Immune response in the asthmatic respiratory tract is mainly driven by CD4+ T helper (Th) cells, represented by Th1, Th2, and Th17 cells, especially Th2 cells. Asthma is a heterogeneous and progressive disease, reflected by distinct phenotypes orchestrated by τh2 or non-Th2 (Th1 and Th17) immune responses at different stages of the disease course. Heterogeneous cytokine expression within the same Th effector state in response to changing conditions in vivo and interlineage relationship among CD4+ T cells shape the complex immune networks of the inflammatory airway, making it difficult to find one panacea for all asthmatics. Here, we review the role of three T helper subsets in the pathogenesis of asthma from different stages, highlighting timing is everything in the immune system. We also discuss the dynamic topography of Th subsets and pathogenetic memory Th cells in asthma.
Objective: Asthma drug research has been increasing yearly, and its clinical application value has increasingly attracted attention. This study aimed to analyze the development status, research hotspots, research frontiers, and future development trends of the research works on drugs for patients with asthma, especially severe asthma.Methods: Asthma drug-related articles published between 1982 and 2021 were retrieved from the Web of Science Core Collection (WOSCC) database, and only articles published in English were included. CiteSpace and VOSviewer software were utilized to conduct collaborative network analysis of countries/regions, institutions, keywords, and co-citation analysis of references.Results: A total of 3,234 asthma drug-related eligible articles were included. The United States was in a leading position, and Karolinska Institute (Sweden) was the most active institution. The most prolific journal in this field was Journal of Asthma, and the most cited journal was Journal of Allergy and Clinical Immunology. Keyword co-occurrence studies suggested that the current hotspots and frontiers were as follows: ① asthma: fully revealing the potential of existing conventional asthma drugs, determining the best drug delivery system, and indicating the best combination. To continue to explore potential targets for severe asthma or other phenotypes. Inhaled glucocorticoids and budesonide are still one of the important aspects of current asthma drug research and ② severe asthma: the research and development of new drugs, especially monoclonal antibodies including omalizumab, mepolizumab, and benralizumab to improve asthma control and drug safety, have become a research hotspot in recent years, highlighting the importance of “target” selection.Conclusion: This study demonstrates the global research hotspots and trends of the research works on drugs for patients with asthma/severe asthma. It can help scholars quickly understand the current status and hotspots of research in this field.
Objectives In this study, we measured the hematologic and spirometric parameters of native Tajik and Kyrgyz highlanders in the Pamir Mountains to investigate adaptations to high altitude stressors. Methods Hematological parameters including arterial oxygen saturation (SaO2), red blood cell (RBC) counts, and hemoglobin (Hb) concentration were measured on Sarikoli Tajik (n = 80; 3100 m), Wakhi Tajik (n = 48; 3500 m), and Kyrgyz (n = 64; 3250 m) in comparison to lowland Uyghurs (n = 50; 1300 m). Spirometric parameters including forced vital capacity (FVC), the first second of forced expiration (FEV1), and forced expiratory flow between 25% and 75% (FEF25‐75) were measured. We also reported mountain sickness symptoms in these highlanders and conducted a multivariate regression analysis to analyze the association between these symptoms and the measured parameters. Results SaO2 of Sarikoli Tajik, Wakhi Tajik, and Kyrgyz (91%‐93.5%) are significantly lower than lowland Uyghurs, yet are comparable to other native highlanders at a similar altitude. RBC counts and Hb concentrations of all three highland populations are significantly increased compared to Uyghurs. FVC is lower in Sarikoli Tajik, Wakhi Tajik, and Kyrgyz (male: 3.48‐3.86 L, female: 2.47‐2.78 L) compared to Uyghurs. Combined with normal FEV1, elevated FEV1/FVC ratio, and FEF25‐75, the spirometric patterns of these highlanders indicate restrictive lung disease. A high prevalence of mountain sickness symptoms such as headache and nausea was found in all three highland populations, and are attributed to low FVC and aging by regression analysis. Conclusion Tajik and Kyrgyz highlanders showed adaptation in SaO2, RBC, and Hb level, but poor performance in spirometry, which causes mountain sickness.
Background. Cycloastragenol (CAG) has been reported to alleviate airway inflammation in ovalbumin- (OVA-) induced asthmatic mice. However, its specific mechanisms remain unclear. Objective. This study is aimed at investigating the effects of CAG on asthma, comparing its efficacy with dexamethasone (DEX), and elucidating the mechanism of CAG’s regulation. Methods. The asthma mouse model was induced by OVA. CAG at the optimal dose of 125 mg/kg was given every day from day 0 for 20-day prevention or from day 14 for a 7-day treatment. We observed the preventive and therapeutic effects of CAG in asthmatic mice by evaluating the airway inflammation, AHR, and mucus secretion. Lung proteins were used for TMT-based quantitative proteomic analysis to enunciate its regulatory mechanisms. Results. The early administration of 125 mg/kg CAG before asthma happened prevented asthmatic mice from AHR, airway inflammation, and mucus hypersecretion, returning to nearly the original baseline. Alternatively, the administration of CAG during asthma also had the same therapeutic effects as DEX. The proteomic analysis revealed that the therapeutical effects of CAG were associated with 248 differentially expressed proteins and 3 enriched KEGG pathways. We then focused on 3 differentially expressed proteins (ITGAL, Syk, and Vav1) and demonstrated that CAG treatment downregulated ITGAL, Syk, and Vav1 by quantitative real-time PCR, western blot analysis, and immunohistochemical staining. Conclusion. These findings suggest that CAG exerts preventive and protective effects on asthma by inhibiting ITGAL, Syk, and the downstream target Vav1.
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