Diagnostic value of fractional exhaled nitric oxide combined with small airway function test for chronic cough / 中国基层医药

Objective:To investigate the value of fractional exhaled nitric oxide (FeNO) combined with small airway function test to replace bronchial provocation test and induced sputum test in differentiating cough variant asthma (CVA) from eosinophilic bronchitis (EB).Methods:The clinical data of 105 patients with chronic cough admitted to The Third People's Hospital of Hubei, Jianghan University from January 2018 to December 2021 were retrospectively analyzed. These patients consisted of 40 patients with CVA (CVA group), 25 patients with EB (EB group), and 40 patients with other chronic coughs (other chronic cough group). FeNO and lung function were compared between groups. The value of FeNO, small airway function, and their combination in differentiating CVA from EB were analyzed using the receiver operating characteristic curves.Results:FeNO level was the highest in the CVA group [33.0 (30.0, 37.8) ppb], followed by the EB group [28.0 (25.5, 32.0) ppb], and the lowest in other chronic cough group [13.0 (11.0, 15.0) ppb]. There was significant difference in FeNO level between groups ( H value = 79.00, P < 0.05). There were no significant differences in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1), FEV 1/FVC, peak expiratory flow (PEF) between groups (all P > 0.05). Maximal mid-expiratory flow (MMEF) [74 (66.0, 77.4) in the CVA group, 80 (79.0, 83.3) in the EB group, 88.0 (86.4, 90.0) in other chronic coughs group], FEF25 (%) [70.0 (60.3, 75.1) in the CVA group, 78.0 (74.1, 85.0) in the EB group, 81.7 (78.9, 86.3) in other chronic coughs group], FEF50 (%) [75.2 (67.1, 80.8) in the CVA group, 80.6 (75.7, 85.9) in the EB group, 89.4 (87.0, 90.5) in other chronic coughs group], FEF75 (%) [76.4 (68.7, 85.8) in the CVA group, 80.9 (77.4, 89.7) in the EB group, 90.8 (87.2, 94.2) in other chronic coughs group] were significantly lower in the CVA group than those in other chronic coughs group. With the exception of FEF25 (%), MMEF (%), FEF50 (%), and FEF75 (%) were significantly lower in the EB group compared with other chronic coughs group. MMEF (%) and FEF25 (%) in the CVA group were significantly lower compared with the EB group. There were significant differences in MMEF (%), FEF50 (%), and FEF75 (%) between groups ( H = 62.82, 47.04, 47.41, 49.11, all P < 0.01). There were significant differences in FEF50 (%) and FEF75 (%) between CVA and EB groups (both P > 0.05). In binary logistic regression equation, FeNO and MMEF (%) were important indexes to distinguish CVA from EB ( P < 0.05). Bronchial provocation test and induced sputum test were used as the gold standard to distinguish CVA from EB. When FeNO and MMEF (%) were used separately to distinguish CVA from EB, the optimal threshold value was 30.0 ppb and 77.7 respectively, the area under the receiver operating characteristic curve was 0.77 and 0.82 respectively, the diagnostic sensitivity was 70% and 77.5% respectively, and the diagnostic specificity was 72% and 88% respectively. When FeNO and MMEF (%) were used in combination to distinguish CVA from EB, the area under the receiver operating characteristic curve was 0.89, and the diagnostic sensitivity and specificity was 75% and 96% respectively. Conclusion:FeNO and MMEF (%) can be used to distinguish CVA from EB. FeNO combined with MMEF (%) has a higher value in distinguishing CVA from EB than FeNO and MMEF alone.

Risk factors for the development of airway hyperresponsiveness in patients with allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

Allergic rhinitis（AR） is an independent risk factor for allergic asthma. Some AR patients may have developed airway hyperresponsiveness（AHR） in the absence of asthma symptoms. In this stage, AHR is often neglected due to the absence of typical asthma symptoms. Exploring the clinically relevant risk factors for AHR in patients with AR, as well as the clinical indicators and biomarkers to predict AHR in patients with AR, is of great significance to the prevention of the occurrence of AHR and asthma. This review summarized the risk factors for the development of AHR in AR patients, and gave hints to the prevention of AHR in AR patients.

