There is a considerable number of individuals who exhibit features of both asthma and chronic obstructive pulmonary disease (COPD), defined as asthma-COPD overlap (ACO). Many studies have reported that these patients have a greater burden of symptoms, including cough and dyspnea, and experience more exacerbations and hospitalizations than those with non-ACO COPD or asthma. Although diagnostic criteria for ACO have not yet been clearly established, their clinical significance remains to be determined. As interest in ACO grows, related studies have been conducted in South Korea as well. The present review summarizes ACO-related studies in South Korea to better understand Korean ACO patients and guide further research. Several cohort studies of asthma and COPD and population-based studies for ACO were reviewed and the key results from demographics, clinical features, lung function, biomarkers, treatment, and prognosis were summarized.
Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.
Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents and surgical approaches may be beneficial in patients with CPFE, but further studies are needed.
Background: Farinelli breathing (FB) exercise is a typical breathing exercise used by singers. This study aimed to compare effects of FB exercise and diaphragmatic breathing (DB) exercise on respiratory function and symptoms in patients with chronic obstructive pulmonary disease (COPD).Methods: Sixteen patients aged 51–80 years with mild or moderate COPD were recruited for this study. They were divided into two groups: DB group (n=8) and FB group (n=8). Both groups received complete breathing exercise training five times per week for 8 weeks. Their respiratory functions, COPD symptoms, cytokine levels, and oxidative stress variables were analyzed during pre- and post-tests. Dependent variables were compared between pre- and post-tests using paired t-tests. An independent t-test was used to compare variables between the groups. Differences were considered significant at p<0.05.Results: The maximal expiratory pressure (MEP), maximum oxygen consumption (VO2max), and COPD Assessment Test (CAT) scores changed significantly in the DB group after the 8-week intervention compared to those at pre-test, whereas force vital capacity, forced expiratory volume in the first second, maximum voluntary ventilation, maximal inspiratory pressure (MIP), MEP, VO2max, CAT score, tumor necrosis factor-α, and malondialdehyde level changed significantly in the FB group at post-test compared to those at pre-test. Moreover, both MIP and MEP in the FB group were significantly higher than those in the DB group.Conclusion: FB exercise improved respiratory functions and COPD symptoms of patients with COPD. It might be an alternative breathing exercise in pulmonary rehabilitation programs for patients with COPD.
Background: The expression of calcium signaling pathway molecules is altered in various carcinomas, which are related to the proliferation and altered characteristics of cancer cells. However, changes in calcium signaling in anti-cancer drugresistant cells (bearing a T790M mutation in epidermal growth factor receptor [EGFR]) remain unclear.Methods: Afatinib-mediated changes in the level of store-operated Ca2+ entry (SOCE)-related proteins and intracellular Ca2+ level in non–small cell lung cancer cells with T790M mutation in the EGFR gene were analyzed using western blot and ratiometric assays, respectively. Afatinib-mediated autophagic flux was evaluated by measuring the cleavage of LC3B-II. Flow cytometry and cell proliferation assays were conducted to assess cell apoptosis and proliferation.Results: The levels of SOCE-mediating proteins (ORAI calcium release-activated calcium modulator 1 [ORAI1], stromal interaction molecule 1 [STIM1], and sarco/endoplasmic reticulum Ca2+ ATPase [SERCA2]) decreased after afatinib treatment in non–small cell lung cancer cells, whereas the levels of SOCE-related proteins did not change in gefitinibresistant non–small cell lung cancer cells (PC-9/GR; bearing a T790M mutation in EGFR ). Notably, the expression level of SOCE-related proteins in PC-9/GR cells was reduced also responding to afatinib in the absence of extracellular Ca2+. Moreover, extracellular Ca2+ influx through the SOCE was significantly reduced in PC-9 cells pre-treated with afatinib than in the control group. Additionally, afatinib was found to decrease the level of SOCE-related proteins through autophagic degradation, and the proliferation of PC-9GR cells was significantly inhibited by a lack of extracellular Ca2+.Conclusion: Extracellular Ca2+ plays important role in afatinib-mediated autophagic degradation of SOCE-related proteins in cells with T790M mutation in the EGFR gene and extracellular Ca2+ is essential for determining anti-cancer drug efficacy.
