Brain-derived neurotrophic factor promotes airway smooth muscle cell proliferation in asthma through regulation of transient receptor potential channel-mediated autophagy.

OBJECTIVE: Increased proliferation of airway smooth muscle cells (ASMCs) is a key feature of airway remodeling in asthma. This study aims to determine whether brain-derived neurotrophic factor (BDNF) regulates ASMC proliferation and airway remodeling via the transient receptor potential channels (TRPCs)/autophagy axis. METHODS: Human ASMCs were isolated and passively sensitized with human asthmatic serum. Protein levels of BDNF and its receptor TrkB, TRPC1/3/6, autophagy markers, intracellular Ca2+ concentration ([Ca2+]i), LC3 immunofluorescence, cell proliferation, cell cycle population were examined. Wistar rats were sensitized with OVA to establish asthma models. RESULTS: In asthmatic serum-sensitized human ASMCs, BDNF overexpression or recombinant BDNF (rhBDNF) increased TrkB/TRPC1/3/6 axis, [Ca2+]i, autophagy level, cell proliferation, cell number in the S+G2/M phase and decreased cell number in the G0/G1 phase, whereas BDNF knockdown exerted the opposite effects. Furthermore, TRPC channel blocker SKF96365 and TRPC1/3/6 knockdown reversed the effects of the rhBDNF-mediated induction of [Ca2+]i, autophagy level, cell proliferation and cell number in the S+G2/M phase. Moreover, the autophagy inhibitor (3-MA) rescued the rhBDNF-mediated induction of cell proliferation and cell number in the S+G2/M phase. Further in vivo assays revealed that BDNF altered the pathology of airway remodeling, promoted the infiltration of inflammatory cells, promoted the proliferation of ASMCs, and upregulated the protein levels of TrkB, TRPC1/3/6, and autophagy markers in asthma model rats. CONCLUSION: We conclude that BDNF promotes ASMCs proliferation in asthma through TRPC-mediated autophagy induction.

Amygdalin alleviated TGF-ß-induced epithelial-mesenchymal transition in bronchial epithelial cells.

OBJECTIVE: Transforming growth factor-beta TGF-ß-induced epithelial-mesenchymal transition (EMT) in bronchial epithelial cells contributes to airway wall remodeling in asthma. This study aims to explore the role of amygdalin, an active ingredient in bitter almonds, in TGF-ß-induced EMT in bronchial epithelial cells and to elucidate the possible mechanisms underlying its biological effects. METHODS: An asthmatic mouse model was established through ovalbumin induction. Primary mouse bronchial epithelial cells and a human bronchial epithelial cell line were incubated with transforming growth factor-beta (TGF-ß) to induce EMT, whose phenotype of cells was evaluated by the expressions of EMT markers [alpha-smooth muscle actin (α-SMA), vimentin, and fibronectin] and cell migration capacity. A co-immunoprecipitation assay was performed to assess the ubiquitination of heparanase (HPSE). RESULTS: In asthmatic model mice, amygdalin treatment relieved airway wall remodeling and decreased expressions of EMT markers (α-SMA and vimentin). In TGF-ß-treated bronchial epithelial cells, amygdalin treatment decreased the mRNA and protein levels of EMT markers (α-SMA, vimentin, and fibronectin) without impairing cell viability. Through the Swiss Target Prediction database, HPSE was screened as a candidate downstream target for amygdalin. HPSE overexpression further promoted TGF-ß-induced EMT while the HPSE inhibitor suppressed TGF-ß-induced EMT in bronchial epithelial cells. In addition, HPSE overexpression reversed the inhibitory effect of amygdalin on TGF-ß-induced EMT in bronchial epithelial cells. The following mechanism exploration revealed that amygdalin downregulated HPSE expression by enhancing ubiquitination. CONCLUSION: Our study showed that amygdalin inhibited TGF-ß-induced EMT in bronchial epithelial cells and found that the anti-EMT activity of amygdalin might be related to its regulatory effect on HPSE expression.

SRSF1 promotes ASMC proliferation in asthma by competitively binding CCND2 with miRNA-135a.

