Persistence of rhinovirus RNA and IP-10 gene expression after acute asthma

Background and objective: Viral nucleic acid may be detected for up to 6 months after an acute asthma deterioration, but the pattern and consequences of viral persistence after acute asthma are incompletely understood. This study investigates the frequency of viral persistence after acute asthma, assesses viral infectivity and determines the host inflammatory responses to viral persistence. Methods: Adults and children presenting to hospital with acute asthma and a confirmed respiratory virus infection were studied acutely and at recovery 4–6 weeks later by clinical evaluation and induced sputum for viral and inflammatory mediator detection. Results: Viral RNA was detected during both acute asthma and recovery visits in 17 subjects (viral persistence), whereas in 22 subjects viral RNA had cleared by recovery (viral clearance). The following viruses were detected at recovery: human rhinovirus: 16; respiratory syncytial virus: 2; influenza: 2. In subjects with viral persistence, eight isolates were different to the virus detected at Visit 1. Forty‐four per cent of the human rhinovirus isolates were infective at recovery. Asthma and infection severity were similar in the viral clearance and viral persistence groups. Viral persistence was associated with elevated IL‐10 mRNA and inducible protein‐10 gene expression. Conclusions: Respiratory viral detection after acute asthma is common, and most often persistence is with non‐infective human rhinovirus. There is a host inflammatory response with an altered cytokine environment, and the viral RNA can be source of persistent infection. These effects may have longer‐term consequences in asthma.     

The relation between serum vitamin D levels,viral infections and severity of attacks in children with recurrent wheezing

Introduction and ObjectivesVitamin D deficiency is associated with increased susceptibility to infections and wheezing. We aimed to evaluate the relation between vitamin D levels, viral infections and severity of attacks in children with recurrent wheezing.Materials and methodsA total of 52 patients who applied with wheezing, at the ages of 12–60 months with a history of three or more wheezing attacks in the last year and 54 healthy children were included. Sociodemographic data, risk factors for recurrent wheezing, and the severity of the wheezing attacks were recorded. 25(OH)D3, calcium, phosphor, alkaline phosphatase and parathormone levels of all children were measured. Nasopharyngeal samples of the patients for viruses were studied by multiplex polymerase chain reaction.ResultsFor the patient group, being breastfed for six months or less, history of cesarean section, cigarette exposure, humid home environment, and family history of allergic disease were significantly higher compared with the control group. Serum vitamin D levels in the patient group were significantly lower compared to the control group. There was no significant relationship between vitamin D levels and hospitalization, oxygen or steroid therapy. Virus was detected in 38 patients (73%). Rhinovirus (63.2%) was the most frequently detected virus. Coinfection was found in 14 (36.8%) patients. There was no statistically significant difference between detection of virus and vitamin D levels.ConclusionsCigarette exposure, being breastfed six months or less, humid home environment, history of cesarean section, family history of allergic disease and vitamin D deficiency might be risk factors for recurrent wheezing.     

中药辅助治疗支气管哮喘急性发作50例疗效观察

目的探讨射干麻黄汤联合小青龙汤辅助治疗支气管哮喘急性发作的临床疗效。方法选取2012年1月至2014年1月收治的支气管哮喘患者100例,随机分为观察组和对照组,每组50例。对照组患者予常规西医治疗。观察组患者在同对照组患者治疗的基础上加用射干麻黄汤联合小青龙汤辅助治疗。2周后比较两组患者的临床疗效以及两组患者治疗前后FEV1、FVC、PEF及中医症候积分的变化。结果观察组患者治疗总有效率(96.0%)显著高于对照组患者(78.0%),两组比较差异有统计学意义(P0.01),秩和检验结果显示观察组患者临床疗效显著优于对照组患者(P0.05)。治疗后两组患者的FEV1、FVC、PEF均较治疗前显著升高,且观察组患者的FEV1、FVC、PEF明显高于对照组患者,差异有统计学意义(P0.01)。治疗后两组患者的中医症候积分均较治疗前明显降低,观察组患者治疗后的中医症候积分显著低于对照组,差异有统计学意义(P0.01)。结论射干麻黄汤联合小青龙汤辅助治疗支气管哮喘急性发作能明显提高疗效,明显改善患者的临床症状及肺功能,值得推广和应用。     

