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Background and Purpose: In endovascular procedures, inadequate deployment of a flow diverter stent is a highly concerning technical complication that can lead to acute parent vessel occlusion and ischaemic events. This study aimed to assess the off-label use of the Comaneci device in managing technical difficulties associated with flow diversion., Materials and Methods: We conducted an analysis of all flow diverter procedures documented in our prospectively collected database. Our objective was to identify patients with inadequately deployed implants who underwent Comaneci stent-angioplasty. Both Comaneci 17 and Comaneci 21 devices were utilized to address and remediate technical complications related to stent deployment. We reviewed anatomical features, technical details, intraprocedural complications, as well as clinical and angiographic outcomes., Results: Thirty-one Comaneci devices were employed to remediate 31 inadequately deployed flow diverter stents. Successful resolution of technical complications associated with flow diverter placement was achieved in all attempted cases. No clinically significant complications were attributed to the technique, and no mortality was observed during the study., Conclusion: Technical issues arising from flow diverter stent deployment are formidable complications. Familiarity with appropriate corrective manoeuvres is essential to achieve successful outcomes. The Comaneci device can be safely and effectively incorporated into the range of techniques used to rectify inadequately deployed stents.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry., Materials and Methods: This is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO 2 ) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model., Results: Among 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38-3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60-4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p  < 0.0019). Also, the C-index values slightly improved from 0.674 to 0.691 for mortality., Conclusion: The GAP6 model adding nadir SpO 2 during 6WMT for an indicator of functional capacity improves prediction ability with C-index and AUC. Additional multinational study is needed to confirm these finding and validate the applicability and accuracy of this risk assessment system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Jang, Jang, Kim, Chung, Yoo, Jeong, Song, Lee, Choi, Kim, Kim, Park, Park, Jegal, Lee, Uh, Kim, Kim, Shin, Lee, Yang, Lee, Kim, Lee, Choi, Kang, Heo, Lee and Park.)

Background: Pirfenidone, an antifibrotic medication approved for the treatment of idiopathic pulmonary fibrosis (IPF), often requires dose reduction owing to adverse events. In this study, we evaluated if pirfenidone's reduced dose has any impact on clinical outcomes in patients with IPF. Methods: We used the data of a prospective post-marketing study of pirfenidone conducted at 10 hospitals in South Korea from 2014 to 2017. Dose reduction was defined when the pirfenidone dose was temporarily or permanently reduced to manage adverse events or when the treatment dose failed to reach the standard dose. Study patients were classified based on the most frequently administered dose during 48-week follow-up-1800 mg, 1,200 mg, and <1,200 mg/days. The following clinical outcomes were compared between the groups: death, hospitalization, acute exacerbation, pulmonary function decline, and changes in severity of dyspnea and cough. Results: The median follow-up duration in all 143 patients was 11 months. During the study period, 70.6% experienced at least one dose reduction. Patients treated with standard-dose pirfenidone tended to be young and had the lowest diffusing capacity. Pulmonary function changes did not differ depending on the pirfenidone dose. The three groups were not significantly different in terms of the proportion of death, hospitalization, and acute exacerbation. The symptom changes were also similar between the groups. Conclusion: Reduced doses did not negatively impact clinical outcomes compared with the standard-dose pirfenidone in patients with IPF. Dose reduction may be a useful method to manage adverse events while maintaining therapeutic efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kang, Chung, Park, Oh, Lee, Kim, Park, Uh, Kim, Jegal and Song.)

Purpose: Various adjunctive devices have been reported to be helpful during the endovascular coiling of complex, wide-necked cerebral aneurysms. This study aimed to describe the utilization of a recently introduced intrasaccular neck-bridging implant specifically designed to facilitate coil embolization., Methods: We retrospectively reviewed eight consecutive patients who underwent treatment for intracranial aneurysms with the Nautilus intrasaccular bridging system between February 2022 to May 2022. We evaluated the angiographic appearances of treated aneurysms at the end of the procedure and early follow-up, the clinical status and complications., Results: Eight patients with eight cerebral aneurysms (3 men and 5 women, mean age 52.8 years (range 39-66) were analyzed. Five of the treated aneurysms were managed in an acute case scenario. There were no technical difficulties while executing the technique. No other procedural adverse events were documented. Immediate complete occlusion of the aneurysm was seen in 6 patients, neck remnant in 1 and stable aneurysm reperfusion in one case. Early radiological follow-up was available in five patients, and the observed occlusion rates were - RR class I in all radiologically screened aneurysms., Conclusion: Nautilus-assisted coil embolization represents a rapid and safe solution for complex cerebral aneurysms. In our opinion this device symbolizes a significant step forward in treating intracranial aneurysms. We believe that the technique's actual value consists of the fact that the device is fully compatible with the modern low-profile microcatheter technology and does not involve the need for antiplatelet medications.

Coronavirus disease 2019 (COVID-19) has become a major health burden worldwide, with over 450 million confirmed cases and 6 million deaths. Although the acute phase of COVID-19 management has been established, there is still a long way to go to evaluate the long-term clinical course or manage complications due to the relatively short outbreak of the virus. Pulmonary fibrosis is one of the most common respiratory complications associated with COVID-19. Scarring throughout the lungs after viral or bacterial pulmonary infection have been commonly observed, but the prevalence of post- COVID-19 pulmonary fibrosis is rapidly increasing. However, there is limited information available about post-COVID-19 pulmonary fibrosis, and there is also a lack of consensus on what condition should be defined as post-COVID-19 pulmonary fibrosis. During a relatively short follow-up period of approximately 1 year, lesions considered related to pulmonary fibrosis often showed gradual improvement; therefore, it is questionable at what time point fibrosis should be evaluated. In this review, we investigated the epidemiology, risk factors, pathogenesis, and management of post-COVID-19 pulmonary fibrosis.

