ObjectiveTo explore the diagnostic value of fractional exhaled nitric oxide (FeNO) in adult asthma.MethodsPubMed, Embase, Cochrane Library, Wanfang, CNKI and VIP databases were searched for relevant literatures from the time of database establishment to February 2021. Data analysis were made by Revman and Stata.ResultsA total of 44 articles with 47 records and 9654 subjects were included. The diagnosis sensitivity, specificity, positive and negative predictive value of FeNO were 0.71 (95%CI 0.65 - 0.76), 0.80 (95%CI 0.75 - 0.84), 3.47 (95%CI 2.86 - 4.21), and 0.37 (95%CI 0.31 - 0.43), respectively. The diagnostic odds ratio was 9.49 (95%CI 7.13 - 12.61), and the area under the receiver operating characteristic curve was 0.82 (95%CI 0.79 - 0.85).ConclusionsFeNO has certain diagnostic value in diagnosis of asthma. Types of asthma, region and cut-off value all have impact on the diagnostic efficiency of FeNO.
ObjectiveTo explore the predictive value of fractional exhaled nitric oxide (FeNO) in the treatment response of adult asthmatic patients. Methods64 adult outpatients with asthma from Peking Union Hospital between March and September 2013 were recruited in the study. All patients completed asthma control test (ACT) together with exhaled nitric oxide (FeNO) and pulmonary function test. Then the patients were classified into a higher FeNO group (n=33) and a normal FeNO group (n=31) according to FeNO level. All patients accepted regular inhaled ICS/LABA treatment (salmeterol and fluticasone 50/250). Three months later all patients reaccepted ACT,FeNO and pulmonary function test. ResultsThe ACT score increased in all patients,and was significantly higher in the higher FeNO group than that in the normal FeNO group[22.07±5.49 vs. 19.23±5.48,t=2.893,P<0.05]. The complete control rate of the higher FeNO group was higher than that in the normal FeNO group (42.42% vs. 19.35%,χ2=3.960,P<0.05). The FEV1 and FEV1%pred of two groups both increased significantly (P<0.05),but there was no significant difference between two groups (P>0.05). Correlation analysis showed that FeNO and the declined rate of FeNO was negatively correlated with the ACT score(r=-0.302,P<0.05;r=0.674,P<0.01) and positively correlated with the improvement of ACT score (r=0.514,P<0.01;r=0.674,P<0.01). No significant correlation was found between FeNO and FEV1 or FEV1%pred. ConclusionThe effect of ICS/LABA therapy is better for asthma patients with higher FeNO. FeNO can be used for predicting the response to ICS/LABA therapy in patients with asthma and guiding the treatment.
Objective Chronic obstructive pulmonary disease( COPD) is highly heterogeneous. In theory, the patients with same clinical manifestations, treatment response and prognosis can be classified into one phenotype, which may have same biological or physiological mechanisms. In this study the profiles of patients with COPD including body mass index( BMI) , Goddard score, fractional exhaled nitric oxide( FeNO) were analyzed in order to find some special phenotypes.Methods Patients with COPD at stable stage in Ruijin Hospital from May 2011 to February 2012 were evaluated with COPD assessment test ( CAT) in Chinese version, St. George’s Respiratory Questionnaire( SGRQ) , hospital anxiety and depression( HAD) rating scale, pulmonary function test, and 6-minute walking test ( 6MWT) . Baseline data was collected including height, weight, drug use, times of exacerbation, etc. Results A total of 126 patients were recruited. The patients with low BMI had poorer quality of life, lower FEV1 , poorer diffusion function, and higher Goddard score, and was easier to develop anxiety and depression. The patients with high BMI had lower oxygen saturation at rest. We failed to define a certain kind of phenotype according to FeNO. The patients of emphysema phenotype( assessed by Goddard score) had lower BMI, decreased lung diffusion capacity, and poorer quality of life. Conclusion The study can define COPD patients into some special phenotypes( low BMI and emphysema phenotype) , but failed to define a certain kind of phenotype according to FeNO.
