IL35 attenuated LPS-induced acute lung injury by regulating macrophage polarization.

BACKGROUND: Interleukin 35 (IL35) has been reported to play a role in acute lung injury (ALI); however, the current results regarding the relationship between IL35 and ALI are inconsistent. Therefore, we aimed to further determine the function of IL35 in ALI in mice and the potential mechanism in this paper. MATERIALS AND METHODS: Hematoxylin-eosin (HE) staining and Masson staining were used to evaluate lung injury in mice. Immunohistochemical staining was used to evaluate the expression of IL35 p35, TLR4 and MD2 and the Bax/Bcl2 and p-P65/P65 ratios. The expression levels of IL35 EBi3, CD68, CD206 and MPO were assessed by immunofluorescence staining. RT-PCR was used to examine the expression levels of IL1ß and IL6. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect apoptotic cells. RESULTS: Overexpression of IL35 alleviated LPS-induced ALI in mice. IL35 overexpression decreased the expression of CD68 and increased the expression of CD206 in mice with ALI. Furthermore, upregulation of IL35 expression obviously reduced the expression of MPO, IL1ß and IL6 in the lung tissues of mice with ALI. Mechanistically, IL35 suppressed the TLR4/NFκB-P65 pathway, leading to the promotion of the M1 to M2 macrophage transition and alleviation of inflammation in mice with ALI. CONCLUSIONS: IL35 relieved LPS-induced inflammation and ALI in mice by regulating M1/M2 macrophage polarization and inhibiting the activation of the TLR4/NFκB-P65 pathway.

High-flow nasal cannula versus conventional oxygen therapy in acute COPD exacerbation with mild hypercapnia: a multicenter randomized controlled trial.

BACKGROUND: High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain. METHODS: This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90. RESULTS: Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0-13.0] vs. 8.0 [interquartile range, 7.0-11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613-$3782] vs. $2005 [interquartile range, $1439-$2968]). There were no significant differences in other secondary outcomes between groups. CONCLUSIONS: In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups. TRIAL REGISTRATION: NCT03003559 . Registered on December 28, 2016.

Effect of prone position in patients with acute respiratory distress syndrome supported by venovenous extracorporeal membrane oxygenation: a retrospective cohort study.

BACKGROUND: The application of prone position (PP) in acute respiratory distress syndrome (ARDS) supported by venovenous extracorporeal membrane oxygenation (VV-ECMO) is controversial. OBJECTIVES: To evaluate the safety and efficacy of application of PP during VV-ECMO in patients with ARDS. METHODS: This was a single-center, retrospective study of patients who met the Berlin definition of ARDS, and were supported with VV-ECMO. We divided the patients into two groups. The prone group included patients who were supported by VV-ECMO, and experienced at least one period of PP, while those without PP during VV-ECMO were defined as the supine group. Propensity score matching (PSM) at a ratio of 1:1 was introduced to minimize potential confounders. The primary outcomes were the complications of PP and the change of arterial oxygen pressure/fraction of the inspiration (PaO2/FiO2) ratio after PP. The secondary outcomes were hospital survival, ICU survival, and ECMO weaning rate. RESULTS: From April 2013 to October 2020, a total of 91 patients met the diagnostic criteria of ARDS who were supported with ECMO. 38 patients (41.8%) received at least one period of PP during ECMO, while 53 patients (58.2%) were maintained in supine position during ECMO. 22 minor complications were reported in the prone group and major complications were not found. The other ECMO-related complications were similar between two groups. The PaO2/FiO2 ratio significantly improved after PP compared with before (174.50 (132.40-228.25) mmHg vs. 158.00 (122.93-210.33) mmHg, p < 0.001). PSM selected 25 pairs of patients with similar characteristics. Hospital survival or ICU survival did not differ between the two groups (40% vs. 28%, p = 0.370; 40% vs. 32%, p = 0.556). Significant difference of ECMO weaning rate between two groups was not found (56% vs. 32%, p = 0.087). CONCLUSIONS: PP during VV-ECMO was safe and could improve oxygenation. A large-scale and well-designed RCT is needed in the future.

High-Flow Nasal Oxygen in Coronavirus Disease 2019 Patients With Acute Hypoxemic Respiratory Failure: A Multicenter, Retrospective Cohort Study.

