiratory system to spill out and pollute the surrounding environment, increase the risk of nosocomial infection including medical staff, but also interfere with the implementation of lung protective ventilation strategy and aggravate ventilator-induced lung injury. In addition, studies have shown that a lot of medical staff have nosocomial infections, especially staff involved in tracheal intubation, extubation and other airway related operations. In addition to enhancing personal protective measures, it is crucial to safeguard healthcare workers from aerosol contamination and minimize associated risks during airway management. At present, there are few researches on the temporary sealing of airway lines and ventilator system, and there is a lack of clear guidance. This review summarizes the research status in related fields to provide a reference for corresponding solutions and programs.
Humans ; Respiratory Distress Syndrome/etiology* ; Respiration, Artificial ; Ventilator-Induced Lung Injury/prevention & control* ; Severe Acute Respiratory Syndrome ; COVID-19 ; Clinical Relevance

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a severe critical condition marked by rapid progression and high fatality. It results from direct/indirect lung-related or systemic triggers, leading to widespread injury of lung epithelial and endothelial cells. Its pathogenesis involves uncontrolled inflammation and breakdown of the lung's blood-air barrier due to leaky blood vessels and epithelial damage. Current management of ALI/ARDS remains primarily supportive, offering symptomatic relief but limited improvement in prognosis, necessitating deeper exploration of upstream pathogenic mechanisms to identify safer and more effective therapies. Exosomal microRNAs (miRNA), small extracellular vesicles (40-150 nm) containing non-coding single-stranded RNAs, regulate post-transcriptional cellular processes and participate in ALI/ARDS pathophysiology. Studies reveal that exosomes transport proteins, nucleic acids, and miRNAs to recipient cells, mediating intercellular communication. In ALI/ARDS models, exosomal miRNAs delivered to alveolar epithelial cells, endothelial cells, macrophages, and neutrophils critically modulate autophagy, pyroptosis, apoptosis, proliferation, inflammatory signaling, macrophage polarization, and neutrophil activation, either exacerbating or alleviating disease progression. Recent advances in engineering techniques have enhanced the therapeutic potential of exosomal miRNAs by overcoming limitations of natural exosomes. This review focuses on exosomal miRNA-mediated regulation of ALI/ARDS pathogenesis across key cell types, providing insights for novel therapeutic strategies.
Exosomes ; Humans ; MicroRNAs ; Acute Lung Injury ; Respiratory Distress Syndrome ; Animals

OBJECTIVE: To systematically evaluate the impact of aspirin on the pulmonary inflammatory response in animal models of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Experimental research on aspirin therapy or prevention of ALI/ARDS in animal models were searched in PubMed, Web of Science, Cochrane library, Embase, China biology medicine, CNKI, Wanfang, VIP. The search time limit was from the establishment of the database to July 17, 2023. The control group established the ALI/ARDS model without any pharmacological intervention. The intervention group was given aspirin or aspirin-derived compounds or polymeric-aspirin (Poly-A) at different time points before and after the preparation of the model, of which there was no restriction on the dosage form, dosage, mode of administration, or number of doses. The primary outcome indicators included bronchoalveolar lavage fluid (BALF) or lung tissue myeloperoxidase (MPO) activity, interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and the counts of neutrophils in BALF. Two researchers screened the literature and extracted information based on inclusion and exclusion criteria. Literature quality was assessed by the bias risk assessment tool SYRCLE. RevMan 5.3 software was used for data synthesis and statistical analysis. RESULTS: A total of 17 papers were eventually included, involving a total of 449 animal models, all of which were murine. One paper was at high risk of bias and the rest 16 papers were at moderate risk of bias. Meta-analysis showed that compared with the control group, the neutrophil count in BALF [standardized mean difference (SMD) = -5.06, 95% confidence interval (95%CI) was -7.00 to -3.12, P < 0.000 01], the myeloperoxidase (MPO) activity in BALF or lung tissue (SMD = -3.45, 95%CI was -4.43 to -2.47, P < 0.000 01), the TNF-α level in BALF or lung tissue (SMD = -2.78, 95%CI was -3.58 to -1.98, P < 0.000 01), and the IL-1β level in BALF or lung tissue (SMD = -3.12, 95%CI was -4.56 to -1.69, P < 0.000 1) were significantly decreased in the ALI/ARDS model of the intervention group. CONCLUSIONS Aspirin reduces the level of lung inflammation in animal models of ALI/ARDS. However, there are problems of poor quality and significant heterogeneity of the included studies, which still need our further validation.
Animals ; Acute Lung Injury/drug therapy* ; Aspirin/pharmacology* ; Respiratory Distress Syndrome/drug therapy* ; Disease Models, Animal ; Bronchoalveolar Lavage Fluid/chemistry* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-1beta/metabolism* ; Peroxidase/metabolism* ; Lung/metabolism* ; Neutrophils/drug effects*

