Introduction: A significant proportion of severe asthma patients require oral corticosteroids (OCS) to maintain symptom control. Prolonged OCS predisposes patients to hypothalamicpituitary-adrenal axis suppression which can be lifethreatening. Biologic therapies are effective steroid-sparing options suitable for select severe asthma patients. We evaluated steroid tapering outcomes and adrenal function during biologic therapy in a tertiary severe asthma clinic. Results: A total of 43 patients were included. Median age was 66 years (interquartile range [IQR] 60–74), and 65% were male. Mepolizumab was the most used (17 patients), followed by benralizumab (15), tezepelumab (6), dupilumab (4), and omalizumab (1). Median baseline prednisolone dose was 10 mg (IQR 5–10). Median lowest dose achieved was 3 mg (IQR 0–3), sustained for at least 4 weeks in 90.7% of patients. Median reduction in prednisolone dose was 5 mg (IQR 5–7.25). In all, 42% of patients successfully discontinued maintenance steroids. Adrenal function was assessed using morning serum cortisol (n = 37) and/or SST (n = 28). Evidence of adrenal insufficiency was identified in 19 patients (44%), including 15 patients with failed SST and four with low morning cortisol suggestive of adrenal suppression. Morning serum cortisol was indeterminate in four patients. A total of 17 patients were referred to endocrinology. During steroid tapering, 11 asthma-related hospital admissions and eight emergency department presentations occurred, involving 10 patients. Conclusion Biologics facilitate the reduction of the OCS burden in severe asthma. Tertiary adrenal suppression is common during steroid tapering and requires prompt biochemical assessment and endocrinology referral. Structured monitoring of adrenal function is essential during biologicfacilitated steroid tapering in routine clinical practice.
Biological Products ; Steroids ; Asthma

BACKGROUND

Bronchial asthma is one of the most common chronic childhood diseases encountered in the primary care setting. Adherence to recommendations from clinical practice guidelines on asthma can be utilized as an indicator of quality of care when evaluating the implementation of the universal health care in the Philippines.

To determine the clinical profile of pediatric patients with bronchial asthma; and to evaluate the prescription patterns for asthma treatment in a primary care setting.

This was a retrospective cohort study that involved review of the electronic medical records in a rural site of the Philippine Primary Care Studies (PPCS). All patients less than 19 years old who were diagnosed with asthma from April 2019 to March 2021 were included. Quality indicators for asthma care were based on adherence to recommendations from the 2019 Global Initiative for Asthma (GINA) Guidelines.

This study included 240 asthmatic children with mean age of 6 years (SD ± 4.9) and a slight male preponderance (55.4%). Majority (138 children or 57.5%) were less than 6 years old. Out of the 240 children, 224 (93.3%) were prescribed inhaled short-acting beta-agonists (SABA) and 66 (27.5%) were prescribed oral SABA. Only 14 children (5.8%) were prescribed inhaled corticosteroids (ICS), with 13 children (5.4%) given ICS with longacting beta-agonists (LABA) preparations, and one child (0.4%) given ICS alone. Quality indicators used in this study revealed underutilization of ICS treatment across all age groups, and an overuse of SABA-only treatment in children 6 years old and above. Moreover, 71.3% of the total patients were prescribed antibiotics despite the current GINA recommendation of prescribing antibiotics only for patients with strong evidence of lung infection, such as fever or radiographic evidence of pneumonia.

There were 240 children diagnosed with asthma over a 2-year period in a rural community, with a mean age of 6 years old and a slight male predominance. This quality-of-care study noted suboptimal adherence of rural health physicians to the treatment recommendations of the GINA guidelines, with overuse of SABA and underuse of ICS for asthma control.

