Effects of montelukast treatment and withdrawal on fractional exhaled nitric oxide and lung function in children with asthma

BACKGROUND: Leukotriene receptor antagonists (LTRAs) reduce fractional exhaled nitric oxide (Feno) concentrations in children with asthma, but the effect of LTRA withdrawal on Feno and lung function is unknown. We aimed to study the effect of treatment and withdrawal of montelukast, a LTRA, on airway inflammation as reflected by Feno and lung function in children with asthma. METHODS: A double-blind, randomized, placebo controlled, parallel group study was undertaken in 14 atopic children with mild persistent asthma who were treated with oral montelukast (5 mg/d for 4 weeks) and 12 atopic children with mild persistent asthma who received matching placebo. A follow-up visit was performed 2 weeks after montelukast or placebo withdrawal. RESULTS: Montelukast reduced Feno concentrations by 17% (p = 0.067), an effect that was more pronounced (35%) [p = 0.0029] when children with seasonal atopy who were exposed to relevant allergens during the treatment phase were excluded from analysis (n = 3). Compared to those at the end of treatment, Feno concentrations were increased 2 weeks after montelukast withdrawal (p = 0.023) concomitant with a reduction in absolute FEV(1) values (p = 0.011), FEV(1) percentage of predicted values (p = 0.006), FEV(1)/FVC ratio (p = 0.002), and forced expiratory flow at 25% to 75% of FVC values (p = 0.021). These changes were not observed in the placebo group. CONCLUSIONS: LTRAs reduce Feno concentrations in children with asthma, and withdrawal can result in increased Feno values and worsening of lung function in children with asthma.     

The effect of montelukast on exhaled nitric oxide and lung function in asthmatic children 2 to 5 years old

OBJECTIVE: The study was undertaken to investigate the influence of once-daily treatment with montelukast (Singulair; MSD; Glattbrugg, Switzerland) on levels of exhaled nitric oxide (eNO) and lung function in preschool children with asthma. METHODS: A total of 30 children (19 girls), 2 to 5 years of age, in whom asthma had been newly diagnosed, who had a positive first-degree family history of asthma and a positive allergy test result, were allocated to undergo a 1-week run-in period of montelukast treatment. eNO and airway resistance were measured in all patients before (visit 1) and after the run-in period (visit 2), and after treatment with montelukast (4 mg once daily) for 4 weeks (visit 3). RESULTS: There were no significant differences in all parameters before and after the run-in period. However, the mean (SD) levels of eNO and the mean (SD) levels of airway resistance after treatment at visit 3 were 11.6 parts per billion (ppb) [9.5 ppb] and 1.15 kPa/L/s (0.26 kPa/L/s), respectively, and were significantly lower compared to values of 33.1 ppb (12.0 ppb) and 1.28 kPa/L/s (0.23 kPa/L/s), respectively, before treatment (p < 0.001) and at visit 2 (p = 0.01). There was no significant change in mean bronchodilator responsiveness between visit 3 (13.2%; SD, 6.8%) and visit 1/visit 2 (13.3%; SD, 7.0%; p = 0.47). CONCLUSION: We have shown that montelukast has a positive effect on lung function and airway inflammation as measured by nitric oxide level in preschool children with allergic asthma.     

Formoterol, montelukast, and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide

BACKGROUND: It has been proposed that asthma control may be achieved in part by minimizing airway inflammation. The simultaneous effects of inhaled steroids associated with long-acting beta-agonists and leukotriene antagonists on pulmonary function and airway inflammation are still largely unexplored in children with moderate persistent asthma. OBJECTIVES: The aim of this study was to investigate the effects of add-on therapy with long-acting beta-agonists and leukotriene antagonists on FEV1 and exhaled nitric oxide levels (FENO) in children. METHODS: Forty-eight steroid-na?ve atopic asthmatic children, 7-11 years of age, were randomly treated in four groups for two consecutive one-month periods, as follows: (1) first month: budesonide 200 microg twice daily; second month: budesonide 400 microg twice daily; (2) first month: budesonide 200 microg twice daily+formoterol 9 microg twice daily; second month: budesonide 200 microg twice daily+montelukast 5mg once daily; (3) first month: budesonide 200 microg twice daily+montelukast 5mg once daily; second month budesonide 200 microg+formoterol 9 microg twice daily; (4) first and second month: budesonide 400 microg twice daily. RESULTS: All treatments resulted in a significant increase in lung function and a decrease in FENO compared with values at baseline. Budesonide+montelukast in combination was the most effective treatment for reducing FENO levels. CONCLUSION: This study demonstrates that add-on therapy with montelukast plus low-dose budesonide is more effective than the addition of long-acting beta-agonists or doubling the dose of budesonide for controlling FENO in asthmatic children.     

