The Impact of Air Pollution, Including Asian Sand Dust, on Respiratory Symptoms and Health-related Quality of Life in Outpatients With Chronic Respiratory Disease in Korea: A Panel Study / 예방의학회지

OBJECTIVES: Air pollution is a growing concern in Korea because of transboundary air pollution from mainland China. A panel study was conducted to clarify the effects of air pollution on respiratory symptoms and health-related quality of life (HR-QoL) in outpatients with and without chronic obstructive pulmonary disease (COPD) in Korea. METHODS: Patients filled out a questionnaire including self-reported HR-QoL in February and were followed up in May and July. The study was conducted from 2013 to 2015, with different participants each year. Air quality parameters were applied in a generalized estimating equation as independent variables to predict factors affecting HR-QoL. RESULTS: Lower physical fitness scores were associated with Asian sand dust events. Daily activity scores were worse when there were high concentrations of particulate matter (PM) less than 10 μm in diameter (PM10). Lower social functioning scores were associated with high PM less than 2.5 μm in diameter and nitrogen dioxide (NO2) concentrations. High NO2 concentrations also showed a significant association with mental health scores. Weather-related cough was prevalent when PM10, NO2, or ozone (O3) concentrations were high, regardless of COPD severity. High PM10 concentrations were associated with worsened wheezing, particularly in COPD patients. CONCLUSIONS: The results suggest that PM, NO2, and O3 cause respiratory symptoms leading to HR-QoL deterioration. While some adverse effects of air pollution appeared to occur regardless of COPD, others occurred more often and more intensely in COPD patients. The public sector, therefore, needs to consider tailoring air pollution countermeasures to people with different conditions to minimize adverse health effects.

Asian Sand Dust Up-Regulates MUC4 Expression in Human Upper Airway Epithelial Cells / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Asian sand dust (ASD) is a meteorological phenomenon that occurs in spring time in Korea. ASD is composed of various organic and inorganic materials, which induce airway inflammation. MUC4 is an important membrane-bound mucin gene in the human airway, and its expression is increased in pathologic proliferative lesions such as nasal polyps. However, the effect of ASD on MUC4 in human airway epithelial cells is unclear. Therefore, this study aimed to investigate the effect and signaling pathway of ASD on MUC4 expressions in human airway epithelial cells. METERIALS AND METHOD: The effect and signaling pathway of ASD on MUC4 expressions were investigated in NCI-H292 cells and in the primary cultures of human nasal epithelial cells using reverse transcription-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering ribonucleic acid (siRNA). RESULTS: ASD induced MUC4 expression and the activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). An ERK1/2 MAPK inhibitor and a p38 MAPK inhibitor inhibited the ASD-induced MUC4 expression. In addition, the knockdowns of ERK1, ERK2 and p38 MAPK by the respective siRNA blocked the ASD-induced MUC4 mRNA expression. ASD induced toll-like receptor 4 (TLR4) mRNA expression. The knockdown of TLR4 by TLR4 siRNA blocked the phosphorylation of ERK1/2 and p38 MAPK, and the ASD-induced MUC4 mRNA expression. CONCLUSION: These results show that ASD induces MUC4 expressions via TLR4-dependent ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells.

Asian Sand Dust Enhances the Inflammatory Response and Mucin Gene Expression in the Middle Ear

OBJECTIVES: Asia sand dust (ASD) is known to cause various human diseases including respiratory infection. The aim of this study was to examine the effect of ASD on inflammatory response in human middle ear epithelial cells (HMEECs) in vitro and in vivo. METHODS: Cell viability was assessed using the cell counting kit-8 assay. The mRNA levels of various genes including COX-2, TNF-a, MUC 5AC, MUC 5B, TP53, BAX, BCL-2, NOX4, and SOD1 were analyzed using semiquantitative realtime polymerase chain reaction. COX-2 protein levels were determined by western blot analysis. Sprague Dawley rats were used for in vivo investigations of inflammatory reactions in the middle ear epithelium as a result of ASD injection. RESULTS: We observed dose-dependent decrease in HMEEC viability. ASD exposure significantly increased COX-2, TNF-a, MUC5AC, and MUC5B mRNA expression. Also, ASD affected the mRNA levels of apoptosis- and oxidative stress-related genes. Western blot analysis revealed a dose-dependent increase in COX-2 production. Animal studies also demonstrated an ASD-induced inflammatory response in the middle ear epithelium. CONCLUSION: Environmental ASD exposure can result in the development of otitis media.

Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust

OBJECTIVES: The primary aim of this study is to evaluate the gene expression profile of Asian sand dust (ASD)-treated human middle ear epithelial cell (HMEEC) using microarray analysis. METHODS: The HMEEC was treated with ASD (400 microg/mL) and total RNA was extracted for microarray analysis. Molecular pathways among differentially expressed genes were further analyzed. For selected genes, the changes in gene expression were confirmed by real-time polymerase chain reaction. RESULTS: A total of 1,274 genes were differentially expressed by ASD. Among them, 1,138 genes were 2 folds up-regulated, whereas 136 genes were 2 folds down-regulated. Up-regulated genes were mainly involved in cellular processes, including apoptosis, cell differentiation, and cell proliferation. Down-regulated genes affected cellular processes, including apoptosis, cell cycle, cell differentiation, and cell proliferation. The 10 genes including ADM, CCL5, EDN1, EGR1, FOS, GHRL, JUN, SOCS3, TNF, and TNFSF10 were identified as main modulators in up-regulated genes. A total of 11 genes including CSF3, DKK1, FOSL1, FST, TERT, MMP13, PTHLH, SPRY2, TGFBR2, THBS1, and TIMP1 acted as main components of pathway associated with 2-fold down regulated genes. CONCLUSION: We identified the differentially expressed genes in ASD-treated HMEEC. Our work indicates that air pollutant like ASD, may play an important role in the pathogenesis of otitis media.

Asian Sand Dust Enhances Allergen-Induced Th2 Allergic Inflammatory Changes and Mucin Production in BALB/c Mouse Lungs

PURPOSE: Recent studies have reported that Asian sand dust (ASD) has a potential risk of aggravating airway inflammation. The purpose of this study was to investigate the effect of ASD on inflammation and mucin production in the airways of allergic mice. METHODS: Forty BALB/c female mice were divided into four groups: saline (group 1); ASD (group 2); ovalbumin (OVA) alone (group 3); and OVA+ASD (group 4). OVA-specific immunoglobulin E (IgE) in serum and interleukin (IL)-4, IL-5, IL-13, and interferon-gamma (IFN-gamma) in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Hematoxylin & eosin (H&E) and Periodic acid-Schiff (PAS) staining was performed on lung tissues. In addition, immunohistochemical staining for IL-4, IL-5, MUC5AC, and transforming growth factor alpha (TGF-alpha) was conducted. RESULTS: Serum IgE levels were significantly higher in group 4 than in group 3 (P<0.05). IL-4 and IL-5 in BALF were significantly higher in group 4 than in group 3 (P<0.05, respectively). Based on H&E staining, inflammatory cell numbers were significantly greater in group 4 than in the other groups (P<0.05). The number of PAS-positive cells was also significantly greater in groups 3 and 4 than in groups 1 and 2 (P<0.05). The numbers of IL-4 and IL-5-positive cells were higher in group 4 than in group 3 (P<0.05). The number of MUC5AC and TGF-alpha-positive cells were also higher in group 4 than in group 3 (P<0.05). CONCLUSIONS: Our data suggest that ASD increases cytokine expression and mucin production in an allergic murine model. The increased inflammatory reactions were related to cytokine production.

The Effect of Asian Sand Dust in Allergic Inflammation of Allergic Mouse / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Asian sand dust (ASD) is known to aggravate the respiratory symptoms in patients with bronchial asthma. However, the effect of ASD in allergic rhinitis is not known. The objective of this study was to investigate whether ASD can activate the allergic inflammation in allergic mouse model. MATERIALS AND METHOD: Forty female BALB/c mice were divided into 4 groups. Group 1 was nebulized with saline and group 2 with ASD. Group 3 was nebulized with ovalbumin (OVA) only and Group 4 with OVA plus ASD after intraperitoneal injection with OVA. The allergic symptom scores were checked. The mouse OVA specific IgE/IgG1, IL-4, IL-5 and IFN-gamma were measured by ELISA. The nasal mucosa was examined for the expression of IL-4 and IL-5 by immunohistochemical stain. RESULTS: The average symptom score was increased in Group 4 compared to Group 3 (p< 0.05). The IgE was significantly increased in Group 4 compared to Group 3 (p< 0.01). The IL-4 level of nasal lavagefluid (NALF) was significantly increased in Group 4 compared to Group 3 (p< 0.05). The IL-5 level showed no significant difference between the Group 3 and Group 4 both in the serum and NALF. The level of IFN-gamma was not changed in NALF. Immunohistochemical staining showed that the positive cells for IL-4 were expressed in epithelial layer and submucous gland and the positive cells were more increased in Group 4 than in Group 3. CONCLUSION: In allergic mouse model, ASD has shown to activate the allergic inflammatory reaction by the stimuli of Th2 cytokineproduction.