Assessing airway inflammation: from guessing to quantitative measurements

Diagnosing asthma and following the response to treatment have relied on lung function measurements. Improved knowledge of the cellular events leading to airflow limitation has led to new clinical methods to assess the inflammatory component of the disease. Induced sputum analysis and exhaled nitric oxide (NO) measurements are already tools for clinical practice. New cell-specific inflammatory markers and further innovations in the testing of exhaled air, e.g. breath condensates and technical development of simple methods and devices, will also benefit the busy practitioner in near future. Assessing airway inflammation by quantitative measurements, instead of guessing, will also strengthen the role of anti-inflammatory medication as first-line treatment of asthma, even in its mildest forms.     

护理干预在呼出气一氧化氮测定哮喘患者气道炎性反应评估中的作用

目的探讨规范化护理干预在呼出气一氧化氮（FENO）测定哮喘患者气道炎性反应评估中的作用。方法将62例哮喘患者随机分为干预组32例和对照组30例,2组均在治疗前后行呼出气一氧化氮测定。对照组给予常规方法测定,干预组在常规方法基础上给予护理干预。对2组患者的测定舒适状况、满意度、治疗疗效进行对比分析。结果测定舒适度、满意度交及治疗的疗效干预组明显优于对照组,差异有统计学意义。结论规范化护理干预在呼出气一氧化氮测定中可排除检测中的不良干扰,提高测定水平的准确性,对于改善哮喘患者临床症状、缓解气道炎性反应有—定的的临床指导意义,值得推荐使用。     

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。     

靶向Th17细胞免疫治疗中重度哮喘的作用

支气管哮喘（简称哮喘）是多种炎症细胞和炎性介质参与的慢性气道炎症性疾病。Thl/Th2免疫反应失衡是哮喘主要的发病机制,而嗜酸粒细胞性气道炎症和气道高反应性为哮喘的显著临床特征。Th17细胞通过活化和募集中性粒细胞,促进气道炎症发生发展,尤其与中重度哮喘密切相关。Th17细胞为中重度哮喘提供了潜在的治疗靶点。深入研究Th17细胞分化调控机制,有望为治疗中性粒细胞性哮喘带来新的愿景。     

Traditional and new approaches to asthma monitoring

Once the diagnosis of asthma is established, monitoring must be implemented to achieve asthma control. Because of the variability of asthma, monitoring is a long-term commitment to effectively adjust treatment and assure that therapy goals are met. This paper reviews the definition of asthma control, including the dimensions of impairment and risk, and the 2007 National Asthma Education and Prevention Program's Expert Panel Report 3, Guidelines for the Diagnosis and Management of Asthma, recommendations for periodic assessment and monitoring of effective control. New approaches to asthma monitoring, such as airway hyperresponsiveness, sputum eosinophils, exhaled nitric oxide, and pharmacogenetic measurements, will be critiqued.     

Markers of lung disease in exhaled breath: nitric oxide

Management of airway inflammation requires proper monitoring and treatment to improve long-term outcomes. However, achieving this goal is difficult, as current methods have limitations. Although nitric oxide (NO) was first identified 200 years ago, its physiological importance was not recognized until the early 1980s. Many studies have established the role of NO as an essential messenger molecule in body systems. In addition, studies have demonstrated a significant relationship between changes in exhaled NO levels and other markers of airway inflammation. The technique used to measure NO in exhaled breath is noninvasive, reproducible, sensitive, and easy to perform. Consequently, there is growing interest in the use of exhaled NO in the management of asthma and other pulmonary conditions. The purpose of this review is to promote a basic understanding of the physiologic actions of NO, measurement techniques, and ways that research findings might translate to future application in clinical practice. Specifically, the article will review the role of exhaled NO in regard to its historical background, mechanisms of action, measurement techniques, and implications for clinical practice and research.     

Asthma: a case study,review of pathophysiology,and management strategies

PURPOSE: To review the pathophysiology of asthma, present a case study, and provide management strategies for treating this common, yet complex disorder in children and adults. DATA SOURCES: Selected clinical guidelines, clinical articles, and research studies. CONCLUSIONS: Asthma is a chronic inflammatory airway disorder with acute exacerbations that currently affects approximately 14 million-15 million children and adults in the United States. Costs for asthma are staggering and nurse practitioners (NPs) are frequently presented with management decisions for the acute treatment and chronic management of this disorder. Disparities exist with the occurrence of asthma between race and gender. Additionally, there is an increased incidence in acute exacerbations resulting from poor long-term control and follow-up care among the socioeconomically disadvantaged. IMPLICATIONS FOR PRACTICE: Standards of care, along with new and emerging treatment strategies, guide NPs in providing the most comprehensive care to those affected with this chronic disorder. Knowledge about the pathophysiology of asthma and correlated to the case presentation enhances understanding treatment strategies for NPs who are often faced with providing care for patients with this chronic disorder that may sometimes present in an acute exacerbation.     