Relationship between exhaled air temperature and exhaled nitric oxide in childhood asthma.

Airway inflammation is a characteristic of asthma. Exhaled nitric oxide (eNO) has been demonstrated to be related to actual levels of airway inflammation in asthmatic patients. The purpose of this study was to investigate whether the temperature of exhaled air is related to eNO levels. Temperature of exhaled air and eNO were measured in 52 asthmatic children with a cross-sectional design. A significant relationship was demonstrated between eNO and temperature of peak and plateau exhaled air temperature. The relationship between both the peak and the plateau values and eNO was more evident when it was corrected for environmental temperature. These results suggest a relationship between exhaled nitric oxide and the temperature of exhaled air in asthmatic patients not treated with systemic steroids.     

呼出气一氧化氮在支气管哮喘中的变化及与肺功能的相关性

目的 探讨呼出气一氧化氮(FENO)在哮喘各期中的变化及与肺功能的关系.方法 对急性发作期、慢性持续期、临床缓解期共计54例哮喘患者及19例健康人进行FENO、第1秒用力呼气量( FEV1)检测.结果 FENO、FEV1在哮喘急性发作期[(57.59±32.24)ppb和(1.72±0.33)L]、慢性持续期[(40.02±15.68)ppb和(2.41±0.23)L]、缓解期[(26.71±6.07)ppb和(2.82±0.29)L]及对照组[(14.74±3.42)ppb和(2.93±0.13)L]之间比较,除FEV1在缓解期与对照组比较差异无统计学意义(P＞0.05)外,差异均有统计学意义(F=19.555,163.096,P＜0.01).急性发作期FENO与FEV1之间存在负相关(r=-0.666,P=0.005),慢性持续期(r=-0.288,P=0.176)及缓解期(r=-0.246,P=0.457)的FENO与FEV1无相关性.结论 支气管哮喘患者FENO值增高,可用于评估哮喘的控制程度.     

Lung function and exhaled nitric oxide levels in infants developing chronic lung disease

Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To determine whether the results of serial exhaled nitric oxide (eNO) measurements during the perinatal period differed between infants who did and did not develop CLD. In addition, we wished to assess whether eNO results were more predictive of CLD development than lung function test results or readily available clinical data (gestational age and birthweight). The patients were 24 infants with a median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels, functional residual capacity (FRC), and compliance of the respiratory system (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12 infants who developed CLD were of significantly lower birthweight and gestational age than the rest of the cohort; in addition, they had lower median FRC (P < 0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week after birth. Construction of receiver operator characteristic (ROC) curves demonstrated that the CRS and FRC results on Day 3 were the best predictors of CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively. Early lung function test results, but not eNO levels, are useful in predicting CLD development, but are not significantly better than birthweight.     

Alterations of exhaled nitric oxide in pre-term infants with chronic lung disease.

Animal models suggest that reduced nitric oxide (NO) synthase activity results in lower values of exhaled NO (eNO) present at birth in those individuals who are going to develop chronic lung disease of infancy (CLDI). Online tidal eNO was measured in 39 unsedated pre-term infants with CLDI (mean gestational age (GA) 27.3 weeks) in comparison with 23 healthy pre-term (31.6 weeks) and 127 term infants (39.9 weeks) at 44 weeks post-conceptional age, thus after the main inflammatory response. NO output (NO output (V'(NO)) = eNO x flow) was calculated to account for tidal- flow-related changes. Sex, maternal atopic disease and environmental factors (smoking, caffeine) were controlled for. The mean eNO was not different (14.9 ppb in all groups) but V'(NO) was lower in CLDI compared with healthy term infants (0.52 versus 0.63 nL x s(-1)). Values for healthy pre-term infants were between these two groups (0.58 nL x s(-1)). Within all pre-term infants (n = 62), V'(NO) was reduced in infants with low GA, high clinical risk index for babies scores and longer duration of oxygen therapy but not associated with post-natal factors, such as ventilation or corticosteroid treatment. After accounting for flow, the lower nitric oxide output in premature infants with chronic lung disease of infancy is consistent with the hypothesis of nitric oxide metabolism being involved in chronic lung disease of infancy.     

