The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases.

Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.

A prospective, open-label, randomized clinical trial to evaluate the efficacy and safety of remimazolam in patients undergoing EBUS-TBNA: REST trial design.

BACKGROUND: Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains undetermined. The REST trial (NCT06275594) will be a prospective randomized study of remimazolam in patients undergoing EBUS-TBNA with conscious sedation. The primary aim is to evaluate whether remimazolam is safe and effective for moderate sedation during EBUS-TBNA compared to real-world midazolam and on-label midazolam. METHODS: The REST trial will recruit 330 patients from four university hospitals with mediastinal lesions suspected of being lung cancer who are eligible for EBUS-TBNA under moderate sedation. The participants will be randomized into groups using remimazolam, real-world midazolam, and on-label midazolam (US prescribing information dosage) to perform EBUS-TBNA for procedural sedation. The primary endpoint will be procedural success using composite measures. DISCUSSION: The REST trial will prospectively evaluate the efficacy and safety of remimazolam during EBUS-TBNA under moderate sedation. It will provide information for optimizing sedation modalities and contribute to practical benefits in patients undergoing EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06275594). Prospectively registered on 15 February 2024.

Assessment of Inhaler Satisfaction and Determinants of High Satisfaction Among Korean COPD Patients.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) recommend considering patient preference when choosing an inhaler device. However, few studies have assessed both inhaler satisfaction and factors associated with high inhaler satisfaction. Therefore, we assessed inhaler satisfaction and determinants of high satisfaction in Korean COPD patients. METHODS: COPD patients were prospectively enrolled from January 2018 to November 2019. The 308 inhalers used by the 261 participants in this study included dry powder inhalers (Turbuhaler, Breezhaler, Ellipta, Diskus, and Genuair), a soft mist inhaler (Respimat), and pressurized metered dose inhalers (pMDIs). Inhaler satisfaction was assessed by the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. High inhaler satisfaction was defined as an FSI-10 ≥ 43. RESULTS: Among 261 COPD patients, 163 (62.5%) were highly satisfied with their inhaler device. The rates of high inhaler satisfaction for Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair, Respimat, and pMDI usage were 40.0%, 67.2%, 66.7%, 50.0%, 55.6%, 63.4%, and 45.0%, respectively (P = 0.215). In univariate analyses, higher body mass index, non-current smoker, GOLD grades I and II, a modified Medical Research Council (mMRC) score < 2, lower inhaler puff burden, once daily usage of inhaler, and good inhaler adherence were associated with high inhaler satisfaction. In multivariate analyses, an mMRC score < 2, and good inhaler adherence were independently associated with high inhaler satisfaction. CONCLUSION: High inhaler satisfaction was associated with dyspnea symptom and good inhaler adherence in COPD patients. Effective strategies are needed including appropriate inhaler device selection, consideration of patient preference, and repeated inhaler education to improve patient satisfaction of inhalers.

Utility of Radial Probe Endobronchial Ultrasound Guided Transbronchial Lung Biopsy in Bronchus Sign Negative Peripheral Pulmonary Lesions.

