呼出气一氧化氮联合相关因素对咳嗽变异性哮喘的诊断价值评价

目的 :评价呼出气一氧化氮(Fe NO)检测单独或联合咳嗽变异性哮喘(cough variant asthma,CVA)相关因素对诊断CVA的有效性和准确性。方法:连续纳入2010年8月至2011年10月本院呼吸科门诊因慢性咳嗽行支气管激发试验检查的患者297例,记录病史并测定呼出气Fe NO水平,以支气管激发试验阳性作为CVA诊断的金标准,绘制ROC曲线,探讨诊断CVA的Fe NO临界点。建立Logisitic回归模型,通过分析筛选与CVA相关的因素,根据ROC曲线评价Fe NO联合其他相关因素对CVA的诊断价值。结果:145例患者支气管激发试验阳性并排除其他疾病被诊断为CVA(哮喘组),152例支气管激发试验阴性患者诊断为非哮喘的慢性咳嗽(非哮喘组)。1哮喘组患者Fe NO水平明显高于非哮喘组[(45.33±38.86)ppb比(26.28±23.86)ppb,P     

呼出气一氧化氮对哮喘的诊断作用及与过敏原sIgE的关系

目的探讨呼出气一氧化氮(FeNO)对哮喘的诊断作用及与过敏原特异性IgE抗体(sIgE)的关系。方法选取2017年8月至2019年8月收治的98例疑似哮喘患儿进行观察,收集所有患儿的临床特征指标,检测肺功能及FeNO浓度,分析FeNO对哮喘的诊断作用及其与过敏原sIgE的关系。结果哮喘组的FeNO水平高于非哮喘组(P<0.05)。血清过敏原sIgE阳性患儿的Fe NO水平高于阴性患儿(P<0.05)。经Pearson相关性分析得出,FeNO水平与血清过敏原sIgE、血清总IgE和血清过敏原种类呈显著正相关(r=0.703、0.624、0.719,P<0.05)。结论FeNO在哮喘中具有一定的诊断价值,与过敏原sIgE存在显著的相关性,可为临床诊断与治疗哮喘提供有利参考依据。     

Low‐intensity ultrasound increases endothelial cell nitric oxide synthase activity and nitric oxide synthesis

Summary. Low‐intensity ultrasound (US) increases tissue perfusion in ischemic muscle through a nitric oxide (NO)‐dependent mechanism. We have developed a model to expose endothelial cells to well‐characterized acoustic fields in vitro and investigate the physical and biological mechanisms involved. Human umbilical vein endothelial cells (HUVEC) or bovine aortic endothelial cells (BAEC) were grown in tissue culture plates suspended in a temperature‐controlled water bath and exposed to US. Exposure to 27 kHz continuous wave US at 0.25 W cm^?2 for 10 min increased HUVEC media NO by 102 ± 19% (P < 0.05) and BAEC by 117 ± 23% (P < 0.01). Endothelial cell NO synthase activity increased by 27 ± 24% in HUVEC and by 32 ± 16% in BAEC (P < 0.05 for each). The cell response was rapid with a significant increase in NO synthesis by 10 s and a maximum increase after exposure for 1 min. By 30 min post‐exposure NO synthesis declined to baseline, indicating that the response was transient. Unexpectedly, pulsing at a 10% duty cycle resulted in a 46% increase in NO synthesis over the response seen with continuous wave US, resulting in an increase of 147 ± 18%. Cells responded to very low intensity US, with a significant increase at 0.075 W cm^?2 (P < 0.01) and a maximum response at 0.125 W cm^?2. US caused minor reversible changes in cell morphology but did not alter proliferative capacity, indicating absence of injury. We conclude that exposure of endothelial cells to low‐intensity, low‐frequency US increases NO synthase activity and NO production, which could be used to induce vasodilatation experimentally or therapeutically.     

