Learnable latent embeddings for joint behavioural and neural analysis.

Mapping behavioural actions to neural activity is a fundamental goal of neuroscience. As our ability to record large neural and behavioural data increases, there is growing interest in modelling neural dynamics during adaptive behaviours to probe neural representations1-3. In particular, although neural latent embeddings can reveal underlying correlates of behaviour, we lack nonlinear techniques that can explicitly and flexibly leverage joint behaviour and neural data to uncover neural dynamics3-5. Here, we fill this gap with a new encoding method, CEBRA, that jointly uses behavioural and neural data in a (supervised) hypothesis- or (self-supervised) discovery-driven manner to produce both consistent and high-performance latent spaces. We show that consistency can be used as a metric for uncovering meaningful differences, and the inferred latents can be used for decoding. We validate its accuracy and demonstrate our tool's utility for both calcium and electrophysiology datasets, across sensory and motor tasks and in simple or complex behaviours across species. It allows leverage of single- and multi-session datasets for hypothesis testing or can be used label free. Lastly, we show that CEBRA can be used for the mapping of space, uncovering complex kinematic features, for the production of consistent latent spaces across two-photon and Neuropixels data, and can provide rapid, high-accuracy decoding of natural videos from visual cortex.

Components of the Chronic Obstructive Pulmonary Disease Assessment Test Associated with the Exacerbation of Severe Chronic Obstructive Pulmonary Disease Patients.

INTRODUCTION: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) score is widely used for evaluating the health status of patients diagnosed with COPD. The aim of this study was to identify which components of the CAT are associated with exacerbations in severe COPD patients. METHODS: Using data from the Korean COPD Subgroup Study (KOCOSS), we identified 3,440 COPD patients, among which 1,027 patients are classified as having severe COPD based on spirometry results. The CAT scores on 8 items were evaluated and classified into respiratory and non-respiratory categories. We analyzed the association between CAT item scores and moderate-to-severe exacerbations during study enrollment and the following years. RESULTS: Patients with a history of moderate-to-severe exacerbations had higher scores on non-respiratory CAT components. Longitudinal CAT scores on all items after enrollment were higher in the moderate-to-severe exacerbation group. Additionally, the frequency of severe exacerbations was associated with specific CAT components related to limited activities, confidence leaving home, sleeplessness, and energy. CONCLUSIONS: This study revealed that the non-respiratory CAT component scores were statistically significant factors for predicting the moderate-to-severe exacerbation of severe COPD patients. Non-respiratory symptoms and functional limitations should be considered in patients with severe COPD. Interventions, such as pulmonary rehabilitation, may be needed to improve patients' overall well-being and prevent exacerbations.

Isolated respiratory tract microorganisms and clinical characteristics in asthma exacerbation of obese patients: a multicenter study.

BACKGROUND: Viral infection is a risk factor for asthma exacerbation (AE). However, bacterial infections related to AE in adults are poorly known. On the other hand, obese patients with asthma have their own clinical and biological characteristics compared with non-obese patients. METHODS: We investigated the differences in isolated pathogens for AE between obese and non-obese patients with asthma. We included 407 patients with AE from 24 medical centers in Korea. Microorganisms isolated from culture, RT-PCR or serologic tests using lower respiratory tract specimens were retrospectively investigated. RESULTS: A total of 171 obese and 236 non-obese patients with asthma were included for analysis. Compared to non-obese patients, obese patients were associated with women (77.2% vs. 63.6%), never smoker (82.5% vs. 73.9%), shorter duration of asthma (7.9 ± 8.4 vs. 10.5 ± 10.1 years), less history of pulmonary tuberculosis (8.8% vs. 17.4%), and more comorbidity of allergic rhinitis (48.5% vs. 0.8%). Viral and/or bacterial infections were detected in 205 patients (50.4%) with AE. The numbers of patients with viral only, bacterial only, or both infections were 119, 49, and 37, respectively. The most commonly isolated bacterium was Streptococcus pneumoniae, followed by Pseudomonas aeruginosa and Chlamydia pneumoniae. Obese patients showed a lower incidence of Chlamydia pneumoniae infection. In the non-obese group, bacterial infection, especially Chlamydia pneumoniae infection, was significantly associated with the duration of systemic corticosteroid use (13.6 ± 19.8 vs. 9.7 ± 6.7 days, p = 0.049). CONCLUSION: Bacterial infection was associated with a longer period of corticosteroid use in the non-obese group. Acute Chlamydia pneumoniae infection was less associated with obese patients with AE. Further well-designed studies are needed to evaluate microorganisms and the efficacy of antibiotics in patients with AE.

