Relationship between montelukast and behavioral problems in preschool children with asthma

Background: There is insufficient clarity regarding whether or not drugs used in asthma cause behavioral problems in children.Methods: A total of 155 individuals, categorized into an asthma group (n = 95) and a control group (n = 60), were enrolled in the current prospective controlled study. The asthma group consisted of patients receiving treatment (inhaled corticosteroids [ICS] or montelukast) for at least 1 month. Check Behavior Checklist (CBCL) for ages 1.5–5 scores for the asthma and controls were compared. The asthma group was divided into two subgroups based on prophylactic therapy received, ICS and montelukast, and these groups’ CBCL scores were also compared. Results: The asthma group consisted of 95 children (ICS subgroup 45, montelukast subgroup 50) and the healthy control group of 60 cases. The mean total CBCL score was higher in the asthma group than in the control group (42 vs 32, respectively, P = 0.001). Internalization and externalization scores were also higher in the asthma group compared to the control group (P = 0.004 and P = 0.005, respectively). No significant difference was determined in terms of CBCL scores between the ICS and montelukast groups (P = 0.3). Montelukast was discontinued in one asthmatic child due to hallucination.Conclusion: This study determined a higher rate of behavioral problems in preschool children with asthma compared to healthy children. In contrast to other studies in the literature, we determined no difference in terms of total CBCL, and internalization and externalization scores of children with asthma who received ICS and montelukast. Nevertheless, it should be kept in mind that montelukast may cause serious neuropsychiatric events such as hallucination.

The effect of combination probiotic lactobacillus brevis and leuconostoc mesenteroides on tgf-β and il-12 expression in ileum

Background: Asthma is a disease of the respiratory tract in the form of chronic inflammation. Chronic inflammation is one of them characterized by the remodeling of the airways mediated by the anti-inflammatory cytokine TGF-β. In addition there are also several immune cells that play a role such as macrophages, dendritic, neutrophils as producers of IL-12. The presence of the gut-lung axis allows the spread of inflammatory cytokines from the lungs to the intestines and vice versa. Lactobacillus brevis and Leuconostoc mesenteroides have the potential to modulate the immune system through its colonization of the gut. The study aimed to look at the effect of probiotics combined Lactobacillus brevis and Leuconostoc mesenteroides on the expression of TGF-β and IL-12 in the asthma model mouse ileum. Method: This experimental post-test only control group design study used 18 Sprague-Dawley mice. The mice were divided into 3 groups at random: control group (KI), asthma treatment (KII), asthma treatment with a combination of Lactobacillus brevis and Leuconostoc mesenteroides (KIII). Sensitization of asthma with OVA through intraperitoneal injection on days 0 and 14 and through inhalation on days 21 -63. Administration of combination probiotics per oral per day on days 21-63 after inhalation of OVA. The ileum network was taken on the 64th day and measured the expression of TGF-βand IL-12 with immunohistochemical methods and analyzed the percentage proportion of TGF-βand IL-12. Data analysis were conducted by One way ANOVA test and continued post hoc tests. Results: The percentage calculation of the proportion of TGF-βin thecontrol group (KI), asthma group (KII), and the combination group of L.brevis and L.mesenteroides (KIII) is 22.4 ± 15.27; 1.6 ± 2.12; 19.4 ± 6.65. While the percentage calculation of il-12 proportion in each group consecutively were 24.3 ± 19.67; 64.63 ± 9.90; 51 ± 16.62. One way ANOVA Test results on the percentage proportion of TGF-βhave a p value of 0.013 (p<0.05) which means there is a significant difference in the entire group. Furthermore, the Post Hoc Games-Howell test was conducted and obtained a p value of 0.003 (p<0.05) between the asthma group (KII) and the combination group of L.brevis and L.mesenteroides (KIII) which means there are significant differences between the two groups. One way ANOVA Test results on the percentage proportion of IL-12 have a p value of 0.011 (p<0.05) which means there is a significant difference in the entire group. Furthermore, the Post Hoc LSD test was conducted and obtained a p value of 0.001 (p<0.05) between the control group Post Hoc analyses was conducted and obtained a p value of 0.002 (p<0.05) with number of errors was 11.353 between the control group (KI) and asthma group (KII) which means there are significant differences between the two groups. Conclusion: The probiotic administration of lactobacillus brevis and Leuconostoc mesenteroides had no effect on the expression of TGF-β and had no effect on il-12 expression in the asthma model mouse ileum. It is necessary to do research on mice with asthma using combinations with other bacteria in order to get maximum effect. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 175-183

The Effect of Curcuma longa on Inflammatory Mediators and Immunological, Oxidant, and Antioxidant Biomarkers in Asthmatic Rats