BACKGROUND: The presence of the bronchus sign on chest computed tomography is associated with an increased diagnostic yield of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB). However, the utility of RP-EBUS-TBLB for bronchus sign negative peripheral pulmonary lesions (PPLs) remains unknown. We investigated the utility of RP-EBUS-TBLB in bronchus sign negative PPLs. METHODS: We retrospectively reviewed data from 109 patients who underwent RP-EBUS for bronchus sign negative PPLs from January 2019 to August 2020. TBLB was performed using RP-EBUS with a guide sheath and without fluoroscopy. The EBUS visualization and TBLB diagnostic yields were assessed. Multivariable logistic regression analyses were used to identify factors affecting the EBUS visualization and diagnostic yields. RESULTS: The EBUS visualization yield was 74.1% (68/109). Of the 109 lung lesions, 92 were definitively diagnosed. The overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 50.5% (55/109), 34.9% (29/83), 100% (26/26), 100% (29/29), and 32.5% (26/80), respectively. In multivariable analyses, the size of the lesion (≥ 20 mm; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.16-5.93; P = 0.021) and the distance from the pleura (> 10 mm; OR, 2.37; 95% CI, 1.02-5.52; P = 0.045) were associated with EBUS visualization. Regarding diagnostic yield, having the probe within the lesion (OR, 28.50; 95% CI, 6.26-129.85; P < 0.001) and a solid lesion (OR, 14.58; 95% CI, 2.64-80.38; P = 0.002) were associated with diagnostic success. Pneumothorax and hemoptysis occurred in 3.7% (4/109) and 0.9% (1/109), respectively, of the patients. CONCLUSION: RP-EBUS-TBLB using a GS can be considered a diagnostic method in bronchus sign negative solid PPLs. Having the probe within the lesion and a solid lesion were important for diagnostic success. Complication rates were acceptable.

Quantitative Assessment of Chest CT Patterns in COVID-19 and Bacterial Pneumonia Patients: a Deep Learning Perspective.

BACKGROUND: It is difficult to distinguish subtle differences shown in computed tomography (CT) images of coronavirus disease 2019 (COVID-19) and bacterial pneumonia patients, which often leads to an inaccurate diagnosis. It is desirable to design and evaluate interpretable feature extraction techniques to describe the patient's condition. METHODS: This is a retrospective cohort study of 170 confirmed patients with COVID-19 or bacterial pneumonia acquired at Yeungnam University Hospital in Daegu, Korea. The Lung and lesion regions were segmented to crop the lesion into 2D patches to train a classifier model that could differentiate between COVID-19 and bacterial pneumonia. The K-means algorithm was used to cluster deep features extracted by the trained model into 20 groups. Each lesion patch cluster was described by a characteristic imaging term for comparison. For each CT image containing multiple lesions, a histogram of lesion types was constructed using the cluster information. Finally, a Support Vector Machine classifier was trained with the histogram and radiomics features to distinguish diseases and severity. RESULTS: The 20 clusters constructed from 170 patients were reviewed based on common radiographic appearance types. Two clusters showed typical findings of COVID-19, with two other clusters showing typical findings related to bacterial pneumonia. Notably, there is one cluster that showed bilateral diffuse ground-glass opacities (GGOs) in the central and peripheral lungs and was considered to be a key factor for severity classification. The proposed method achieved an accuracy of 91.2% for classifying COVID-19 and bacterial pneumonia patients with 95% reported for severity classification. The CT quantitative parameters represented by the values of cluster 8 were correlated with existing laboratory data and clinical parameters. CONCLUSION: Deep chest CT analysis with constructed lesion clusters revealed well-known COVID-19 CT manifestations comparable to manual CT analysis. The constructed histogram features improved accuracy for both diseases and severity classification, and showed correlations with laboratory data and clinical parameters. The constructed histogram features can provide guidance for improved analysis and treatment of COVID-19.

Prognostic Factors for Severe Coronavirus Disease 2019 in Daegu, Korea.

BACKGROUND: Since its first detection in December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection has spread rapidly around the world. Although there have been several studies investigating prognostic factors for severe COVID-19, there have been no such studies in Korea. METHODS: We performed a retrospective observational study of 110 patients with confirmed COVID-19 hospitalized at a tertiary hospital in Daegu, Korea. Demographic, clinical, laboratory, and outcome data were collected and analyzed. Severe disease was defined as a composite outcome of acute respiratory distress syndrome, intensive care unit care, or death. RESULTS: Diabetes mellitus (odds ratio [OR], 19.15; 95% confidence interval [CI], 1.90-193.42; P = 0.012), body temperature ≥ 37.8°C (OR, 10.91; 95% CI, 1.35-88.36; P = 0.025), peripheral oxygen saturation < 92% (OR, 33.31; 95% CI, 2.45-452.22; P = 0.008), and creatine kinase-MB (CK-MB) > 6.3 (OR, 56.84; 95% CI, 2.64-1,223.78, P = 0.010) at admission were associated with higher risk of severe COVID-19. The likelihood of development of severe COVID-19 increased with an increasing number of prognostic factors. CONCLUSION: In conclusion, we found that diabetes mellitus, body temperature ≥ 37.8°C, peripheral oxygen saturation < 92%, and CK-MB > 6.3 are independent predictors of severe disease in hospitalized COVID-19 patients. Appropriate assessment of prognostic factors and close monitoring to provide the necessary interventions at the appropriate time in high-risk patients may reduce the case fatality rate of COVID-19.