OBJECTIVES: An ongoing outbreak of coronavirus disease 2019 is spreading globally. Acute hypoxemic respiratory failure is the most common complication of coronavirus disease 2019. However, the clinical effectiveness of early high-flow nasal oxygen treatment in patients with coronavirus disease 2019 with acute hypoxemic respiratory failure has not been explored. This study aimed to analyze the effectiveness of high-flow nasal oxygen treatment and to identify the variables predicting high-flow nasal oxygen treatment failure in coronavirus disease 2019 patients with acute hypoxemic respiratory failure. DESIGN: A multicenter, retrospective cohort study. SETTING: Three tertiary hospitals in Wuhan, China. PATIENTS: Forty-three confirmed coronavirus disease 2019 adult patients with acute hypoxemic respiratory failure treated with high-flow nasal oxygen. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean age of the enrolled patients was 63.0 ± 9.7 years; female patients accounted for 41.9%. High-flow nasal oxygen failure (defined as upgrading respiratory support to positive pressure ventilation or death) was observed in 20 patients (46.5%), of which 13 (30.2%) required endotracheal intubation. Patients with high-flow nasal oxygen success had a higher median oxygen saturation (96.0% vs 93.0%; p < 0.001) at admission than those with high-flow nasal oxygen failure. High-flow nasal oxygen failure was more likely in patients who were older (p = 0.030) and male (p = 0.037), had a significant increase in respiratory rate and a significant decrease in the ratio of oxygen saturation/FIO2 to respiratory rate index within 3 days of high-flow nasal oxygen treatment. In a multivariate logistic regression analysis model, male and lower oxygen saturation at admission remained independent predictors of high-flow nasal oxygen failure. The hospital mortality rate of the cohort was 32.5%; however, the hospital mortality rate in patients with high-flow nasal oxygen failure was 65%. CONCLUSIONS: High-flow nasal oxygen may be effective for treating coronavirus disease 2019 patients with mild to moderate acute hypoxemic respiratory failure. However, high-flow nasal oxygen failure was associated with a poor prognosis. Male and lower oxygenation at admission were the two strong predictors of high-flow nasal oxygen failure.

Increased physiological dead space in mechanically ventilated COVID-19 patients recovering from severe acute respiratory distress syndrome: a case report.

BACKGROUND: An ongoing outbreak of coronavirus disease 2019 (COVID-19) is spreading globally. Recently, several articles have mentioned that the early acute respiratory distress syndrome (ARDS) caused by COVID-19 significantly differ from those of ARDS due to other causes. Actually, we newly observed that some mechanically ventilated COVID-19 patients recovering from severe ARDS (more than 14 days after invasive ventilation) often experienced evidently gradual increases in CO2 retention and minute ventilation. However, the underlying mechanics remain unclear. CASE PRESENTATION: To explain these pathophysiological features and discuss the ventilatory strategy during the late phase of severe ARDS in COVID-19 patients, we first used a metabolic module on a General Electric R860 ventilator (Engstrom Carestation; GE Healthcare, USA) to monitor parameters related to gas metabolism, lung mechanics and physiological dead space in two COVID-19 patients. We found that remarkably decreased ventilatory efficiency (e.g., the ratio of dead space to tidal volume 70-80%, arterial to end-tidal CO2 difference 18-23 mmHg and ventilatory ratio 3-4) and hypermetabolism (oxygen consumption 300-400 ml/min, CO2 elimination 200-300 ml/min) may explain why these patients experienced more severe respiratory distress and CO2 retention in the late phase of ARDS caused by COVID-19. CONCLUSION: During the recovery period of ARDS among mechanically-ventilated COVID-19 patients, attention should be paid to the monitoring of physiological dead space and metabolism. Tidal volume (8-9 ml/kg) could be increased appropriately under the limited plateau pressure; however, barotrauma should still be kept in mind.

Incidence and outcomes of acute respiratory distress syndrome in intensive care units of mainland China: a multicentre prospective longitudinal study.

