BACKGROUND:Combined pulmonary fibrosis and emphysema (CPFE) is a distinct yet clinically underrecognised syndrome. Interstitial pneumonia is a common pulmonary manifestation of connective tissue diseases (CTDs), and some CTD-interstitial lung disease (CTD-ILD) patients have concurrent emphysema that is frequently overlooked clinically. OBJECTIVES:This study explored the clinical characteristics and factors associated with emphysema in CTD-ILD patients to guide clinical management. DESIGN:This single-centre retrospective study included patients with CTD-related lung diseases from the ILD database of Xiangya Hospital. Patients were screened with standardised respiratory disease keywords and verified by chest HRCT. All eligible cases were stratified into CTD-ILD and CTD-CPFE groups based on emphysema presentation on re-assessed HRCT images. METHODS:Admission data, including demographics, comorbidities, inflammatory biomarkers, autoimmune antibodies, HRCT findings, pulmonary function test results and in-hospital treatment information, were collected for subsequent grouped analysis. RESULTS:445 CTD-ILD patients were included, and 48 (10.8%) were CPFE. Patients with CPFE were predominantly male (68.8%), had a higher prevalence of a smoking history (68.8% vs 31.2%, p < 0.001), a lower body mass index (BMI) (20.4 vs 22.2 kg/m2, P = 0.004), and a higher prevalence of prior tuberculosis (TB) (14.6% vs 4.3%, p = 0.009). Multivariable regression analysis showed that sex, BMI, smoking status, and history of TB were independently associated with CPFE. Male sex was associated with a markedly increased likelihood of CPFE (p = 0.003). TB was associated with increased likelihood, whereas higher BMI was associated with reduced likelihood (odds ratio: 33 and 0.57, respectively). CONCLUSION:CTD-CPFE may represent a distinct subgroup within CPFE, with several characteristic features, including a relatively lower prevalence of smoking history. A low BMI and a history of TB were associated with the presence of CPFE, highlighting the potential importance of nutritional and immune status in patients with CTD-ILD.

Background:Idiopathic pulmonary fibrosis (IPF) exhibits notable sex-based disparities and male patients with IPF are significantly more numerous than female patients. Therefore, the female patients are often overlooked and under-investigated. This study aimed to evaluate the clinical characteristics and all-cause mortality in female patients with IPF in Chinese population. Methods:This retrospective cohort study included IPF patients registered at Xiangya Hospital of Central South University and the First Affiliated People's Hospital of Shaoyang University from January 2015 to May 2024. The data on age, sex, body mass index, smoking (pack-years), forced expiratory volume in one second to forced vital capacity, diffusing capacity of the lung for carbon monoxide percentage of predicted (DLCO %pred), diffusing capacity divided by the alveolar volume (DLCO/VA), laboratory analysis, comorbidities, and antifibrotic therapy were collected. The patients were followed-up to collect the data on all-cause mortality. Results:A total of 583 patients were enrolled and 116 (19.9%) of them were female. Female patients had higher levels of forced expiratory volume in one second to forced vital capacity, DLCO %pred, DLCO/VA, arterial oxygen partial pressure (Pao2), and total cholesterol, while a lower smoking (pack-years), haemoglobin, blood urea, uric acid, myoglobin, and creatine kinase. The proportion of lung cancer and antifibrotic therapy were lower in female patients (P < 0.05). Logistic regression analysis showed that haemoglobin (odds ratio (OR) = 0.813; 95% confidence interval (CI) = 0.706-0.937) and blood urea (OR = 0.158; 95% CI = 0.030-0.849) as negatively associated with female, while total cholesterol (OR = 14.699; 95% CI = 1.892-114.190) and DLCO %pred (OR = 1.112; 95% CI = 1.005-1.229) were positively associated (P < 0.05). Over a median follow-up period of 31.0 (12.0-64.0) months, a total of 489 patients with IPF were analysed the all-cause mortality and 101 (20.7%) of them were female. Cox regression analysis revealed that female patients had significantly lower all-cause mortality compared to males (hazard ratio = 0.168; 95% CI = 0.031-0.920, P < 0.05). Conclusions:Significant differences in clinical characteristics and prognosis were observed between male and female IPF patients in Chinese population. Specifically, female patients exhibited better pulmonary function, higher Pao2, and lower all-cause mortality than male patients. Therefore, gender differences should be systematically evaluated in the diagnostic and therapeutic approach to IPF, and targeted strategies should be developed to optimise treatment outcomes in female patients.