Background and Purpose: Recently, avant-garde combinations of ancillary devices as an adjunct to coil embolization for acutely ruptured and wide-necked cerebral aneurysms have emerged. This study sought to investigate the feasibility, safety and durability of the simultaneous combination of temporary neck-bridging devices plus balloon-assisted coiling (BAC) to treat acutely ruptured and wide-necked cerebral aneurysms., Methods: A retrospective review was performed of patients with ruptured and wide-necked intracranial bifurcation aneurysms treated with temporary stent plus balloon-assisted coiling. Anatomical features, technical details, intraprocedural complications, clinical and angiographic results were reviewed. Preprocedural and follow-up clinical statuses were evaluated using the modified Rankin scale (mRS)., Results: A total of 21 patients (mean age 54.5 years, range 37-72 years) were identified. The immediate postprocedural angiography revealed complete aneurysm occlusion in 85.7% (18/21) of the cases. A periprocedural complication developed in 9.5% of the cases. There was no mortality in this study. The permanent morbidity rate was 4.7%. Long-term follow-up angiography was performed in 18 of 21 patients (85.7%) (the mean follow-up period was 21 months). The rate of complete aneurysm occlusion at final follow-up was 89.4%., Conclusion: The results of this study confirmed that temporary stent plus balloon-assisted coiling is a durable and relatively safe endovascular technique for the treatment of ruptured wide-necked bifurcation aneurysms located in both the posterior and anterior cerebral circulation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The main cause of death in pulmonary embolism (PE) is right-heart failure due to acute pressure overload. In this sense, extracorporeal membrane oxygenation (ECMO) might be useful in maintaining hemodynamic stability and improving organ perfusion. Some previous studies have reported ECMO as a bridge to reperfusion therapy of PE. However, little is known about the patients that benefit from ECMO., Methods: Patients who underwent ECMO due to pulmonary thromboembolism at a single university-affiliated hospital between January 2010 and December 2018 were retrospectively reviewed., Results: During the study period, nine patients received ECMO in high-risk PE. The median age of the patients was 60 years (range, 22-76 years), and six (66.7%) were male. All nine patients had cardiac arrests, of which three occurred outside the hospital. All the patients received mechanical support with veno-arterial ECMO, and the median ECMO duration was 1.1 days (range, 0.2-14.0 days). ECMO with anticoagulation alone was performed in six (66.7%), and ECMO with reperfusion therapy was done in three (33.3%). The 30-day mortality rate was 77.8%. The median time taken from the first cardiac arrest to initiation of ECMO was 31 minutes (range, 30-32 minutes) in survivors (n=2) and 65 minutes (range, 33-482 minutes) in non-survivors (n=7)., Conclusion: High-risk PE with cardiac arrest has a high mortality rate despite aggressive management with ECMO and reperfusion therapy. Early decision to start ECMO and its rapid initiation might help save those with cardiac arrest in high-risk PE.

Background: The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients., Methods: Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015., Results: A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-agephysiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality., Conclusion: In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.

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).

Background: Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein with a large extracellular domain with overexpression of the prostatic tumour cells. Several small molecules of PSMA ligands of inhibitors binding to the active site of PSMA were developed. [99mTc]Tc-PSMA-T4 is a new radiopharmaceutical (Polatom) for imaging loco-regional metastases and/or local relapse in patients with prostate cancer. The purpose of this work was to evaluate the clinical application of SPECT-CT imaging with [99mTc]Tc-PSMA-T4 in patients with recurrent prostate cancer., Material and Methods: Thirty-six patients with prostate cancer, aged 60-80 years with biochemical relapse of PSA (ranged from 0.1 to 73 ng/mL) were included. Three patients were studied after tru-cut biopsy, hormonal and cytoreductive radiotherapy and 33 patients out of 36 - after radical treatment (total prostatectomy or definitive radiotherapy of the tumour). All of them underwent whole-body imaging examinations with subsequent target SPECT-CT studies of the pelvis, abdomen and/or chest, 1-3 hrs post i.v. administration of [99mTc]Tc-PSMA-T4. The average activity dose was 6.3 MBq/kg in a man of 70 kg. A Dual-head SPECT-CT gamma camera with a low dose CT scan (Symbia T2, Siemens) was used. The images were interpreted based on all other clinical and radiological data. Follow-up could be conducted in 11/36 patients during that period., Results: Normal biodistribution of the radiopharmaceutical with high activity background was observed in the liver, spleen, kidneys, lacrimal and salivary glands, bowels and urinary bladder. Positive imaging for local relapse in the prostate bad was imaged in 21 patients, lymph node metastases - in 16 cases, bone lesions - in 10 cases, pulmonary metastases - in 2 cases, hepatic lesions were visualised in one of them and in another - adrenal suprarenal metastasis with intensive tracer uptake significant for overexpression of PSMA. There was a suspicion for local recurrences in 4 patients with negative MRT studies who were followed up. In 3 cases, previously treated bone metastases were partially negative without tracer uptake, only some progressive bone lesions were positive. Five patients were with negative results. Sensitivity was 84.37% (27/32), specificity - 100% (4/4) and accuracy - 86.11% (31/36)., Conclusions: In conclusion SPECT-CT imaging with [99mTc]Tc-PSMA-T4 could be applied in patients with prostate cancer for the diagnosis of recurrent disease to determine personalized treatment for each patient. Specific uptake of this tracer, depicted by SPECT-CT images has clinical importance of identifying and assessing PSMA expression before consideration of Radio Ligand Therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA. SPECT-CT imaging with [99mTc]PSMA is promising and reliable nuclear medicine approach to monitoring therapeutic effect after treatment and for restaging of the disease.

