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Vol.87 No.1

Andrea R. Levine, M.D., M.S.(Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD) ; Carolyn S. Calfee, M.D., M.A.S.(Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA) pp.1-11 https://doi.org/10.4046/trd.2023.0104
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Abstract

Acute respiratory distress syndrome (ARDS) is a common cause of severe hypoxemiadefined by the acute onset of bilateral non-cardiogenic pulmonary edema. The diagnosisis made by defined consensus criteria. Supportive care, including prevention offurther injury to the lungs, is the only treatment that conclusively improves outcomes. The inability to find more advanced therapies is due, in part, to the highly sensitive butrelatively non-specific current syndromic consensus criteria, combining a heterogenouspopulation of patients under the umbrella of ARDS. With few effective therapies,the morality rate remains 30% to 40%. Many subphenotypes of ARDS have been proposedto cluster patients with shared combinations of observable or measurable traits. Subphenotyping patients is a strategy to overcome heterogeneity to advance clinicalresearch and eventually identify treatable traits. Subphenotypes of ARDS have beenproposed based on radiographic patterns, protein biomarkers, transcriptomics, and/ormachine-based clustering of clinical and biological variables. Some of these strategieshave been reproducible across patient cohorts, but at present all have practical limitationsto their implementation. Furthermore, there is no agreement on which strategy isthe most appropriate. This review will discuss the current strategies for subphenotypingpatients with ARDS, including the strengths and limitations, and the future directionsof ARDS subphenotyping.

Youlim Kim, M.D., Ph.D.(Division of Pulmonary and Allergy, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea) ; Sang Hyuk Kim, M.D.(Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Dongguk University Gyeongju Hospital, Dongguk University College of Medicine, Gyeongju) pp.12-21 https://doi.org/10.4046/trd.2023.0103
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Abstract

The management of severe asthma presents a significant challenge in asthma treatment. Over the past few decades, remarkable progress has been made in developingnew treatments for severe asthma, primarily in the form of biological agents. Theseadvances have been made possible through a deeper understanding of the underlyingpathogenesis of asthma. Most biological agents focus on targeting specific inflamma tory pathways known as type 2 inflammation. However, recent developments have introduceda new agent targeting upstream alarmin signaling pathways. This opens up newpossibilities, and it is anticipated that additional therapeutic agents targeting variouspathways will be developed in the future. Despite this recent progress, the mainstay ofasthma treatment has long been inhalers. As a result, the guidelines for the appropriateuse of biological agents are not yet firmly established. In this review, we aim to emphasizethe current state of biological therapy for severe asthma and provide insights intoits future prospects.

Chae Uk Chung, M.D., Ph.D.(Chungnam National University Hospital) ; Yeonhee Park, M.D., Ph.D.(Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon,) pp.22-30 https://doi.org/10.4046/trd.2023.0037
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Abstract

Tumor immune evasion is a complex process that involves various mechanisms, suchas antigen recognition restriction, immune system suppression, and T cell exhaustion. The tumor microenvironment contains various immune cells involved in immune evasion. Recent studies have demonstrated that granulocyte colony-stimulating factor(G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce immuneevasion in lung cancer by modulating neutrophils and myeloid-derived suppressorcells. Here we describe the origin and function of G-CSF and GM-CSF, particularlytheir role in immune evasion in lung cancer. In addition, their effects on programmeddeath-ligand 1 expression and clinical implications are discussed.

Jung Seop Eom, M.D., Ph.D.(Pusan National University School of Medicine) ; Mi-Hyun Kim, M.D., Ph.D.(Pusan National University School of Medicine) ; Soo Han Kim, M.D., Ph.D.(Department of Internal Medicine, Pusan National University School of Medicine, Busan, Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea) ; Min Ki Lee, M.D., Ph.D.(Pusan National University School of Medicine) pp.31-39 https://doi.org/10.4046/trd.2023.0085
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Abstract

