Purpose: To investigate the biometric characteristics of eyes with pseudoexfoliation syndrome (PEX) according to the anterior chamber depth (ACD) by comparing them to patients with acute angle closure (AAC) and a control group. Methods: A total of 130 eyes of 121 subjects (PEX, 49 eyes; AAC, 28 eyes; and control, 53 eyes) were included in the study. Axial length (AL), ACD, and lens thickness (LT) were measured with an IOL Master® 700 (Carl Zeiss Meditec, Jena, Germany). The total PEX (PXall) group was divided into a PEX with deep ACD group (PXd) and a shallow ACD group (PXs) based on an ACD of 2.70 mm. We compared the biometric results among the PXall, PXd, PXs, AAC, and control groups. Results: There was no significant difference in AL between the PXall and control groups; however, the PXall group had a shallower ACD and thicker lenses. After dividing the PXall group into two groups based on ACD, the PXd group showed no difference in LT compared to the control group (p = 0.113). The LT of the PXs group was thicker than those of the PXd and control groups (p < 0.001 and p < 0.001, respectively). The PXs group had longer ALs than the AAC group (p = 0.025); however, there was no difference in LT or in the ratio of LT to AL (p = 0.222 and p = 0.076, respectively). Conclusions The biometric characteristics were different in eyes with PEX based on ACD. PEX patients with deep ACDs showed no difference in biometry compared to the control group; however, PEX patients with shallow ACDs showed characteristics of a thick LT, similar to AAC patients. There was no difference in the ratio of LT to AL among groups.

Background/Aims: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a key role in Th2-mediated inflammation, both directly by promoting the proliferation of naïve CD4 Th2 cells, and indirectly by activating dendritic cells (DCs). TSLP-activated DCs induce the expansion of chemoattractant receptor homologous molecule expressed on Th2 (CRTH2)+ CD4+ Th2 memory cells, which undergo a Th2 response and express prostaglandin D2 (PGD2) synthase. CRTH2, a PGD2 receptor, is a selective Th2-cell surface marker. We investigated the effects of an anti-TSLP antibody (Ab) and a CRTH2 antagonist, as well as their mechanisms of action, in a mouse model of acute asthma. Methods: BALB/c mice were sensitized and challenged with ovalbumin. We then evaluated the effects of the administration of an anti-TSLP Ab either alone or together with a CRTH2 antagonist on cell counts, Th2 cytokine levels in bronchoalveolar fluid, and the levels of epithelium-derived cytokines such as TSLP, interleukin (IL) 33, and IL-25 in lung homogenates, as well as airway hyper-responsiveness (AHR). Results: Anti-TSLP Ab and the CRTH2 antagonist significantly attenuated eosinophilic airway inflammation, AHR, and the expression of Th2 cytokines. The expression of GATA-3 and the levels of IL-33 and IL-25 in lung tissues were affected by the combined anti-TSLP and CRTH2 antagonist treatment. Conclusions These results suggest that the dual blockade of TSLP and CRTH2 may serve as an effective treatment target for eosinophilic asthma.

Background: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. Methods: Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. Results: In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. Conclusion CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

Background: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. Methods: Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. Results: In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. Conclusion CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

BACKGROUND/AIMS: We explored the effects of intermittent normobaric hyperoxia alone or combined with chemotherapy on the growth, general morphology, oxidative stress, and apoptosis of benzo[a]pyrene (B[a]P)-induced lung tumors in mice. METHODS: Female A/J mice were given a single dose of B[a]P and randomized into four groups: control, carboplatin (50 mg/kg intraperitoneally), hyperoxia (95% fraction of inspired oxygen), and carboplatin and hyperoxia. Normobaric hyperoxia (95%) was applied for 3 hours each day from weeks 21 to 28. Tumor load was determined as the average total tumor numbers and volumes. Several markers of oxidative stress and apoptosis were evaluated. RESULTS: Intermittent normobaric hyperoxia combined with chemotherapy reduced the tumor number by 59% and the load by 72% compared with the control B[a]P group. Intermittent normobaric hyperoxia, either alone or combined with chemotherapy, decreased the levels of superoxide dismutase and glutathione and increased the levels of catalase and 8-hydroxydeoxyguanosine. The Bax/Bcl-2 mRNA ratio, caspase 3 level, and number of transferase-mediated dUTP nick end-labeling positive cells increased following treatment with hyperoxia with or without chemotherapy. CONCLUSIONS: Intermittent normobaric hyperoxia was found to be tumoricidal and thus may serve as an adjuvant therapy for lung cancer. Oxidative stress and its effects on DNA are increased following exposure to hyperoxia and even more with chemotherapy, and this may lead to apoptosis of lung tumors.
Animals ; Apoptosis ; Carboplatin* ; Caspase 3 ; Catalase ; DNA ; Drug Therapy ; Female ; Glutathione ; Humans ; Hyperoxia* ; Lung Neoplasms* ; Lung* ; Mice ; Oxidative Stress ; RNA, Messenger ; Superoxide Dismutase ; Tumor Burden