Comparison of positive and negative pressure extubation after mechanical ventilation in intensive care unit patients / 中华危重病急救医学

Objective:To investigate the effect of positive and negative pressure extubation on mechanical ventilation patients in the intensive care unit (ICU).Methods:A prospective randomized controlled study was performed, 105 ICU patients who successfully passed the spontaneous breathing test (SBT) after mechanical ventilation of Nanjing Jiangbei Hospital Affiliated to Nantong University from January 2019 to March 2021 were enrolled. According to random number table method, they were randomly divided into positive pressure extubation group (53 cases) and negative pressure extubation group (52 cases). During extubation, all patients were placed in semi-decubitus position (raising the head of bed at an angle range from 30°- 45°), the secretions from mouth, nose, throat and trachea were removed. In the negative pressure extubation group, the sputum suction tube was inserted into the tracheal tube and passed over the distal opening to carry out continuous negative pressure suction in the tracheal tube after disconnecting the ventilator. Meanwhile, after the tracheal tube balloon was evacuated, the sputum suction tube was pulled out together with the tracheal tube. In the positive pressure extubation group, the patients were guided to inspiratory forcibly under the original SBT mode. When the patients reached the inspiratory peak, the ballon was evacuated and the tracheal tube was removed. After extubation, all patients were given nasal catheter oxygen inhalation (oxygen flow 5 L/min). Arterial blood gas analysis indexes [pH value, arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2)] were recorded 5 minutes and 1 hour after extubation in both groups. Vital signs (including tachypnea, tachycardia, elevated blood pressure and decreased oxygen saturation) and complications (including severe cough, airway hyperresponsiveness and pneumonia) were observed 30 minutes after extubation in both groups. Results:Five minutes after extubation, blood gas analysis showed that the PaO 2 of positive pressure extubation group was significantly higher than that of negative pressure extubation group [mmHg (1 mmHg≈0.133 kPa): 123.4±30.2 vs. 111.0±21.1, P < 0.05], the pH value and PaCO 2 in positive pressure extubation group were slightly lower than that of negative pressure extubation group [pH value: 7.411±0.042 vs. 7.419±0.040, PaCO 2 (mmHg): 39.7±4.7 vs. 40.5±5.6], but the differences were not statistically significant (both P > 0.05). One hour after extubation, the pH value, PaO 2 and PaCO 2 in positive pressure extubation group were slightly lower than those in negative pressure extubation group, but the differences were not statistically significant. Within 30 minutes after extubation, the incedences of tachypnea, tachycardia, elevated blood pressure and oxygen desaturationin in positive pressure extubation group were significantly lower than those in negative pressure extubation group [tachypnea: 9.4% (5/53) vs. 28.8% (15/52), tachycardia: 15.1% (8/53) vs. 32.7% (17/52), elevated blood pressure: 11.3% (6/53) vs. 30.8% (16/52), oxygen desaturation: 7.5% (4/53) vs. 34.6% (18/52), all P < 0.05], the incidence of severe cough in positive pressure extubation group was significantly lower than that in negative pressure extubation group [9.4% (5/53) vs. 30.8% (16/52), P < 0.05], but there was no significant difference in the incidence of complications of airway hyperresponsiveness between the two groups [1.9% (1/53) vs. 5.8% (3/52), P > 0.05]. No pneumonia occurred in both groups within 48 hours after extubation. Conclusion:The positive pressure extubation method can ensure full oxygenation of patients undergoing mechanical ventilation in ICU, avoid hypoxia, and reduce the occurrence of hypoxia and severe cough, which is more conducive to the stability of vital signs.

The anti-asthma effect of Mahuang decoction based on P38 MAPK/NF-KB signaling pathway and its mechanism / 中国药理学通报

Aim To explore the intervention effect of Mahuang decoction on airway remodeling and airway hyperresponsiveness in asthmatic rats based on the p38MAPK/NF-KB signaling pathway. Methods Network pharmacology was used to screen the potential signaling pathway of Mahuang decoction in treating asthma. The asthma model was replicated, and the airway reactivity and the pathologic changes of lung tissues of rats were observed. The concentrations of related indexes in rat serum and the expressions of key genes in murine pulmonary tissues were assessed. Results The results of network pharmacology identified 186 candidate targets, and pathway analysis showed that the treatment mechanism for asthma mainly involved Toll like receptor, mitogen activated protein kinase (MAPK), T cell receptor and so on. Mahuang decoction reduced the airway mucus secretion, attenuated the subcutaneous collagen deposition in the airway, and decreased the airway reactivity significantly. It also obviously inhibited the concentrations of VEGF, TGF-ßl, ET - 1, OPN and bJ-GF in rat serum, and the mRNA expressions of p38MAPK, NF-i