呼出气一氧化氮在哮喘诊断中的价值及与肺功能相关性

目的 阐明呼出气一氧化氮（eNO）在不同呼吸系疾病的诊断价值及哮喘患者中eNO与不同肺功能结果的相关性.方法 呼吸系疾病患者共398人,同时检测eNO值、FEV1%预计值、支气管舒张试验.结果 哮喘eNO值明显高于其他呼吸系疾病eNO值.哮喘患者中支气管舒张试验阳性组eNO≥50 ppb占53.8%;支气管舒张试验阴性组eNO＜50 ppb占63.4%.按肺功能严重度分组,各组间eNO值无明显差异.结论 eNO是诊断哮喘可靠的标志物之一;哮喘患者中eNO值与支气管舒张试验结果存在一定相关性,与肺功能严重度无明显关联.     

Changes of exhaled nitric oxide during steroid treatment of childhood asthma.

Exhaled nitric oxide (eNO) is elevated in several inflammatory airway diseases and is significantly reduced by anti-inflammatory treatment with inhaled steroids. The aim of this randomized, open clinical trial was to evaluate eNO in relation to conventional lung function parameters at rest and after exercise during sequential changes of inhaled steroids in children with persistent asthma. The study consisted of a 4 week run-in period, a 4 week washout phase and a randomized treatment period during which only one group was treated again with inhaled budesonide. After run-in, eNO was reduced to normal values, and rose again during washout. In the patients randomized to steroid treatment, eNO was again decreased, whereas it remained unchanged in the untreated patients. Forced expiratory volume in one second and forced vital capacity at rest and after exercise improved significantly after run-in, but showed no difference after randomization. However there was a strong correlation of eNO with patient compliance. Exhaled nitric oxide was able to differentiate between children briefly treated with or without steroids, the conventional lung-function variables however could not. In practice exhaled nitric oxide may thus be a valuable parameter to monitor adherence to steroids, but less suitable to describe physiologically relevant impairments of lung function.     

喘息婴幼儿潮气肺功能、呼出气一氧化氮及过敏原研究

目的:研究喘息婴幼儿潮气肺功能和呼出气一氧化氮(FeNO)的变化,着重探讨过敏体质在其中的潜在作用。方法:纳入成都市妇女儿童中心医院呼吸科2018年2月至2019年1月收治的急性下呼吸道感染婴幼儿285例,回顾性分析患儿的一般资料,喘息的危险因素,喘息与潮气肺功能及FeNO的关系,并通过亚组分析探究过敏因素在其中的作用...     

哮喘急性发作FeNO与外周血嗜酸粒细胞及肺功能的相关性研究

目的探讨支气管哮喘急性发作期患者呼出气一氧化氮(FeNO)水平与疾病急性发作严重程度的相关性。方法选取我院86例门诊或住院哮喘急性发作期患者作为研究对象,并分为轻度组、中度组及重度组,采用瑞典奈尔斯(NIOX)一氧化氮测定仪检测FeNO数值,并选取同期34例健康体检者为对照组,所有研究对象均行外周血Eos计数、肺功能检测及呼出气一氧化氮水平检测,统计并分析相关数据。结果哮喘组(轻度组、中度组、重度组)与对照组FeNO测量值、外周血Eos计数、肺功能各项指标均存在明显差异,差异具有统计学意义(P0.05),随哮喘急性发作的严重程度增加,FeNO值明显增加,轻度组、中度组与重度组间差异具有显著性(P0.05);FeNO水平与外周血Eos均呈正相关(r=0.612,P0.05),但与肺功能各指标均无明显相关性。结论 FeNO可作为哮喘急性发作的评测指标,根据FeNO值的高低,可以一定程度评价哮喘发作的严重度。     

支气管哮喘患者呼出气一氧化氮、肺功能、ACQ7评分之间的相关性研究

目的 探讨呼出气一氧化氮(FeNO)、肺通气功能及支气管哮喘(简称哮喘)控制水平的相关关系,寻找适用于哮喘患者的气道炎症监测及管理的方法.方法 按GINA 2008标准入选我院门诊2010年3月至2011年6月就诊65例确诊为哮喘的患者 进行FeNO测定 同时测定肺功能 记录第1秒用力呼气容积(FEV1)、第1秒用力呼...     

