Objective:To analyze the diagnostic efficacy of Aspergillus-specific immunoglobulin G antibody (Asp IgG) in suspected non-neutropenic invasive pulmonary aspergillosis (IPA). Methods:This was a case-control investigation involving 648 patients with suspected non-neutropenic IPA admitted to the Respiratory and Critical Care Medicine Departments of 11 tertiary hospitals in Jiangsu Province between September 2020 and July 2023 via a non-random sampling method.Based on inclusion and exclusion criteria,306 eligible patients were ultimately enrolled and assigned into the IPA group (108 cases) and non-IPA group (198 cases).Using an Asp IgG level of ≥80 AU/ml as the positive threshold,non-IPA patients were further divided into the Asp IgG false-positive group (67 cases) and Asp IgG true-negative group (131 cases).Clinical data were collected,including gender,age,body mass index,smoking history,intensive care unit (ICU) admission status,underlying pulmonary diseases,diabetes,usage of glucocorticoids,usage of immunosuppressants,chest CT findings,Asp IgG levels,galactomannan antigen (GM) test results,culture results,next-generation sequencing (NGS) results,specific Aspergillus infection types in IPA patients,pathogen detection via culture or NGS,and infection markers.Receiver operator characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of Asp IgG in non-neutropenic IPA.Using the final diagnosis as the gold standard,the diagnostic performance of Asp IgG,GM test,culture,and bronchoalveolar lavage fluid (BALF) NGS for non-neutropenic IPA was assessed.Multivariate logistic regression was used to analyze factors influencing false-positive Asp IgG in non-IPA patients.The diagnostic accuracy of combining Asp IgG with other fungal detection methods for non-neutropenic IPA was also analyzed. Results:In the IPA group,there were 83 males and 25 females,with an average age of 69 (60,75) years.In the non-IPA group,there were 138 males and 60 females,with an average age of 65 (54,74) years.There was no significant difference in gender between the two groups ( P>0.05).However,compared with the non-IPA group,patients in the IPA group had significantly older age,and higher ICU admission rate,rate of intravenous or oral glucocorticoids usage,proportion of pulmonary consolidation on chest CT,and Asp IgG levels (all P<0.05).There was no significant difference in Asp IgG levels among IPA patients with only Aspergillusfumigatus infection,only Aspergillusflavus infection,only Aspergillusniger infection or mixed Aspergillus infections ( H＝3.16, P＝0.367).ROC curve analysis showed that the area under the curve of Asp IgG in diagnosing non-neutropenic IPA was 0.676 (95% CI:0.611-0.741).When the cutoff value for Asp IgG was set at 80 AU/ml,the sensitivity was 60.2% and the specificity was 66.2%.Among different fungal detection methods,the highest false-positive rate was seen in Asp IgG testing (cutoff value of 80 AU/ml,33.8%),followed by Asp IgG (cutoff value of 120 AU/ml,16.7%),BALF NGS (9.5%),BALF GM test (7.0%),serum GM test (4.5%),sputum culture (1.4%),and BALF culture (0%).In the Asp IgG false-positive group,non-IPA patients exhibited significantly higher rates of ICU admission,diabetes prevalence,inhaled glucocorticoids usage,and detection rates of Candida species, Acinetobacter baumannii,and Klebsiella pneumoniae compared to those in the Asp IgG true-negative group (all P<0.05).Multivariate logistic regression analysis showed that underlying lung diseases ( OR＝2.547,95% CI:1.173-5.529),diabetes ( OR＝2.584,95% CI:1.132-5.899),detection of Candida species ( OR＝3.500,95% CI:1.203-10.178),and detection of Acinetobacter baumannii ( OR＝3.978,95% CI:1.070-14.790) were independent risk factors for false-positive Asp IgG in non-IPA patients (all P<0.05).Among patients with suspected non-neutropenic IPA with positive Asp IgG,72.2% (26/36) were ultimately diagnosed with non-neutropenic IPA if only one other fungal detection method was positive,and 100% (36/36) if two or more other fungal detection methods were positive. Conclusion:Asp IgG has certain diagnostic efficacy for non-neutropenic IPA,but it has a relatively high false-positive rate.The reliability of Asp IgG testing in diagnosing IPA is reduced in patients with underlying lung diseases,diabetes,or those with detected Candida species or Acinetobacter baumannii.Combining results from other fungal detection methods may facilitate the distinguishment of IPA patients from those with suspected non-neutropenic IPA and positive Asp IgG results.