benralizumab在重症嗜酸粒细胞型哮喘治疗中的价值

支气管哮喘是一种常见的呼吸道慢性炎症性疾病,部分患者根据指南用药治疗后症状仍得不到控制,尤其在一些嗜酸粒细胞升高患者,吸入糖皮质激素及长效β2受体激动剂治疗后仍不能得到充分控制。benralizumab是一种人源化白细胞介素-5（IL-5）受体抗体,本文就benralizumab基本特性、临床应用现况、与其他IL-5抗体的比较以及应用前景等方面进行综述。     

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。     

Small,Prospective, Observational,Pilot Study in Patients with Severe Asthma after Discontinuation of Omalizumab Treatment

Purpose

Omalizumab has demonstrated clinical efficacy in severe allergic asthma by reducing exacerbation rates and increasing quality of life. However, data concerning its sustained effect after treatment discontinuation are still needed.

穴位疗法对支气管哮喘缓解期患者炎症因子及临床疗效的影响

目的探讨穴位疗法对支气管哮喘缓解期患者炎症因子及临床疗效的影响。 方法将入选的支气管哮喘缓解期患者按随机数字表法分为治疗组和对照组,每组30例,治疗组给予穴位疗法,对照组给予舒利迭治疗,共治疗4周。观测2组患者治疗前、治疗1个月后（近期）和停止治疗3个月后（远期）的哮喘控制测试（ACT）积分、治疗1个月后（近期）哮喘控制情况（完全控制、部分控制、未控制）以及患者治疗前、治疗1个月后（近期）和停止治疗3个月后（远期）的白介素5（IL-5）、白介素10（IL-10）的含量,并对2组患者的ACT积分、近期疗效及IL-5和IL-10的含量进行统计学分析比较。 结果①治疗前,治疗组和对照组患者的ACT积分分别为（14.11±3.24）和（13.75±3.02）分,组间差异无统计学意义（P>0.05）。治疗后,治疗组近期和远期的ACT积分［（21.56±1.81）和（24.03±0.78）分］均明显高于同期对照组［（18.71±1.63）和（22.15±0.96）分］,组间差异有统计学意义（P<0.05);②治疗组近期控制哮喘的总有效率（93.33%）明显高于对照组（70.00%）,且组间差异有统计学意义（χ2＝5.455,P<0.05）;③治疗组治疗后近期和远期的IL-5和IL-10炎症因子的含量较组内治疗前明显改善且优于同期对照组（P<0.05）。 结论穴位疗法通过调节IL-5和IL-10炎症因子含量水平,降低气道炎症,控制支气管哮喘症状,提高患者的临床疗效。     

2021年《ERS临床实践指南：5~16岁儿童哮喘的诊断》解读

哮喘是儿童期最常见的慢性呼吸道炎症性疾病之一,严重影响儿童的生活质量。然而目前关于儿童哮喘缺乏诊断的金标准,对哮喘的过度诊断和诊断不足十分常见。因此,正确且早期识别儿童哮喘对于提高哮喘控制水平、改善预后显得至关重要。2021年4月,欧洲呼吸学会（ERS）发布了5 ~ 16岁儿童哮喘诊断的临床实践指南,该指南主要针对5 ~ 16岁儿童哮喘的诊断问题提供循证证据及指导建议,现就该指南制定方法、诊断要点及推荐等作一浅析。     

Symptom perception and asthma control

Objectives: Asthma control is the goal of asthma management. The perception of asthma symptoms represents a cornerstone aspect in this issue. The visual analogue scale (VAS) has been proposed as a useful tool for assessing respiratory symptoms perception. The present cross-sectional real-life study investigated whether VAS assessment of asthma symptoms perception could predict asthma control level. Methods: This cross-sectional study included a total of 370 (153 males, mean age 39.9 years) patients with asthma. Perception of asthma symptoms was assessed by VAS; clinical examination, lung function, fraction of exhaled nitric oxide (FeNO) measurement, Asthma Control Test (ACT) and Hospital Anxiety Depression Scale questionnaires were also evaluated. Results: Asthma was well controlled in 47% of patients. Considering most of the evaluated parameters, there were significant differences among patients with well-controlled, partly controlled and uncontrolled asthma. VAS values were significantly (p < 0.001) different considering the asthma control level. VAS score were significantly related with ACT scores (p < 0.001). A VAS <6 was able to reliably predict uncontrolled asthma (area under the curve: 0.74; odds ratio: 5.16). Conclusion: The present real-life study demonstrates that asthma symptoms assessment by VAS might be useful for approximately predicting uncontrolled asthma in particular conditions, such as at home or at the general practitioner’s office.     

