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Kyunghee Lee,1 Jieun Hwang,2 Chang Min Lee3 1Department of Healthcare Management, Eulji University of Korea, Seongnam, Republic of Korea; 2College of Health and Welfare, Department of Health Administration, Dankook University, Cheonan, Republic of Korea; 3Department of Gastroenterology, Changwon Hanmaeum Hospital, Changwon, Republic of KoreaCorrespondence: Jieun Hwang, College of Health and Welfare, Department of Health Administration, Dankook University, Cheonan, Republic of Korea, Email hwang0310@dankook.ac.krPurpose: Comorbidities of a principal diagnosis have varying impacts on disease and require different management depending on the onset timing. This study investigated the usefulness of present-on-admission (POA), specifically focusing on decubitus ulcers, delirium, and hypokalemia, as an indicator of healthcare quality.Patients and Methods: We analyzed patient discharge data for 14 years from 2006 to 2019 using Korean National Hospital Discharge In-Depth Injury Survey (KNHDIS).Results: Out of 3,231,731 discharged patients, 19,871 had secondary diagnosis codes for decubitus ulcers (n=10,390, 52.3%), delirium (n=6103, 30.7%), or hypokalemia (n=3378, 17.0%). Analysis of patients with secondary diagnoses of decubitus ulcers, delirium, or hypokalemia revealed notable differences in demographics, including gender distribution, mean age, admission route, insurance type, surgical intervention rates, mortality rates, and length of stay (LOS). Among patients with one of the top 20 principal diagnoses, those with secondary diagnoses of decubitus ulcers, delirium, or hypokalemia exhibited higher odds of surgery, increased mortality risks, and longer LOS compared to those without these secondary diagnoses.Conclusion: All three of these diseases commonly occur postoperatively or during treatment and thus should be designated as potentially preventable complications that require special attention, and should also be considered as quality-of-care indicators.Keywords: healthcare quality evaluation indicators, present on admission, POA, decubitus ulcers, delirium, hypokalemia

Haw-Ming Huang,1,2 Ping-Han Wu,3 Po-Chien Chou,4 Wen-Tien Hsiao,5 Hsin-Ta Wang,4 Hsin-Pei Chiang,3 Chi-Ming Lee,6 Shwu-Huey Wang,6 Yu-Cheng Hsiao2,7 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 2Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 3Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4School of Organic and Polymeric, National Taipei University of Technology, Taipei, Taiwan; 5Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 6Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan; 7Cell Physiology and Molecular Image Research Center, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Yu-Cheng Hsiao; Ping-Han WuTaipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, TaiwanTel +886-291-937-9783Fax +886 2 27362295Email ychsiao@tmu.edu.tw; gahwclbjwph@gmail.comIntroduction: It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe3O4) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection.Methods: LMWHA and Fe3O4 NPs were produced using γ-ray irradiation and chemical co-precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs.Results: Florescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA-IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells.Discussion: Overall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.Keywords: hyaluronic acid, Fe3O4 nanoparticles, TOF-SIMS, MRI

