Jung-Wan Yoo

Purpose: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease of unknown etiology that primarily affects older adults. It is characterized by worsening dyspnea, declining lung function, and poor prognosis. This review summarizes current approaches to IPF diagnosis and treatment.Current concepts: Diagnosis requires a multidisciplinary approach integrating clinical, radiological, and, when necessary, histopathological findings. A key feature is the usual interstitial pneumonia pattern on high-resolution computed tomography and/or lung biopsy. Pirfenidone and nintedanib appear to slow the decline in lung function, including forced vital capacity (FVC), and are recommended as first-line therapies. Clinical trials of novel agents are ongoing, with several recent trials yielding promising findings. Non-pharmacological management, including pulmonary rehabilitation, oxygen therapy, and symptom control, is essential for comprehensive care. Lung transplantation remains the only curative option and should be considered in eligible patients.Discussion and conclusion: Early, accurate IPF diagnosis is essential and requires a multidisciplinary approach that integrates clinical, radiological, and histopathological findings, as outlined in the 2018 and 2022 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines. Pirfenidone and nintedanib remain the cornerstone antifibrotic agents for pharmacological treatment, slowing FVC decline and reducing the risk of acute exacerbation. Emerging agents, including nerandomilast and inhaled treprostinil, have shown promise in recent phase 3 clinical trials. Non-pharmacological strategies, including pulmonary rehabilitation, oxygen therapy, and palliative care, are integral to comprehensive management. Despite these advances, IPF remains a progressive and fatal disease, underscoring the need for continued research into novel therapeutic strategies.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization.Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge.Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty.Conclusion: Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: Endothelial activation and stress index (EASIX) reflects endothelial dysfunction or damage. Because endothelial dysfunction is one of the key mechanisms, a few studies have shown the clinical usefulness of original and age-adjusted EASIX (age-EASIX) in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical utility of age-EASIX in predicting intensive care unit (ICU) mortality in critically ill patients with COVID-19 in South Korea.Methods: Secondary analysis was performed using clinical data retrospectively collected from 22 nationwide hospitals in South Korea between January 1, 2020, and August 31, 2021. Patients were at least 19 years old and admitted to the ICU for severe COVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactate dehydrogenase (U/L)×creatinine (mg/dL)/platelet count (109 cells/L)] and age-EASIX (EASIX×age) were calculated and log2-transformed.Results: The mean age of 908 critically ill patients with COVID-19 was 67.4 years with 59.7% male sex. The mean log2 age-EASIX was 7.38±1.45. Non-survivors (n=222, 24.4%) in the ICU had a significantly higher log2 age-EASIX than of survivors (8.2±1.52 vs. 7.1±1.32, p<0.001). log2 age-EASIX was significantly associated with ICU mortality (odds ratio, 1.541; 95% confidence interval, 1.322 to 1.796; p<0.001) and had a better area under the receiver operating characteristic curve than of the sequential organ failure assessment (SOFA) score in predicting ICU mortality (0.730 vs. 0.660, p=0.001).Conclusion: Age-EASIX is significantly associated with ICU mortality and has better discriminatory ability than the SOFA score in predicting ICU mortality.

Background: Development of frailty at hospital discharge affects clinical outcomes in in critically ill survivors with COVID-19 who had no frailty before hospitalization. Objective: Describe the prevalence of new frailty using clinical frailty scale (CFS) and evaluate its associated factors in critically ill survivors with COVID-19 who never had pre-hospitalization frailty. Methods: Clinical data of nationwide retrospective cohort collected from 22 hospitals during January 1 2020 thorough Augus 31 2021 were secondarily analyzed. Patients were at least 19 years old and survived to discharge after admission to ICU due to severe COVID-19. Development of new frailty was defined as CFS was 5 or greater at hospital discharge. Results: Among 669 critically ill and non-frail patients with COVID-19 who admitted to ICU and survived at discharge, mean age was 65.2 ± 12.8 year old and the male sex was 62.5%. 50.2% patients received mechanical ventilation. Mean CFS of total patients at admission was 2.4 ± 0.9. New frailty developed in 27.8% (186/483). Patients with new frailty were older and had more comorbidities. They also stayed longer in ICU and hospital compared to those without frailty. In multivariable analysis, older age, cardiovascular disease, CFS 3-4 before hospitalization, increased C reactive protein, longer duration of treatment of corticosteroid, use of MV and ECMO were identified as associated factors for new frailty. Conclusion: New frailty at hospital discharge is common and associated with several modifiable factors in critically ill patients with severe COVID-19.