Outpatient management of asthma in children age 5–11 years: Guidelines for practice

Purpose: To increase awareness among nurse practitioners (NPs) regarding diagnostic and treatment guidelines for asthma for the 5–11 year age group recently updated by the National Asthma Education Prevention Program-Expert Panel 3 (NAEPP-EPR3).
Data sources: NAEPP-EPR3 guidelines for the diagnosis and management of asthma released from the National Heart, Lung, and Blood Institute in August 2007, selected clinical trials, meta-analyses, and clinical reviews.
Conclusions: Recent research has revealed that children suffering from asthma in the United States are underdiagnosed and their asthma is poorly controlled. Compelling evidence supports that children classified as having persistent asthma following NAEPP-EPR3 guidelines benefit from daily inhaled corticosteroid therapy, yet many are misclassified and undertreated.
Implications for practice: With application of current guidelines from NAEPP-EPR3, NPs can more effectively assess, diagnose, treat, and foster a collaborative self-management plan for children age 5–11 years. These interventions will result in an improved quality of life and decreased health risks for this young population.     

支气管哮喘患者呼出气一氧化氮与血嗜酸性粒细胞数量及比例和免疫球蛋白E的相关性分析

[目的]探讨支气管哮喘(简称哮喘)患者的呼出气一氧化氮(FeNO)与血嗜酸性粒细胞(Eos)及血Eos占白细胞总数的百分比(Eos%)和血总免疫球蛋白E(TIgE)的相关性.[方法]选择2014年10月至2015年9月本院收治的哮喘患者80例为观察组,随机抽取同期来本院进行正常体检的健康志愿者80例为对照组,比较两组的呼出气FeNO、血Eos、Eos%及TIgE水平,并分析FeNO水平与其他指标的相关性.[结果]观察组呼出气FeNO为(51.48±13.09)ppb,明显高于对照组(11.29±4.37)ppb;观察组的哮喘控制测试(ACT)评分为(15.39±3.21)分,明显低于对照组(23.64±4.29)分,其差异均有统计学意义(P<0.05);观察组Eos、Eos%及TIgE水平分别为(264.28±32.19)×10 6/L、(6.39±1.21)%、(134.38±19.73)kU/L,均明显高于对照组[(67.49±9.74) ×10 6/L、(1.21±0.59)%、(92.10±11.49)kU/L],差异均有显著性(均P<0.05);相关性分析显示, FeNO水平与TIgE水平无相关性(P>0.05),与Eos计数和Eos%水平呈正相关性(P<0.05).[结论]呼出气FeNO检测作为一种无创性操作检查,其检测结果能够直接反映哮喘患者的慢性气道炎症状况,尤其是对于嗜酸粒细胞性炎症反应,且有利于评估哮喘疾病严重程度,值得临床推广应用.     

Predictors of response to therapy with omalizumab in patients with severe allergic asthma – a real life study

Objectives: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab.

Methods: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician’s global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders.

Results: Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV₁ and FEV₁/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV₁ (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709).

Conclusion: Lower baseline FEV₁ and higher IL-13 levels in induced sputum supernatant were predictors of response to omalizumab. Patients with higher baseline serum IgE levels, shorter disease duration and higher blood eosinophils may experience a late response and might benefit from a more prolonged treatment before being characterized as non-responders.     

DASH for asthma: A pilot study of the DASH diet in not-well-controlled adult asthma

