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Purpose: Epithelial-mesenchymal transition (EMT) involved in asthmatic airway remodeling. Thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine, was a key component in airway immunological response in asthma. But the role of TSLP in the EMT process was unknown. We aimed to access whether TSLP could induce EMT in airway epithelia and its potential mechanism. Materials and Methods: Human bronchial epithelial (HBE) cells were incubated with TSLP or transforming growth factor beta 1 (TGF-β1) or both. SB431542 was used to block TGF-β1 signal while TSLP siRNA was used to performed TSLP knockdown. Changes in E-cadherin, vimentin, collagen I and fibronectin level were measured by real-time PCR, western blot and immunofluorescence staining. Expressions of TGF-β after TSLP administration were measured by real-time PCR, western blot and ELISA. Results: TSLP induced changes of EMT relevant markers alone and promoted TGF-β1-induced EMT in HBEs. Intracellular and extracellular expression of TGF-β1 were upregulated by TSLP. SB431542 blocked changes of EMT relevant markers induced by TSLP. Knockdown of TSLP not only reduced TSLP and TGF-β1 expression but also inhibited changes of EMT relevant markers induced by TGF-β1 in HBEs. Conclusions: TSLP could induce early stage of EMT in airway epithelial cells through upregulation of TGF-β1. This effect may act as a targeting point for suppression of asthma. [ABSTRACT FROM AUTHOR]

Objective: To investigate the alterative spectrum and trends of aeroallergens sensitization in children with allergic rhinitis (AR) in Guangzhou, China in the past 10 years.Participants and Methods: In this retrospective study, 4,111 children with complaints of nasal hyper-reactivity who visited the Pediatric Department and/or Otolaryngology Department from January 2007 to November 2016 were enrolled. Serum specific immunoglobulin E was measured and positive detection was made in 3,328 patients, who were, therefore, diagnosed with AR. Positive rates and trends of different aeroallergens sensitization were assessed. The tendency of positive rates changing over the years, and the difference and trends in positive rate of aeroallergen sensitization that occurred in subgroups of gender, age, and season were determined and analyzed with logistic regression.Results: The percentage of detected common aeroallergens in AR children was (from high to low) 81.07%, 34.44%, 14.72%, 11.81%, 6.04%, and 3.70% for house dust mites (HDMs), cat-dog dander, cockroach, mold mixture, tree pollen mixture, and herb pollen mixture, respectively. An ascending trend of aeroallergens sensitization or AR (odds ratio [OR] =1.116, 95% CI: 1.086-1.146) was found. Interestingly, an increasing trend of cat-dog dander and mold sensitization was found in AR children (OR =1.164, 95% CI: 1.133-1.196; OR =1.169, 95% CI: 1.120-1.223) in this retrospective study, while HDMs sensitization held a steady trend (OR =0.983, 95% CI: 0.961-1.007).Conclusion: In the increasing trend of aeroallergens sensitization or AR, HDMs sensitization still held the majority. But emphasis should be made on pet allergy for young children with AR in the context of ascending trend of sensitization to cat-dog dander. [ABSTRACT FROM AUTHOR]

This study investigated the concentrations and seroprevalence of immunoglobulin G (IgG) antibodies against pertussis, diphtheria, tetanus, measles, mumps and rubella among children in Guangzhou, China. We conducted a cross-sectional study focusing on the post-vaccination immune statuses of children on scheduled immunisation. Human IgG antibody against six diseases were measured using commercial enzyme-linked immunosorbent assay kits. Of 620 subjects, the male-to-female ratio was 2.04 (416/204). Seroprevalence (81.97% vs 90.20%) and IgG concentrations (686.55 IU/mL vs 884.26 IU/mL, P < 0.05) for measles, tetanus (0.94 IU/mL vs 1.21 IU/mL) and rubella (34.33 IU/mL vs 47.37 IU/mL) were all higher in females. No differences based on sex were observed in the seroprevalence and IgG concentrations for anti-pertussis antibodies, anti-diphtheria antibodies and anti-mumps. Slight increase in seroprevalence and IgG concentration occurred with anti-pertussis antibodies after primary and booster vaccinations (from 0.00% [1 m], 5.45% [6 m], to 17.14% [1.5 yr]; and from 8.57% [5 yr] to 15.79% [6 yr]). Although no booster vaccination was given after age 6 yr, the seroprevalence and IgG concentration for anti-pertussis antibodies remained relatively stable. For diphtheria, tetanus, measles and rubella, seroprevalence reached their peaks after the primary and first booster vaccination. A plateau occurred after age 1.5 yr with a declining trend in subjects >8–10 yr. The IgG concentrations of these 4 pathogens showed a dramatic increase after primary vaccination, with steadily declining trends thereafter. For mumps, subjects showed increased seroprevalence and IgG concentration after the primary mumps-containing vaccination in 1.5-yr-olds (from 7.14% to 57.14%; 52.13 IU/mL to 214.18 IU/mL); however, following that low seroprevalence levels (from 42.86% to 80.00%) were observed. The post-vaccination immune statuses against diphtheria, tetanus, measles and rubella were relatively satisfactory, compared to those against pertussis and mumps. Booster vaccination against pertussis and mumps at appropriate time should be considered. [ABSTRACT FROM AUTHOR]