Background: Wide-necked cerebral aneurysms in the setting of acute subarachnoid hemorrhage (SAH) remain difficult to treat with endovascular methods despite recent progress in the neuroendovascular field., Objective: To evaluate the effectiveness and safety of the Comaneci device (Rapid Medical, Israel) in endovascular coil embolization of acutely ruptured, wide-necked sidewall, or bifurcation cerebral aneurysms., Methods: We retrospectively reviewed 45 anterior communicating artery, 24 internal carotid artery, 21 middle cerebral artery bifurcation, 15 anterior cerebral artery, and 13 posterior circulation aneurysms, which were treated using Comaneci-assisted coil embolization from August 2017 to January 2019. We evaluated procedural complications, clinical outcomes, and mid-term angiographic follow-up. Immediate and 90 d-clinical outcome and radiological follow-up were obtained in all patients., Results: Comaneci-assisted coil embolization was performed in 118 acutely ruptured aneurysms. The technique was carried out successfully in all cases. Simultaneous application of 2 separated Comaneci devices was performed in 8/118 cases (6.77%). Periprocedural thromboembolic complications related to the device were seen in 7/118 cases (5.93%) and severe vasospasm of the parent artery after manipulation of the Comaneci device occurred in 5/118 cases (4.2%). The procedural-related morbidity rate was 2.54%, and there was no procedural related mortality. Among the available survivors, angiographic follow-ups were obtained at 3 and 6 mo, and complete aneurysmal obliteration was confirmed in 81/112 (72.3%) and 75/112 (66.9%) cases, respectively. Mid-term follow-up reviewed total recanalization rate of 14.28%., Conclusion: Comaneci-assisted embolization of wide-necked intracranial aneurysms in patients presenting with acute SAH is associated with high procedural safety and adequate occlusion rates. Furthermore, dual antiplatelet therapy can be safely avoided in this patient group., (© Congress of Neurological Surgeons 2020.)

Background: The p48 MW Flow Modulation Device (phenox, Bochum Germany) is a low profile flow diverter stent (FDS), designed for implantation into intracranial arteries with a diameter of less than 3.5 mm., Objective: To evaluate the safety and efficacy of the p48 MW FDS in the treatment of unruptured aneurysms located at intracranial arteries with less than 3.5 mm diameter based on a retrospective analysis from a single tertiary neurovascular center., Methods: A prospectively maintained database was retrospectively reviewed to identify all cases of intracranial saccular aneurysms treated electively with the p48 MW device. Records were made of basic demographics, aneurysmal characteristics, interventional procedures, adverse events, clinical outcomes and occlusion rates on angiographic follow-ups., Results: A total of 77 aneurysms and 74 patients were included. The mean size of the treated aneurysms was 3.5 ± 2.4 mm and the mean aspect ratio was 1.3 ± 0.4. A total of 80 endovascular procedures were performed with a total of 12 (15%) adverse events leading to two (2.5%) permanent morbidities/mortalities. Technical issues were encountered in 3 (3.9%) cases. Adequate occlusion of the treated aneurysm was recorded in 55.6% and 63.9% on the first and latest available DSA follow-ups, respectively. There were no cases of side-branch occlusion., Conclusions: The p48 MW is an easy-to-use implant with very good safety margins. Side branch occlusion and significant in-stent stenosis are infrequently encountered. The time from implantation to sufficient aneurysm occlusion takes longer than with FDS with lower porosity.

Aim: The efficacy and safety of pirfenidone have been previously demonstrated in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). However, the effect of pirfenidone in patients with advanced IPF remains unclear. Here, we investigated the effects of pirfenidone against advanced IPF in a real-world setting., Methods: A prospective nationwide post-marketing study was conducted on 258 patients from 10 Korean institutions. Patients with a predicted forced vital capacity (FVC) less than 50% or a diffusing capacity of the lung for carbon monoxide (DLco) less than 35% at baseline were classified as the advanced IPF group., Results: Of 219 patients included in the analysis, the majority were male (76.3%); the mean age was 67.3 years, and the advanced group accounted for 17.8% of the patients. The median treatment duration was 298 days. Among the subjects, 86.3% experienced adverse events (AEs), of which a decreased appetite (32.4%) and a photosensitivity reaction (13.7%) were the most frequent. The incidence of AEs was similar between the advanced and non-advanced groups (92.3% vs. 85.0%, respectively; p = 0.229). Although the overall discontinuation rate was higher in the advanced group than in the non-advanced group (74.4% vs. 50.0%, respectively; p = 0.006), the percentages of the patients who discontinued treatment as a result of AEs were similar in both groups (20.5% vs. 23.3%, respectively; p = 0.704). In all patients, the rates of decline in the predicted FVC and DLco over 48 weeks were - 4.3 ± 1.3% and - 4.4 ± 1.7%, respectively. There was no between-group difference in the rate of lung function decline., Conclusions: Pirfenidone used for the treatment of patients with IPF in a real-world setting was well tolerated, with an acceptable safety profile and a consistent therapeutic effect, regardless of the disease severity., Trial Registration: ClinicalTrials.gov NCT03761082; the trial was retrospectively registered on December 3, 2018.

