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Objective: In a previous study we have shown that, in the presence of interleukin (IL)-33, repeated, per-nasal challenge of murine airways with Streptococcus pneumoniae ( S. pneumoniae ) organisms induces human asthma-like airways inflammation. It is not clear, however, whether this effect is unique or manifest in response to other common respiratory pathogens. Methods: To explore this, airways of BALB/c mice were repeatedly challenged per-nasally with formaldehyde-inactivated bacterial bodies in the presence or absence of murine recombinant IL-33. Serum concentrations of S.pneumoniae , Moraxella catarrhalis ( M.catarrhalis ) and Haemophilus influenzae ( H.influenzae ) lysates-specific IgE were measured in patients with asthma and control subjects. Results: We showed that in the presence of IL-33, repeated, per-nasal airways exposure to the bodies of these bacteria induced airways hyperresponsiveness (AHR) in the experimental mice. This was accompanied by cellular infiltration into bronchoalveolar lavage fluid (BALF), eosinophilic infiltration and mucous hypertrophy of the lung tissue, with elevated local expression of some type 2 cytokines and elevated, specific IgG and IgE in the serum. The precise characteristics of the inflammation evoked by exposure to each bacterial species were distinguishable. Conclusions: These results suggest that in the certain circumstances, inhaled or commensal bacterial body antigens of both Gram-positive ( S. pneumoniae ) and Gram-negative ( M. catarrhalis and H. influenzae ) respiratory tract bacteria may initiate type 2 inflammation typical of asthma in the airways. In addition, we demonstrated that human asthmatic patients manifest elevated serum concentrations of M.catarrhalis- and H.influenzae- specific IgE.

Allergic asthma is a complex inflammatory disorder predominantly orchestrated by T helper 2 (Th2) lymphocytes. The anti-inflammatory protein Clara Cell 10-kDa (CC10), also known as secretoglobin family 1A member 1 (SCGB1A1), shows promise in modulating respiratory diseases. However, its precise role in asthma remains unclear. This study examines the potential of CC10 to suppress allergic asthma inflammation, specifically assessing its regulatory effects on Th2 cell responses and dendritic cells (DCs). Lower CC10 levels in asthma were observed and correlated with increased IgE and lymphocytes. Cc10 -/- mice exhibited exacerbated allergic airway inflammation marked by increased inflammatory cell infiltration, Th2 cytokines, serum antigen-specific IgE levels, and airway hyperresponsiveness (AHR) in house dust mite (HDM)-induced models. Conversely, recombinant CC10 significantly attenuated these inflammatory responses. Intriguingly, CC10 did not directly inhibit Th cell activation but significantly downregulated the population of CD11b + CD103 - DCs subsets in lungs of asthmatic mice and modulated the immune activation functions of DCs through NF-κB signaling pathway. The mixed lymphocyte response assay revealed that DCs mediated the suppressive effect of CC10 on Th2 cell responses. Collectively, CC10 profoundly mitigates Th2-type allergic inflammation in asthma by modulating lung DC phenotype and functions, highlighting its therapeutic potential for inflammatory airway conditions and other related immunological disorders., (© 2024. The Author(s).)

Background: Inhaler concordance and the peak inspiratory flow rate (PIFR) are important determinants of treatment effects in patients with chronic airway diseases. Adequate PIFR is required for driving aerosol medication into the lower respiratory tract. However, the relationship between them has not been discussed previously. This study aimed to describe the characteristics of inhaler concordance and PIFR in Chinese patients with chronic airway diseases and discuss the associated variables and the relationship between them., Methods: In this single-centre, observational study, a total of 680 patients with chronic airway diseases were enrolled from July 2021 to April 2023. We collected data on the socio-demographic and clinical variables of inhaler concordance using the test of adherence to inhalers (TAI) and PIFR. Multivariate logistic regression was conducted to examine variables related to inhaler concordance and PIFR., Results: A total of 49.4% of patients had low concordance. Patients with chronic obstructive pulmonary disease (COPD) were more concordant than patients with asthma (mean TAI score: 43.60 vs 41.20; p<0.01), while there was no difference in concordance between the asthma-COPD overlap group and the asthma or COPD group. Suboptimal PIFR (adjusted OR, 1.61; 95% CI 1.04 to 2.51) increased the risk of poor concordance among all patients, while triple therapy (adjusted OR, 0.60; 95% CI 0.35 to 0.86) reduced the risk. A total of 54.9% of patients had suboptimal PIFR. Older age, lower educational level, use of dry powder inhalers and lower forced expiratory volume in 1 s % predicted were significantly correlated with insufficient PIFR. Subgroup analysis revealed a greater proportion of patients with insufficient PIFR during exacerbation than during the stable phase (61.7% vs 43.5%, p<0.001)., Conclusion: Inhaler concordance was low, and suboptimal PIFR was a risk factor for poor concordance among Chinese patients with chronic airway diseases. In addition, current inhalation devices may not be suitable, and PIFR reassessment should be considered for patients with COPD during exacerbation., Trial Registration Number: The study was registered in chictr.org.cn (ChiCTR2100052527) on 31 October 2021., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The dosage of ovalbumin (OVA) during the sensitization stage is considered a crucial factor in the development of airway hyperresponsiveness (AHR). However, the inconsistent dosages of sensitizing OVA used in current studies and the lack of research on their impact on AHR are notable limitations., Methods: We examined the impact of increasing sensitizing doses of OVA in a murine asthma model, which entailed initial sensitization with OVA followed by repeated exposure to OVA aerosols. BALB/c mice were primed with doses of OVA (0, 10, 20, 50, and 100 μg) plus 1 mg Alum on Days 0 and 7, and were challenged with OVA aerosols (10 mg/mL for 30 min) between Days 14 and 17. Antigen-induced AHR to methacholine (MCh), as well as histological changes, eosinophilic infiltration, and epithelial injury were assessed., Results: The result indicated that there are striking OVA dose-related differences in antigen-induced AHR to MCh. The most intense antigen-induced AHR to MCh was observed with sensitization at 50 μg, while weaker responses were seen at 10, 20, and 100 μg. Meanwhile, there was a significant increase in eosinophil count with sensitization at 50 μg. The changes of AHR were correlated with total cells count, lymphocytes count, eosinophils count, and basophils count in bronchoalveolar lavage fluid; however, it did not correlate with histological changes such as cellular infiltration into bronchovascular bundles and goblet cell hyperplasia of the bronchial epithelium., Conclusion: Overall, this study demonstrated that sensitization with 50 μg of OVA resulted in the most significant AHR compared to other dosages. These findings may offer valuable insights for future research on mouse asthma modeling protocols., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objectives: Inhaler satisfaction is an important factor affecting inhaler adherence and the efficacy of inhalers in chronic airway diseases. Using a scientific and effective method to assess patients' satisfaction with inhalers is of great significance for improving clinical outcomes. The Feeling of Satisfaction with Inhaler-10 (FSI-10) is specifically designed to assess patients' inhaler satisfaction in chronic airway diseases, but the application research on this scale is not available in China. This study aims to evaluate the reliability and validity of the Chinese version of FSI-10, describe the current status of inhaler satisfaction and discuss the associated variables in Chinese patients with chronic airway disease., Methods: Based on the English version of FSI-10, items of the Chinese version of FSI-10 were determined after forward⁃backward translation and cultural adaption. Totally, 322 patients with chronic obstructive pulmonary disease (COPD) and asthma were enrolled from the Second Xiangya Hospital of Central South University from June to October 2022. We collected associated clinical variables and inhaler satisfaction using the Chinese version of FSI-10. The content validity of the scale was expressed by content validity index (CVI) and the construct validity was analyzed by exploratory factor analysis (EFA). The reliability of the scale was expressed by Cronbach's α coefficient, the split-half reliability and test-retest reliability. A multivariate logistic regression was conducted to examine variables related to inhaler satisfaction., Results: The reliability and validity analysis showed that the CVI was 0.983. One factor was extracted from the Chinese version of FSI-10 and the cumulative variance contribution rate was 73.114%. The Cronbach's α of the scale was 0.913, the Guttman's half-reliability coefficient was 0.905, and the test-retest reliability was 0.727 ( P <0.001). In addition, the total score of the scale for patients was 38.92±4.26 points and the proportion of high satisfaction (the score of FSI-10≥40) in patients with COPD was significantly lower than that in asthma patients (71.3% vs 87.9%, P <0.01). Older age (age≥70 years) was a risk factor of lower inhaler satisfaction and asthma diagnosis was a protective factor., Conclusions: The Chinese version of FSI-10 has good reliability and validity in patients with COPD and asthma, which may be further promoted and applied in patients with chronic airway disease in China. Doctors should regularly evaluate the inhaler satisfaction of patients with chronic airway diseases, especially for those elder or with severe symptoms and a long course of illness.

