气道反应性监测在儿童哮喘治疗中的指导意义

目的 探讨气道反应性检测在儿童哮喘治疗中的指导意义.方法 对38例确诊的支气管哮喘患儿,分别在治疗前,治疗后3个月、1年、2年进行常规肺功能检查,同时吸人浓度倍倍递增的乙酰甲胆碱进行支气管激发试验,测定最大呼气流量(PEF)、一秒钟用力呼气容积(FEV1)、最大呼气中段流最(MMEF)及比气道传导率下降35%或以上时吸入乙酰甲胆碱浓度(PC35 sGaw).PC35 sGaw≤8 mg/ml为激发试验阳性,观察随防时间为2年.结果 所有患儿对吸入糖皮质激素 长效β2激动剂(ICS LABA)的联合治疗反应良好,97.4%的患儿达到临床完全控制.治疗后肺功能仅2例存在轻微异常,FEV1、MMEF、PEF随治疗时间的增加明显升高,较治疗前差异有统计学意义.气道反应性测定在治疗后3个月、1年、2年PC35 sGaw浓度分别为(0.735±0.573)mg/ml、(1.47±1.289)mg/ml及(3.827±2.258)mg/ml,但至2年时仍有57.9%的患儿支气管激发试验阳性,均为轻度气道高反应.结论 哮喘临床指标达到完全控制的时间早于气道反应性达到理想水平的时间,气道反应性指标在联合治疗长期随访以及调整治疗方案中的价值优于临床症状和肺功能,PC35 sGaw可作为评价疗效、指导治疗方案调整的指标之一.     

呼出气温度对儿童哮喘气道炎症变化的预测意义

目的 探讨呼出气温度（EBT）对哮喘患儿气道炎症变化的预测意义。方法 选择门诊初诊时符合纳入标准的哮喘患儿60例作为哮喘组,另选60例健康儿童作为对照组,应用最新的三代产品（X-halo）检测EBT水平,记录儿童哮喘控制测试（C-ACT）评分,比较哮喘组和对照组EBT水平和C-ACT评分差异。1个月后复诊根据患儿C-ACT评分,将其分为良好控制组、部分控制组和未控制组,检测三组EBT和FeNO水平,比较三组EBT水平和C-ACT评分差异,分析EBT和FeNO相关性。追溯其初诊资料,比较初诊时三组EBT水平和C-ACT评分差异,最后比较复诊和初诊时三组EBT水平和C-ACT评分的差异。结果 初诊时,哮喘组EBT水平显著高于对照组（P < 0.05）,C-ACT评分显著低于对照组（P < 0.05）。复诊时,不同控制水平的三组EBT比较差异有统计学意义,即未控制组 > 部分控制组 > 良好控制组（P < 0.05）;三组C-ACT评分比较差异亦有统计学意义,即良好控制组 > 部分控制组 > 未控制组（P < 0.05）。三组初诊EBT水平和C-ACT评分的组间比较差异均无统计学意义（P > 0.05）。与初诊时比较,复诊时良好控制组EBT明显降低（P < 0.05）,部分控制组和未控制组均明显升高（P < 0.05）;良好控制组和部分控制组C-ACT评分均明显升高（P < 0.05）,未控制组明显降低（P < 0.05）。复诊时未控制组EBT和FeNO水平呈正相关（P < 0.05）。结论 EBT对儿童哮喘气道炎症的变化具有预测意义。     

鼻病毒与气道炎症研究进展

鼻病毒(RV)可以感染下呼吸道.随着PCR技术的发展,RV检出率明显增加.RV在呼吸道感染中所起到的作用也越来越得到重视.RV感染后释放多种炎性介质,引发RV相关的炎症反应.通过减低肺功能,诱发气道高反应和上调支气管上皮细胞上的黏附因子表达等机制造成相应下气道机能障碍,从而导致通常的呼吸道症状.RV感染后可以产生气道高反应,哮喘发作时可以检测出病毒,其中最常见的是RV.RV诱导的早期喘息是反复喘息的重要危险因素.RV感染可能是比呼吸道合胞病毒感染更重要的造成反复喘息的预警因素.     