Clinical Efficacy on Erchentang Combined with Sanzi Yangqintang in Treatment of Cough Variant Asthma in Children with Phlegm Evil Accumulation Lung Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Erchentang combined with Sanzi Yangqintang in the treatment of cough variant asthma （CVA） in children with phlegm-evil accumulation lung syndrome and its influence on airway inflammation and airway hyperresponsiveness （AHR）. Method:A total of one hundred and sixteen children were randomly divided into observation group and control group 58 cases in each group. Patients in both groups took montelukast sodium chewable tablets orally， 5 mg/time， once daily， at night before bedtime. In observation group， patients took Erchentang and Sanzi Yangqintang modified granules orally. While patients in control group took Erchentang and Sanzi Yangqintang placebo granules orally. Treatment course continued six weeks for two groups. Before and after treatment， the cough symptom scores and phlegm evil accumulating lung syndrome scores were recorded every week. The cough remission time and cough disappearance time were recorded， followed up for 24 weeks to record cough recurrence. Leicester Cough quality of life questionnaire （LCQ） was scored before and after treatment. The ratio of induced sputum eosinophils （EOS） and the levels of interleukin-4 （IL-4）， IL-5， IL-12， IL-13 were measured before and after treatment. The cumulative doses of exhaled nitric oxide （FeNO） and methacholine （PD20） were measued before and after therapy. Safety evaluation was conducted. Result:The scores of cough symptom and phlegm-evil accumulation lung syndrome at different time points were decreased gradually in two groups of children after treatment （<italic>F</italic>_{control group}=5.277， <italic>F</italic>_{observation group}=7.636，<italic>P</italic><0.01）. The scores of cough symptom and phlegm-evil accumulation in the lung syndrome of observation group were lower than those in control group （<italic>P</italic><0.01） at the same period. The durations of cough relief and cough disappearance in observation group were shorter than those in control group （<italic>P</italic><0.01）. Within 24 weeks of follow-up， the recurrence rate of children in observation group was 68.97% （40/58）， lower than 84.48% （49/58） in control group （<italic>χ</italic>²=3.917，<italic>P</italic><0.05）. Children in observation group had fewer relapses than those in control group （<italic>P</italic><0.01）. The total LCQ scores and scores of all dimensions in observation group were higher than those in control group （<italic>P</italic><0.01）. The EOS， IL-4， IL-5 and IL-13 levels in observation group were lower than the data in control group， and IL-12 level was higher than that in control group （<italic>P</italic><0.01）. FeNO of children in observation group was lower than that in control group （<italic>P</italic><0.01）， while PD20 was more than that of control group （<italic>P</italic><0.01）. The total effective rate of clinical curative effect of children in observation group was 96.55% （56/58）， which was higher than 82.76% （48/58） in control group （<italic>χ</italic>²=5.948，<italic>P</italic><0.05）. Conclusion:Erchentang combined with Sanzi Yangqintang for children with CVA phlegm evil accumulation lung syndrome can further control the symptoms of cough， shorten the course of cough， improve the quality of life， and reduce airway inflammation and AHR， reduce the recurrence rate. The clinical efficacy is better than using montelukast only， and it is safe and has good clinical value.

Effect of Jianpi Bufei Prescription on cAMP/PKA/CREB Signaling Pathway in Juvenile Asthma Rats / 中国实验方剂学杂志