Association Between Air Pollution and Viral Infection in Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Respiratory pathogen infections and air pollution are main causes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Air pollution has a direct effect on the airway epithelial barrier and the immune system, which can have an influence on infection. However, studies on the relationship between respiratory infections and air pollutants in severe AECOPD are limited. Thus, the objective of this study was to investigate the correlation between air pollution and respiratory pathogen in severe AECOPD. METHODS: This multicenter observational study was conducted by reviewing electronic medical records of patients with AECOPD at 28 hospitals in South Korea. Patients were divided into four groups according to the comprehensive air-quality index (CAI) used in Korea. Identification rates of bacteria and viruses of each group were analyzed. RESULTS: Viral pathogens were identified in 270 (36.7%) of 735 patients. Viral identification rate was different (P = 0.012) according to air pollution. Specifically, the virus detection rate was 55.9% in the group of CAI 'D' with the highest air pollution. It was 24.4% in the group of CAI 'A' with the lowest air pollution. This pattern was clearly seen for influenza virus A (P = 0.042). When further analysis was performed with particulate matter (PM), the higher/lower the PM level, the higher/lower the virus detection rate. However, no significant difference was found in the analysis related to bacteria. CONCLUSION: Air pollution may make COPD patients more susceptible to respiratory viral infections, especially influenza virus A. Thus, on days with poor air quality, COPD patients need to be more careful about respiratory infections.

Clinical Characteristics of Non-Smoking Chronic Obstructive Pulmonary Disease Patients: Findings from the KOCOSS Cohort.

Chronic obstructive pulmonary disease (COPD) has been regarded as a disease of smokers, but the prevalence of non-smoking COPD patients have been reported to be considerable. We investigated differences in clinical characteristics between smoking and non-smoking COPD patients. We used data from the Korea COPD Subgroup Study (KOCOSS) database, which is a multicenter cohort that recruits patients from 54 medical centres in Korea. Comprehensive comparisons of smoking and non-smoking COPD patients were performed based on general characteristics, exacerbations, symptom scores, radiological findings, and lung-function tests. Of the 2477 patients included in the study, 8.1% were non-smokers and 91.9% were smokers. Non-smoking COPD patients were more likely to be female and to have a higher body mass index and lower level of education. Non-smoking COPD patients had more comorbidities, including hypertension, osteoporosis, and gastroesophageal reflux disease, and experienced more respiratory and allergic diseases. No significant differences in exacerbation rates, symptom scores, or exercise capacity scores were observed between the two groups. Smoking COPD patients had more emphysematous lung according to the radiological findings, and non-smoking patients had more tuberculosis-destroyed lung and bronchiectasis. Lung-function testing revealed no significant difference in the forced expiratory capacity in 1 sec between the two groups, but smokers had more rapid lung-function decline in the 5 years of follow-up data. We found differences in general characteristics and radiological findings between smoking and non-smoking COPD patients. No significant differences in exacerbation or symptom scores were observed, but decline in lung function was less steep in non-smoking patients.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2053088 .