气道重塑与儿童哮喘

气道炎症和气道重塑（airway remodelling）是支气管哮喘（以下简称哮喘）的两个主要病理学特征。哮喘是一种非特异性气道炎症性疾病这一点已经形成共识,嗜酸粒细胞（EOS）、T淋巴细胞、肥大细胞、上皮细胞和中性粒细胞等多种细胞和细胞组分参与哮喘的气道炎症。尽管当前国际上把哮喘气道重塑的研究提到了重要议事日程,但是目前国内外通用的哮喘诊治方案均强调对气道炎症的控制,较少关注气道重塑的诊断和治疗的研究。现就气道重塑的特点,儿童哮喘与气道重塑的关系。激素在气道重塑的作用以及参与气道重塑的神经信号通路作一综述。     

儿童哮喘的小气道功能

传统观念认为儿童支气管哮喘是一种可逆性的支气管痉挛,在缓解期可无任何症状。近年来的研究发现缓解期的症状虽然可逆,但气道的炎症并未消失,仍存在着气道高反应性。我们对儿童哮喘缓解期进行激发试验显示,不但在激发时而且在缓解期也普遍存在着小气道功能的下降,提示小气道的炎性改变可能是气道反应性增高的病理学基础之一。     

气道重逆与儿童哮喘

重塑(remodelling)在牛津字典中描述为重新塑造(model again)或重建(reconstruct),是指人体器官受到损伤后的一种自然反应,即修复(repair)。哮喘的本质是气道慢性炎症,初始可引起气道的功能性改变(functional change),由于炎症反复不断刺激,日久后演变为气道的结构性改变(structuralchange),表现为气道壁增厚;包括气道细胞外基质     

气道平滑肌与哮喘气道炎症

气道炎症是支气管哮喘最主要最基本的发病环节，炎症因子作用于支气管结构组织尤其气道平滑肌细胞使之发生结构和功能的改变，从而产生气道重建和气道高反应性。气道平滑肌受炎症因子等作用后，发生增殖及表型可塑性的改变而合成分泌多种炎症因子，促进炎症的发展并使炎症持久化慢性化。     

气道平滑肌与哮喘气道炎症

气道炎症是支气管哮喘最主要最基本的发病环节，炎症因子作用于支气管结构组织尤其气道平滑肌细胞使之发生结构和功能的改变，从而产生气道重建和气道高反应性。气道平滑肌受炎症因子等作用后，发生增殖及表型可塑性的改变而合成分泌多为症因子，促进炎症的发展并使炎症持久化慢性化。     

孟鲁司特对儿童哮喘炎症因子的影响

目的探讨孟鲁司特对儿童哮喘炎症因子的影响。方法将80例6～14岁中度哮喘患儿随机分口服孟鲁司特5mg/d、吸入布地奈德200μg/d、孟鲁司特5mg/d口服并吸入布地奈德100μg/d3组,持续治疗12周。于治疗开始和第12周进行临床评估和肺功能检查,同步进行外周血嗜酸性粒细胞(Eos)计数、血及痰液嗜酸性粒细胞阳离子蛋白(ECP)、IL5和TNFα水平的检测。结果哮喘患儿治疗后临床和肺功能明显改善;治疗开始患儿血ECP、IL5、TNFα水平和Eos计数均显著高于正常对照组(P均<0.01);血Eos计数与ECP浓度呈显著正相关(P<0.01),血IL5水平与ECP浓度呈显著正相关(P<0.01);治疗后血ECP、IL5、TNFα水平和Eos计数较治疗前明显降低(P<0.01);痰液ECP、TNFα和IL5含量显著低于治疗前(P<0.01)。结论孟鲁司特可抑制哮喘中Eos引起的呼吸道炎症,降低血和痰液ECP、IL5、TNFα水平。抑制效应可能是孟鲁司特抗哮喘呼吸道炎症的重要机制。     