Introduction: Many asthmatic patients are exposed to cigarette smoke actively or passively, which contributes to asthma exacerbation and poor control. This study is to explore the effects of cigarette smoke on pathological changes in murine surrogate of asthma., Methods: C57BL/6 mice were sensitised and challenged with ovalbumin (OVA) to establish a surrogate of asthma and then administered with cigarette smoke extract (CSE). Airways hyperresponsiveness (AHR) was measured using the Flexivent system. Histological staining (haematoxylin-eosin [HE], periodic acid Schiff [PAS], Congo red and Masson's trichrome) was employed to measure pathological changes in sections of lung tissue of experimental mice. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of total and OVA-specific IgE, cytokines and chemokines (eotaxin-1, IL-13, IL-1β, TNF-α, IL-17A, IL-33) in the lung tissue homogenates. Immunoreactivity for vWF and α-SMA in lung tissue sections was detected by immunohistochemistry., Results: Exposure of the animals to CSE significantly reduced OVA-induced AHR, the number of eosinophils in bronchoalveolar lavage fluid (BALF) and eosinophils infiltrating into the lung tissue, as well as concentrations of some cytokines in lung homogenate. In contrast, it significantly enhanced the number of macrophages and M2 in BALF, as well as collagen deposition, smooth muscle thickness and alveolar destruction in lung tissue., Conclusion: CSE inhibits OVA-induced AHR, changes inflammation 'phenotypes', while accelerates some aspects of airways remodelling, which might contribute to worse symptoms and be refractory to anti-inflammation therapies for asthmatics., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Although bronchodilators and glucocorticoids can reduce the symptoms of cough and asthma to a certain extent, the adverse drug reactions and recurrence after recovery still trouble clinicians. Acupoint catgut embedding is effective in preventing and treating acute recurrence and deterioration of COPD, but its clinical efficacy remains controversial. Therefore, this study evaluated the clinical efficacy and safety of acupoint catgut embedding combined with conventional Western medicine for COPD through meta-analysis., Methods: Pubmed, the Cochrane Library, Web of Science, Sinomed, China Knowledge Network, VIP, and Wanfang databases were searched, with a time frame from database creation to November 2022. Meta-analysis was performed with Revman 5.3. Publication bias was assessed by Stata 15.0., Results: Seventeen studies were listed, with a total sample size of 1516 cases. Meta-analysis showed that compared with conventional western medicine, acupoint catgut embedding combined with conventional western medicine could effectively improve the total effective rate of clinical symptoms of stable COPD [RR = 1.21, 95%CI (1.13, 1.29), P < .00001], forced expiratory volume in 1 second (FEV1) [mean difference (MD) = 0.04, 95%CI (0.00, 0.09), P = .04],the percentage of forced expiratory volume in 1 second predicted value [MD = 1.13, 95%CI (0.38,1.88), P = .003], acute exacerbation of chronic obstructive pulmonary disease [MD = -0.73, 95%CI (-1.04, -0.42), P < .00001], COPD assessment test score [MD = -2.39, 95%CI (-3.65, -1.13), P = .0002], the improved medical research council respiratory questionnaire score (mMRC score) [MD = -0.15, 95%CI (-0.29, -0.02),P = .03], 6-minute walk distance [MD = 28.16, 95%CI (17.31, 39.00), P < .00001], the production of inflammatory factor interleukin-8 [MD = -9.65, 95%CI (-10.44, -8.86), P < .00001], but the adverse event rate was comparable[RR = 1.39, 95%CI (0.28,6.91), P = .69]. However, there was no significant difference in forced expiratory volume in 1 second/forced vital capacity and TNF-α between the acupoint catgut embedding combined group and the conventional western medication group. Harbord test showed no significant publication bias., Conclusion: The clinical efficacy of acupoint catgut embedding combined with conventional western medicine for stable COPD is better than that of conventional western medicine, and the safety may be equivalent to that of conventional western medicine, which has the value of further research exploration., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Asthma is a common chronic respiratory disease characterized by airways inflammation, hyperresponsiveness and remodeling. IL-37, an anti-inflammatory cytokine, consists of five splice isoforms, that is, a-e. Although it has been previously shown that recombinant human IL-37b is able to inhibit airway inflammation and hyperresponsiveness in animal models of asthma, the effects and difference of other IL-37 isoforms, such as IL-37a on features of asthma are unknown., Methods: Animal models of chronic asthma were established using IL-37a and IL-37b transgenic mice with C57BL/6J background and wild-type (WT) mice sensitized and nasally challenged with ovalbumin (OVA). Airway hyperresponsiveness was measured using FlexiVent apparatus, while histological and immunohistological stainings were employed to measure airways inflammation and remodeling indexes, including goblet cell metaplasia, mucus production, deposition of collagen, hypertrophy of airway smooth muscles and pulmonary angiogenesis., Results: Compared to WT mice, both IL-37a and IL-37b transgenic mice had significant reduced airway hyperresponsiveness and the declined total numbers of inflammatory cells, predominant eosinophils into airways and lung tissues. Furthermore, all features of airways remodeling, including degrees of mucus expression, collagen deposition, hypertrophy of smooth muscles, thickness of airways and neovascularization markedly decreased in IL-37 transgenic mice compared with OVA-treated WT mice., Conclusion: Our data suggest that both IL-37a and IL-37b isoforms are able to not only ameliorate airways inflammation and airways hyperresponsiveness, but also greatly reduce airways structural changes of animal models of chronic asthma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study investigated multimorbidity patterns among middle-aged and older Chinese people and whether healthcare costs varied among different multimorbidity patterns., Methods: Data were from the 2011-2018 waves of the China Health and Retirement Longitudinal Study (CHARLS). We included 20,855 unique observations with information coming from their last wave of interviews and aged at least 45 years or older. Latent class analysis (LCA) was performed to classify individuals with common multimorbidity clusters based on 14 self-reported chronic diseases. Healthcare costs were from participants' self-reports and categorized into outpatient, inpatient, and self-treatment. Two-part regression was performed to analyze the association of multimorbidity patterns with healthcare costs., Results: Five multimorbidity clusters were identified: minimal disease, arthritis, cardiovascular disease (CVD), lung/asthma, and multisystem morbidity. The multisystem morbidity group had the highest use in all three types of healthcare and the highest self-treatment cost. Compared with the minimal disease group, the other four groups did not show significant differences in outpatient costs. Relative to the minimal disease group, the lung/asthma group reported lower inpatient costs., Conclusion: Healthcare use and costs varied across multimorbidity patterns among middle-aged and older Chinese people. Implementing an integrated care plan for multimorbidity is suggested to improve the cost-effectiveness of healthcare provision and reduce the financial burden of the healthcare system. Reimbursement policy design should also take multimorbidity patterns into account., Competing Interests: Declaration of Competing Interest All the authors have no financial or any other kind of personal conflicts with this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Data from NHANES 2001-2018 were used to examine the relationship between metabolism score for visceral fat (METS-VF) and asthma prevalence., Methods: We assessed the association between METS-VF and asthma disease using multiple logistic regression analysis from the National Health and Nutrition Examination Survey (NHANES), 2001-2018, followed by subgroup analysis for sensitive populations. To determine whether METS-VF and asthma disease had a non-linear relationship, smooth curve fitting was used, and threshold effect analysis was used to verify the relationship., Results: Among the 36,876 participants, 4,919 self-reported having asthma. When all confounders were controlled for, a positive association was found between METS-VF and asthma prevalence (OR = 1.27, 95% CI: 1.22,1.32), and this positive association was stronger with elevated METS-VF (P for trend = 0.01). According to the smooth curve fitting analysis, METS-VF and asthma prevalence do not have a linear relationship. The double-segmented threshold effect analysis suggested a negative correlation but no statistically significant difference between METS-VF less than 5.24 and asthma prevalence (OR = 0.60, 95% CI: 0.33, 0.91). Besides, other METS-VF showed positive associations with asthma prevalence before and after the effective inflection point. According to subgroup analysis, METS-VF is associated with asthma prevalence among participants aged 40 - 59, male, Mexican American, with hypertension and diabetes, and without asthma history., Conclusion: A positive correlation between METS-VF and asthma was observed and this positive correlation was non-linear, and participants with METS-VF above 5.24 should be cautious about the high risk of asthma. The relationship should be given more attention to participants who are aged 40-59 years old, male, Mexican American, have hypertension, diabetes, and who do not have a family history of asthma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Han, Chen, Gao, Yang and Huang.)

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease characterized by progressive airflow limitation. The complex biological processes of COPD include protein hydrolysis tissue remodeling, innate immune inflammation, disturbed host-pathogen response, abnormal cellular phenotype conversion, and cellular senescence. Extracellular vesicles (EVs) (including apoptotic vesicles, microvesicles and exosomes), are released by almost all cell types and can be found in a variety of body fluids including blood, sputum and urine. EVs are key mediators in cell-cell communication and can be used by using their bioactive substances (DNA, RNA, miRNA, proteins and other metabolites) to enable cells in adjacent and distant tissues to perform a wide variety of functions, which in turn affect the physiological and pathological functions of the body. Thus, EVs is expected to play an important role in the pathogenesis of COPD, which in turn affects its acute exacerbations and may serve as a diagnostic marker for it. Furthermore, recent therapeutic approaches and advances have introduced EVs into the treatment of COPD, such as the modification of EVs into novel drug delivery vehicles. Here, we discuss the role of EVs from cells of different origins in the pathogenesis of COPD and explore their possible use as biomarkers in diagnosis, and finally describe their role in therapy and future prospects for their application. Graphical Abstract., (© 2023. The Author(s).)