Background: The remarkable efficacy of osimertinib in non‒small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy.Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed.Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7–50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30–0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12–0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib.Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.
Background: One goal of the End tuberculosis (TB) Strategy is to see no TB-affected households experiencing catastrophic costs. Therefore, it is crucial for TB-elimination programs to identify catastrophic costs and their main drivers in order to establish appropriate health and social measures. This study aimed to measure the percent of catastrophic costs experienced by Egyptian TB patients and to identify its determinants.Methods: We conducted a prospective cohort study with 151 Egyptian TB patients recruited from two chest dispensaries from the Cairo governate from May 2019 to May 2020. We used a validated World Health Organization TB patient-cost tool to collect data on patients’ demographic information, household income, and direct and indirect expense of seeking TB treatment. We considered catastrophic TB costs to be total costs exceeding 20% of the household’s annual income.Results: Of the patients, 33% experienced catastrophic costs. The highest proportion of the total came in the pretreatment stage. Being the main breadwinner, experiencing job loss, selling property, and the occurrence of early coronavirus disease 2019 lockdown were independent determinants of the incidence of catastrophic costs. Borrowing money and selling property were the most-often reported coping strategies adopted.Conclusion: Despite the availability of free TB care under the Egyptian National TB Program, nearly a third of the TB patients incurred catastrophic costs. Job loss and being the main breadwinner were among the significant predictors of catastrophic costs. Social protection mechanisms, including cash assistance and insurance coverage, are necessary to achieve the goal of the End TB Strategy.
Background: Post-tuberculosis (TB) sequelae is a commonly encountered clinical entity, especially in high TB burden countries. This may represent chronic anatomic sequelae of previously treated TB, with frequent symptomatic presentation. This pilot study was aimed to investigate the pulmonary functions and systemic inflammatory markers in patients with post-TB sequelae (PTBS) and to compare them with post-TB without sequelae (PTBWS) participants and healthy controls.Methods: A total of 30 participants were enrolled, PTBS (n=10), PTBWS (n=10), and healthy controls (n=10). Pulmonary function tests included spirometry and measurement of airway impedance by impulse oscillometry. Serum levels of matrix metalloproteinase (MMP)-1, transforming growth factor-β, and interferon-γ were estimated.Results: Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC, and peak expiratory flow were significantly lower in PTBS as compared to controls. SVC and FEV1 were significantly less in PTBS as compared to PTBWS. Total airway impedance (Z5), total airway resistance (R5), central airway resistance (R20), area of reactance (Ax), and resonant frequency (Fres) were significantly higher and respiratory reactance at 5 and 20 Hz (X5, X20) were significantly lower in PTBS as compared to PTBWS. Spirometry parameters correlated with impulse oscillometry parameters in PTBS. Serum MMP-1 level was significantly higher in PTBS as compared to other groups.Conclusion: Significant pulmonary function impairment was observed in PTBS, and raised serum MMP-1 levels compared with PTBWS and healthy controls. Follow-up pulmonary function testing is recommended after treatment of TB for early diagnosis and treatment of PTBS.
Background: The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients.Methods: Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015.Results: A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-agephysiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.Conclusion: In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.
Background: The aim of this study was to evaluate the long-term (5-year) clinical outcomes of patients who received intensive care unit (ICU) treatment using Korean nationwide data.Methods: All patients aged >18 years with ICU admission according to Korean claims data from January 2008 to December 2010 were enrolled. These enrolled patients were followed up until December 2015. The primary outcome was ICU mortality.Results: Among all critically ill patients admitted to the ICU (n=323,765), patients with cancer showed higher ICU mortality (18.6%) than those without cancer (13.2%, p<0.001). However, there was no significant difference in ICU mortality at day 28 among patients without cancer (14.5%) and those with cancer (lung cancer or hematologic malignancies) (14.3%). Compared to patients without cancer, hazard ratios of those with cancer for ICU mortality at 5 years were: 1.90 (1.87–1.94) for lung cancer; 1.44 (1.43–1.46) for other solid cancers; and 3.05 (2.95–3.16) for hematologic malignancies.Conclusion: This study showed that the long-term survival rate of patients with cancer was significantly worse than that of general critically ill patients. However, short term outcomes of critically ill patients with cancer were not significantly different from those of general patients, except for those with lung cancer or hematologic malignancies.