The effects of Curcuma longa (C. longa) on total and differential WBC, inflammatory and immunologic mediators, and oxidant and antioxidant biomarkers in bronchoalveolar lavage fluid (BALF) of rats model of asthma were assessed. Animals were divided to 5 groups including control (C), asthma (sensitized to ovalbumin), and asthmatic groups treated with 0.75, 1.50, and 3.00 mg/ml C. longa (CL) and 1.25 μg/ml dexamethasone (D) (8 rats in each group). Total and differential WBC count, concentrations of phospholipase A2 (PLA2), total protein (TP), interferon-gamma (IFN-γ), interleukin-4 (IL-4), immunoglobulin E (IgE), NO2, NO3, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and thiol in BALF were assessed. Total and most differential WBC counts and BALF levels of PLA2, TP, IgE, IL-4, and oxidants in asthma group were higher but antioxidants and IFN-γ levels as well as IFN-γ/IL-4 ratio were lower than control group ( p < 0.001 for all cases). Total WBC and levels of PLA2, IgE, NO2, and NO3 were significantly reduced following treatment with C. longa, compared to asthma group ( p < 0.001 for all cases). In groups treated with dexamethasone and two higher concentrations of C. longa, neutrophil and eosinophil counts as well as TP, IL-4, and MDA levels were significantly decreased but IFN-γ, IFN-γ/IL-4 ratio, and antioxidants were increased (except IFN-γ/IL-4 ratio), compared to asthma group ( p < 0.05 to p < 0.001). Compared to dexamethasone, C. longa exerted more pronounced effects on lung inflammation, oxidative stress, and immune system in asthmatic rats.

Alteration of lung tissues proteins in birch pollen induced asthma mice before and after SCIT

Subcutaneous immunotherapy (SCIT) is a classic form of allergen-specific immunotherapy that is used to treat birch pollen induced allergic asthma. To investigate the underlying molecular mechanisms of SCIT, we aimed to profile lung samples to explore changes in the differential proteome before and after SCIT in mice with allergic asthma. Fresh lungs were collected from three groups of female BALB/c mice: 1) control mice, 2) birch pollen-induced allergic mice, and 3) birch pollen-induced allergic mice with SCIT. Tandem mass tag (TMT) labelling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the lung proteome in the mice. Ingenuity pathway analysis (IPA) and Gene Ontology (GO) classification analysis were applied to identify differentially expressed proteins (DEPs) and crucial pathways. The screened DEPs were validated by immunohistochemistry analysis. A total of 317 proteins were upregulated and 184 proteins were downregulated in the asthma group compared to those of the control group. In contrast, 639 DEPs (163 upregulated and 456 downregulated proteins) were identified after SCIT in comparison with those of the asthma group. Among the 639 DEPs, 277 proteins returned to similar levels as those of the relative non-asthma condition. Bioinformatic analysis revealed that the 277 proteins played a significant role in the leukocyte extravasation signaling pathway. The leukocyte extravasation signaling pathway and related DEPs were of crucial importance in birch pollen SCIT.

Role of Aspergillus fumigatus sensitization in Patients with Asthma- COPD Overlap compared to asthma patients

Background Distinguishing asthma from COPD can be difficult especially among old age and smokers. Some patients have common features of asthma and COPD.1 (GINA, 2018). Hence, the definition of asthma COPD overlap (ACO) was developed. ACO is a considerable risk factor for healthcare utilization versus the general population, the asthma population and the COPD population.2(Minchul Kim et al., 2019). Fungal sensitization increase severity of asthma. Aim of the study To compare the prevalence of aspergillus fumigatus sensitization among ACO patients versus asthmatic patients and healthy normal control. Patients and Methods 90 individuals were included; 30 diagnosed as bronchial asthma (According to GINA 2018), 30 ACO patients and 30 healthy normal control. All are group matched to age and sex and selected from the allergy and chest outpatient clinics at Ain shams University hospitals. Total IgE, skin test for Aspergillus and spirometry were done to all participants. Results Aspergillus sensitization was more prevalent among ACO group compared to asthma group however, all control individuals were negative to aspergillus. FEV1 was significantly lower among ACO and asthma groups when compared to control. FEV1 increased significantly in the three groups after albuterol inhalation. Conclusion sensitization to Aspergillus was more among ACO patients compared to Asthma and control groups.