Plasma nitric oxide metabolite in women with primary Raynaud's phenomenon and in healthy subjects

Primary Raynaud's phenomenon (PRP) is characterized by cold- or stressinduced transient attacks of impaired skin circulation in fingers and/or toes. PRP displays seasonal variation with less severe symptoms in the summer. The aetiology has not been clarified. The aims of the present study were (a) to assess the influence of cold exposure on the plasma levels of the nitric oxide (NO) metabolite, nitrate, in patients with PRP and in healthy control subjects; and (b) to investigate whether there is a seasonal variation in these plasma levels. In a group of women with PRP and matched control subjects, venous blood was sampled before and at the end of a 40-min period of whole-body cooling. The study was performed with the same protocol on two occasions; once in the winter and once in the summer. A seasonal variation was detected with higher plasma levels of nitrate in the winter than in the summer, both in PRP and in control subjects. However, the plasma level of nitrate was not changed in response to cold exposure on any occasion, either in the patient or in the control group. Our study indicates that NO formation is up-regulated in response to cold weather in both study groups. However, NO formation does not seem to be increased in response to wholebody cooling, either in PRP patients or in healthy subjects. Further investigations are required to reveal whether the observed seasonal variation in NO formation is a universal phenomenon in man.     

A novel anti-ischemic nitric oxide donor (LA419) reduces thrombogenesis in healthy human subjects

BACKGROUND: Platelet and endothelial production of nitric oxide (NO) is known to be impaired in coronary artery disease patients. Compounds that release NO (e.g. nitrates) have antiplatelet effects, but at supratherapeutic doses with hypotensive side effects. OBJECTIVES: To investigate the antithrombotic effect on human blood of a novel NO donor (LA419) with known anti-ischemic properties but without hypotensive side effects and to compare with abciximab. PATIENTS/METHODS: Healthy subjects (n = 8; 32 +/- 3 years) received daily aspirin starting three days prior to the study day. Treatments (LA419 10 and 20 microm, and abciximab 4 microm) were added ex vivo to non-anticoagulated blood, and the antithrombotic properties were assessed by measuring changes in thrombus size from pretreatment baseline in the Badimon perfusion chamber at low and high shear rates. Platelet surface adhesion using a Cone and Platelet Analyzer (CPA) and platelet fibrinogen-receptor activation with flow cytometry were also evaluated. RESULTS: At low shear rates, LA419 displayed a reduction in thrombus area of 43% +/- 8% (10 microm) and 56% +/- 6% (20 microm), whereas at high shear rates the reductions were 44% +/- 3% (10 microm) and 62% +/- 6% (20 microm). Platelet surface adhesion with the CPA was also reduced. Abciximab exhibited a strong inhibitory effect on thrombus formation, platelet surface adhesion and fibrinogen receptor activation. CONCLUSIONS: The novel NO donor, LA419, shows a strong antithrombotic effect in human blood, which is comparable to abciximab, especially under high shear rate conditions. Our observations suggest that the availability of an NO donor could prove beneficial in the prevention of thrombotic complications of cardiovascular disease. Further clinical studies are warranted.     

肺泡气一氧化氮在初始治疗前低FeNO哮喘患者治疗中的价值

目的 探讨初始治疗前低呼出气一氧化氮(FeNO)哮喘患者中,肺泡气一氧化氮(CaNO)水平升高能否作为吸入糖皮质激素/长效β2受体激动剂(ICS+LABA)治疗获益的预测因子.方法 收集该院呼吸与危重症医学科就诊的具有哮喘临床特征、舒张试验阳性且FeNO≤50 ppb的患者60例作为研究对象,依据CaNO水平是否升高分...     

呼出气一氧化氮对呼吸机相关性肺炎的早期诊断意义

目的:探讨呼出气一氧化氮(FeNO)对呼吸机相关性肺炎(VAP)的早期诊断意义。方法:选择入住首都医科大学附属复兴医院重症医学科(ICU)需要进行有创机械通气的患者。收集患者人口学资料,第1、3、5、7天FeNO、白细胞计数(WBC)、降钙素原(PCT)及预后指标,前瞻性观察FeNO是否对VAP具有早期诊断意义。按照入ICU的主要原因分为肺内炎症组、肺外炎症组及非炎症组;将机械通气时间≥3 d的患者,根据14 d内是否发生VAP分为VAP组和非VAP组。结果:肺内炎症组患者FeNO浓度明显高于肺外炎症组及非炎症组(P0.05)。与非VAP组患者相比,VAP组患者第3天和第5天的FeNO明显升高,其对VAP的发生与否有良好的临床预测价值(第3天:AUC 0.87,P0.001,分界点6.5 ppb,敏感性76.9%,特异性81.4%;第5天:AUC 0.75,P=0.001,分界点为5.5 ppb,敏感性73.1%,特异性67.4%)。与非VAP组患者相比,VAP组患者28 d内非机械通气时间缩短(P0.05)、ICU住院时间延长(P0.05)。结论:肺炎患者FeNO明显升高,升高的FeNO对VAP有很好的临床预测价值,在临床中可以作为VAP的一项生物标志物。     

