Data Analysis-Driven Precise Asthmatic Treatment by Targeting Mast Cells.

BACKGROUND: Although the importance of mast cells in asthma has been studied, mast cellsinduced global changes in lungs are largely unknown. Data-driven identification contributes to discovering significant biomarkers or therapeutic targets, which are the basis of effective clinical medications. OBJECTIVE: This study aims to explore the effects of mast cells on gene expression in asthmatic lungs, and to assess the curative effects of inhaled budesonide (BUD). METHODS: Pulmonary gene expression in KitWsh mice with or without mast cell engraftment was analyzed with R software. Functional enrichment of Gene Ontology and KEGG was carried out through the DAVID online tool. Hub genes were identified with String and Cytoscape software. RESULTS: The array analyses showed that the mast cell engraftment enhanced inflammation/immune response, cytokine/chemokine signal, and monocyte/neutrophil/lymphocyte chemotaxis. Interleukin (IL)-6 was identified to be a significant hub gene with the highest interaction degree. Based on this, the effects of BUD were investigated on the aspects of anti-inflammation. BUD's treatment was found to reduce serum IL-6 content and pulmonary inflammation in ovalbumin-induced asthma rats. The treatment also downregulated beta-tryptase expression both in lung tissues and serum. Morphologically, the accumulation and degranulation of mast cells were significantly suppressed. Notably, the effects of BUD on inflammation and degranulation were comparable with Tranilast (a classic mast cell inhibitor), while a remarkable synergy was not observed. CONCLUSION: This study presented a unique pulmonary gene profile induced by mast cell engraftment, which could be reversed through blockage of mast cells or inhaled BUD.

Epidemiologic and clinical characteristics of 10 children with coronavirus disease 2019 in Changsha, China.

BACKGROUND: The outbreak of a new coronavirus, first reported in Wuhan, China, is spreading around the world. Information on the characteristics of children with Coronavirus Disease 2019 (COVID-19) is limited. METHODS: In this retrospective study, we recruited 10 children infected with SARS-COV-2 from January 27 to March 10, 2020, in Changsha, China. We report the epidemiological, clinical, laboratory, and high-resolution CT findings for these children. Qualitative descriptive analysis was used to describe the key results. RESULTS: Ten children were included. Three were male and seven were female. Three were from Wuhan, Hubei Province, and seven were from Changsha. All had a history of close contact with adults with COVID-19 before the onset of disease. Clinical manifestations included fever in four cases, respiratory symptoms in three cases, febrile convulsions in one case, vomiting in one case, abdominal pain in one case, and asymptomatic infection in two cases. All the children tested positive for nucleic acid in throat swabs at admission. Stool swabs of three cases were positive for nucleic acid after several days of fever. In nine children, blood routine results were normal, whereas in one case the white blood cell count was elevated. In four cases, CT findings of the lungs showed light ground-glass opacities, one case showed changes similar to bronchopneumonia, and the remaining cases were normal. All were treated with symptomatic support without complications. CONCLUSION: Our findings indicate that intrafamily transmission may be the main form of transmission of COVID-19 in children, and persistent intestinal excretion of virus is another characteristic among children. The results of stool swab tests should be considered for discharge and release from isolation.

Pretreatment With Inactivated Bacillus Calmette-Guerin Increases CD4+CD25+ Regulatory T Cell Function and Decreases Functional and Structural Effects of Asthma Induction in a Rat Asthma Model.

Bacillus Calmette-Guerin (BCG) has been shown to have therapeutic effects on asthma through CD4+CD25+ regulatory T cells (Tregs). We sought to assess pretreatment with inactivated BCG on CD4+CD25+ Tregs and its functional and structural effects in rat asthma model. The rat asthma model was established using ovalbumin (OVA) sensitization and challenge. Ten rats were pretreated with BCG prior to OVA and received continued BCG injections during OVA challenge (BCG+OVA group), 10 rats were treated with OVA alone (OVA group), and 10 rats were treated with saline (control group). After 9 weeks, histamine dihydrochloride effect on airway resistance was measured. Number of CD4+CD25+ Tregs was measured by flow cytometry, expression of Foxp3 and CTLA-4 mRNA was measured, and serum TGF-ß levels were determined. Differential cell count in bronchoalveolar lavage fluid (BALF) was determined, and lung tissue was processed and stained with hematoxylin and eosin, Masson's trichrome, and alcine blue and periodic acid Schiff's reaction to evaluate inflammatory cell infiltration, collagen deposition, and presence of goblet cells, respectively. BCG treatment led to an increase in CD4+CD25+ Tregs, as well as an increase in Foxp3 and CTLA-4 expression and serum TGF-ß levels. In addition, we observed a decrease in histamine dihydrochloride-induced airway resistance, a decrease in inflammatory leukocytes in BALF, and a decrease in airway remodeling indicators in BCG+OVA-treated rats compared with OVA-treated rats. Intradermally injected inactivated BCG has the potential to improve airway inflammation, airway resistance, and airway remodeling through a mechanism that may involve CD4+CD25+ Tregs.

