Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. @*Materials and Methods@#Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. @*Results@#A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. @*Conclusion@#Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Prediction of Postoperative Lung Function in Lung Cancer Patients Using Machine Learning Models / 결핵및호흡기질환

Background@#Surgical resection is the standard treatment for early-stage lung cancer. Since postoperative lung function is related to mortality, predicted postoperative lung function is used to determine the treatment modality. The aim of this study was to evaluate the predictive performance of linear regression and machine learning models. @*Methods@#We extracted data from the Clinical Data Warehouse and developed three sets: set I, the linear regression model; set II, machine learning models omitting the missing data: and set III, machine learning models imputing the missing data. Six machine learning models, the least absolute shrinkage and selection operator (LASSO), Ridge regression, ElasticNet, Random Forest, eXtreme gradient boosting (XGBoost), and the light gradient boosting machine (LightGBM) were implemented. The forced expiratory volume in 1 second measured 6 months after surgery was defined as the outcome. Five-fold cross-validation was performed for hyperparameter tuning of the machine learning models. The dataset was split into training and test datasets at a 70:30 ratio. Implementation was done after dataset splitting in set III. Predictive performance was evaluated by R2 and mean squared error (MSE) in the three sets. @*Results@#A total of 1,487 patients were included in sets I and III and 896 patients were included in set II. In set I, the R2 value was 0.27 and in set II, LightGBM was the best model with the highest R2 value of 0.5 and the lowest MSE of 154.95. In set III, LightGBM was the best model with the highest R2 value of 0.56 and the lowest MSE of 174.07. @*Conclusion@#The LightGBM model showed the best performance in predicting postoperative lung function.

Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non–Small Cell Lung Cancer: Updated Analysis of the RESET Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non–small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group). @*Materials and Methods@#In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes. @*Results@#The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5). @*Conclusion@#This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

Tiotropium Bromide Improves Neutrophilic Asthma by Recovering Histone Deacetylase 2 Activity

Background@#The value of tiotropium bromide (TIO) in neutrophilic asthma was meaningful in previous study. We hypothesized that TIO’s mechanism of action is associated with histone deacetylase 2 (HDAC2) activity, which is key for controlling the transcription of inflammatory cytokines and usually downregulated in neutrophilic asthma. @*Methods@#The effects of TIO and dexamethasone (DEX) on HDAC2 activity, nuclear factor kappa B (NF-κB), and C-X-C motif chemokine ligand 1 (CXCL1) were evaluated in neutrophilic asthma mouse model (C57BL, 6-week-old). An in-vitro study was conducted using primary human bronchial/tracheal epithelial (HBE) cells from asthma patients.Western blot analyses were performed for phospho-phospholipase Cγ-1 (PLCγ-1) and inositol trisphosphate (IP3 ) receptors (IP3 R) with treating lipopolysaccharide (LPS) and TIO. @*Results@#Ovalbumin was used to induce eosinophilic inflammation in this study. After neutrophilic asthma was induced by LPS (O+L group), HDAC2 activity was diminished with increased NF-κB activity and CXCL1 compared to the control group. TIO significantly improved NF-κB activity, CXCL1, and HDAC2 activity compared with the O+L group in in-vivo study (P < 0.05, each). Western blot analyses showed that LPS treated HBE cells from asthma patients increased PLCγ-1 and diminished IP3 receptor levels. After TIO treatment, recovery of IP3 R and improved PLCγ-1 levels were observed. @*Conclusion@#These results support the hypothesis that TIO modulates inflammation by recovering HDAC2 activity from the acetylcholine-stimulated inflammation cascade in neutrophilic asthma. The detailed inflammation cascade of recovering HDAC2 activity by TIO might be associated with PLCγ-1-IP3-IP3R mediated intracellular calcium ion pathway.