Background: Aberrant epithelial remodeling and/or abnormalities in mucociliary apparatus in airway epithelium contribute to infection and inflammation. It is uncertain if these changes occur in both large and small airways in non-cystic fibrosis bronchiectasis (non-CF bronchiectasis). In this study, we aim to investigate the histopathology and inflammatory profile in the epithelium of bronchi and bronchioles in bronchiectasis., Methods: Excised lung tissue sections from 52 patients with non-CF bronchiectasis were stained with specific cellular markers and analyzed by immunohistochemistry and immunofluorescence to assess the epithelial structures, including ciliated cells and goblet cells morphology. Inflammatory cell counts and ciliary proteins expression levels of centrosomal protein 110 (CP110) and dynein heavy chain 5, axonemal (DNAH5) were assessed., Results: Epithelial hyperplasia is found in both bronchi and bronchioles in all specimens, including hyperplasia and/or hypertrophy of goblet cells. The median cilia length is longer in hyperplastic epithelium [bronchi: 8.16 (7.03-9.14) µm, P<0.0001; bronchioles: 7.46 (6.41-8.48) µm, P<0.0001] as compared to non-hyperplastic epithelium (bronchi: 5.60 µm; bronchioles: 4.89 µm). Hyperplastic epithelium is associated with overexpression of CP110 and decreased intensity of DNAH5 expression in both bronchial and bronchiolar epithelium. Though infiltration of neutrophils is predominant (63.0% in bronchi and 76.7% in bronchioles), eosinophilic infiltration is also present in the mucosa of bronchi (30.8%) and bronchioles (54.8%)., Conclusions: Aberrant epithelial remodeling with impaired mucociliary architecture is present in both large and small airways in patients with refractory non-CF bronchiectasis. Future studies should evaluate the interplay between these individual components in driving chronic inflammation and lung damage in patients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Airway remodeling is a hallmark of bronchial asthma. Our group has previously reported that the thymic stromal lymphopoietin (TSLP), an airway epithelial-derived cytokine, has a central role in the pathogenesis of airway remodeling, and that toll-like receptor (TLR) 4 signaling in epithelial cells may trigger T-helper 2 (Th2) immune responses by overexpression of TSLP. However, it is currently unclear whether TLR4 is a target in the treatment of airway remodeling in asthma. The present study established a house dust mite (HDM)-induced chronic asthmatic model in female BALB/c mice and treated the HDM-exposed mice with 3 mg/kg TAK242, as a TLR4 antagonist, 30 min prior to HDM challenge for up to 2 weeks. General structural changes in the airways were subsequently evaluated and the levels of TSLP in the bronchoalveolar lavage fluid (BALF) and interleukin (IL)-4, IL-13 and interferon (IFN)-γ in the blood serum were determined. Results indicated that TAK242 treatment markedly reduced pathological changes in the airways of HDM-induced asthmatic mice, as demonstrated by reductions in airway wall thickening, peribronchial collagen deposition and subepithelial fibrosis. Furthermore, airway hyperresponsiveness to inhaled methacholine and the levels of TSLP in the BALF and IL-4, IL-13 and IFN-γ in the peripheral blood were significantly reduced by TAK242 treatment (P<0.05). Furthermore, the shift in the IFN-γ/IL-4 ratio induced by HDM treatment was significantly reversed following TAK242 pretreatment, which indicated that TAK242 modulated Th1/Th2 immune homeostasis in the chronic asthma mouse model. The present findings in a chronic asthma mouse model suggest that TAK242 may be an efficient treatment for airway remodeling, possibly through the inhibition of TSLP overexpression and Th2 airway inflammation.

Background and Purpose: Early or primary application of high-frequency oscillatory ventilation (HFOV) has been recently suggested not to offer benefit to patients with acute respiratory distress syndrome (ARDS). However, the rescue effects of HFOV on severe pediatric acute respiratory distress syndrome (PARDS) with hypoxemia refractory to conventional mechanical ventilation (CMV) remain unclear. This study aimed to determine whether severe PARDS children would benefit from HFOV when oxygenation deteriorated on CMV and to identify any potential risk factors related to mortality., Patients and Methods: In a retrospective and observational study, 48 children with severe PARDS between January 2009 and July 2015 were divided into two groups: 26 in HFOV group and 22 in CMV group. Data regarding demographic, underlying conditions, arterial blood gases and clinical outcomes were collected and analyzed., Results: The arterial partial pressure of oxygen (PaO 2 )/fraction of inspiration oxygen (FiO 2 ) ratio and PaO 2 improved significantly during HFOV, whereas arterial partial pressure of carbon dioxide (PaCO 2 ) and oxygenation index decreased. There was no statistical difference in the in-hospital mortality between the groups ( P =0.367). The odds ratio of survival in HFOV group was 2.74 (95% confidence interval 0.52 to 14.58, P =0.237). The pediatric intensive care unit length of stay and total ventilation duration were longer in HFOV group ( P =0.048 and P =0.000, respectively). Vasoactive agents were used more frequently in HFOV group ( P =0.007). The incidence of new air leak was similar between the two groups ( P =0.674). The presence of multiple organ dysfunction syndrome and heavier body weight were identified as predictors of mortality in the HFOV group ( P =0.006 and P =0.020, respectively)., Conclusion: HFOV as an efficient alternative therapy could significantly improve hypoxemia and promote CO 2 removal in severe PARDS children when oxygenation progressively worsens on CMV., Competing Interests: The authors report no conflicts of interest in this work.