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The onion maggot, Delia antiqua (Meigen), is one of the most important insect pests to agricultural crops within Allium genus, such as onions and garlic, worldwide. This study was conducted to understand the seasonal abundance of this pest, with special reference to the hot summer effect (HSE), which was incorporated into the model of summer diapause termination (SDT). We assumed that hot summer temperatures arrested the development of pupae during summer diapause. The estimated SDT curve showed that it occurred below a high-temperature limit of 22.1 °C and peaked at 16 °C. Accordingly, HSE resulted in delaying the late season fly abundance after summer, namely impacting the third generation. In Jinju, South Korea, the activity of D. antiqua was observed to cease for more than two months in the hot summer and this pattern was well described by model outputs. In the warmer Jeju Island region, Korea, the late season emergence was predicted to be greatly delayed, and D. antiqua did not exhibit a specific peak in the late season in the field. The abundance patterns observed in Korea were very different from those in countries such as the United States, Canada, and Germany. These regions are located at a much higher latitude (42° N to 53° N) than Korea (33° N to 35° N), and their HSE was less intense, showing overlapped or slightly separated second and third generation peaks. Consequently, our modeling approach for the summer diapause termination effectively explained the abundance patterns of D. antiqua in the late season. Also, the model will be useful for determining spray timing for emerging adults in late summer as onion and garlic are sown in the autumn in Korea.

Temperature-dependent development of Helicoverpa armigera (Hüber) fed with an artificial diet was studied at different temperatures. The instar pathway (IPW) defined as the number of instars prior to pupation significantly affected larval development time, with higher IPW leading to longer larval development time. The IPW was determined at the fifth instar to proceed to 6-7 IPW, when the development time of fifth instar was largely shortened. Accordingly, the development time after the fourth instar was combined (i.e., the fifth-seventh instar) as a single stage to simplify the various IPW and applied to develop phenology models. In linear models, the lower threshold temperature (LT) and thermal constant (degree-days, DD) for each stage were estimated. DD based on the common LT of 10.7 °C were 43, 287, and 191 DD for eggs, larvae, and pupae, respectively. DD model (253.6 DD with LT 10.3 °C for larvae and 181.5 DD with 11.6 °C for pupae) showed good performance in predicting the 50% occurrences of pupae and adults. In nonlinear models, stage transition (ST) models were constructed using the development rate and distribution models to simulate the proportion of individuals shifted from one stage to the next stage. The ST model showed good performance, indicating an average discrepancy of 1.74 days at 25%, 50%, 75%, and 90% adult emergence. Our models developed here will be useful to predict the phenology of H. armigera in the field and to construct a deterministic population model in the future., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT , RTEL1 , common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Fall armyworm, Spodoptera frugiperda (J.E. Smith), is a notorious invasive pest native to subtropical and tropical regions in the Western Hemisphere. It has recently invaded and established in south Asian countries and in South Korea only seasonally. Longevity, survival, and fecundity of fall armyworm were examined at different temperatures (16, 20, 24, 28, and 32°C) and an oviposition model was developed. The maximum observed fecundity was 1,485 eggs per female at 22.0°C, which decreased to ca. 815 eggs at 32.0°C. Female longevity decreased as the temperature increased up to 24°C, and then was constant around 13-14 d until temperature reached 32°C, ranging from 33.1 d at 16.0°C to 13.1 d at 32.0°C. Temperature-dependent total fecundity (TDF) was well described by the extreme value function. Age-specific cumulative oviposition rate (AOR) and age-specific survival rate (ASR) curves were fitted to logistic and sigmoid functions, respectively. The model of female adults' aging rate (1/mean longevity) as a function of temperature was used to calculate the physiological age of fall armyworm females in AOR and ASR models. Three temperature-dependent components of TDF, AOR, and ASR were incorporated to construct the oviposition model, and it was simulated to project corn damage with tentative parameters. When 10 fall armyworm females were assumed, a total of 68-74 corn ears with kernel damage were predicted. Such loss was estimated to be US$75-83 currently in the Korean market., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Androdioecy (the coexistence of males and hermaphrodites) is a rare mating system for which the evolutionary dynamics are poorly understood. Here, we investigate the cottony cushion scale, Icerya purchasi, one of only three reported cases of androdioecy in insects. In this species, female-like hermaphrodites have been shown to produce sperm and self-fertilize. However, males are ocassionally observed as well. In a large genetic analysis, we show for the first time that, although self-fertilization appears to be the primary mode of reproduction, rare outbreeding events do occur in natural populations, supporting the hypothesis that hermaphrodites mate with males and hence androdioecy is the mating system of I. purchasi. Thus, this globally invasive pest insect appears to enjoy the colonization advantages of a selfing organism while also benefitting from periodic reintroduction of genetic variation through outbreeding with males., (© 2021 The Authors. Evolution published by Wiley Periodicals LLC on behalf of The Society for the Study of Evolution.)

Rationale: In recent decades, diagnosis and treatment recommendations for idiopathic pulmonary fibrosis (IPF) have changed. In Korea, the average life expectancy has increased, unmet healthcare needs have been reduced, and the number of computed tomographic examinations performed has nearly doubled. The Korean Interstitial Lung Disease Study Group conducted a nationwide cohort study for idiopathic interstitial pneumonia, including IPF, and established a registry for IPF. Objectives: Using study data collected by the study group, this study aimed to evaluate longitudinal changes in clinical features, diagnosis, treatment, and mortality and analyze the extent to which changes in medication usage affected IPF-associated mortality. Methods: The study population included newly diagnosed patients with IPF from a cohort study (January 2002 to September 2008, n  = 1,839, 2008 group) and prospective registry (January 2012 to August 2018, n  = 1,345, 2018 group). Survival curves were estimated using the Kaplan-Meier method, and Cox regression models were used to identify mortality-associated risk factors in each group. Results: The 2018 group was younger, had fewer symptoms, had less honeycombing, underwent more serologic autoimmune marker and pulmonary function tests, had higher oxygen partial pressure and lower carbon dioxide partial pressure values, was less frequently diagnosed by surgical biopsy, and had better survival than the 2008 group. Steroid use and conservative care declined, whereas N -acetylcysteine use increased in this group. Antifibrotic agents were used in only the 2018 group. In the 2008 group, N -acetylcysteine was associated with lower mortality, whereas conservative care was associated with higher mortality. In the 2018 group, the use of antifibrotic agents was associated with lower mortality, and steroid use was associated with higher mortality. The survival rates in the 2008 and 2018 non-antifibrotic agent subgroups were similar. Conclusions: This study analyzed national IPF cohort data spanning 17 years. In clinical practice, the IPF diagnosis was made earlier, steroid and immunosuppressive agent use was reduced, and antifibrotic agents were administered. The survival of patients with IPF has improved over the decades, and antifibrotic use was consistently associated with improved survival.Clinical trial registered with clinicaltrials.gov (NCT04160715).

The Japanese pine sawyer, Monochamus alternatus Hope (Coleoptera: Cerambycidae), transfers the pine wood nematode, Bursaphelenchus xylophilus (Steiner and Buhrer) that causes pine wilt disease (PWD), especially in Asian countries. The key for the control of PWD is primarily focused on vector management. Thus, understanding the exact life history of M. alternatus is required. Since the late 1980s, the life cycle of M. alternatus has been accepted under the assumption that the final larvae pass four instars in the field. This study is revising the previous error for the life cycle hypothesis of M. alternatus by finding various instar pathways, which pathway is defined as the number of instars that larvae pass through prior to pupation. We confirm experimentally that the overwintered fourth or fifth instar larvae directly pupate to emerge as adults, indicating the presence of four and five instar pathways, respectively. The selection of instar pathway might be determined primarily by habitat temperature. This information will be useful to explain the variation of life history in M. alternatus populations worldwide based on the thermal environments, and also can be served to predict the northern distribution limit by applying the threshold degree-days for the completion of four instar pathway.

Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. Methods: We performed deep targeted resequencing (3.69 Mb of DNA) in cases ( n  = 3,624) and control subjects ( n  = 4,442) across genes and regions previously associated with disease. We tested for associations between disease and 1 ) individual common variants via logistic regression and 2 ) groups of rare variants via sequence kernel association tests. Measurements and Main Results: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant rs35705950, with an odds ratio of 5.45 (95% confidence interval, 4.91-6.06) for one copy of the risk allele and 18.68 (95% confidence interval, 13.34-26.17) for two copies of the risk allele ( P  = 9.60 × 10 -295 ). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in the TERT and RTEL1 gene regions in the risk of IPF, and found that the FAM13A and TERT regions have independent common and rare variant signals. Conclusions: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions, and these genetic variants focus on biological mechanisms of host defense and cell senescence.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright©2019. The Korean Academy of Tuberculosis and Respiratory Diseases.)

Background and Objective: Combined pulmonary fibrosis and emphysema (CPFE) is characterized by preserved lung volume and slower lung function decline. However, it is unclear at what extent emphysema begins to impact respiratory physiology and prognostic characteristics in idiopathic pulmonary fibrosis (IPF). We estimated the extent of emphysema that could be used to define CPFE in IPF., Methods: The extent of emphysema was observed on high-resolution computed tomography scans and measured by a texture-based automated quantification system in 209 IPF patients. We analysed the impact of differences in the extent of emphysema on the annual decline rate and prognostic significance of lung function parameters., Results: The extent of emphysema was ≥5% in 53 patients (25%), ≥10% in 23 patients (11%) and ≥15% in 12 patients (6%). Patients with emphysema to an extent of ≥5% were more frequently men and ever-smokers; they had more preserved lung volume and lower forced vital capacity (FVC) decline rates than those with no or trivial emphysema. The FVC decline rate was a significant predictor of mortality in patients with no or trivial emphysema (hazard ratio (HR): 0.933, P < 0.001) and in patients with an extent of emphysema ≥5% (HR: 0.906, P < 0.001). However, diffusing capacity of the lung for carbon monoxide (DL CO ) was the most significant prognostic factor in those patients with an extent of emphysema ≥10% (HR: 0.972, P = 0.040) and ≥15% (HR: 0.942, P = 0.023). A 10% cut-off value for the extent of emphysema created the most significant difference in the annual FVC decline rate in IPF patients., Conclusion: In IPF, emphysema to an extent of ≥10% affects both the annual decline rate and the prognostic significance of FVC. This extent could be used to define CPFE., (© 2018 Asian Pacific Society of Respirology.)

The objective of this study was to determine the number of instars of Monochamus alternatus Hope (Coleoptera: Cerambycidae) larvae by comparing their head capsule widths (HCW) published in previous studies, as well as additional laboratory experiments. Larvae of M. alternatus showed repeated molting in the laboratory. Most larvae ceased their development at the 10th instar stage. Frequency distributions of HCW for the first, second, and third instar larvae were clearly separated while those of the fourth through 11th instar larvae largely overlapped between successive instars in our results. The HCW values for the first, second, and third instar larvae directly measured for each instar in our study indicated that they were more precise than those of previous reports based on field-collected HCW which might have missed HCW of the first instar larvae or wrongly determined HCW for some instars. Unlike the reports of four instars of previous studies, M. alternatus larvae passed five instars in the field, which was confirmed by the discovery of five pairs of mandibles in the feeding gallery and pupal chamber. Also, the comparative study for the frequency distributions of HCW revealed that most M. alternatus larvae passed five instars. Consequently, the average sizes of HCW for their first, second, and third instar larvae are newly suggested to be 0.896 ± 0.069, 1.291 ± 0.131, and 1.707 ± 0.165 mm (mean ± SD) ., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America.)

Background: Although phase 3 trials showed significant efficacy and acceptable safety profiles for pirfenidone in mild-to-moderate idiopathic pulmonary fibrosis (IPF), data on advanced IPF are limited., Objectives: The study aimed to evaluate the efficacy and safety of pirfenidone in advanced IPF patients., Methods: The clinical data of 138 IPF patients (advanced group: 27%) treated with pirfenidone were retrospectively reviewed and compared between advanced and non-advanced groups. Advanced IPF was defined as (1) forced vital capacity (FVC) < 50% predicted or (2) diffusing capacity for carbon monoxide < 30% predicted., Results: The mean treatment duration was 51.3 weeks, and lung function analysis was performed in 81 patients (17 in the advanced group). Changes in FVC and total lung capacity (TLC) were significantly reduced at 6 months after treatment in both the advanced (ΔFVC [6 months]: -6.3 [before] vs. 0.7% predicted [after]; ΔTLC: -5.3 vs. 0.8) and non-advanced (ΔFVC: -3.4 vs. 0.5; ΔTLC: -3.1 vs. -0.9) groups. The rate of decline in FVC and TLC was significant before treatment, but not after treatment in the advanced (FVC: -1.27 [before] vs. 0.21% predicted/month [after]; TLC: -0.89 vs. -0.15) and non-advanced (FVC: -0.60 vs. -0.20; TLC: -0.54 vs. -0.17) groups. The advanced group showed a similar rate of adverse events (AEs) (78.4 vs. 88.1%, p = 0.270), but more serious AEs (40.5 vs. 10.9%, p < 0.001) including death (24.3 vs. 5.0%, p = 0.002)., Conclusions: In advanced IPF, pirfenidone showed similar efficacy and safety to non-advanced IPF except for serious AEs, which may be due to the advanced status itself., (© 2018 S. Karger AG, Basel.)

Background: Lymphangioleiomyomatosis is a rare disease caused by unregulated activation of mammalian target of rapamycin (mTOR) signalling pathway. Sirolimus showed efficacy in a phase 3 trial of patients with lymphangioleiomyomatosis, but the optimal dose remains unclear., Methods: We investigated the efficacy and safety of low-dose compared with conventional-dose sirolimus. Clinical data of 39 patients with lymphangioleiomyomatosis (mean age, 34.8 years; median treatment period, 29.6 months) who received sirolimus were retrospectively reviewed. Low-dose sirolimus was defined as any dose that maintained mean blood trough levels lower than those maintained with conventional doses (5-15 ng/mL)., Results: Fifty-one percent of patients received low-dose therapy. The rate of decline in lung function decreased after treatment in the whole group (forced expiratory volume in 1 s [FEV 1 ], - 0.12 ± 0.47 [before] vs. 0.24 ± 0.48% predicted/month [after], p = 0.027; diffusing capacity for carbon monoxide [DLco], - 0.33 ± 0.61 vs. 0.03 ± 0.26% predicted/month, p = 0.006) compared with before treatment. In the low-dose group, the rate of decline in FEV 1 (- 0.08 ± 0.38 [before] vs. 0.19 ± 0.51% predicted/month [after], p = 0.264) and DLco (-0.13 ± 0.62 vs. 0.02 ± 0.28% predicted/month, p = 0.679) showed a numeric trend towards improvement after treatment; however, the conventional-dose group showed significant improvement in FEV 1 (- 0.26 ± 0.54 [before] vs. 0.22 ± 0.38 [after] % predicted/month, p = 0.024) and DLco (- 0.55 ± 0.58 vs. 0.04 ± 0.25% predicted/month, p = 0.002) after treatment. Adverse events (AEs) occurred in 89.7% of patients and the most common AEs was hypercholesterolaemia (43.6%), followed by stomatitis (35.9%). The occurrences of AE were similar between the low- and conventional-dose groups (85.0% vs. 94.7%, p = 0.605)., Conclusions: Low-dose sirolimus may stabilise lung function decline in lymphangioleiomyomatosis patients, but its efficacy appears to be inferior to that of conventional-dose sirolimus.