Objective: The objective of this study was to assess whether the weight-adjusted-waist index(WWI) is associated with the prevalence of asthma and age when first asthma onset appears in US adults., Methods: For analysis we selected participants from the National Health and Nutrition Examination Survey(NHANES)database between 2001 and 2018. A dose-response curve was calculated using logistic regression,subgroup analysis,and a dose-response curve., Results: The study included 44480 people over the age of 20,including 6061 reported with asthma, and the increase in asthma prevalence was 15% associated with each unit increase in the WWI, after adjusting for all confounders(odds ratio(OR)=1.15,95% CI:1.11,1.20). The sensitivity analysis was performed by trichotomizing the WWI, and compared to the lowest tertile, the highest tertile WWI group displayed a 29% increase in asthma prevalence(OR=1.29,95% CI:1.19,1.40). A nonlinear correlation was found between the WWI index and the risk of asthma onset, with a threshold saturation effect indicating an inflection point of 10.53 (log-likelihood ratio test, P<0.05), as well as a positive linear correlation with age at first asthma onset., Conclusions: A higher WWI index was associated with an increased prevalence of asthma and an older age of first asthma onset., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Chen, Xu, Li, Zhang, Zhu, He, Chen and Wang.)

T helper 2 (Th2) cytokine production by invariant natural killer T (iNKT) cells is involved in the development of asthma, but the regulation of Th2 cytokines in iNKT cells remains unknown. Although it is known that progranulin (PGRN) induces the production of Th2 cytokines in iNKT cells in vivo, the underlying mechanism is not clear. This study aims to investigate the role of PGRN in iNKT cells. The effects of PGRN on the differentiation of iNKT cells was detected by flow cytometry. Then stimulation of iNKT cells and airway resistance were carried out to evaluate the function of PGRN on iNKT cells. Furthermore, the mechanisms of PGRN in regulating iNKT cells was investigated by RT-PCR, WB, confocal and luciferase reporter assays. The absolute number of iNKT cells decreased in PGRN KO mice despite an increase in the percentage of iNKT cells. Furthermore, analyzing the subsets of iNKT cells, we found that NKT2 cells and their IL-4 production were reduced. Mechanistically, the decrease in NKT2 cells in the PGRN KO mice was caused by increased expression of enhancer of zeste homolog 2 (EZH2), that in turn caused increased degradation and altered nuclear localization of PLZF. Interestingly, PGRN signaling decreased expression of EZH2 and treatment of the PGRN KO mice with the EZH2 specific inhibitor GSK343 rescued the defect in NKT2 differentiation, IL-4 generation, and PLZF expression. Altogether, We have revealed a new pathway (PGRN-EZH2-PLZF), which regulates the Th2 responses of iNKT cells and provides a potentially new target for asthma treatment., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Bronchial asthma (BA) is a chronic inflammatory disease of the airway. Previous research has shown that Yanghe Pingchuan granules (YPGs) exert a precise therapeutic effect on BA. In our previous work, we showed that YPGs improved inflammation of the airways in rat models of BA. Other studies have shown that the pathogenesis of BA is closely related to pyroptosis and that the TOLL-like receptor pathway plays a key role in the mediation of pyroptosis. Therefore, in the present study, we established a rat model of BA by applying the concept of pyroptosis and used the TLR4/NF- κ B/NRLP3 signaling pathway as the target and YPGs as the treatment method. We evaluated the effects of YPGs on airway inflammation and pyroptosis in the model rats by HE staining, Masson's staining, AP-PAS staining, western blotting, and real-time quantitative PCR. The results showed that Yanghe Pingchuan granules could significantly improve the inflammatory response of bronchial tissue in BA rats, reduce the content of inflammatory factors IL-1 β and IL-18, and inhibit the expression of pyroptosis factor. Meanwhile, YPG can block the TLR4/NF- κ B signaling pathway. These findings suggest that YPG may be an effective drug for the treatment of BA by blocking the TLR4/NF- κ B signaling pathway and inhibiting pyroptosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Lingyu Pan et al.)

Objective: The purpose of this study was to evaluate whether there is a correlation between the METS-IR index and asthma among Americans., Methods: In an attempt to establish the relationship between the METS-IR index and asthma prevalence and age at first onset of asthma, we conducted a logistic regression analysis, subgroup analysis, and dose-response curve analysis using the National Health and Nutrition Examination Survey (NHANES) database., Results: In model 3, each unit increase in METS-IR index led to 1.5% increase in asthma prevalence (OR= 1.015, 95% CI: 1.012, 1.018) and an earlier age of onset of asthma by 0.057years (β= -0.057, 95% CI: -0.112, -0.002).Stratified analysis determined that an increase in METS-IR index was associated with asthma prevalence in almost all subgroups, except in the group where it was not known whether a blood relative had asthma, and a positive linear relationship was found between METS-IR index and asthma prevalence, as well as a linear negative relationship with age at asthma onset., Conclusion: Despite the fact that a direct causal relationship cannot be demonstrated, a higher METS-IR index is positively related to asthma prevalence and correspondingly may result in asthma onset at younger ages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Yang, Han, Wang, Zhuang, Zhu and Chen.)

Respiratory tract infection early in life plays a significant role in the pathogenesis of asthma. In the present study we examine, using a murine surrogate, the effects of early life respiratory infection with Streptococcus pneumoniae (SP) on adult asthma induced by sensitisation and exposure to house dust mite (HDM) allergen. Mice (one week old) were infected with SP, then 3 weeks later sensitised to HDM emulsified with Al (OH)3 intraperitoneally and challenged intranasally with same allergen for up to a further 5 weeks to establish the asthma surrogate. Outcome measures were quantified using the FlexiVent apparatus, histology and immunohistology, ELISA and flow cytometry. The murine surrogates of asthma infected with SP early in life exhibited significantly more severe disease compared with the controls of mice without SP infection, as shown by airways responsiveness, inflammatory cellular infiltration of the airways, expression of markers of airways remodelling, serum concentrations of HDM-specific IgE and the concentrations of Th2-type cytokines and the numbers of activated Th2 and ILC2 cells in the lung tissues. These data are compatible with the hypothesis that early-life infection of the airways with SP exacerbates, at least in some individuals, subsequent HDM-induced allergic airways inflammation and associated asthma in adulthood in this murine surrogate., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To evaluate the reliability and validity of the Chinese version of the test of the adherence to inhalers (TAI) in Chinese patients with chronic airway disease. Methods: Based on the English version of TAI, the items of the Chinese version of TAI were determined after forward-backward translation and cultural adaption. Totally, 165 patients with chronic obstructive pulmonary disease (COPD) and asthma were enrolled from Respiratory Clinic of the Second Xiangya Hospital of Central South University from July to November 2021, and a questionnaire survey was conducted using the Chinese version of TAI and the Morisky medication adherence scale 8-item version (MMAS-8). The content validity of the scale was expressed by content validity index (CVI) and the construct validity was analyzed by exploratory factor analysis (EFA). The convergence validity was evaluated by Pearson correlation analysis. The reliability of the scale was expressed by Cronbach's α coefficient, the split-half reliability and test-retest reliability. Results: The CVI was 0.966. There were 10 items in total. Two factors were extracted from the Chinese version of TAI and the cumulative variance contribution rate was 57.236%. The load value of each item was more than 0.400 and the factor attribution of the item was consistent with the original scale. The total score of the Chinese version of TAI was positively correlated with the total score of the MMAS-8( r =0.835, P <0.001). The Cronbach's α of the overall scale was 0.843, the Guttman's half-reliability coefficient was 0.796 and the test-retest reliability was 0.884 ( P <0.001), respectively. Conclusions: The Chinese version of TAI has good reliability and validity, which may be a reliable tool for evaluating the adherence to inhalers of patients with chronic airway disease in China.