Trends and an Online Survey on the Use of Rigid Bronchoscopy in Korea

Background@#Although almost all interventional pulmonologists agree that rigid bronchoscopy is irreplaceable in the field of interventional pulmonology, less is known about the types of diseases that the procedure is used for and what difficulties the operators face during the procedure. The purpose of this study is to evaluate what diseases rigid bronchoscopy is used for, whether it is widely used, and what challenges the operators face in Korea. @*Methods@#We enrolled 14 hospitals in this retrospective cohort of patients who underwent rigid bronchoscopy between 2003 and 2020. An online survey was conducted with 14 operators to investigate the difficulties associated with the procedure. @*Results@#While the number of new patients at Samsung Medical Center (SMC) increased from 189 in 2003–2005 to 468 in 2018–2020, that of other institutions increased from 0 to 238.The proportion of SMC patients in the total started at 100% and steadily decreased to 59.2%.The proportion of malignancy as the indication for the procedure steadily increased from 29.1% to 43.0%, whereas post-tuberculous stenosis (25.4% to 12.9%) and post-intubation stenosis (19.0% to 10.9%) steadily decreased (all P for trends < 0.001). In the online survey, half of the respondents stated that over the past year they performed less than one procedure per month. The fewer the procedures performed within the last year, the more likely collaboration with other departments was viewed as a recent obstacle (Spearman correlation coefficient, r s = −0.740, P = 0.003) and recent administrative difficulties were encountered (r s = −0.616, P = 0.019). @*Conclusion@#This study demonstrated that the number of patients undergoing rigid bronchoscopy has been increasing, especially among cancer patients. For this procedure to be used more widely, it will be important for beginners to systematically learn about the procedure itself as well as to achieve multidisciplinary consultation.

Tiotropium Bromide Has a More Potent Effect Than Corticosteroid in the Acute Neutrophilic Asthma Mouse Model / 결핵및호흡기질환

Background@#Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids. @*Methods@#C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups. @*Results@#Neutrophil counts, T helper 2 cells (TH2)/TH17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05). @*Conclusion@#TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.

Clinical efficacy of adjuvant chemotherapy in stage IB (< 4 cm) non-small cell lung cancer patients with high-risk factors

Background/Aims@#Adjuvant chemotherapy is the standard of care for resected stage II-IIIA non-small cell lung cancer (NCSLC). The efficacy of adjuvant chemotherapy in stage IB (< 4 cm) NSCLC with high-risk factors is controversial. @*Methods@#This retrospective multicenter study included 285 stage IB NSCLC patients with high-risk factors according to the 8th edition tumor, node, metastasis (TNM) classification from four academic hospitals. High-risk factors included visceral pleural invasion, vascular invasion, lymphatic invasion, lung neuroendocrine tumors, and micropapillary histology patterns. @*Results@#Of the 285 patients, 127 (44.6%) were included in the adjuvant chemotherapy group and 158 (55.4%) were included in the non-adjuvant chemotherapy group. The median follow-up was 41.5 months. Patients in the adjuvant chemotherapy group had a significantly reduced recurrence rate and risk of mortality than those in the non-adjuvant chemotherapy group (hazards ratio, 0.408; 95% confidence interval, 0.221 to 0.754; p = 0.004 and hazards ratio, 0.176; 95% confidence interval, 0.057 to 0.546; p = 0.003, respectively). Adjuvant chemotherapy should be particularly considered for the high-risk factors such as visceral pleural involvement or vascular invasion. Based on the subgroup analysis, adjuvant chemotherapy should be considered when visceral pleural involvement is present, even if the tumor size is < 3 cm. @*Conclusions@#Adjuvant chemotherapy may be useful for patients with stage IB NSCLC with high-risk factors and is more relevant for patients with visceral pleural involvement or vascular invasion.

Risk factors for primary lung cancer among never-smoking women in South Korea: a retrospective nationwide population-based cohort study

Background/Aims@#We performed a large-scale, retrospective, nationwide, cohort study to investigate the risk factors for lung cancer among never-smoking Korean females. @*Methods@#The study data were collected from a general health examination and questionnaire survey of eligible populations conducted between January 1, 2003 and December 31, 2004; the data were acquired from the tailored big data distribution service of the National Health Insurance Service. After a 1-year clearance period, 5,860,922 of 6,318,878 never-smoking female participants with no previous history of lung cancer were investigated. After a median follow-up of 11.4 years, 43,473 (0.74%) participants were defined as “newly diagnosed lung cancer”. @*Results@#After adjusting for all variables at baseline, the variables older age, lower body mass index (BMI), less exercise, frequent alcohol drinking, meat-based diet, rural residence, and previous history of cancer were associated with a higher incidence of lung cancer. Low BMI (< 18.5 kg/m2: hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.27 to 1.40) was a significant independent risk factor; as BMI decreased, HR increased. Negative associations between BMI and lung-cancer development were also observed after controlling for age (p for trend < 0.001). Drinking alcohol one to two times a week (HR, 1.25; 95% CI, 1.21 to 1.28) and eating a meat-based diet (HR, 1.08; 95% CI, 1.01 to 1.15) were associated with lung-cancer incidence. @*Conclusions@#Modifiable baseline characteristics, such as BMI, exercise, alcohol consumption, and diet, are risk factors for lung-cancer development among never- smoking females. Thus, lifestyle modifications may help prevent lung cancer.