Tae In Wi,1,* Ji Eun Won,1,* Chan Mi Lee,1 Jeong-Won Lee,2 Tae Heung Kang,1 Byung Cheol Shin,3 Hee Dong Han,1 Yeong-Min Park1 1Department of Immunology, School of Medicine, Konkuk University, Chungju 380-701, South Korea; 2Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Bio/Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, South Korea*These authors contributed equally to this workCorrespondence: Hee Dong Han; Yeong-Min ParkDepartment of Immunology, School of Medicine, Konkuk University, 268 Chungwondae-Ro, Chungju, Chungcheongbuk-Do 380-701, South KoreaTel +82-2-2030-7848; +82-2-2049-6330Fax +82-2-2049-6192Email hanhd@kku.ac.kr; immun3023@kku.ac.krBackground: Epithelial ovarian cancer (EOC) is a fatal gynecologic malignancy that is usually treated with chemotherapy after surgery. However, patients who receive chemotherapy experience severe side effects because of the inherent toxicity and high dose of chemotherapeutics. To overcome these issues, we suggest a combination therapeutic strategy using liposomes encapsulating linalool nanoemulsions (LN-NEs) and doxorubicin (DOX), a chemotherapeutic drug, to increase their synergistic antitumor efficacy and reduce the incidence of side effects from chemotherapeutics for EOC.Methods: The physical properties of LN-NE-DOX-liposomes were characterized by light scattering with a particle size analyzer. Cell viability was determined by MTT assay. Therapeutic efficacy was evaluated in a mouse HeyA8 EOC tumor model of ovarian carcinoma. Additionally, biochemical toxicity was analyzed for levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) using BALB/c nude mice.Results: The size of the liposomes encapsulating LN-NEs and DOX (LN-NE-DOX-liposomes) was 267.0 ± 4.6 nm, with a loading efficiency of 55.1 ± 3.1% and 27.2 ± 0.9% for linalool and DOX, respectively. Cell viability after treatment with LN-NE-DOX-liposomes was significantly decreased compared to that of cells treated with DOX liposomes, and apoptosis was significantly increased. Additionally, LN-NE-DOX-liposomes significantly inhibited HeyA8 EOC tumor growth compared to that of the control (p < 0.01) and DOX-liposome-treated groups (p < 0.05), while decreasing cell proliferation (Ki67) and microvessel density (CD31), and promoting apoptosis (caspase-3) compared to the control (p < 0.05). Moreover, the liposomal formulations induced no significant differences in biochemical toxicity (AST, ALT, and BUN) compared to healthy control mice, indicating that the liposomal formulations showed no overt toxicity in mice.Conclusion: This study demonstrates that the production of LN-NE-DOX-liposomes is a pivotal approach for EOC treatment, suggesting a novel combination therapeutic strategy.Keywords: linalool, liposome, ovarian carcinoma, doxorubicin, combination therapy

Chang-Moon Lee,1 Tai Kyoung Lee,2–5 Dae-Ik Kim,1,6 Yu-Ri Kim,7 Meyoung-Kon Kim,7 Hwan-Jeong Jeong,2–5 Myung-Hee Sohn,2–5 Seok Tae Lim2–5 1Department of Biomedical Engineering, Chonnam National University, Yeosu, Jeollanam-Do, Republic of Korea; 2Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 3Cyclotron Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 4Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 5Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 6School of Electrical, Electronic Communication, and Computer Engineering, Chonnam National University, Yeosu, Jeollanam-Do, Republic of Korea; 7Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seounbuk-Gu, Seoul, Republic of Korea Purpose: In this study, we investigated the absorption and distribution of rhodamine B isothiocyanate (RITC)-incorporated silica oxide nanoparticles(SiNPs) (RITC-SiNPs) after oral exposure, by conducting optical imaging, with a focus on tracking the movement of RITC-SiNPs of different particle size and surface charge. Methods: RITC-SiNPs (20 or 100 nm; positively or negatively charged) were used to avoid the dissociation of a fluorescent dye from nanoparticles via spontaneous or enzyme-catalyzed reactions in vivo. The changes in the nanoparticle sizes and shapes were investigated in an HCl solution for 6 hours. RITC-SiNPs were orally administered to healthy nude mice at a dose of 100 mg/kg. Optical imaging studies were performed at 2, 4, and 6 hours after oral administration. The mice were sacrificed at 2, 4, 6, and 10 hours post-administration, and ex vivo imaging studies were performed. Results: The RITC-SiNPs were stable in the HCl solution for 6 hours, without dissociation of RITC from the nanoparticles and without changes in size and shape. RITC-SiNPs flowed into the small intestine from the stomach and gradually moved along the gut during the experiment. In the ex vivo imaging studies, optical signals were observed mostly in the lungs, liver, pancreas, and kidneys. The orally administered RITC-SiNPs, which were absorbed in the systemic circulation, were eliminated from the body into the urine. The 20 nm RITC-SiNPs showed higher uptake in the lungs than the 100 nm RITC-SiNPs. The distribution of the 100 nm RITC-SiNPs in the liver was higher than that of the 20 nm RITC-SiNPs, but the differences in the surface charge behavior were imperceptible. Conclusion: We demonstrated that the movement of RITC-SiNPs after oral exposure could be traced by optical imaging. Optical imaging has the potential to provide valuable information that will help in understanding the behavior of SiNPs in the body following exposure. Keywords: silica nanoparticles, oral exposure, rhodamine B isothiocyanate, RITC-SiNP