Objective: S100A11 is a member of the S100 calcium-binding protein family and has intracellular and extracellular regulatory activities. We previously reported that S100A11 was differentially expressed in the respiratory tracts of asthmatic rats as compared with normal controls. Here, we aimed to analyze the potential of S100A11 to regulate both allergen-induced airway hyperresponsiveness (AHR) as well as acetylcholine (ACh)-induced hypercontractility of airway smooth muscle (ASM) and contraction of ASM cells (ASMCs)., Methods: Purified recombinant rat S100A11 protein (rS100A11) was administered to OVA-sensitized and challenged rats and then the AHR of animals was measured. The relaxation effects of rS100A11 on ASM were detected using isolated tracheal rings and primary ASMCs. The expression levels of un-phosphorylated myosin light chain (MLC) and phosphorylated MLC in ASMCs were analyzed using Western blotting., Results: Treatment with rS100A11 attenuated AHR in the rats. ASM contraction assays showed that rS100A11 reduced the contractile responses of isolated tracheal rings and primary ASMCs treated with ACh. In addition, rS100A11 markedly decreased the ACh-induced phosphorylation of the myosin light chain in ASMCs. Moreover, rS100A11 also suppressed the contractile response of tracheal rings in calcium-free buffer medium., Conclusion: These results indicate that S100A11 protein can relieve AHR by relaxing ASM independently of extracellular calcium. Our data support the idea that S100A11 is a potential therapeutic target for reducing airway resistance in asthma patients., (© 2022. Huazhong University of Science and Technology.)

Allergic asthma is a complex lung disease characterized by breathlessness, airway inflammation, and obstruction. Allergy and allergic rhinitis (AR) are the main triggers of asthma. Vitamin A is an important supplementary factor for the physiological activation of the immune system. In the present study, we investigated the effects of vitamin A on the exacerbation of allergic asthma symptoms. BALB/c mice were allocated to four groups. Asthma was created in two groups, and in the other two groups, rhinitis was induced. One of the asthma groups and one of the rhinitis groups orally received vitamin A (20 IU/g for 15 days). The levels of Immunoglobulin (Ig) E, histamine, leukotriene B4 (LTB4), Cysteinyl leukotriene receptor (Cys-LT), interleukin (IL)-4, IL-5, IL-13, and IL-35 as well as eosinophil peroxidase activity, were measured. Also, the histopathology of mice lungs was evaluated. The levels of total IgE, LTB4, Cys-LT, IL-4, IL-5, IL-17, and IL-33, eosinophil peroxidase activity, perivascular and peribronchial inflammation significantly decreased in vitamin A-treated asthma and rhinitis groups compared to non-treated groups. Also, IL-13 and histamine levels, hyperplasia of the goblet cell, and hyper-secretion of the mucus insignificantly decreased in vitamin A-treated asthma and rhinitis groups. Asthma and AR are common diseases that are generally developed due to the dysregulation of the immune system. Vitamin A plays an important role in controlling the immunopathologic mechanisms of allergic diseases. Vitamin A could be a useful supplement in managing AR and asthma by decreasing the severity of inflammatory responses. Therefore, control of vitamin A deficiency is recommended in Allergy.

While environmental aeroallergens and epithelial alarmins such as IL-33 are firmly implicated in asthma, the possible role of Streptococcus pneumoniae (S. pneumoniae) antigens is less clear. To explore this, wild-type BALB/c mice were repeatedly challenged per-nasally with IL-33 and inactivated S. pneumoniae, either agent alone or diluent control. Some animals were rested then later re-challenged with inactivated S. pneumoniae alone. Serum concentrations of S. pneumoniae lysates-specific IgE were measured in patients with asthma and control subjects. Interestingly, in the presence of IL-33, repeated exposure to inactivated S. pneumoniae induced asthma-like pathological changes accompanied by a systemic adaptive immune response. Subsequent re-exposure of the sensitized animals to inactivated S. pneumoniae alone was able to induce such changes. The concentration of S. pneumoniae lysates-specific IgE was significantly elevated in the asthma patients. These data suggest that antigens derived from infectious microorganisms may participate in generating the mucosal inflammation which characterizes asthma., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Asthma is a common respiratory disease which is characterized by persistent airway inflammation. Abnormal expression of long non-coding RNAs (lncRNAs) is observed in asthma. However, whether lncRNA nuclear-enriched abundant transcript 1 (NEAT1) regulates asthmatic inflammation and its mechanism still needs to be further investigated. The expression levels of inflammatory factors (tumour necrosis factor (TNF)-α, interleukin (IL)-4, IL-13, and IL-10) were detected using reverse transcription quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). MTT and flow cytometry assays were employed to determine cell proliferation and apoptosis, respectively. Dual luciferase reporter assay was performed to verify the relationship between miR-200a/b and MMP-16 or NEAT1. NEAT1 silencing markedly reduced TNF-α, IL-4, and IL-13 levels, while elevated IL-10 expression, suppressed cell proliferation, and promoted cell apoptosis. However, NEAT1 overexpression elicited the opposite effects on cell proliferation and inflammation cytokines secretion. What is more, NEAT1 negatively regulated miR-200a/b expression, and MMP16 was a target gene of miR-200a/b. miR-200a/b overexpression suppressed inflammation, cell proliferation, and enhanced cell apoptosis through regulation of MMP16. Moreover, MMP-16 overexpression or miR-200a/b inhibition abolished the regulatory effect of sh-NEAT1 on cell inflammation and apoptosis in BEAS-2B cells. NEAT1 acted as the role of sponge for miR-200a/b to regulate MMP-16 expression, thereby promoting asthma progression, suggesting that NEAT1 might have great potential as therapeutic target for asthma.

Although contributions of IL-33 to pulmonary diseases, including asthma, have been well documented, the complexity of such regulation warrants additional exploration. To better understand the involvement of IL-33, we used a murine asthma surrogate based on sensitisation and challenge with dust mite extract in the presence/absence of IL-33. Murine models were established with Dermatophagoides farinae (Der f) to establish (1) the effect of co-administered rmIL-33; (2) the effect of prior glucocorticoid intervention; (3) the effect of IL-33 on challenge with sub-threshold dosage Der f. The effects of rmIL-33 on bone marrow-derived dendritic cells were explored in vitro. Mice challenged with Der f combined with IL-33 compared with diluent control evinced significantly more airways inflammation and local cytokine production which was less sensitive to inhibition by dexamethasone. IL-33 also induced airways hyperresponsiveness, eosinophilic inflammation and cytokine production in lung tissues of animals exposed to sub-threshold dosage of Der f. In vitro, IL-33-stimulated DCs showed a significantly elevated capacity to stimulate CD4 + T cell proliferation and cytokine production and were also significantly more resistant to dexamethasone-induced apoptosis. Our data suggest that IL-33 reduces the threshold for allergen-induced inflammation of the airways in acorticosteroid-resistant fashion possibly in part through acting on DCs, a phenomenon which may be relevant to the development of severe, corticosteroid-resistant airways obstruction in human asthmatic patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A high platform can fix rats without restriction and completely expose the acupoints on the back during acupuncture manipulation. This article describes methods for the fabrication of the high platform, establishes a rat model of asthma and measures changes in respiratory function using a noninvasive and real-time whole-body plethysmography (WBP) system.

Allergic asthma is a common chronic lung inflammatory disease and seriously influences public health. We aim to investigate the effects of formononetin (FMN) and calycosin (CAL), 2 flavonoids in Radix Astragali, on allergic asthma and elucidate possible therapeutic targets. A house dust mite (HDM)-induced allergic asthma mouse model and TNF-α and Poly(I:C) co-stimulated human bronchial epithelial cell line (16HBE) were performed respectively in vivo and in vitro. The role of G protein-coupled estrogen receptor (GPER) was explored by its agonist, antagonist, or GPER small interfering RNA (siGPER). E-cadherin, occludin, and GPER were detected by western blotting, immunohistochemistry, or immunofluorescence. The epithelial barrier integrity was assessed by trans-epithelial electric resistance (TEER). Cytokines were examined by enzyme-linked immunosorbent assay (ELISA). The results showed that flavonoids attenuated pulmonary inflammation and hyperresponsiveness in asthmatic mice. These flavonoids significantly inhibited thymic stromal lymphopoietin (TSLP), increased occludin and restored E-cadherin in vivo and in vitro. The effects of flavonoids on occludin and TSLP were not interfered by ICI182780 (estrogen receptor antagonist), while blocked by G15 (GPER antagonist). Furthermore, compared with PPT (ERα agonist) and DPN (ERβ agonist), G1 (GPER agonist) significantly inhibited TSLP, up-regulated occludin, and restored E-cadherin. siGPER and TEER assays suggested that GPER was pivotal for the flavonoids on the epithelial barrier integrity. Finally, G1 attenuated allergic lung inflammation, which could be abolished by G15. Our data demonstrated that 2 flavonoids in Radix Astragali could alleviate allergic asthma by protecting epithelial integrity via regulating GPER, and activating GPER might be a possible therapeutic strategy against allergic inflammation., (©2020 Society for Leukocyte Biology.)