Background and Purpose: Conventional nonadhesive liquid embolic agents currently are the criterion standard for endovascular embolization of cerebral AVMs. However, inadequate distal penetration into the nidus and unstable proximal plug formation are the major limitations of this approach and of the currently available embolic materials. The aim of this study was to evaluate the hypothetic efficacy of combining liquid embolic agents with different properties and viscosities for use in endovascular embolization of cerebral AVMs., Materials and Methods: From March 2018 to March 2019, sixteen patients with cerebral AVMs (12 women, 4 men; age range, 33-61 years) underwent endovascular embolization with combined liquid embolic agents delivered serially via a single microcatheter. The procedure consists of initial embolization with PHIL 30%, followed by Menox 18 through the same microcatheter. According to the Spetzler-Martin scale, 11 (68.75%) AVMs were grades I-II, 4 (25%) were grade III, and 1 (6.25%) was grade IV. Angiographic, technical, and clinical outcomes were analyzed independently., Results: Combined PHIL and Menox embolization through the same microcatheter via 21 pedicles was performed in these 16 patients. Once the length of the reflux reached approximately 2 cm, PHIL 30% was switched to Menox 18. Antegrade flow and distal penetration of the serially applied liquid embolic agents were observed in all 16 cases. The ability to completely control the flow of the materials and avoid any dangerous proximal reflux was noted in all performed embolizations. The estimated average size reduction of the treated AVMs was 85%, ranging from 50% to 100%. Complete embolization was achieved in 10/16 or 62.5% of the cases. There was no procedure-related complication during or after the embolization. No mortality or postprocedural clinical worsening was seen. Clinical success and complete obliteration were confirmed with at least 1 follow-up angiography in 10/16 patients., Conclusions: Serial delivery of nonadhesive liquid embolic agents via the same microcatheter was safe and effective in our study and may be a potential technique for routine AVM treatment. However, further investigations are required to validate the safety and the efficacy of the method., (© 2020 by American Journal of Neuroradiology.)

Background: Temporary placement of a retrievable neck bridging device, allowing parent vessel flow, is an attractive alternative to balloon remodeling for treatment of ruptured intracranial aneurysms., Objective: To present, in a single-center study, our initial experience with Cascade (Perflow, Israel) in the treatment of ruptured intracranial aneurysms., Methods: During a period of 1.5 months, 12 patients with aneurysmal subarachnoid hemorrhage underwent coil embolization in conjunction with Cascade in our center. Retrospective analysis of prospectively collected angiographic and clinical data was conducted to assess the safety and efficacy of the device., Results: Among all treated patients, 41.7% (5/12) were female, the median age was 55 (47-77) years, the median aneurysm dome size was 5.75 mm (3-9.1), and the median neck size was 3.55 mm (2.3-7.9). Complete obliteration (Raymond 1) was achieved in 75% (9/12) of cases, and intentional residual neck (Raymond 2) was left in three cases (25%). None of the patients received any oral or intravenous antiplatelet therapy perioperatively. No thromboembolic complications, device-related spasm, vessel perforation, or coil entanglement were detected in any of the treated patients., Conclusions: In our initial experience, treatment of wide-neck ruptured intracranial aneurysms with Cascade is safe and effective, without the need for adjuvant antiplatelet therapy. Long-term follow-up data in larger cohorts are needed to confirm these preliminary findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Liquid embolic agents (LEAs) are the determinant tool for successful embolization of cranial arteriovenous shunts. There are few currently available LEAs. The aim of the study was to summarize our initial experience with a recently introduced non-adhesive ethylene vinyl alcohol (EVOH) copolymer based LEA (Menox 18) in the endovascular treatment of cerebral arteriovenous malformations., Methods: From April 2018 to November 2018, 24 patients harboring cerebral arteriovenous malformations underwent endovascular embolization with Menox 18. Clinical features, angiographic results, procedural details, complications, and follow-up details were prospectively collected and retrospectively analyzed., Results: Curative embolization in one endovascular session was achieved in 14/24 (58.3%) of the treated patients. Partial embolization was achieved in 10 patients (42.6%) in whom staged treatment with radiosurgery or microsurgical resection was planned. No mortality was recorded in our series. Clinical complications after embolization occurred in 1/24 (4.66%) patients. No technical complications were noted CONCLUSIONS: Our pilot study suggests that the Menox embolization system offers similar technical and clinical results in comparison with the other currently available LEAs. Further studies with larger cohorts and long term follow-up data are needed to fully evaluate its efficacy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Importance: The endovascular treatment of recurrent wide-necked bifurcation aneurysms at the basilar tip remains very challenging. Many different techniques and devices have emerged in recent years as potential options but results remain less than controversial. The pCANvas is a relatively new device wielding neck-bridging properties with a haemodynamically active membrane acting as blood flow disrupter., Clinical Presentation: We present the clinical case of a patient in whom multiple endovascular and microsurgical attempts failed to achieve the definitive treatment of a large and wide-necked basilar tip aneurysm. The patient underwent successful endovascular implantation of the novel pCANvas device across the recurrent aneurysm neck. The device limited the blood flow to the anerysmal lumen and thus promoted faster thrombosis. Third month follow-up confirmed complete obliteration of the aneurysm., Conclusion: The application of the pCANvas device offers a potential treatment option in difficult and recurrent aneurysms. The endovascular flow disruption is a relatively new feature aiming to create conditions for intraluminal thrombosis and is certainly promising for the treatment of complex bifurcation aneurysms.