Background: Phase 3 trials have shown that nintedanib reduces the decline in forced vital capacity (FVC) in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF) with acceptable safety profiles; however, its effects on advanced IPF are unclear. We investigated the efficacy and safety of nintedanib in patients with advanced IPF., Methods: Prospective data were obtained from 108 IPF patients administered at least one dose of nintedanib. Of these patients, 47.2% had advanced IPF (FVC < 50% predicted, or diffusing capacity < 30% predicted)., Results: The median treatment duration was 42.2 weeks. Nintedanib significantly reduced the decline rate in both FVC (- 0.55% [before] vs. -0.32% [after] predicted/month, p = 0.020) and total lung capacity (TLC) (- 0.35% vs. -0.06% predicted/month, p < 0.001) in all patients. A significant improvement in FVC decline rate after treatment was also observed in the advanced group (- 0.77% vs. -0.22% predicted/month, p = 0.003), but not in the non-advanced group (- 0.41% vs. -0.33% predicted/month, p = 0.564). Adverse events occurred in 97.2% of the cohort, including diarrhoea (50.0%) and anorexia (45.4%). Following adjustment for treatment duration, no inter-group difference in odds ratio was observed for the occurrence of adverse events. However, the advanced group showed a higher frequency of treatment interruption (68.0% vs. 40.0%), mainly as a result of disease progression (47.1% vs. 36.4%)., Conclusions: The efficacy and safety profiles of nintedanib in the advanced group were comparable to those in the non-advanced group except for a higher frequency of discontinuation, which may be due to the advanced status itself.

Models can be useful to help understand population dynamics of insects under diverse environmental conditions and in developing strategies to better manage pest species. Adult longevity and fecundity of Helicoverpa armigera (Hübner) were evaluated against a wide range of constant temperatures (15, 20, 25, 30, 35, and 37.5°C). The modified Sharpe and DeMichele model described adult aging rate and was used to estimate adult physiological age. Maximum fecundity of H. armigera was 973 eggs per female at 25°C decreasing to 72 eggs per female at 37.5°C. The relationship between adult fecundity and temperature was well described by an extreme value function. Age-specific cumulative oviposition rate and age-specific survival rate were well described by a two-parameter Weibull function and sigmoid function, respectively. An oviposition model was developed using three temperature-dependent components: total fecundity, age-specific oviposition rate, and age-specific survival rate. The oviposition model was validated against independent field data and described the pattern of field occurrence of H. armigera egg numbers very well. Our model will be a useful component for population modeling of H. armigera and can be independently used for the timing of sprays in management programs targeting this key pest species.

The clinical course of idiopathic pulmonary fibrosis (IPF) is difficult to predict, partly owing to its heterogeneity. Composite physiologic index (CPI) and gender-age-physiology (GAP) models are easy-to-use predictors of IPF progression. This study aimed to compare the predictive values of these two models. From 2003 to 2007, the Korean Interstitial Lung Disease (ILD) Study Group surveyed ILD patients using the 2002 ATS/ERS criteria. A total of 832 patients with IPF were enrolled in this study. CPI was calculated as follows: 91.0 - (0.65 × %DL CO ) - [0.53 × %FVC + [0.34 × %FEV 1 . GAP stage was calculated based on gender (0-1 points), age (0-2 points), and two physiologic lung function parameters (0-5 points). The two models had similar significant predictive values for patients with IPF (p < 0.001). The area under the curve (AUC) was higher for CPI than GAP for prediction of 1-, 2-, and 3-year mortality in this study. The AUC was higher for surgically diagnosed IPF patients than for clinically diagnosed patients. However, neither CPI nor GAP yielded good predictions of outcomes; the AUC was approximately 0.61~0.65. Although both CPI and GAP stage are significantly useful predictors for IPF, they have limited capability to accurately predict outcomes.

Aims: Autoimmune conditions such as rheumatoid arthritis-related interstitial lung disease (RA-ILD) have been linked to the existence of emphysema in never-smokers. We aimed to quantify emphysema prevalence in RA-ILD never-smokers and investigate whether combined pulmonary fibrosis and emphysema (CPFE) results in a worsened prognosis independent of baseline disease extent., Methods: RA-ILD patients presenting to the Royal Brompton Hospital (n=90) and Asan Medical Center (n=155) had CT's evaluated for a definite usual interstitial pneumonia (UIP) pattern, and visual extents of emphysema and ILD., Results: Emphysema, identified in 31/116 (27%) RA-ILD never-smokers, was associated with obstructive functional indices and conformed to a CPFE phenotype: disproportionate reduction in gas transfer (DLco), relative preservation of lung volumes. Using multivariate logistic regression, adjusted for patient age, gender and ILD extent, emphysema presence independently associated with a CT-UIP pattern in never-smokers (0.009) and smokers (0.02). On multivariate Cox analysis, following adjustment for patient age, gender, DLco, and a CT-UIP pattern, emphysema presence (representing the CPFE phenotype) independently associated with mortality in never-smokers (p=0.04) and smokers (p<0.05)., Conclusion: 27% of RA-ILD never-smokers demonstrate emphysema on CT. Emphysema presence in never-smokers independently associates with a definite CT-UIP pattern and a worsened outcome following adjustment for baseline disease severity., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The effects of corticosteroid-based therapy in patients with idiopathic nonspecific interstitial pneumonia (iNSIP), and factors affecting treatment outcome, are not fully understood. We aimed to investigate the long-term treatment response and factors affecting the treatment outcome in iNSIP patients from a multi-center study in Korea., Methods: The Korean interstitial lung disease (ILD) Study Group surveyed ILD patients from 2003 to 2007. Patients were divided into two groups to compare the treatment response: response group (forced vital capacity (FVC) improves ≥10% after 1 year) and non-response group (FVC <10%). Factors affecting treatment response were evaluated by multivariate logistic regression analysis., Results: A total of 261 patients with iNSIP were enrolled, and 95 patients were followed-up for more than 1 year. Corticosteroid treatment was performed in 86 patients. The treatment group showed a significant improvement in lung function after 1-year: FVC, 10.0%; forced expiratory volume (FEV 1 ), 9.8%; diffusing capacity of the lung for carbon monoxide (DLco), 8.4% (p < 0.001). Sero-negative anti-nuclear antibody (ANA) was significantly related with lung function improvement. Sero-positivity ANA was significantly lower in the response group (p = 0.013), compared to that in the non-response group. A shorter duration of respiratory symptoms at diagnosis was significantly associated with a good response to treatment (p = 0.018)., Conclusion: Treatment with corticosteroids and/or immunosuppressants improved lung function in iNSIP patients, which was more pronounced in sero-negative ANA and shorter symptom duration patients. These findings suggest that early treatment should be considered in iNSIP patients, even in an early disease stage.