Objective To study the effects of L-arginine （L-Arg） on cell proliferation, inducible nitric oxide synthase (iNOS) expression and cell cycle in human colon carcinoma cell line LS174 through nitric oxide (NO) pathway. Methods LS174 cells were cultured in medium with L-Arg at different concentrations for different times. MTT method was employed to evaluate the level of the cell proliferation. The production of NO in culture supernatants of LS174 cell was detected with enzyme reduction of nitrate. The distribution of the cell cycle was detected with the flow cytometry (FCM). The expression level of iNOS in the cells was determined by Western blot and SP immunocytochemical staining method. Results The growth of LS174 was promoted by the L-Arg at low concentration (0.125 mmol/L) and inhibited at high concentrations (0.5， 2， 8 and 32 mmol/L). The level of NO was increased with the increasing concentration of L-Arg in culture medium. To compare with the control group, the ratio of cells at S phase was increased after 48 hours’ treatments with high concentrations (0.5, 2, 8 and 32 mmol/L) of L-Arg (P＜0.05, P＜0.01); while there was no obvious difference after treatments with low concentration (0.125 mmol/L) of L-Arg (Pgt;0.05). With the increase of the concentration of L-Arg, the expression of iNOS was increased as compared with control group. The higher the concentration of L-Arg was, the better the effect. Conclusion L-Arg can induce the expression of iNOS resulting in increase the production of nitric oxide (NO). Low concentration of L-Arg can promote the growth of LS174 cells, while high concentration ones can inhibit growth and proliferation. The high concentration of L-Arg could induce S phase arrestion in the cell cycle.
Objective To assess the variation and its significance of messenger ribonucleic acid(mRNA) expression of endothelial nitric oxide synthase (eNOS) in allografts of common carotid transplantation model in white rabbits. Methods To establish an animal model of common carotid transplantation in vivo, 30 rabbits were divided into four groups with random number table. Group A (n=3): autografts; group B (n=9): allografts with the least treated; group C (n=9): allografts treated by penicillin/streptomycin and preserved under room temperature; group D (n=9): allografts treated by penicillin/streptomycin and cryopreserved in liquid nitrogen. All the transplanted grafts were harvested 1-3 weeks later, then compared and evaluated the histomorphological variation and eNOS mRNA expression. Results The vascular structures of autografts in group A were kept approximately normal, only a few infiltration of inflammatory cells could be found. The structural variations of allografts in other trial groups behaved similarly as, intima proliferation in the 1st week, intima hyperplasia in the 2nd week, and both intima and media hypertrophy in the 3rd week. And also there seemed that luminal thrombosis could be found in all the allografts. Allografts in group B were destructed utmost the worst in all the groups. The expression of eNOS mRNA in allografts of group B was significantly less than that in other groups (Plt;0.05). Conclusion The down-regulation of eNOS mRNA expression might lead to intima hyperplasia and thrombosis of allografts.
Objective To investigate the effect of low-flow inhaling NO for short time on postoperative cardiac and pulmonary functions in infants with congenital ventricular septal defect complicated with severe pulmonary hypertension. Methods Forty-five patients with congenital ventricular septal defect complicated with severe pulmonary hypertension from May 2014 to May 2016 in our hospital were enrolled. There were 19 males and 26 females, whose age ranged from 1 to 22 months (average age: 7.2±14.4 months) and weight ranged from 2.7 to 10.5 kg (average weight: 6.8±3.6 kg). The patients were randomly divided into three groups (n=15 in each): the blank group, the prior inhalation group and the posterior inhalation group. The blank group did not inhale NO, and the prior inhalation group inhalated NO for 10 min after tracheal and intubation. After the opening of the aorta, the posterior inhalation group inhaled NO for 10 min. The concentration of NO was 20 × 10–6. The pressure ratio of pulmonary circulation/systematic circulation, heart index and oxygenation index were calculated and the troponin value of the three groups was monitored 10 min after returning to intensive care unit (ICU) and postoperatively 1 h, 3 h and 24 h. Differences among above indicators between three groups were compared. Results The troponin value of the posterior inhalation group within 3 h increased most, followed by the blank group and the prior inhalation group. Postoperatively 1 h and 3 h, the troponin value of the prior inhalation group was significantly less than that of the blank group and posterior inhalation group (P<0.01) and the value on postoperative 24 h in each group was lower than that on postoperative 3 h. The cardiac index of prior inhalation group was higher than that of the blank group and the posterior inhalation group at each time point. Postoperatively 3 h and 24 has well as 10 min after returning to ICU, the cardiac index in prior inhalation group was significantly higher than that of the posterior inhalation group (P<0.05). The pressure ratio of pulmonary circulation/systematic circulation of posterior inhalation group increased more than that of blank group; the differences in two groups were significant between postoperative 3 h and 10 min after returning to ICU (P<0.01). There was no statistical significance in the pressure ratio on postoperative 24 h and 10 min after returning to ICU (P>0.05) in three groups. The index of oxygenation of the prior inhalation group was higher than that of the blank group and the posterior inhalation group and statistically different from that of posterior inhalation group (P<0.05). Conclusion Inhaling NO 10 min preoperatively can reduce the injury to the heart and lung function effectively, but the result is the opposite when inhalating NO 10 min after aorta opening.