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) share common risk factors. They could therefore be expressed in a single patient. However, the prevalence, clinical characteristics and prognosis of individuals with comorbid IPF and COPD are not known. From 2003 to 2007, the Korean Interstitial Lung Disease Study Group created a register for idiopathic interstitial pneumonia using 2002 ATS/ERS (American Thoracic Society/European Respiratory Society) criteria. Of the 1546 IPF patients assessed, 143 had decreased lung function consistent with COPD (IPF-COPD). COPD was diagnosed based on age (≥40 years) and pulmonary function (forced expiratory volume in 1 sec [FEV 1 ]/forced vital capacity [FVC] ratio < 0.7). The median age of the IPF-COPD group was 71.0 years (interquartile range 66.0-76.0); most patients were male (88.1%). FVC (%) was significantly higher in the IPF-COPD group; however, FEV 1 (%) was significantly lower in the IPF-COPD group ( P < 0.001). Diffusing capacity of the lung for carbon monoxide (DL CO ) was not significantly different between the two groups. In survival analysis, age and FVC (%), but not COPD, were significantly associated with prognosis (respectively P = 0.003, 0.001 and 0.401). COPD severity was also not related to prognosis ( P = 0.935). The prevalence of IPF-COPD was estimated to be ∼9.2% among all IPF patients; prognosis of patients with IPF-COPD was not worse than those with IPF alone. .

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.)

Internal carotid artery (ICA) injury is a rare but potentially life-threatening complication of skull base and neck surgery. Although usually manifested by massive intraoperative haemorrhage, impairment of the ICA might go unnoticed and result in formation of a pseudoaneurysm, causing delayed bleeding. Often additional complications are observed such as thrombosis, spasm, embolism or carotico-cavernous fistula formation. The risk of carotid artery injury in aggressive endonasal skull base surgical interventions ranges from 1% to 9%. Digital subtracted angiography remains the gold standard for evaluation of patients with iatrogenic carotid artery injury as it allows for endovascular treatment at the time of the procedure. Endovascular embolization is currently the preferred method for treating ICA pseudoaneurysms and a successful alternative to the surgical approach. Even though endovascular approaches are considered the safer option, delayed complications have been registered, such as endovascular coil extrusion and migration, which increases the risk of further episodes of bleeding. We present our experience with late coil extrusion in a patient who was previously treated with flow diverter stent and coiling for iatrogenic ICA pseudoaneurysm.

Background: Precipitating hydrophobic injectable liquid is a newly introduced liquid embolic agent for endovascular embolization with some technical advantages over other liquid embolic agents. We present our initial experience with precipitating hydrophobic injectable liquid in the endovascular treatment of cerebral arteriovenous malformations., Methods: From October 2015 to January 2018, 27 patients harboring cerebral arteriovenous malformations underwent endovascular embolization with precipitating hydrophobic injectable liquid 25. Clinical features, angiographic results, procedural details, complications, and follow-up details were retrospectively analyzed., Results: Twenty-seven patients with cerebral arteriovenous malformations were included. Total obliteration in one endovascular session was confirmed for 14/27 (52%) patients. Partial embolization was attained in 13 patients (48%) in whom staged treatment with following radiosurgery or surgery was planned. No mortality was recorded in this series. Complications during or after the embolization occurred in six of 27 (22.2%) patients., Conclusion: In our initial experience, precipitating hydrophobic injectable liquid has acceptable clinical outcome comparable to other liquid embolic agents. Although this is the largest reported study in arteriovenous malformation treatment with precipitating hydrophobic injectable liquid, further studies are needed to validate its safety and efficacy.

Asthma exacerbation is induced by the interaction of genes and environmental factors such as cigarette smoke. NLRP4 counteracts the activity of the inflammasome, which is responsible for asthma exacerbation. In this study, we analyzed the association of single-nucleotide polymorphisms of NLRP4 with the annual rate of exacerbation and evaluated the additive effect of smoking in 1454 asthmatics. Asthmatics possessing the minor allele of rs1696718G > A had more frequent exacerbation episodes than those homozygous for the common allele (0.59 vs. 0.36/year) and the association was present only in current and ex-smokers. There was a significant interaction between the amount smoked and rs16986718 genotypes (p = 0.014) and a positive correlation between the number of annual exacerbation episodes and amount smoked only in rs16986718G > A AA homozygotes. The prevalence of frequent exacerbators (≥2 exacerbation episodes/year) was 2.5 times higher in rs16986718G > A minor allele homozygotes than in common allele homozygotes (12.0% vs. 5.9%). Furthermore, the prevalence was 6 times higher in rs16986718G > A minor allele homozygotes who were current and ex-smokers than in nonsmokers (25.6% vs. 4.1%). The minor allele of rs16986718G > A in NLRP4 may be a genetic marker that predicts asthma exacerbation in adult asthmatics who smoke.

