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Background. The advent of macrolides has led to therapeutic advances in the treatment of Mycobacterium avium complex lung disease (MAC-LD). The aim of this study was to elucidate the treatment outcomes of macrolide-containing regimens. Methods. We performed a systematic review and meta-analysis of published studies reporting treatment outcomes of macrolide-containing regimens for MAC-LD using the Medline, Embase, and Cochrane Library databases through 31 July 2016. The rates of treatment success, default from treatment, and adverse events of macrolide-containing regimens were assessed. Treatment success was defined as either 12 months of sustained culture negativity while on therapy or achievement of culture conversion and completion of the planned treatment without relapse. Results. In total, 16 studies involving 1462 patients were included. The rate of treatment success was 60.0% (95% confidence interval [CI], 55.1%–64.8%). The proportion of patients who defaulted from the treatment was 16.0% (95% CI, 12.3%–19.7%). When a thrice-weekly dosing schedule was available, the default rate was 12.0% (95% CI, 8.9%–15.0%). Adverse events necessitating treatment discontinuation or dosage modification of macrolides were observed in 6.4% of patients (95%, CI, 3.2%–9.5%), and decreased auditory acuity was the most common adverse event. Conclusions. Treatment outcomes of macrolide-containing regimens are relatively poor in terms of both the treatment success and default rates. The default rate could be reduced if a thrice-weekly dosing schedule is available. Clinicians should be aware of decreased auditory function as the most common adverse event associated with macrolide-containing regimens.

BackgroundSmoking has been considered an important risk factor for idiopathic pulmonary fibrosis (IPF) incidence. However, there are no population-based large-scale studies demonstrating the effects of smoking on the development of IPF. We aimed to evaluate the effect of smoking on IPF development using a nationwide population-based cohort.MethodsUsing the Korean National Health Information Database, we enrolled individuals who had participated in the health check-up service between 2009 and 2012. Participants having a prior diagnosis of IPF were excluded. The history of smoking status and quantity was collected by a questionnaire. We identified all cases of incident IPF through 2016 on the basis of ICD-10 codes for IPF and medical claims. Cox proportional hazards models were used to calculate the adjusted HR (aHR) of the development of IPF.ResultsA total of 25 113 individuals (0.11%) with incident IPF were identified out of 23 242 836 participants registered in the database. The risk of IPF was significantly higher in current and former smokers than in never smokers, with an aHR of 1.66 (95% CI 1.61 to 1.72) and 1.42 (95% CI 1.37 to 1.48), respectively. Current smokers had a higher risk of IPF than former smokers (aHR 1.17, 95% CI 1.13 to 1.21). The risk of IPF development increased as the smoking intensity and duration increased.ConclusionSmoking significantly increased the risk of IPF development. Current smokers had a higher risk of IPF than former smokers. A dose–response relationship was observed between smoking and the development of IPF.

Glutathione (GSH) plays diverse roles in the physiological processes, stress defense, growth, and development of plants. This study investigated the effects of exogenous GSH on the biochemical responses of reactive oxygen species and antioxidant levels in rice ( Oryza sativa L. cv. Dasan) seedlings under arsenic (As) stress. As treatment inhibited growth; increased the level of superoxide, hydrogen peroxide, and malondialdehyde; and enhanced the uptake of As by the roots and shoots in hydroponically grown 14-day-old seedlings. Furthermore, it reduced GSH content and GSH redox ratios, which have been correlated with the decrease in ascorbate (AsA) redox state. Whereas the exogenous application of GSH in As-treated seedlings reduced As-induced oxidative stress, improved antioxidant defense systems by maintaining antioxidant and/or redox enzyme homeostasis, and increased the AsA and GSH contents, the GSH application also increased the As translocation from the roots to the shoots. These results indicated that the increase in GSH redox state can be linked to an increase in the AsA redox ratio via the induction of the AsA–GSH cycle. Therefore, the results suggest that exogenous GSH application should be a promising approach to enhance As stress resistance in rice plants.