Background and Objective: Isolated blockade of IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) has been shown to reduce airways inflammation and hyperresponsiveness in murine asthma model. The hypothesis that combined blockade of all three cytokines can accomplish this more effectively has never been addressed., Methods: We studied a murine asthma model employing sensitization and challenge with ovalbumin (OVA) or saline control. To discern the effects of IL-33 blockade, we compared outcomes in strain identical, wild-type and IL-33 receptor (St2 -/- ) gene-deleted mice. We then examined, in the St2 -/- animals, the effects of additional, single or combined blockade of IL-25 and TSLP with blocking antibodies. Outcomes included airways reactivity, inflammatory cellular infiltration, epithelial cell metaplasia, deposition of fibrosis-related proteins, local Th2-type cytokine expression and total and specific serum IgE concentrations measured by ELISA and quantitative immunohistochemistry., Results: St2 -/- gene deletion significantly reduced airways reactivity, inflammatory cellular infiltration, lung tissue expression of Th2 cytokines and fibrosis related proteins and serum total IgE in response to OVA sensitization and challenge. Additional administration of anti-IL-25 and anti-TSLP blocking antibodies to the St2 -/- mice further significantly reduced inflammation, Th2 cytokine expression, airways fibrosis and IgE production, while anti-TSLP alone reduced eosinophil infiltration and local IL-4 expression. The airways inflammatory cellular infiltrate and lung tissue expression of Th2 cytokine, but not fibrosis-related proteins were also reduced in the presence of isotype identical, control antibodies., Conclusion: Combined blockade of these three cytokines may better ameliorate airways pathological changes in this murine asthma model, with implications for human asthma., (© 2019 Asian Pacific Society of Respirology.)

Asthma is an inflammatory disease of the airways and numerous cytokines contribute to this pathogenesis. It is shown that challenge of airways with IL-33 induces asthma-like pathological changes in mice, but the possible downstream cytokines in this process remain to be characterised. To explore this, we compared changes in the airways of wildtype (WT) and IL-9 deficient mice challenged with IL-33. In line with previous report, per-nasal challenge of WT mice with IL-33 significantly increased the responsiveness of the airways along with infiltration of inflammatory cells, goblet cell hyperplasia, collagen deposition and smooth muscle hypertrophy, and the expression of cytokines compared with control group. Surprisingly, all of these pathological changes were significantly attenuated in IL-9 deficient mice following identical IL-33 challenge. These data suggest that IL-9 is one downstream cytokine relevant to the effects of IL-33 in asthmatic airways and consequently a potential therapeutic target for the treatment of asthma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Standard therapy for asthma, a highly heterogeneous disease, is primarily based on bronchodilators and immunosuppressive drugs, which confer short-term symptomatic relief but not a cure. It is difficult to discover novel bronchodilators, although potential new targets are emerging. Traditional Chinese Medicine (TCM) formulas have been used to treat asthma for more than 2000 years, forming the basis for representative asthma treatments., Aim of the Study: Based on the efficacy of TCM formulas, anti-asthmatic herbal compounds bind proteins are potential targets for asthma therapy. This analysis will provide new drug targets and discovery strategies for asthma therapy., Materials and Methods: A list of candidate herbs for asthma was selected from the classical formulas (CFs) of TCM for the treatment of wheezing or dyspnea recorded in Treatise on Cold Damage and Miscellaneous Diseases (TCDMD) and from modern herbal formulas identified in the SAPHRON TCM Database using the keywords "wheezing" or "dyspnea". Compounds in the selected herbs and compounds that directly bind target proteins were acquired by searching the Herbal Ingredients' Targets Database (HITD), TCM Data Bank (TCMDB) and TCM Integrated Database (TCMID). Therapeutic targets of conventional medicine (CM) for asthma were collected by searching Therapeutic Target Database (TTD), DrugBank and PubMed as supplements. Finally, the enriched gene ontology (GO) terms of the targets were obtained using the Database for Annotation Visualization and Integrated Discovery (DAVID) and protein-protein interactions (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The effects of two selected TCM compounds, kaempferol and ginkgolide A, on cellular resistance in human airway smooth muscle cells (ASMCs) and pulmonary resistance in a mouse model were investigated., Results: The list of 32 candidate herbs for asthma was selected from 10 CFs for the treatment of wheezing or dyspnea recorded in TCDMD and 1037 modern herbal formulas obtained from the SAPHRON TCM Database. A total of 130 compounds from the 32 selected herbs and 68 herbal compounds directly bind target proteins were acquired from HITD and TCMDB. Eighty-eight therapeutic targets of CM for asthma were collected by searching TTD and PubMed as supplements. DAVID and STRING analyses showed targets of TCM formulas are primarily related to cytochrome P450 (CYP) family, transient receptor potential (TRP) channels, matrix metalloproteinases (MMPs) and ribosomal protein. Both TCM formulas and CM act on the same types of targets or signaling pathways, such as G protein-coupled receptors (GPCRs), steroid hormone receptors (SHRs), and JAK-STAT signaling pathway. The proteins directly targeted by herbal compounds, TRPM8, TRPA1, TRPV3, CYP1B1, CYP2B6, CYP1A2, CYP3A4, CYP1A1, PPARA, PPARD, NR1I2, MMP1, MMP2, ESR1, ESR2, RPLP0, RPLP1 and RPLP2, are potential targets for asthma therapy. In vitro results showed kaempferol (1 × 10 -2  mM) and ginkgolide A (1 × 10 -5  mM) significantly increased the cell index (P < 0.05 vs. histamine, n = 3) and therefore relaxed human ASMCs. In vivo results showed kaempferol (145 μg/kg) and ginkgolide A (205 μg/kg) significantly reduced pulmonary resistance (P < 0.05 vs. methacholine, n = 6)., Conclusion: Potential target discovery for asthma treatment based on the clinical effectiveness of TCM is a feasible strategy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Asthma is one of the most common chronic diseases in the world, with approximately 300 million asthma patients worldwide. The mortality rate of asthma is 1.6 to 36.7 / 100,000 people, and China has become one of the countries with the highest asthma death rate in the world. Asthma is a chronic allergic airway inflammatory disease. Patients with this disease may have symptoms such as cough, wheezing, and difficulty breathing. For many years, Western medicine has mainly used anti-inflammatory, anti-bronchial spasm, asthma, cough and oxygen to treat this disease, but the effect is not good. Clinical studies in recent years have found that the use of acupuncture in the treatment of bronchial asthma has a good clinical application prospect. This study was conducted to study the effect of using acupuncture to treat asthma., Methods and Analysis: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to November 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of asthma., Ethics and Dissemination: This systematic review will evaluate the efficacy and safety of acupuncture for asthma. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial.

Background: Tetrahydrocurcumin (THC) is the major active metabolite of curcumin, which is a dietary factor derived from Curcuma species. Our previous study demonstrated a significant beneficial effect of THC in mice with allergic asthma. Glucocorticosteroids (GCs) are commonly used drugs in asthma. Whether THC supplementation could promote the beneficial effects of GC therapy on asthma has not yet been reported. The current study aimed to investigate the combined efficacy of GC and THC treatment in a mouse model of allergic asthma., Methods: BALB/c mice were randomly divided into 5 groups: the control group, ovalbumin (OVA)-induced group, and OVA-induced mice treated with dietary THC only, intraperitoneal injection of dexamethasone (DEX) only, or THC combined with DEX. The nasal symptoms, histopathological alterations of lung tissues, lung cytokine production, and Th cell subsets were assessed., Results: THC or DEX had beneficial effects on nasal symptoms and pathological lung changes, and the therapeutic effects between THC and DEX treatment were comparable. Importantly, compared to the monotherapy groups (THC or DEX only), the combination of THC and DEX showed a significantly reduced nasal rubbing frequency, lower mucus hyperproduction, lower Th2 and Th17 cell numbers as well as lower related cytokine levels (IL-4, IL-5, and IL-17A)., Conclusions: Supplementation with THC can enhance the therapeutic effects of DEX to alleviate airway symptoms, lung inflammation, and the Th2 response. Our findings suggest that dietary administration of THC could act as an add-on therapy for asthma treated with GCs., (© 2020 S. Karger AG, Basel.)

Background and Objective: Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology., Methods: Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes., Results: We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P < 0.05 and fold-change >1.5 or <0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were >0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma., Conclusion: Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma., (© 2019 Asian Pacific Society of Respirology.)

Background: Curcumin (Cur), derived from Curcuma species, exhibits anti-inflammatory, antioxidant, and anticancer effects. Although Cur has some beneficial effects on asthma, its clinical application is limited by its low bioavailability. Tetrahydrocurcumin (THC), the major active metabolite of Cur, has multiple biological functions, similarly to Cur, and importantly, it showed enhanced bioavailability in tissues and plasma. However, the effect of THC on asthma has not been reported., Objective: The current study sought to investigate the efficacy of dietary THC on allergic asthma compared to that of Cur in an animal model., Methods: The anti-inflammatory effects of Cur and THC were evaluated in an ovalbumin-induced asthmatic mouse model. The nasal symptoms, pathological alterations of the lung tissues, oxidants and antioxidants, cytokine production, T cell subsets, and Th2-related signalling pathway activity were assessed., Results: Both THC and Cur had beneficial effects on asthmatic mice with regard to nasal symptoms, pathological changes (eosinophils and mucus hyper-production), oxidative stress (malondialdehyde), cytokine production (IL-13), Th17 and cytotoxic T cell subsets, and Th2 signalling pathway (IL-4Rα-Jak1-STAT6 and Jagged1/Jagged2-Notch1/Notch2 axis) activity. THC was more effective than Cur in suppressing tissue eosinophilia, mucus production, and IL-4Rα/Jak1/STAT6 pathway activity. Furthermore, only THC inhibited peripheral eosinophil levels, Th2 cytokines (IL-4 and IL-5), and Th2 cell subsets and enhanced an antioxidant enzyme (glutathione)., Conclusion and Clinical Relevance: The above results demonstrated for the first time that THC was superior to Cur in modulating allergic asthmatic phenotypes, especially attenuating the Th2 response. THC might be a potentially effective agent for asthma treatment., (© 2018 John Wiley & Sons Ltd.)