Background: Fenestration of the basilar artery is a segmental duplication of the vessel due to nonfusion of the embryonal arteries and is the second most common vascular disjunction. Here, we present a single case example demonstrating the utility of the temporary bridging device Comaneci as a new option in the endovascular treatment of ruptured basilar artery aneurysms associated with fenestrations., Case Description: A 57-year-old female patient presented to our hospital with a 3-month history of frequent multiple sentinel severe headaches. At the time of hospitalization, the patient was neurologically intact with a Glasgow Coma Scale score of 15. There was no evidence of focal neurologic deficits or cranial nerve lesions, but there was discrete neck stiffness and a diagnosed saccular aneurysm associated with a fenestration of the basilar artery. After multidisciplinary discussion involving neurosurgeons and interventional neuroradiologists and taking into consideration the patient's clinical presentation and previous history of subarachnoid hemorrhage, as well as the morphology of the posterior circulation aneurysm, endovascular treatment of the basilar fenestration aneurysm was deemed appropriate or simply use was chosen., Conclusions: Our case results are similar to previously published good results of endovascular coiling and add information regarding the relatively new Comaneci device, which helped to achieve considerable packing density of the aneurysmal sac. Using this device lowers the risk of peri- and postoperative complications. We believe that this technique is safer and better than the balloon-assisted and stent-assisted coiling in ruptured case scenarios of wide-neck aneurysms in the posterior circulation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The difficulties in obtaining complete and stable endovascular occlusion are most evident for ruptured aneurysms exhibiting a wide neck and unfavorable geometric features. The aim of our study was to present our experience with the Comaneci temporary bridging device in ruptured wide neck aneurysms., Methods: From May to July 2017, 29 ruptured aneurysms underwent endovascular embolization with the Comaneci device. Angiographic and clinical results were retrospectively analyzed., Results: 29 ruptured intracranial aneurysms from different locations were included. Successful embolization was achieved in all lesions; complete post-procedure occlusion was seen in 25 (86%) cases. Insufficient embolization or neck remnant was observed in four cases (13.7%). Complications probably related, directly related, or indirectly related to the device occurred in 3.44% of patients (1/29 patients). At least one angiographic follow-up was performed in each of the 29 cases. The 12 month follow-up examination has yet to be done., Conclusion: The Comaneci device offers a new promising and reliable technique that can safely support aneurysm coiling occlusion even in a rupture environment. However, long term monitoring of patients treated by this device is mandatory., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Multidisciplinary discussions (MDDs) have emphasized improve medical services and outcomes. We used a multidisciplinary approach to explore whether patient emotional satisfaction and confidence affected treatment outcomes in rheumatic disease (RD)-related interstitial lung disease (ILD)., Methods: From December 2015 to April 2017, we evaluated 23 patients with RD and ILD and 21 with idiopathic pulmonary fibrosis (IPF). Patients with RD and ILD were managed with MDDs. Patients with IPF received standardized medical care by the same pulmonologist. All patients completed brief multiple-choice questionnaires exploring their perceptions of their illnesses and their attitudes toward medical treatment, and completed the Patient Health Questionnaire-2., Results: The MDD patients could more easily identify disease symptoms regardless of age stratification (under 65 age: P = 0.020, 65 years or older: P = 0.003). Among the 65 years or older group, it shows higher levels of illness perception in terms of disease timeline in the MDD group (P = 0.035). Also, the MDD group reported higher levels of satisfaction in terms of the explanations they received and their involvement in discussion, and greater satisfaction with medical staff. However, the groups did not differ significantly between treatment outcomes such as changes in forced vital capacity, the diffusion capacity of carbon monoxide, or changes in high-resolution computed tomography., Conclusions: MDDs afforded satisfactory management compared with standardized medical care. The MDD group felt better attention fromand satisfaction with medical staff, and had greater identification in their treatment. Further research engaging in MDDs with a comparable control group is required., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

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.

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.

Purpose: Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation., Methods: A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters., Results: Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation., Conclusions: Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease)

Background: Most patients with influenza recover spontaneously or following treatment with an anti-viral agent, but some patients experience pneumonia requiring hospitalization. We conducted a retrospective review to determine the incidence and risk factors of pneumonia in hospitalized patients with influenza A or B., Methods: A total of 213 patients aged 18 years or older and hospitalized with influenza between January 2012 and January 2015 were included in this study. A reverse-transcriptase polymerase chain reaction assay was used to detect the influenza A or B virus in the patients' sputum samples. We collected demographic and laboratory data, combined coexisting diseases, and radiologic findings., Results: The incidence of pneumonia was higher in patients in the influenza A group compared to those in the influenza B group (68.6% vs. 56.9%), but this difference was not statistically significant. The presence of underlying respiratory disease was significantly associated with pneumonia in the influenza A group (adjusted odds ratio [OR], 3.975; 95% confidence interval [CI], 1.312-12.043; p=0.015). In the influenza B group, the white blood cell count (adjusted OR, 1.413; 95% CI, 1.053-1.896; p=0.021), platelet count (adjusted OR, 0.988; 95% CI, 0.978-0.999; p=0.027), and existence of an underlying medical disease (adjusted OR, 15.858; 95% CI, 1.757-143.088; p=0.014) were all significantly associated with pneumonia in multivariate analyses., Conclusion: The incidence of pneumonia was 65.7% in hospitalized patients with influenza A or B. The risk factors of pneumonia differed in hospitalized patients with influenza A or B., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright©2017. The Korean Academy of Tuberculosis and Respiratory Diseases)