Background: This study aimed to investigate clinical characteristics of Korean PAP patients and to examine the potential risk factors of PAP., Methods: We retrospectively reviewed medical records of 78 Korean PAP patients diagnosed between 1993 and 2014. Patients were classified into two groups according to the presence/absence of treatment (lavage). Clinical and laboratory features were compared between the two groups., Results: Of the total 78 PAP patients, 60% were male and median age at diagnosis was 47.5 years. Fifty three percent were ever smokers (median 22 pack-years) and 48% had a history of dust exposure (metal 26.5%, stone or sand 20.6%, chemical or paint 17.7%, farming dust 14.7%, diesel 14.7%, textile 2.9%, and wood 2.9%). A history of cigarette smoking or dust exposure was present in 70.5% of the total PAP patients, with 23% having both of them. Patients who underwent lavage (n = 38) presented symptoms more frequently (38/38 [100%] vs. 24/40 [60%], P < 0.001) and had significantly lower PaO 2 and DL CO with higher D(A-a)O 2 at the onset of disease than those without lavage (n = 40) (P = 0.006, P < 0.001, and P = 0.036, respectively). Correspondingly, the distribution of disease severity score (DSS) differed significantly between the two groups (P = 0.001). Based on these, when the total patients were categorized according to DSS (low DSS [DSS 1-2] vs. high DSS [DSS 3-5]), smoking status differed significantly between the two groups with the proportion of current smokers significantly higher in the high DSS group (11/22 [50%] vs. 7/39 [17.9%], P = 0.008). Furthermore, current smokers had meaningfully higher DSS and serum CEA levels than non-current smokers (P = 0.011 and P = 0.031), whereas no difference was found between smokers and non-smokers. Regarding type of exposed dust, farming dust was significantly associated with more severe form of PAP (P = 0.004)., Conclusion: A considerable proportion of PAP patients had a history of cigarette smoking and/or dust exposure, suggestive of their possible roles in the development of PAP. Active cigarette smoking at the onset of PAP is associated with the severity of PAP.

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with significant morbidity and mortality. Similarities have been observed between patients with idiopathic pulmonary fibrosis (IPF) and the UIP (usual interstitial pneumonia) form of RA-ILD. The GAP (gender, age, physiology) model has been shown to predict mortality in patients with IPF, but its ability to predict mortality in RA-ILD is not known., Methods: We identified 309 patients with RA-ILD at 4 academic centers with ongoing longitudinal cohorts of patients with ILD. The primary endpoint was mortality. To handle missing data (n = 219 subjects with complete dataset), multiple imputation by iterative chained equations was used. Using the GAP model as a baseline, we assessed improvements in mortality risk prediction achieved by incorporating additional variables. Model discrimination was assessed using the c-index, and calibration was checked by comparing observed and expected incidence of death., Results: Patients had a mean age of 65 years and were predominantly female (54%). The mean forced vital capacity (FVC) % predicted was 73 and the mean diffusing capacity for carbon monoxide (DL CO ) % predicted was 55. Twenty-four percent of the 236 patients with a high-resolution computed tomography scan available for review had a definite UIP pattern. The original GAP model, including gender, age, FVC%, and DL CO %, had a c-index of 0.746 in our cohort. Calibration of this model was satisfactory at 1, 2 and 3 years. Model discrimination was not meaningfully improved by adding other clinical variables., Conclusion: The GAP model that was derived for IPF performs similarly as a mortality risk prediction tool in RA-ILD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Time to first investigator-reported acute exacerbation was a key secondary end-point in the INPULSIS trials of nintedanib in patients with idiopathic pulmonary fibrosis (IPF).We used the INPULSIS trial data to investigate risk factors for acute exacerbation of IPF and to explore the impact of nintedanib on risk and outcome of investigator-reported and adjudicated confirmed/suspected acute exacerbations. Mortality following these events and events adjudicated as not acute exacerbations was analysed using the log rank test.Risk of acute exacerbations was most strongly associated with the following variables: baseline forced vital capacity (higher risk with lower value), baseline supplemental oxygen (higher risk with use), baseline antacid medication (higher risk with use), treatment (higher risk with placebo), and for confirmed/suspected acute exacerbations, cigarette smoking. Mortality was similar following investigator-reported and adjudicated confirmed/suspected acute exacerbations. Nintedanib had no significant effect on risk of mortality post-exacerbation.Investigator-reported acute exacerbations of IPF are associated with similar risk factors and outcomes as adjudicated confirmed/suspected acute exacerbations., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Purpose: To investigate the frequency of childhood sleep problems at pediatric clinics in Seoul and Gyeonggi provinces., Methods: Children (n=936) and their parents who visited 5 primary and 1 secondary pediatric outpatient clinics were invited to complete a Pediatric Sleep Questionnaire., Results: Among patients, 901 (96.3%) answered questionnaires in sufficient detail for evaluation. The participant's mean age was 4.35±3.02 years (range, 0-18 years). The male to female ratio was 1:0.93 (466 boys, 435 girls). Habitual snoring (>3 day/week) was reported in 16.9% of the participants. The prevalence of habitual snoring in children <2 years and those between 2-5 years was 9% and 18%, respectively. Sleep disordered breathing was found in 15.1% (106 of 700) of children >2 years. Insomnia was reported in 13.2% of children. The prevalence of sleepwalking, night terrors, and bruxism, is 1.6%, 19%, and 21.1%, respectively. Snoring was associated with increased incidence of sleepwalking, night terrors, and bruxism. Age was associated with insomnia and habitual snoring ( P <0.05). Insomnia was more prevalent in younger (21%) than in older children (6%). Snoring was more frequent in both preschool (34%) and school-aged children (33%). The frequency of sleep disordered breathing and insomnia did not vary significantly with gender. However, snoring was more prevalent in boys., Conclusion: Sleep problems are frequent among children in Korea. Children with snoring have an increased risk of sleepwalking, night terror, and bruxism. Primary clinicians should consider children's sleep habits to improve their health., Competing Interests: Conflict of interest: No potential conflicts of interest relevant to this article was reported.

Background: There is a debate that older patients with idiopathic pulmonary fibrosis (IPF) have a worse prognosis. We evaluated whether age affects the survival of patients with IPF., Methods: The Korean Interstitial Lung Disease (ILD) Research Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF. A total of 1,663 patients with IPF were stratified into three groups according to age: (I) <60 years (n=309); (II) 60-69 years (n=613); and (III) ≥70 years (n=741)., Results: The 1-, 3- and 5-year observed survival rates were 83.0%, 62.6%, and 49.2% in the total population, respectively. The 1-, 3-, and 5-year relative survival rates were 85.7%, 69.1%, and 58.0% in all patients, respectively. The observed survival rate of the group ≥70 years of age was significantly lower than those of the other groups (P<0.001). In contrast, no significant difference in relative survival rate was detected among the three age groups. Compared with patients less than 60 years of age, patients with above 70 years of age had not increased risk of worse relative survival [P=0.252; hazard ratio (HR), 1.11; 95% confidence interval (CI), 0.76-1.64]., Conclusions: The prognosis of patients above 70 years of age with IPF was not different to that of patients less than 60 years of age, using relative survival rate. Age may not affect survival in patients with IPF., Competing Interests: The authors have no conflicts of interest to declare.