A Survey of of interval training on the expression of ICAM, VCAM and galectin-3 proteins in the heart tissue of asthmatic rats

Background: Asthma is a heterogeneous disease whose inflammatory processes are involved in the pathophysiology of atherosclerosis and endothelial dysfunction, and increases the prevalence of cardiovascular disease. This study was designed to investigate the effect of 8 weeks of interval training on some of the effective factors in atherosclerosis in heart tissue of asthmatic rats. Methods: In this experimental study, 15 rats were randomly divided into three groups of sham, asthma, and asthmatic-interval training. The model of asthma was induced by intraperitoneal injection of 1 ml ovalbumin for 2 weeks, and then asthmatic-interval training rats for 8 weeks participated in interval training. During the training protocol period, twice weekly intraperitoneal injections of ovalbumin 1 ml, and were placed into a glass container exposed to 5% ovalbumin spray. 48 hours after the last training session, the rats were anesthetized and their hearts were ejected. The levels of proteins expression of ICAM, VCAM, and galectin-3 were measured by immunohistochemistry, and western blotting, respectively. Data were analyzed using one-way ANOVA in SPSS at the significant level α=0.05. Results: The results of this study showed that the expression of ICAM (P=0.001), VCAM (P=0.001), and galectin-3 (P=0.001) was significantly increased in heart tissue of asthma rats. Whereas, interval training decreased the expression of ICAM (P=0.001), VCAM (P=0.001), and galectin-3 (P=0.01) proteins in the asthmatic-interval training group compared to the asthma group. Conclusions: It seems that, interval training is effective in preventing atherosclerosis in patients with asthma.

Dexmedetomidine Reduces IL-4 and IgE Expression Through Downregulation of TLR4/NF-κ Signaling Pathway to Alleviate Airway hyperresponsiveness in OVA Mice

Background: Asthma is a disease that affects health worldwide. It is characterised by inflammation and airway hyperreactivity. Because airway hyperreactivity can occur in other diseases, perioperative airway hyperreactivity is more insidious and widespread than in asthma and has serious implications that need to be addressed urgently. The use of dexmedetomidine in acute asthma and lung protection has been reported, but the exact mechanism is unclear. Objective: To investigate the effectiveness and mechanisms associated with dexmedetomidine in airway hyperresponsiveness.Methods: Forty BALB/c female mice were randomly divided into five groups: group K (blank group), group A (asthma group), group HD (asthma + dexmedetomidine treatment group), group TH (asthma + yohimbine group) and group HT (asthma + dexmedetomidine + yohimbine group), and the airway resistance of group K, group A and group HD were analysed by invasive airway resistance assay, ELISA assay, immunohistochemistry and q-PCR, respectively. Airway resistance; IL-4 and IgE levels in serum and BLAF; and IL-4, IL-13, Muc5AC, NFκB, TLR2, TLR4 and TSLP1 protein levels in lung tissues of the 5 groups were analysed by invasive airway resistance assay, ELISA, immunohistochemistry and qPCR. RESULTS: Compared with group A, there were statistical differences in airway resistance (P < 0.05); LIL-4 and IgE (P < 0.05) in serum and BLAF; and Muc5AC, TLR4 and NFκB protein contents (P < 0.05) in lung tissues in the HD group. Conclusion: 1. Dexmedetomidine can attenuate airway hyperresponsiveness in the OVA asthma model; 2. Dexmedetomidine reduced the production of IL-4 and IgE by down-regulating the TLR4/NF-κB signaling pathway, thereby reducing the lung inflammatory response and airway hyperresponsiveness in the OVA-induced asthma model.

Dexmedetomidine Reduces IL-4 and IgE Expression Through Downregulation of TLR4/NF-κB Signaling Pathway to Alleviate Airway Hyperresponsiveness in OVA Mice

Background: Asthma is a disease that affects health worldwide. It is characterised by inflammation and airway hyperreactivity. Because airway hyperreactivity can occur in other diseases, perioperative airway hyperreactivity is more insidious and widespread than in asthma and has serious implications that need to be addressed urgently. The use of dexmedetomidine in acute asthma and lung protection has been reported, but the exact mechanism is unclear. Objective: To investigate the effectiveness and mechanisms associated with dexmedetomidine in airway hyperresponsiveness.Methods: Forty BALB/c female mice were randomly divided into five groups: group K (blank group), group A (asthma group), group HD (asthma + dexmedetomidine treatment group), group TH (asthma + yohimbine group) and group HT (asthma + dexmedetomidine + yohimbine group), and the airway resistance of group K, group A and group HD were analysed by invasive airway resistance assay, ELISA assay, immunohistochemistry and q-PCR, respectively. Airway resistance; IL-4 and IgE levels in serum and BLAF; and IL-4, IL-13, Muc5AC, NFκB, TLR2, TLR4 and TSLP1 protein levels in lung tissues of the 5 groups were analysed by invasive airway resistance assay, ELISA, immunohistochemistry and qPCR. Results: Compared with group A, there were statistical differences in airway resistance (P < 0.05); LIL-4 and IgE (P < 0.05) in serum and BLAF; and Muc5AC, TLR4 and NFκB protein contents (P < 0.05) in lung tissues in the HD group. Conclusion: 1. Dexmedetomidine can attenuate airway hyperresponsiveness in the OVA asthma model; 2. Dexmedetomidine reduced the production of IL-4 and IgE by down-regulating the TLR4/NF-κB signaling pathway, thereby reducing the lung inflammatory response and airway hyperresponsiveness in the OVA-induced asthma model.