Comparison of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung adenocarcinoma harboring different epidermal growth factor receptor mutation types.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation types are associated with efficacy of EGFR TKIs. We investigated the clinical outcomes of afatinib, erlotinib, and gefitinib according to EGFR mutation type in patients with lung adenocarcinoma. METHODS: Between May 2010 and December 2018, we investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations who received EGFR TKIs. Efficacies of EGFR TKIs such as response rate, progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated according to exon 19 deletion (E19del), L858R point mutation (L858R) and uncommon mutations. RESULTS: The frequency of E19del was 48.2%, that of L858R was 42.4%, and that of uncommon mutations was 9.4%. E19del and L858R were associated with superior PFS and OS compared with uncommon mutations. Erlotinib showed significantly inferior OS than other TKIs (30.8 ± 3.3 in erlotinib vs. 39.1 ± 4.3 in afatinib vs. 48.4 ± 6.3 in gefitinib; p = 0.031) in patients with L858R. Gefitinib showed significantly inferior PFS (4.6 ± 1.1 in gefitinib vs. 11.6 ± 2.7 in afatinib vs. 10.6 ± 2.7 in erlotinib; p = 0.049) in patients with uncommon mutations. CONCLUSION: Afatinib was significantly associated with a longer PFS, presenting constant effectiveness in all EGFR mutation types. Caution may be needed on the use of erlotinib for L858R and the use of gefitinib for uncommon EGFR mutations.

Silicone-induced lymphadenopathy mimicking recurrence of breast cancer on positron emission tomography-computed tomography, correctly diagnosed on ultrasound.

Silicone-induced lymphadenopathy is a rare complication associated with silicone breast implants. It is usually asymptomatic and found incidentally during imaging. We report a case of silicone lymphadenopathy in a patient who had undergone a mastectomy and breast reconstruction for breast cancer. During follow-up, a positron emission tomography-computed tomography examination revealed lymph nodes that were suspicious for cancer recurrence. However, sonography was able to correctly diagnose silicone-induced lymphadenopathy and exclude cancer metastasis.

Outcome of Regular Inhaled Treatment in GOLD A Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: The 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends regular bronchodilator therapy in all group A patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: The aim of this study was to evaluate whether regular inhaled treatment in group A patients with COPD improves their health outcomes, including exacerbations and symptoms. METHODS: We recruited patients from 2 Korean prospective cohorts. Eligible COPD patients had a modified Medical Research Council (mMRC) dyspnea score of <2, a St. George's Respiratory Questionnaire for COPD (SGRQ-C) total score of <25, and had no more than 1 exacerbation and no hospitalizations during the previous year. Incidence rates of exacerbations and changes in symptom scores were analyzed. RESULTS: After propensity score matching, there were 107 patient pairs, with and without regular inhaled treatment, who were followed up for mean times of 2.6 and 3.1 years, respectively. The incidence rates of exacerbations in those with and without regular treatment were not significantly different (incidence rate ratio 1.24 [95% CI 0.68 to 2.25]). Significant differences in favor of regular treatment were observed at 6 and 12 months for the SGRQ-C total scores (mean between-group difference -4.7 [95% CI -7.9 to -1.6] and -4.8 [95% CI -7.9 to -1.7], respectively). Regular treatment with a long-acting bronchodilator was also associated with significantly better scores on the SGRQ-C (mean between-group difference -5.0 [95% CI -8.6 to -1.4]) compared to no regular treatment at 12 months of follow-up. CONCLUSIONS: Regular inhaled treatment in group A patients with COPD was associated with a symptomatic benefit but not with a reduction of exacerbation rates.

Spontaneous remission of advanced progressive poorly differentiated non-small cell lung cancer: a case report and review of literature.

BACKGROUND: Spontaneous remission (SR) of cancer is a very rare phenomenon of unknown mechanism. In particular, SR of non-small cell lung cancer (NSCLC) has been scarcely reported. We present the case of a 74-year-old woman with advanced, poorly differentiated NSCLC (highly expressing programmed death ligand-1 [PD-L1]) that progressed despite multiple lines of chemotherapy but then spontaneously remitted. CASE PRESENTATION: The patient presented with hemoptysis and was diagnosed with stage IIIA poorly differentiated NSCLC via bronchoscopic biopsy. She had an unremarkable medical history and moderate performance status. The initial treatment plan was surgery after neoadjuvant chemotherapy. Despite conventional chemotherapy, follow-up chest computed tomography (CT) showed gradual tumor progression and she decided against further treatment after fifth-line chemotherapy. However, the size of lung mass was markedly decreased on follow-up chest CT one year after ceasing chemotherapy. Also, follow-up positron emission tomography images showed decreased metabolic activity in the lung mass and a percutaneous biopsy specimen from the diminished lung mass revealed no viable tumor cells. A diagnosis of SR of NSCLC was confirmed, and the patient was without tumor progression on follow-up nine months later. Later, PD-L1 immunostaining revealed high positivity (> 99%) in initial tumor cells. CONCLUSION: Our case showing SR of poorly advanced NSCLC refractory to multiple lines of chemotherapy suggested the association between immunity and tumor regression.