Background: The clinical course of idiopathic pulmonary fibrosis (IPF) varies widely. Although the GAP model is useful for predicting mortality, survivals have not yet been validated for each GAP score. We aimed to elucidate how prognosis is related to GAP score and GAP stage in IPF patients., Methods: The Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate various characteristics in IPF patients from 2003 to 2007. Patients were diagnosed according to the 2002 criteria of the ATS/ERS. We enrolled 1,685 patients with IPF; 1,262 had undergone DL CO measurement. Patients were stratified based on GAP score (0-7): GAP score Group 0 (n = 26), Group 1 (n = 150), Group 2 (n = 208), Group 3 (n = 376), Group 4 (n = 317), Group 5 (n = 138), Group 6 (n = 39), and Group 7 (n = 8)., Results: Higher GAP score and GAP stage were associated with a poorer prognosis (p < 0.001, respectively). Survival time in Group 3 was lower than those in Groups 1 and 2 (p = 0.043 and p = 0.039, respectively), and higher than those in groups 4, 5, and 6 (p = 0.043, p = 0.032, and p = 0.003, respectively). Gender, age, and DL CO (%) differed significantly between Groups 2 and 3. All four variables in the GAP model differed significantly between Groups 3 and 4., Conclusion: The GAP system showed significant predictive ability for mortality in IPF patients. However, prognosis in IPF patients with a GAP score of 3 were significantly different from those in the other stage I groups and stage II groups of Asian patients.

Background: Because of the highly variable clinical course of rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP), the prediction of patient prognosis is important., Objective: The aim of this study was to investigate the role of blood biomarkers as prognostic predictors in the patients with RA-UIP., Methods: The blood levels of biomarkers (Krebs von den Lungen-6 [KL-6], surfactant protein-A [SP-A], matrix metalloproteinase-7 [MMP-7], interleukin-6 [IL-6], and interleukin-32 [IL-32]) were retrospectively compared with the clinical courses of 62 patients with RA-UIP., Results: The median follow-up period was 33.4 months. RA-UIP progressed in 15 patients (45.2%) during one year of follow-up. We found that KL-6 and IL-6 were significant predictors of short-term (1 year) prognosis. Multivariate logistic regression analysis showed that the odds ratio (OR) for KL-6 was 1.001 (95% confidence interval [CI]: 1.000-1.003, p = 0.077) and that the OR for IL-6 was 1.040 (95% CI: 1.002-1.080, p = 0.039) for short-term disease progression. The addition of KL-6 and IL-6 to the clinical parameters (concordance index [C-index]: 0.958, p = 0.053) predicted short-term disease progression better than the clinical parameter alone (C-index: 0.853). In addition, patients with high levels of KL-6 (≥933 U/mL) had shorter survival than those with low levels of KL-6 (<933 U/mL) (median survival: 51 vs. 96 months, p = 0.019)., Conclusions: The results of this retrospective study suggested that KL-6 and IL-6 could be used as predictors of short-term disease progression. In addition, high levels of KL-6 could be used as a predictor of mortality. Additional studies involving a larger patient cohort are warranted.

Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.

Background: Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci., Results: We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta  = 3.7 × 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB1*15:01 P = 1.3 × 10(-7) and DQB1*06:02 P = 6.1 × 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB1*15:01 and DQB1*06:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 × 10(-16))., Conclusions: We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regulation in addition to altered protein structure. These studies reveal the importance of the HLA region for risk of fIIP and a basis for the potential etiologic role of auto-immunity in fIIP.

A new high-performance liquid chromatography with ​fluorescence detection (HPLC-FLD) method was developed for determination of piperazine residues in food animal products. Samples were extracted with formic acid in water and purified using the PCX cartridge. Following purification, the samples were derivatized using dansyl chloride, and the analyte was separated using water/acetonitrile as a mobile phase. The calibration curves showed good linearity over a concentration range of 20-120 ng/g with coefficient of determination (R(2))⩾0.996. The intra-day accuracy (presented as recovery %) and precision (presented as relative standard deviation, RSD %) were 81-97.3% and 0.83-6.87%, whereas, the inter-day values were 80.5-96.8% and 1.7-6.8%, respectively. The limit of quantification (LOQ) was 20 ng/g, which was considerably lower than the maximum residue limit (MRL). The developed method was used to monitor market samples, and piperazine was not detected in any of the samples. To our knowledge, this is the first study in which the detection of piperazine in various food and animal products by using a sensitive and reliable analytical method has been described., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The fecundity and longevity of Ascotis selenaria (Denis & Schiffermüller 1775) female adults were examined at constant temperatures ranging from 13-35°C. Adult longevity decreased as the temperature increased and ranged from 26.2 d at 13.1°C to 5.2 d at 34.3°C. The maximum observed fecundity of A. selenaria was 2,420 eggs per female at 19.4°C, which decreased to ca 100 eggs per female at 34.3°C. Female adult aging rates (one per median longevity) were well described by a sigmoid equation in the range of 13-35°C used to calculate the physiological age of adults. The relationship between total fecundity and temperature was well described by an extreme value function. Age-specific cumulative oviposition rate and age-specific survival rate curve were fitted to a three-parameter Weibull function. An oviposition model for A. selenaria was developed using the estimated three temperature-dependent submodels: total fecundity, age-specific cumulative oviposition, and age-specific survival rate models. The oviposition model was simulated using pheromone catches of A. selenaria females as input value. Simulated egg populations were subjected to egg stage emergence model to project first-instar populations. Overall, the output of our simulation described the field occurrence pattern of A. selenaria first-instar populations in 2009 and 2010., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Although a multidisciplinary approach has become an important criterion for an idiopathic pulmonary fibrosis (IPF) diagnosis, lung biopsies remain crucial. However, the prognosis of patients with surgically diagnosed IPF (sIPF) is uncertain. We aimed to investigate the prognosis of patients with clinically diagnosed IPF (cIPF) and sIPF. In this retrospective observational study, the Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate the clinical, physiological, radiological, and survival characteristics of patients with IPF from January 1, 2003 to December 31, 2007. Patients were recruited from 54 universities and teaching hospitals across the Republic of Korea. IPF diagnoses were established according to the 2002 American Thoracic Society (ATS)/European Respiratory Society criteria (ERS) guideline. A total of 1685 patients with IPF (1027 cIPF and 658 sIPF) were enrolled. Patients with sIPF were significantly younger, predominantly female, and nonsmokers (all P < 0.001). sIPF group had significantly better initial pulmonary function. The proportion of computed tomography-based honeycomb findings of patients with cIPF was higher than in those with sIPF (P < 0.001). A Kaplan-Meier analysis showed that the sIPF group had a better prognosis (P = 0.001). A survival analysis showed that age, pulmonary function parameters, pulmonary oxygen tension, honeycombing change, and combined lung cancer had a significant influence on patient prognosis. However, there was no significant difference in prognosis between the cIPF and sIPF groups after adjusting for GAP (gender, age, physiology) stage. The patients with sIPF had better clinical features than those with cIPF. However, after adjusting for GAP stage, the sIPF group showed similar prognoses as the cIPF group. This study showed that after adjusting for GAP stage, the prognosis of patients with IPF is the same regardless of the diagnostic method used.