ObjectiveTo evaluates the values of fractional exhaled nitric oxide (FENO) in the treatment of chronic cough prospectively.MethodsSubjects with chronic cough were recruited from the outpatient clinic of China-Japan Friendship Hospital. All the patients accepted FENO tests, sputum cell counts, pulmonary function tests, bronchial provocation tests, serum IgE, cough symptom scores and Leicester Cough Questionnaire before and after treatment of 4 weeks.ResultsThere were 29 patients with cough variant asthma (CVA), 19 patients with eosinophilic bronchitis (EB) and 39 patients with other causes. The baseline FENO level of the subjects whose coughs were relieved after inhaled corticosteroids (ICS) therapy of 4 weeks was (63±42) ppb, significantly higher than those with bad-response [(28±13) ppb, P<0.01]. The proportion of FENO decrease after ICS therapy was not only significantly related to the proportion of eosinophilic decrease (r=0.54, P<0.01), but also significantly related to the proportion of decrease of cough symptom scores (r=0.48, P<0.01). To distinguish the good responders from bad responders, the optimal baseline FENO cutoff value was 36 ppb, with sensitivity of 82%, specificity of 93%, positive predictive value of 94%, negative predictive value of 87%, accuracy of 83%.ConclusionsThere is a good relationship between the FENO decreasing levels after ICS therapy and the reliefs of cough symptoms in the CVA and EB patients. Chronic cough patients with FENO value more than 36 ppb are indicated to respond to ICS therapy.
Objective To study the relationship between the expression ratio of induced nitric oxide synthase (iNOS) over glial fibrillary acidic protein (GFAP) and the time of injury after brain concussion in rat, in order to acquire a new visual angle for determining injury time of cerebral concussion. Methods Eighty-five healthy Sprague-Dawley rats were divided into three groups randomly: model group (n=25), experimental group (n=55), and control group (n=5). The rats in the model group were used to confirm the attack hight to make the model of brain concussion; according to the time of execution, rats in the experimental group were then subdivided into 11 groups with 5 rats in each subgroup, and their execution time was respectively hour 0.5, 1, 3, 6, 12, 24, 48, 96, 168, 240, and 336; the rats in the control group were executed after fed for 24 hours. After the model of cerebral concussion was established through freefalling dart method, hematoxylin-eosin staining and immunohistochemistry staining of iNOS and GFAP were conducted for the brain of the rats. All related experimental results were studied by using microscope with image analytical system and homologous statistics. Results The ratio of positive expression of iNOS over that of GFAP increased gradually during hour 0.5- 3 after injury in brain (from 5.03 to 10.47). At the same time, the positive expression of iNOS increased significantly (from 14.61% to 37.45%). However, the increase of the positive expression of GFAP was not obvious. Between hour 3 and 12, the ratio began to decline to 4.98, which was still at a high level, and during the same time period, the positive expressions of iNOS and GFAP also experienced the same change pattern. Later, the ratio began to decline between hour 12 and 336 after injury (from 4.98 to 0.95). All ratios at this time were lower than those between hour 0.5 and 12. The positive expression of iNOS and GFAP both increased to a climax before declining. Conclusions The ratio of positive expression of iNOS over GFAP and the respective change pattern of iNOS and GFAP can be used as the evidence of estimating the injury time of cerebral concussion. We can use the ratio of two or more markers to provide a new visual angle for concluding the concussion injury time.