BACKGROUND: Asthma is an inflammatory syndrome characterized by airway hyperresponsiveness, bronchial inflammation, and airway remodeling. Abnormal proliferation of airway smooth muscle cells (ASMCs) is the main pathological feature of asthma. This study investigated the function and mechanism of serine arginine-rich splicing factor 1 (SRSF1) in ASMC proliferation in asthma. METHODS: SRSF1 expressions in the bronchi of ovalbumin-induced asthmatic mice and IgE-treated mouse ASMCs (mASMCs) were evaluated using quantitative real-time PCR and Western blot. The localization and expression of SRSF1 in the bronchi of asthmatic mice were assessed by immunohistochemistry. Functionally, gain- and loss-of-function assays, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were conducted. Mechanistically, RNA degradation assay, RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter gene assays were carried out. RESULTS: SRSF1 was highly expressed in the bronchi of ovalbumin-induced asthma mice and IgE-treated mASMCs and was mainly located in the nucleus. Experiments on the function of SRSF1 showed that the silencing of SRSF1 induced the cell cycle of mASMC arrest and restrained mASMC proliferation. Investigations into the mechanism of SRSF1 revealed that SRSF1 and miR-135a are competitively bound to the 3'UTR region of Cyclin D2 (CCND2). SRSF1 overexpression repressed the degradation of CCND2 mRNA, and miR-135a negatively regulated CCND2 expression. Furthermore, SRSF1 knockdown inhibited ASMC proliferation in asthma mouse models by regulating the levels of miR-135a and CCND2. CONCLUSION: SRSF1 knockdown repressed ASMC proliferation in asthma by regulating miR-135a/CCND2 levels.

Associations between comorbidities and annual incidence plus frequency of asthma exacerbation hospitalisation during the past year: data from CARN study.

PURPOSE: While asthma comorbidities are associated with higher health care utilisation, lower quality of life and poorer asthma control, the impact of asthma comorbidities on hospitalisation for asthma exacerbation (H-AX) remains less recognised. We aim to analyse the impact of asthma comorbidities on H-AX. METHODS: Based on a national survey on asthma control and disease perception (CARN 2015 study), we analysed the impact of comorbidities on annual incidence and frequency of H-AX in China. Information on demographic characteristics, asthma comorbidities and annual incidence and frequency of H-AX were presented in this study. RESULTS: Among 3875 ambulatory asthma patients, 75.9% (2941/3875) had comorbidities, and 26.4% (1017/3858) experienced H-AX during past year. After adjusting for confounding factors such as demographic data, smoking status and asthma control, COPD [OR = 2.189, 95% CI (1.673, 2.863)] and coronary heart disease [OR = 1.387, 95% CI (1.032, 1.864)] were associated with higher annual incidence, while allergic rhinitis [OR = 0.692, 95% CI (0.588, 0.815)] was associated with lower annual incidence, of H-AX. In terms of frequency, allergic rhinitis [OR = 1.630, 95% CI (1.214, 2.187)], COPD [OR = 1.472, 95% CI (1.021, 2.122)] and anxiety [OR = 2.609, 95% CI (1.051, 6.477)] showed statistically significant correlation with frequent H-AX. CONCLUSIONS: COPD and coronary heart disease were associated with higher annual incidence, while allergic rhinitis was associated with lower annual incidence of H-AX. Allergic rhinitis, COPD and anxiety were associated with frequent H-AX. Comorbidities may have an important role in the risk and frequency of annual hospitalisations due to asthma exacerbation. The goal of asthma control should rely on a multi-disciplinary treatment protocol.

Asthma Management Using the Mobile Asthma Evaluation and Management System in China.