After the successful development of targeted therapy and immunotherapy for the treatmentof advanced-stage non-small cell lung cancer (NSCLC), these innovative treatmentoptions are rapidly being applied in the adjuvant setting for early-stage NSCLC. Some adjuvants that have recently been approved include osimertinib for epidermalgrowth factor receptor-mutated tumors and atezolizumab and pembrolizumab forselected patients with resectable NSCLC. Numerous studies on various targeted therapiesand immunotherapy with or without chemotherapy are currently ongoing in theadjuvant setting. However, several questions regarding optimal strategies for adjuvanttreatment remain unanswered. The present review summarizes the available literature,focusing on recent advances and ongoing trials with targeted therapy and immunotherapyin the adjuvant treatment of early-stage NSCLC.

Jin Woo Song, M.D., Ph.D.(Asan Medical Center, University of Ulsan College of Medicine, Seoul) ; Jae Ha Lee, M.D., Ph.D.(Department of Internal Medicine, Inje University Haeundae Paik Hospital) pp.40-51 https://doi.org/10.4046/trd.2023.0087
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Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumoniawith a very poor prognosis. Accurate diagnosis of IPF is essential for good outcomesbut remains a major medical challenge due to variability in clinical presentationand the shortcomings of existing diagnostic tests. Medical history collection is the firstand most important step in the IPF diagnosis process; the clinical probability of IPF is high if the suspected patient is 60 years or older, male, and has a history of cigarettesmoking. Systemic assessment for connective tissue disease is essential in the initialevaluation of patients with suspected IPF to identify potential causes of interstitial lungdisease (ILD). Radiologic examination using high-resolution computed tomographyplays a pivotal role in the evaluation of patients with ILD, and prone and expiratory computedtomography images can be considered. If additional tests such as surgical lungbiopsy or transbronchial lung cryobiopsy are needed, transbronchial lung cryobiopsyshould be considered as an alternative to surgical lung biopsy in medical centers withexperience performing this procedure. Diagnosis through multidisciplinary discussion(MDD) is strongly recommended as MDD has become the cornerstone for diagnosisof IPF, and the scope of MDD has expanded to monitoring of disease progression andsuggestion of appropriate treatment options.

Seok-Ho Hong, Ph.D.(Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon) ; Ji-Hye Jung, B.S.(Departments of Internal Medicine, Kangwon National University School of Medicine, Chuncheon) ; Se-Ran Yang, Ph.D.(Departments of Thoracic and Cardiovascular Surgery, Kangwon National University School of Medicine, Chuncheon) ; Woo Jin Kim, M.D., Ph.D.(Department of Internal Medicine, Kangwon National University School of Medicine) ; Chin Kook Rhee, M.D., Ph.D.(The Catholic University of Korea) pp.52-64 https://doi.org/10.4046/trd.2023.0131
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Abstract

Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive functional features of in vivo alveolar tissue. In particular, the incorporation of immunecells such as macrophages into hPSC-AO systems is crucial for disease modeling andsubsequent drug screening. In this review, we summarize current methods for differentiatingalveolar epithelial cells from hPSCs followed by AO generation and their applicationsin disease modeling, drug testing, and toxicity evaluation. In addition, we reviewhow current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellularheterogeneity, and maturity. pulmonary disease, and respiratory infections injure the alveoli; the damage evoked ismostly irreversible and occasionally leads to death. Achieving a detailed understandingof the pathogenesis of these fatal respiratory diseases has been hampered by limitedaccess to human alveolar tissue and the differences between mice and humans. Thus,the development of human alveolar organoid (AO) models that mimic in vivo physiologyand pathophysiology has gained tremendous attention over the last decade. In recentyears, human pluripotent stem cells (hPSCs) have been successfully employed togenerate several types of organoids representing different respiratory compartments,including alveolar regions. However, despite continued advances in three-dimensionalculture techniques and single-cell genomics, there is still a profound need to improvethe cellular heterogeneity and maturity of AOs to recapitulate the key histological and