S100A9 is an endogenous danger signal that promotes and exacerbates the neutrophilic inflammatory response. To investigate the role of S100A9 in neutrophilic asthma, S100A9 levels were measured in sputum from 101 steroid-naïve asthmatics using an ELISA kit and the levels were significantly correlated with percentages of neutrophils in sputum. Intranasal administration of recombinant S100A9 markedly increased neutrophil numbers at 8h and 24h later with concomitant elevation of IL-1β, IL-17, and IFN-γ levels. Treatment with an anti-S100A9 antibody restored the increased numbers of neutrophils and the increased airway resistance in OVA/CFA mice toward the levels of sham-treated mice. Concomitantly, the S100A9 and neutrophil elastase double positive cells were markedly reduced with attenuation of IL-1β, IL-17, and IFN-γ levels by the treatment with the anti-S100A9 antibody. Our data support a role of S100A9 to initiate and amplify the neutrophilic inflammation in asthma, possibly via inducing IL-1β, IL-17 and IFN-γ., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/aims: Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inf lammasome. In this study, we elucidated whether NLRP3 -inf lammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation., Methods: RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of interleukin-1β (IL-1β), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry., Results: NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of IL-1β in RAW 264.7 cells. The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC. CSE and DEPs increased the secretion of IL-1β in lung tissues from both the normal and elastase-induced emphysema groups. The secretion of IL-1β by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: 309 ± 19 pg/mL vs. 151 ± 13 pg/mL, respectively, p < 0.05; DEP: 350 ± 24 pg/mL vs. 281 ± 15 pg/mL, respectively, p < 0.05). NAC inhibited CSE- and DEP-induced IL-1β secretion in both the normal and elastase-induced emphysema groups. NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC., Conclusions: The NLRP3-inf lammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC.

Purpose: Comparisons of the characteristics of chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome (ACOS) have been the focus of several studies since the diseases were defined by the Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. However, no consensus is available yet. In this study, we aimed to compare the characteristics of asthma-COPD overlap (ACO) and COPD., Methods: We retrospectively reviewed 1,504 patients with COPD in a Korean COPD Subtype Study cohort. The occurrence of ACO was defined as a positive response to a bronchodilator (an increase in forced expiratory volume in 1 second [FEV1] of 12% and 200 mL)., Results: Among 1,504 patients with COPD, 223 (14.8%) were diagnosed with ACO. Men (95.5%) and current smokers (32.9%) were more prevalent in the ACO group compared with the pure COPD group (90.5% and 25.3%, respectively; P=0.015 and P=0.026, respectively). Patients with ACO had a better quality of life (St. George's Respiratory Questionnaire for COPD score=31.0±18.0 [mean±standard deviation]) than those with pure COPD (35.3±19.1) (P=0.002). Although the prevalence of acute exacerbation was not different between the 2 groups, patients with severe exacerbation required hospital admission significantly more frequently in the pure COPD group than in the ACO group. Patients with ACO showed a higher likelihood of FEV1 recovery than those with pure COPD (P<0.001)., Conclusions: We suggest that ACO is characterized by less severe symptoms, and therefore it might lead to rare severe exacerbation and the possibility of lung function recovery., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease)

Background: Ozone is well known as an important component of ambient air pollutants. Ozone can aggravate respiratory symptoms in patients with bronchial asthma, but, not in healthy person. We hypothesized asthma itself may show different response to ozone compared to nonasthma., Objective: This study was performed to evaluate the differences of response to ozone between normal and asthmatic mice model in terms of status of oxidant injury and antioxidant activity., Methods: Three parts per million of ozone was exposed to ovalbumin (OVA)-induced murine asthma model for 3 hours at 3, 7, 14, 21 days after completion of asthma model. Airway responsiveness to methacholine was measured after completion of asthma model. Bronchoalveolar lavage (BAL), protein extraction from lung for Western blot and immunohistochemistry of 4-hydroxy-2-nonenal (4-HNE), proliferating cell nuclear antigen (PCNA), NF-E2 related factor 2 (Nrf-2), and activity of glutathione were performed at before and each ozone exposure day., Results: Airway hyper-responsiveness and increased eosinophils in BAL fluid were observed in asthma model. In asthma model, the expression of 4-HNE already more increased at baseline (without ozone) compared to those in sham model. This increased expression is more enhanced at 3 days after ozone exposure. The expression of PCNA was significantly increased in OVA-model compared to those in sham model. The expression of Nrf-2 was observed at baseline, and 3 and 7 days after exposure ozone in asthma model, but not in sham model. The activity of glutathione increased significantly after exposure of ozone, but not in sham model., Conclusion: Murine asthma model has enhanced oxygen toxicity and antioxidant activity response to ozone.

Interstitial lung disease (ILD) occurs in 15% of patients with collagen vascular disease (CVD), referred to as connective tissue disease (CTD). Despite advances in management strategies, ILD continues to be a significant cause of mortality in patients with CVD-associated ILD (CTD-ILD). There is a lack of randomized, clinical trials assessing pharmacological agents for CTD-ILD, except in cases of ILD-associated systemic sclerosis (SSc). This may be due to the lack of CTD cases available, the difficulty of histological confirmation of ILD, and the various types of CTD and ILD. As a result, evidence-based pharmacological treatment of CTD-ILD is not yet well established. CTD-ILD presents with varying degrees of histology, from inflammation to fibrosis, and a wide spectrum of clinical manifestations, from minimal symptoms to respiratory failure. This renders it difficult for clinicians to make decisions regarding treatment options, observational strategies, optimal timing for interventions, and the appropriateness of pharmacological agents for treatment. There is no specific treatment for reversing fibrosis-like idiopathic pulmonary fibrosis in a clinical setting. This review describes pharmacological interventions for SSc-ILD described in randomized control trials, and presents an overview of recent advances of CTD-ILD-dependent treatments based on the types of CTD.