Kim TW, et al. J Korean Med Sci. 2024 Feb;39:e75. https://doi.org/10.3346/jkms.2024.39.e75

Repetitive sequence-based PCR (rep-PCR) is a potential epidemiological technique that can provide high-throughput genotype fingerprints of heterogeneous Mycobacterium strains rapidly. Previously published rep-PCR primers, which are based on nucleotide sequences of Gram-negative bacteria may have low specificity for mycobacteria. Moreover, it was difficult to ensure the continuity of the study after the commercial rep-PCR kit was discontinued. Here, we designed a novel rep-PCR for Mycobacterium intracellulare, a major cause of nontuberculous mycobacterial pulmonary disease with frequent recurrence. We screened the 7,645 repeat sequences for 200 fragments from the genome of M. intracellulare ATCC 13950 in silico, finally generating five primers with more than 90% identity for a total of 226 loci in the genome. The five primers could make different band patterns depending on the genome of three different M. intracellulare strains using an in silico test. The novel rep-PCR with the five primers was conducted using 34 bacterial samples of 7 species containing 25 M. intracellulare clinical isolates, compared with previous published rep-PCRs. This shows distinguished patterns depending on species and blotting assay for 6 species implied the sequence specificity of the five primers. The Designed rep-PCR had a 95–98% of similarity value in the reproducibility test and showed 7 groups of fingerprints in M. intracellulare strains. Designed rep-PCR had a correlation value of 0.814 with VNTR, reference epidemiological method. This study provides a promising genotype fingerprinting method for tracing the recurrence of heterogeneous M. intracellulare.

Yoo H, et al. J Korean Med Sci. 2023 Mar;38(14):e106. https://doi.org/10.3346/jkms.2023.38.e106

Background: Serum biomarkers associated with severe non-cystic fibrosis (CF) bronchiectasis are currently lacking. We assessed the association of serum fibrinogen, adiponectin, and angiopoietin-2 levels with the severity and exacerbation of bronchiectasis. Methods: Serum levels of fibrinogen, adiponectin, and angiopoietin-2 were measured and compared in patients with stable non-CF bronchiectasis (n = 61) and healthy controls (n = 16). The correlations between the three biomarkers and the bronchiectasis severity index (BSI) or FACED scores were assessed. Univariate and multivariate linear regression analyses were performed to identify variables independently associated with BSI and FACED scores in patients with bronchiectasis. Additionally, the exacerbation-free survival was compared between groups of patients with high and low fibrinogen levels, while the predictors of exacerbation were analyzed using Cox proportional hazards regression. Results: Patients with non-CF bronchiectasis carried higher fibrinogen (3.00 ± 2.31 vs. 1.52 ± 0.74 µg/mL; p = 0.016) and adiponectin (12.3 ± 5.07 vs. 9.17 ± 5.30 µg/mL; p = 0.031) levels compared with healthy controls. The serum level of angiopoietin-2 was comparable between the two groups (1.49 ± 0.96 vs. 1.21 ± 0.79 ng/mL, p = 0.277). Correlations of adiponectin and angiopoietin-2 with BSI and FACED scores were not significant. However, there were significant correlations between fibrinogen and both BSI (r = 0.428) and FACED scores (r = 0.484). Multivariate linear regression analysis revealed that fibrinogen level was an independent variable associated with both BSI and FACED scores. A total of 31 (50.8%) out of 61 patients experienced exacerbation during the follow-up period of 25.4 months. Exacerbation-free survival was significantly longer in patients with low fibrinogen levels than in those with high fibrinogen (log-rank test, p = 0.034). High fibrinogen levels and Pseudomonas colonization were independent risk factors for future exacerbation (HR 2.308; p = 0.03 and HR 2.555; p = 0.02, respectively). Conclusions: Serum fibrinogen, but not adiponectin or angiopoietin-2, is a potential biomarker closely associated with the severity and exacerbation of non-CF bronchiectasis.

Although a few studies comparing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and non-SARS-CoV-2 respiratory viruses have been reported, clinical features and outcomes comparing SARS-CoV-2 and non-SARS-CoV-2 respiratory viruses associated acute respiratory distress syndrome (ARDS) are still lacking. We retrospectively identified patients with SARS-CoV-2 (November 2020 to January 2022) and non-SARS-CoV-2 respiratory viruses associated ARDS (February 2015 to November 2020) at a single tertiary hospital. Their clinical data were obtained by medical record review. All viral infections were confirmed by RT-PCR. Thirty-one SARS-CoV-2 and seventy-one patients with non-SARS-CoV-2 respiratory viruses associated ARDS patients were identified. Influenza (62%) was the most common in non-SARS-CoV-2 respiratory viruses associated ARDS patients. Patients with SARS-CoV-2 were more likely to be female and had higher body mass index, lower clinical frailty, APACHE II, and SOFA score than those with non-SARS-CoV-2 respiratory viruses. All patients with SARS-CoV-2 were treated with corticosteroids and used more high-flow nasal oxygen than those with non-SARS-CoV-2 respiratory viruses. The concomitant respiratory bacterial infection was significantly higher in non-SARS-CoV-2 respiratory viruses than SARS-CoV-2. Although there were no significant differences in the 28-, 60-day, and in-hospital mortality rates between SARS-CoV-2 and non-SARS-CoV-2 respiratory viruses associated ARDS, the duration of mechanical ventilation and length of hospital stay were significantly longer in patients with SARS-CoV-2 than those with non-SARS-CoV-2 respiratory viruses. Although the severity of illness and the concomitant bacterial infection rate were lower in patients with SARS-CoV-2 associated ARDS, mortality rates did not differ from non-SARS-CoV-2 respiratory viruses associated ARDS.