小儿哮喘不同时期气道炎症改变的探讨

为探讨小儿哮喘不同时期气道炎症的改变 ,指导临床治疗 ,测定30例哮喘患儿在急性发作期和缓解期血浆丙二醛(MDA)浓度、过氧化物歧化酶(SOD)活力、嗜酸粒细胞阳离子蛋白(ECP)含量、血清总IgE和肺功能最大呼气流速(PEFR)的变化 ,且与18例正常对照组儿童比较。结果显示 ,哮喘患儿急性发作期MDA、ECP、总IgE比缓解期明显升高 ,而SOD、PEFR明显下降(P均<0.01) ,与对照组比较差异有显著性(P均<0.01) ;与对照组比较 ,缓解期MDA、ECP、总IgE也有明显升高(P<0.01) ,SOD明显下降(P<0.01) ,PEFR差异无显著性(P>0.05)。提示 ,哮喘患儿在急性发作期气道炎症加重 ,存在气道狭窄与阻塞 ,哮喘缓解期可以无临床症状 (PEFR正常) ,但气道炎症持续存在。因此,若要终止长期吸入糖皮质激素治疗 ,监测气道炎症改变非常重要     

Nitric oxide metabolites in induced sputum: a noninvasive marker of airway inflammation in asthma

OBJECTIVE: This study was designed to examine for nitric oxide (NO) metabolites in induced sputum as a marker of airway inflammation in asthmatic children. DESIGN. Prospective interventional SETTING: Pediatric Allergy and Asthma Clinic of a tertiary care referral hospital in Northern India. SUBJECTS: Twenty-one children with asthma who were not receiving corticosteroids for the preceding 3 months and 10 healthy controls were enrolled. METHODS: Hypertonic saline-induced sputum was obtained at study entry in controls, and at study entry and after 6 weeks of inhaled corticosteroid (ICS) therapy in asthmatic children. Fresh expectorated sputum was treated with dithiothreitol and cytospinned for cell count. NO metabolites were measured in the supernatant by the modified Griess reaction. RESULTS: Asthmatic children, compared with controls, had significantly higher concentration of NO metabolites (22.4 +/- 209.69 vs 39.2 +/- 15.9 (moL/L, P <0.01) and a higher percentage of eosinophils (15.3 +/- 12.0 vs 0.8 +/- 1.1%, P <0.01) in induced sputum. Both NO metabolites and eosinophil percentage declined following treatment with ICS for 6 weeks (P <0.01). CONCLUSION: The study confirms that the level of NO metabolites is increased in the tracheobronchial secretions of asthmatic children and decreases following ICS therapy. Measurement of NO metabolites in induced sputum may be useful for monitoring airway inflammation in children with asthma.     

Non‐invasive markers of airway inflammation and remodeling in childhood asthma

To evaluate the relationship between pro‐inflammatory and pro‐remodeling mediators and severity and control of asthma in children, the levels of IL‐8, MMP‐9, TIMP‐1 in induced sputum supernatants, the number of sputum eosinophils, as well as FeNO, were investigated in 35 asthmatic children, 12 with intermittent (IA) and 23 with moderate asthma (MA), and 9 controls (C). The patients with asthma were followed for 1 yr and sputum was obtained twice during the follow‐up. Biomarker levels were correlated with the number of exacerbations. We found that IL‐8, MMP‐9, TIMP‐1 and the numbers of eosinophils in induced sputum, as well as FeNO, were increased in children with IA and MA in comparison to C. The ongoing inflammation was confirmed by increased nuclear p65 NF‐κB subunit localization in sputum cells. In MA, FeNO measurements, sputum eosinophils and IL‐8 levels, positively correlated with the occurrence of disease exacerbations during a 1‐yr follow‐up. According to FeNO, sputum eosinophils and IL‐8 sputum concentrations, and the number of exacerbations, two distinct phenotypes of MA were identified. This study shows that the presence of bronchial inflammation is detectable in the airways of some IA, as well as in the airways of MA, despite the regular ICS treatment. This study also proposes the need to perform large prospective studies to confirm the importance of measuring specific biomarkers in induced sputum, concomitantly to FeNO analyses, to assess sub‐clinical airway inflammation and disease control in children with asthma.     