PURPOSE: As stated in the Global Initiative for Asthma, there are still some asthmatic patients who have not achieved asthma control. Mobile is a useful tool for asthma management. We aimed to compare the advantages of mobile management with traditional management in improving adherence and control of asthma. METHODS: In this prospective, multicentre, randomized, controlled and parallel-group study, we enrolled patients with poor adherence and uncontrolled asthma at 32 hospitals in 28 provinces in China. Patients were randomly assigned to the mobile management or traditional management groups for 12 months. The primary endpoint was the proportion of patients with good adherence (Medication Adherence Report Scale for Asthma [MARS-A] score ≥ 45) for 6 months. This study is registered at ClinicalTrials.gov (NCT02917174). RESULTS: Between April 2017 and April 2018, 923 patients were eligible for randomization (mobile group, n = 461; traditional group, n = 462). Dropout was 84 (18.2%) in the mobile management group and 113 (24.4%) patients in the traditional management group. The proportion of patients with good adherence was significantly higher in the mobile management group than in the traditional management group (66.0% vs. 58.99%, P = 0.048). The mobile management group showed higher mean MARS-A score (at 1, 6, 9, and 12 months) and asthma control test scores (at 6 and 9 months), and lower total lost rate to follow-up within 12 months than the traditional management group. CONCLUSIONS: Mobile asthma management can improve adherence and asthma control compared to traditional management. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02917174.

Exosomal transfer of activated neutrophil-derived lncRNA CRNDE promotes proliferation and migration of airway smooth muscle cells in asthma.

Activated neutrophil-derived exosomes reportedly contribute to the proliferation of airway smooth muscle cells (ASMCs), thereby aggravating the airway wall remodeling during asthma; however, the specific mechanism remains unclear. Lipopolysaccharide (LPS)-EXO and si-CRNDE-EXO were extracted from the media of human neutrophils treated with LPS and LPS + si-CRNDE (a siRNA targets long non-coding RNA CRNDE), respectively. Human ASMCs were co-cultured with LPS-EXO or si-CRNDE-EXO, and cell viability, proliferation and migration were measured. The interplay of colorectal neoplasia differentially expressed (CRNDE), inhibitor of nuclear factor kappa B kinase subunit beta (IKKß) and nuclear receptor subfamily 2 group C member 2 (TAK1) was explored using RNA immunoprecipitation (RIP) and Co-IP assays. A mouse model of asthma was induced using ovalbumin. CRNDE was upregulated in LPS-EXO and successfully transferred from LPS-treated neutrophils to ASMCs through exosome. Mechanically, CRNDE loaded in LPS-EXO reinforced TAK1-mediated IKKß phosphorylation, thereby activating the nuclear factor kappa B (NF-κB) pathway. Functionally, silencing CRNDE in LPS-EXO, an IKKß inhibitor, and an NF-κB inhibitor all removed the upregulation of cell viability, proliferation and migration induced by LPS-EXO in ASMCs. In the end, the in vivo experiment demonstrated that CRNDE knockdown in neutrophils effectively reduced the thickness of bronchial smooth muscle in a mouse model for asthma. Activated neutrophils-derived CRNDE was transferred to ASMCs through exosomes and activated the NF-κB pathway by enhancing IKKß phosphorylation. The latter promoted the proliferation and migration of ASMCs and then contributed to airway remodeling in asthma.

LincRNA-p21 promotes classical macrophage activation in acute respiratory distress syndrome by activating NF-κB.

Background: Previous studies have revealed the important role of alveolar macrophages (AMs) in the pathogenesis of acute respiratory distress syndrome (ARDS) and potential anti-inflammatory properties of lincRNA-p21. This study aims to study the association between lincRNA-p21 and active AMs to understand the molecular mechanisms of AMs-mediated inflammatory responses in ARDS.Methods: This study was mainly investigated in mice with the intratracheal instillation of lipopolysaccharide (LPS) or LPS-treated AMs. The expression of lincRNA-p21 and classical macrophage markers, IL-12ß and iNOS, was detected by quantitative RT-PCR, while NF-κB p65 translocation was measured by western blotting analysis. And, NF-κB activity was analyzed through luciferase report assays. Gain- and loss-of-function studies were also performed for further investigations.Results: Elevated lincRNA-p21 levels were observed in both LPS-induced ARDS mice and LPS-treated AMs, with upregulated expression of IL-12ß and iNOS, namely M1 activation, and p65 nuclear translocation. Further in vitro studies showed that LPS-induced M1 activation could be counteracted by both lincRNA-p21 inhibition and inhibited NF-κB activation. Moreover, both p65 nuclear translocation and NF-κB activity were promoted by lincRNA-p21 overexpression, while lincRNA-p21 inhibition showed a negative effect on LPS-induced p65 nuclear translocation and increase of NF-κB activity. Additionally, LPS-induced lung injuries could be attenuated by lincRNA-p21 inhibition in vivo.Conclusion: This study revealed elevated lincRNA-p21 levels in LPS-induced ARDS and investigated the potential role of lincRNA-p21 in LPS-induced pro-inflammatory response via NF-κB/p65 mediated pathways, suggesting the potential application of lincRNA-p21 for ADRS therapy.