The alarmin cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) play a critical role in asthma pathogenesis by inducing mucosal Th2-type cytokine production. Although environmental exposure to aeroallergens has been proposed as an alarmin trigger in asthma, there has been no systematic parallel study of the effects of allergen exposure on the expression of these cytokines in the airways of human asthmatics. Using single and sequential double immunohistochemistry, we evaluated the numbers and phenotypes of IL-25-, IL-33-, and TSLP-immunoreactive cells in sections of bronchial biopsies from mild atopic asthmatics ( n = 16) before and 24 h after allergen inhalational challenge. Allergen challenge highly increased expression of baseline immunoreactivity for IL-25, IL-33, and TSLP, both in the bronchial epithelium and submucosa ( p < 0.001), to a degree that correlated with the extent of the late phase of airway obstruction. Aside from epithelial cells, the principal source of immunoreactivity for all three alarmins, TSLP, and IL-33 immunoreactivity colocalized principally with endothelial cells and mast cells, neutrophils, and fibroblasts, whereas IL-25 immunoreactivity colocalized principally with eosinophils as well as endothelial cells, mast cells, and fibroblasts. The data implicate that allergen challenge directly increases airway alarmin expression in atopic asthmatics to a degree correlating with increase late-phase airway obstruction, affirming these molecules as potential molecular targets for the inhibition of allergen-induced airway inflammation and obstruction., (Copyright © 2018 by The American Association of Immunologists, Inc.)

The epithelial cytokines IL-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been implicated in asthma pathogenesis because they promote Th2-type cytokine synthesis, but their expression is relatively poorly documented in "real-life" human asthma. Using bronchoalveolar lavage fluid (BALF), we measured airway concentrations of these mediators and compared them with those of Th1- and Th2-type cytokines, airway infiltration of neutrophils and eosinophils, and lung function in a large group of asthmatic patients with a range of disease severity ( n = 70) and control subjects ( n = 30). The median BALF concentrations of IL-33, TSLP, IL-4, IL-5, IL-13, and IL-12p70, but not IL-25, IL-2, or IFN-γ, were significantly elevated in asthmatics compared with controls ( p < 0.05). The concentrations of IL-33 and TSLP, but not IL-25, correlated inversely with the lung function (forced expiratory volume in the first second) of asthmatics (IL-33: r = -0.488, p < 0.0001; TSLP: r = -0.565, p < 0.0001) independently of corticosteroid therapy. When divided according to disease severity and corticosteroid therapy, all subgroups of asthmatics had elevated median numbers of eosinophils in BALF, whereas the patients with more severe disease who were treated with corticosteroids had higher numbers of neutrophils compared with milder asthmatics not so treated and control subjects ( p < 0.05). The data implicate TSLP and IL-33 in the pathogenesis of asthma that is characterized by persistent airway inflammation and impaired lung function despite intensive corticosteroid therapy, highlighting them as potential molecular targets., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Background: There are limited population based data on the prevalence of asthma in China. The China Asthma and Risk factors Epidemiologic (CARE) survey was designed to understand the prevalence and risk factors for asthma in mainland China., Objectives: The CARE survey aims to demonstrate the prevalence and risk factors of asthma in mainland China among adolescents (age >14 years) and adults., Methods: The survey was performed between February 2010 and August 2012 in eight provinces/cities of seven areas in mainland China. The inhabitants (age, >14 years) recruited in this survey were through multi-stage cluster random sampling. Asthma diagnosis was based on medical history and lung function tests. Multivariable logistic regression was used to analyzed the risk factors for asthma., Results: The study included 164 215 subjects (men, 79 692 [48.53%]; women, 84 523 [51.47%]). 2034 (1.24%) were asthmatic patients. Among all asthmatic patients, 521 (25.61%) were newly diagnosed. Univariable regression analysis showed that risk factors for asthma included smoking, first-degree relatives with asthma, allergic rhinitis, chronic bronchitis, COPD, pollinosis, allergic pneumonia, concomitant allergic diseases, BMI and raising pets. Multivariable logistic regression indicated that asthma risk factors included women, age stratification, smoking, first-degree relatives suffering from asthma or pollinosis, combined with allergic rhinitis, eczema or GERD., Conclusions: We speculated that the prevalence of asthma is increasing in mainland China among individuals aged >14 years in the past 10 years. A number of risk factors were identified. The risk factors of asthma would be further elucidated in our future work., Clinical Implications: Our CARE study highlights that asthma epidemic in mainland China should be paid more attention., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Previous studies suggest that caesarean section (CS) may increase the risk of asthma in children, but none of them could preclude potential confounding effects of underlying medical indications for CS. We aim to assess the association between CS itself (without medical indications) and risk of childhood asthma., Methods: We conducted a hospital-based case-control study on childhood asthma with 573 cases and 812 controls in Shanghai. Unconditional logistic regression models in SAS were employed to control for potential confounders., Results: Our study found that CS without medical indication was significantly associated with elevated asthma risk (adjusted OR = 1.58 [95% CI 1.17-2.13]). However, this risk was attenuated in children fed by exclusive breastfeeding in the first six months after birth (adjusted OR = 1.39 [95% CI 0.92-2.10]). In contrast, the risk was more prominent in children with non-exclusive breastfeeding or bottle feeding (adjusted OR = 1.91 [95% CI 1.22-2.99])., Conclusions: CS without medical indication was associated with an increased risk of childhood asthma. Exclusive breastfeeding in infancy may attenuate this risk.

Bacillus Calmette-Guerin (BCG) is a potent agent for the prevention of tuberculosis. Current studies have regarded BCG as an immunomodulator. However, there is little information on whether it can be used to inhibit airway inflammation and airway remodeling caused by asthma. Therefore, in this study, we investigate the role of epithelial-mesenchymal transition (EMT) in airway inflammation and airway remodeling as well as the possible therapeutic mechanism of BCG for the treatment of asthma. Wistar rats were sensitized and challenged by ovalbumin for 2 weeks or 8 weeks. BCG was subcutaneously administered daily before every ovalbumin challenge to determine its therapeutic effects. The 2 weeks model group showed extensive eosinophilia, chronic inflammatory responses, bronchial wall thickening, airway epithelium damage, increased levels of transforming growth factor β 1 (TGF-β 1 ) in both bronchoalveolar lavage fluid and sera, decreased expression of epithelial marker E-cadherin, and increased expressions of mesenchymal markers α-smooth muscle actin (α-SMA) and Fibronectin (Fn). Except for inflammatory responses, all responses were more significant in the 8 weeks model group which displayed characteristics of airway remodeling including subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. When compared with the model groups, BCG administration inhibited airway inflammation and airway remodeling, decreased TGF-β 1 levels, upregulated expression of E-cadherin, and downregulated expression of α-SMA and Fn. The present study suggests for the first time that increased secretion of TGF- β 1 induced by asthmatic chronic inflammation may result in EMT, which is one of the most important mechanisms of airway inflammation and airway remodeling seen with asthma. BCG alleviates airway inflammation and airway remodeling by preventing TGF-β 1 induced EMT, therefore BCG may be a new therapy for treating asthma.

Introduction: Tracheal papilloma presenting as asthma is a rare occurrence., Case Study: We report a case of a 32-year-old male patient who presented with features of asthma. Flexible bronchoscopy demonstrated a large growth arising from the lower end of the trachea. Successful treatment using snare loop and argon plasma coagulation (APC) of the polyploidal growth was performed via flexible bronchoscope., Results: The patient had immediate relief of airway obstruction and histopathological examination of the neoplasm demonstrated features of papilloma., Conclusion: Primary tracheal papilloma is mimicker of asthma, CT scan should be considered in patients with persistent chronic cough, or stridor. Endoscopic papillectomy is a safe and effective treatment and should be considered as first-line therapy for tracheal papilloma.