Chang-Moon Lee,1–4,* Hwan-Jeong Jeong,1–4,* Kuk-No Yun,1–3 Dong Wook Kim,1–4 Myung-Hee Sohn,1–4 Jong Kwon Lee,5 Jayoung Jeong,5 Seok Tae Lim1–4 *These authors contributed equally to this work.1Department of Nuclear Medicine; 2Cyclotron Research Center; 3Research Institute of Clinical Medicine; 4Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-Do, Republic of Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Osong-Eup, Chungchungbuk-Do, Republic of KoreaBackground: Understanding how nanomaterials are distributed in the body after exposure is important for assessing whether they are safe. In this study, we investigated the behavior and accumulation of nanoscaled and submicron-scaled zinc oxide (ZnO) particles in the body using optical imaging following oral exposure.Methods: To trace these nanoparticles in the body, ZnO nanoparticles were conjugated with a monoreactive hydroxysuccinimide ester of Cy5.5 (Cy5.5-NHS), and the conjugation-stabilizing effect of Cy5.5 on the nanoparticles was evaluated in simulated gastric fluid (pH 1.2) for 7 hours. To compare the distribution of Cy5.5-NHS and Cy5.5-conjugated ZnO nanoparticles, Cy5.5-NHS 0.5 mg/kg and Cy5.5-conjugated ZnO nanoparticles 250 mg/kg were administered orally to healthy rats. We collected blood from the rats at predesignated time points for 7 hours after administration, and optical imaging studies were performed at 1, 2, 3, 5, and 7 hours after dosing. To investigate the extent of nanoparticle accumulation in the organs and tissues, the mice were sacrificed at 23 hours after administration, and the organs were removed and imaged.Results: Cy5.5-conjugated ZnO nanoparticles were stable in simulated gastric fluid for 7 hours. The signal intensity of Cy5.5-NHS in blood was highest 3 hours after oral administration, and Cy5.5-conjugated ZnO nanoparticles showed the highest signal intensity in blood 5–7 hours after administration. In vivo optical images indicated that Cy5.5-NHS showed optical signals in the lung, liver, and gastrointestinal tract after oral administration, whereas Cy5.5-conjugated ZnO nanoparticles were seen only in the gastrointestinal tract. Seven hours following administration, biodistribution studies demonstrated that Cy5.5-NHS accumulated in the lung and liver, and Cy5.5-conjugated ZnO nanoparticles resulted in a strong signal in the kidney and liver. Different-sized ZnO nanoparticles showed dissimilar patterns of biodistribution in ex vivo optical images.Conclusion: ZnO nanoparticles are absorbed into the tissues following oral exposure and their behavior can be monitored and evaluated using optical imaging.Keywords: zinc oxide nanoparticles, biodistribution, optical imaging, oral administration

John E Chandler1, Cameron M Lee1, Alexander P Babchanik1, C David Melville1, Michael D Saunders2, Eric J Seibel11Human Photonics Laboratory, Department of Mechanical Engineering, University of Washington, Seattle, WA, USA; 2Digestive Disease Center, University of Washington Medical Center, Seattle, WA, USAPurpose: Direct visualization of pancreatic ductal tissue is critical for early diagnosis of pancreatic diseases and for guiding therapeutic interventions. A novel, ultrathin (5 Fr) scanning fiber endoscope (SFE) with tip-bending capability has been developed specifically to achieve high resolution imaging as a pancreatoscope during endoscopic retrograde cholangiopancreatography (ERCP). This device has potential to dramatically improve both diagnostic and therapeutic capabilities during ERCP by providing direct video feedback and tool guidance to clinicians.Methods: Invasiveness of the new tip-bending SFE was evaluated by a performance comparison to ERCP guide wires, which are routinely inserted into the pancreatic duct during ERCP. An in vitro test model with four force sensors embedded in a synthetic pancreas was designed to detect and compare the insertion forces for 0.89 mm and 0.53 mm diameter guide wires as well as the 1.7 mm diameter SFE. Insertions were performed through the working channel of a therapeutic duodenoscope for the two types of guide wires and using a statistically similar direct insertion method for comparison to the SFE.Results: Analysis of the forces detected by the sensors showed the smaller diameter 0.53 mm wire produced significantly less average and maximum forces during insertion than the larger diameter 0.89 mm wire. With the use of tip-bending and optical visualization, the 1.7 mm diameter SFE produced significantly less average force during insertion than the 0.89 mm wire at every sensor, despite its larger size. It was further shown that the use of tip-bending with the SFE significantly reduced the forces at all sensors, compared to insertions when tip-bending was not used.Conclusion: Combining high quality video imaging with two-axis tip-bending allows a larger diameter guide wire-style device to be inserted into the pancreatic duct during ERCP with improved capacity to perform diagnostics and therapy.Keywords: endoscopic retrograde cholangiopancreatography (ERCP), scanning fiber endoscope (SFE), pancreatic cancer, minimally invasive therapy