Sepsis is one of the main causes of acute respiratory distress syndrome (ARDS), which continues to be a common cause of high mortality in intensive care units (ICUs). Despite tremendous advances in basic science and clinical research, the high mortality of ARDS remains a major clinical challenge. Currently, there is a lack of specific and effective therapeutic approaches for ARDS, with treatment primarily focused on supporting organ function. This article provided a comprehensive discussion and summary of respiratory support strategies for sepsis associated with ARDS.

Background The presence of fibrotic interstitial lung disease (ILD) is relatively common in patients with emphysema. This has been designated combined pulmonary fibrosis and emphysema (CPFE). CPFE had worse prognosis than emphysema alone. Krebs von den Lungen-6 (KL-6) levels as a biomarker of alveolar type 2 epithelial cell injury, which is widely used to identify the presence of ILD, whether it can differentiate CPFE from COPD remains unknown. Methods 259 patients from Xiangya Hospital with diagnosis of COPD, with or without ILD, and who had KL-6 tests were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. Results Among 259 patients, 52 patients were diagnosed with CPFE. The mean age was 67.39 ± 8.14 yeas. CPFE patients had higher ratio of rheumatic diseases (21.2% vs 7.2%, P=0.003). CPFE patients exhibited higher values of FEV1 (1.97 vs 1.57, P=0.002) and FEV1/FVC ratio (69.46 vs 57.64, P<0.001) compared to COPD patients. CPFE patients had higher eosinophil counts, percentage of eosinophils, lactate dehydrogenase, total bilirubin levels and lower platelet counts. Serum KL-6 levels were higher in CPFE group compared to COPD group (574.95 vs 339.30 U/mL, P<0.001). Multiple logistic regression showed that KL-6 level was an independent predictive factor for the presence of ILD among COPD patients. The AUC of serum KL-6 levels to differentiate CPFE was 0.711, with 95% CI being 0.635 to 0.787. The cutoff point of KL-6 level was 550.95 U/mL with 57.7% sensitivity and 79.7% specificity for the discrimination of CPFE from COPD. Conclusion CPFE patients show higher KL-6 levels compared to isolated COPD, suggesting the potential of KL-6 as a practical screening tool for interstitial lung disease, specifically CPFE. A KL-6 threshold of 550.95 U/mL in COPD patients may indicate a high need for high-resolution chest computed tomography to detect fibrosis.

BACKGROUND:Interferon regulatory factor-1 (IRF1) is a transcription factor that plays a significant role in various biological processes, including inflammatory injury, viral infection, cell death, and immune responses, and it has been extensively studied in the context of different lung diseases. However, the mechanism underlying its involvement in lung fibrosis remains largely unknown. METHODS:Wild type (WT) mice, IRF1 global-null mice (Irf1-/-) were subjected to a bleomycin-induced lung fibrosis model to enable examination of the role of IRF1 in lung fibrosis. Proteomic analysis of lung tissue from WT and Irf1-/- mice treated with saline or bleomycin was performed to explore the mechanism of IRF1 in regulating lung fibrosis. RESULTS:In the bleomycin-induced fibrosis mouse model, increased expression of IRF1 was observed. Irf1 knockout mice displayed decreased lung fibrosis relative to WT mice following treatment with bleomycin. The protein expression of fibronectin, as assessed by the Western blot analysis of lung tissues, was downregulated in Irf1-/- mice. We observed a similar reduction in collagen content using hydroxyproline detection. Histologically, there was less collagen deposition in the lungs of Irf1-/- mice compared with WT mice. Proteomics data revealed that IRF1 may be involved in lung fibrosis via the regulation of ferroptosis. We determined that paraoxonase 1(PON1), a poorly characterized protein in lung fibrosis, was upregulated in Irf1-/- mice following exposure to bleomycin. In vitro experiments revealed that IRF1 could regulate the level of GSH and MDA through PON1. We also determined that PON1 levels were lower in the plasma of IPF patients compared with healthy controls. CONCLUSION:Our data highlight the importance of IRF1 in the fibrotic process, and PON1 may be a potential mediator of IRF1 in the progression of lung fibrosis.