OBJECTIVES: To evaluate the incidence and mortality of acute respiratory distress syndrome (ARDS) in medical/respiratory intensive care units (MICUs/RICUs) to assess ventilation management and the use of adjunct therapy in routine clinical practice for patients fulfilling the Berlin definition of ARDS in mainland China. METHODS: This was a multicentre prospective longitudinal study. Patients who met the Berlin definition of ARDS were included. Baseline data and data on ventilator management and the use of adjunct therapy were collected. RESULTS: Of the 18,793 patients admitted to participating ICUs during the study timeframe, 672 patients fulfilled the Berlin ARDS criteria and 527 patients were included in the analysis. The most common predisposing factor for ARDS in 402 (77.0) patients was pneumonia. The prevalence rates were 9.7% (51/527) for mild ARDS, 47.4% (250/527) for moderate ARDS, and 42.9% (226/527) for severe ARDS. In total, 400 (75.9%) patients were managed with invasive mechanical ventilation during their ICU stays. All ARDS patients received a tidal volume of 6.8 (5.8-7.9) mL/kg of their predicted body weight and a positive end-expository pressure (PEEP) of 8 (6-12) cmH2O. Recruitment manoeuvres (RMs) and prone positioning were used in 61 (15.3%) and 85 (16.1%) ventilated patients, respectively. Life-sustaining care was withdrawn from 92 (17.5%) patients. When these patients were included in the mortality analysis, 244 (46.3%) ARDS patients (16 (31.4%) with mild ARDS, 101 (40.4%) with moderate ARDS, and 127 (56.2%) with severe ARDS) died in the hospital. CONCLUSIONS: Among the 18 ICUs in mainland China, the incidence of ARDS was low. The rates of mortality and withdrawal of life-sustaining care were high. The recommended lung protective strategy was followed with a high degree of compliance, but the implementation of adjunct treatment was lacking. These findings indicate the potential for improvement in the management of patients with ARDS in China. TRIAL REGISTRATION: Clinicaltrials.gov NCT02975908 . Registered on 29 November 2016-retrospectively registered.

Expression profiling analysis of long noncoding RNAs in a mouse model of ventilator-induced lung injury indicating potential roles in inflammation.

The key regulators of inflammation underlying ventilator-induced lung injury (VILI) remain poorly defined. Long noncoding RNAs (lncRNAs) have been implicated in the inflammatory response of many diseases; however, their roles in VILI remain unclear. We, therefore, performed transcriptome profiling of lncRNA and messenger RNA (mRNA) using RNA sequencing in lungs collected from mice model of VILI and control groups. Gene expression was analyzed through RNA sequencing and quantitative reverse transctiption polymerase chain reaction. A comprehensive bioinformatics analysis was used to characterize the expression profiles and relevant biological functions and for multiple comparisons among the controls and the injury models at different time points. Finally, lncRNA-mRNA coexpression networks were constructed and dysregulated lncRNAs were analyzed functionally. The mRNA transcript profiling, coexpression network analysis, and functional analysis of altered lncRNAs indicated enrichment in the regulation of immune system/inflammation processes, response to stress, and inflammatory pathways. We identified the lncRNA Gm43181 might be related to lung damage and neutrophil activation via chemokine receptor chemokine (C-X-C) receptor 2. In summary, our study provides an identification of aberrant lncRNA alterations involved in inflammation upon VILI, and lncRNA-mediated regulatory patterns may contribute to VILI inflammation.

Circulating and Pulmonary T-cell Populations Driving the Immune Response in Non-HIV Immunocompromised Patients with Pneumocystis jirovecii Pneumonia.

Background: Previous studies in human subjects have mostly been confined to peripheral blood lymphocytes for Pneumocystis infection. We here aimed to compare circulating and pulmonary T-cell populations derived from human immunodeficiency virus (HIV)-uninfected immunocompromised patients with Pneumocystis jirovecii pneumonia (PCP) in order to direct new therapies. Methods: Peripheral blood and bronchoalveolar lavage samples were collected from patients with and without PCP. Populations of Th1/Tc1, Th2/Tc2, Th9/Tc9, and Th17/Tc17 CD4+ and CD8+ T cells were quantified using multiparameter flow cytometry. Results: No significant differences were found between PCP and non-PCP groups in circulating T cells. However, significantly higher proportions of pulmonary Th1 and Tc9 were observed in the PCP than in the non-PCP group. Interestingly, our data indicated that pulmonary Th1 was negatively correlated with disease severity, whereas pulmonary Tc9 displayed a positive correlation in PCP patients. Conclusions: Our findings suggest that pulmonary expansion of Th1 and Tc9 subsets may play protective and detrimental roles in PCP patients, respectively. Thus, these specific T-cell subsets in the lungs may serve as targeted immunotherapies for patients with PCP.

