For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the ‘missing’ heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.
Lung cancer remains the most common cause of cancer-related deaths worldwide. Although there are many possible treatments, including targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors, new therapeutic strategies are needed to improve clinical outcomes. Immunotherapy through the use of immune checkpoint inhibitors has provided one of the most important breakthroughs in the management of solid tumors, including lung cancers, and has shown promising results in numerous clinical trials. This review will present the current status of immunotherapy for lung cancer and future perspectives on these treatments.
Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only first-line drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient’s condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.
Background: Chronic cough is defined as a cough lasting more than 8 weeks and socio-economic burden of chronic cough is enormous. The characteristics of chronic cough in Korea are not well understood. The Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) published guidelines on cough management in 2014. The current study evaluated the clinical characteristics of chronic cough in Korea and the efficacy of the KATRD guidelines. Methods: This was a multi-center, retrospective observational study conducted in Korea. The participants were over 18 years of age. They had coughs lasting more than 8 weeks. Subjects with current pulmonary diseases, smokers, ex-smokers with more than 10 pack-years or who quit within the past 1 year, pregnant women, and users of cough-inducing medications were excluded. Evaluation and management of cough followed the KATRD cough-management guidelines. Results: Participants with chronic cough in Korea showed age in the late forties and cough duration of more than 1 year. Upper airway cough syndrome was the most common cause of cough, followed by cough-variant asthma (CVA). Gastro-esophageal reflux diseases and eosinophilic bronchitis were less frequently observed. Following the KATRD cough-management guidelines, 91.2% of the subjects improved after 4 weeks of treatment. Responders were younger, had a longer duration of cough, and an initial impression of CVA. In univariate and multivariate analyses, an initial impression of CVA was the only factor related to better treatment response. Conclusion: The causes of chronic cough in Korea differed from those reported in other countries. The current Korean guidelines proved efficient for treating Korean patients with chronic cough.
Background: Fractional exhaled nitric oxide (FeNO) is regarded as a potential biomarker for identifying eosinophilic inflammation. We aimed to evaluate the clinical implication of FeNO and its influence on inhaled corticosteroids (ICS) prescription rate in Korean chronic obstructive pulmonary disease (COPD) patients. Methods: FeNO level and its association with clinical features were analyzed. Changes in the prescription rate of ICS before and after FeNO measurement were identified. Results: A total of 160 COPD patients were divided into increased (≥25 parts per billion [ppb], n=74) and normal (<25 ppb, n=86) FeNO groups according to the recommendations from the American Thoracic Society. Compared with the normal FeNO group, the adjusted odds ratio for having history of asthma without wheezing and with wheezing in the increased FeNO group were 2.96 (95% confidence interval [CI], 1.40–6.29) and 4.24 (95% CI, 1.37–13.08), respectively. Only 21 out of 74 patients (28.4%) with increased FeNO prescribed ICS-containing inhaler and 18 of 86 patients (20.9%) with normal FeNO were given ICS-containing inhaler. Previous exacerbation, asthma, and wheezing were the major factors to maintain ICS at normal FeNO level and not to initiate ICS at increased FeNO level. Conclusion: Increased FeNO was associated with the history of asthma irrespective of wheezing. However, FeNO seemed to play a subsidiary role in the use of ICS-containing inhalers in real-world clinics, which was determined with prior exacerbation and clinical features suggesting Th2 inflammation.
Background: Programmed death-ligand 1 (PD-L1) expression is tested by immunohistochemistry (IHC)—22C3, SP263, and SP142. The aim of this study is to evaluate the correlation among the three methods of PD-L1 IHC in non-small cell lung cancer (NSCLC) and clinical significance of PD-L1 expression in lung adenocarcinoma with an epidermal growth factor receptor (EGFR)–tyrosine kinase domain mutation. Methods: The results of 230 patients who were pathologically confirmed as having NSCLC; tested using PD-L1 IHC 22C3, SP263, and SP142 methods; and evaluated via the peptide nucleic acid clamping method to confirm EGFR mutation, were analyzed in this study. Results: 164 patients underwent both the SP263 and 22C3 tests. There was a significant positive correlation between the outcomes of the two tests (Spearman correlation coefficient=0.912, p<0.001), with a derived regression equation as follows: 22C3=15.2+0.884×SP263 (R2=0.792, p<0.001). There was no relationship between the expression of PD-L1 and clinical parameters, including EGFR–tyrosine kinase inhibitor (TKI) mutation. The PD-L1 expression in patients treated with EGFR-TKI yielded a 2-month-shorter progression period than that in the PD-L1–negative group. However, this did not reach statistical significance (PD-L1<1% vs. PD-L1≥1%, 10 months vs. 8 months). Conclusion: The results of the 22C3 and those of SP263 methods were in good correlation with one another. Since the PD-L1 expression is not influenced by the EGFR mutation, it is necessary to perform a PD-L1 test to set the treatment direction in the patients with EGFR-mutant NSCLC.
Background: Circulating tumor cells (CTCs) are frequently detected in patients with advanced-stage malignant tumors and could act as a predictor of poor prognosis. However, there is a paucity of data on the relationship between CTC number and primary tumor volume in patients with lung cancer. Therefore, our study aimed to evaluate the relationship between CTC number and primary tumor volume in patients with lung adenocarcinoma. Methods: We collected blood samples from 21 patients with treatment-naive lung adenocarcinoma and 73 healthy individuals. To count CTCs, we used a CTC enrichment method based on fluid-assisted separation technology. We compared CTC numbers between lung adenocarcinoma patients and healthy individuals using propensity score matching, and performed linear regression analysis to analyze the relationship between CTC number and primary tumor volume in lung adenocarcinoma patients. Results: CTC positivity was significantly more common in lung adenocarcinoma patients than in healthy individuals (p<0.001). The median primary tumor volume in CTC-negative and CTC-positive patients was 10.0 cm3 and 64.8 cm3, respectively. Multiple linear regression analysis showed that the number of CTCs correlated with primary tumor volume in lung adenocarcinoma patients (β=0.903, p=0.002). Further subgroup analysis showed a correlation between CTC number and primary tumor volume in patients with distant (p=0.024) and extra-thoracic (p=0.033) metastasis (not in patients with distant metastasis). Conclusion: Our study showed that CTC numbers may be associated with primary tumor volume in lung adenocarcinomas patients, especially in those with distant metastasis.