Background: The recommended delivery mode for bronchodilators in bronchodilator responsiveness (BDR) testing remains controversial. Objective: To compare the efficacy of salbutamol administration using a nebulizer versus a metered-dose inhaler (MDI) with spacer in BDR testing. Design: A retrospective study. Methods: This study examined the data of patients with chronic obstructive pulmonary disease who completed BDR testing between 1 December 2021 and 30 June 2022, at Xiangya Hospital, Central South University. After administering 400 μg of salbutamol through an MDI with spacer or 2.5 mg using a nebulizer, the changes in forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC) were analyzed in patients with moderate-to-very severe spirometric abnormalities [pre-bronchodilator FEV 1 percentage predicted values (FEV 1 %pred) ⩽59%]. Significant responsiveness was assessed as >12% and >200 mL improvement in FEV 1 and/or FVC or >10% increase in FEV 1 %pred or FVC percentage predicted values (FVC%pred) from pre- to post-bronchodilator administration. Results: Of the enrolled 894 patients, 83.2% were male (median age, 63 years). After propensity score matching, 240 pairs of patients were selected. The increment in FEV 1 and increased FEV 1 relative to the predicted value (ΔFEV 1 %pred) were significantly higher in patients <65 years and those with severe spirometric abnormalities in the nebulization group than patients in the MDI group (all p < 0.05). Compared with MDI with spacer, patients who used nebulization had a 30 mL greater increase in ΔFEV 1 (95% CI: 0.01–0.05, p = 0.004) and a 1.09% greater increase in ΔFEV 1 %pred (95% CI: 0.303–1.896, p = 0.007) from baseline. According to the > 12% and >200 mL increase criterion, the significant BDR rate with nebulization was 1.67 times higher than that with an MDI with spacer (OR = 1.67, 95% CI: 1.13–2.47, p = 0.009). Conclusion: Salbutamol delivered using a nebulizer may be preferable to an MDI with spacer in certain circumstances. Nebulization has the potential to increase responsiveness to salbutamol in BDR testing. Keywords bronchodilator responsiveness , chronic obstructive pulmonary disease , nebulization , metered-dose inhaler , salbutamol , spirometry