It's Time for Latent Tuberculosis Infection Screening in HIV-infected Individuals

No abstract available.

Trends and Updated Statistics of Lung Cancer in Korea / 결핵

No abstract available.

Corrigendum: Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model / 결핵및호흡기질환

In this article, the statement of ethical statement about animal experiment was omitted.

Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model / 결핵

BACKGROUND: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. METHODS: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. RESULTS: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p < 0.05 and p < 0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon γ, and tumor necrosis factor α in the CAM+DXM group than in the monotherapy group (p < 0.001, p < 0.05, and p < 0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p < 0.05). CONCLUSION: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model / 결핵및호흡기질환

BACKGROUND@#Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids.@*METHODS@#C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed.@*RESULTS@#Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p < 0.05 and p < 0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon γ, and tumor necrosis factor α in the CAM+DXM group than in the monotherapy group (p < 0.001, p < 0.05, and p < 0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p < 0.05).@*CONCLUSION@#Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

The role of hypoxia on the acquisition of epithelial-mesenchymal transition and cancer stemness: a possible link to epigenetic regulation

A hypoxic microenvironment leads to cancer progression and increases the metastatic potential of cancer cells within tumors via epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. The hypoxic response pathway can occur under oxygen tensions of < 40 mmHg through hypoxia-inducible factors (HIFs), which are considered key mediators in the adaptation to hypoxia. Previous studies have shown that cellular responses to hypoxia are required for EMT and cancer stemness maintenance through HIF-1α and HIF-2α. The principal transcription factors of EMT include Twist, Snail, Slug, Sip1 (Smad interacting protein 1), and ZEB1 (zinc finger E-box-binding homeobox 1). HIFs bind to hypoxia response elements within the promoter region of these genes and also target cancer stem cell-associated genes and mediate transcriptional responses to hypoxia during stem cell differentiation. Acquisition of stemness characteristics in epithelial cells can be induced by activation of the EMT process. The mechanism of these phenotypic changes includes epigenetic alterations, such as DNA methylation, histone modification, chromatin remodeling, and microRNAs. Increased expression of EMT and pluripotent genes also play a role through demethylation of their promoters. In this review, we summarize the role of hypoxia on the acquisition of EMT and cancer stemness and the possible association with epigenetic regulation, as well as their therapeutic applications.

Effect of intranasal rosiglitazone on airway inflammation and remodeling in a murine model of chronic asthma

BACKGROUND/AIMS: Asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Peroxisome proliferator-activated receptors have been reported to regulate inflammatory responses in many cells. In this study, we examined the effects of intranasal rosiglitazone on airway remodeling in a chronic asthma model. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated intranasally with rosiglitazone with or without an antagonist during OVA challenge. We determined airway inflammation and the degree of airway remodeling by smooth muscle actin area and collagen deposition. RESULTS: Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, compared with control mice. Additionally, the mice developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of rosiglitazone intranasally inhibited the eosinophilic inflammation significantly, and, importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. Expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) was increased in the OVA group and decreased in the rosiglitazone group. Co-treatment with GW9660 (a rosiglitazone antagonist) and rosiglitazone increased the expression of TLR-4 and NF-kappaB. CONCLUSIONS: These results suggest that intranasal administration of rosiglitazone can prevent not only air way inf lammation but also air way remodeling associated with chronic allergen challenge. This beneficial effect is mediated by inhibition of TLR-4 and NF-kappaB pathways.