Abstract Introduction Metabolic syndrome is known to increase the risk of several cancers. However, the association between lung cancer and metabolic syndrome remains unclear. Thus, we investigated the impact of metabolic syndrome on the incidence of lung cancer. Methods This study enrolled participants in a health screening program provided by the Korean National Health Insurance Service between January 2009 and December 2012. The incidence of lung cancer was observed until December 2016. We analyzed the risk of lung cancer according to the presence of metabolic syndrome, metabolic syndrome components, and number of metabolic syndrome components. Results During the study, 45 635 new cases of lung cancer were recorded among 9 586 753 participants. The presence of metabolic syndrome and all its components was positively associated with the risk of lung cancer in men after multivariate adjustment (hazard ratio [HR] of metabolic syndrome 1.15; 95% confidence interval [CI], 1.12-1.18). The risk of lung cancer increased with the number of components present. The effect of metabolic syndrome on the increasing risk of lung cancer is may be higher in underweight male ever-smokers than in other participants. Conclusion Metabolic syndrome was associated with an increased risk of lung cancer in men. Moreover, the higher the number of metabolic syndrome components, the higher the risk of lung cancer.

Background. Mycobacterium abscessus and Mycobacterium massiliense are grouped as the Mycobacterium abscessus complex. The aim of this study was to elucidate the differences between M. abscessus and M. massiliense lung diseases in terms of progression rate, treatment outcome, and the predictors thereof. Methods. Between 1 January 2006 and 30 June 2015, 56 patients and patients were diagnosed with M. abscessus and M. massiliense lung diseases, respectively. The time to progression requiring treatment and treatment outcomes were compared between the 2 groups of patients, and predictors of progression and sustained culture conversion with treatment were analyzed. In addition, mediation analysis was performed to evaluate the effect of susceptibility to clarithromycin on treatment outcomes. Results. During follow-up, 21 of 56 patients with M. abscessus lung diseases and 21 of 54 patients with M. massiliense lung diseases progressed, requiring treatment. No difference was detected in the time to progression between the 2 patient groups. Lower body mass index, bilateral lung involvement, and fibrocavitary-type disease were identified as predictors of disease progression. Among the patients who began treatment, infection with M. massiliense rather than M. abscessus and the use of azithromycin rather than clarithromycin were associated with sustained culture conversion. The difference in treatment outcomes was partly mediated by the organism's susceptibility to clarithromycin. Conclusions. Progression rates were similar but treatment outcomes differed significantly between patients with lung disease caused by M. abscessus and M. massiliense. This difference in treatment outcomes was partly explained by the susceptibility of these organisms to clarithromycin.

Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined. We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59-0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76-0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19-2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk. These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.

Background The proportion of never‐smokers with non‐small cell lung cancer (NSCLC) is increasing, but that in Korea has not been well addressed in a large population. We aimed to evaluate the proportion and clinical features of never‐smokers with NSCLC in a large single institution. Methods We analyzed clinical data of 1860 consecutive patients who were newly diagnosed with NSCLC between June 2011 and December 2014. Results Of the 1860 NSCLC patients, 707 (38.0%) were never‐smokers. The proportions of women (83.7% vs. 5.6%) and adenocarcinoma (89.8% vs. 44.9%) were higher among never‐smokers than among ever‐smokers. Significantly more never‐smokers were diagnosed at a younger median age (65 vs. 68 years, P < 0.001) and earlier stage (stage I–II, 44.5% vs. 38.9%, P = 0.015) compared with ever‐smokers. Epidermal growth factor receptor mutations (57.8% vs. 24.4%, P < 0.001) and anaplastic lymphoma kinase rearrangements (7.8% vs. 2.8%, P < 0.001) were more common in never‐smokers, whereas Kirsten rat sarcoma viral oncogene homolog mutations (5.8% vs. 9.6%, P = 0.021) were less frequently encountered in never‐smokers than in ever‐smokers. Never‐smokers showed longer survival after adjusting for the favorable effects of younger age, female sex, adenocarcinoma histology, better performance status, early stage disease, being asymptomatic at diagnosis, received antitumor treatment, and the presence of driver mutations (hazard ratio, 0.624; 95% confidence interval, 0.460–0.848; P = 0.003). Conclusions More than one‐third of the Korean patients with NSCLC were never‐smokers. NSCLC in never‐smokers had different clinical characteristics and major driver mutations and resulted in longer overall survival compared with NSCLC in ever‐smokers.