To the Editor:Invasive ventilation is a necessary form of respiratory support in the intensive care unit. Noninvasive ventilation (NIV) is frequently used as a sequential respiratory support following extubation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) to prevent the recurrence of respiratory failure, avoid reintubation, and improve the prognosis.[1] However, some patients may have a poor tolerance to NIV, and possibly leading to the development of face pressure ulcers and dys-expectoration. A high-flow nasal cannula (HFNC) delivers a heated and humidified air–oxygen mixture at high flow through a nasal cannula. In recent years, HFNC has been widely used in respiratory support in children and adults and accepted as a sequential therapy in patients after extubation. Studies have shown that HFNC is not inferior to NIV in hypoxemic respiratory failure, especially in some specific conditions.[2,3] These conditions include patients at high risk of respiratory failure after extubation, post-extubation application for acute respiratory failure, and prevention of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. Nevertheless, several confounding mediators such as hypercapnia or dys-expectoration, were not taken into account in above trials.In our clinical work, we have observed that the effect of HFNC seemed to be not inferior or even superior to NIV after extubation, particularly in AECOPD patients with hypercapnia and dys-expectoration. Thus, this retrospective analysis was conducted to determine whether hypercapnic patients with AECOPD can benefit from sequential HFNC therapy after extubation. This retrospective analysis was approved by the Institutional Research Ethics Committee of Xiangya Hospital (No. 201607593), and the patients were recruited from the respiratory intensive care unit (RICU) of Xiangya Hospital from June 2016 to December 2021. All patients provided the written informed consent. Patients were included if they met the following criteria: (1) diagnosed with AECOPD; (2) invasive ventilation for ≥48 h; (3) use HFNC or NIV as sequential therapy after extubation; (4) partial pressure of arterial carbon dioxide (PaCO2) ≥50 mmHg before extubation; and (5) positive end-expiratory pressure ≤8 cmH2O at extubation. Patients were excluded if they had a tracheotomy or alternation between HFNC and NIV after extubation. HFNC or NIV was chosen by an experienced respiratory therapist. In the HFNC group, the initial settings were a flow of 50 L/min, fraction of inspiration oxygen (FiO2) of 0.5, and temperature of 37°C. The settings were then adjusted according to pulse oximetry (SpO2), with a target SpO2 of 88–92%. If the flow rate was 40 L/min, FiO2 was <0.4, the patient's SpO2 was 88–92%, and could sustain for >4 h, then standard oxygen therapy was used instead of HFNC. Normal nasal cannula oxygenation with an oxygen flow rate of 1–2 L/min was applied. The initial settings for the NIV group were as follows: inspiratory positive airway pressure of 8 cmH2O, expiratory positive airway pressure of 4 cmH2O, and FiO2 of 0.5. The settings were then adjusted according to tidal volume and SpO2, with the goal of a tidal volume of 6–20 mL/kg and SpO2 >92%. NIV was changed to standard oxygen therapy if the patient met the following criteria: controlled underlying disease that induced dyspnea, arterial blood pH >7.30, and an arterial partial pressure of oxygen >50 mmHg, inhaled oxygen concentrations <0.35, and hemodynamic stability. The included patients were categorized into two groups according to HFNC or NIV application after extubation. Furthermore, each group was subsequently divided into two subsets by the sputum volume within 24 h after extubation: ≥20 mL/day subset (excessive phlegm) and <20 mL/day subset (little phlegm). Thereafter, the patients remained in the same group, regardless of any changes in their daily sputum volume. Continuous data with a normal distribution are shown as mean ± standard deviation, and were compared using the independent-samples t-test. Continuous data with a non-normal distribution are shown as median (Q1, Q3), and were compared using the Mann–Whitney U test. Categorical data were expressed as number (percentage), and the group differences were analysed with the chi-squared test or Fisher's exact test. A P-value <0.05 was considered statistically significant. We included 257 patients with AECOPD in the final analysis [Supplementary Figure 1, https://links.lww.com/CM9/B610]. Patients in the HFNC and NIV groups had comparable baseline characteristics on admission to the intensive care unit. Additionally, there were no significant differences in baseline characteristics, such as sex, age, smoking history, the acute physiologic assessment and chronic health evaluation II (APACHE II) score, preexisting comorbidities [Supplementary Table 1, https://links.lww.com/CM9/B610], and critical parameters within 24 h before extubation (e.g., respiratory rate, heart rate, mean arterial pressure, arterial blood pH, partial pressure of oxygen (PaO2)/FiO2, and PaCO2) [Supplementary Table 1, https://links.lww.com/CM9/B610]. There were no significant differences in the reintubation rate within 72 h, length of hospital stay after extubation in the RICU, or hospital mortality between the HFNC and NIV groups. However, HFNC treatment had a lower reintubation rate within 72 h (P = 0.010) and a shorter length of hospital stay (P <0.001) after extubation in the RICU than NIV treatment in patients with sputum volume ≥20 mL within 24 h after extubation, but not in those with a daily sputum volume <20 mL [Table 1]. We did not find any difference in hospital mortality between the two groups in overall analysis or stratification analysis based on sputum volume within 24 h after extubation. Table 1 - Outcomes comparation of HFNC or NIV in acute exacerbation of chronic obstructive pulmonary disease patients after extubation. Outcomes Study groups χ 2/z-value P-value HFNC (n = 114) NIV (n = 143) Reintubation within 72 h All patients 15 (13.2) 27 (18.9) 1.520‡ 0.218 Sputum volume within 24 h after extubation ≥20 mL* 8 (10.4) 22 (26.2) 6.616‡ 0.010 Sputum volume within 24 h after extubation <20 mL† 7 (18.9) 5 (8.5) 1.414‡ 0.204 LOS after extubation in RICU (days) All patients 4 (3, 5) 4 (4, 6) -2.116§ 0.068 Sputum volume within 24 h after extubation ≥20 mL* 4 (3, 5) 5 (4, 7) -3.853§ <0.001 Sputum volume within 24 h after extubation <20 mL† 4 (3, 5) 4 (3, 4) 1.554§ 0.364 Hospital mortality All patients 11 (9.6) 18 (12.6) 0.547‡ 0.460 Sputum volume within 24 h after extubation ≥20 mL* 7 (9.1) 12 (14.3) 1.042‡ 0.308 Sputum volume within 24 h after extubation <20 mL† 4 (10.8) 6 (10.2) 0.000‡ 1.000 Data are presented as n (%) and median with the 25th and 75th percentile. *HFNC: n = 77, NIV: n = 84; †HFNC: n = 37, NIV: n = 59; ‡χ2 value; §Z value. HFNC: High-flow nasal cannula oxygen therapy; LOS: Length of stay; NIV: Non-invasive ventilation; RICU: Respiratory intensive care unit. In the current retrospective analysis, we found that HFNC as a sequential therapy following extubation was not inferior to NIV therapy in hypercapnic patients with AECOPD. More importantly, HFNC was superior to NIV as a sequential therapy in patients with AECOPD and excessive phlegm after extubation. We speculate that positive pressure ventilation of the mouth and nose with NIV support may not be conducive to sputum expulsion, and infection control and relief of airflow limitation in these patients may also be compromised. Another potential reason for the superiority of HFNC may be the superior tolerability and better comfort of HFNC compared with NIV. Doshi et al[4] found that 29% of NIV failure was attributed to treatment intolerance, which was significantly higher than that of HFNC (4%). HFNC is designed to avoid claustrophobia. The heating and humidification features of HFNC enable delivery of gas at an absolute humidity of 44 mg H2O/L and a temperature of 37°C, which effectively promotes mucus removal and avoids side effects such as mucosal dryness.[5] This evidence further supports the results of the superiority of HFNC to NIV in patients with AECOPD and excessive sputum in our study. A strength of this study is that we found that HFNC as sequential therapy following extubation was not inferior to NIV therapy in hypercapnic patients with AECOPD, and to some extent, even superior to NIV in these patients with excessive phlegm. However, there are also some limitations to this study. First, the sample size was relatively small. Second, recall bias may exist in this retrospective study, and the use of NIV or HFNC was dependent on the experience of physicians, which could have also led to choice bias. Overall, this study shows that HFNC as sequential therapy is non-inferior to NIV for hypercapnic patients with AECOPD after extubation. Funding This study was supported by grants from the National Natural Science Foundation of China (Nos. 81770080 and 82100037), the Xiangya Hospital-Beida Weiming Clinical Rehabilitation Research Fund (No. XYWM2015I20) and the Ministry of Science and Technology of the People's Republic of China (No. 2016YFC1304204), the National Science Foundation for Postdoctoral Scientists of China (No. 2021TQ0375), Hunan Outstanding Postdoctoral Innovative Talents Program (No. 2021RC2018), the Youth Foundation of Xiangya Hospital (No. 2020Q06), and Hainan Provincial Medical and Health Research Project (No. 2001032061A2010). Conflicts of interest None.