Analysis of residual quantities of contaminants in foods of animal origin is crucial for quality control of consumer products. This study was aimed to develop a simple and raid analytical method for detection of tetramisole and diethylcarbamazine using gradient liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Tetramisole, diethylcarbamazine, and guaifenesin (as an internal standard) were extracted from milk, eggs, and porcine muscle using acetonitrile followed by partitioning at -20 °C for 1h. No extract purification was deemed necessary. The analytes were separated on C18 column using ammonium formate both in water and methanol. Good linearity was achieved over the tested concentration range with R(2) ⩾ 0.974. Recovery at two fortification levels ranged between 67.47% and 97.38%. The intra- and inter-day precisions were <20%. The limit of quantification was 0.2 and 2 ng/g for tetramisole and diethylcarbamazine, respectively. An analytical survey of samples purchased from large markets showed that none of the samples contained any of the target analytes. To the best of our knowledge, this is the first report on the quantitative determination of tetramisole and diethylcarbamazine in animal food products., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: A population model can be a useful tool to understand population dynamics under various environmental factors, and can be useful for evaluating the efficacy of new management practices. This study was conducted to construct an oviposition model of overwintered Scirtothrips dorsalis as a part of its whole population model., Results: Adult longevity decreased with increasing temperature and ranged from 44.7 days at 13 °C to 9.9 days at 33 °C. S. dorsalis showed a maximum fecundity of 52.6 eggs female(-1) at 21 °C, which declined to 13.9 eggs female(-1) at 33 °C. Egg development time decreased from 28.41 days at 13 °C to 5.14 days at 29 °C and 5.5 days at 33 °C. An oviposition model was developed on the basis of three temperature-dependent submodels: total fecundity, age-specific oviposition rate and age-specific survival rate models, Conclusion: The oviposition model outputs followed the field occurrence patterns of S. dorsalis egg populations well, with a peak time discrepancy of 3-4 days. Our model should be useful for population modelling of S. dorsalis in agricultural crops. Furthermore, the present model can be independently used for the timing of spraying against S. dorsalis in IPM programmes of various crops., (© 2014 Society of Chemical Industry.)

A multiclass, multiresidue determination method is reported for the detection of ten veterinary drugs, including scopolamine, metoclopramide, acriflavine, berberine, tripelennamine, diphenhydramine, acrinol, triamcinolone, loperamide, and roxithromycin in pork, milk, and eggs. The method involves a simple extraction using 0.1% formic acid in acetonitrile, followed by defatting with n-hexane, centrifugation, and filtration prior to liquid chromatography with tandem mass spectrometric analysis. As ion suppression and enhancement effects are reported, matrix-matched calibrations are used for quantification, with determination coefficients ≥0.9765. For the majority of the tested analytes, the intra- and interday accuracy (expressed as recovery %) range from 70.6 to 94.6% and from 70.1 to 93.3%, respectively, and the precision (expressed as relative standard deviation) ranges from 0.5 to 19.8% and from 2.8 to 18.4% in all matrices. The limits of quantification range between 0.5 and 10 ng/g. The validated tandem mass spectrometry method is successfully applied to market samples; the target analytes are not detected in any of the tested samples. In terms of accuracy, no extract cleanup is deemed necessary. The developed method is feasible for the simultaneous detection of the tested analytes in pork, milk, and eggs., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

With the overarching aim to develop a simple and reliable method for the quantitative analysis of polypeptide antibiotics in various livestock products, the content of bacitracin, and polymyxin B in pork, beef, chicken, milk, and eggs was analyzed using colistin sulfate as an internal standard. The extracted samples were eluted via solid-phase extraction using 2% formic acid in acetonitrile/methanol (1:1, v/v). The two polypeptides were identified and quantified based on the intensities of mass fragments from the respective triply charged precursor ions (bacitracin: 474.97 amu and polymyxin B: 402 amu) at the defined retention time windows using liquid chromatography with electrospray ionization tandem mass spectrometry in time-scheduled multiple reaction monitoring mode. The calibration curves showed good linearity over the concentration range 50-2500 ng/mL with determination coefficients ≥ 0.991. The mean recoveries were in the range 80.3-88.8% with relative standard deviations <13% for all samples. The limits of quantitation ranged from 30-250 ng/g. The developed method was applied to market samples, but the target analytes were not detected in any of the samples. The developed method is reliable for the simultaneous detection of bacitracin and polymyxin B in pork, beef, chicken, milk, and eggs., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The purpose of this study was to evaluate the CT characteristics of newly developed lung cancer on CT studies obtained during follow-up of idiopathic interstitial pneumonia (IIP) before the appearance of identifiable tumors to the time of detectable lung cancer and thereafter., Materials and Methods: The study sample included 66 cancers diagnosed in 63 patients with IIP and lung cancer (59 men, four women; median age, 64 years; range, 40-85 years) between October 1998 and July 2012. Two radiologists independently reviewed 193 CT scans, determined the earliest presence of cancer and IIP, and evaluated tumor size, lobar and axial location, shape, and tumor density. Delay in clinical diagnosis and doubling time were measured with first and second follow-up CT examinations., Results: Interobserver agreement was good (κ > 0.77). The median tumor size was 17 mm (range, 5-30 mm) for the 46 T1a and 20 T1b cancers. Most of the tumors (42 [63.6%]) were located in the lower lobes. Thirty-five tumors (53.0%) were at the interface between fibrotic cyst and normal lung, and 21 (31.8%) were in the midst of fibrotic lung cysts. Most of the tumors had a round or oval shape (52 [78.8%]) and were solid (62 [93.9%]). The median delay in diagnosis was 46 days (range, 8-760 days). The first median doubling time was 77 days (range, 15-525 days), and the second was 53 days (27-248)., Conclusion: New lung cancers during CT follow-up of IIP usually appear as small solid nodules with a round or oval shape. Most cancers are located at the interface between fibrotic cyst and normal lung or in the midst of fibrotic cysts of the lower lobes of subpleural lung.

In the present study we analyzed the anti-proliferative effect of tocilizumab, a humanized recombinant monoclonal interleukin 6 receptor (IL-6R) antibody, against non-small cell lung cancer (NSCLC) cells, including A549, H460, H358 and H1299 cells. The cell cycle distribution of NSCLCs was analyzed using fluorescence-activated cell sorting and gene expression using quantitative polymerase chain reaction. Cell lysates treated with tocilizumab were immunoblotted with antibodies against signal transducer and activator of transcription 3 (STAT3), phospho-STAT3, extracellular-signal-regulated kinases (ERK), phospho-ERK, nuclear factor κB (NFκB) and phospho-NFκB. Significant growth inhibition of NSCLC cells was observed following treatment with tocilizumab. Proliferation was significantly decreased by approximately 10-40% in A549, H460, H1299 and H358 cells, with an inhibition rate that was comparable with that of the typical anticancer drugs methotrexate and 5-fluorouracil. NSCLC cell populations were accumulated in the sub-G1 phase by treatment with tocilizumab. Western blot analyses revealed a possible activation of the NFκB pathway by tocilizumab. Overall, these data indicate that tocilizumab has anticancer potency via apoptosis induction as an agonistic IL-6R regulator. Therefore, we suggest that this anti-IL-6R antibody may be utilized as a new targeting molecule for NSCLC therapies.

This article describes the difference between the computed tomography (CT) findings in patients with newly detected pulmonary nontuberculous mycobacterial infection (NTM-IIP) and Cancer-IIP. We retrospectively evaluated 35 NTM-IIP and 78 Cancer-IIP patients in reference to their null idiopathic interstitial pneumonia CT (n = 113), using >10 years of data. Two independent radiologists analyzed the CT characteristics and the axial location of the main opacity. The interobserver agreement was good (κ > 0.771). The NTM-IIP patients were older (P = 0.034). The median size of the main opacity in the NTM-IIP (27 mm; 11-73) was larger (19 mm; 5-60; P = 0.002). Consolidation (n = 30; 85.7%; odds ratio [OR], 45) and cavities (n = 14; 40%, OR, 25) were more common in NTM-IIP (all P < 0.001). The midst of the fibrotic cysts including honeycomb cysts (n = 16; 45.7%, OR, 4.95) was more common in NTM-IIP (P = 0.006). NTM-IIP appeared larger, with more frequent consolidation and cavities, and was more likely to have been located in the midst of the fibrotic cysts including honeycomb cysts at the CT, which showed that it was older than Cancer-IIP.