Spatial estimates of crop evapotranspiration with high accuracy from the field to watershed scale have become increasingly important for water management, particularly over irrigated agriculture in semiarid regions. Here, we provide a comprehensive assessment on patterns of annual agricultural water use over California's Central Valley, using 30-m daily evapotranspiration estimates based on Landsat satellite data. A semiempirical Priestley-Taylor approach was locally optimized and cross-validated with available field measurements for major crops including alfalfa, almond, citrus, corn, pasture, and rice. The evapotranspiration estimates explained >70% variance in daily measurements from independent sites with an RMSE of 0.88 mm day-1. When aggregated over the Valley, we estimated an average evapotranspiration of 820 ± 290 mm yr-1 in 2014. Agricultural water use varied significantly across and within crop types, with a coefficient of variation ranging from 8% for Rice (1,110 ± 85 mm yr-1) to 59% for Pistachio (592 ± 352 mm yr-1). Total water uses in 2016 increased by 9.6%, as compared to 2014, mostly because of land-use conversion from fallow/idle land to cropland. Analysis across 134 Groundwater Sustainability Agencies (GSAs) further showed a large variation of agricultural evapotranspiration among and within GSAs, especially for tree crops, e.g., almond evapotranspiration ranging from 339 ± 80 mm yr-1 in Tracy to 1,240 ± 136 mm yr-1 in Tri-County Water Authority. Continuous monitoring and assessment of the dynamics and spatial heterogeneity of agricultural evapotranspiration provide data-driven guidance for more effective land use and water planning across scales.

The 2017–2027 National Academies' Decadal Survey, Thriving on Our Changing Planet, recommended Surface Biology and Geology (SBG) as a “Designated Targeted Observable” (DO). The SBG DO is based on the need for capabilities to acquire global, high spatial resolution, visible to shortwave infrared (VSWIR; 380–2500 nm; ~30 m pixel resolution) hyperspectral (imaging spectroscopy) and multispectral midwave and thermal infrared (MWIR: 3–5 μm; TIR: 8–12 μm; ~60 m pixel resolution) measurements with sub-monthly temporal revisits over terrestrial, freshwater, and coastal marine habitats. To address the various mission design needs, an SBG Algorithms Working Group of multidisciplinary researchers has been formed to review and evaluate the algorithms applicable to the SBG DO across a wide range of Earth science disciplines, including terrestrial and aquatic ecology, atmospheric science, geology, and hydrology. Here, we summarize current state-of-the-practice VSWIR and TIR algorithms that use airborne or orbital spectral imaging observations to address the SBG DO priorities identified by the Decadal Survey: (i) terrestrial vegetation physiology, functional traits, and health; (ii) inland and coastal aquatic ecosystems physiology, functional traits, and health; (iii) snow and ice accumulation, melting, and albedo; (iv) active surface composition (eruptions, landslides, evolving landscapes, hazard risks); (v) effects of changing land use on surface energy, water, momentum, and carbon fluxes; and (vi) managing agriculture, natural habitats, water use/quality, and urban development. We review existing algorithms in the following categories: snow/ice, aquatic environments, geology, and terrestrial vegetation, and summarize the community-state-of-practice in each category. This effort synthesizes the findings of more than 130 scientists.

The prototypical genetic autoimmune disease is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, a severe pediatric disease with limited treatment options. IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the feasibility of gene correction, which will be instrumental for the development of therapeutic approaches for other genetic autoimmune diseases.