BACKGROUND:Delayed treatment leads to increased mortality in critically ill patients with invasive pulmonary aspergillosis (IPA). We aimed to develop and validate a prediction score based on novel biomarkers and clinical risk factors to identify IPA in immunocompetent patients in the intensive care unit (ICU).METHODS:A retrospective study was conducted to collect medical information and novel biomarkers upon ICU admission. Risk factors adopted for the final prediction score were identified using multivariate logistic regression analysis.RESULTS:We retrospectively collected 1841 critical ill patients between January 2018 and August 2022. Patients with IPA had higher C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio, systemic immune-inflammation index and lower prognostic nutritional index (PNI). Chronic obstructive pulmonary disease (COPD), continuous renal replacement therapy (CRRT), high dose of corticosteroids, broad-spectrum antibiotics, blood galactomannan (GM) positivity and high CAR were independent risk factors for IPA and were entered into the final prediction score. The score had good discrimination, with the area under receiver operating characteristic curve of 0.816 and 0.780 for the training and validation cohorts, respectively, and good calibration.CONCLUSION:A score based on six clinical and novel immunological biomarkers showed promising predictive value for antifungal treatment in immunocompetent ICU patients.

Background: The recommended delivery mode for bronchodilators in bronchodilator responsiveness (BDR) testing remains controversial. Objective: To compare the efficacy of salbutamol administration using a nebulizer versus a metered-dose inhaler (MDI) with spacer in BDR testing. Design: A retrospective study. Methods: This study examined the data of patients with chronic obstructive pulmonary disease who completed BDR testing between 1 December 2021 and 30 June 2022, at Xiangya Hospital, Central South University. After administering 400 μg of salbutamol through an MDI with spacer or 2.5 mg using a nebulizer, the changes in forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC) were analyzed in patients with moderate-to-very severe spirometric abnormalities [pre-bronchodilator FEV 1 percentage predicted values (FEV 1 %pred) ⩽59%]. Significant responsiveness was assessed as >12% and >200 mL improvement in FEV 1 and/or FVC or >10% increase in FEV 1 %pred or FVC percentage predicted values (FVC%pred) from pre- to post-bronchodilator administration. Results: Of the enrolled 894 patients, 83.2% were male (median age, 63 years). After propensity score matching, 240 pairs of patients were selected. The increment in FEV 1 and increased FEV 1 relative to the predicted value (ΔFEV 1 %pred) were significantly higher in patients <65 years and those with severe spirometric abnormalities in the nebulization group than patients in the MDI group (all p < 0.05). Compared with MDI with spacer, patients who used nebulization had a 30 mL greater increase in ΔFEV 1 (95% CI: 0.01–0.05, p = 0.004) and a 1.09% greater increase in ΔFEV 1 %pred (95% CI: 0.303–1.896, p = 0.007) from baseline. According to the > 12% and >200 mL increase criterion, the significant BDR rate with nebulization was 1.67 times higher than that with an MDI with spacer (OR = 1.67, 95% CI: 1.13–2.47, p = 0.009). Conclusion: Salbutamol delivered using a nebulizer may be preferable to an MDI with spacer in certain circumstances. Nebulization has the potential to increase responsiveness to salbutamol in BDR testing.