An oral toxicity study of several pregnancy category X drugs was performed in female ICR mice. The drugs were administered orally once daily for 3 days at doses of 1, 10 and 100 μg/kg for isotretinoin; 6.7, 67 and 670 μg/kg for misoprostol; 83, 830 and 8,300 μg/kg for methotrexate; 3.3, 33 and 330 μg/kg for mifepristone; and 25, 250 and 2,500 μg/kg for levonorgestrel. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry and necropsy findings were examined. Following administration of methotrexate at 8,300 μg/kg, a number of animals exhibited decreased spontaneous activity, and one animal died. In the hematological analysis, compared with those treated with the control, the animals treated with the drugs exhibited similar significant decreases in the number of granulocytes and granulocyte differentiation, and increases in lymphocyte differentiation. In the serum biochemical analysis, animals receiving high doses of the five drugs demonstrated significant changes in uric acid, glucose, alkaline phosphatase, total bilirubin, lipase, total cholesterol and calcium. At necropsy, intestinal redness was frequently observed in animals that received the high dose of methotrexate. Uterus enlargement and ovary dropsy were also detected in the groups receiving mifepristone and levonorgestrel. Despite the short-term exposure, these drugs exhibited significant side effects, including white blood cell toxicity, in the mouse model. Category X drugs can be traded illegally via the internet for the purpose of early pregnancy termination. Thus, illegal abuse of the drugs should be further discouraged to protect mothers.

Background: Previous studies have investigated the relationship between occupational and environmental agents and idiopathic pulmonary fibrosis (IPF). However, there have been few studies regarding the prognosis of patients with IPF according to patient occupation., Methods: We investigated whether occupational dust exposure was associated with clinically decreased lung function and poor prognosis. The Korean Interstitial Lung Disease Research Group conducted a national survey to evaluate the clinical, physiologic, radiologic, and survival characteristics of patients with IPF. A total of 1,311 patients with IPF were stratified into five groups according to their occupation: (1) unemployed or homemakers (n = 628); (2) farmers, fishers, or ranchers (n = 230); (3) sales or service personnel (n = 131); (4) clerical or professional personnel (n = 151); and (5) specific dust-exposed workers (n = 171)., Results: The mean age of subjects at diagnosis, was 67.5 ± 9.7 years. Current smokers were 336 patients, 435 were exsmokers, and 456 were never smokers. Dust-exposed workers showed early onset of IPF (61.3 ± 8.6 years; P < .001) and a longer duration of symptoms at diagnosis (17.0 ± 28.2 months; P = .004). Aging (P = .001; hazard ratio [HR], 1.034; 95% CI, 1.014-1.054), FVC % predicted at diagnosis (P = .004; HR, 0.984; 95% CI, 0.974-0.995), and dust-exposure occupation (P = .033; HR, 1.813; 95% CI, 1.049-3.133) were associated with mortality., Conclusions: These findings indicate that occupational dust may be an aggravating factor associated with a poor prognosis in IPF.

Background: Polymorphisms in the MUC5B promoter, TOLLIP, and nine additional genetic loci have been associated with idiopathic pulmonary fibrosis (IPF) within non-Hispanic white populations. It is unknown whether these variants account for risk of IPF in other racial/ethnic populations. We conducted a candidate single nucleotide polymorphism (SNP) association study in cohorts of Mexican and Korean patients with IPF., Methods: We chose 12 SNPs from 11 loci that are associated with IPF among non-Hispanic whites and genotyped these SNPs in cohorts of Mexican (83 patients, 111 control subjects) and Korean (239 patients, 87 control subjects) people. Each SNP was tested for association with IPF, after adjusting for age and sex., Results: The MUC5B promoter SNP rs35705950 was associated with IPF in the Mexican (OR = 7.36, P = .0001), but not the Korean (P = .99) cohort. The SNP in IVD (chromosome15, rs2034650) was significantly associated with pulmonary fibrosis in both the Mexican (OR = 0.40, P = .01) and Korean (OR = 0.13, P = .0008) cohorts. In the Korean cohort, there were no other variants associated with disease. In the Mexican cohort, SNPs on chromosomes 3, 4, and 11 were also associated with disease., Conclusions: The strongest identified genetic risk factor for IPF among the non-Hispanic white population, the MUC5B promoter polymorphism, is also a strong risk factor in a Mexican population, but is very rare in a Korean population. The majority of genetic variants that account for risk of IPF in groups other than non-Hispanic whites are unknown. Hispanic and Asian populations should be studied separately to identify genetic risk loci for IPF.

Background: Although the increased risk of coronary artery disease (CAD) in the patients with idiopathic pulmonary fibrosis (IPF) has been reported, there was few detailed information on the risk factors for CAD in IPF. The aim of this study was to investigate the prevalence of CAD in IPF with analysis of other risk factors., Methods: The subjects were 460 patients (mean age, 65 years; 79% male; 74% current or ex-smoker) diagnosed as IPF at Asan Medical Center and 1,925 controls matched with age, gender, smoking habits, and date of IPF diagnosis from the cohort of Korean Heart Study. Cardiovascular risk factors and prevalence of CAD in both groups were compared and the incidence of newly developed CAD during follow-up was also analyzed., Results: IPF group was more diabetic, and control group had a higher proportion of hypertension and hypercholesterolemia. The prevalence of CAD in IPF group (7%) was two times higher than that of control group (3%). Multivariate analysis revealed that age (OR, 1.04; 95% CI, 1.02-1.07), hypertension (OR, 2.13; 95% CI, 1.36-3.33), hypercholesterolemia (OR, 3.85; 95% CI, 2.51-5.88), and IPF (OR, 2.64; 95% CI, 1.68-4.14) were significant risk factors for CAD. During follow-up (median: 2.5 years for IPF and 4.4 years for controls), the incidence of newly diagnosed CAD was higher in the patients with IPF (6.8%) compared to controls (2.8%) (RR, 1.92; 95% CI, 1.08-3.43)., Conclusions: IPF itself was an independent risk factor for CAD after the adjustment of age, hypertension, diabetes, and hypercholesterolemia.

The present study investigated the preventive effect of ω-3 fatty acids against cholesterol gallstone (CG) formation. CG formation was induced in C57BL/6J mice using a lithogenic diet (LD). The mice were divided into four treatment groups: i) LD, ii) LD plus eicosapentaenoic acid (EPA), iii) LD plus docosahexaenoic acid (DHA) and iv) LD plus EPA plus DHA. Subsequent to feeding the mice the LD for four weeks, EPA and/or DHA (70 mg/kg/day) were orally administered for eight weeks. The mice in the EPA treatment groups exhibited significantly less gallstone formation than those in the LD group. By contrast, DHA treatment only slightly suppressed gallstone formation. The expression of mucin 2, 5AC, 5B and 6 was significantly decreased in the gallbladders of mice in the EPA groups (70-90%) and the LD plus DHA group (30-50%), compared with that in the mice in the LD group. In addition, the mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase was significantly decreased in the livers of mice in the EPA treatment group compared with that in the livers of mice in the LD group. In conclusion, EPA was found to have a dominant anti-lithogenic effect in C57BL/6J mice.