To gain the fundamental understanding of deformation mechanisms in an aluminum-containing austenitic high-Mn steel (Fe-32Mn-8.9Al-0.78 C (wt.%)), in-situ straining transmission electron microscopy (TEM) analysis is conducted. The in-situ observation during the deformation demonstrates that the plastic deformation is accommodated by the pronounced planar dislocation gliding followed by the formation of slip bands (SBs) and highly dense dislocation walls (HDDWs). Experimental evidences of the glide plane softening can be obtained from the interaction between the gliding perfect dislocations and the L’1 2 ordered precipitates in the austenite matrix. Furthermore, the observation of the localized cross-slip of dislocations at the slip band intersections enables to understand why slip bands are extensively developed without mutual obstructions between the slip bands. The enhanced strain hardening rate of the aluminum-containing austenitic high-Mn steels can be attributed to the pronounced planar dislocation glides followed by formation of extensive slip band which prevent premature failure by suppressing strain localization.

Background: Preserved ratio impaired spirometry (PRISm) patients have more frequent respiratory symptoms and an increased risk of mortality. However, studies on comorbidities in these patients are lacking. Objectives: We investigated the association between PRISm and comorbidities using the Korea National Health and Nutrition Examination Survey (KNHANES). Method: This cross-sectional study included participants aged ≥50 years from the KNHANES (2007–2015). Participants who did not undergo spirometry or performed inadequately were excluded. We classified participants into 3 groups according to spirometry: PRISm (forced expiratory volume in one second [FEV1] /forced vital capacity [FVC] ≥ 0.7 and FEV1 <80%), chronic obstructive pulmonary disease (COPD) (FEV1/ FVC <0.7), and normal. Multivariate logistic regression analyses were used to evaluate the risk of comorbidities in the PRISm group compared to that in the normal group. Result: The study included 17,515 participants: 12,777 (73.0%), 1,563 (8.9%), and 3,175 (18.1%) in normal, PRISm, and COPD groups, respectively. After adjustment for known risk factors of each disease, hypertension (adjusted odds ratio [95% confidence interval]; 1.31 [1.14–1.50]), diabetes (1.51 [1.29–1.78]), hypercholesterolemia (1.20 [1.04–1.37]), obesity (1.31 [1.15–1.48]), ischemic heart disease (1.58 [1.13–2.22]), chronic renal disease (2.31 [1.09–4.88]), and thyroid disease (1.41 [1.09–1.83]) risks were significantly higher in the PRISm group than in the normal group. The average number of comorbidities was 2.45 in the PRISm group, which was higher than that in the normal (2.1) and COPD (2.03) groups (p < 0.05). Conclusion: The number of comorbidities was significantly higher in the PRISm group than in others. Hypertension, diabetes, obesity, ischemic heart disease, chronic renal disease, and thyroid disease were associated with PRISm after adjustment for risk factors.

We investigated the effect of κ-carbide precipitates on the strain hardening behavior of aged Fe–Mn-Al-C alloys by microstructure analysis. The κ-carbides-strengthened Fe–Mn-Al-C alloys exhibited a superior strength-ductility balance enabled by the recovery of the strain hardening rate. To understand the relation between the κ-carbides and strain hardening recovery, dislocation gliding in the aged alloys during plastic deformation was analyzed through in situ tensile transmission electron microscopy (TEM). The in situ TEM results confirmed the particle shearing mechanism leads to planar dislocation gliding. During deformation of the 100 h-aged alloy, some gliding dislocations were strongly pinned by the large κ-carbide blocks and were prone to cross-slip, leading to the activation of multiple slip systems. The abrupt decline in the dislocation mean free path was attributed to the activation of multiple slip systems, resulting in the rapid saturation of the strain hardening recovery. It is concluded that the planar dislocation glide and sequential activation of slip systems are key to induce strain hardening recovery in polycrystalline metals. Thus, if a microstructure is designed such that dislocations glide in a planar manner, the strain hardening recovery could be utilized to obtain enhanced mechanical properties of the material.