Exhaled nitric oxide concentration and amniotic fluid nitrite concentration during pregnancy

Abstract. We have assessed fetal and maternal nitric oxide (NO) production in pregnancy. Exhaled NO and amniotic fluid nitrite concentrations were measured by chemiluminescence between 10 and 42 weeks of pregnancy. Exhaled NO concentrations did not alter significantly during gestation. In contrast, there was a significant change in mean amniotic fluid nitrite concentration in late pregnancy ( P < 0.001). The finding of decreased amniotic nitrite concentrations after 37 weeks of gestation support the hypothesis that reduced NO production may contribute to increased uterine activity in late pregnancy.     

大鼠创伤性脑水肿一氧化氮及其合成酶的变化

目的：探讨脑损伤后一氧化氮（ＮＯ）及一氧化氮合酶（ＮＯＳ）与脑水肿的关系。方法：建立大鼠创伤性脑水肿模型,按不同时间点处死动物,测定其脑含水量及静脉血ＮＯ 和脑组织中ＮＯＳ。结果：脑创伤后脑含水量随静脉血ＮＯ的增加而增加,组织ＮＯＳ则随ＮＯ 的增加而下降。结论：创伤性脑水肿与血ＮＯ 有密切相关性,组织中ＮＯＳ则是该过程的可能催化剂     

Exhaled nitric oxide after inhalation of isotonic and hypotonic solutions in healthy subjects.

Airway nitric oxide (NO) homoeostasis is influenced by chemical and mechanical stimuli in humans; airway epithelium, which is an important site of NO production, is sensitive to osmotic challenge. The effect of inhaled hypotonic solutions on exhaled NO (eNO) is not known. In this study we evaluated the effect of ultrasonically nebulized distilled water (UNDW), a hypotonic indirect stimulus, on eNO levels. A total of 10 non-smoking healthy subjects were enrolled in the study. eNO was detected by chemiluminescence, and specific airway conductance (sGaw) was measured by plethysmography. Bronchial challenges with UNDW and with an isotonic solution were performed according to a double-blind experimental design. Baseline levels of eNO were 28.1+/-14.7 p.p.b. UNDW did not cause any significant change in sGaw (from 0.190+/-0.029 to 0.181+/-0.036 cm H(2)O x s(-1)). With respect to baseline values, the eNO concentration decreased significantly after inhalation of 8 or 16 ml of UNDW (from 26.0+/-13.1 to 17.2+/-8.5 and 16.6+/-7.7 p.p.b. respectively; P<0.001, n=10). After bronchial challenge with UNDW, eNO was significantly reduced in comparison with after inhalation of the isotonic solution. In five subjects, pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor NO synthesis, decreased NO levels from 21.7+/-8.5 to 10.0+/-3.3 p.p.b. Subsequent inhalation of 16 ml of UNDW did not cause any further decrease in NO levels (10.1+/-3.7 p.p.b.; not significant compared with L-NAME). We conclude that inhalation of aqueous solutions decreases eNO levels in healthy subjects, and that this effect is not associated with any significant change in airway calibre. The UNDW-induced decrease in eNO is not enhanced by pretreatment with the NO synthase inhibitor L-NAME, suggesting that inhaled solutions may interfere with the airway NO pathway in humans.     

呼出气一氧化氮测定在支气管哮喘诊断和管理中的价值

慢性气道炎症是支气管哮喘的本质。临床上急需能客观准确地反映气道炎症的炎性标志物来指导哮喘的诊断和管理,呼出气一氧化氮(FeNO)测定是一种符合临床需要的快速检测方法,现就FeNO在哮喘诊断、气道炎症监测、哮喘严重程度评级及预测哮喘发作等方面的研究进展做一综述。     

Validation study of nasal nitric oxide measurements using a hand-held electrochemical analyser

