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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

Is Performance of a Modified Eucapnic Voluntary Hyperpnea Test in High Ventilation Athletes Reproducible?

PURPOSE: Exercise-induced bronchoconstriction (EIB) is common in “high ventilation” athletes, and the Eucapnic Voluntary Hyperpnea (EVH) airway provocation test is the standard EIB screen. Although the EVH test is widely used, the in-test performance in high ventilation athletes as well as the reproducibility of that performance has not been determined. Reproducibility of pre- and post-test spirometry and self-reported atopy/cough was also examined. METHODS: High ventilation athletes (competitive swimmers; n=11, 5 males) completed an atopy/cough questionnaire and EVH testing (operator controlled FiCO₂) on 2 consecutive days. RESULTS: Swimmers achieved 85%±9% and 87%±9% of target FEV1 volume on days 1 and 2, respectively, (P=0.45; ICC 0.57 [0.00-0.86]) resulting in a total ventilation of 687 vs 684 L [P=0.89, ICC 0.89 (0.65-0.97]) equating to 83%±8% and 84%±9% of predicted total volume (ICC 0.54 [0.00-0.85]) between days 1 and 2. FiCO₂ required to maintain eucapnic conditions was 2.5%. Pre-test FEV1 was less on day 2 (P=0.04; ICC >0.90). Day 1 to 2 post-test FEV1 was not different, and 4 swimmers were EIB positive (>10% fall in pre-post FEV1) on day 1 (3 on day 2). CONCLUSIONS: EVH in-test performance is reproducible however required less FiCO₂ than standard protocol and the swimmers under-ventilated by 125 and 139 L/min for days 1 and 2, respectively. How this affects EIB diagnosis remains to be determined; however, our results indicate a post-test FEV1 fall of ≥20% may be recommended as the most consistent diagnostic criterion.

Relationship between Bronchodilator Response, Airway Hyperresponsiveness, and Exhaled Nitric Oxide Levels in Patients with Suspected Bronchial Asthma / 대한내과학회지

BACKGROUND/AIMS: Exhaled nitric oxide (NO) has been extensively investigated as a marker of airway inflammation in asthma, and fractional exhaled nitric oxide (FeNO) is recognized as a useful tool for its evaluation. The aim of this study was to investigate the relationships between FeNO levels and bronchodilator response (BDR), and between FeNO and mannitol-induced airway hyperresponsiveness (AHR), in patients with suspected asthma. METHODS: Clinical variables were collected from patients aged ≥ 13 years with suspected bronchial asthma and measured levels of FeNO. These levels were compared with patient values for forced expiratory volume in the first second (FEV1) and forced expiratory flow at 25 and 75% of the pulmonary volume (FEF(25-75%)) in bronchodilator response tests under control conditions, and during bronchial provocation with mannitol. Correlations and receiver operating characteristic (ROC) curves between FeNO levels and each test were assessed. RESULTS: A total of 259 patients were included in the analysis. The mean ages of the two test groups were 41.1 and 47.8 years, respectively. FeNO levels were strongly correlated with bronchodilator response (%) and with the mannitol dose producing a 15% fall in FEV1 (PD15). On the other hand, FeNO levels were only weakly correlated with FEF(25-75%). The optimal cut-off values for FeNO to predict a positive BDR and AHR were 38.5 and 29.5 parts per billion, respectively. CONCLUSIONS: This study suggests that FEV1 and FEF(25-75%) airway responses correlate with FeNO levels in patients with suspected bronchial asthma. FeNO levels may help to predict positive responses to BDR and AHR.

Nonspecific Bronchoprovocation Test / 결핵및호흡기질환

Bronchial asthma is a disease characterized by the condition of airway hyper-responsiveness, which serves to produce narrowing of the airway secondary to airway inflammation and/or various spasm-inducing stimulus. Nonspecific bronchoprovocation testing is an important method implemented for the purpose of diagnosing asthma; this test measures the actual degree of airway hyper-responsiveness and utilizes direct and indirect bronchoprovocation testing. Direct bronchoprovocation testing using methacholine or histamine may have superior sensitivity as these substances directly stimulate the airway smooth muscle cells. On the other hand, this method also engenders the specific disadvantage of relatively low specificity. Indirect bronchoprovocation testing using mannitol, exercise, hypertonic saline, adenosine and hyperventilation serves to produce reactions in the airway smooth muscle cells by liberating mediators with stimulation of airway inflammatory cells. Therefore, this method has the advantage of high specificity and also demonstrates relatively low sensitivity. Direct and indirect testing both call for very precise descriptions of very specific measurement conditions. In addition, it has become evident that challenge testing utilizing each of the various bronchoconstrictor stimuli requires distinct and specific protocols. It is therefore important that the clinician understand the mechanism by which the most commonly used bronchoprovocation testing works. It is important that the clinician understand the mechanism of action in the testing, whether direct stimuli (methacholine) or indirect stimuli (mannitol, exercise) is implemented, when the testing is performed and the results interpreted.