Hospitalization Due to Asthma Exacerbation: A China Asthma Research Network (CARN) Retrospective Study in 29 Provinces Across Mainland China.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients. METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed. RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%). CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.

Long non-coding RNA-HAGLR suppressed tumor growth of lung adenocarcinoma through epigenetically silencing E2F1.

Emerging evidence indicates that long noncoding RNAs (LncRNAs) are new players in gene regulation but their mechanisms of action are mainly undocumented. In this study, we investigated LncRNA alterations that contribute to lung cancer by analyzing published microarray data in Gene Expression Obminus (GEO) and The Cancer Genome Atlas RNA (TCGA) sequencing data. Here, we reported that HAGLR (also called HOXD-AS1) was frequently down-regulated in lung adenocarcinoma (LUAD) tissues, and decreased HAGLR expression was clinically associated with shorter survival of LUAD patients. Preclinical studies using multiple LUAD cells and in vivo mouse model indicated that HAGLR could attenuate LUAD cell growth in vitro and in vivo. Mechanistically, HAGLR could physically interact with DNMT1, and recruit DNMT1 on E2F1 promoter to increase local DNA methylation. Overall, our study demonstrated that HAGLR promoted LUAD progression by recruiting DNMT1 to modulate the promoter methylation and expression of E2F1, which expanded potential therapeutic strategies for LUAD treatment.

GAS5 promotes airway smooth muscle cell proliferation in asthma via controlling miR-10a/BDNF signaling pathway.

AIMS: To explore the role of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in the cell proliferation of airway smooth muscle cells (ASMCs) in asthma. MATERIALS AND METHODS: An asthma rat model was established by ovalbumin sensitization and challenge. The expression of GAS5, miR-10a and BDNF mRNA and protein was determined with qRT-PCR and western blot, separately. The targeting relationship between GAS5 and miR-10a was examined with RNA immunoprecipitation and RNA pull-down assay; the interaction between miR-10a and BDNF was evaluated by luciferase reporter assay. Cell Proliferation Assay (MTS) was used for ASMC proliferation detection. Knock-down of GAS5 was performed in asthmatic rats to determine the effects of GAS5 in vivo. KEY FINDINGS: Compared with control group, the inspiratory resistance and expiratory resistance were increased in asthma group; and the expression of GAS5, miR-10a and BDNF was higher, lower and higher, respectively. The expression of GAS5 and miR-10a was elevated and repressed, respectively, by platelet-derived growth factor-BB (PDGF-BB). GAS5 functioned as a bait of miR-10a. GAS5 regulates BDNF expression through miR-10a. PDGF-BB promotes the cell proliferation of ASMCs through miR-10a/BDNF. Knock-down of GAS5 significantly decreased airway hyperresponsiveness in asthmatic rats. SIGNIFICANCE: The lncRNA GAS5/miR-10a/BDNF regulatory axis played an important role in promoting ASMCs proliferation, thus contributing to asthma.

The effects of transient receptor potential channel (TRPC) on airway smooth muscle cell isolated from asthma model mice.