Prognostic Accuracy of the SIRS, qSOFA, and NEWS for Early Detection of Clinical Deterioration in SARS-CoV-2 Infected Patients.

BACKGROUND: The case fatality rate of coronavirus disease 2019 (COVID-19) is estimated to be between 4.3% and 11.0%. Currently there is no effective antiviral treatment for COVID-19. Thus, early recognition of patients at high risk is important. METHODS: We performed a retrospective observational study of 110 patients with severe acute respiratory syndrome coronavirus 2 infection. We compared the effectiveness of three scoring systems: the Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS) systems, for predicting the prognosis of COVID-19. The area under the receiver operating characteristic curve (AUROC) was used for these assessments, and Kaplan-Meier survival curves were used to identify the cumulative risk for 28-day mortality according to the NEWS stratification. RESULTS: For predicting 28-day mortality, NEWS was superior to qSOFA (AUROC, 0.867 vs. 0.779, P < 0.001), while there was no significant difference between NEWS and SIRS (AUROC, 0.867 vs. 0.639, P = 0.100). For predicting critical outcomes, NEWS was superior to both SIRS (AUROC, 0.918 vs. 0.744, P = 0.032) and qSOFA (AUROC, 0.918 vs. 0.760, P = 0.012). Survival time was significantly shorter for patients with NEWS ≥ 7 than for patients with NEWS < 7. CONCLUSION: Calculation of the NEWS at the time of hospital admission can predict critical outcomes in patients with COVID-19. Early intervention for high-risk patients can thereby improve clinical outcomes in COVID-19 patients.

Risk Factors Associated with Misuse of Soft Mist Inhaler in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The use of inhaled bronchodilators is the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Although the soft mist inhaler (SMI) was developed to overcome the disadvantages of pressurized metered dose and drug powder inhalers, misuse during handling has been frequently observed in many studies. However, few studies have focused on SMI misuse among patients with COPD. Thus, we aimed to assess and identify the risk factors associated with SMI misuse among patients with COPD. Patient and Methods: In this prospective, observational, cross-sectional study, we enrolled patients with COPD who were undergoing SMI treatment between January 2018 and March 2020. An advanced nurse practitioner assessed the participants' handling of the device by using a check list. Results: Among 159 participants, 136 (85.5%) reported inhaler misuse. Duration of COPD and COPD assessment test (CAT) scores were positively associated with inhaler misuse; adherence and education level were negatively associated with inhaler misuse. In the multivariable analysis, a low educational level (less than high school), high CAT score (≥ 10), and short duration of COPD (≤ 2 years) were identified as risk factors for SMI misuse. Conclusion: SMI misuse remains common among patients with COPD. Therefore, clinicians should pay close attention to their patients using SMIs, especially in the early period after the diagnosis of COPD.

Endobronchial Ultrasound Using Guide Sheath-Guided Transbronchial Lung Biopsy in Ground-Glass Opacity Pulmonary Lesions without Fluoroscopic Guidance.