Objective:To investigate the effect of Jianpi Bufei prescription （JPBFP） on airway inflammation， airway hyperresponsiveness （AHR）， and cyclic adenosine monophosphate （cAMP） signaling pathway activity in ovalbumin （OVA）-sensitized and challenged juvenile asthma rats. Method:Seventy-five male SD rats were randomly divided into a blank group （<italic>n</italic>=15） and an experimental group （<italic>n</italic>=60）. The rats in the experimental group were sensitized by aluminum hydroxide gel containing 0.2% OVA and stimulated by aerosol inhalation of normal saline containing 1% OVA to induce an asthma model， followed by assignment into the following groups： a model group （<italic>n</italic>=15）， a JPBFP group （<italic>n</italic>=15， 8.37 g·kg^-1·d^-1）， an aminophylline group （<italic>n</italic>=15， 40 mg·kg^-1·d^-1）， and a dexamethasone group （<italic>n</italic>=15， 0.1 mg·kg^-1·d^-1）. AHR was detected by the pulmonary function analyzer， changes in inflammatory cells by white blood cell （WBC） count and differential blood count in bronchoalveolar lavage fluid （BALF）， and pathological changes of lung tissues by hematoxylin-eosin （HE）， Masson， and periodic acid-schiff （PAS） staining. The interleukin （IL）-4， IL-5， IL-13， interferon （IFN）-<italic>γ</italic>， and tumor necrosis factor （TNF）-<italic>α</italic> levels in serum and the cAMP level in plasma were tested by the enzyme-linked immunosorbent assay （ELISA）. Protein kinase A （PKA） expression in lung tissues was detected by immunohistochemistry. The cAMP-response element-binding protein （CREB） mRNA and protein expression in lung tissues was detected by the real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Result:Compared with the blank group， the model group showed increased lung resistance， decreased pulmonary compliance （<italic>P</italic><0.05）， elevated WBC count and proportion of eosinophils in BALF （<italic>P</italic><0.05）， up-regulated levels of IL-4， IL-5， IL-13， and TNF-<italic>α</italic> in peripheral blood， declining IFN-<italic>γ</italic> level （<italic>P</italic><0.01）， severe pathological changes of lung tissues， dwindled cAMP， and down-regulated PKA and CREB expression （<italic>P</italic><0.01）. Compared with the model group， JPBFP inhibited AHR， reduced WBC count and proportion of eosinophils in BALF and lung resistance （<italic>P</italic><0.05）， improved pathological changes of lung tissues， increased pulmonary compliance， and up-regulated cAMP in serum and PKA and CREB expression in lung tissues （<italic>P</italic><0.01）. Conclusion:JPBFP can improve AHR， inhibit airway inflammation， and alleviate lung injury in asthma rats. Its mechanism may be related to the up-regulation of the activity of the cAMP/PKA/CREB signaling pathway.

Progress on mycoplasma pneumoniae in the pathogenesis of asthma / 国际儿科学杂志

Mycoplasma pneumoniae(MP)infection and asthma are common respiratory diseases in children, and they are closely related.MP infection induces asthma attacks, and anti-MP infection treatment can help control the degree in children with asthma.This article describes the relationship between MP infection and asthma, and provides a theoretical basis for the treatment of asthma.MP infection can damage the airway and cause chronic cough and bronchial asthma attacks.MP infects the airway epithelium and secretes community-acquired respiratory distress syndrome toxin(CARDS Tx)combined with the airway mucosa to cause the airway epithelial damage, and promotes the body to form a TH2-mediated immune response, mediates the production of specific IgE, and then triggers the release of inflammatory mediators involved in asthma; the increase of inflammatory factors released after MP infection will also cause exhaled breath.Fractional exhaled nitric oxide(FeNO)is elevated, which can lead to airway hyperresponsiveness and airway remodeling.In view of treatment, when treating MP infections with macrolide drugs, they can also have anti-inflammatory and immunomodulatory effects on the airways, which can reduce the steroid dose required by children with steroid-dependent asthma, reduce the frequency of asthma attacks and prolong remission period in children with asthma.

Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating the SIRT2-p65 pathway / 医学前沿

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.

Effect of neurokinin 1 receptor antagonist on airway inflammation and hyperresponsiveness in asthmatic mice / 中国小儿急救医学

Objective@#To investigate the effects of neurokinin-1 receptor antagonist WIN 62, 577 on airway inflammation and airway hyperresponsiveness in asthmatic mice.@*Methods@#Thirty-two BALB/c mice(Specific-pathogen-free grade) were randomly divided into 4 groups: control group, asthmatic group, WIN 62, 577 intervention group and dexamethasone group.The asthmatic group, the WIN 62, 577 intervention group, and the dexamethasone group were given intraperitoneal injection of 0.2 ml of OVA sensitization solution at 0 d, 7 d, and 14 d, respectively.Then the asthmatic group, WIN 62, 577 group and dexamethasone group were given OVA challenge solution(4% OVA solution) by inhalation once a day for 30 min from 21 d to 28 d for 7 consecutive days.The WIN 62, 577 intervention group was given WIN 62, 577 300 μg intraperitoneal injection 1 h before each challenge; the dexamethasone group was given intraperitoneal injection of dexamethasone 2 mg/kg 1 h before each challenge.The airway responsiveness of each group of mice was detected by non-invasive pulmonary function test.The bronchoalveolar lavage fluid(BALF) was obtained for inflammatory count.The HE staining of lung tissue was used to observe airway inflammation in mice.@*Results@#Compared with the asthmatic group, the mice in the WIN 62, 577 intervention group showed less restlessness, standing upright, crouching back, scratching the ears and scratching the cheeks, shortness of breath and cyanosis of the lips.After inhaling different concentrations of acetylcholine, the Penh value of mice in the WIN 62, 577 intervention group and the dexamethasone group was significantly lower than that in the asthmatic group(P<0.05). Compared with the asthmatic group, the number of WBC and EOS in BALF decreased significantly in the WIN 62, 577 intervention group and the dexamethasone group(P<0.01). HE staining showed that the inflammatory changes in the lung tissue of mice in the WIN 62, 577 intervention group were significantly reduced, the bronchial epithelium did not fall off significantly, the mucosal edema was not obvious, the smooth muscle proliferation was reduced, and the inflammatory cell infiltration was reduced, similar to the airway changes in the dexamethasone group.@*Conclusion@#Neurokinin-1 receptor antagonist WIN 62, 577 can reduce airway inflammation and airway hyperresponsiveness in asthmatic mice.