Hye Jung Park, M.D., Ph.D.(Departments of 1Internal Medicine and Yonsei University College of Medicine, Seoul, Korea) ; Yong Jun Choi, M.D.(1Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul) ; Min Jae Lee, M.D.(Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul) ; Min Kwang Byun, M.D., Ph.D.(Department of Internal Medicine, Gangnam Severance Hospital) ; Sangho Park, B.S.(1Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul) ; Jimyung Park, M.D., Ph.D.(Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul) ; Dongil Park, M.D., Ph.D.(Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon) ; Sang-Hoon Kim, M.D., Ph.D.(Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul) ; Young Sam Kim, M.D., Ph.D.(Severance Hospital, Younsei University Health System, Yonsei University College of Medicine, Seoul) ; Seong Yong Lim, M.D., Ph.D.(Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul) ; Kwang Ha Yoo, M.D. Ph.D.(Konkuk University School of Medicine) ; Ki-Suck Jung, M.D., Ph.D(Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang) pp.65-79 https://doi.org/10.4046/trd.2023.0028
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Abstract

Background: Exhaled condensates contain inflammatory biomarkers; however, theirroles in the clinical field have been under-investigated. Methods: We prospectively enrolled subjects admitted to pulmonology clinics. Wecollected exhaled breath condensates (EBC) and analysed the levels of six and 12biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively. Results: Among the 123 subjects, healthy controls constituted the largest group (81participants; 65.9%), followed by the preserved ratio impaired spirometry group (21patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strongpositive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specificversion of St. George’s Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725,p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). GranzymeB showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078,p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positivecorrelation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophiland basophil counts showed positive correlations with pro-collagen I alpha 1(ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forcedexpiratory volume in 1 second (FEV1)/forced vital capacity demonstrated significantcorrelation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1alpha (ρ=0.3897 and p=0.0068). FEV1 exhibited significant correlation with CCL11/eotaxin(ρ=0.4445 and p=0.0017). Conclusion: Inflammatory biomarkers in EBC might be useful to predict quality of lifeconcerning respiratory symptoms and serologic markers. Further studies are needed.

Hend M. Esmaeel, M.B.B.S., M.D.(Department of Chest Diseases and Tuberculosis, Faculty of Medicine Sohag University, Sohag, Egypt) ; Kamal A. Atta, M.B.B.S., M.D.(Department of Chest Diseases and Tuberculosis, Faculty of Medicine Sohag University, Sohag, Egypt) ; Safiya Khalaf, M.B.B.S.(Department of Chest Diseases and Tuberculosis, Faculty of Medicine Sohag University, Sohag, Egypt) ; Doaa Gadallah, M.B.B.S., M.D.(Department of Chest Diseases and Tuberculosis, Faculty of Medicine Sohag University, Sohag, Egypt) pp.80-89 https://doi.org/10.4046/trd.2023.0030
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Abstract

Background: There are many methods of evaluating diaphragmatic function, includingtrans-diaphragmatic pressure measurements, which are considered the key rule of diagnosis. We studied the clinical usefulness of chest ultrasonography in evaluating stablechronic obstructive pulmonary disease (COPD) patients and those in exacerbation,focusing on diaphragmatic measurements and their correlation with spirometry andother clinical parameters. Methods: In a prospective case-control study, we enrolled 100 COPD patients dividedinto 40 stable COPD patients and 60 patients with exacerbation. The analysis included20 age-matched controls. In addition to the clinical assessment of the study population,radiological evaluation included chest radiographs and chest computed tomography. Transthoracic ultrasonography (TUS) was performed for all included subjects. Results: Multiple A lines (more than 3) were more frequent in COPD exacerbation thanin stable patients, as was the case for B-lines. TUS significantly showed high specificity,negative predictive value, positive predictive value, and accuracy in detecting pleuraleffusion, consolidation, pneumothorax, and lung mass. Diaphragmatic measurementswere significantly lower among stable COPD subjects than healthy controls. Diaphragmaticthickness and excursion displayed a significant negative correlation with bodymass index and the dyspnea scale, and a positive correlation with spirometry measures. Patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) groupD showed lower diaphragmatic measurements (thickness and excursion). Conclusion: The TUS of COPD patients both in stable and exacerbated conditions andthe assessment of diaphragm excursion and thickness by TUS in COPD patients andtheir correlations to disease-related factors proved informative and paved the way forthe better management of COPD patients.