Spontaneous breathing in patients with severe acute respiratory distress syndrome receiving prolonged extracorporeal membrane oxygenation.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in awake, spontaneously breathing and non-intubated patients (awake ECMO) may be a novel therapeutic strategy for severe acute respiratory distress syndrome (ARDS) patients. The purpose of this study is to assess the feasibility and safety of awake ECMO in severe ARDS patients receiving prolonged ECMO (> 14 days). METHODS: We describe our experience with 12 consecutive severe ARDS patients (age, 39.1 ± 16.4 years) supported with awake ECMO to wait for native lung recovery during prolonged ECMO treatment from July 2013 to January 2018. Outcomes are reported including the hospital mortality, ECMO-related complications and physiological data on weaning from invasive ventilation. RESULTS: The patients received median 26.0 (15.5, 64.8) days of total ECMO duration in the cohort. The longest ECMO support duration was 121 days. Awake ECMO and extubation was implemented after median 10.2(5.0, 42.9) days of ECMO. Awake ECMO was not associated with increased morbidity. The total invasive ventilation duration, lengths of stay in the ICU and hospital in the cohort were 14.0(12.0, 37.3) days, 33.0(22.3, 56.5) days and 46.5(27.3, 84.8) days, respectively. The hospital mortality rate was 33.3% (4/12) in the cohort. Survivors had more stable respiratory rate and heart rate after extubation when compared to the non-survivors. CONCLUSIONS: With carefully selected patients, awake ECMO is a feasible and safe strategy for severe pulmonary ARDS patients receiving prolonged ECMO support to wait for native lung recovery.

Landscape of transcription and long non-coding RNAs reveals new insights into the inflammatory and fibrotic response following ventilator-induced lung injury.

BACKGROUND: Mechanical ventilation can cause ventilator-induced lung injury (VILI) and lung fibrosis; however, the underlying mechanisms are still not fully understood. RNA sequencing is a powerful means for detecting vitally important protein-coding transcripts and long non-coding RNAs (lncRNAs) on a genome-wide scale, which may be helpful for reducing this knowledge gap. METHODS: Ninety C57BL/6 mice were subjected to either high tidal volume ventilation or sham operation, and then mice with ventilation were randomly allocated to periods of recovery for 0, 1, 3, 5, 7, 14, 21, or 28 days. Lung histopathology, wet-to-dry weight ratio, hydroxyproline concentration, and transforming growth factor beta 1 (TGF-ß1) levels were determined to evaluate the progression of inflammation and fibrosis. To compare sham-operated lungs, and 0- and 7-day post-ventilated lungs, RNA sequencing was used to elucidate the expression patterns, biological processes, and functional pathways involved in inflammation and fibrosis. RESULTS: A well-defined fibrotic response was most pronounced on day 7 post-ventilation. Pairwise comparisons among the sham and VILI groups showed a total of 1297 differentially expressed transcripts (DETs). Gene Ontology analysis determined that the stimulus response and immune response were the most important factors involved in inflammation and fibrosis, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed that mechanistic target of rapamycin (mTOR), Janus kinase-signal transducer and activator of transcription (JAK/STAT), and cyclic adenosine monophosphate (cAMP) signaling were implicated in early inflammation; whereas TGF-ß, hypoxia inducible factor-1 (HIF-1), Toll-like receptor (TLR), and kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways were significantly involved in subsequent fibrosis. Additionally, 332 DE lncRNAs were identified and enriched in the processes of cellular and biological regulation. These lncRNAs may potentially regulate fibrosis through signaling pathways such as wingless/integrase-1 (Wnt), HIF-1, and TLR. CONCLUSIONS: This is the first transcriptome study to reveal all of the transcript expression patterns and critical pathways involved in the VILI fibrotic process based on the early inflammatory state, and to show the important DE lncRNAs regulated in inflammation and fibrosis. Together, the results of this study provide novel perspectives into the potential molecular mechanisms underlying VILI and subsequent fibrosis.

Different effects of cardiac and diaphragm function assessed by ultrasound on extubation outcomes in difficult-to-wean patients: a cohort study.