Hemoptysis requiring bronchial artery embolization in patients with nontuberculous mycobacterial lung disease.

BACKGROUND: Although infections caused by nontuberculous mycobacteria (NTM) are increasing in prevalence, there are few data about hemoptysis in patients with NTM lung disease. This study investigated the characteristics and prognosis of hemoptysis secondary to NTM infection. METHODS: Following a retrospective review of cases managed between 2006 and 2016, 183 patients with NTM lung disease were enrolled and analyzed. RESULTS: Among 183 patients with NTM lung disease, Mycobacterium intracellulare (n = 64, 35%) was the major cause of NTM infection, followed by M. avium (n = 59, 32.2%) and M. abscessus complex (n = 40, 21.9%). Hemoptysis developed in 78 patients (42.6%), among whom 33 (42.3%) required bronchial artery embolization (BAE). Between patients with and without hemoptysis, there were no significant differences with respect to sex, radiographic manifestations, distribution over 3 lobes on chest computed tomography, history of pulmonary tuberculosis, antiplatelet or anticoagulation therapy, and species of NTM. However, mean age at diagnosis was significantly lower in the hemoptysis group in univariate and multivariate analyses (65.7 ± 12.8 vs. 59.7 ± 11.8, P = 0.002, odds ratio: 0.969, 95% confidence interval: 0.944-0.996). Among patients with hemoptysis, those requiring medical therapy and those requiring BAE were not significantly different in terms of demographic characteristics, radiographic manifestations, and distribution over 3 lobes. All patients who received BAE showed immediate clinical improvement, no procedure-related complications, and none of them died during the period under review. CONCLUSIONS: NTM lung disease patients commonly experienced hemoptysis without specific risk factors except for relatively young age. Although some patients with hemoptysis needed BAE, the success rate of BAE was high, and there were no serious complications associated with BAE.

Clinical characteristics of patients with newly developed acute cholecystitis after admission to the intensive care unit.

INTRODUCTION: Critical care patients have many risk factors for acute cholecystitis (AC). However, less data are available regarding newly developed AC in critically ill patients. OBJECTIVES: To investigate the clinical features of AC occurring in critically ill patients after admission to an intensive care unit (ICU). METHODS: We performed a retrospective cohort study from January 2006 to August 2016 at a tertiary care university hospital. We included patients diagnosed with AC with or without gallstones after ICU admission. All cases of AC were confirmed by gastroenterologists or general surgeons. We excluded patients with AC diagnosed before or at the time of ICU admission. RESULTS: A total of 38 patients were diagnosed with AC after ICU admission between January 2006 and August 2016. Seventeen (44.7%) had acute acalculous cholecystitis, while 21 (55.3%) had acute calculous cholecystitis. The median age was 73 years (interquartile range = 63-81 years), and 22 (57.9%) patients were male. The most common reason for ICU admission was pneumonia or sepsis. The median interval from ICU admission to diagnosis of AC was 11 days (interquartile range = 4.8-22.8 days). Before AC diagnosis, almost 90% of patients used total parenteral nutrition, 68% used opioids, 76% were mechanically ventilated, and 42% received vasoactive drugs. More than half of patients underwent cholecystectomy, and all surgically resected gallbladders had pathology results for cholecystitis. Gangrenous cholecystitis was observed in five patients with acute calculous cholecystitis. The overall mortality was 42.1%, and 1/3 of these deaths were directly associated with AC. The average length of stay in the ICU and hospital was 26.5 and 44.5 days, respectively. CONCLUSION: The development of AC in the ICU should be carefully monitored, especially in patients who have been infected and admitted to the ICU for more than 10 days. Proper diagnosis and treatment at a critical time could be lifesaving.

Inhaled corticosteroids in COPD and the risk of lung cancer.

