A score for predicting invasive pulmonary aspergillosis in immunocompetent critically ill patients.

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.

A prediction model for acute respiratory distress syndrome in immunocompetent adults with adenovirus-associated Pneumonia: a multicenter retrospective analysis.

BACKGROUND: In 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. METHODS: Data 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. RESULTS: Of 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. CONCLUSION: A 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.

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.

Clinical characteristics of severe coronavirus disease 2019 patients with chronic obstructive pulmonary disease. / é‡åž‹æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žåˆå¹¶æ ¢æ€§é˜»å¡žæ€§è‚ºç–¾ç— æ‚£è€ ä¸´åºŠç‰¹å¾.

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.

[Fractional exhaled nitric oxide in bronchial inflammatory lung diseases].

OBJECTIVE: To explore the change of fractional exhaled nitric oxide (FeNO) and its correlation with forced expiratory volume in the first second (FEV1), the first second forced expiratory volume percentage of forced vital capacity (FEV1/FVC) in bronchial asthma and chronic obstructive pulmonary disease (COPD). METHODS: FeNO, FEV1 and FEV1/FVC were measured in 57 suspected asthmatics (21 acute onsets, 12 non-acute and 24 non-asthma), 38 COPD patients (25 acute exacerbations and 13 stable stages) and 26 healthy subjects. RESULTS: In the 57 suspected asthmatic patients, when the optimal cut off value of FeNO was 20.15 PPb, which was used to diagnose asthma and differentiate asthma and non-asthma, the positive predictive value, the negative predictive value, the sensitivity and the specificity was 94.1%, 95.7%, 97.0%, and 91.7% respectively. There was significant difference in the FeNO level between the 33 asthmatics and 26 healthy subjects (P<0.05). There was also significant difference in the FeNO level between the acute onset and the non-acute (P<0.05), but not in the FEV1 and FEV1/FVC level (both P>0.05). There was no significant correlation between FeNO and FEV1, FEV1/FVC in patients with asthma (r=-0.186, -0.236, both P>0.05). There was significant difference in the levels of FeNO, FEV1 and FEV1/FVC between the 38 COPD patients and the 26 healthy subjects (all P<0.05), and also between the 25 acute exacerbations and 13 stable COPDs (all P<0.05), but not between the 13 stable COPDs and 26 healthy subjects (all P>0.05). FeNO was not correlated with FEV1 and FEV1/FVC level in COPD patients (r=-0.167, -0.285, both P>0.05). CONCLUSION: FeNO level is increased obviously in patients with asthma. The optimal cut off value of FeNO at 20.15 PPb can differentiate asthma and non-asthma with high sensitivity and specificity. FeNO is higher for the acute onset than non-acute, which may be useful to evaluate the control degree. FeNO level is increased in COPD patients in the acute exacerbations, but there is no change in stable COPD patients compared with the healthy subjects.

Serum Krebs von den Lungen-6 as a potential biomarker for distinguishing combined pulmonary fibrosis and emphysema from chronic obstructive pulmonary disease: A retrospective study.

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.

Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testing: a retrospective study.

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 (FEV1) and forced vital capacity (FVC) were analyzed in patients with moderate-to-very severe spirometric abnormalities [pre-bronchodilator FEV1 percentage predicted values (FEV1%pred) ⩽59%]. Significant responsiveness was assessed as >12% and >200 mL improvement in FEV1 and/or FVC or >10% increase in FEV1%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 FEV1 and increased FEV1 relative to the predicted value (ΔFEV1%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 ΔFEV1 (95% CI: 0.01-0.05, p = 0.004) and a 1.09% greater increase in ΔFEV1%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.

Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testingBronchodilator responsiveness testing is commonly undertaken as an important part of spirometry testing to determine the degree of volume and airflow improvement after bronchodilator administration. BDR testing results may affect patients' diagnosis and treatment. This study compared the effects of two delivery models (a metered dose inhaler (MDI) with spacer and nebulization) on responsiveness to bronchodilators and the results of bronchodilator responsiveness testing among patients with chronic obstructive pulmonary disease. We found that the increment in forced expiratory volume in one second were significantly higher in patients aged <65 years and in those with severe spirometric abnormalities in the nebulization group than in those in the MDI group. The study provides evidence that salbutamol delivered by a nebulizer is preferable to an MDI with spacer in patients <65 years and in those with severe spirometric abnormalities and could increase positive responsiveness to bronchodilators. The study will assist in clinical decision-making by selecting the appropriate dosing regimen for different patients.

Serum Krebs von den Lungen-6 is associated with in-Hospital mortality of patients with severe Community-Acquired Pneumonia: A retrospective cohort study.

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.

KL-6 levels in the connective tissue disease population: typical values and potential confounders-a retrospective, real-world study.

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 ß 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.

Comparison of clinical, laboratory and radiological characteristics between Chlamydia psittaci and adenovirus pneumonias: a multicenter retrospective study.

OBJECTIVES: Pneumonia caused by Chlamydia psittaci is a significant global public health issue. Symptom onset and laboratory characteristics may be confused with those of other respiratory viral infections, including adenovirus pneumonia. We aimed to determine differences in clinical presentations and establish a simple nomogram to differentiate C. psittaci and adenovirus pneumonias. METHODS: We conducted a multicenter retrospective study in 10 tertiary general hospitals to compare patients with either C. psittaci (n = 78) or adenovirus (n = 102) pneumonia. A multivariable logistic regression model was used to identify risk factors of C. psittaci pneumonia that were used to establish a nomogram. RESULTS: C. psittaci and adenovirus pneumonia showed certain similar clinical symptoms, including fever, dyspnea, and fatigue, but differed in other characteristics. The multivariate logistic regression showed that age, sex, nervous system symptoms, lymphocyte count, C-reactive protein level, and bilateral lung lesions were risk factors for C. psittaci pneumonia. After incorporating these six factors, the established nomogram achieved a good concordance value (0.949 [95% CI 0.917-0.982]) in differentiating the types of pneumonia, with well-fitting calibration curves. CONCLUSION: Despite having similar clinical features, the variables of age, sex, nervous system symptoms, lymphocytes, C-reactive protein levels, and bilateral lung lesions were combined into a clinically useful nomogram for the rapid and early differentiation of C. psittaci pneumonia from adenovirus pneumonia. This nomogram may help improve treatments and clinical outcomes.