[Effects of suplatast tosilate on airway inflammation and interleukin-5 in asthmatic rats].

OBJECTIVE: To study the effects of suplatast tosilate (IPD) on the airway inflammation and expression of interleukin-5 in asthmatic rats. METHODS: Fifty adult male Sprague-Dawley rats (4-week- old) were randomly assigned to five groups: placebo control, untreated asthma, budesonide(BUD)-treated asthma , early or late IPD intervention group (n=10 rats each). Asthmatic mode was prepared by ovalbumin sensitizion and challenge. Inflammatory cells and the percentage of EOS were detected in bronchoalveolar lavage fluid (BALF). The lung tissues were removed to detect the lung histomorphology. Gene expression of IL-5 was measured by reverse transcription-polymerase chain reaction (RT-PCR). Levels of interleukin 5 (IL-5) in BALF were measured using ELISA. RESULTS: The inflammatory cells and the percentage of EOS in BALF, IL-5 levels in BALF and IL-5 mRNA expression in the lung tissues were obviously higher in the untreated asthma group than the control group (P<0.05), while the parameters in the IPD or BUD-treated asthma groups were significantly lower than the untreated asthma group (P<0.05). CONCLUSIONS: IPD treatment can alleviate airway inflammation in asthmatic rats, possibly through inhibiting IL-5 mRNA transcripts.

Suplatast tosilate ameliorates airway hyperreactivity and inflammation through inhibition of the GATA­3/IL­5 signaling pathway in asthmatic rats.

Airway hyperreactivity and inflammation are important factors in the aggravation of lung function. Suplatast tosilate (IPD) is a novel and unique anti­asthma clinical compound. However, the mechanisms of IPD action in the inhibition of asthma remain to be elucidated. The present study aimed to investigate the role of the GATA binding protein 3 (GATA­3)/interleukin (IL)­5 signaling pathway in IPD­induced inhibition of asthma. Sprague­Dawley rats were sensitized by intraperitoneal injection with ovalbumin (OVA) to establish an animal model of asthma. IPD was administered continuously (C­IPD) or at a later stage (L­IPD). Budesonide (BUD) was used as a positive control. Airway resistance and the expression of genes at the mRNA and protein levels were measured. Morphological changes in lung tissue and the percentage of eosinophils (EOS) in peripheral blood were observed and correlation analysis was performed. The results revealed that sensitization by OVA significantly increased airway resistance and the percentage of EOS in peripheral blood and induced significant inflammatory changes in lung tissue, as demonstrated by thick epithelium, goblet cell hyperplasia and submucosal cell infiltration. In addition, sensitization by OVA was found to markedly upregulate IL­5 mRNA and protein expression. Airway resistance was found to positively correlate with the expression of IL­5 in the rat lung tissues. Sensitization by OVA was also observed to markedly enhance GATA­3 protein expression and GATA­3 levels were found to positively correlate with airway resistance and IL­5 levels. Similar to the effect of BUD, treatment with C­IPD or L­IPD was found to significantly attenuate OVA­induced increases in airway resistance and the percentage of EOS in peripheral blood. Notably, treatment with C­IPD or L­IPD markedly reduced the OVA-induced expression of IL­5 and GATA­3. In the present study, IPD intervention was demonstrated to ameliorate airway hyperreactivity and inflammation and the mechanisms may involve inhibition of the GATA­3/IL­5 signaling pathway.

[Results of skin prick test in young children with wheezing or allergic diseases].

OBJECTIVE: To study the characteristics of allergic reactions to common aeroallergens in young children with wheezing or allergic diseases by examining the results of skin prick test in children under 5 years old. METHODS: A total of 196 children under 5 years old, from a district of Changsha City sampled between September 1 to December 31, 2010, were assigned into two groups according to the presence of wheezing or allergic diseases: allergen screening (n=102) and control (n=94). Skin prick tests were performed on both groups. RESULTS: The positive rate of skin prick test in the allergen screening group was 61.8% (63/102), and this was significantly higher than in the control group (9.6%, 9/94; P<0.05). In the allergen screening group, the positive rate of skin prick test in children with both recurrent wheezing and allergic rhinitis was significantly higher than in children with wheezing alone (P<0.05). The frequency of wheezing was positively correlated with a positive skin prick test (r=0.91; P<0.05). The positive rate of skin prick test for mites was significantly higher than for other aeroallergens (24.2% vs 3.5%; P<0.05) in the allergen screening group. Skin prick testing of the children for dermatophagoides farinae showed a higher positive rate than for dermatophagoides pteronyssinus (50.0% vs 14.7%; P<0.05). CONCLUSIONS: Wheezing in early childhood may be associated with the occurrence of asthma. Skin prick testing contributes to the diagnosis of allergic diseases and assessment of allergic reactions to aeroallergens in children with wheezing.