This study analyzed the recurrence rate and risk factors for recurrence of Mycobacterium avium complex (MAC) lung disease in patients successfully treated for this disease. The medical records of 158 patients successfully treated for MAC lung disease at a tertiary referral center in South Korea between March 2000 and December 2009 were retrospectively analyzed. Recurrence was recorded, and factors associated with recurrence were analyzed. The mean age of the 158 patients was 60.7 ± 11.1 years. The etiologic agent was Mycobacterium avium in 77 patients (48.7%) and Mycobacterium intracellulare in 81 patients (51.3%). Radiographic features included nodular bronchiectatic disease in 95 (60.1%), fibrocavitary disease in 49 (31.0%), and an unclassifiable form in 14 (8.9%) patients. Almost all (98.7%, 156/158) patients had been previously treated with a macrolide-containing regimen, and 68 (43.0%) patients had received treatment with an aminoglycoside. During a median follow-up of 43.8 months after completion of therapy, 50 patients (31.6%) experienced recurrence, at a median of 11.9 months after treatment completion. Multivariate analysis showed that only the nodular bronchiectatic form of the disease (hazard ratio, 2.39; 95% confidence interval, 1.19 to 4.81) was independently associated with an increased risk of recurrence. Recurrence after successful treatment is frequent in patients with MAC lung disease. The recurrence rate was significantly higher in patients with the nodular bronchiectatic form than in those with the fibrocavitary form or an unclassifiable form of the disease., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Undifferentiated connective tissue disease (UCTD) involves conditions characterized by both having symptoms of connective tissue disease (CTD) and autoantibodies but not fulfilling the criteria of a specific CTD. The frequency or prognosis of the usual interstitial pneumonia (UIP) pattern in UCTD is unknown, which may be confused with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the frequency of the UIP pattern in interstitial pneumonia related to UCTD and compare its prognosis with that of IPF and UCTD-nonspecific interstitial pneumonia (UCTD-NSIP)., Methods: The medical records of 788 patients presumptively diagnosed with idiopathic interstitial pneumonia at Asan Medical Center from January 2005 to December 2012 were retrospectively reviewed. UCTD was diagnosed according to the criteria by Corte and colleagues, and the prognoses were compared between UCTD-UIP and UCTD-NSIP and between UCTD-UIP and IPF., Results: Among 105 patients with UCTD (13.3% of total subjects), 44 had a UIP pattern (by surgical lung biopsy: 24; by high-resolution CT scan: 20), 29 had a nonspecific interstitial pneumonia pattern (by surgical lung biopsy), and nine had an organizing pneumonia pattern (by biopsy). The overall survival of the UCTD-UIP group was shorter than that of the UCTD-NSIP group (P = .021) but significantly better than that of the IPF group (P = .042)., Conclusions: A UIP pattern, which seems to be frequent in UCTD, showed a poorer prognosis than that of UCTD-NSIP. However, the prognosis of UCTD-UIP was significantly better than that of IPF, highlighting the importance of searching for underlying UCTD in suspected IPF cases.

Background: Mycobacterium abscessus complex is the second most common organism isolated from patients with nontuberculous mycobacterial (NTM) lung disease in South Korea. This study aimed to compare clinical features and treatment outcomes of M. abscessus and Mycobacterium massiliense lung disease., Methods: We retrospectively identified stored clinical isolates of M. abscessus complex as either M. abscessus or M. massiliense and reviewed medical records to compare clinical characteristics and treatment responses. All patients were treated empirically over several months with multidrug regimens, including a macrolide and one or more parenteral agents., Results: Of the 249 patient isolates tested, 128 (59 with M. abscessus and 69 with M. massiliense) met the American Thoracic Society diagnostic criteria for NTM pulmonary disease, and treatment outcomes were analyzed in 48 patients (26 with M. abscessus and 22 with M. massiliense). The clinical and radiologic findings were similar between the two groups. Although the durations of parenteral and total treatment were significantly shorter in patients with M. massiliense than in those with M. abscessus (4.7 months vs 7.4 months, P = .006, and 12.1 months vs 16.3 months, P = .043), the treatment success rate was significantly higher in patients with M. massiliense (95.5%) than in M. abscessus cases (42.3%, P < .001)., Conclusion: Patients with M. massiliense pulmonary infection responded better to this antibiotic strategy than those with M. abscessus infection. A shortened duration of treatment may be sufficient for M. massiliense pulmonary infection., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to describe computed tomography (CT) findings of nontuberculous mycobacterial (NTM) pulmonary infection in patients with idiopathic interstitial pneumonias (IIP) in comparison with those in patients without IIP., Methods: From November 2001 to October 2012, 810 patients in the NTM registry were retrospectively reviewed. Among them, 42 patients (mean age, 69.7 years; 32 men and 10 women) who were diagnosed as having IIP by either histological or radioclinical criteria were included in our study. Eighty-two age- and sex-matched immunocompetent patients with NTM pulmonary infection and without IIP were selected as the control group. Medical records and CT scans were reviewed. Formal radiologic reports obtained before diagnosis of NTM infection were also reviewed., Results: Lobar/segmental consolidation (85.7%) was the most common CT finding in the IIP group, whereas branching centrilobular nodules (95.1%), traction bronchiectasis (79.3%), and volume decrease (58.5%) were common in the control group. Frequencies of these findings were significantly different between the 2 groups (P < 0.001). Most of consolidations were associated with cavity (83.3%) without dominant zonal distribution. Pneumonia or fungal infection (n = 20) was the most common radiologic diagnosis in the IIP group., Conclusions: The NTM pulmonary infection in IIP patients is characterized as lobar/segmental consolidation with/without cavity, different to immunocompetent patients without IIP, and can mimic other diseases especially bacterial/fungal infection.

We aimed to investigate the treatment outcomes of patients with refractory Mycobacterium avium complex (MAC) lung disease treated with regimens containing drugs with unclear efficacy. Of all patients diagnosed with MAC lung disease between April 2004 and September 2012 at a tertiary referral center in South Korea, the outcomes of 51 patients treated with regimens containing drugs with unclear efficacy (clofazimine, moxifloxacin, rifabutin, and linezolid) because of treatment failure after receiving standard treatment were retrospectively analyzed. The mean age (standard deviation) of the 51 patients was 59.0 (10.3) years and 29 (56.9%) were male. The etiologic agent was M. avium in 17 patients (33.3%) and Mycobacterium intracellulare in 34 patients (66.7%); 42 patients (82.4%) had the fibrocavitary form of the disease. Of the 51 patients, 26, 28, 35, and 7 received clofazimine-, moxifloxacin-, rifabutin-, and linezolid-containing regimens (numbers are not mutually exclusive), with median drug administration durations of 147, 128, 209, and 88 days, respectively. Overall, 8 patients (15.7%) had a favorable response. Treatment outcomes did not differ by drug regimen or even by the combination of more than 2 drugs. The treatment outcomes of patients with refractory MAC lung disease were unsatisfactory with regimens containing possibly effective drugs such as clofazimine, moxifloxacin, rifabutin and linezolid., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Cigarette smoking is a key factor in the development of numerous pulmonary diseases. An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n=41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n=100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11-0.21), among the pathologists 0.36 (95% CI 0.32-0.40) and among the radiologists 0.43 (95% CI 0.35-0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease. Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease., (©ERS 2014.)