无创性检查对哮喘长期缓解患儿气道炎症的评价

目的探索常用无创性检查对哮喘长期缓解的评价。方法选择45例哮喘患儿,分发作组、短期缓解组、长期缓解组;另设对照组12例。检测肺功能、乙酰甲胆碱(Mch)支气管激发试验、诱导痰液计数EOS%、酶联免疫荧光法测定痰液及血清嗜酸性细胞阳离子蛋白(ECP)、ELISA法检测痰液及血清IL-5。结果①46.15%长期缓解期患儿FEF75<80%预计值,高于对照组(P<0.05);FEF25为(106.3±14.8)%,高于发作组(P<0.05)。②长期缓解患儿气道高反应性(AHR)与对照组差异无统计学意义(P>0.05)。③缓解期患儿痰液EOS%,血清ECP,痰液、血清IL-5与对照组比较差异均无统计学意义(P>0.05);痰液ECP高于对照组(P<0.05)。④各小气道通气指标与Mch激发试验、痰液EOS%、ECP、IL-5呈负相关(P均<0.05)。⑤小气道阻塞哮喘患儿AHR重于小气道功能正常者(P<0.05),小气道阻塞患儿各小气道指标与痰IL-5呈负相关(P<0.05)。⑥Mch激发试验与痰液、血清ECP,痰液IL-5呈正相关(P均<0.05)。⑦两组缓解期患儿肺功能,AHR,痰液EOS%、ECP、IL-5,血清ECP、IL-5差异均无统计学意义(P均>0.05)。⑧上述指标对哮喘长期缓解无预测价值(P>0.05)。结论长期缓解哮喘患儿存在一定程度小气道功能异常及气道炎症,痰液ECP是反映气道炎症更敏感的指标。研究所选取的无创性检查对评价哮喘缓解均有一定指导作用,但对哮喘长期缓解无预测价值。     

The role of inflammation in childhood asthma

The role of inflammation in adult asthma is well known, involving a cascade of immunological stimulation in which mast cells and eosinophils play pivotal roles. However, the assessment of airway inflammation in children is more difficult as the invasive methods used in adults cannot ethically be used for this purpose alone. Nevertheless, limited data from studies using invasive methodology, and studies using novel non-invasive techniques such as sputum induction and nitrous oxide exhalation, are improving knowledge. The immunopathology in childhood asthma appears to mirror that in adult sufferers. The inflammatory processes are evident at an early age in wheezing infants who later develop asthma, and there are different "wheezing phenotypes" in children with atopic asthma or viral associated wheeze. The mechanisms underlying childhood asthma are dependent not only on increased numbers of inflammatory cells in the airways, but also increased activation of these cells. In vitro data have shown that corticosteroids can inhibit the secretion of proinflammatory compounds from alveolar macrophages, suggesting a potential important role for these agents in halting the development of asthma. Techniques for measuring inflammation in infants need to be refined, in order to provide increased knowledge and accurate monitoring of the disease. It is hoped that this will enable the development of early interventions to minimise the impact of asthma in infants who are identified as being susceptible.     

Advances in the management of childhood asthma

For children with daily asthma symptoms, the most effective preventative therapy is inhaled corticosteroids (ICS). Most children experience good symptom control on relatively low doses (<400 μg/day). If frequent symptoms persist despite treatment with ICS 400 μg/day, beneficial add-on therapies include long-acting beta-2 agonists, leukotriene receptor antagonists and slow-release theophyllines. These should be tried sequentially before the dose of ICS is increased.Non-atopic children with episodic viral-triggered wheezing are extremely unlikely to respond to regular ICS. They might best be treated with ‘when-required’ high-dose beta-2 agonists with or without oral steroids.Children with frequently recurrent or chronic non-specific coughing are unlikely to have asthma. However, a clear response of symptoms to a trial of inhaled steroids and relapse when stopping therapy remains useful in identifying those with true cough-variant asthma.It remains to be seen how effective anti-IgE antibody therapy will be.     