Oral anticoagulant therapy is frequently and increasingly prescribed for patients at risk of arterial or venous thromboembolism (VTE). Although elective surgical or invasive procedures have necessitated temporary interruption of anticoagulants, managing these patients has been performed empirically and been poorly investigated. This study was designed to evaluate the adequacy of perioperative anticoagulation using enoxaparin. This was a retrospective, single-center study that evaluated the efficacy and safety of therapeutic-dose enoxaparin for bridging therapy in patients on long-term warfarin at Soonchunhyang University Hospital in Korea between August 2009 and July 2011. Warfarin was discontinued 5 days before surgery, and enoxaparin was administered twice daily by subcutaneous injection at a dose of 1 mg per kg from 3 days before the procedure to the last dose 24 hours before the procedure. Anticoagulation was restarted if proper hemostasis had been confirmed. There were 49 patients, of whom 25 (51%) were men, and the mean age was 63 years. Thirty-four (69%) received warfarin therapy for VTE, and 9 (18%) for atrial fibrillation. Twenty-nine patients (59%) underwent major surgery and 20 (41%) minor surgery. The mean postoperative duration of enoxaparin was 4 days. No patients had thromboembolic complications through 30 days after the procedure. The overall 30-day mortality rate was 0%. In conclusion, our findings demonstrate that bridging therapy with therapeutic-dose enoxaparin is feasible and associated with a low incidence of major bleeding and no thromboembolic complications. However, the optimal approach to managing patients perioperatively is uncertain and requires further evaluation., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2017 The Korean Academy of Medical Sciences.)

Background: Innate T helper type 2 (Th2) immune responses mediated by interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been shown to play an important role in pulmonary fibrosis of animal models; however, their clinical implications remain poorly understood., Methods: TSLP, IL-25, and IL-33 concentrations were measured in bronchoalveolar lavage fluids obtained from normal controls (NCs; n = 40) and from patients with idiopathic pulmonary fibrosis (IPF; n = 100), non-specific interstitial pneumonia (NSIP; n = 22), hypersensitivity pneumonitis (HP; n = 20), and sarcoidosis (n = 19)., Results: The TSLP and IL-33 levels were significantly higher in patients with IPF relative to the NCs (p = 0.01 and p = 0.0001, respectively), NSIP (p = 4.95E - 7 and p = 0.0002, respectively), HP (p = 0.00003 and p = 0.000005, respectively), and sarcoidosis groups (p = 0.003 and p = 0.0001, respectively). However, the IL-25 levels were not significantly different between NC and IPF group (p = 0.432). Receiver operating characteristic curves of the TSLP and IL-33 levels revealed clear differences between the IPF and NC groups (AUC = 0.655 and 0.706, respectively), as well as between the IPF and the other lung disease groups (AUC = 0.786 and 0.781, respectively). Cut-off values of 3.52 pg/μg TSLP and 3.77 pg/μg IL-33 were shown to differentiate between the IPF and NC groups with 99.2 and 94.3% accuracy. Cut-off values of 4.66 pg/μg TSLP and 2.52 pg/μg IL-33 possessed 99.4 and 93.2% accuracy for differentiating among the IPF and other interstitial lung disease groups., Conclusions: Innate immune responses may be associated with the development of IPF. Furthermore, the IL-33 and TSLP levels in BAL fluids may be useful for differentiating IPF from other chronic interstitial lung diseases.

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the complex interaction of cells involved in chronic inflammation and fibrosis. Global gene expression of a homogenous cell population will identify novel candidate genes., Methods: Gene expression of fibroblasts derived from lung tissues (8 IPF and 4 controls) was profiled, and ontology and functional pathway were analyzed in the genes exhibiting >2 absolute fold changes with p-values < 0.05. CCL8 mRNA and protein levels were quantified using real-time PCR and ELISA. CCL8 localization was evaluated by immunofluorescence staining., Results: One hundred seventy eight genes differentially expressed and 15 genes exhibited >10-fold change. Among them, 13 were novel in relation with IPF. CCL8 expression was 22.8-fold higher in IPF fibroblasts. The levels of CCL8 mRNA and protein were 3 and 9-fold higher in 14 IPF fibroblasts than those in 10 control fibroblasts by real-time PCR and ELISA (p = 0.022 and p = 0.026, respectively). The CCL8 concentrations in BAL fluid was significantly higher in 86 patients with IPF than those in 41 controls, and other interstitial lung diseases including non-specific interstitial pneumonia (n = 22), hypersensitivity pneumonitis (n = 20) and sarcoidosis (n = 19) (p < 0.005, respectively). Cut-off values of 2.29 pg/mL and 0.43 pg/mL possessed 80.2 and 70.7% accuracy for the discrimination of IPF from NC and the other lung diseases, respectively. IPF subjects with CCL8 levels >28.61 pg/mL showed shorter survival compared to those with lower levels (p = 0.012). CCL8 was expressed by α-SMA-positive cells in the interstitium of IPF., Conclusions: Transcriptome analysis identified several novel IPF-related genes. Among them, CCL8 is a candidate molecule for the differential diagnosis and prediction of survival.

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: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1-induced EMT in experimental lung fibrosis and clarify its mechanism of action., Methods: The A549 alveolar epithelial cell line was treated with TGF-β1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-β1 receptor type 1 (TβRI) and type 2 (TβRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice., Results: TGF-β1-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-β1-induced change of the EMT phenotype. ApoA1 inhibited the TGF-β1-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-β1-induced increase in TβRI and TβRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium., Conclusion: Our data demonstrate that ApoA1 inhibits TGF-β1-induced EMT in experimental lung fibrosis.

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.