A New Perspective to Understand the Late Season Abundance of Delia antiqua (Diptera: Anthomyiidae): A Modeling Approach for the Hot Summer Effect.

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 (Lepidoptera: Noctuidae) at constant temperatures: instar pathways and stage transition models with semifield validation.

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.

Fecundity and Longevity of Spodoptera frugiperda (Lepidoptera: Noctuidae) at Constant Temperatures and Development of an Oviposition Model.

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.

Sex, males, and hermaphrodites in the scale insect Icerya purchasi.

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.

Longitudinal Changes in Clinical Features, Management, and Outcomes of Idiopathic Pulmonary Fibrosis. A Nationwide Cohort Study.

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).

A new direction to understand the life cycle of the Japanese pine sawyer considering the selection strategy of instar pathways.

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.

Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis.

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.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 2. Idiopathic Pulmonary Fibrosis.

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.

The Developmental Characteristics for the Head Capsule Width of Monochamus alternatus (Coleoptera: Cerambycidae) Larvae and Determination of the Number of Instars.

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) .

Effects of emphysema on physiological and prognostic characteristics of lung function in idiopathic pulmonary fibrosis.

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 (DLCO ) 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.

Efficacy and Safety of Pirfenidone in Advanced Idiopathic Pulmonary Fibrosis.

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.

Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis.

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 [FEV1], - 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 FEV1 (- 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 FEV1 (- 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.

Efficacy and safety of nintedanib in advanced idiopathic pulmonary fibrosis.

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.

Fecundity and Egg Laying in Helicoverpa armigera (Lepidoptera: Noctuidae): Model Development and Field Validation.

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.

Comparison of CPI and GAP models in patients with idiopathic pulmonary fibrosis: a nationwide cohort study.

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 × %DLCO) - [0.53 × %FVC + [0.34 × %FEV1. 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.

Prevalence and Effects of Emphysema in Never-Smokers with Rheumatoid Arthritis Interstitial Lung Disease.

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.

Factors affecting treatment outcome in patients with idiopathic nonspecific interstitial pneumonia: a nationwide cohort study.

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 (FEV1), 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.

Clinical significance of cigarette smoking and dust exposure in pulmonary alveolar proteinosis: a Korean national survey.

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 PaO2 and DLCO with higher D(A-a)O2 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.

Sleep problems in children and adolescents at pediatric clinics.

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.