Leukotriene D4 bronchial provocation test for detection of airway hyper-responsiveness in children / 南方医科大学学报

OBJECTIVE@#To explore the value of leukotriene D4 (LTD4) bronchial provocation test (BPT) in detection of airway hyper-responsiveness (AHR) in children.@*METHODS@#A total of 151 children aged 6 to 14 years, including 86 in remission of asthma and 65 with acute bronchitis, who were followed up in our respiratory clinic between November, 2017 and August, 2018. The children were randomly divided into LTD4 group (78 cases) and methacholine (MCH) group (73 cases). In LTD4 group, the 78 children underwent LTD4-BPT, including 46 with asthma and 32 children having re-examination for previous episodes of acute bronchitis; in MCH group, the 73 children underwent MCH-BPT, including 40 with asthma and 33 with acute bronchitis. MCH-BPT was also performed in the asthmatic children in the LTD4 group who had negative responses to LTD4 after an elution period. The major adverse reactions of the children to the two BPT were recorded. The diagnostic values of the two BPT were evaluated using receiver-operating characteristic (ROC) curve.@*RESULTS@#There was no significant difference in the results of basic lung function tests between LTD4 group and MCH group (>0.05). The positive rate of BPT in asthmatic children in the LTD4 group was significantly lower than that in the MCH group (26.1% 72.5%; < 0.05). The positive rate of BPT in children with previous acute bronchitis in the LTD4 group was lower than that in the MCH group (3.1% 15.2%). The positive rate of MCH-BPT in asthmatic children had negative BPT results in LTD4 group was 58.8%, and their asthma was mostly mild. The sensitivity was lower in LTD4 group than in MCH group (0.2609 0.725), but the specificity was slightly higher in LTD4 group (0.9688 vs 0.8485).The area under ROC curvein LTD4 group was lower than that in MCH group (0.635 0.787). In children with asthma in the LTD4 group, the main adverse reactions in BPT included cough (34.8%), shortness of breath (19.6%), chest tightness (15.2%), and wheezing (10.9%). The incidence of these adverse reactions was significantly lower in LTD4 group than in MCH group ( < 0.05). Serious adverse reactions occurred in neither of the two groups.@*CONCLUSIONS@#LTD4-BPT had high safety in clinical application of children and was similar to the specificity of MCH-BPT. However, it had low sensitivity, low diagnostic value, and limited application value in children's AHR detection.

2,4,6,-trihydroxy-3-geranylacetophenone (tHGA) Suppresses Chronic Allergic Airway Inflammation in Ovalbumin-Sensitized Mice via Intraperitoneal Route

@#Introduction: Asthma is a condition characterized by eosinophilic airway inflammation and remodelling that involves several pathological changes, including subepithelial fibrosis, mucus hypersecretion, smooth muscle growth, and vascular changes. The present study aimed to determine the effect of tHGA administered intraperitoneally in a chronic asthma mouse model that closely mimics the human asthma. Methods: Ovalbumin-sensitized and challenged BALB/c mice were i.p. administered with tHGA at different doses (20 and 2 mg/kg). Respiratory function was measured, and brochoalveolar lavage, blood and lung samples were then obtained and analyzed. Results: The airways of OVA-induced mice developed increased pulmonary inflammation with increased levels of cytokines, chemokines, and changes in vascular permeability. Intraperitoneal administration of tHGA in OVA-induced mice significantly and dose-dependently inhibited the airway inflammation, production of immunoglobulin E, Th2-type cytokines and chemokines, and inflammatory mediators. Treatment with tHGA also significantly reduced the airway hyperresposiveness in response to increased methacholine doses. Conclusion: This study demonstrates that the efficacy of tHGA in alleviating chronic asthmatic symptoms in mouse model improved significantly when administered intraperitoneally compared to oral route. Furthermore, this study also supports that tHGA has a therapeutic potential in chronic asthma management by acting as a cysteinyl leukotrienes (CysLT) inhibitor