ObjectiveThrough measuring fractional exhaled nitric oxide (FeNO) and eosinophil levels of peripheral blood in chronic obstructive pulmonary disease (COPD) patients with different phenotype of acute exacerbation frequency, to predict the therapeutic effect of glucocorticoid therapy and guide the clinical treatment of different subtypes patients with acute exacerbations of COPD.MethodsA total of 127 patients with acute exacerbation of COPD in Suining Central Hospital from February 2017 to October 2019 were recruited. They were divided four groups according to the number of acute exacerbations in the past one year and the treatment scheme, ie. a frequent acute exacerbation with glucocorticoid treatment group (34 cases), a frequent acute exacerbation with non-glucocorticoid treatment group (31 cases), a non-frequent acute exacerbation with glucocorticoid treatment group (30 cases), and a non-frequent acute exacerbation with non-glucocorticoid treatment group (32 cases). FeNO value, eosinophil ratio in peripheral blood, COPD assessment test (CAT) score, and interleukin-8 (IL-8) concentration were measured before and on the 10th day of treatment, and the differences within group and between groups before and after treatment were compared.ResultsCAT score, FeNO, eosinophil ratio and IL-8 level in the four groups were significantly improved on the 10th day after treatment (all P<0.05). The declines of FeNO value, eosinophil ratio, and IL-8 level on the 10th day of treatment compared with those before treatment in the frequent acute exacerbation with glucocorticoid treatment group and the frequent acute exacerbations with non-glucocorticoid treatment group were larger than those in the non-frequent acute exacerbation with glucocorticoid treatment group and the non-frequent acute exacerbation with non-glucocorticoid treatment group (all P<0.05). The declines of FeNO value, blood eosinophil ratio and IL-8 level in the frequent acute exacerbation with glucocorticoid treatment group were also statistically significantly larger than those in the frequent acute exacerbations with non-glucocorticoid treatment group (all P<0.05). The improvement of CAT score in the frequent acute exacerbation with glucocorticoid treatment group was greater than that in other three groups (all P<0.05). There was no significant difference in CAT score between the non-frequent acute exacerbation with glucocorticoid treatment group and the non-frequent acute exacerbation with non-glucocorticoid treatment group (P>0.05).ConclusionsThe degree of airway inflammation is more obvious in patients with frequent acute exacerbation phenotype of COPD. FeNO value can reflect the level of airway inflammation in patients with frequent acute exacerbation of COPD and evaluate the response to glucocorticoid therapy.
ObjectiveTo explore the hemodynamic effects of inhaled nitric oxide (iNO) on postoperative hemodynamic in patients with cyanotic congenital heart disease (CHD) combined with decreased pulmonary blood flow.MethodsFrom 2014 to 2018, there were 1 764 patients who received corrective repair of cyanotic CHD with decreased pulmonary blood flow in the Department of Pediatric Cardiac Surgery of Fuwai Hospital. We included 61 patients with the ratio of right ventricular systolic pressure to systolic blood pressure (SBP) ≥75% after weaning from cardiopulmonary bypass. There were 41 males and 20 females, with the age of 20.5 (9.0, 39.0) months and weight of 12.5±7.8 kg. The patients were divided into two groups: a conventional group (33 patients, conventional therapy only) and a combined therapy group (28 patients, iNO combined with conventional therapy). The hemodynamics during the first 24 hours after iNO therapy and the in-hospital outcomes of the two groups were investigated and compared.ResultsThere was no statistical difference between the two groups in demographic characteristics and surgical parameters (P>0.05). The hemodynamic effects of iNO within 24 hours included the decrease in the vasoactive inotropic score (VIS, 21.6±6.6 vs. 17.3±7.2, P=0.020) along with the increase in blood pressure (SBP: 73.7±9.7 mm Hg vs. 90.8±9.1 mm Hg, P<0.001) , the decrease in central venous pressure (10.0±3.1 mm Hg vs. 7.9±2.1 mm Hg, P=0.020), the decrease in lactate (2.2±1.7 mmol/L vs. 1.2±0.5 mmol/L, P<0.001) and increase in urine output [2.8±1.7 mL/(kg·h) vs. 4.9±2.2 mL/(kg·h), P<0.001]. The decrease of VIS at 24 h after the surgery in the conventional therapy group was not statistically significant (22.1±7.9 vs. 20.0±8.5, P=0.232). Besides, we discovered that the need for renal replacement therapy (RRT) was less in the combined therapy group than that in the conventional therapy group, especially in the moderate complicated surgery [risk adjustment in congenital heart surgery (RACHS-1) ≤3] subgroup (9.5% vs. 40.7%, P=0.016).ConclusionIn pediatric patients after corrective repair of cyanotic and pulmonary blood follow decreased CHD with increased pulmonary vascular resistance, iNO combined with conventional therapy can improve the hemodynamics effectively. Compared with the conventional therapy, the combined therapy with iNO can decrease the VIS and the need for RRT, which is beneficial to the postoperative recovery of patients.