BACKGROUND: Ultrasound is a convenient tool to evaluate cardiac and diaphragm function. The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography (TTE) and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed in predicting extubation outcomes independently, however their different roles in the weaning process have not been determined until now. METHODS: We designed a cohort study to preform diaphragm ultrasound and TTE before and after the spontaneous breathing trial (SBT) in difficult-to-wean patients. Patients considered for enrollment should succeed on a SBT and have been extubated. They were followed up with the events of respiratory failure within 48 h, and divided into the respiratory failure and extubation success subgroups. Relevant risk factors predicting respiratory failure were analysed by a multivariate logistic regression model. Then, each subgroup was assessed with respect to re-intubation within 1 week, and divided into the re-intubation and non-intubation subgroups. Furthermore, relevant risk factors predicting re-intubation were also analysed in each subgroup. The area under the curve (AUC) and optimum cut-off value were identified by the receiver operating characteristic curve. RESULTS: Among 60 patients, 29 cases developed respiratory failure within 48 h, and 14 cases were re-intubated or died within 1 week, respectively. Multivariate logistic regression analysis showed that E/Ea (average) after SBT [odds ratio (OR) 1.450, 95% confidence intervals (CI) 1.092-1.926, P = 0.01] and left ventricular ejection fraction were associated with respiratory failure. The AUC of E/Ea (average) after SBT was 0.789, and a cut-off value ≥ 12.5 showed the highest diagnostic accuracy with a sensitivity and specificity of 72.4% and 77.4%, respectively. Furthermore, in the respiratory failure subgroup only DE (average) after SBT was associated with re-intubation (OR 0.690, CI 0.499-0.953, P = 0.024). The AUC of DE (average) after SBT was 0.805, and a cut-off value ≤ 12.6 mm showed the highest diagnostic accuracy with a sensitivity and specificity of 80% and 68.4%, respectively. CONCLUSIONS: E/Ea (average) after SBT could help predict respiratory failure within 48 h. However, DE (average) after SBT could help predict re-intubation within 1 week in the respiratory failure subgroup.

Spontaneous breathing with biphasic positive airway pressure attenuates lung injury in hydrochloric acid-induced acute respiratory distress syndrome.

BACKGROUND: It has been proved that spontaneous breathing (SB) with biphasic positive airway pressure (BIPAP) can improve lung aeration in acute respiratory distress syndrome compared with controlled mechanical ventilation. The authors hypothesized that SB with BIPAP would attenuate lung injury in acute respiratory distress syndrome compared with pressure-controlled ventilation. METHODS: Twenty male New Zealand white rabbits with hydrochloric acid aspiration-induced acute respiratory distress syndrome were randomly ventilated using the BIPAP either with SB (BIPAP plus SB group) or without SB (BIPAP minus SB group) for 5 h. Inspiration pressure was adjusted to maintain the tidal volume at 6 ml/kg. Both groups received the same positive end-expiratory pressure level at 5 cm H2O for hemodynamic goals. Eight healthy animals without ventilatory support served as the control group. RESULTS: The BIPAP plus SB group presented a lower ratio of dead space ventilation to tidal volume, a lower respiratory rate, and lower minute ventilation. No significant difference in the protein levels of interleukin-6 and interleukin-8 in plasma, bronchoalveolar lavage fluid, and lung tissue were measured between the two experimental groups. However, SB resulted in lower messenger ribonucleic acid levels of interleukin-6 (mean ± SD; 1.8 ± 0.7 vs. 2.6 ± 0.5; P = 0.008) and interleukin-8 (2.2 ± 0.5 vs. 2.9 ± 0.6; P = 0.014) in lung tissues. In addition, lung histopathology revealed less injury in the BIPAP plus SB group (lung injury score, 13.8 ± 4.6 vs. 21.8 ± 5.7; P < 0.05). CONCLUSION: In hydrochloric acid-induced acute respiratory distress syndrome, SB with BIPAP attenuated lung injury and improved respiratory function compared with controlled ventilation with low tidal volume.

A Novel Approach for the Detection and Severity Grading of Chronic Obstructive Pulmonary Disease Based on Transformed Volumetric Capnography.