This study aimed to validate whether transient receptor potential channel1 (TRPC1) and TRPC3 participate in the regulation the proliferation of airway smooth muscle cells (ASMCs) through modulating calcium ion (Ca2+ ) influx in vitro. Chronic model of murine asthma was induced and ASMCs isolated from asthmatic mice were used in this whole study. TRPC1 and TRPC3 were upregulated in asthmatic mouse ASMCs and selected for further investigation. Ca2+ concentration and the cell viability of asthmatic mouse ASMCs were significantly higher than that from non- asthma mice, however, TRPC channels blocker SKF96365 alleviated these effects. Furthermore, TRPC1 or TRPC3 overexpression markedly increased Ca2+ concentration and significantly induced the viability of ASMCs; whereas TRPC1 or TRPC3 knockdown exerted the completely conversed effects. Moreover, knockdown of TRPC1 and TRPC3 also exerted different effects on the protein expression of growth-related proteins p-p38, p-JNK, cleaved caspase-3 and Bcl-2, as well as on cell cycle. Finally, we found Ca2+ chelator EGTA or BAPTA-AM significantly diminished the effects of si-TRPC1 and si-TRPC3 on the cell viability, cell cycle, and the protein expression of p-p38, p-JNK, cleaved caspase-3, and Bcl-2 in asthmatic mouse ASMCs. Our findings demonstrated that the effects of TRPC1 and TRPC3 on the cell viability and cell cycle of ASMCs were, at least partially, through regulating Ca2+ influx.

LncRNA H19 promotes epithelial-mesenchymal transition (EMT) by targeting miR-484 in human lung cancer cells.

Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types. However, the molecular basis for this observation has not been characterized in lung cancer, especially during epithelial mesenchymal transition (EMT) progression. Cell viability, migration, invasion, and apoptosis were measured using trypan blue exclusion assay, Transwell migration/invasion assay, and flow cytometry, respectively. Quantitative RT-PCR was used to measure relative expressions of H19, microR-484 (miR-484), and Rho associated coiled-coil containing protein kinase 2 (ROCK2). Western blot was used to measure expressions of apoptosis-, EMT-, and c-Jun N-terminal kinase (JNK) pathway-related proteins. Luciferase reporter assay was used to identify the target of H19. H19 was highly expressed in both lung cancer tissues and cells. Suppression of H19 significantly decreased A549 cell viability, migration, and invasion, but promoted apoptosis. Overexpression of H19 promoted cell migration, invasion, and EMT process. miR-484 was a target of H19 and overexpression of it reversed the effects of H19 on EMT. miR-484 regulated the expression of ROCK2. Mechanistic study revealed that suppressing H19 decreased the expression of proteins in JNK pathway, and ROCK2 was the main downstream molecule of H19. H19 promoted EMT in lung cancer A549 cells by negatively regulating miR-484.

Schisandrin B down-regulated lncRNA BCYRN1 expression of airway smooth muscle cells by improving miR-150 expression to inhibit the proliferation and migration of ASMC in asthmatic rats.

OBJECTIVE: The mechanism of Schisandrin B on the proliferation and migration of airway smooth muscle cells (ASMCs) in asthmatic rats was explored. METHODS: SD rats were divided into three groups: control (group 1), model (group 2) and model + Schisandrin B (group 3). miR-150 and lncRNA BCYRN1 levels were measured by qRT-PCR. The combination of BCYRN1 and miR-150 was detected by RNA pull down. ASMCs' viability/proliferation/migration were examined by WST-1 assay and 24-well Transwell system. RESULTS: Schisandrin B up-regulated miR-150 expression and down-regulated BCYRN1 expression in sensitized rats. Schisandrin B reversed the expression of miR-150 and BCYRN1 in MV-treated ASMCs. In addition, Schisandrin B inhibited the viability, proliferation and migration of MV-induced ASMCs. We also found miR-150 inhibited BCYRN1 expression which was proved by experiments using ASMCs transfected with miR-150 inhibitor. CONCLUSION: Schisandrin B increased miR-150 expression and decreased BCYRN1, and BCYRN1 expression was inhibited by miR-150, which indicated that Schisandrin B could regulate BCYRN1 through miR-150.

LncRNAs BCYRN1 promoted the proliferation and migration of rat airway smooth muscle cells in asthma via upregulating the expression of transient receptor potential 1.