Background Exhaled nitric oxide (NO) measurement is a simple and non‐invasive method for monitoring airway inflammation. Similarly, nasal NO has been proposed as a surrogate marker in inflammatory diseases of the upper airways, e.g. allergic rhinitis. A new portable analyser using an electrochemical sensor has been developed for measurements of exhaled NO, and its reproducibility and comparison with other analysers has been tested recently in healthy subjects and in patients with lower airways disease. The application of this hand‐held analyser in nasal NO analysis was tested and compared to the gold standard represented by a chemiluminescence analyser. Materials and methods Thirty subjects including 15 patients with allergic rhinitis (AR) and 15 healthy subjects (HS) were studied. The intraindividual variability, calculated as the difference in nasal NO levels between two measurements from a single nasally exhaled breath manoeuvre, and the comparison between the electrochemical analyser (NIOX MINO, Aerocrine) and a chemiluminescence analyser (NOA, Sievers) were performed. Results In AR patients mean nasal NO was 59·0 ± 16·3 p.p.b. with the MINO and 58·3 ± 15·6 p.p.b. with the NOA. In HS nasal NO was 49·1 ± 10·8 p.p.b. with the MINO and 49·8 ± 8·2 p.p.b. with the NOA. The Bland‐Altman analysis showed bias values of 0·005 ± 3·6 with the 95% limits of agreement from –6·97 to 6·98 p.p.b. Conclusion Measurements of nasal NO levels with a hand‐held electrochemical analyser are reproducible and the results are comparable to a stationary chemiluminescence analyser.     

Repeatability of successive measurements with a portable nitric oxide analyser in patients with suggested or diagnosed asthma

The objective of our study was to determine the repeatability of successive measurements of exhaled nitric oxide (NO) with a portable device (NIOX MINO^®). We assembled a sample of 332 pairs of repeated NO measurements acquired in the same session. The mean of the two successive measurements varied from 4.0 to 279.5 parts per billion (ppb). The mean coefficient of repeatability (CoR) of the entire study sample was 2.4?ppb. The difference between paired measurements increased slightly with increasing fractional exhaled nitric oxide (FENO); for the mean FENO of 24.0?ppb the calculated CoR was 2.2 and for the FENO of 54?ppb it was 3.2?ppb. The difference between paired observations for FENO values <50?ppb was significantly lower than that for values >50?ppb (p<0.001). The demonstrated repeatability of successive measurements with the device supports the view that, when the exhalation manoeuvre is technically valid and FENO is within normal limits, repeated determinations of FENO are generally not necessary for screening. In other cases, the mean value of two successive measurements would represent a more reliable measurement result.     

呼出气一氧化氮检测在哮喘儿童孟鲁司特治疗中的应用价值

目的探讨呼出气一氧化氮(FeNO)检测在哮喘儿童孟鲁司特治疗中的应用价值。 方法选择2013年5月至2014年5月于复旦大学附属上海市第五人民医院儿科门诊就诊的5～14岁哮喘儿童,共40例。给予入组患儿孟鲁司特常规治疗12周,随访6次并检测入组患儿FeNO水平,测定晨起呼气峰流速(PEF),并计算PEF占预计值的百分比(PEF%pred),记录儿童哮喘控制评分(C-ACT)。根据孟鲁司特治疗前及治疗12周时的哮喘控制水平分级变化,将入组患儿分为显效组和无效组,采用SPSS 17.0对不同分组的临床资料进行分析。最后有31例患儿完成为期12周的研究,其中显效组21例,无效组10例。 结果两组患儿在哮喘病史时间[(2.36±2.03)年,(3.60±1.51)年]、病情分级(部分控制/未控制)(16/5,1/9)、起始C-ACT评分[(20.71±0.85)分,(19.30±1.57)分]、起始FeNO水平[(9.93±7.69)ppb,(32.52±22.70)ppb]方面比较,均差异具有统计学意义(t＝1.72,χ²＝11.98,t＝3.29,t＝4.15;均P<0.05)。显效组患儿起始FeNO水平为(9.93±7.69)ppb,孟鲁司特治疗12周,前后测量结果比较,差异无统计学意义(F＝0.51,P>0.05);无效组患儿治疗前起始FeNO水平为(32.52±22.70)ppb,孟鲁司特治疗12周,前后测量结果之间差异无统计学意义(F＝0.56,P>0.05)。两组患儿孟鲁司特治疗后,PEF%pred、C-ACT评分均提高,6次测量结果之间均差异具有统计学意义(F＝4.63,6.06,50.67,6.09;均P<0.05)。两组患儿孟鲁司特治疗12周期间,除显效组患儿治疗2周时FeNO水平与PEF%pred呈正相关(r＝0.44,P<0.05)外,FeNO水平与PEF%pred、FeNO水平、C-ACT评分无相关性(P>0.05)。 结论FeNO与PEF%pred、C-ACT评分相比暂不具有明显的疗效监测价值,哮喘患儿的病史、病情分级、起始C-ACT评分、起始FeNO水平等因素可能会影响孟鲁司特的疗效。     