Chronic Obstructive Pulmonary Disease (COPD), as the third leading cause of death worldwide, is a major global health issue. The early detection and grading of COPD are pivotal for effective treatment. Traditional spirometry tests, requiring considerable physical effort and strict adherence to quality standards, pose challenges in COPD diagnosis. Volumetric capnography (VCap), which can be performed during natural breathing without requiring additional compliance, presents a promising alternative tool. In this study, the dataset comprised 279 subjects with normal pulmonary function and 148 patients diagnosed with COPD. We introduced a novel quantitative analysis method for VCap. Volumetric capnograms were converted into two-dimensional grayscale images through the application of Gramian Angular Field (GAF) transformation. Subsequently, a multi-scale convolutional neural network, CapnoNet, was conducted to extract features and facilitate classification. To improve CapnoNet's performance, two data augmentation techniques were implemented. The proposed model exhibited a detection accuracy for COPD of 95.83%, with precision, recall, and F1 measures of 95.21%, 95.70%, and 95.45%, respectively. In the task of grading the severity of COPD, the model attained an accuracy of 96.36%, complemented by precision, recall, and F1 scores of 88.49%, 89.99%, and 89.15%, respectively. This work provides a new perspective for the quantitative analysis of volumetric capnography and demonstrates the strong performance of the proposed CapnoNet in the diagnosis and grading of COPD. It offers direction and an effective solution for the clinical application of capnography.

The application of impulse oscillometry system based on machine learning algorithm in the diagnosis of chronic obstructive pulmonary disease.

Objective. Diagnosing chronic obstructive pulmonary disease (COPD) using impulse oscillometry (IOS) is challenging due to the high level of clinical expertise it demands from doctors, which limits the clinical application of IOS in screening. The primary aim of this study is to develop a COPD diagnostic model based on machine learning algorithms using IOS test results.Approach. Feature selection was conducted to identify the optimal subset of features from the original feature set, which significantly enhanced the classifier's performance. Additionally, secondary features area of reactance (AX) were derived from the original features based on clinical theory, further enhancing the performance of the classifier. The performance of the model was analyzed and validated using various classifiers and hyperparameter settings to identify the optimal classifier. We collected 528 clinical data examples from the China-Japan Friendship Hospital for training and validating the model.Main results. The proposed model achieved reasonably accurate diagnostic results in the clinical data (accuracy = 0.920, specificity = 0.941, precision = 0.875, recall = 0.875).Significance. The results of this study demonstrate that the proposed classifier model, feature selection method, and derived secondary feature AX provide significant auxiliary support in reducing the requirement for clinical experience in COPD diagnosis using IOS.

A narrative review of progress in the application of artificial intelligence in acute respiratory distress syndrome: subtypes and predictive models.

Background and Objective: Acute respiratory distress syndrome (ARDS) occurs in different populations, and it is very challenging to manage heterogeneous patient groups. Artificial intelligence (AI) aids in interpreting complex data of patients with ARDS and can be used to detect adverse events as it can automatically capture complex relationships. This review aimed to explore the application and progress of AI in ARDS (e.g., subgroup classification of patients with ARDS via unsupervised clustering and supervised predictive models for early detection) and identify the current ARDS-related problems that can be solved using AI. Methods: This comprehensive and narrative review was performed to obtain information about the application of AI in ARDS and summarize its subtypes and predictive models. Key Content and Findings: The current applications of AI and machine learning in ARDS include ARDS subgroup classification, diagnosis, and survival prediction. In this review, the current problems that should be addressed by AI in ARDS were identified, and our findings may serve as a useful reference for its translational use in the ARDS field. Conclusions: Owing to the discovery of hyper- and hypoinflammatory subtypes, individualized treatment of ARDS is possible, and diagnosis and survival prediction are essential in disease management and planning. However, prospective studies should clarify the reliability and generalizability of the results using AI and machine learning and performing bedside testing in larger populations to establish a more stable and time-resilient model. Therefore, a consensus on conducting and reporting machine learning studies in medicine should be urgently established.

High-flow nasal cannula may prolong the length of hospital stay in patients with hypercapnic acute COPD exacerbation.