Phosgene is not only a dangerous asphyxiating chemical warfare agent, but also an important chemical raw material, which is widely used in chemical production. According to statistics, there are more than 1 000 phosgene production enterprises in China, with an annual production volume of more than 3 million tons and hundreds of thousands of employees. Therefore, once the leakage accident occurs during production, storage and transportation, it often causes a large number of casualties. In the past 20 years, phosgene poisoning accidents in China have occurred from time to time, and due to the weak irritation, high density, and high concentration of phosgene at the scene of the accident, it often results in acute high-concentration inhalation of the exposed, triggering acute lung injury (ALI), and is very likely to progress to acute respiratory distress syndrome (ARDS), with a mortality rate up to 40%-50%. In view of the characteristics of sudden, mass, concealed, rapid and highly fatal phosgene, and the mechanism of its toxicity and pathogenicity is still not clear, there is no effective treatment and standardized guidance for the sudden group phosgene poisoning. In order to improve the efficiency of clinical treatment and reduce the mortality, this paper has summarized the pathophysiological mechanism of phosgene poisoning, clinical manifestations, on-site treatment, research progress, and innovative clinical therapies by combining the extensive basic research on phosgene over the years with the abundant experience in the on-site treatment of sudden mass phosgene poisoning. This consensus aims to provide guidance for the clinical rescue and treatment of patients with sudden mass phosgene poisoning, and to improve the level of treatment.
Humans ; Phosgene ; Chemical Warfare Agents ; Acute Lung Injury/drug therapy* ; Respiratory Distress Syndrome/therapy* ; Treatment Outcome

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response. Regrettably, the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition. Xuebijing (XBJ), a traditional Chinese medicine recognized for its potent anti-inflammatory properties, exhibits promise as a potential therapeutic agent for ALI/ARDS. This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism. To this end, we established an LPS-induced ALI model and treated ALI mice with XBJ. Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%. Moreover, XBJ substantially suppressed the production of TNF-α, IL-6, and IL-1β in the lung tissue. Subsequently, we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses. Furthermore, we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-α production. Therefore, this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-α release.
Animals ; Mice ; Alveolar Epithelial Cells ; Pyroptosis ; Gasdermins ; Lipopolysaccharides/adverse effects* ; Tumor Necrosis Factor-alpha ; Acute Lung Injury/drug therapy* ; Respiratory Distress Syndrome

PURPOSE: Despite improved quality of intensive care, acute respiratory distress syndrome (ARDS) significantly contributes to mortality in critically ill children. As pre-existing definitions of ARDS were adult-oriented standards, the Pediatric Acute Lung Injury Consensus Conference (PALICC) group released a new definition of pediatric ARDS. In this study, we aimed to assess the performance of PALICC definition for ARDS risk stratification. METHODS: Total 332 patients who admitted to the intensive care unit at Severance Hospital from January 2009 to December 2016 and diagnosed as having ARDS by either the PALICC definition or the Berlin definition were retrospectively analyzed. Patient characteristics and mortality rates were compared between the individual severity groups according to both definitions. RESULTS: The overall mortality rate was 36.1%. The mortality rate increased across the severity classes according to both definitions (26% in mild, 37% in moderate and 68% in severe by the PALICC definition [P<0.001]; 20% in mild, 32% in moderate and 64% in severe by the Berlin definition [P<0.001]). The mortality risk increased only for severe ARDS in both definitions (hazard ratio [95% confidence interval]: 2.279 [1.414–3.672], P=0.001 by the PALICC definition; 2.674 [1.518–4.712], P=0.001 by the Berlin definition). There was no significant difference in mortality discrimination between the 2 definitions (difference in integrated area under the curve: 0.017 [−0.018 to 0.049]). CONCLUSION: The PALICC definition demonstrated similar discrimination power on PARDS' severity and mortality as the Berlin definition.
Acute Lung Injury* ; Berlin ; Child ; Consensus* ; Critical Care ; Critical Illness ; Discrimination (Psychology) ; Humans ; Intensive Care Units ; Mortality ; Respiratory Distress Syndrome, Adult* ; Retrospective Studies

BACKGROUND/AIMS: Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance. METHODS: We retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined. RESULTS: The histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate. CONCLUSIONS: The histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.
Acute Lung Injury ; Berlin ; Biopsy* ; Humans ; Korea ; Lung Diseases, Interstitial ; Lung* ; Mortality ; Pathology ; Population Characteristics* ; Respiratory Distress Syndrome, Adult* ; Retrospective Studies

ObjectiveAcute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance (AFC) in ARDS.