Diagnosing ground-glass opacity (GGO) pulmonary lesions poses challenges. This study evaluates the utility of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) in diagnosing GGO pulmonary lesions. A total of 1651 RP-EBUS procedures were performed during the study period. This study analyzed 115 GGO lesions. The EBUS visualization yield was 80.1%. Of 115 lesions, 69 (60%) were successfully diagnosed. The average size of diagnosed lesions was significantly larger than that of undiagnosed lesions (21.9 ± 7.3 vs. 17.1 ± 6.6 mm, p < 0.001). Diagnostic yield varied by lesion size: 50.0% for lesions <20 mm, 65.1% for 20-30 mm lesions, and 85.7% for lesions >30 mm. The mixed blizzard sign on EBUS appeared in 60.6% of mixed GGO lesions, with no cases in pure GGO lesions. Multivariable analyses showed that lesion size (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.00-1.16; p < 0.001) and mixed blizzard sign on EBUS (OR, 20.92; CI, 7.50-58.31; p < 0.001) were significantly associated with diagnostic success. Pneumothorax and hemoptysis occurred in 1.7% and 2.6% of patients, respectively. RP-EBUS-TBLB without fluoroscopic guidance is a viable diagnostic approach for GGO pulmonary lesions with acceptable complications.

Durvalumab Consolidation After Chemoradiotherapy in Elderly Patients With Unresectable Stage III NSCLC: A Real-World Multicenter Study.

BACKGROUND: The PACIFIC trial demonstrated survival benefit of durvalumab after concurrent chemoradiotherapy (CCRT) in unresectable stage III non-small-cell lung cancer. Data on the effectiveness and safety of durvalumab in elderly patients is lacking. METHODS: This retrospective study was conducted between September 2017 and September 2022. Progression-free survival (PFS), overall survival (OS), recurrence patterns, first subsequent treatment after recurrence, factors associated with survival outcomes, and adverse events (AEs) were compared. RESULTS: Of the 286 patients, 120 (42.0%) were ≥ 70 years and 166 (58.0%) were < 70 years. The median PFS (17.7 vs. 19.4 months; P = .43) and median OS (35.7 months vs. not reached; P = .13) were similar between 2 groups. Proportion of patients who completed durvalumab was lower in elderly patients (27.5% vs. 39.2%; P = .040). In elderly patients, ECOG PS 0 or 1 was associated with better PFS, and being male and having received a cisplatin-based regimen during CCRT were factors associated with better and worse OS, respectively. In patients aged < 70 years, a PD-L1 ≥ 50% was associated with improved PFS and OS. Elderly patients experienced more treatment-related AEs, grade 3/4 AEs, permanent discontinuation of durvalumab, and treatment-related deaths. Among the AEs leading to permanent discontinuation or death, pulmonary AE was significantly more common in elderly patients. CONCLUSION: Durvalumab demonstrated similar outcomes in elderly compared to younger patients. However, AEs were more common in elderly patients. Thus, judicious selection of patients and chemotherapy regimens, coupled with careful AE monitoring, are important factors for ensuring optimal durvalumab treatment.

Endobronchial ultrasound-guided re-biopsy of non-small cell lung cancer with acquired resistance after EGFR tyrosine kinase inhibitor treatment.