BACKGROUND: High-flow nasal cannula (HFNC) is increasingly used in patients with acute exacerbation of COPD (AECOPD). We aimed to confirm whether the baseline bicarbonate is an independent predictor of outcomes in patients with hypercapnic AECOPD receiving HFNC. METHODS: This was a secondary analysis of a multicentre randomised trial that enrolled 330 patients with non-acidotic hypercapnic AECOPD supported by HFNC or conventional oxygen treatment (COT). We compared the length of stay (LOS) in hospital and the rate of non-invasive positive pressure ventilation (NPPV) use according to baseline bicarbonate levels using the log-rank test or Cox proportional hazard model. RESULTS: In the high bicarbonate subgroup (n = 165, bicarbonate 35.0[33.3-37.9] mmol/L, partial pressure of arterial carbon dioxide [PaCO2] 56.8[52.0-62.8] mmHg), patients supported by HFNC had a remarkably prolonged LOS in hospital when compared to COT (HR 1.59[1.16-2.17], p = 0.004), whereas patients in the low bicarbonate subgroup (n = 165, bicarbonate 28.8[27.0-30.4] mmol/L, PaCO2 48.0[46.0-50.0] mmHg) had a comparable LOS in hospital regardless of respiratory support modalities. The rate of NPPV use in patients with high baseline bicarbonate level was significantly higher than that in patients with low baseline bicarbonate level (19.4 % vs. 3.0 %, p < 0.0001). Patients with high bicarbonate level in HFNC group had a lower rate of NPPV use compared to COT group (15.4 % vs. 23.0 %, p = 0.217). CONCLUSIONS: Among patients with non-acidotic hypercapnic AECOPD with high baseline bicarbonate level, HFNC is significantly associated with a prolonged LOS in hospital, which may be due to the reduced escalation of NPPV treatment. TRIAL REGISTRATION: clinicaltrials.gov (NCT03003559).

Rutin alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation.

Whether rutin relieves ventilator-induced lung injury (VILI) remains unclear. Here, we used network pharmacology, bioinformatics, and molecular docking to predict the therapeutic targets and potential mechanisms of rutin in the treatment of VILI. Subsequently, a mouse model of VILI was established to confirm the effects of rutin on VILI. HE staining showed that rutin alleviated VILI. TUNEL staining showed that rutin reduced apoptosis in the lung tissue of mice with VILI, and the same change was observed in the ratio of Bax/Bcl2. Furthermore, rutin reduced the expression of NLRP3, ASC, Caspase1, IL1ß, and IL18 in the lung tissues of mice with VILI. Mechanistically, rutin suppressed the TLR4/NF-κB-P65 pathway, which promoted the M1 to M2 macrophage transition and alleviated inflammation in mice with VILI. Rutin relieved NLRP3 inflammasome activation by regulating M1/M2 macrophage polarization and inhibiting the activation of the TLR4/NF-κB-P65 pathway, resulting in the amelioration of VILI in mice.

Incidence, outcomes and risk factors of barotrauma in veno-venous extracorporeal membrane oxygenation for acute respiratory distress syndrome.

BACKGROUND: Although acute respiratory distress syndrome (ARDS) patients are provided a lung rest strategy during extracorporeal membrane oxygenation (ECMO) treatment, the exact conditions of barotrauma is unclear. Therefore, we analyzed the epidemiology and risk factors for barotrauma in ARDS patients using ECMO in a single, large ECMO center in China. METHODS: A retrospective analysis was performed on 127 patients with ARDS received veno-venous (VV) ECMO who met the Berlin definition. The epidemiology and risk factors for barotrauma during ECMO were analyzed. RESULTS: Among 127 patients with ARDS treated with ECMO, barotrauma occurred in 24 (18.9%) during ECMO and 9 (7.1%) after ECMO decannulation, mainly in the late stage of ARDS (75%) and ≥8 days during ECMO (54.2%). Univariate and multivariate analyses showed that younger ARDS patients (OR = 0.953, 95%CI 0.923-0.983, p = 0.003) and those with pneumocystis jirovecii pneumonia (PJP) (OR = 3.15, 95%CI 1.070-9.271, p = 0.037), elevated body temperature after establishing ECMO (OR = 2.997, 95%CI 1.325-6.779, p = 0.008) and low platelet count after establishing ECMO (OR = 0.985, 95%CI 0.972-0.998, p = 0.02) had an increased risk of barotrauma during ECMO. There was no difference in ventilator parameters between patients with and without barotrauma. Barotrauma during ECMO was mainly related to the etiology of the disease and disease state. CONCLUSION: There is a high incidence of barotrauma in ARDS patients during ECMO, even after ECMO decannulation. Young age, PJP, elevated body temperature and low platelet count after establishing ECMO are risk factors of barotrauma, and those patients should be closely monitored by imaging, especially in the late stage of ARDS.