The Arabian Sea circulation is forced by strong monsoonal winds and is characterized by vigorous seasonally reversing currents, extreme differences in sea surface salinity, localized substantial upwelling, and widespread submesoscale thermohaline structures. Its complicated sea surface temperature patterns are important for the onset and evolution of the Asian monsoon. This article describes a program that aims to elucidate the role of upper-ocean processes and atmospheric feedbacks in setting the sea surface temperature properties of the region. The wide range of spatial and temporal scales and the difficulty of accessing much of the region with ships due to piracy motivated a novel approach based on state-of-the-art autonomous ocean sensors and platforms. The extensive data set that is being collected, combined with numerical models and remote sensing data, confirms the role of planetary waves in the reversal of the Somali Current system. These data also document the fast response of the upper equatorial ocean to monsoon winds through changes in temperature and salinity and the connectivity of the surface currents across the northern Indian Ocean. New observations of thermohaline interleaving structures and mixing in setting the surface temperature properties of the northern Arabian Sea are also discussed.

The electronic structure of LiC6 has been investigated by soft X-ray absorption and emission spectroscopies. The results reveal that upon full lithiation of graphite, the Li 2s electrons are transferred into the carbon π* states in a near rigid-band behavior, resulting in the increased density of states near EF and the shift of σ* states to lower energies. In addition, the resonant inelastic X-ray scattering spectra of LiC6 do not show strong dispersive features as that of graphite, indicating that the crystal momentum is not conserved during the scattering process due to the delocalization of electrons in the intermediate state.

Tomentosin, a sesquiterpene lactone, is known to possess various biological activities. However, its anticarcinogenic activity against human hepatocellular carcinoma (HCC) cells has not been investigated in detail. Thus, this study aimed to elucidate the cytotoxic mechanism of tomentosin in human HCC cell lines HepG2 and Huh7. WST-1, cell counting, and colony formation assay results showed that treatment with tomentosin decreased the viability and suppressed the proliferation rate of HepG2 and Huh7 cells in a dose- and time-dependent manner. Cell cycle analysis revealed increased population of cells at the SubG1 and G2/M stage, and decreased population of cells at the G0/1 stage in HepG2 and Huh7 cells treated with tomentosin. Annexin V/propidium iodide double staining and TUNEL assay results showed increased apoptotic cell population and DNA fragmentation in HepG2 and Huh7 cells treated with tomentosin. Western blotting analysis results showed that tomentosin treatment significantly increased the expression level of Bax, Bim (short form), cleaved PARP1, FOXO3, p53, pSer15p53, pSer20p53, pSer46p53, p21, and p27, but decreased the expression of Bcl2, caspase3, caspase7, caspase9, cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclinB1, cyclinD1, cyclinD2, cyclinD3, and cyclinE in a dose-dependent manner. Taken together, this study revealed that tomentosin, which acted through cell cycle arrest and apoptosis, may be a useful therapeutic option against HCC. [ABSTRACT FROM AUTHOR]

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, alveolar destruction, and airway and vascular remodeling. However, the mechanisms that lead to these diverse alterations have not been defined.Objectives: We hypothesized that IL-18 plays a central role in the pathogenesis of these lesions.Methods: We generated and characterized lung-specific, inducible IL-18 transgenic mice.Measurements and Main Results: Here we demonstrate that the expression of IL-18 in the mature murine lung induces inflammation that is associated with the accumulation of CD4(+), CD8(+), CD19(+), and NK1.1(+) cells; emphysema; mucus metaplasia; airway fibrosis; vascular remodeling; and right ventricle cardiac hypertrophy. We also demonstrate that IL-18 induces type 1, type 2, and type 17 cytokines with IFN-γ-inhibiting macrophage, lymphocyte, and eosinophil accumulation while stimulating alveolar destruction and genes associated with cell cytotoxicity and IL-13 and IL-17A inducing mucus metaplasia, airway fibrosis, and vascular remodeling. We also highlight interactions between these responses with IL-18 inducing IL-13 via an IL-17A-dependent mechanism and the type 1 and type17/type 2 responses counterregulating each another.Conclusions: These studies define the spectrum of inflammatory, parenchymal, airway, and vascular alterations that are induced by pulmonary IL-18; highlight the similarities between these responses and the lesions in COPD; and define the selective roles that type 1, type 2, and type 17 responses play in the generation of IL-18-induced pathologies. [ABSTRACT FROM AUTHOR]