VGX-1027 inhibits PM2.5-induced lung inflammation and airway hyperresponsiveness in mice / 中国药理学通报

Aim: To investigate whether VGX-1027 could prevent PM2.5-induced mouse lung inflammation and airway hyperresponsiveness. Methods: Fortyeight C57BL/6 mice were randomly divided into control group, VGX-1027(50 mg · kg-1) + PBS group, PM2.5 group, VGX-1027 (12. 5 mg · kg-1) + PM2.5 group, VGX-1027(25 mg · kg-1) + PM2.5 group, and VGX-1027(50 mg · kg-1) + PM2.5 group. Mice were injected intraperitoneally with PBS or corresponding doses of VGX-1027 one hour before intranasal instillation of PBS or PM2.5(7. 8 mg · kg-1) for two consecutive days. 24 hours after last intranasal instillation, airway hyperresponsiveness and bronchoalveolar lavage fluid (BALF) cell numbers were measured. Lung inflammation scores were evaluated by HE staining and the levels of inflammatory cytokines in BALF were detected by ELISA, and the expressed levels of NLRP3 and caspase-1, as well as the phosphorylation levels of NF-kB protein were determined using Western blotting. Results: PM2.5 intranasal instillation induced significant lung inflammation and airway hyperresponsiveness. In the PM2.5 group, VGX-1027 at 12. 5 mg · kg-1 did not inhibit PM2.5-induced airway hyperresponsiveness and lung inflammatory infiltration compared to PM2.5-instilled mice; however, VGX-1027 at 25 and 50 mg · kg-1 inhibited PM2.5-induced airway hyperresponsiveness and lung inflammatory infiltration, decreased the number of inflammatory cells and the levels of inflammatory factors in BALF, and down-regulated NLRP3 and caspase-1 expression, as well as the phosphorylation levels of NF-κB. Conclusion: VGX-1027 could inhibit PM2.5-induced lung inflammation and airway hyperresponsiveness in mice.

Hyperresponsiveness to Boiled Egg Yolk in Early Life Leads to Prolonged Egg Allergy

Hen's egg is the most common allergen in IgE-mediated food allergy among children in Japan. Although the majority of patients with egg allergy can eat heated egg yolk safely because of its low allergenicity, severely allergic patients show an immediate-type reaction to heated egg yolk. We hypothesized that patients with hyperresponsiveness to boiled egg yolk may have difficulty in acquiring tolerance to egg. The purpose of this study was to examine the prognosis of patients with hyperresponsiveness to boiled egg yolk. Data from 121 patients with egg allergy who underwent oral food challenge (OFC) with boiled egg yolk between January 2012 and December 2013 were analyzed retrospectively. The proportion of patients who could consume heated whole egg 3 years after OFC was 15.4% in the OFC-positive group and 75.8% in the OFC-negative group. Hyperresponsiveness to boiled egg yolk in early life might lead to prolonged egg allergy in children. This finding might aid in the selection of an appropriate population requiring practical immunotherapy.

Characteristics of airway hyperresponsiveness in children with chest tightness variant asthma / 中华实用儿科临床杂志

Objective To analyze the characteristics of airway hyperresponsiveness and fractional exhaled ni-tric oxide (FeNO)in children with chest tightness variant asthma (CTVA)in comparison with cough variant asthma (CVA)and the typical asthma. Methods From January 2012 to June 2015,37 atypical asthma children with chest tightness as the sole presenting manifestation were selected as subjects (CTVA group). Meanwhile,100 children who were newly diagnosed as CVA and 100 children who were newly diagnosed as typical asthma were selected as control group. All of the children in 3 groups had completed FeNO measurement,spirometry and with either positive result of bronchial provocation test or positive result of bronchial dilation test. The differences in FeNO and spirometry data among 3 groups were analyzed. Results FeNO was 11. 0(6. 0,33. 0)ppb in CTVA group,but 28. 0(16. 0,52. 0) ppb in typical asthma group,which indicated that FeNO was significantly lower in CTVA group than that in typical asth-ma group (P < 0. 05). The accumulated provocative dose of methacholine resulted in a 20％ (PD20-FEV 1 )drop in forced expiratory volume in 1 second (FEV 1 ),which was 0. 480(0. 145,0. 663)mg in CTVA group and 0. 180 (0. 097, 0. 463)mg in typical asthma group. PD20-FEV 1 was significantly higher in CTVA group than that in typical asthma group,and the difference was statistically significant(P < 0. 05). FeNO was 18. 5(8. 0,34. 0)ppb and PD20-FEV 1 was 0. 330(0. 120,0. 730)mg in CVA group,which had no statistically significant differences between CTVA group and CVA group(all P > 0. 05). Conclusion CTVA children have lower airway hyperresponsiveness and lower FeNO than typical asthma children. CTVA children may have similar airway hyperresponsiveness as CVA children.

