Airway remodeling is a key characteristic of chronic asthma, particularly in patients with a fixed airflow limitation. The mechanisms underlying airway remodeling are poorly understood, and no therapeutic option is available. The Wnt/β-catenin signaling pathway is involved in various physiological and pathological processes, including fibrosis and smooth muscle hypertrophy. In this study, we investigated the roles of Wnt/β-catenin signaling in airway remodeling in patients with asthma. Wnt7a mRNA expression was prominent in induced sputum from patients with asthma compared with that from healthy controls. Next, we induced a chronic asthma mouse model with airway remodeling features, including subepithelial fibrosis and airway smooth muscle hyperplasia. Higher expression of Wnt family proteins and β-catenin was detected in the lung tissue of mice with chronic asthma compared to control mice. Blocking β-catenin expression with a specific siRNA attenuated airway inflammation and airway remodeling. Decreased subepithelial fibrosis and collagen accumulation in the β-catenin siRNA-treated mice was accompanied by reduced expression of transforming growth factor-β. We further showed that suppressing β-catenin in the chronic asthma model inhibited smooth muscle hyperplasia by downregulating the tenascin C/platelet-derived growth factor receptor pathway. Taken together, these findings demonstrate that the Wnt/β-catenin signaling pathway is highly expressed and regulates the development of airway remodeling in chronic asthma.

PurposeAlthough mild to moderate asthma is much more common, the morbidity and mortality of severe asthma are much higher. This study was performed to identify and analyze the clinical characteristics of severe asthma in Korea.MethodsWe registered patients with severe refractory asthma into the Severe Asthma Registry supported by the Severe Asthma Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology. Patients were enrolled since 2010 from the 15 university hospitals nationwide in Korea. Severe asthma was defined according to modified European Respiratory Society/American Thoracic Society criteria. Information on demographics, medical history, pulmonary function tests and skin prick tests was collected; the clinical characteristics of severe asthmatics were analyzed from the collected data.ResultsA total of 489 patients were enrolled with a mean age of 62.3; 45% are male. Sixty percent of patients received Global Initiative for Asthma step 4 treatment, and 30% received step 5 treatment. The most common comorbidities were allergic rhinitis (58.7%). Aspirin hypersensitivity was observed in 14.0%. Approximately half (53.9%) are non-smokers. Atopy was proven in 38.5% of the patients. Regarding asthma medications, inhaled corticosteroids and long-acting β-agonist combination inhalers were most commonly prescribed (96.5%), followed by leukotriene antagonists (71.0%). A recombinant anti-immunoglobulin E monoclonal antibody (omalizumab) has been used in 1.8% of the patients. The mean forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were 78.7%, 67.5% and 67.9% of predicted values, respectively. The mean Asthma Control Test and quality of life questionnaire scores were 16.5 out of 25 and 59.5 out of 85, respectively.ConclusionsThe baseline characteristics of severe asthma patients in the Korea Severe Asthma Registry were analyzed and reported for the first time. With this cohort, further prospective studies should be performed to search for ways to improve management of severe refractory asthma.

PurposeThis study aimed to compare the diagnostic performance of contrast-enhanced digital mammography (CEDM) and contrast-enhanced magnetic resonance imaging (CEMRI) in preoperative evaluations, and to evaluate the effect of each modality on the surgical management of women with breast cancer.MethodsThis single-center, prospective study was approved by the Institutional Review Board, and informed consent was obtained from all patients. From November 2016 to October 2017, 84 patients who were diagnosed with invasive carcinoma (69/84) and ductal carcinoma in situ (15/84), and underwent both CEDM and CEMRI, were enrolled. Imaging findings and surgical management were correlated with pathological results and compared. The diagnostic performance of both modalities in the detection of index and secondary cancers (multifocality and multicentricity), and occult cancer in the contralateral breast, was compared. The authors also evaluated whether CEDM or CEMRI resulted in changes in the surgical management of the affected breast due to imaging-detected findings.ResultsEighty-four women were included in the analysis. Compared with CEMRI, CEDM demonstrated a similar sensitivity (92.9% [78/84] vs. 95.2% [80/84]) in detecting index cancer (p=0.563). For the detection of secondary cancers in the ipsilateral breast and occult cancer in the contralateral breast, no significant differences were found between CEDM and CEMRI (p=0.999 and p=0.999, respectively). Regarding changes in surgical management, CEDM resulted in similar changes compared with CEMRI (30.9% [26/84] vs. 29.7% [25/84], p=0.610). Regarding changes in surgical management due to false-positive findings, no significant differences were found between CEDM and CEMRI (34.6% [9/26] vs. 44.0% [11/25], p=0.782).ConclusionCEDM demonstrated a diagnostic performance comparable with CEMRI in depicting index cancers, secondary cancers, and occult cancer in the contralateral breast. CEDM demonstrated similar changes in surgical management compared with CEMRI.

Rationale: Two adipokines, leptin and adiponectin, regulate metabolic and inflammatory systems reciprocally. The role of adiponectin in chronic obstructive pulmonary disease (COPD) has been studied. However, there are few data evaluating the relationship of plasma leptin with COPD severity or progression.Objectives: The objective of this study was to evaluate the relationship of leptin, adiponectin, and the leptin/adiponectin ratio with COPD severity and progression according to COPD phenotypes.Methods: Plasma leptin and adiponectin levels were measured in 196 subjects with COPD selected from the Korean Obstructive Lung Disease cohort. Using a linear regression model and mixed linear regression, we determined the relationship of plasma leptin and adiponectin levels and the leptin/adiponectin ratio to COPD severity and progression over 3 years.Measurements and Main Results: The concentration of adiponectin in plasma positively correlated with percent emphysema on initial computed tomography (CT) (adjusted P = 0.022), whereas plasma leptin concentrations and the leptin/adiponectin ratio exhibited a significant inverse correlation with initial FEV 1 (adjusted P = 0.013 for leptin and adjusted P = 0.041 for leptin/adiponectin ratio). Increased plasma leptin and leptin/adiponectin ratio were significantly associated with change in percent emphysema over 3 years (adjusted P = 0.037 for leptin and adjusted P = 0.029 for leptin/adiponectin ratio), whereas none of the adipokines demonstrated an association with FEV 1 decline over the 3-year period.Conclusions: Plasma adiponectin and leptin vary according to COPD phenotypes. Plasma leptin and the leptin/adiponectin ratio, but not adiponectin, were significantly associated with changes in CT-assessed emphysema, suggesting a potential role as a biomarker in emphysema progression in patients with COPD.