OBJECTIVE: To observe the skin surface temperature at the related back-shu points in the patients with the different levels of pulmonary ventilation function in chronic persistent asthma, and to explore the correlation between the skin temperature at the back-shu points and pulmonary ventilation function indexes based on "lung governing the skin and hair". METHODS: Sixty-one patients with chronic persistent asthma, based on the level of pulmonary ventilation function, were assigned into a reduced pulmonary ventilation function group (reduced function group, 32 cases) and a normal pulmonary ventilation function group (normal function group, 29 cases). In the two groups, the skin surface temperature was measured in the sites of bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23); and the pulmonary ventilation function indexes (the percentage of predicted value of forced vital capacity [FVC%pred], the percentage of predicted value of forced expiratory volume in the first second [FEV1%pred], the percentage of predicted value of FEV1/FVC [FEV1/FVC%pred] and the percentage of predicted value of the peak expiratory flow [PEF%pred]) were recorded. The correlation between the skin surface temperature of acupoints and pulmonary ventilation function was analyzed. RESULTS: Compared with the normal function group, the surface skin temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was higher in the reduced function group (P<0.05, P<0.01). Compared with the normal function group, FEV1%pred, FEV1/FVC%pred and PEF%pred were decreased in the reduced function group (P<0.001). There was no significant difference in FVC%pred between the two groups (P>0.05). The skin surface temperature at the bilateral Feishu (BL13), Geshu (BL17), Pishu (BL20) and Shenshu (BL23) was negatively correlated with FVC%pred, FEV1%pred, FEV1/FVC%pred and PEF%pred in 61 patients with chronic persistent asthma (P<0.001, P<0.01, P<0.05). CONCLUSION The skin surface temperature at back-shu points is elevated in line with the the decline of pulmonary ventilation function in the patients with chronic persistent asthma, presenting a negative correlation with pulmonary ventilation function indexes. It is preliminarily verified that back-shu point is characterized by reflecting the visceral disorders.
Humans ; Female ; Male ; Asthma/therapy* ; Middle Aged ; Adult ; Skin Temperature ; Lung/physiopathology* ; Acupuncture Points ; Pulmonary Ventilation ; Aged ; Chronic Disease/therapy* ; Young Adult ; Hair

OBJECTIVE: To analyze the research progress, hotspots, frontier trends and existing limitations of acupuncture and moxibustion treatment for respiratory diseases in the past decade using bibliometric and scientific knowledge mapping methods. METHODS: Literature on acupuncture and moxibustion treatment for respiratory diseases published from January 1st, 2014 to June 30th, 2024, from CNKI, VIP, Wanfang, PubMed and Web of Science was retrieved. CiteSpace 6.1.R6 and VOSviewer V1.6.20 were used to perform visual analysis, including keyword co-occurrence and clustering, and to construct knowledge maps of acupuncture and moxibustion treatment for respiratory diseases. RESULTS: A total of 1,106 Chinese articles and 185 English articles were included. High-frequency keywords focused on clinical diseases, treatment methods, efficacy observation, mechanisms etc. The main respiratory diseases treated with acupuncture and moxibustion included chronic obstructive pulmonary disease (COPD), asthma and cough. Commonly used acupoints included Feishu (BL13), Zusanli (ST36), Dazhui (GV14) and Shenshu (BL23), primarily involving the bladder meridian of foot-taiyang, conception vessel and lung meridian of hand-taiyin. Among the treatment methods dominated by acupuncture and moxibustion, the primary treatment method was electroacupuncture combined with moxibustion, and acupoint application was supplemented, with increasing emphasis on integrative Chinese and Western medicine and acupuncture combined with medication. The therapeutic mechanisms involved anti-inflammatory effects and inhibition of airway remodeling, with targets mainly associated with the NF-κB signaling pathway. CONCLUSION Acupuncture and moxibustion demonstrates certain advantages in treating respiratory diseases such as COPD, asthma and cough, with mechanisms related to anti-inflammatory effects and inhibition of airway remodeling. Future research should focus on multi-center, large-sample, high-quality clinical and experimental studies to explore the optimal clinical treatment protocols and underlying mechanisms.
Moxibustion/trends* ; Humans ; Acupuncture Therapy/trends* ; Acupuncture Points ; Asthma/therapy* ; Pulmonary Disease, Chronic Obstructive/therapy*

Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

Objective To observe the effect of m⁶A methylation regulation on Notch1 pathway on the homing of BMSCs in asthma, and the intervention study of traditional Chinese medicine compound Yanghe Pingchuan Granules. Methods Rat bone mesenchymal stem cells(BMSC)and bronchial epithelial cells were cocultured. The extracted cells were divided into: bronchial epithelial cell group, asthma bronchial epithelial cell+mesenchymal stem cell co-culture group (co-culture group), co-culture cell+normal serum group, coculture cell+serum containing optimal drug group, siRNA FTO+normal serum group, siRNA FTO-NC+normal serum group, and siRNA FTO+serum containing optimal drug group. The vitality and cell cycle changes of co-cultured cells were detected. The level and markers of homing BMSC were detected by immunofluorescence staining. The expression of Notch1 pathway related genes were detected by qRT-PCR. The expression of Notch1 pathway related proteins were detected by Western blot. Results Compared with bronchial epithelial cell group, the co-cultured cell group showed an increase in the homing level of BMSCs and the expression of C-X-C motif chemokine receptor 4 (CXCR4), stromal cell-derived factor 1 (SDF-1), Notch1, transcription factor recombination signal binding protein-J (RBP-J), and hairy enhancer of split 1 (Hes1) proteins. Compared with the co-cultured cell group and co-cultured cell+normal serum group, the co-cultured cell+serum containing optimal drug group showed an increase in the homing level of BMSCs and the expressions of CXCR4 and SDF-1, while the protein and mRNA levels of Notch1 and Hes1 decreased. Compared with the siRNA FTO-NC+normal serum group, the siRNA FTO+normal serum group showed an increase in the levels of Notch1, activated Notch1, RBP-J, Hes1 protein, and cell viability, while the level of homing BMSC decreased. Compared with siRNA FTO+normal serum group, the levels of Notch1, RBP-J mRNA, activated Notch1, and Hes1 protein decreased, while the level of homing BMSCs increased in siRNA FTO+serum containing optimal drug group. The levels of Notch1, RBP-J, and Hes1 mRNA were reduced in the co-cultured cells+serum containing optimal drug group. Compared with siRNA FTO+serum containing optimal drug group, the expressions of Notch1, activated Notch1, RBP-J, Hes1 protein and cell viability decreased, while the level of homing BMSCs increased in the co-cultured cells+serum containing optimal drug group. Conclusion Yanghe Pingchuan Granules may promote the homing of BMSCs in asthma and alleviate asthma inflammation by upregulating the expression of FTO and inhibiting the expression of downstream genes in the Notch1 signaling pathway.
Animals ; Receptor, Notch1/genetics* ; Mesenchymal Stem Cells/cytology* ; Asthma/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Rats ; Coculture Techniques ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Epithelial Cells/metabolism* ; Rats, Sprague-Dawley ; Cells, Cultured ; Male

Objective Through integrative bioinformatics analysis of multi-source transcriptomic data, potential biomarkers to asthma epithelial cells were identified. The expression of these candidate target was subsequently validated in lung tissues and epithelial cells from asthma models. Methods The gene expression profile data of epithelial cells from three asthma patient cohorts and corresponding healthy controls were integrated from the Gene Expression Omnibus (GEO) database. Differential expression analysis and gene co-expression network analysis were performed to identify key genes and biological pathways associated with asthma. The key genes were validated in lung tissues and epithelial cells in asthma animal models. Results Differential gene expression analysis revealed 1121 upregulated and 1484 downregulated genes in epithelial cells from asthma patients compared with healthy controls. The biological pathway enrichment analysis revealed that the upregulated genes were mainly involved in glycosylation processes, whereas the downregulated genes were mainly associated with immune cell differentiation process. The gene co-expression network analysis revealed that module 9, enriched in glycosylation-related pathways, was significantly positively correlated with asthma, whereas module 17, associated with insulin and other signaling pathways, showed a significant negative correlation with asthma. We identified the genes of polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5), pyrroline-5-carboxylate reductase 1 (PYCR1), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as key genes within module 9, all of which were significantly upregulated in asthma. Finally, we validated that the expression levels of GALNT5, PYCR1, and CEACAM5 were significantly upregulated in epithelial cells from asthmatic lung tissue. Additionally, using a rat asthma model, we further confirmed that the protein levels of these three genes were significantly upregulated in lung tissues of the model group. Conclusion Through data integration and experimental validation, this study identified key genes and biological pathways closely associated with asthma pathogenesis. These findings provide a novel theoretical basis and potential targets for the diagnosis and treatment of asthma.
Asthma/metabolism* ; Humans ; Epithelial Cells/metabolism* ; Animals ; Biomarkers/metabolism* ; Gene Expression Profiling ; Transcriptome ; Gene Regulatory Networks ; Rats ; Computational Biology