支气管哮喘患者呼出气一氧化氮、肺功能、ACQ7评分之间的相关性研究

目的探讨呼出气一氧化氮(FeNO)、肺通气功能及支气管哮喘(简称哮喘)控制水平的相关关系,寻找适用于哮喘患者的气道炎症监测及管理的方法。方法按GINA2008标准入选我院门诊2010年3月至2011年6月就诊65例确诊为哮喘的患者,进行FeNO测定,同时测定肺功能,记录第1秒用力呼气容积(FEV1)、第1秒用力呼气容积占预计值百分比(FEV1%pred)、用力肺活量(FVC)、FEV1/FVC、呼气峰流速(PEF)、FEF25/75、FEF25/75%等指标,行诱导痰检测,记数嗜酸粒细胞的比率(EOS%)。进行哮喘控制问卷(ACQ7)及哮喘控制测试(ACT)调查表的填写。结果经多元逐步回归分析,FeNO的值主要受到年龄、FEF25/75、FEF25/75%、日间症状的影响,与体质量指数、过敏等因素无显著相关关系,与FEV1、FEV1%pred、ACQ7评分、ACT评分等亦无显著相关(P0.05),FeNO与诱导痰EOS%呈显著正相关(r=0.327,P=0.022)。ACQ7与FEV1、FEV1%pred呈显著负相关(分别是r=-0.491,P=0.000,r=-0.469,P=0.012)。结论 FeNO能够客观反映气道EOS炎症水平,年龄越小、日间症状越明显、小气道阻力越高,FeNO水平越高。结合肺功能指标和FeNO更能全面反映哮喘疾病现况及控制水平。     

The clinical significance of exhaled nitric oxide in asthma

Asthma is an inflammatory disease of the airways, for which many therapeutic options are available. Guidelines for the management of asthma suggest a stepwise approach to pharmacotherapy based on assessment of asthma severity and control. However, the assessment of asthma control presently relies on surrogate measures, such as the frequency of symptoms or the frequency of use of short-acting beta₂-adrenergic agonists. There is no simple, noninvasive technique for the assessment of severity of actual airway inflammation in asthma. The collection and analysis of nitric oxide (NO) levels in exhaled breath has recently become feasible in humans. Based on increased exhaled NO (eNO) levels in patients with asthma, eNO analysis has been proposed as a novel, noninvasive approach to the assessment and monitoring of airway inflammation, and as a basis for adjustments in asthma therapy. In the present paper, the relationship of elevated eNO levels in asthma with inflammatory, physiological and clinical markers of asthma in adults was reviewed. Use of eNO is a promising tool for diagnosing asthma, for monitoring asthma control and for guiding optimal anti-inflammatory asthma therapy. However, because of many unresolved questions, eNO cannot be recommended at present for routine clinical management of adults with asthma.     

老年支气管哮喘患者FeNO与肺功能的相关性

目的探讨老年支气管哮喘患者呼出气一氧化氮(Fe NO)水平与肺功能的相关性。方法对68例老年哮喘患者给予吸入舒利迭和异丙托溴铵喷雾剂,疗程为1个月。比较50例健康体检者及哮喘患者治疗前、治疗后Fe NO、肺功能变化,采用哮喘控制测试(ACT)评分评价其疗效。结果与对照组比较,哮喘组治疗前Fe NO、Eos、N水平明显升高,各肺功能指标明显下降(P0.05);治疗后,各指标均明显改善(P0.05),PEF、FEV1、Eos、N基本恢复至对照组水平(P0.05);治疗后完全控制组、部分控制组各项指标均优于未控制组,完全控制组Fe NO、Eos、N水平均明显低于部分控制组(P0.05);治疗前,哮喘组患者Fe NO水平与Eos、N呈正相关(P0.05),与肺功能指标呈负相关(P0.05),但治疗后,Fe NO水平与Eos、N呈正相关(P0.05)。结论 Fe NO水平在哮喘患者中明显升高,结合肺功能检查,有助于提高老年哮喘的诊断及治疗水平。