The effect of acute ethanol intoxication on salivary proteins of innate and adaptive immunity

Background: Human salivary proteins: peroxidase, lysozyme, lactoferrin, and IgA, participate in the protection of oral tissues, as well as upper digestive and respiratory tracts, against a number of microbial pathogens. In the current study, we investigated the effect of acute consumption of a large dose of ethanol on representative human salivary proteins of the innate and adaptive immune systems. Methods: Eight healthy male volunteers drank an average of 2.0 g (1.4 to 2.5 g/kg) body weight of ethanol, in the form of vodka, in the 6‐hour period. Samples of resting whole saliva were collected 12 hours before, then 36 and 108 hours after, the alcohol consumption. The levels of total protein, immunoglobulin A, lysozyme and lactoferrin as well as peroxidase activity were determined in saliva. Results: At 36 hours after alcohol consumption, salivary protein and lysozyme concentrations as well as peroxidase activity were significantly decreased (p = 0.002, p = 0.043, and p = 0.003, respectively), in comparison to the values obtained at 12 hours before drinking. Between 36 and 108 hours after alcohol consumption, the salivary protein and lysozyme concentrations, as well as peroxidase activity showed a tendency to increase, although at 108 hours after the drinking session, the concentration of protein and peroxidase activity were still significantly lower than before drinking. There was no significant change in the level of lactoferrin, after the drinking session. The salivary concentration of IgA tended to increase at 36 hours after alcohol consumption, and at 108 hours it was significantly higher (p = 0.028), when compared to IgA concentration in the saliva collected before drinking (from 8% to 26% and 32% of total protein content, respectively). Conclusion: Our report is the first to show that acute ingestion of relatively large, yet tolerable dose of alcohol, significantly disturbs salivary antimicrobial defense system. Reduced lysozyme level and decreased peroxidase activity may contribute to increased susceptibility to infections, when acute alcohol intake coincides with exposure to pathogens.     

布地奈德联合特异性免疫治疗对支气管哮喘患儿1，25-二羟维生素D3及IL-6、IL-10水平的影响

目的探究布地奈德联合特异性免疫治疗对支气管哮喘患儿1,25-二羟维生素D3及白介素6(interleukin-6, IL-6)、白介素10(interleukin-10, IL-10)水平的影响。 方法选取我院2017年6月至2019年6月73例支气管哮喘患儿作为研究对象,分为观察组38例和对照组35例。对照组给予布地奈德治疗,观察组则再联合舌下含服粉尘螨滴剂行特异性免疫治疗。比较治疗前后两组患儿哮喘症状评分、肺功能和血清1,25-二羟维生素D3及IL-6、IL-10水平。 结果治疗1年、2年后,两组患者哮喘症状及ACT评分均有下降,且观察组患者哮喘症状及ACT评分分别为(0.95±0.46、0.46±0.38)分和(1.14±0.51、0.74±0.42)分,差异均有统计学意义(P<0.05)。观察组患者肺功能观察组患者第1 s用力呼气量(forced expiratory volume in 1 s, FEV₁)、用力肺活量(forced vital capacity, FVC)、FEV₁%预计值、FVC%预计值及FEV₁/FVC和对照组比较均明显上升(P<0.05)。治疗后,两组患儿血清IgE、IL-6水平下降,1,25-二羟维生素D3和IL-10水平明显升高,且观察组上述指标均明显优于对照组(P<0.05)。 结论特异性免疫疗法联合布地奈德治疗儿童支气管哮喘可有效增加患儿血清1,25-二羟维生素D3和IL-10水平,减少IgE及IL-6,改善机体组织过敏原的免疫耐受能力,同时还能显著改善哮喘症状及肺功能,具有良好的临床疗效。     