BACKGROUND: Long noncoding RNAs (lncRNAs) played important roles in several biological processes through regulating the expression of protein. However, the function of lncRNA BCYRN1 in airway smooth muscle cells (ASMCs) has not been reported. METHODS: Male Sprague-Dawley (SD) rats were divided into control and asthma groups and the ovalbumin (OVA) model was constructed. The expression of BCYRN1 and transient receptor potential 1 (TRPC1) were detected in the ASMCs separated from these rats. Then 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) assay, Roche real-time cell analyzer (RTCA) DP assay and Transwell cell migration assay were performed to detect the effect of BCYRN1 on the viability/proliferation and migration of ASMCs. RNA pull-down assays and RNA immunoprecipitation assay were used to identify and verify the binding between BCYRN1 and TRPC1. Inspiratory resistance and expiratory resistance were measured in OVA challenged rats with BCYRN1 knockdown. RESULTS: We foundthe high expression of BCYRN1 and TRPC1 in asthma groups and ASMCs treated with PDGF-BB. Overexpression of BCYRN1 greatly promoted the proliferation and migration of ASMCs. In addition,TRPC1 overexpression reversed the function of si-BCYRN1 indecreasing the viability/proliferation and migration of ASMCs treated with PDGF-BB. BCYRN1 could up-regulate the protein level of TRPC1 through increasing the stability of TRPC1. Finally, we found that BCYRN1 knockdown reduced the inspiratory resistance and expiratory resistance in OVA challenged rats. CONCLUSION: Our study indicated that BCYRN1 promotedthe proliferation and migration of rat ASMCs in asthma via upregulating the expression of TRPC1.

Schisandrin B inhibits the proliferation of airway smooth muscle cells via microRNA-135a suppressing the expression of transient receptor potential channel 1.

Airway smooth muscle cell (ASMC) was known to involve in the pathophysiology of asthma. Schisandrin B was reported to have anti-asthmatic effects in a murine asthma model. However, the molecular mechanism involving in the effect of Schisandrin B on ASMCs remains poorly understood. Sprague-Dawley rats were divided into three groups: rats as the control (Group 1), sensitized rats (Group 2), sensitized rats and intragastric-administrated Schisandrin B (Group 3). The expression of miR-135a and TRPC1 was detected in the rats from three groups. Platelet-derived growth factor (PDGF)-BB was used to induce the proliferation of isolated ASMCs, and the expression of miR-135a and TRPC1 was detected in PDGF-BB-treated ASMCs. Cell viability was examined in ASMCs transfected with miR-135a inhibitor or si-TRPC1. The expression of TRPC1 was examined in A10 cells pretreated with miR-135a inhibitor or miR-135a mimic. In this study, we found that Schisandrin B attenuated the inspiratory and expiratory resistances in sensitized rats. Schisandrin B upregulated the mRNA level of miR-135a and decreased the expression of TRPC1 in sensitized rats. In addition, Schisandrin B reversed the expression of miR-135a and TRPC1 in PDGF-BB-induced ASMCs. Si-TRPC1 abrogated the increasing proliferation of ASMCs induced by miR-135a inhibitor. We also found that miR-135a regulated the expression of TRPC1 in the A10 cells. These results demonstrate that Schisandrin B inhibits the proliferation of ASMCs via miR-135a suppressing the expression of TRPC1.

[Clinical efficacies of inhaled corticosteroids plus theophylline in the treatment of bronchial asthma].