Asthma is a chronic inflammatory disease of the airway involving various cellular players. Among the different phenotypes of asthma, neutrophilic asthma is often associated with severe airway inflammation and a notable resistance to corticosteroid treatment. Macrophages, as innate immune cells, play a crucial role in the pathogenesis of neutrophilic asthma. They regulate neutrophil recruitment and activation to promote the progression of airway inflammation. During this process, macrophages also undergo changes in aspects such as efferocytosis. We reviewed the recent research progresses regarding the role of macrophages in the pathogenesis of neutrophilic asthma, aiming to provide valuable insights for future studies in this area.
Humans ; Asthma/pathology* ; Neutrophils/pathology* ; Macrophages/immunology* ; Animals ; Phagocytosis

OBJECTIVES: To study the expression of the transcription factor GATA1 in bronchial asthma (referred to as asthma) and its effect on the expression level of the asthma susceptibility gene orosomucoid 1-like protein 3 (ORMDL3), along with the underlying molecular mechanisms. METHODS: The study included 28 cases of moderate asthma, 46 cases of severe asthma, and 12 normal controls from the Gene Expression Omnibus (GEO) database. The mRNA expression levels of GATA1 and ORMDL3 were analyzed among the asthma patients and the normal controls, including their correlation. The pGL-185/58 plasmid was co-transfected with GATA1 gene siRNA (si-GATA1 group) and siRNA negative control (si-control group) into BEAS-2B cells. Bioinformatics methods were used to predict GATA1 binding sites in the promoter region of the ORMDL3 gene. The dual-luciferase reporter gene system was employed to assess the promoter activity of ORMDL3, while real-time quantitative PCR and Western blotting were used to measure the mRNA and protein expression levels of GATA1 and ORMDL3. Chromatin immunoprecipitation (ChIP) assays were conducted to determine whether GATA1 binds to the promoter region of ORMDL3. RESULTS: The expression levels of GATA1 and ORMDL3 mRNA were significantly higher in the severe asthma group compared to the normal control group (P<0.001). Positive correlations were observed between GATA1 mRNA and ORMDL3 mRNA expression levels in both the moderate and severe asthma groups (r=0.636 and 0.341, respectively; P<0.05). In BEAS-2B cells, the dual-luciferase reporter assay revealed that ORMDL3 promoter luciferase activity, as well as ORMDL3 mRNA and protein expression levels, were lower in the si-GATA1 group compared to the si-control group (P<0.05). ChIP assay results demonstrated that GATA1 could bind to the promoter region of ORMDL3. CONCLUSIONS The expression of GATA1 is increased in asthma patients, which may regulate the promoter activity and expression of the asthma susceptibility gene ORMDL3.
Humans ; Asthma/etiology* ; GATA1 Transcription Factor/analysis* ; Membrane Proteins/physiology* ; Male ; Female ; Promoter Regions, Genetic ; Child ; Transcription, Genetic ; Gene Expression Regulation ; Adolescent ; RNA, Messenger/analysis*

Combined allergic rhinitis and asthma syndrome (CARAS) is one of the common chronic airway inflammatory diseases in children. With the development of epigenetics, research on CARAS has gradually extended from protein levels to molecular levels, such as transcription and post-transcriptional regulation. N6-methyladenosine (m6A) methylation and ferroptosis have emerged as promising research hotspots in recent years, playing crucial roles in tumors, growth and development, and allergic diseases. This paper aims to summarize the characteristics of m6A and ferroptosis, along with their roles in the onset and progression of CARAS in children, thereby providing new insights and strategies for the diagnosis and treatment of childhood CARAS.
Humans ; Adenosine/physiology* ; Asthma/etiology* ; Ferroptosis ; Rhinitis, Allergic/etiology* ; Child