PURPOSE: The incidence of inflammatory bowel disease (IBD) is rapidly increasing, and several reports have described the renal complications of IBD. We sought to evaluate the clinical manifestations of renal complications in children with IBD in order to enable early detection and prompt treatment of the complications. METHODS: We retrospectively reviewed the medical records of 456 children and adolescents aged < 20 years who had been diagnosed with IBD since 2000. We analyzed patient age, sex, medication use, IBD disease activity, and clinical manifestations of renal symptoms. RESULTS: Our study comprising 456 children with IBD included 299 boys (65.6%) and 157 girls (34.4%). The study included 346 children with Crohn disease and 110 children with ulcerative colitis. The incidence of kidney-related symptoms was 14.7%, which was significantly higher than that in normal children. We observed 26 children (38.8%) with isolated hematuria, 30 children (44.8%) with isolated proteinuria, and 11 children (16.4%) with hematuria and concomitant proteinuria. A renal biopsy was performed in 7 children. Histopathological examination revealed immunoglobulin A nephropathy in 5 children (71.4%). All children presented with mild disease and well-controlled disease activity of IBD. CONCLUSION: Children with IBD are more likely to show kidney-related symptoms than healthy children and adolescents are. Therefore, regular screening of urine and evaluation of renal function in such children are necessary for early detection of renal complications.
Adolescent* ; Biopsy ; Child* ; Colitis, Ulcerative ; Crohn Disease ; Female ; Glomerulonephritis, IGA ; Hematuria ; Humans ; Incidence ; Inflammatory Bowel Diseases* ; Kidney ; Mass Screening ; Medical Records ; Proteinuria ; Retrospective Studies

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. However, little is known about the potential use of serum levels of VEGF as a biomarker for asthma. We investigated the differences in VEGF levels among normal controls, stable asthma patients, and those with exacerbation of acute asthma. All subjects were young males. METHODS: We measured VEGF levels in each patient group, and examined any serial changes in those with acute exacerbation. RESULTS: VEGF levels were significantly higher in stable asthmatic patients and even more so in acute asthmatic patients, compared to healthy controls. However, there was no correlation between VEGF levels and forced expiratory volume in 1 second in patients with stable asthma. In addition, there were no correlations between VEGF levels and asthma control test scores. In patients with acute exacerbation, VEGF levels significantly increased during the acute period; their levels decreased gradually at 7 and 14 days after treatment. CONCLUSIONS: Compared to normal control patients, the serum levels of VEGF were elevated in stable asthma patients and even more elevated in patients with acute exacerbation. However, the role of VEGF as a biomarker in stable asthma is limited. In patients with acute exacerbation, VEGF levels were associated with clinical improvements.
Asthma* ; Forced Expiratory Volume ; Humans ; Male* ; Vascular Endothelial Growth Factor A*

BACKGROUND/AIMS: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. METHODS: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. RESULTS: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. CONCLUSIONS: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.
Adult ; Dyspnea ; Hematologic Neoplasms ; Humans ; Immunocompromised Host* ; Logistic Models ; Organ Transplantation ; Pneumocystis jirovecii* ; Pneumocystis* ; Pneumonia ; Pneumonia, Pneumocystis ; Polymerase Chain Reaction* ; Prevalence ; Retrospective Studies ; Risk Factors ; Transplants

BACKGROUND/AIMS: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. METHODS: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. RESULTS: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. CONCLUSIONS: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.
Adult ; Dyspnea ; Hematologic Neoplasms ; Humans ; Immunocompromised Host* ; Logistic Models ; Organ Transplantation ; Pneumocystis jirovecii* ; Pneumocystis* ; Pneumonia ; Pneumonia, Pneumocystis ; Polymerase Chain Reaction* ; Prevalence ; Retrospective Studies ; Risk Factors ; Transplants

BACKGROUND/AIMS: Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated with fluticasone and/or nilotinib intranasally during the OVA challenge. RESULTS: Mice chronically exposed to OVA developed eosinophilic airway inflammation and showed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Both fluticasone and nilotinib attenuated airway smooth muscle thickening. However, only nilotinib suppressed fibrotic changes, demonstrating inhibition of collagen deposition. Fluticasone reduced pro-inflammatory cells, such as eosinophils, and several cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, induced by repeated OVA challenges. On the other hand, nilotinib reduced transforming growth factor β1 levels in bronchoalveolar lavage fluid and inhibited fibroblast proliferation significantly. CONCLUSIONS: These results suggest that fluticasone and nilotinib suppressed airway remodeling in this chronic asthma model through anti-inflammatory and anti-fibrotic pathways, respectively.
Adrenal Cortex Hormones ; Airway Remodeling ; Animals ; Asthma* ; Bronchoalveolar Lavage Fluid ; Collagen ; Cytokines ; Eosinophils ; Female ; Fibroblasts ; Fluticasone* ; Hand ; Humans ; Inflammation ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Mice ; Muscle, Smooth ; Ovalbumin ; Ovum ; Protein-Tyrosine Kinases ; Receptors, Platelet-Derived Growth Factor ; Transforming Growth Factors