This pilot study aims to provide effect size confidence intervals, clinical trial and intervention feasibility data, and procedural materials for a full-scale randomized controlled trial that will determine the efficacy of Dietary Approaches to Stop Hypertension (DASH) as adjunct therapy to standard care for adults with uncontrolled asthma. The DASH diet encompasses foods (e.g., fresh fruit, vegetables, and nuts) and antioxidant nutrients (e.g., vitamins A, C, E, and zinc) with potential benefits for persons with asthma, but it is unknown whether the whole diet is beneficial. Participants (n = 90) will be randomized to receive usual care alone or combined with a DASH intervention consisting of 8 group and 3 individual sessions during the first 3 months, followed by at least monthly phone consultations for another 3 months. Follow-up assessments will occur at 3 and 6 months. The primary outcome measure is the 7-item Juniper Asthma Control Questionnaire, a validated composite measure of daytime and nocturnal symptoms, activity limitations, rescue medication use, and percentage predicted forced expiratory volume in 1 second. We will explore changes in inflammatory markers important to asthma pathophysiology (e.g., fractional exhaled nitric oxide) and their potential to mediate the intervention effect on disease control. We will also conduct pre-specified subgroup analyses by genotype (e.g., polymorphisms on the glutathione S transferase gene) and phenotype (e.g., atopy, obesity). By evaluating a dietary pattern approach to improving asthma control, this study could advance the evidence base for refining clinical guidelines and public health recommendations regarding the role of dietary modifications in asthma management.     

哮喘患者吸入激素用药依从性研究进展

支气管哮喘(哮喘)是一种气道慢性炎症疾病,激素是最有效的控制气道炎症的药物,但目前哮喘患者吸入激素用药依从性偏低.本文从用药依从性定义、激素用药依从性现状、评价方法、影响因素及干预措施等方面对哮喘患者吸入激素用药依从性的研究进展作一综述.

Abstract：

Bronchial asthma (asthma) is a kind of chronic airway inflammatory disease. Corticosteroid is the most effective drugs used to control airway inflammation.However, the medication compliance of the patient who inhale corticosteroid is still very low at present.This article mainly summarized the process on the medication compliance of the inhaled corticosteroid from the following aspects: the definition, the present situation , the evaluation methods, the affecting factors and the interventions.     

Solving insomnia electronically: Sleep treatment for asthma (SIESTA): A study protocol for a randomized controlled trial

BackgroundChronic insomnia is associated with poor asthma control. Cognitive-behavioral treatment for insomnia (CBT-I) is an efficacious and durable treatment for comorbid insomnia in medical and psychiatric disorders. However, the efficacy and potential accompanying mechanisms of CBT-I have not been examined in asthma. The purpose of this study is to test the efficacy of a CBT-I intervention on sleep and asthma control in adults with insomnia and asthma. We will also explore airway inflammation (i.e., exhaled nitric oxide, blood eosinophils) as a potential biological mechanism linking improvements in sleep with improvements in asthma control.MethodsThe study is a single center, parallel group, randomized controlled trial. Two hundred and ten adults with insomnia and asthma that is not well-controlled will be randomized to either a 9-week Internet-based CBT-I program (Sleep Healthy Using the Internet (SHUTi)) or an enhanced usual care condition which utilizes an online educational video about insomnia. The primary sleep outcome is insomnia severity measured by the Insomnia Severity Index. Secondary sleep outcomes are sleep quality and wrist actigraph-recorded sleep parameters. Asthma control will be assessed by the Asthma Control Test, Asthma Quality of Life Questionnaire, pulmonary function testing, and self-report of asthma exacerbations and asthma-related healthcare utilization. Treatment outcomes will be measured at baseline, 9 weeks, and 6 months.DiscussionThis trial has the potential to identify a novel strategy for improving asthma control. Findings may advocate for the inclusion of treatment of comorbid insomnia into current asthma management practice guidelines.     

孟鲁司特钠联合布地奈德福莫特罗粉吸入剂治疗支气管哮喘的临床效果及其对患者炎性因子水平、肺功能、免疫功能的影响

目的探讨孟鲁司特钠联合布地奈德福莫特罗粉吸入剂治疗支气管哮喘的临床效果及其对患者炎性因子水平、肺功能、免疫功能的影响。方法将150例支气管哮喘患者根据治疗方法分为对照组和试验组,各75例。对照组在常规治疗基础上使用布地奈德福莫特罗粉吸入剂,试验组在对照组的基础上再联合孟鲁司特钠片进行治疗。比较两组的治疗效果、炎症因子水平、免疫功能、肺功能及不良反应发生情况。结果试验组的治疗总有效率高于对照组(P<0.05);治疗后,两组的TNF-α、IL-5、IgE水平均低于治疗前,IgA和IgG水平、PEF、FEV1、FEV1/FVC均高于治疗前,且试验组优于对照组(P<0.05);两组的不良反应总发生率无显著差异(P>0.05)。结论孟鲁司特钠联合布地奈德福莫特罗粉吸入剂治疗支气管哮喘患者的临床疗效显著,可以有效降低机体的炎症因子水平,改善肺功能和免疫功能,同时不会增加不良反应的发生率,值得临床推广应用。