呼出气一氧化氮与胸腺基质淋巴细胞生成素在咳嗽变异性哮喘中的临床意义

目的研究咳嗽变异性哮喘(CVA)与呼出气一氧化氮(FeNO)、胸腺基质淋巴细胞生成素(TSLP)的相关性,推测其在CVA病理生理中的可能机制。方法收集2016年7月至2018年12月就诊于包头市中心医院呼吸科门诊及住院的病例:CVA患者67例(CVA组),嗜酸性粒细胞支气管炎(EB)患者8例(EB组)。选择同期健康体检者14名(健康对照组)。分别进行FeNO及血清TSLP的含量测定。采用单因素方差分析比较3组间上述资料的差异,不同组间的两两比较采用LSD-t检验法。采用Pearson相关分析分析CVA组FeNO与TSLP指标间的相关性。采用多元线性回归分析分析影响CVA组FeNO水平的因素,采用逐步法筛选变量(α入=0.10,α出=0.15)纳入合适的变量。结果FeNO水平在CVA组、EB组和健康对照组之间差异具有统计学意义(F=7.344,P=0.001);CVA患者FeNO水平显著高于健康对照组[(60.88±42.85)×10^-9 mol/L vs(17.64±4.91)×10^-9 mol/L],差异具有统计学意义(t=4.35,P<0.001);EB组FeNO水平高于健康对照组[(66.50±42.35)×10^-9 mol/L vs(17.64±4.91)×10^-9 mol/L)],差异具有统计学意义(t=2.71,P=0.008);CVA组患者和EB组患者比较,差异无统计学意义(P>0.05)。CVA组TSLP水平明显高于EB组[(421.60±111.65)ng/L vs(338.81±119.98)ng/L];EB组TSLP水平明显高于健康对照组[(338.81±119.98)ng/L vs(233.34±51.39)ng/L];CVA组血清TSLP水平显著高于健康对照组,差异均具有统计学意义(t=4.11、7.36、5.88,P均<0.001)。血清总IgE浓度在CVA组、EB组和健康对照组中比较,差异均无统计学意义(P>0.05)。CVA组FeNo与血清TSPL值呈正相关(r=0.258,P=0.035)。TSPL值、身高对FeNO水平均有影响。结论(1)FeNO和血清TSLP水平均与气道炎症相关。(2)单一的FeNO测定可能不能作为CVA与EB的鉴别标准。(3)血清TSLP水平参与了气道炎症的发生和发展,有助于慢性咳嗽CVA和EB的诊断和鉴别诊断。     

雾化吸入氯胺酮对哮喘大鼠肺组织一氧化氮及一氧化氮合酶的影响

目的通过建立大鼠支气管哮喘模型,观察不同浓度氯胺酮对哮喘大鼠肺组织iNOS活性及NO含量的影响。方法SD大鼠随机分成对照组(N组)、哮喘模型组(A组)、不同浓度氯胺酮预处理组(分别为K1组、K2组)和地塞米松组(D组),每组8只。A组大鼠用卵白蛋白辅以百日咳杆菌菌苗和氢氧化铝为佐剂注射致敏,2周后雾化吸入卵蛋白激发哮喘;氯胺酮处理组大鼠用同样方法致敏,但在激发前分别给予雾化吸入氯胺酮25 g/L(K1组)和50 g/L(K2组);D组在激发前给予雾化吸入0.01%地塞米松;N组用生理盐水替代卵蛋白进行注射和吸入。每组分别测定其肺组织NO2-/NO3-水平、肺组织诱导型NOS(iNOS)和原生型NOS(cNOS)活性水平,并用免疫组织化学法观察iNOS在大鼠哮喘模型肺组织中的分布。结果A组肺组织中NO2-/NO3-和iNOS水平升高,iNOS和肺组织NO2-/NO3-水平呈高度正相关;K1、K2组肺组织中NO2-/NO3-和iNOS水平低于A组(P<0.05);D组肺组织中NO2-/NO3-和iNOS水平亦低于A组(P<0.05)。结论25 g/L或50 g/L的氯胺酮雾化吸入可抑制哮喘大鼠肺组织iNOS活性,降低NO含量,减轻大鼠肺部炎症。     