Clinical features of chronic cough with airway hyper-responsiveness in children / 中华实用儿科临床杂志

Objective To study the clinical features and spirometry of children with chronic cough and positive findings by bronchial provocation test.Methods Four hundred and fifty children with chronic cough from 3 hospitals of Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong Medical University School of Medicine,Gong Li Hospital of Pudong New Area,Pudong Hospital,were enrolled in this study from December 2012 to December 2014,and among them,373 cases completed the questionnaires,spirometry and bronchial provocation test.The differences in clinical features and spirometry between the bronchial provocation test positive group and negative group were compared.And the further evaluation of their clinical value was performed.Results Two hundred and thirty-six cases of children with bronchial provocation tests positive showed much higher rate of dry [72.03％ (170/236 cases)] and night cough[58.90％ (139/236 cases)] than those in the negative group[27.00％ (37/137 cases),22.63％ (31/137cases)],and the differences were significant (x2 =71.154,45.973,all P ＜0.01).Children in positive group also had higher morbidity of eczema[52.12％ (123/236 cases)],allergic conjunctivitis [24.15％ (57/236 cases)] and inhaled allergy history[40.25％ (95/236 cases)] than those in negative group[32.85％ (45/137 cases),10.95％ (15/137cases),18.98％ (26/137 cases)],and there existed significant differences (x2 =13.006,9.701,17.904,all P ＜0.01).And they also had higher asthma heredity [18.22％ (43/236 cases)] than that in negative group [9.49％(13/137 cases)],and the difference was significant (x2 =5.179,P =0.023);with worse small airway function [50.85％ (120/137 cases) vs 36.50％ (50/137 cases)] (x2 =7.197,P =0.007).For further study,the sensitivity and specificity for dry cough were both high(72.03％ and 72.99％).For specificity,family history was the most highest one (90.51％),and night cough and allergic conjunctivitis were also high.Conclusions Pulmonary function tests to reflect small airway function abnormalities,combined with a family history of asthma and chronic cough in children related to eczema,allergic conjunctivitis,and inhalation allergy history clinical features,can better predict airway hyperresponsiveness.

Effects of exogenous H2 S on O3-induced airway hyperresponsiveness and airway remodeling in a mouse model of asthma / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the effects of exogenous hydrogen sulfide ( H2 S) on ozone ( O3 )-induced air-way hyperresponsiveness and airway remodeling in a mouse model of asthma.METHODS: Female SPF C57BL/6 mice were randomized as control group, O3 group and NaHS+O3 group.Half an hour before O3 treatment, the mice in control group and O3 group were intraperitoneally injected with normal saline, while the mice in NaHS+O3 group were intraperito-neally injected with NaHS ( H2 S donor);then the mice in O3 and NaHS+O3 group were treated with O3 , while the mice in control group breathed clean air.After 4 weeks, the airway responsiveness and tracheal ring tension were measured.The bronchial basement membrane circle diameter ( Pbm) and the total area of the wall ( Wat) were determined with HE stai-ning and standardized to measure airway remodeling.The changes of goblet epithelial cells in the lung tissue were deter-mined with AB-PAS staining.RESULTS:Airway tension of O3 group was significantly higher than that in control group, but that in NaHS+O3 group was obviously lower than that in O3 group and had no significant difference compared with con-trol group.Compared with control group, the tension of tracheal ring stimulated by methacholine in O3 group increased sig-nificantly, but that in NaHS+O3 group decreased obviously compared with O3 group and had no significant change com-pared with control group.Compared with control group, bronchial wall thickness in O3 group increased significantly, but that in NaHS+O3 group decreased obviously compared with O3 group and increased significantly compared with control group.Compared with control group, goblet epithelial cell proportion in the total area of airway epithelial cells in O3 group increased significantly, but that in NaHS+O3 group decreased compared with O3 group and increased significantly com-pared with control group.CONCLUSION:Exogenous H2 S reduces O3-induced airway hyperresponsiveness and airway re-modeling, thus providing a new target for clinical drug treatment of asthma.

Immunomodulatory Effects of Ambroxol on Airway Hyperresponsiveness and Inflammation

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

Changes in small airway function in patients with non-allergic rhinitis / 医学研究生学报

Objective Small airway hypofunction is an early manifestation of asthmatic airway injury and is found in patients with non-asthma allergic rhinitis.However, no report has been seen on the changes of small airway function in patients with non-aller-gic rhinitis ( NAR) .This study was to investigate the possibility of small airway lesion in NAR patients and its relationship with airway responsiveness by observing the changes of small airway function in NAR patients without asthma and/or lower airway symptoms. Methods We recruited 324 subjects for this study, including 262 NAR patients and 62 healthy controls, and assigned them to an air-way hyperresponsiveness (AHR) and a non-airway hyperresponsiveness (nAHR) group.All the subjects underwent medical history collection, nasal examination, allergen skin prick test, blood routine test, serum total immunoglobin E assay, pulmonary function test, and bronchial challenge test. Results Compared with the healthy con-trols, the NAR patients showed remarkably lower predicted percenta-ges of maximal mid-expiratory flow ([85.6 ±17.1] vs [81.3 ± 19.9]%), mid-expiratory flow (MEF) with 75% of forced vital ca-pacity (FVC) expired ([96.1 ±16.1] vs [88.8 ±23.1]%), MEF with 50%of FVC expired ([88.4 ±17.8] vs [84.8 ±20.8]%), and MEF with 25%of FVC expired ([92.7 ±25.9] vs [82.9 ± 28.7]%) (P0.05).The positive rate of AHR was 6.1% (16/246) in the NAR group.All the indices of small airway function were significantly lower in the AHR than in the nAHR group (P <0.01). Conclusion NAR patients are apt to undergo obvious changes in small airway function, some with AHR, which is associated with lower airway function changes.