Inhaled corticosteroids (ICS) might reduce the risk of lung cancer by controlling airway inflammation in patients with chronic obstructive pulmonary disease (COPD) because both are associated with chronic inflammation. The objective was to assess the impact of ICS on lung cancer risk reduction in COPD patients. We performed a nested case-control study based on the database of the National Health Insurance Service-National Sample Cohort, a nationally representative cohort of 1,125,691 participants in Korea followed over 11 years. The eligible population was patients aged 30-89 years who were newly diagnosed with COPD and initiated inhaled medications after diagnosis. Cases were defined as individuals diagnosed with lung cancer after the initiation of inhaled medications and were matched with controls by propensity score at a 1:4 ratio. We identified 265 individuals with lung cancer, matched with 1,060 controls. Use of ICS was associated with reduced risk of lung cancer (adjusted hazard ratio [aHR] 0.74, 95% CI 0.57-0.96). The high cumulative ICS dose group, defined as those above the third quartile of ICS dose distribution, had a lower risk of lung cancer than the low cumulative dose group (aHR 0.51, 95% CI 0.34-0.75). The effect of ICS on lung cancer risk reduction was more remarkable in former smokers than current smokers. Additionally, the result was consistent in men regardless of the classification according to ICS use, while it was not significant in women. ICS, particularly at high cumulative dose, might be associated with decreased risk of lung cancer in patients with COPD. Severe COPD frequently warrants treatment with inhaled corticosteroids, which exert immunomodulatory and antiproliferative effects. Despite an association between COPD and increased lung cancer risk, patients on ICS appear to have a reduced likelihood of developing lung cancer. Here, analyzing data from the National Health Insurance Service-National Sample Cohort in Korea, the authors show that ICS use is associated with decreased lung cancer risk in COPD patients. An inverse dose-response relationship was detected, whereby increasing cumulative ICS dose was associated with decreasing lung cancer risk. The effect was most pronounced in men and former smokers.

Urinary desmosine is associated with emphysema severity and frequent exacerbation in patients with COPD.

BACKGROUND AND OBJECTIVE: Matrix degradation is a key feature of chronic obstructive pulmonary disease (COPD). Desmosine and isodesmosine (desmosines) are excreted in urine following matrix degradation. The main purpose of this study was to investigate the association between computed tomography (CT) emphysema indices and urinary desmosines in patients with COPD. METHODS: A total of 152 subjects were selected from the Korean Obstructive Lung Disease cohort. Their urine samples were assayed for desmosines using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The cohort was divided into emphysema-dominant (n = 80) and non-emphysema dominant- (n = 72) groups according to the CT emphysema index. RESULTS: The level of urinary desmosines was significantly higher in the emphysema-dominant group. Significant differences were also observed between the two groups for body mass index and lung function. Multivariate analysis indicated that a high level of urinary desmosines was a significant independent predictor of emphysema (relative risk: 2.6; 95% CI: 1.11-6.09; P = 0.028). The percentage of frequent exacerbators was significantly higher in the high urinary desmosine group in the first year of follow-up (P = 0.041). The mean number of exacerbations was higher in the high urinary desmosine group, although this difference was not statistically significant (P = 0.067). The changes in emphysema index did not differ between the two urinary desmosine groups over 3 years of follow-up. CONCLUSION: This study indicates that the level of urinary desmosines measured by LC-MS/MS methods is associated with the CT emphysema index. Urinary desmosine can be a useful predictor in identifying frequent exacerbators.

Clinical outcomes and prognostic factors in patients directly transferred to the intensive care unit from long-term care beds in institutions and hospitals: a retrospective clinical study.