Diagnosis and monitoring of childhood asthma

Diagnosis of asthma is clinical, however due to varied presentations in childhood both under and over diagnosis are possible. A good number of cases may not present with wheeze but may have a cough variant asthma. Episodic symptoms of airflow obstruction and reversibility are two very important features of asthma. Many congenital (Cystic fibrosis) and acquired conditions (foreign body) may cause wheezing in childhood and should be ruled out clinically or by specific investigations. Spirometry and peak expiratory flow rates help in objective assessment and are good tools for monitoring chronic patients. Total IgE has no role in diagnosis. There is now emphasis on co-management of asthma and patient/parents should be trained to keep symptoms records and wherever possible peak flow records. They should also be taught proper interpretation of readings for stepping up therapy in case of worsening.     

Cough, airway inflammation, and mild asthma exacerbation

Background: Prospective data on the temporal relation between cough, asthma symptoms, and airway inflammation in childhood asthma is unavailable. Aims and methods: Using several clinical (diary, quality of life), lung function (FEV₁, FEV₁ variability, airway hyperresponsiveness), cough (diary, cough receptor sensitivity (CRS)), and inflammatory markers (sputum interleukin 8, eosinophilic cationic protein (ECP), myeloperoxidase; and serum ECP) of asthma severity, we prospectively described the course of these markers in children with asthma during a non-acute, acute, and resolution phase. A total of 21 children with asthma underwent these baseline tests; 11 were retested during days 1, 3, 7, and 28 of an exacerbation. Results: Asthma exacerbations were characterised by increased asthma and cough symptoms and eosinophilic inflammation. Sputum ECP showed the largest increase and peaked later than clinical scores. Asthma scores consistently related to cough score only early in the exacerbation. Neither CRS nor cough scores related to any inflammatory marker. Conclusion: In mild asthma exacerbations, eosinophilic inflammation is dominant. In asthmatic children who cough as a dominant symptom, cough heralds the onset of an exacerbation and increased eosinophilic inflammation, but cough scores and CRS do not reflect eosinophilic airway inflammation.     

呼出气一氧化氮测定与哮喘的气道炎症

哮喘是一种常见病和多发病,其病理基础是气道炎症,而对哮喘气道炎症的监测是防治哮喘的关键.NO是近年来研究较多的一种生物活性物质,已证实其与许多炎症介质相关,在哮喘的发病机制中具有重要作用.目前认为呼出气中NO测定是反映哮喘气道炎症的新型无创伤性及敏感的生物指标,因而呼出气中NO测定对哮喘的诊断、治疗、病情监控和预后评估均有十分重要的意义.呼出气中NO测定技术的开展具有广阔的临床应用前景.     

诱导痰液与哮喘患儿气道炎症的关系探讨

目的探讨简便有效的诱导痰液及细胞分析方法,了解儿童哮喘发作期气道炎症的特点。方法运用高渗盐水雾化吸入诱导痰液的方法,收集３７例哮喘发作期患儿、４８例正常儿童（对照组）痰液。一部分痰液经二硫苏糖醇（ＤＴＴ）液化后,在血球计数板上行细胞总计数;另一部分痰液涂片经瑞氏、甲苯胺蓝染色行细胞分类计数。结果哮喘组８４％取痰成功,诱导过程中呼气峰流速（ＰＥＦ）未见下降（Ｐ＞００５）。痰液细胞总计数哮喘组为（１１２±８９）×１０９／Ｌ,对照组为（７１±６２）×１０９／Ｌ（Ｐ＜００５）。嗜酸性粒细胞、肥大细胞在哮喘发作期气道中明显升高（Ｐ＜００１）。结论诱导痰液分析、评判哮喘患儿气道炎症是一种安全、可靠的新研究方法;嗜酸性细胞、肥大细胞为哮喘发作的主要效应细胞。