BACKGROUND: Few studies assessed the use of endobronchial ultrasound (EBUS)-guided re-biopsy for detecting the T790M mutation after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure. METHODS: A total of 2996 EBUS procedures were performed during the study period (January 2019-June 2022). In total, 44 consecutive patients who underwent EBUS-guided re-biopsy (56 procedures) for detecting the T790M mutation were analyzed. The success rates and T790M mutation frequencies were analyzed according to the re-biopsy site and EBUS method. Multivariate logistic regression analyses were used to identify factors affecting the likelihood of the T790M mutation. RESULTS: The success rates for the mutation analyses using EBUS with a guide-sheath (EBUS-GS), EBUS guided transbronchial needle aspiration (EBUS-TBNA), and EBUS-GS with EBUS-TBNA for re-biopsy were 80.6% (29/36), 93.3% (14/15), and 100% (5/5), respectively. Patients who underwent lymph node biopsy using EBUS-TBNA had an increased rates of the T790M mutation compared with those undergoing lung biopsy using EBUS-GS (EBUS-TBNA, 60.0%; EBUS-GS with EBUS-TBNA, 40.0%; EBUS-GS, 11.1%; p < 0.001). In multivariate analysis, the use of a first-generation EGFR-TKI (odds ratio [OR], 4.29; 95% confidence interval [CI], 1.05-17.58; p = 0.043) was associated with occurrence of the T790M mutation. Re-biopsy of the metastatic site tended to be associated with a higher T790M mutation rate. Mild hemoptysis occurred in 3.6% (2/56) of the patients. CONCLUSIONS: EBUS-guided re-biopsy can be used for detecting the T790M mutation in patients who failed EGFR-TKI therapy. The T790M mutation frequency differed according to the re-biopsy site. The use of a first-generation EGFR-TKI was an independent predictor of the T790M mutation.

Low diffusion capacity predicts poor prognosis in extensive stage small cell lung cancer: a single-center analysis of 10 years.

BACKGROUND: Poor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients. METHODS: This retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco < 60% group and DLco ≥ 60% groups. OS and predictors of poor OS were analyzed. RESULTS: The median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco < 60% group. Multivariate analysis revealed that DLco < 60% (odds ratio [OR], 1.609; 95% confidence interval [CI], 1.062-2.437; P = 0.025), number of metastases (OR, 1.488; 95% CI, 1.262-1.756; P < 0.001), and < 4 cycles of first-line chemotherapy (OR, 3.793; 95% CI, 2.530-5.686; P < 0.001) were associated with poor OS. Forty (28.2%) patients received < 4 cycles of first-line chemotherapy; the most common reason for this was death (n = 22, 55%) from grade 4 febrile neutropenia (n = 15), infection (n = 5), or massive hemoptysis (n = 2). The DLco < 60% group had a shorter median OS than the DLco ≥ 60% group (10.6 ± 0.8 vs. 4.9 ± 0.9 months, P = 0.003). CONCLUSIONS: In this study, approximately one quarter of the ED-SCLC patients had DLco < 60%. Low DLco (but not forced expiratory volume in 1 s or forced vital capacity), a large number of metastases, and < 4 cycles of first-line chemotherapy were independent risk factors for poor survival outcomes in patients with ED-SCLC.

Clinical implications of wheezing in patients with chronic obstructive pulmonary disease.

Background: Studies on the prevalence of wheezing in both the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) and non-ACO groups, as well as the clinical characteristics of wheezing patients in each group, are rare. We examined the prevalence of wheezing in ACO patients and non-ACO patients, respectively. In addition, we aimed to determine clinical characteristics of patients with wheezing compared to those without wheezing in the ACO and non-ACO groups. Methods: We analyzed the data from the Korean COPD Subgroup Study (KOCOSS), a multicenter prospective cohort. We classified patients into four groups according to whether they were ACO patients or had self-reported wheezing based on the patient's answer to the COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C): ACO with wheezing, ACO without wheezing, non-ACO with wheezing, and non-ACO without wheezing. Clinical characteristics and exacerbations during 1-year follow up were compared among four groups. Results: Wheezing was present in about 56% of patients in the ACO and non-ACO groups. In both groups, patients with wheezing exhibited more severe symptoms, worse lung function, and a higher risk of exacerbation than those without wheezing. There was no association between blood eosinophil count and wheezing in both the ACO and non-ACO groups. During 1-year follow-up, the ACO with wheezing group experienced exacerbations the most frequently, followed by the non-ACO with wheezing group. Moreover, wheezing was an independent predictor of the risk of exacerbation in patients with COPD, irrespective of both the ACO phenotype and the severity of airflow limitation. The exacerbation risk was higher in COPD patients who experienced wheezing more frequently. Conclusions: Wheezing, reflecting more prominent airflow limitation and predicting exacerbation development, may serve as a severe phenotype of COPD rather than being indicative of an ACO phenotype.