Larry Ellee Nyanti, M.R.C.P.I.(Medical Department, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu) ; Muhammad Aklil Abd Rahim, Dr.P.H.(Department of Public Health Medicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu) ; Nai-Chien Huan, M.R.C.P.(Department of Respiratory Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia) pp.91-99 https://doi.org/10.4046/trd.2023.0107
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Abstract

Background: Tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) areoften difficult to differentiate owing to the overlapping clinical features. Observationalstudies demonstrate that the ratio of lactate dehydrogenase to adenosine deaminase(LDH/ADA) is lower in TPE compared to PPE, but integrated analysis is warranted. Methods: We conducted a systematic review to evaluate the diagnostic accuracy of theLDH/ADA ratio in differentiating TPE and PPE. We explored the PubMed and Scopusdatabases for studies evaluating the LDH/ADA ratio in differentiating TPE and PPE. Results: From a yield of 110 studies, five were included for systematic review. The cutoffvalue for the LDH/ADA ratio in TPE ranged from <14.2 to <25. The studies demonstratedhigh heterogeneity, precluding meta-analysis. Quality Assessment of DiagnosticAccuracy Studies Tool 2 assessment revealed a high risk of bias in terms of patientselection and index test. Conclusion: LDH/ADA ratio is a potentially useful parameter to differentiate betweenTPE and PPE. Based on the limited data, we recommend an LDH/ADA ratio cutoff valueof <15 in differentiating TPE and PPE. However, more rigorous studies are needed tofurther validate this recommendation.

Hyun-Kyung Lee, M.D., Ph.D.(Inje University Busan Paik Hospital, Busan, Korea) ; Hyo Jin Kim, M.D.(Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan) ; Hongyeul Lee, M.D.(Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan) ; Ji Young Yang, M.D.(Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan) ; Jae Ha Lee, M.D.(Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan,) ; Seung Won Ra, M.D., Ph.D.(Division of Pulmonary Medicine, Department of Internal Medicine, Ulsan University Hospital) ; SungMin Hong, M.D.(Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan) ; Ho Young Lee, M.D.(1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan) ; Sung Hyun Kim, M.D.(1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan) ; Mi-Yeong Kim, M.D., Ph.D.(Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan) pp.100-114 https://doi.org/10.4046/trd.2023.0077
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Abstract

Background: Long-term oxygen therapy (LTOT) improves the survival of patients withhypoxemia due to chronic respiratory diseases. The clinical outcomes of LTOT arestrongly associated with patient adherence. To improve the adherence of patients,physicians have focused on the efficacy of LTOT. However, poor adherence may stemfrom patients’ perceptions of LTOT. Herein we evaluated patients’ perceptions of LTOTaffecting adherence. Methods: We conducted a cross-sectional survey study using descriptive, open, andclosed-ended questionnaire. Patients using oxygen therapy (OT) or requiring it butavoiding OT responded to the questionnaires at three university hospitals. Results: Seventy-nine patients responded to the questionnaires. The number of patientsusing home and portable OT was 69 (93%) and 37 (46.3%), respectively. Patientswith good adherence were 22 (30.1%). Among patients with good adherence, 90.9%used oxygen according to physicians’ prescriptions whereas only 37.3% of those withpoor adherence followed physicians’ prescriptions (p<0.01). The reasons for avoidingusing home OT were fear of permanent use (50%), unwanted attention (40%), and lackof symptoms (40%). They avoided portable OT because of unwanted attention (39%),heaviness (31.7%), and lack of symptoms (21.6%). Conclusion: Patients on LTOT had the perception of the misunderstanding the effectsof OT and of psychosocial barriers to initiate or use LTOT. Considering these findings,health professionals need to provide effective education on the purpose of LTOT toimprove patient adherence to OT and provide sufficient support for the management ofpsychosocial barriers in patients using LTOT.

Tuberculosis & Respiratory Diseases