Background: In January 2015, South Korea’s government raised the cigarette tax, and the retail price of cigarettes abruptly increased by 80% compared to the previous year. This research aimed to determine the effect of this increase on smoking cessation among South Korean smokers. Methods: We analyzed data collected by the 2013–2015 South Korea National Health and Nutrition Examination Survey of 15,203 South Koreans over 19 years old using regression analysis. We examined the recent non-smoking period of nonsmoking people, prepared according to the survey, and analyzed the recent smoking cessation ratio. Results: Among smokers, from 2013 to 2014, the smoking cessation rate was 7.2%, and it increased to 9.9% in 2015 after the increase in the cigarette tax. In 2015, the recent smoking cessation rate was higher among people over the age of 60 (odds ratio [OR], 2.67) compared to those between the ages of 40 and 49. The recent smoking cessation rate was higher among people with below elementary education (OR, 2.28) and above university education (OR, 1.94) compared to high school, higher for those with apartments (OR, 1.74) compared to general type residences, and higher among those with a household income in the low-middle quartile (Q2) (OR, 2.32) compared to the highest quartile (Q4). Conclusion: This innovative policy including increase in cigarette prices affected smoking cessation, and its impact varied by sub-group of smokers in South Korea.
Background: Use of appropriate antibiotics for the treatment of pneumonia is integral in patients admitted to intensive care units (ICUs). Although it is recommended that empirical treatment regimens should be based on the local distribution of pathogens in patients with suspected hospital-acquired pneumonia, few studies observe patients admitted to ICUs with nursing home–acquired pneumonia (NHAP). We found factors associated with the use of inappropriate antibiotics in patients with pneumonia admitted to the ICU via the emergency room (ER). Methods: We performed a retrospective cohort study of 83 pneumonia patients with confirmed causative bacteria admitted to ICUs via ER March 2015–May 2017. We compared clinical parameters, between patients who received appropriate or inappropriate antibiotics using the Mann-Whitney U, Pearson’s chi-square, and Fisher’s exact tests. We investigated independent factors associated with inappropriate antibiotic use in patients using multivariate logistic regression. Results: Among 83 patients, 30 patients (36.1%) received inappropriate antibiotics. NHAP patients were more frequently treated with inappropriate antibiotics than with appropriate antibiotics (47.2% vs. 96.7%, p<0.001). Methicillin-resistant Staphylococcus aureus was more frequently isolated from individuals in the inappropriate antibiotics–treated group than in the appropriate antibiotics–treated group (7.5% vs. 70.0%, p<0.001). In multivariate analysis, NHAP was independently associated with the use of inappropriate antibiotics in patients with pneumonia admitted to the ICU via ER. Conclusion: NHAP is a risk factor associated with the use of inappropriate antibiotics in patients with pneumonia admitted to the ICU via the ER.
Background: Same-day sputum microcopy is recommended in areas where sputum smear microscopy external quality assessment (EQA) is effectively implemented and sturdy. In Addis Ababa, the status of EQA and drop-out of same-day sputum smear microcopy has not yet been assessed. The objective of this study was to assess the quality of same-day sputum smear microscopy and diagnostic drop-out of presumptive tuberculosis (TB) patients in health facilities (HFs) across Addis Ababa, Ethiopia. Methods: Amulti-analysis was conducted from September 2016 to July 2017 to determine the status of external quality assessment and diagnostic drop-out of presumptive TB patients registered for same-day sputum smear microscopy. Data was coded and entered in Microsoft Excel, and subsequently transferred and analyzed using SPSS version 20.0. Results: The drop-out of same-day sputum smear microscopy was 209 (6.2%). More than 33% of the specimens collected for purposes of same-day sputum smears were of poor quality. Among the selected HFs for the study: 13 (46.4%) used filter reagents prior to sputum smear staining while 75% of the selected HFs for the study used smear microscopy services interruption in a year. The sensitivity and specificity of the HFs participating in regional quality assessment scheme for the diagnosis of TB was 97.4% and 99.6%, respectively. Conclusion: The diagnostic drop-out of same-day sputum smear microscopy was high in Addis Ababa. Strengthening EQA, competency-based laboratory professionals training on sputum smear microscopy might reduce the reading errors in sputum smear. Awareness creation of the community on the benefits gained from completion of specimen provision for the same-day approach decreases diagnostic drop-out and enhances TB control program.
Background: The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. Methods: Fifty-four patients with TB/TM and HIV co-infection were enrolled for this study. Group 1 comprised of 23 patients treated with E and H intravenously, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. The concentrations of H and E in blood serum were detected using a chromatographic method. Results: A significant improvement in the clinical symptoms and X-ray signs in patients treated intravenously with H and E was observed and compared to group 2. The sputum Mycobacterium tuberculosis positivity was observed during the second month of the treatment in 25.0% of patients from group 1 and 76.1% of the patients from the control group (p=0.003). In addition, nine patients (39.1%) died up to 6 months when H and E were prescribed intravenously compared with 22 (70.9%) in group 2 (p=0.023). Conclusion: In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.