BACKGROUND:Currently, no ideal biomarker can accurately stratify the risk of patients with severe community-acquired pneumonia (SCAP). This study aimed to evaluate the role of serum Krebs von den Lungen-6 (sKL-6) in predicting in-hospital mortality in adults with SCAP. METHODS:In this retrospective cohort study, 249 severe pneumonia adult patients were recruited between 6 May 2021 to 30 April 2023 in Xiangya Hospital of Central South University. The sKL-6 level within 48 h of admission was measured, and the primary outcome assessed was in-hospital mortality. Multivariable logistic regression analysis was performed to calculate adjusted odds ratios (OR) with 95% confidence intervals (CI). Survival curves were plotted and subgroup analyses were conducted, stratified by relevant covariates. RESULTS:A total of 249 patients were included in the study,with 124 patients having normal sKL-6 levels, and 125 patients having abnormal sKL-6 levels. The overall in-hospital mortality rate was 28.9% (72 out of 249 patients). Univariate and multivariate logistic regression analysis revealed that the patients with abnormal sKL-6 levels had a higher risk of in-hospital mortality compared to those with normal sKL-6 levels, both in the total SCAP patient population (OR: 5.38, 95%CI: 2.41-12.01, P < 0.001) and the non-COVID-19 SCAP patients subgroup (OR: 8.12, 95%CI: 3.16-20.84, P < 0.001). Subgroup and interaction analyses confirmed the stability of the relationship between sKL-6 levels and in-hospital mortality(P for interaction > 0.05). Kaplan-Meier survival curves showed that patients with abnormal sKL-6 levels had a higher in-hospital mortality rate than those with normal sKL-6 levels (P < 0.05). However, the results of restricted cubic spline plots(RCS) analysis demonstrated a nonlinear association between sKL-6 levels (as a continuous variable) and in-hospital mortality in patients with SCAP. Similar results were observed in non-COVID-19 SCAP patients. Furthermore, the receiver operating characteristic curve (ROC) analysis revealed that sKL-6 had superior predictive performance compared to existing biomarkers (e.g., APACHE-II, SOFA, BUN/Cr, PCT, and D-dimer) for in-hospital mortality in non-COVID-19 SCAP patients. CONCLUSION:sKL-6 is a practical and useful biomarker for predicting in-hospital mortality in patients with SCAP.

BackgroundIn recent years, the number of human adenovirus (HAdV)-related pneumonia cases has increased in immunocompetent adults. Acute respiratory distress syndrome (ARDS) in these patients is the predominant cause of HADV-associated fatality rates. This study aimed to identify early risk factors to predict early HAdV-related ARDS.MethodsData from immunocompetent adults with HAdV pneumonia between June 2018 and May 2022 in ten tertiary general hospitals in central China was analyzed retrospectively. Patients were categorized into the ARDS group based on the Berlin definition. The prediction model of HAdV-related ARDS was developed using multivariate stepwise logistic regression and visualized using a nomogram.ResultsOf 102 patients with adenovirus pneumonia, 41 (40.2%) developed ARDS. Overall, most patients were male (94.1%), the median age was 38.0 years. Multivariate logistic regression showed that dyspnea, SOFA (Sequential Organ Failure Assessment) score, lactate dehydrogenase (LDH) and mechanical ventilation status were independent risk factors for this development, which has a high mortality rate (41.5%). Incorporating these factors, we established a nomogram with good concordance statistics of 0.904 (95% CI 0.844-0.963) which may help to predict early HAdV-related ARDS.ConclusionA nomogram with good accuracy in the early prediction of ARDS in patients with HAdV-associated pneumonia may could contribute to the early management and effective treatment of severe HAdV infection.