Extracorporeal membrane oxygenation in immunocompromised patients with acute respiratory failure: A retrospective cohort study.

BACKGROUND: The clinical indications of extracorporeal membrane oxygenation (ECMO) in immunosuppressed patients are not clear. This study aimed to analyse the effectiveness of ECMO and to identify the risk factors for the mortality of ECMO in immunocompromised patients with acute respiratory failure. METHODS: This retrospective, cohort study included 46 confirmed immunocompromised patients with acute hypoxemic respiratory failure treated with ECMO between July 2014 and August 2020. The clinical features and outcomes of the survival group and the non-survival group were statistically analysed. RESULTS: The mean age of the enrolled patients was 60.0 (50.0, 66.0) years; male patients accounted for 60.9% of patients, and the mean CD4 level was 213 cells/µL (150.3, 325.3). The hospital mortality rate of the cohort was 67.4% (31/46 patients). Patients in the survival group showed a higher rate of receiving awake ECMO (11/15 vs. 4/31; p = 0.006), a lower rate of acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT) (1/15 vs. 12/31; p = 0.035), fewer platelet transfusion units (0/15 vs. 2/31 units; p = 0.039) and a lower rate of ventilator-associated pneumonia (2/15 vs. 19/31; p = 0.006). In a multivariate Cox regression analysis model, intubated ECMO (hazard ratio = 1.77, 95% confidence interval: 1.34-2.32, p < 0.001) and AKI requiring CRRT (1.37, 95% confidence interval: 1.14-1.61, p = 0.003) were identified as independent risk factors for mortality. CONCLUSIONS: In-hospital mortality has remained high in ECMO-treated immunocompromised patients with acute respiratory failure. Intubated ECMO and AKI receiving CRRT during ECMO treatment may predict ECMO failure in immunocompromised patients with ARF. A primarily awake ECMO strategy seems feasible in some selected immunocompromised patients.

Clinical characteristics and prognosis of pneumonia-related bloodstream infections in the intensive care unit: a single-center retrospective study.

Background: Bloodstream infections (BSI) are one of the most severe healthcare-associated infections in intensive care units (ICU). However, there are few studies on pneumonia-related BSI (PRBSI) in the ICU. This study aimed to investigate the clinical and prognostic characteristics of patients with PRBSI in the ICU and to provide a clinical basis for early clinical identification. Methods: We retrospectively collected data from patients with bacterial BSI in a single-center ICU between January 1, 2017, and August 31, 2020. Clinical diagnosis combined with whole-genome sequencing (WGS) was used to clarify the diagnosis of PRBSI, and patients with PRBSI and non-PRBSI were analyzed for clinical features, prognosis, imaging presentation, and distribution of pathogenic microorganisms. Results: Of the 2,240 patients admitted to the MICU, 120 with bacterial BSI were included in this study. Thirty-two (26.7%) patients were identified as having PRBSI based on the clinical diagnosis combined with WGS. Compared to patients without PRBSI, those with PRBSI had higher 28-day mortality (81.3 vs.51.1%, p = 0.003), a higher total mortality rate (93.8 vs. 64.8%, p = 0.002), longer duration of invasive mechanical ventilation (median 16 vs. 6 days, p = 0.037), and prolonged duration of ICU stay (median 21 vs. 10 days, p = 0.004). There were no differences in other baseline data between the two groups, but patients with PRBSI had extensive consolidation on chest radiographs and significantly higher Radiographic Assessment of Lung Edema scores (mean 35 vs. 24, p < 0.001). The most common causative organisms isolated in the PRBSI group were gram-negative bacteria (n = 31, 96.9%), with carbapenem-resistant gram-negative bacteria accounting for 68.8% (n = 22) and multidrug-resistant bacteria accounting for 81.3% (n = 26). Conclusion: Pneumonia-related BSI is an important component of ICU-BSI and has a poor prognosis. Compared to non-PRBSI, patients with PRBSI do not have typical clinical features but have more severe lung consolidation lesions, and should be alerted to the possibility of their occurrence when combined with pulmonary gram-negative bacterial infections, especially carbapenem-resistant bacteria. Further multicenter, large-sample studies are needed to identify the risk factors for the development of PRBSI and prevention and treatment strategies.