Data SourcesArticles published up to September 2017 were selected from the PubMed, with the keywords of "alveolar fluid clearance" or "lung edema" or "acute lung injury" or "acute respiratory distress syndrome", and "specialized pro-resolving mediators" or "lipoxin" or "resolvin" or "protectin" or "maresin" or "alveolar epithelial cells" or "aspirin-triggered lipid mediators" or "carbon monoxide and heme oxygenase" or "annexin A1".

Study SelectionWe included all relevant articles published up to September 2017, with no limitation of study design.

ResultsSpecialized pro-resolving mediators (SPMs), as the proinflammatory mediators, not only upregulated epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporins levels, but also improved Na,K-ATPase activity to promote AFC in ARDS. In addition to the direct effects on ion channels and pumps of the alveolar epithelium, the SPMs also inhibited the inflammatory cytokine expression and improved the alveolar epithelial cell repair to enhance the AFC in ARDS.

ConclusionsThe present review discusses a novel mechanism for pulmonary edema fluid reabsorption. SPMs might provide new opportunities to design "reabsorption-targeted" therapies with high degrees of precision in controlling ALI/ARDS.

Acute Lung Injury ; metabolism ; Animals ; Cystic Fibrosis Transmembrane Conductance Regulator ; metabolism ; Humans ; Respiratory Distress Syndrome, Adult ; metabolism

ObjectiveExposure 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 SourcesThis review was based on articles published in PubMed databases up to January, 2018, with the following keywords: "chlorine," "bromine," "lung injury," and "ARDS."

Study SelectionThe original articles and reviews including the topics were the primary references.

ResultsBased 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.

ConclusionsAt 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.

Acute Lung Injury ; chemically induced ; Animals ; Chlorine ; toxicity ; Halogens ; toxicity ; Humans ; Lung ; drug effects ; pathology ; Respiratory Distress Syndrome, Adult ; drug therapy

OBJECTIVE: To explore the incidence and risk factors for the acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) after resection of esophageal carcinoma. METHODS: We retrospectively analyzed 422 consecutive patients admitted to the Department of Critical Care Medicine with esophageal carcinoma undergoing esophagectomy from January 2010 to December 2016 in Peking University Cancer Hospital. ALI/ARDS were diagnosed, the patients were divided into ALI/ARDS group and control group without ALI/ARDS, the differences of clinical features were contrasted between the two groups, and the multivariate Logistic regression modeling was used to identify the independent risk factors for ALI/ARDS. RESULTS: In the study, 41 ALI/ARDS cases were diagnosed, making up 9.7% (41/422) of all the enrolled patients undergoing esophagectomy. Comparisons of the ALI/ARDS group and the control group indicated significant statistical differences in the average length of their hospital stay [(18.9±9.7) d vs. (14.8±3.6) d, P=0.011], the proportion of the patients who needed mechanical ventilation support [51.2% (21/41) vs. 9.4% (36/381), P<0.001] and in-hospital mortality [31.7% (13/41) vs. 5.0% (19/381), P<0.001]. Univariate analysis showed significant differences between the patients with ALI/ARDS and without ALI/ARDS in smoking history (P=0.064), preoperative forced expiratory volume in one second/forced vital capacity (FEV1/FVC) (P=0.020), diffusing capacity of the lung for carbon monoxide (DLCO) (P=0.011), body weight index (BMI) (P=0.044), American Society of Anesthesiologists (ASA) physical status classification (P=0.049) and one lung ventilation duration (P=0.008), while multivariate Logistic regression analysis indicated that preoperative FEV1/FVC (OR=1.053, P=0.016, 95%CI 1.010-1.098), ASA physical status classification (OR=2.392, P=0.033, 95%CI 1.073-5.335) and one lung ventilation duration (OR=0.994, P=0.028, 95%CI 0.989-0.999) were the independent risk factors for ALI/ARDS after esophagectomy. CONCLUSION ALI/ARDS was a serious complication in patients undergoing esophagectomy associated with increment in length of hospital stay and in-hospital mortality. Multivariate Logistic regression analysis indicated that preoperative FEV1/FVC, ASA classification and one lung ventilation duration were the independent risk factors for ALI/ARDS after esophagectomy. Carefully assessing the patient before operation, shortening one lung ventilation duration were the key points in preventing ALI/ARDS after esophagectomy.
Acute Lung Injury/etiology* ; Esophagectomy/adverse effects* ; Humans ; Respiration, Artificial ; Respiratory Distress Syndrome/etiology* ; Retrospective Studies ; Risk Factors