Dexmedetomidine Reduces IL-4 and IgE Expression Through Downregulation of TLR4/NF-κB Signaling Pathway to Alleviate Airway Hyperresponsiveness in OVA Mice

Background: Asthma is a disease that affects health worldwide. It is characterised by inflammation and airway hyperreactivity. Because airway hyperreactivity can occur in other diseases, perioperative airway hyperreactivity is more insidious and widespread than in asthma and has serious implications that need to be addressed urgently. The use of dexmedetomidine in acute asthma and lung protection has been reported, but the exact mechanism is unclear. Objective: To investigate the effectiveness and mechanisms associated with dexmedetomidine in airway hyperresponsiveness.Methods: Forty BALB/c female mice were randomly divided into five groups: group K (blank group), group A (asthma group), group HD (asthma + dexmedetomidine treatment group), group TH (asthma + yohimbine group) and group HT (asthma + dexmedetomidine + yohimbine group), and the airway resistance of group K, group A and group HD were analysed by invasive airway resistance assay, ELISA assay, immunohistochemistry and q-PCR, respectively. Airway resistance; IL-4 and IgE levels in serum and BLAF; and IL-4, IL-13, Muc5AC, NFκB, TLR2, TLR4 and TSLP1 protein levels in lung tissues of the 5 groups were analysed by invasive airway resistance assay, ELISA, immunohistochemistry and qPCR. Results: Compared with group A, there were statistical differences in airway resistance (P < 0.05); LIL-4 and IgE (P < 0.05) in serum and BLAF; and Muc5AC, TLR4 and NFκB protein contents (P < 0.05) in lung tissues in the HD group. Conclusion: 1. Dexmedetomidine can attenuate airway hyperresponsiveness in the OVA asthma model; 2. Dexmedetomidine reduced the production of IL-4 and IgE by down-regulating the TLR4/NF-κB signaling pathway, thereby reducing the lung inflammatory response and airway hyperresponsiveness in the OVA-induced asthma model.

MiR-182/Sestrin2 affects the function of asthmatic airway smooth muscle cells by the AMPK/mTOR pathway

Background and Objectives Asthma is a chronic inflammatory airway disease and brings heavy economic and spiritual burdens to patients’ families and the society. Airway smooth muscle cells (ASMCs) affect the development of asthma by secreting cytokines, growth factors, and prostates. The stress-inducing protein, Sestrin2, plays a vital role in antioxidant defense. The aim of this study is to investigate the role of Sestrin2 in asthma and its corresponding molecular mechanism. Materials and Methods Airway remodeling was induced by construction of asthma rat model. Primary ASMCs were isolated through combining tissue block adherence and enzymatic digestion and identified by immunofluorescence staining. Gene expression was measured by quantitative real-time PCR (qPCR) and western blot (WB) experiments. Cell viability, proliferation, migration, and calcium flow of ASMCs were measured by Cell Counting Kit-8 (CCK-8), 5-ethynyl-deoxyuridine (EdU), Transwell, and Fluo-3AM, respectively. The binding of miR-182 and Sestrin2 3′-untranslated region (3′-UTR) was measured by luciferase reporter system and RNA-binding protein immunoprecipitation (RIP) analysis. Results Sestrin2 expression was upregulated in asthma rat model and cell model. Overexpression of Sestrin2 enhanced the growth, migration, and calcium flow, and inversely, repression of Sestrin2 was reduced in ASMCs from the asthma group. MiR-182, one of the microRNAs (miRNAs) that possesses the potential to regulate Sestrin2, was downregulated in ASMCs from the asthma group. Further experiments revealed that Sestrin2 was inhibited by miR-182 and that overexpression of Sestrin2 reversed the miR-182–induced inhibition of the cellular progression of ASMCs from the asthma group. This study further investigated the downstream signaling pathway of Sestrin2 and found that increased expression of Sestrin2 activated 5′-adenosine monophosphate-activated protein kinase (AMPK), leading to the inactivation of mammalian target of rapamycin (mTOR) and thus promoting the growth, migration, and calcium flow of ASMCs from the asthma group. Conclusion This study investigated the role of Sestrin2 for the first time and further dissected the regulatory factor of Sestrin2, ultimately elucidating the downstream signaling pathway of Sestrin2 in asthma, providing a novel pathway, and improving the understanding of the development and progression of asthma.