Background: Environmental factors may play important roles in asthma, but findings have been inconsistent., Objective: The goal of this study was to determine the associations between early life exposures, environmental factors, and asthma in urban and rural children in southeast China., Methods: A screening questionnaire survey was conducted in 7,164 children from urban Guangzhou and 6,087 from rural Conghua. In the second stage, subsamples of 854 children (419 from Guangzhou, 435 from Conghua) were recruited for a case-control study that included a detailed questionnaire enquiring on family history, early life environmental exposures, dietary habits, and laboratory tests (including histamine airway provocation testing, skin prick tests, and serum antibody analyses). House dust samples from 76 Guangzhou families and 80 Conghua families were obtained to analyze levels of endotoxins, house dust mites, and cockroach allergens., Results: According to the screening survey, the prevalence of physician-diagnosed asthma was lower in children from Conghua (3.4%) than in those from Guangzhou (6.9%) (P < .001). A lower percentage of asthma was reported in rural subjects compared with urban subjects (2.8% vs. 29.4%; P < .001) in the case-control study. Atopy (OR, 1.91 [95% CI, 1.58-2.29]), parental atopy (OR, 2.49 [95% CI, 1.55-4.01]), hospitalization before 3 years of age (OR, 2.54 [95% CI, 1.37-4.70]), high consumption of milk products (OR, 1.68 [95% CI, 1.03-2.73]), and dust Dermatophagoides farinae group 1 allergen (OR, 1.71 [95% CI, 1.34-2.19]) were positively associated with asthma. Living in a crop-farming family at < 1 year of age (OR, 0.15 [95% CI, 0.08-0.32]) and dust endotoxin levels (OR, 0.69 [95% CI, 0.50-0.95]) were negatively associated with asthma., Conclusions: Rural children from an agricultural background exhibited a reduced risk of asthma. Early life exposure to crop farming and high environmental endotoxin levels might protect the children from asthma in southern China., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies suggest that maternal antibiotics exposure during pregnancy may increase the risk of childhood asthma, but the results were inconsistent. Furthermore, most studies did not examine periconception period as an exposure window. We aim to assess the associations between maternal exposure to specific antibiotics before and during pregnancy and the risk of asthma in early childhood., Methods: Data from the Collaborative Perinatal Project were used. Maternal exposure to antibiotics before and during pregnancy was recorded at each prenatal visit. A total of 39,907 singleton children were followed up to 7 years of age. Multilevel multiple logistic regression models were used to control for potential confounders and account for multiple pregnancies per woman., Results: Maternal use of penicillin or chloramphenicol was associated with an increased risk of asthma in the offspring (adjusted odds ratio = 1.21, 95% confidence interval 1.08-1.36 for penicillin; 1.72 [1.14-2.59] for chloramphenicol). The risk was significantly increased if penicillin or chloramphenicol was used in the 1st trimester (1.09 [1.04-1.13] for penicillin and 1.23 [1.01-1.51] for chloramphenicol)., Conclusion: Maternal exposure to certain antibiotics is associated with childhood asthma by 7 years of age. Early pregnancy may be a sensitive window.

Objective: Through the analysis of relevant data of China Asthma and Risk factors Epidemiologic investigation (CARE study), we understand the status quo of management and insights of asthma patients in our country., Methods: Using multi-stage random cluster sampling method, epidemiological survey was performed on the prevalence rate in 8 provinces (cities) of China residents who aged over 14 years from 2009 to 2010. Detailed epidemiological data was collected via face-to-face home visit interview among 2 034 asthmatics who were diagnosed in the last epidemiology survey. Asthma was diagnosed based upon case history, clinical signs and lung function test. The SPSS12.0 software was conducted for statistical analysis and the status of asthma control was investigated., Results: This survey has shown that 22.71% (462/2 034) asthmatics had ever taken a lung functional test in the past year. A total of 294 (14.45%) people had peak flow meters but only 1.62% (33/2 034) regularly used it daily. There were 22.42% (456/2 034) asthmatics aware that bronchial asthma is characterized by chronic airway inflammation. 14.85% (302/2 034) asthmatics understood that the treatment goal of this disease is long-term good control or complete control. This survey has found that 59.64% (1 213/2 034) patients complained that asthma has affected their work, life and entertainment, including 8.90% (181/2 034) asthmatics dependent on instruments in daily life and 4.57% attempting to suicide. This suggested that allergic asthma has seriously decreased the quality of life., Conclusion: Therefore it is necessary to educate the asthmatics, guide the patients to the long-term management and standardized therapy and raise the level of disease understanding, thus reducing the burden of disease to society. Gaining better insight of patient's attitude about self-care is critical to the improvement of asthma management.

Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV) was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs) were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma.

Polymorphisms in the β subunit of the high affinity receptor for IgE (FcεRIβ) and interferon-γ (IFN-γ) genes may influence the risk of asthma. However, the results in Asian population are still debatable. We performed a meta-analysis to ascertain the association between the FcεRIβ E237G, FcεRIβ -109C/T, and IFN-γ 874T/A polymorphisms and asthma in an Asian population. Databases including PubMed, Chinese National Knowledge Infrastructure (CNKI), Weipu, and Wan Fang (Chinese) databases were searched to find the relevant studies. The effect summary odds ratio (OR) with 95% confidence interval (CI) was calculated. There was no significant difference in dominant model and allele model (EG + GG vs. EE: OR = 1.14, 95%CI = 0.94-1.40; G vs. E: OR = 1.13, 95%CI = 0.95-1.34) for FcεRIβ E237G, and no significant association was observed in the subgroup analysis by age and atopic status. A significantly decreased risk of asthma was observed in allelic model (C vs. T: OR=0.88, 95%CI=0.80-0.98) for FcεRIβ -109C/T, significant association was found in dominant model (AT+TT vs. AA: OR=0.56, 95% CI=0.33-0.97) for IFN-γ 874T/A. This meta-analysis suggested that FcεRIβ E237G is not an influencing factor for asthma in Asian population. FcεRIβ -109C/T and IFN-γ 874T/A polymorphisms may be influencing factors for asthma in the Asian population.

The CD80/CD86-CD28 axis is a critical pathway for immuno-corrective therapy, and the cytotoxic T lymphocyte antigen 4 (CTLA4) is a promising immunosuppressor targeting the CD80/CD86-CD28 axis; however, its use for asthma therapy needs further optimization. A human CTLA4 fused with the IgCγ Fc (CTLA4Ig) and mouse CC chemokine receptor type7 (CCR7) coding sequences were inserted into a recombinant adenovirus (rAdV) vector to generate rAdV-CTLA4Ig and rAdV-CCR7. The naive dendritic cells (DCs) were infected with these rAdVs to ensure CCR7 and CTLA4Ig expression. The therapeutic effects of modified DCs were evaluated. rAdV-CTLA4Ig and rAdV-CCR7 infected DCs improved all asthma symptoms. Inflammatory cell infiltration and cytokine analysis showed that rAdV-CTLA4Ig and rAdV-CCR7-modified DC therapy reduced the number of eosinophils and lymphocyte and neutrophil infiltration in the lung. Interestingly, assessment of the humoral immunity showed that the IL-4 and IFNγ levels of the rAdV-CTLA4Ig and rAdV-CCR7-modified DC-treated mice decreased significantly and did not reverse the Th1/Th2 balance. DCs expressing CCR7 displayed guidance ability for DC migration, primarily for DCs in the inflammatory lung. Additionally, the rAdVs caused an inflammatory response by inducing DC differentiation, inflammatory cell infiltration and changes in cytokines; however, mice transplanted with rAdV-green fluorescent protein (GFP)-infected DCs displayed no asthma manifestations. In conclusion, CTLA4Ig-modified DCs exhibited a therapeutic effect on asthma, and CCR7 may guide DC homing. The combination of these two molecules may be a model for precision-guided immunotherapy.

Objective: Base on the China asthma and risk factors epidemiologic investigation (CARE study), we analyzed the current status of asthma control in China., Methods: With the multi-stage random cluster sampling method, epidemiological survey was performed among Chinese residents who aged over 14 years in 8 provinces (cities) from 2010 to 2011. Detailed clinic data of 2 034 asthma patients were collected via face-to-face home visit . Asthma was diagnosed based upon the history, clinical signs and lung function tests. The SPSS 12.0 was conducted for statistics analysis., Results: This survey found that the prevalence rate of asthma in China was 1.24% (2 034/164 215), including 973 male and 1 061 female patients, with a mean age of (56 ± 18) years old. Consistent with the Global Initiative for Asthma (GINA) guidelines, 40.51% (824/2 034) and 42.58% (866/2 034) of our patients achieved control and partial control, respectively. According to the asthma control test (ACT) estimates, 15.63% (318/2 034) and 49.46% (1 006/2 034) of patients achieved full control (ACT 25) and well control(ACT 20-24), respectively. In the past year, 22.62% (460/2 034) of patients reported hospitalized and 26.99% (549/2 034) of patients reported emergency room visit at least one time due to asthma exacerbation. 61.80% (1 257/2 034) of patients were on daily us of medication. Inhaled corticosteroids (ICS) plus a long-acting β2 agonist (LABA) or solely ICS were used in 6.39% and 14.75% of patients, respectively. Theophylline treatment accounted for 29.11% (592/2 034). Oral glucocorticoid and oral leukotriene modifier (LTRA) treatment accounted for 9.49% (193/2 034) and 3.10% (63/2 034), respectively. According to the survey, 34.51% (702/2 034) of asthma patients reported a history of smoking . The percentage of asthma control in non smoking patients was higher than in smoking patients [43.24% (576/1 332) and 35.33% (248/702), respectively]. Meanwhile, the rates of both hospitalization and emergency due to asthma exacerbation in smoking asthma patients were significantly higher than nonsmoking asthma patients (27.35% and 31.77%, 20.12% and 24.47%, respectively)., Conclusions: The situation of asthma control has been improved in China. However, compared with GINA guidelines, there is still a considerable gap. Smoking is one of the crucial factors that affect asthma control.