BACKGROUND: There has been a steady increase in the aging population and an increase in the need for long-term care beds in institutions and hospitals (LTCHs) in Korea. The aim of this study was to investigate prognosis and to identify factors contributing to mortality of critically ill patients with respiratory problems who were directly transferred to intensive care units (ICU) from LTCHs. METHODS: Following a retrospective review of clinical data and radiographic findings between July 2009 and September 2016, we included 111 patients with respiratory problems who had visited the emergency room (ER) transferred from LTCHs due to respiratory symptoms and who were then admitted to the ICU. RESULTS: The mean age of the 111 patients was 79 years, and 71 patients (64%) were male. Pneumonia developed in 98 patients (88.3%), pulmonary thromboembolism in 4 (3.6%) and pulmonary tuberculosis in 3 (2.7%). Overall mortality was 19.8% (22/111). Multiple-drug-resistant (MDR) pathogens (odds ratio [OR], 17.43; 95% confidence interval [CI], 1.96-155.40) and serum albumin levels < 2.15 g/dL, which were derived through ROC (sensitivity, 72.7%; specificity, 85.4%) (OR, 28.05; 95% CI, 5.47-143.75), were independent predictors for mortality. The need for invasive ventilation (OR, 2.74; 95% CI, 1.02-7.32) and history of antibiotic use within the 3 months (OR, 3.23; 95% CI, 1.32-7.90) were risk factors for harboring MDR pathogens. CONCLUSIONS: The presence of MDR pathogens and having low serum albumin levels may be poor prognostic factors in patients with respiratory problems who are admitted to the ICU from LTCHs. A history of antibiotic use within the 3 months and the need for invasive ventilation can be helpful in choosing the appropriate antibiotics to combat MDR pathogens at the time of admission.

Association between Genetic Variations of MERTK and Chronic Obstructive Pulmonary Disease in Koreans.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease. To date, a large number of clinical studies have been conducted to investigate the association between genetic variations and COPD. However, little is known regarding the genetic susceptibility of Koreans to this disease. MER receptor tyrosine kinase (MERTK) plays important roles in the inhibition of inflammation and in the clearance of apoptotic cells. Here, we investigated the association between genetic variations in MERTK and the development of COPD in Koreans. METHODS: We conducted genetic analysis of MERTK using genomic DNA samples from 87 patients with COPD and 88 healthy controls and compared the frequency of each variation or haplotype between the patient and control groups. Subsequently, the effect of each variation was evaluated using in vitro assays. RESULTS: Ten variations were identified in this study, four of them for the first time. In addition, we found that the frequency of each variation or haplotype was comparable between the patient and control groups. However, we observed that the frequency for the wild-type haplotype was higher in the control group, compared to that in the group of patients with COPD, in the subgroup analysis of current smokers, although the difference was not statistically significant (P = 0.080). In in vitro assays, we observed that none of the variations affected the activity of the promoter or the expression of MERTK. CONCLUSION: Our findings indicate that the susceptibility to COPD is not related to the genetic variations or haplotypes of MERTK in Koreans.

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.

Predicting survival of patients with idiopathic pulmonary fibrosis using GAP score: a nationwide cohort study.

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 DLCO 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 DLCO (%) 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.

Vitamin D Deficiency Is Associated with Rapid Decline in Exercise Capacity in Male Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Vitamin D is suggested to play a role in airway and systemic inflammation in chronic obstructive pulmonary disease (COPD). Low serum 25-hydroxyvitamin D (25-OHD) levels have been suggested to be associated with lower lung function and poorer exercise capacity in COPD. OBJECTIVES: The main purpose of this study was to investigate the effects of vitamin D deficiency on the change in exercise capacity in male COPD patients. METHODS: A total of 156 male subjects were selected from the Korean Obstructive Lung Disease cohort. Vitamin D deficiency was subdivided into three subgroups: mild, moderate, and severe deficiency groups. Rapid decline was defined as an annual rate of change in exercise capacity ≥17 m. Exercise capacity was assessed by 6-minute walk distance (6MWD). RESULTS: Significant differences were observed in the serum levels of 25-OHD, the number of patients with vitamin D sufficiency, and moderate-to-severe deficiency between rapid decliners (n = 40) and non-rapid decliners (n = 116). No differences were found between the groups for age, smoking status, lung function, and 6MWD. Multivariate analysis showed that vitamin D deficiency was independently related to rapid decline in exercise capacity (p = 0.028). A statistically significant difference was observed among the subgroups of vitamin D deficiency in terms of the change in exercise capacity (p < 0.001). The annual decline in exercise capacity was prominent in the severe deficiency group (23.1 m/year). CONCLUSION: This study shows that vitamin D deficiency is associated with rapid decline in exercise capacity in male patients with COPD.

Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study Team Cohort.

The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies.

IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.