Foreign-body aspiration into the lower airways in adults; multicenter study.

BACKGROUND: Foreign-body aspiration is common in children aged 6 months to 3 years. However, with the aging population and increasing prevalence of disabilities such as hemiparesis and neuromuscular diseases in adults, an increased incidence of aspiration is expected. METHODS: This was a multicenter retrospective, observational study in four major referral hospitals in Daegu, South Korea, between 2000 and 2019. We included patients aged over 18 years who were evaluated for tracheobronchial foreign-body aspiration by flexible bronchoscopy. Comorbidities, type and location of foreign body, and radiologic findings were recorded. RESULTS: Of 138 patients who underwent flexible bronchoscopy for tracheobronchial foreign body aspiration, 91 (65.9%) were men; the mean age was 66.3 (range: 29-87) years. A history of definite choking was present in 60 (43.5%) patients. The most common site of the foreign body was the right bronchus intermedius (27.5%). The most common type of aspirated foreign body was teeth (37.7%), followed by chicken bone (15.2%), nuts (14.5%) and fish bone (9.4%). Iatrogenic events accounted for 37.0% of the cases of aspiration, and the foreign body was successfully removed by flexible bronchoscopy in 91.3% of cases. CONCLUSION: Foreign-body aspiration is not rare, even in adults who do not have predisposing factors. Iatrogenic events accounted for about 40% of all cases of foreign body aspiration. In adults, flexible bronchoscopy is relatively safe and has a high success rate for foreign-body removal.

Humoral and Cellular Responses to COVID-19 Vaccines in SARS-CoV-2 Infection-Naïve and -Recovered Korean Individuals.

In the face of a global COVID-19 vaccine shortage, an efficient vaccination strategy is required. Therefore, the immunogenicity of single or double COVID-19 vaccination doses (ChAdOX1, BNT162b2, or mRNA-1273) of SARS-CoV-2-recovered individuals was compared to that of unvaccinated individuals with SARS-CoV-2 infection at least one year post-convalescence. Moreover, the immunogenicity of SARS-CoV-2-naïve individuals vaccinated with a complete schedule of Ad26.CoV2.S, ChAdOX1, BNT162b2, mRNA-1273, or ChAdOX1/BNT162b2 vaccines was evaluated. Anti-SARS-CoV-2 S1 IgG antibody (S1-IgG), pseudotyped virus-neutralizing antibody titer (pVNT50), and IFN-γ ELISpot counts were measured. Humoral immune responses were significantly higher in vaccinated than in unvaccinated recovered individuals, with a 43-fold increase in the mean pVNT50 values. However, there was no significant difference in the pVNT50 and IFN-γ ELISpot values between the single- and double-dose regimens. In SARS-CoV-2-naïve individuals, antibody responses varied according to the vaccine type: BNT162b2 and mRNA-1273 induced similar levels of S1-IgG to those observed in vaccinated, convalescent individuals; in contrast, pVNT50 was much lower in SARS-CoV-2-naïve vaccinees than in vaccinated recovered individuals. Therefore, a single dose of ChAdOX1, BNT162b2, or mRNA-1273 vaccines would be a good alternative for recovered individuals instead of a double-dose regimen.

Developing a Diagnostic Bundle for Bronchiectasis in South Korea: A Modified Delphi Consensus Study.

BACKGROUND: Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea. METHODS: A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement). RESULTS: The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers. CONCLUSION: Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.