Objective: To survey the risk factors of asthma among the people aged over 14 years in China., Methods: Home visits for completing epidemiological questionnaires in accordance with stratified cluster random sampling survey were conducted in 8 provinces (cities) of China residents aged over 14 years from February 2010 to August 2011. Asthma was diagnosed based upon case history, clinical signs and lung function test. The SPSS 12.0 software was used for statistic analyses for the epidemiological status of asthma., Results: Sampling population was composed of 180 099 subjects. Among 164 215 valid questionnaires, there were 79 692 males and 84 523 females, 2 034 had asthma. The overall prevalence rate was 1.2% (2 034/164 215). Correlation analyses showed that the risk factors were smoking (OR = 1.697, 95%CI: 1.547-1.861), breast feeding (OR = 0.801, 95%CI: 0.670-0.959), genetics (OR & 95%CI >1, asthma (OR = 10.440, 95%CI: 8.991-12.112)), complications (OR & 95%CI >1), body mass index (compared with normal weight, overweight (OR = 1.360, 95%CI: 1.212-1.531), obesity (OR = 10.631, 95%CI: 9.570-11.801)) and petting (OR & 95%CI >1)., Conclusion: Among Chinese asthmatics aged over 14, their risk factors include host (genetics & obesity) and environmental (smoking, breastfeeding, complications & pets) factors.

Evidence shows that asthma originates in early life. Studies have found that phototherapy and/or neonatal jaundice may be associated with asthma. We investigated the association between neonatal bilirubin levels and childhood asthma without phototherapy intervention in the Collaborative Perinatal Project, a multicenter prospective cohort study conducted in the United States from 1959 to 1965. A total of 54,795 livebirths were included, and 40,063 children were followed up until 7 years of age or older. Total serum bilirubin (TSB) levels were examined at 48 hours postpartum in newborns with birthweights of 2,250 g or more. Information on asthma and other diseases through age 7 years was summarized and confirmed by a group of pediatricians and child neurologists. Among 28,807 term infants, the overall prevalence of asthma was 5.26%. Risks of asthma increased with both maximum TSB levels and TSB levels at 48 hours postpartum (P for trend < 0.01). Neonatal maximum TSB levels greater than 15 mg/dL were associated with a 61% increase in the risk of childhood asthma (odds ratio = 1.61, 95% confidence interval: 1.04, 2.08) after adjustment for confounders. In this prospective cohort study of infants born at a time when phototherapy was unavailable, neonatal hyperbilirubinemia was associated with an increased risk of childhood asthma.

Introduction: The role of soluble OX40 ligand (sOX40L) in adult bronchial asthma is unclear. This study aims to determine the serum concentrations of sOX40L in adult patients with bronchial asthma, and discussed its relationship with pulmonary function., Materials and Methods: We measured the pulmonary function using the spirometer and detected the serum concentrations of sOX40L by enzyme linked immunosorbent assay (ELISA) in 19 healthy persons in the control group, 58 acute asthmatic adult patients who were grouped according to their disease severity: 18 mild grade, 24 moderate grade, 16 severe grade, and 24 persons in a stable asthmatic group., Results: The serum concentrations of sOX40L in asthmatic adult patients (6.80 ± 4.95 ng/L) were distinctly higher than those in the control group (3.98 ± 2.83 ng/L, P <0.05), and they were negatively correlated with pulmonary function indexes (FEV1%, FVC%, FEV1/FVC) (r = -0.754, P <0.01, r = -0.557, P <0.01, r = -0.457, P <0.01, respectively). Moreover, the serum concentrations of sOX40L showed obvious differences among control, mild, moderate, and severe groups (3.98 ± 2.83, 4.87 ± 1.89, 6.97 ± 5.91, 8.71 ± 5.18 ng/L, respectively; P <0.01). The concentrations of sOX40L decreased to the same extent as the control group after therapeutic treatments were provided to the asthmatic adult patients., Conclusion: The concentrations of sOX40L were found to be high in adult asthmatic patients and were associated with the severity of the disease. Therefore, sOX40L could be a potential inflammatory mediator in the pathogenesis of asthma.

Objective: To explore the effects of CTLA4Ig gene-modified dendritic cells on the mechanism of immune regulation in asthma with Th2 superiority., Methods: Newborn BALB/c mice are randomly divided into 2 groups of AdCTLA4Ig-DC intervention and AdGFP modified dendritic cells (AdGFP-DC) intervention by randomization (n = 10 each). CTLA4Ig gene-modified dendritic cells (AdCTLA4Ig-DC) and AdGFP-DC were infused separately. Newborn BALB/c mice in both groups were fed for 6 - 8 weeks. Additional 6 - 8 weeks BALB/c mice were randomly divided into 2 groups of control and asthma (n = 10 each). The saline-sensitized/challenged mice received an intraperitoneal injection while inhalation was administered in the control group. Ovalbumin (OVA) was used similarly in the remaining three groups. The manifestations of OVA challenged mice in each group, bronchoalveolar lavage fluid (BALF) eosinophils and pathological changes in airway were observed to examine the effects of CTLA4Ig gene-modified dendritic cells on airway inflammation. The levels of IgE, Interleukin (IL)-4, IL-10 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA)., Results: Rapid respiration and pulmonary inflammatory infiltration were obvious in the asthma group. CTLA4Ig gene-modified dendritic cells transfused neonatally significantly improved the symptoms of asthma in adulthood and reduced the infiltration of inflammatory cells in bronchial submucosa. The levels of IgE and IL-4 in serum and BALF in the AdCTLA4Ig-DC intervention group were significantly lower than those in the asthma group (IgE: (3.9 ± 1.3)× 10(5) pg/ml vs (5.3 ± 1.7)× 10(5) pg/ml and (22.9 ± 11.8)× 10(3) pg/ml vs (122.0 ± 59.6)× 10(3) pg/ml, IL-4: (70.5 ± 7.0) pg/ml vs (88.7 ± 9.2) pg/ml and (46.9 ± 2.9) pg/ml vs (73.3 ± 8.7) pg/ml, all P < 0.05). The levels of IL-10 in serum and BALF in the AdCTLA4Ig-DC intervention group were significantly higher than those in the asthma group ((442 ± 8) pg/ml vs (227 ± 11) pg/ml, (83 ± 42) pg/ml vs (27 ± 11) pg/ml, both P < 0.05). The levels of IFN-γ in serum and BALF in AdCTLA4Ig-DC intervention group showed no significant difference with those in the asthma group (both P > 0.05). The eosinophil level in BALF was significantly lower than that in the asthma group ((18.5 ± 1.9)× 10(4)/ml vs (62.3 ± 6.7)× 10(4)/ml, P < 0.05)., Conclusions: CTLA4Ig gene-modified dendritic cells transfused neonatally may reduce the secretion of Th2 cytokines in OVA-sensitized/challenged adult mice. The expression of CTLA4Ig gene induces immune tolerance in asthma.

Objective: To evaluate the frequency of sensitization to Aspergillus antigens and the prevalence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients., Methods: Two hundred consecutive non-smoking outpatients with asthma (≥ 18 years) underwent skin testing with aeroallergens, peripheral eosinophil counting, measurements of total serum IgE level and specific IgE against Aspergillus fumigatus, radiologic investigations and pulmonary function tests., Results: Eleven patients (5.5%) had a positive skin reactivity to Aspergillus antigens. Five of these 11 patients (45.5%) met the diagnostic criteria of ABPA, an overall prevalence of 2.5% (5/200). There were 2 males and 3 females, aging from 19 to 62 years, with a disease duration from 15 to 40 years. All of the patients had asthmatic symptoms such as cough and wheeze. Moderate to severe obstructive ventilatory defect was found in 4 patients. Total serum IgE levels and specific IgE against Aspergillus fumigates were elevated significantly in all the patients, and elevated eosinophil count was found in 3 patients. Three cases were diagnosed as ABPA-CB because of the presence of central bronchiectasis on HRCT., Conclusions: The prevalence of ABPA in Chinese patients with asthma was underestimated. Clinical features of ABPA were similar to asthma alone, but with longer duration and more severe lung function defect. Sensitization to Aspergillus, increased eosinophils and total serum IgE levels were important indicators for the diagnosis of ABPA.