Smoking habits and nicotine dependence of North Korean male defectors

BACKGROUND/AIMS: The smoking rates and patterns in the North Korean population are not well known. More than 20,000 North Korean defectors have settled in South Korea; thus, we can estimate the current North Korean smoking situation using this group. METHODS: All North Korean defectors spend their first 3 months in a South Korean facility learning to adapt to their new home. We retrospectively analyzed the results from a questionnaire conducted among North Korean male defectors in this facility from August 2012 to February 2014. RESULTS: Of 272 men, 84.2% were current smokers, 12.5% were ex-smokers, and 3.3% were non-smokers. The mean age of this group was 35.9 ± 11.3 years, and smoking initiation occurred at a mean age of 18.2 ± 4.7 years. Among the subjects, 78.1% had a family member who smoked. Of the 221 current smokers, 67.4% responded that they intended to quit smoking. Fagerström test and Kano test for social nicotine dependence (KTSND) results for current smokers were 3.35 ± 2.26 and 13.76 ± 4.87, respectively. Question 9 on the KTSND (doctors exaggerate the ill effects of smoking) earned a significantly higher score relative to the other questions and a significantly higher score in current smokers compared with non-smokers. CONCLUSIONS: The smoking rate in North Korean male defectors was higher than that indicated previously. However, interest in smoking cessation was high and nicotine dependence was less severe than expected. Further investigation is needed to identify an efficient method for North Korean smokers to stop smoking.

Uterine Cervix Metastasis in Lung Adenocarcinoma with Anaplastic Lymphoma Kinase Rearrangement

The importance of anaplastic lymphoma kinase (ALK) as an oncogene in non-small cell lung cancer (NSCLC) has emerged as a major concern due to a dramatic clinical effect of targeted therapy. As compared with the research for targeted therapy, the study about clinicopathological characteristics for ALK positive NSCLC hasn't been worked enough. Here, we describe a 35-year-old woman diagnosed with stage IVb NSCLC with ALK rearrangement. During evaluating her disease, a metastatic lesion to uterine cervix was found. Although lung cancer metastasis to female genital tract is rare, we also present case series that show a metastasis to the female genital tract in NSCLC with ALK rearrangement. These case series could suggest that ALK positive NSCLC has distinct metastatic pattern.

Extensive Bilateral Lemierre Syndrome due to Methicillin-Resistant Staphylococcus epidermidis in a Patient with Lung Adenocarcinoma / 결핵및호흡기질환

Lemierre syndrome (LS) is a septic thrombophlebitis of the internal jugular vein (IJV) following an oropharyngeal infection. LS is commonly caused by normal anaerobic flora and treated with appropriate antibiotics and anticoagulation therapy. Although the incidence of disease is very rare, 15% cases of LS are fatal even in the antibiotic era because of disseminated septic thromboemboli. We reported a case of extensive bilateral LS due to methicillin-resistant Staphylococcus epidermidis in a 63-year-old female with lung adenocarcinoma. Initial examination revealed a retropharyngeal abscess; hence, intravenous ceftriaxone and steroid were initiated empirically. However, pulmonary thromboembolism developed and methicillin-resistant S. epidermidis was identified in the bacterial culture. Despite intensive antibiotic and anticoagulation therapies, extensive septic thrombophlebitis involving the bilateral IJV and superior vena cava developed. Adjunctive catheter-directed thrombolysis and superior vena cava stenting were performed and the patient received antibiotic therapy for an additional 4 weeks, resulting in complete recovery.

Transformation into large-cell neuroendocrine carcinoma associated with acquired resistance to erlotinib in nonsmall cell lung cancer

No abstract available.

Pleural Fluid Pentraxin-3 for the Differential Diagnosis of Pleural Effusions / 결핵및호흡기질환

BACKGROUND: Conventional biomarkers cannot always establish the cause of pleural effusions; thus, alternative tests permitting rapid and accurate diagnosis are required. The primary aim of this study is to assess the ability of pentraxin-3 (PTX3) in order to diagnose the cause of pleural effusion and compare its efficacy to that of other previously identified biomarkers. METHODS: We studied 118 patients with pleural effusion, classified as transudates and exudates including malignant, tuberculous, and parapneumonic effusions (MPE, TPE, and PPE). The levels of PTX3, C-reactive protein (CRP), procalcitonin (PCT) and lactate in the pleural fluid were assessed. RESULTS: The levels of pleural fluid PTX3 were significantly higher in patients with PPE than in those with MPE or TPE. PTX3 yielded the most favorable discriminating ability to predict PPE from MPE or TPE by providing the following: area under the curve, 0.74 (95% confidence interval, 0.63-0.84), sensitivity, 62.07%; and specificity, 81.08% with a cut-off point of 25.00 ng/mL. CONCLUSION: Our data suggests that PTX3 may allow improved differentiation of PPE from MPE or TPE compared to the previously identified biomarkers CRP and PCT.