Objective:To investigate the efficacy and safety of mepolizumab in the treatment of patients with eosinophilic granulomatosis with polyangiitis (EGPA).Methods:This was a non-randomized controlled trials study.Purposive sampling was used to collect data of 20 EGPA patients treated with mepolizumab at the First Affiliated Hospital of Guangzhou Medical University from August 2021 to December 2023.The study evaluated the differences in Birmingham Vasculitis Activity Score (BVAS), blood eosinophil count and percentage, forced expiratory volume in one second (FEV1) as a percentage of predicted value (FEV 1%pred), and oral corticosteroid (OCS) maintenance dose before and after treatment to assess the efficacy of mepolizumab and observe the safety of patients during treatment. Results:Among the 20 patients with EGPA, there were 17 females (85.0%), with an average age of 42.0 (30.8, 52.5)years.After 4 months of treatment, the total response rate was 85.0%.The blood eosinophil count decreased from 0.7 (0.5, 1.5)×10 9/L to 0.1 (0, 0.1)×10 9/L ( Z=3.88, P<0.001). The FEV 1%pred increased from 70.4% (49.7%, 85.2%) to 79.9% (72.0%, 101.5%)( Z=2.24, P=0.025). The fractional exhaled nitric oxide (FeNO) level decreased from 80.0 (35.0, 111.5) ppb to 51.6 (28.3, 65.4) ppb ( Z=2.54, P=0.011). The oral corticosteroid (OCS) dosage was reduced from 25.0 (16.3, 30.0) mg/d to 5.9 (5.0, 7.5) mg/d ( Z=3.83, P<0.001). After 12 months of treatment, 5 patients still show significant improvement inthe above clinical indicators compared to those before treatment.The clinical indicator changes before and after treatment between the standard dose group (300 mg/4 weeks) and the non-standard dose group (100 mg/4 weeks) were compared.The results showed no significant statistical difference in reducing BVAS scores, decreasing blood eosinophil counts, improving lung function indicators (FEV 1%pred), and reducing OCS dosage after 4 months of treatment ( P>0.05). Among the 20 patients, a total of 125 injections were administered, with only one instance of rash occurring post-injection of mepolizumab, which was tolerable. Conclusions:Mepolizumab has shown good efficacy in the treatment of EGPA, canreduce the maintenance dose of OCS andimprove lung function, and demonstrates good safety with no observed serious adverse events.Both the standard dose group and the non-standard dose group can effectively manage the symptoms and reduce the OCS usage in EGPA.
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease with unclear etiology and pathogenesis.Currently, there is no effective treatment.In the past few decades, multiple clinical trials have been conducted to determine the safety and efficacy of pharmacological treatments for IPF patients.So far, only two drugs, pirfenidone and nintedanib, have been proven to effectively slow down the functional decline and disease progression of IPF, which were approved by the U. S.Food and Drug Administration (FDA) in 2014.In addition, the specific therapeutic effects and mechanisms of a series of anti-fibrotic drugs targeting the pathogenesis of IPF, including connective tissue growth factor, autotaxin, lysophosphatidic acids, and integrin αvβ6, require further investigation.This review summarizes the advances of pharmacological therapy for IPF and provides ideas and basis for the research and development of novel targeted drugs.
Objective:To explore the clinical application of laser ablation to benign granulomatous tracheal stenosis.Methods:It was an observational study involving 30 patients with benign granulomatous tracheal stenosis who were treated with laser ablation in the Department of Respiratory and Critical Care Medicine, Changzhou Second People's Hospital Affiliated to Nanjing Medical University from January 2019 to September 2022 using the non-random sampling method. Other interventional treatment measures like electric snares and argon gas knife were combined with laser ablation if necessary. The airway diameter, improvement of tracheal stenosis, shortness of breath score, dyspnea index, pulmonary function indicators, occurrence of adverse reactions, partial pressure of oxygen in the arterial blood (PaO 2), partial pressure of carbon dioxide in the arterial blood (PaCO 2) and arterial oxygen saturation (SaO 2) were recorded. Bronchoscopy or chest CT was regularly re-examined to analyze restenosis. Patients were followed up and the quality of life was assessed