NOS及NO在介导Aβ神经毒性和阿尔茨海默病发病机制中的作用

目的观察诱导型一氧化氮合酶(iNOS)抑制剂胍氨酸(AG)及神经元型一氧化氮合酶(nNOS)抑制剂7-硝基吲哚(7-NI)对β淀粉样蛋白1-40(Aβ1-40)在体神经毒性的干预,进一步探讨一氧化氮合酶(NOS)及一氧化氮(NO)在Aβ神经毒性和Alzheimer病(AD)发病机制中的介导作用。方法雄性SD大鼠35只,随机分为正常对照,生理盐水注射,Aβ1-40注射,AG+Aβ1-40,7-NI+Aβ1-40,花生油(Peanutoil,PO)+Aβ1-40、生理盐水+Aβ1-40共7组,每组5只。观察各组大鼠的Y迷宫学习记忆作业及局部神经元损伤情况。结果Aβ1-40海马组大鼠Y迷宫作业的获得和再现尝试次数均显著增加,分别是(27.8±2.3)和(19.7±4.7)次,与前两组比较有显著性意义(F获得=146.438,P获得=0.000;F再现=113.654,P再现=0.000)。海马齿状回颗粒细胞背侧带受损长度为(1.93±0.26)mm,局部胶质细胞反应明显。AG可逆转Aβ1-40导致的学习记忆和神经元损伤,其获得和再现尝试次数分别为(14.6±4.9)次和(8.5±2.1)次,与Aβ1-40注射组比较明显减少(F获得=146.438,P获得=0.000;F再现=113.654,P再现=0.000)。细胞带受损长度为(0.41±0.21)mm,胶质细胞反应减轻。7-NI则无干预作用。结论iNOS/NO参与了在体条件下对Aβ神经毒性的介导,在AD发病机制中具有重要作用。     

AMP challenge induces a decrease in FE(NO) in asthmatic subjects modulated by nedocromil

BACKGROUND: Allergen challenge results in an immediate reduction in exhaled nitric oxide (FE(NO)) followed by a long-term increase. To study mast cell activation in relation to nitric oxide (NO), the study investigated the effect of inhaled adenosine monophosphate (AMP) as a mast cell activator and mast cell stabilizer - nedocromil sodium - on FE(NO). The NO synthase (NOS) iso-enzyme involved was studied by the NOS inhibitor aminoguanidine. MATERIALS AND METHODS: A double-blind, placebo-controlled, cross-over study was performed in two parts. Part I: eight atopic asthmatic subjects inhaled nedocromil or placebo before the AMP challenge. Spirometry and FE(NO) were measured at intervals over a 24-h period. Part II: seven subjects inhaled aminoguanidine before an identical protocol was used, as in Part I. RESULTS: Part I: AMP challenge caused a significant decrease from baseline FE(NO)[placebo, 28.9 (20.3-37.4)%, P < 0.002 and nedocromil, 20.9 (8.2-33.6)%, P < 0.01]. Nedocromil gave partial protection against this decrease in FE(NO). The time-FE(NO) curve (AUC(0-24)) differed significantly between nedocromil and placebo: 2.7% (-3.6 to -9) vs. -6.6% (-12 to -1.3) FE(NO) changes h(-1), P < 0.002, respectively. Nedocromil protected against AMP-induced bronchoconstriction (AMP PC(20)) [nedocromil 182 (72.5-291) mg mL(-1) vs. placebo 21.7 (10.7-33) mg mL(-1), P < 0.002]. Part II: nebulized aminoguanidine resulted in a significant reduction in FE(NO) from baseline and was greater than after AMP alone (P = 0.006). Nedocromil increased AMP PC(20), but no longer protected against the late decrease in FE(NO). CONCLUSIONS: The AMP challenge caused a reduction in FE(NO) as a result of prior treatment with nedocromil. Aminoguanidine abolished the nedocromil-induced protection on the late reduction in FE(NO), but not on AMP PC(20). Inducible NOS was implicated in the late FE(NO) decrease after the AMP challenge.