卡介苗对急性哮喘发作者Th1/Th2及气道炎症的影响及降低住院率作用的研究

目的 探讨卡介苗对急性哮喘发作者 Th1/Th2及气道炎症的影响及降低住院率的作用.方法 选取98例急性哮喘患者,随机分为观察组与对照组,每组49例.对照组采取常规支气管舒张剂解痉平喘治疗,观察组在对照组基础上口服卡介苗.比较2组治疗前后的哮喘症状评分、肺功能指标、IL-4、干扰素γ(IFN-γ)水平、外周血Th1/Th2细胞比、不良反应总发生率及随访1年期间的再住院情况.结果 观察组治疗后的哮喘症状评分为 (1.61±0.36)分,低于对照组 (t=17.961, P<0.05);FEV1%pred与最大呼气流速占预计值百分比 (PEV%pred)分别为 (71.56±9.44)%、(79.41±5.12)%,高于对照组 (t=8.062、13.599,P值均<0.05).观察组治疗后的IL-4为 (21.22± 3.41)ng/L,低于对照组 (t=9.567,P<0.05);IFN-γ为 (154.36±9.67)ng/L,高于对照组 (t=22.041,P<0.05).观察组治疗后的 Th1、Th1/Th2分别为 (17.62±3.77)%、(3.78±0.64),高于对照组 (t=4.634、14.058,P值均<0.05);Th2为 (4.66±1.11)%,低于对照组 (t=10.637,P<0.05).2组不良反应总发生率为12.24%、10.20%,差异无统计学意义 (χ2=0.102,P >0.05).观察组急性加重再住院率为14.28%,低于对照组的33.33% (χ2=4.863,P <0.05);平均发作次数[(1.21±0.08)次]少于对照组 [(1.41±0.12)次](t=9.193,P<0.05).结论 口服卡介苗治疗急性哮喘可有效纠正Th1/Th2失衡、抑制气道炎症反应,缓解患者症状,且可减少发作、降低住院率,操作简便、安全性高.     

血必净对急性胰腺炎患者血清炎症因子及氧自由基的影响

目的探讨血必净治疗急性胰腺炎的疗效及其对患者血清炎症因子和氧自由基的影响。方法将118例急性胰腺炎患者随机分为血必净治疗组及对照组,治疗组在对照组治疗基础上加用血必净。记录患者腹痛、腹胀缓解时间及住院天数,检测两组患者入院第l天、第7天血清C反应蛋白（CRP）、白介素-6（IL-6）、肿瘤坏死因子-α（TNF—α）、丙二醛（MDA）、超氧化物歧化酶（SOD）水平,并进行比较。结果血必净治疗组患者腹痛、腹胀缓解时间及住院天数均显著低于对照组（P〈0．01）,入院治疗第7天血清CRP、IL-6、TNF-α、MDA水平低于对照组（P〈0．05）,SOD水平显著高于对照组（P〈0．01）。结论血必净可有效降低急性胰腺炎患者血清炎症因子水平,清除氧自由基,改善临床症状,缩短住院时间。     

The effects of vitamin D3 supplementation on some metabolic and inflammatory markers in diabetic nephropathy patients with marginal status of vitamin D: A randomized double blind placebo controlled clinical trial

AimsDiabetic nephropathy is known to be an independent risk factor in the progression of renal and cardiovascular disorders. Due to the association between vitamin D deficiency and diabetic nephropathy, vitamin D deficiency in the diabetic nephropathy population, this study conducted to examine the effects of Vitamin D₃ on metabolic and inflammatory parameters in patients with diabetic nephropathy.MethodsThis eight-week, randomized, double-blind, placebo-controlled trial was carried out on 50 diabetic nephropathy patients with marginal status of vitamin D. Participants were randomly assigned to two groups: control and intervention. Participants received a vitamin D3 (50000 IU) supplement weekly on a specific day. Fasting blood samples were collected from all patients at their entry to the study, and eight weeks after intervention.ResultsAnalyses showed significance differences in physical activity between the intervention and placebo groups (P = 0.018). There were no significant differences between the percentage changes of HbA1c, insulin and, inflammatory parameters such as TNF-α and IL-6 (P > 0.05), while the percentage change of FBS was significantly higher in the placebo group compared to the treatment one (P < 0.0001). Lower levels of FBS (P < 0.0001), insulin (P < 0.069), HOMA-IR (P < 0.001), TNF-α (P< 0.002) and IL-6 (P < 0.037) were found after supplementation in treatment group. However, the phosphorous and protein percentage change in urine were lower (P = 0.07) and higher (P = 0.003) between groups.ConclusionsIt was found that vitamin D supplementation can be regarded as an effective way to prevent the progression of diabetic nephropathy by reducing levels of proteinuria, and inflammatory markers such as TNF-α and IL-6.     