using the Karnofsky Performance Scale (KPS). Results:Among the 30 patients, 22 cases had granulation tissue hyperplasia after tracheostomy, 4 cases had granulation tissue hyperplasia after tracheal intubation, and 4 cases had granulation tissue hyperplasia after tracheal stent placement. All patients were treated with laser ablation under a direct vision of the bronchoscope. A total of 43 laser ablations were performed on 30 patients. One week after laser ablation treatment, the airway diameter ([2.63±1.61] mm vs [8.96±2.25] mm, t=13.55), degree of tracheal stenosis ([80.63±11.96] vs [31.87±9.56], t=20.22), and shortness of breath score ([3.53±0.57] points vs [1.13±0.35] points, t=19.48), dyspnea index (Grade 0: 0[0.0%] vs 18[60.0%], Grade Ⅰ: 0[0.0%] vs 4 [13.3%], Grade Ⅱ: 0[0.0%] vs 7[23.3%], Grade Ⅲ: 4 [13.3%] vs 1[0.3%], Grade Ⅳ: 10[33.3%] vs 0[0.0%], Grade V: 16[53.3%] vs 0[0.0%], Z=46.32), lung function indicators (forced expiratory volume in 1 second: [1.37±0.13] L vs [1.76±0.15] L, t=12.64; forced vital capacity: [2.31±0.15] L vs [2.70±0.15] L, t=11.55), blood gas analysis indicators (PaO 2: [84.57±6.03] mmHg vs [94.57±4.07] mmHg, t=8.14; PaCO 2: [59.50±4.03] mmHg vs [42.30±2.77] mmHg, t=18.57; SaO 2: [82.63±4.41] mmHg vs [93.60±1.57] mmHg, t=12.64; 1 mmHg=0.133 kPa) and KPS score (<50 points: 17[56.7%] vs 5[16.7%]; 50-80 points: 12[40.0%] vs 16[53.3%]; >80 points: 1[3.3%] vs 9[30.0%], Z=3.64) were all significantly improved compared with those before treatment (all P<0.05). After 5-month follow-up on stenotic patients with enlarged airways, 13 cases developed restenosis after airway enlargement. Among all patients, 1 case developed tracheomalacia after surgery, and no serious adverse events were reported. After 5 months of the follow-up, effective rate was 90.0% (27/30). Conclusions:The short-term efficacy of laser ablation in patients with benign granulomatous tracheal stenosis is significant, but the long-term efficacy needs further evaluation.
Objective:To study the regulatory effect of circular RNAs (circRNAs) circ_0003998 on promoting the epithelial-mesenchymal transition (EMT) of lung adenocarcinoma cells and the underlying mechanism.Methods:It was an experimental study.The lung epithelial cell line BEAS-2B and lung adenocarcinoma cell lines A549, H1299, H1395, H1975 were cultured, and the expression levels of circ_0003998 and miR-218 in each cell lines were detected.A549 cells were transfected with small interfering RNA(siRNA) negative control (si-NC), circ_0003998 siRNA (si-circ_0003998), si-circ_0003998+ miR-NC inhibitor, si-circ_0003998+ miR-218 inhibitor, miR-NC or miR-218.Cell migration was detected by Transwell assay.The expression levels of circ_0003998, Bmi-1 mRNA, E-cadherin mRNA, N-cadherin mRNA and miR-218 were detected by fluorescent quantitative polymerase chain reaction.The protein levels of Bmi-1, E-cadherin and N-cadherin were detected by Western blotting.Dual-luciferase reporter assay was performed to detect the targeting relationship between miR-218 and circ_0003998, and that between miR-218 and Bmi-1.Rescue experiments were performed to verify that the role of silenced miR-218 in reversing the regulatory effect of si-circ_0003998.Results:Circ_0003998 was upregulated in lung adenocarcinoma cell lines than that of lung epithelial cell lines, and miR-218 was downregulated (all P<0.05), with the most significant changes in A549 cells.Knockdown of circ_0003998 downregulated circ_0003998 ( t=15.21), and protein and mRNA levels of N-cadherin ( t=7.82 and 9.76, respectively) and Bmi-1 ( t=9.93 and 12.02, respectively), reduced the number of migratory cells ( t=15.53), and upregulated miR-218 ( t=11.51) and the protein and mRNA levels of E-cadherin ( t=7.28 and 10.00, respectively) (all P<0.001). The luciferase activity of wild-type circ_0003998 plasmid and wild-type Bmi-1 plasmid in cells overexpressing miR-218 was significantly lower than those transfected with miR-NC ( t=13.61 and 14.68, respectively, all P<0.001). Compared with those transfected with si-circ_0003998+ miR-NC inhibitor, A549 cells transfected with si-circ_0003998+ miR-218 inhibitor presented significantly higher number of migratory cells, protein and mRNA levels of N-cadherin and Bmi-1, but lower expression level of miR-218 and protein and mRNA levels of E-cadherin (all P<0.05). Conclusions:Circ_0003998 promotes EMT of lung adenocarcinoma cells through the miR-218/Bmi-1 axis.