Incidence and Prognostic Factors of Respiratory Viral Infections in Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: Severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) that require hospitalization and emergency department visits are associated with considerable morbidity and mortality. Respiratory viral infection is an important cause of severe AECOPD. We evaluated the incidence and prognostic factors of viral infection in severe AECOPD. Patients and Methods: We performed a retrospective study of 262 cases of severe AECOPD in 192 patients who required hospitalization and emergency department visits at a tertiary teaching hospital in Daegu, Korea. A multiplex polymerase chain reaction panel using a nasopharyngeal swab sample was performed to detect viral infection. Results: Viral infection was detected in 108 events (41.2%) from 96 patients. The most common virus was rhinovirus/enterovirus (27.5%), followed by influenza virus (22.5%), respiratory syncytial virus (13.3%), parainfluenza virus (12.5%), coronavirus (12.5%), metapneumovirus (7.5%), and adenovirus (4.2%). Virus-positive exacerbations, compared to virus-negative exacerbations, had a higher frequency of symptoms of rhinopharyngitis, higher neutrophil count and C-reactive protein (CRP) level, and lower eosinophil count. Multivariate analysis demonstrated that elevated CRP levels (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.24-6.15), symptoms of rhinopharyngitis (OR, 1.98; 95% CI, 1.03-3.78), low eosinophil count (OR, 1.74; 95% CI, 1.03-2.92), and inhaled corticosteroid (ICS) use (OR, 1.70; 95% CI 1.04-2.80) were associated with viral infection in severe AECOPD. Conclusion: The incidence of viral infection in severe AECOPD was 41.2%, and the most commonly detected virus was rhinovirus/enterovirus. Increased CRP level, symptoms of rhinopharyngitis, low eosinophil count, and use of ICS were associated with viral infection in severe AECOPD.

Radial probe endobronchial ultrasound-guided transbronchial lung biopsy for the diagnosis of cavitary peripheral pulmonary lesions.

BACKGROUND: Cavitary peripheral pulmonary lesions (PPLs) are often diagnosed via transthoracic needle biopsy. However, today, radial probe endobronchial ultrasound (RP-EBUS) is widely used to diagnose PPLs. The efficacy and safety of RP-EBUS-guided transbronchial lung biopsy (RP-EBUS-TBLB) used to diagnose cavitary PPLs remain poorly known. We investigated the utility of RP-EBUS-TBLB using a guide sheath (GS) without fluoroscopy to diagnose PPLs. METHODS: Of 743 RP-EBUS procedures conducted to diagnose PPLs performed at our institution from January 2019 to October 2020, we analyzed 77 cavitary PPLs. TBLB was performed using RP-EBUS with a GS without fluoroscopy. The diagnostic accuracy and complications were assessed. All lung lesions with a definitive diagnosis were included in analyses. RESULTS: The overall diagnostic accuracy was 85.7% (66/77). Of malignant lesions (n = 34), 29 (85.3%) were diagnosed successfully. Of benign lesions (n = 43), 37 (86.0%) were diagnosed successfully. In multivariate analyses, a thicker cavity wall (≥10 mm, odds ratio [OR] 14.22, 95% confidence interval [CI] 2.58-78.35, p = 0.002) and EBUS imaging with the probe within the lesion (OR 12.02, 95% CI 1.91-75.53, p = 0.008) independently affected diagnostic success. The likelihood of success increased with increasing thickness of the cavity wall (p < 0.001, test for trend). The specimens obtained for molecular confirmation of malignancy were satisfactory. There were four cases of infection (5.2%) and three cases of pneumothorax (3.9%). CONCLUSIONS: RP-EBUS-TBLB of cavitary PPLs affords high diagnostic accuracy with acceptable complication rates.

Delayed onset of mediastinitis with tracheomediastinal fistula following endobronchial ultrasound-guided transbronchial needle aspiration; A case report.

Infectious complications after endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are rare but serious. Here, we report a very rare case of delayed onset of mediastinitis with tracheomediastinal fistula after EBUS-TBNA. Surgical debridement was performed, antibiotics were administered, and the postoperative course of the patient was good. Careful monitoring is needed to prevent the possible development of infectious complications after EBUS-TBNA.