Moderating effect of gender on the prospective relation of physical activity with psychosocial outcomes and asthma control in adolescents: a longitudinal study

Objective: Adolescents with asthma experience more psychosocial and physiological problems compared to their healthy peers. Physical activity (PA) might decrease these problems. This study was the first observational longitudinal study to examine whether habitual PA could predict changes in psychosocial outcomes (i.e. symptoms of anxiety and depression, quality of life [QOL] and stress) and asthma control over time in adolescents with asthma and whether gender moderated these relationships. Methods: Adolescents with asthma (N?=?253; aged 10–14 years at baseline) were visited at home in the spring/summer of 2012 and 2013. They completed questionnaires assessing their habitual PA, symptoms of anxiety and depression, QOL, perceived stress and asthma control. Path analyses using Mplus were conducted to examine longitudinal relationships among habitual PA, psychosocial outcomes and asthma control (controlled for body mass index, age and gender). Using multi-group analyses, we examined whether gender moderated these relationships. Results: Path analyses in the total group showed that habitual PA did not predict changes in psychosocial outcomes or asthma control over time. Multi-group analyses showed that gender moderated the relation of habitual PA with anxiety and depression. Habitual PA only significantly predicted a decrease in anxiety and depression over time for girls but not for boys. Conclusions: Increasing habitual PA in girls with asthma might decrease their symptoms of anxiety and depression.     

The second Euro Heart Survey on acute coronary syndromes: Characteristics, treatment, and outcome of patients with ACS in Europe and the Mediterranean Basin in 2004.

AIMS: Our study aimed to examine the management of acute coronary syndromes (ACS) in Europe and the Mediterranean basin, and to compare adherence to guidelines with that reported in the first Euro Heart Survey on ACS (EHS-ACS-I), 4 years earlier. METHODS AND RESULTS: In a prospective survey conducted in 2004 (EHS-ACS-II), data describing the characteristics, treatment, and outcome of 6385 patients diagnosed with ACS in 190 medical centres in 32 countries were collected. ACS with ST-elevation was the initial diagnosis in 47% of patients, no ST-elevation in 48%, and undetermined electrocardiographic pattern in 5% of patients. Comparison of data collected in 2000 and 2004 showed similar baseline characteristics, but greater use of recommended medications and coronary interventions in EHS-ACS-II. Among patients with ST-elevation, the use of primary reperfusion increased slightly (from 56 to 64%), with a significant shift from fibrinolytic therapy to primary percutaneous coronary intervention (PPCI). The use of PPCI rose from 37 to 59% among those undergoing primary reperfusion therapy. Analysis of data in 34 centres that participated in both surveys showed even greater improvement with respect to the use of recommended medical therapy, interventions, and outcome. CONCLUSION: Data from EHS-ACS-II suggest an increase in adherence to guidelines for treatment of ACS in comparison with EHS-ACS-I.     

Low-dose l-isoproterenol versus salbutamol in hospitalized pediatric patients with severe acute exacerbation of asthma: A double-blind,randomized controlled trial

BackgroundAlthough the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial.MethodsHospitalized patients aged 1–17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 μg/kg/h) or salbutamol (500 μg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991.ResultsFrom December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were −2.9 (2.5) in the l-isoproterenol group and −0.9 (2.3) in the salbutamol group (difference −2.0, 95% confidence interval −3.1 to −0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group.ConclusionsLow-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.     

Effect of nitric oxide synthase inhibition on haemodynamics and outcome of patients with persistent cardiogenic shock complicating acute myocardial infarction: a phase II dose-ranging study.