Methacholine bronchial provocation test in patients with asthma: serial measurements and clinical significance

BACKGROUND/AIMS: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. CONCLUSIONS: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.

Efficacy of Lianhua Dingchuan Tablets in bronchial asthma / 复旦学报（医学版）

Objective To evaluate the efficacy of Lianhua Dingchuan Tablets in bronchial asthma.Methods Fifty BALB/C mice were randomly and equally divided into control (Con) group,ovalbumin (OVA) group,dexamethasone (DEX) group,high-dose Lianhua group,low-dose Lianhua group.The mice were sensitized and challenged with OVA plus aluminium hydroxide to establish asthmatic model and were pre-treated 30 minutes before challenge.Specific airway resistance (sRaw) was used to evaluate airway hyperresponsiveness,and airway inflammatory changes were measured.ELISA and Magnetic Luminex(R) were used to quantified the levels of IL-4,IL-13 and INF-γ.Results Airway resistance significantly decreased in DEX group and High-dose Lianhua group (P＜0.05).Levels of inflammatory cells and IL-13 in BALF evidently reduced in DEX group,high-dose Lianhua group and low-dose Lianhua group (P ＜ 0.05),while IL-13 level in serum only decreased in DEX group.There was no significant changes in the levels of IL 4 and INF γ among those groups.Conclusions Lianhua Dingchuan Tablets might relieve the symptoms of asthma by reducing IL-13 level and inhibiting the airway inflammation.

Study on correlation between FeNO, bronchial hyperresponsiveness and asthma control in preschool children / 重庆医学

Objective To find out the association between the indicators(pulse concussion lung function test index) of bronchial hyperresponsiveness (BHR) with fractional concentration of exhaled nitric oxide (FeNO) at different control periods among preschool asthmatic children.Methods Totally 74 asthmatic children in the pediatric department of our hospital from April 2015 to February 2017 were enrolled in this study,and 25 children undergoing the lung function and FeNO examination served as the controls,aged 3-5 years old.The cases were divided into three groups according to the standard in 2016 version of the Prevention and Treament Guide of Children Bronchial Asthma:asthma control group(n =26),asthma non-control;group(n =48) and control group (n=25).All data of FeNO,resistance of the respiratory system at 5 Hz(R5),resistance of the respiratory system at 5 Hz (R20),difference of R5 and R20(R5-20),reactance area (AX),reactance of the respiratory system at 5 Hz (X5) and resonant frequency of reactance (Fres) were collected.The FeNO,pulse concussion lung function test value and their association were analyzed.Results (1) The FeNO value of asthma the non-control group was significantly higher than that of the asthma control group and the control group,which were 34.00 ± 18.17,20.23± 11.07 and 28.00± 17.30 respectively.The AX detection value of the asthma non-control group was significantly higher than that of the control group(37.29 ± 15.27 vs.30.17 ± 9.50,P＜0.05).(2)R20 had weak correlation with FeNO in the control group(P＜0.05),while R20 had no correlation with FeNO in the non-control group and control group (P＞0.05).FeNO had no obvious correlation with R5,R520,AX,X5 and Fres in the asthma non-control group,asthma control group and control group(P＞0.05).Conclusion In preschool children with asthma,FeNO can reflect the airway eosinophilic inflammation control,and does not reflect the airway hyperresponsiveness.Thereforeit ie needed to combined with FeNO and IOS indicators (airway hyperresponsiveness index AX,etc.),which can more precisely judge whether asthma being controlled.