OBJECTIVE: To explore the therapeutic efficacies of inhaled corticosteroids (ICS) plus low-dose theophylline for moderate bronchial asthma. METHODS: A total of 280 patients with moderate bronchial asthma at People's Hospital of Zhengzhou University between January 2011 and December 2011 were recruited and randomized into 2 groups: observation group with inhaled budesonide 400 µg/d plus aminophylline tablet (0.1 g, 3 times/day, oral administration and control group with inhaled budesonide 320 µg/day plus formoterol 9 µg/day. The course of treatment was around 6 months. The forced expiratory volume in one second % predicted (FEV1% predicted), interleukin (IL)-4, IL-5 and IgE of peripheral blood were compared before and after treatment. RESULTS: Before and 6 months after treatment, the values of FEV1 % predicted, IL-4, IL-5 and IgE for the observed group were 68% ± 6% and 76% ± 6%, (14.5 ± 4.4) and (7.2 ± 2.6) ng/L, (27.4 ± 6.2) and (24.2 ± 5.9) ng/L, (771 ± 130) × 10(3) and(592 ± 104) × 10(3) U/L, respectively, while those for the control group were 66% ± 8% and 77% ± 6%, (13.7 ± 4.3) and (7.7 ± 4.0) ng/L, (26.9 ± 5.8) and (24.6 ± 4.8) ng/L, (752 ± 154) and (604 ± 122) × 10(3) U/L, respectively. There were significant improvements in both groups (all P < 0.05). No differences existed between two groups (all P > 0.05). CONCLUSION: Compared with ICS plus inhaled long-acting ß2-agonists (LABA), ICS plus low-dose theophylline shows similar efficacies in the improvement of lung function and the control of airway inflammation for asthmatics.

ß-Lactamases in amoxicillin-clavulanate-resistant Escherichia coli strains isolated from a Chinese tertiary hospital.

A total of 52 strains were resistant to amoxicillin-clavulanate by disk diffusion method in a Chinese tertiary hospital from July 2011 to December 2011. Among these isolates, 2 isolates possessed a phenotype consistent with production of inhibitor-resistant temoniera (TEM) (IRT) ß-lactamase, and the TEM-type gene was cloned into strains of Escherichia coli JM109 cells. Both had no blaTEM mutations and were identified as TEM-1 ß-lactamase producers. As a result, no IRT ß-lactamase was detected. Multiplex PCR detected most of these strains produced TEM-1 enzymes, and plasmid-mediated AmpC ß-lactamase and oxacillinase-1 ß-lactamases are important mechanisms of resistance as well.

Procalcitonin-guided antibiotic use in acute exacerbations of idiopathic pulmonary fibrosis.

OBJECT: To assess the clinical value of procalcitonin to guide antibiotic therapy in acute exacerbations of idiopathic pulmonary fibrosis. METHODS: Patients with acute exacerbations of idiopathic pulmonary fibrosis were randomly assigned to the procalcitonin-guided group (antibiotic use guided by a procalcitonin threshold of 0.25 ng/ml) or the routine treatment group (antibiotic use according to routine practice). Follow up of clinical outcomes were assessed at baseline and 30 days later. RESULTS: Baseline characteristics including demographics, clinical characteristics and laboratory results were similar between groups. PCT guidance resulted in a significant reduction of antibiotic treatment duration (8.7 ± 6.6 compared to 14.2 ± 5.2 days in the routine treatment group). Fewer patients were exposed to antibiotics treatment in the PCT group (26 patients) compared with the control group (35 patients). Treatment success, mortality rate, days of hospitalization and ventilation therapy were similar between the two groups. CONCLUSION: Procalcitonin-guided antibiotic therapy of patients with acute exacerbation of idiopathic pulmonary fibrosis may result in reduced exposure to antibiotics without adversely affecting patient outcomes.

Tracheal stenting for primary tracheal mucosa-associated lymphoid tissue lymphoma.

Primary tracheal mucosa-associated lymphoid tissue (MALT) lymphoma is extremely rare. We report a 49-year-old female patient with the complaint of dyspnea. Fiberoptic bronchoscopy showed polypoid, variable-sized and irregular nodules causing narrowing of the tracheal lumen from the proximal trachea to the left main bronchus. Because of severe stenosis in the airway and the severity of symptoms, this case was unresectable. The patient was then treated successfully with placement of an endobronchial stent through bronchofibroscopy. After the placement of the stent, bronchoscopic biopsy was performed. Pathological analysis confirms a diagnosis of MALT-associated malignant lymphoma. We performed systemic chemotherapy on the patient. The temporary stent was removed after the reduction of the stenosis. This is the first case in which tracheal MALT lymphoma was treated successfully following tracheal stent insertion guided by bronchofibroscopy. Temporary tracheal stenting can be a favorable choice for a patient with tracheal stenosis caused by primary tracheal MALT lymphoma.