Background:Delayed diagnosis further increases the mortality of invasive candidiasis (IC) in intensive care unit (ICU) patients. This study aimed to develop and validate a score based on novel serological biomarkers and clinical risk factors for predicting IC in immunocompetent ICU patients.Methods:We retrospectively collected clinical data and novel serological markers on admission to ICU. Multivariate logistic regression was used to identify the risk factors associated with IC, which were adopted to establish a scoring system.Results:Patients with IC had a higher C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR) and lower prognostic nutritional index than those without IC. The NLR, CAR, sepsis, total parenteral nutrition, 1,3-β-D-glucan (BDG)-positivity, and Sequential Organ Failure Assessment score were identified as independent risk factors for IC by multivariate logistic regression analysis and entered into the final scoring system. The area under receiver operating characteristic curve of the score were 0.883 and 0.892, respectively, in the development and validation cohort, higher than Candida score (0.883 vs.0.730, p < 0.001).Conclusion:We established a parsimonious score based on NLR, CAR, BDG-positivity, and clinical risk factors, which can accurately identify IC in ICU patients to give treatment on time and reduce mortality.

Background:Krebs von den Lungen 6 (KL-6) is a potential biomarker for determining the severity of interstitial lung disease (ILD) in patients with connective tissue disease (CTD). Whether KL-6 levels can be affected by potential confounders such as underlying CTD patterns, patient-associated demographics, and comorbidities needs further investigation.Methods:From the database created by Xiangya Hospital, 524 patients with CTD, with or without ILD, were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers, autoimmune antibodies, and the KL-6 level at admission. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. The percent of predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and computed tomography (CT) scans were used to determine the severity of ILD.Results:Univariate linear regression analysis showed that BMI, lung cancer, TB, lung infections, underlying CTD type, white blood cell (WBC) counts, neutrophil (Neu) counts, and hemoglobin (Hb) were related to KL-6 levels. Multiple linear regression confirmed that Hb and lung infections could affect KL-6 levels independently; the β were 9.64 and 315.93, and the P values were 0.015 and 0.039, respectively. CTD-ILD patients had higher levels of KL-6 (864.9 vs 463.9, P < 0.001) than those without ILD. KL-6 levels were closely correlated to the severity of ILD assessed both by CT and DLCO%. Additionally, we found that KL-6 level was an independent predictive factor for the presence of ILD and further constructed a decision tree model to rapidly determine the risk of developing ILD among CTD patients.Conclusion:KL-6 is a potential biomarker for gauging the incidence and severity of ILD in CTD patients. To use this typical value of KL-6, however, doctors should take Hb and the presence of lung infections into account.

Alveolar epithelial cell damage is an important determinant of the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the molecular mechanisms of alveolar epithelial death during the development of ALI/ARDS remain unclear. In this study, we explore the role of miR-29a-3p in ALI/ARDS and its molecular mechanism. Plasma samples were collected from healthy controls and ARDS patients. Mice were intratracheally instilled with lipopolysaccharide (LPS) to establish acute lung injury. N6-adenosine (m6A) quantification, RNA-binding protein immunoprecipitation, cell viability assay, quantitative real-time polymerase chain reaction, and western blotting were performed. We found that miR-29a-3p was down-regulated in plasma of ARDS patients and lung tissue of ALI model mice, and miR-29a-3p agomir injection down-regulated the levels of the inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the lungs, reducing alveolar epithelial cell PANoptosis as evaluated by the downregulation of Z-DNA binding protein 1 (ZBP1), gasdermin D (GSDMD), caspase-3, caspase-8, and mixed lineage kinase domain-like protein (MLKL), ultimately improving lung injury in the ALI model mice. Mechanism studies demonstrated that the knockout of methyltransferase 3 (N6-adenosine-methyltransferase complex catalytic subunit) removed the m6A modification of miR-29a-3p and reduced miR-29a-3p expression. Our findings suggest that miR-29a-3p is a potential target that can be manipulated for ALI/ARDS.