AIMS: Previous studies suggested haemodynamic benefits and, possibly, mortality reduction with the use of nitric oxide synthase (NOS) inhibition in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). We assessed preliminary efficacy and safety of four doses of l-n-monomethyl-arginine (l-NMMA), a non-selective NOS inhibitor, in patients with AMI complicated by CS despite an open infarct-related artery. METHODS AND RESULTS: Patients (n = 79) were randomly assigned to a bolus and 5 h infusion of placebo or 0.15, 0.5, 1.0, or 1.5 mg/kg of l-NMMA. The primary outcome measure was absolute change in mean arterial pressure (MAP) at 2 h. Fifteen minutes after study drug initiation, mean change in MAP was -4.0 mmHg in the placebo group and 5.8 (P = 0.02), 4.8 (P = 0.02), 5.1 (P = 0.07), and 11.6 (P < 0.001) mmHg in the four l-NMMA groups, respectively (all vs. placebo). Mean change in MAP at 2 h was -0.4, 4.4, 1.8, -4.1, and 6.8 mmHg in the placebo and four l-NMMA groups, respectively (all P = NS). CONCLUSION: l-NMMA resulted in modest increases in MAP at 15 min compared with placebo but there were no differences at 2 h.     

Prognostic impact of KMT2E transcript levels on outcome of patients with acute promyelocytic leukaemia treated with all‐trans retinoic acid and anthracycline‐based chemotherapy: an International Consortium on Acute Promyelocytic Leukaemia study

The KMT2E (MLL5) gene encodes a histone methyltransferase implicated in the positive control of genes related to haematopoiesis. Its close relationship with retinoic acid–induced granulopoiesis suggests that the deregulated expression of KMT2E might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of KMT2E expression on the prognosis of 121 APL patients treated with ATRA and anthracycline‐based chemotherapy. Univariate analysis showed that complete remission (P = 0·006), 2‐year overall survival (OS) (P = 0·005) and 2‐year disease‐free survival (DFS) rates (P = 0·037) were significantly lower in patients with low KMT2E expression; additionally, the 2‐year cumulative incidence of relapse was higher in patients with low KMT2E expression (P = 0·04). Multivariate analysis revealed that low KMT2E expression was independently associated with lower remission rate (odds ratio [OR]: 7·18, 95% confidence interval [CI]: 1·71–30·1; P = 0·007) and shorter OS (hazard ratio [HR]: 0·27, 95% CI: 0·08–0·87; P = 0·029). Evaluated as a continuous variable, KMT2E expression retained association with poor remission rate (OR: 10·3, 95% CI: 2·49–43·2; P = 0·001) and shorter survival (HR: 0·17, 95% IC: 0·05–0·53; P = 0·002), while the association with DFS was of marginal significance (HR: 1·01; 95% CI: 0·99–1·02; P = 0·06). In summary, low KMT2E expression may predict poor outcome in APL patients.     

Effect of one-anastomosis gastric bypass on cardiovascular risk factors in patients with vitamin D deficiency and morbid obesity: A secondary analysis

Background and aimsBariatric patients often suffer from vitamin D (VD) deficiency, and both, morbid obesity and VD deficiency, are related to an adverse effect on cardiovascular disease (CVD) risk. Therefore, we assessed the change of known CVD risk factors and its associations during the first 12 months following one-anastomosis gastric bypass (OAGB).Methods and resultsIn this secondary analysis, CVD risk factors, medical history and anthropometric data were assessed in fifty VD deficient (25-hydroxy-vitamin D (25(OH)D) <75 nmol/l) patients, recruited for a randomized controlled trial of VD supplementation. Based on previous results regarding bone-mass loss and the association between VD and CVD risk, the study population was divided into patients with 25(OH)D ≥50 nmol/l (adequate VD group; AVD) and into those <50 nmol/l (inadequate VD group; IVD) at 6 and 12 months (T6/12) postoperatively. In the whole cohort, substantial remission rates for hypertension (38%), diabetes (30%), and dyslipidaemia (41%) and a significant reduction in CVD risk factors were observed at T12. Changes of insulin resistance markers were associated with changes of total body fat mass (TBF%), 25(OH)D, and ferritin. Moreover, significant differences in insulin resistance markers between AVD and IVD became evident at T12.ConclusionThese findings show that OAGB leads to a significant reduction in CVD risk factors and amelioration of insulin resistance markers, which might be connected to reduced TBF%, change in 25(OH)D and ferritin levels, as an indicator for subclinical inflammation, and an adequate VD status.Registered at clinicaltrials.gov(Identifier: NCT02092376) and EudraCT (Identifier: 2013-003546-16).