Therapeutic Effects of Tubastatin A Hcl in Chronic Murine Asthma Model / 中国医科大学学报

Objective To investigate the effects of Tubastatin A Hcl,a selective HDAC6 inhibitor,on the development of chronic asthmatic mice with airway inflammation,airway remodeling and airway hyperresponsiveness. Methods BALB/C mice were randomly divided into control group, asthma group,dexamethasone group and Tubastatin A Hcl group. The airway resistance,total cells and different cells in BALF,IL?4,IL?5,TGF?β1 were detected by ELISA. HE、AB?PAS and Masson trichrome staining were carried out to assess the airway inflammation and remodeling. Immuno?histochemical staining and western blotting were adopted to determine the expression ofα?SMA and TGF?β1. Results After drugs treatment,air?way resistance decreased,and levels of IL?4,IL?5,TGF?β1,total inflammatory cells and eosinophils in BALF were relieved. Meanwhile,inflamma?tory cells infiltration,goblet cells metaplasia and collagen deposition in lung tissue were also reduced,but all of above the effects of dexamethasone were better than Tubastatin A Hcl. The expression ofα?SMA and TGF?β1 in the lung tissue decreased significantly after treatment ,in which Tu?bastatin A Hcl were slightly better than dexamethasone treatment. Conclusion Tubastatin A Hcl can effectively relieve airway inflammation ,air?way remodeling and airway hyperresponsiveness in chronic asthmatic mice ,but its effect of anti?inflammatory is worse than dexamethasone treat?ment,while it is better than dexamethasone in the effect of relief airway remodeling.

The effect of the asthmatic mice's airway inflammation and bronchial hyperresponsiveness treated with curcumin / 国际儿科学杂志

Objective To investigate the effect of the asthmatic mice's airway inflammation and bronchial hyperresponsiveness treated with curcumin.Methods The mice were divided into three teams randomly,the normal mice,the asthmatic mice and the curcumin mice.The mice of three teams were detected by lung function,Giemsa dying,HE and PAS dying,and ELISA.Results After the Mch concentration of 6.25 g/L,the value of Penh in asthmatic mice was higher than the control mice,which was sighifiantly different(P ＜ 0.01).However,the value of Penh in curcumin team was lower than asthmatic mice,which was sighifiantly different (P ＜0.01).The number of total white blood cells and eosinophils was higher in asthmatic mice than the contol,which was sighifiantly different(P ＜0.01).However,the number in curcumin team was lowered than asthmatic team(P ＜ 0.01).The IgE content of BALF in asthmatic mice was higher than the control,which was significantly different(P ＜ 0.01).However,the content in curcumin team was lowered than the asthmatic mice,which had a significant difference(P ＜0.01).Pathology of HE staining in asthmatic mice showed the thickening bronchial wall,narrow lumen,peribronchial and perivascular infiltration with a large number of eosinophil-based inflammatory cells,lumen with many inflammatory secretions.However,the curcumin team was alleviated than the asthmatic mice.There were more goblet cells and more mucus secretion in the asthmatic mice by PAS staining.However,the curcumin team was alleviated than the asthmatic mice.Conclusion Curcumin can alleviate the airway inflammation,mucus secretion,airway hyperresponsiveness and the IgE content of bronchoalveolar lavege fluid.

Role of astograph methacholine provocation test in diagnosis of bronchial asthma / 实用医学杂志

Objective To evaluate the diagnostic value of astograph methacholine provocation test for bronchial asthma.Methods A total of 238 asthma patients and 499 non-asthma patients participated in the detection by astograph methacholine provocation test.Statistical methods were used to analyze the differences of astograph parameters and find the indicators of asthma diagnosis and the critical value.Results Dmin,Cmin and PD15 were much lower in the asthma group (P ＜ 0.01),compared with the the non-asthma group,when SGrs,SGrs/Grs cont were much higher (P ＜ 0.01).SGrs was relevant with Dmin,Cmin,PD15 in the asthma group (P =0.000;r =0.685,r =0.657,r =0.639) as well as the SGrs/Grs cont did (P =0.000,r =0.775;r =0.740,r =0.708).In ROC analysis,Dmin presented an AUC of 0.661,the cutoff value was 2.71 unit,with a sensitivity of 0.739 and specificity of 0.551.PD15 presented an AUC of 0.746,the cutoff value was 4.856 5 unit,with a sensitivity of 0.693 and specificity of 0.684.Conclusion Astograph methacholine provocation test shows good sensitivity and specificity in the diagnosis of asthma,particularly when Dmin ≤ 2.71 Unit or PD15 ≤ 4.8565 Unit as the cutoff value.