Objective Pneumocystis jirovecii pneumonia (PCP) is a life-threatening disease associated with a high mortality rate among immunocompromised patient populations. Invasive mechanical ventilation (IMV) is a crucial component of treatment for PCP patients with progressive hypoxemia. This study explored the risk factors for IMV and established a model for early predicting the risk of IMV among patients with PCP. Methods A multicenter, observational cohort study was conducted in 10 hospitals in China. Patients diagnosed with PCP were included, and their baseline clinical characteristics were collected. A Boruta analysis was performed to identify potentially important clinical features associated with the use of IMV during hospitalization. Selected variables were further analyzed using univariate and multivariable logistic regression. A logistic regression model was established based on independent risk factors for IMV and visualized using a nomogram. Results In total, 103 patients comprised the training cohort for model development, and 45 comprised the validation cohort to confirm the model’s performance. No significant differences were observed in baseline clinical characteristics between the training and validation cohorts. Boruta analysis identified eight clinical features associated with IMV, three of which were further confirmed to be independent risk factors for IMV, including age (odds ratio [OR] 2.615 [95% confidence interval (CI) 1.110–6.159]; p = 0.028), oxygenation index (OR 0.217 [95% CI 0.078–0.604]; p = 0.003), and serum lactate dehydrogenase level (OR 1.864 [95% CI 1.040–3.341]; p = 0.037). Incorporating these three variables, the nomogram achieved good concordance indices of 0.829 (95% CI 0.752–0.906) and 0.818 (95% CI 0.686–0.950) in predicting IMV in the training and validation cohorts, respectively, and had well-fitted calibration curves. Conclusions The nomogram demonstrated accurate prediction of IMV in patients with PCP. Clinical application of this model enables early identification of patients with PCP who require IMV, which, in turn, may lead to rational therapeutic choices and improved clinical outcomes.

OBJECTIVES:Coronavirus disease 2019 (COVID-19) in elderly and patients with chronic respiratory diseases (COPD) had a poor prognosis. COPD is one of the most common chronic respiratory diseases. We explore the epidemiological characteristics of patients with severe COVID-19 with COPD patients in order to provide medical evidence for the prevention and treatment of severe COVID-19.METHODS:We retrospectively analyzed the clinical baseline characteristics, treatment strategies, disease progression and prognosis of 557 severe COVID-19 patients admitted to the West Court of Union Hospital of Huazhong University of Science and Technology from January 29, 2020 to April 8, 2020.RESULTS:A total of 465 patients with severe COVID-19 were enrolled in the study, including 248 (53.3%) males and 217 (46.7%) females. The median age of severe COVID-19 patients was 62.0 years, and 53 patients were complicated with COPD. Common symptoms at the onset included fever (78.5%), dry cough (67.1%), shortness of breath (47.3%) and fatigue (40.9%). Compared with non-COPD patients, patients with COPD had significantly lower levels of SpO2 in admission (90.0% vs 92.0%, P=0.014). In terms of laboratory examinations, patients with COPD had higher levels of C-reactive protein, interleukin-6, procalcitonin, total bilirubin, blood urea nitrogen, serum creatinine, lipoprotein (a), high-sensitivity troponin I, and D-dimer, while had lower levels of platelet counts, albumin and apolipoprotein AI. Severe COVID-19 patients with COPD had higher Sequential Organ Failure Assessment scores [3.0(2.0, 3.0) vs 2.0(2.0, 3.0), P=0.038] and CURB-65 score [1.0(1.0, 2.0) vs1.0(0.0, 1.0), P<0.001], and a higher proportion of progressing to critical illness (28.3% vs 10.0%, P<0.001) with more complications [e.g. septic shock (15.1% vs 6.1%, P=0.034)], had higher incidence rates of antibiotic therapies (90.6% vs 77.2%, P=0.025), non-invasive (11.3% vs 1.7%, P<0.001) and invasive mechanical ventilation (17.0% vs 8.3%, P=0.039), ICU admission (17.0% vs 7.5%, P=0.021) and death (15.1% vs 6.1%, P=0.016). Cox proportion hazard model was carried out, and the results showed that comorbid COPD was an independent risk factor for severe COVID-19 patients progressing to critical type, after adjusting for age and gender [adjusted hazard ratio (AHR)=2.38(1.30-4.37), P=0.005] and additionally adjusting for chronic kidney diseases, hypertension, coronary heart disease [AHR=2.63(1.45-4.77), P<0.001], or additionally adjusting for some statistically significant laboratory findings [AHR=2.10(1.13-3.89), P=0.018].CONCLUSIONS:Severe COVID-19 patients with COPD have higher levels of disease severity, proportion of progression to critical illness and mortality rate. Individualized treatment strategies should be adopted to improve the prognosis of severe COVID-19 patients.

Hypervirulent Klebsiella pneumoniae (hvKP) causes invasive infections and leads to high morbidity and mortality rates. Here, we report the case of a Chinese man with diabetes mellitus who developed acute respiratory distress syndrome and septic shock due to hvKP belonging to the K1 strain. The patient was treated with venovenous extracorporeal membrane oxygenation and continuous renal replacement therapy, in combination with antibiotics and recovered well. Clinicians should be aware of fatal infections caused by hvKP and investigate the best treatment options for patients at various stages of infection.

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.