Treating the wheezing infant

The management of infants and small children with asthma is a challenging task because of the many issues unique to this age group that deserve special consideration. The diagnosis of asthma is limited by inherent difficulties in obtaining objective measures of lung function and airway inflammation. In persistently symptomatic patients, the decision to initiate controller therapy is not as great an issue as it is in infants and young children with recurrent episodic wheeze in whom early intervention may allow a window of opportunity potentially to alter the course of the disease. The reality is that even if atopy has been consistently implicated in the development of persistent asthma, there is not a well-established set of criteria by which patients who are likely to benefit from early intervention controller therapy can be identified. Hence, large prospective studies need to be performed evaluating the impact of early pharmacologic intervention on the natural history of infantile asthma. Many areas needing investigation involve what medications to use, how best to deliver the medications, and how to monitor the response to treatment. Only a few medications have been approved for use in this population. Long-term studies evaluating available drugs such as inhaled glucocorticoids, LABAs, and the leukotriene-modifying agents in young children still need to be performed.     

Markers of eosinophilic inflammation and tissue re-modelling in children before clinically diagnosed bronchial asthma

Chronic inflammatory changes in the bronchial mucosa have been well documented in patients with established asthma. Much less is known of the changes, which occur in the airways of children early in the evolution of their disease with most of the information based on indirect markers of inflammation only. We evaluated markers of inflammation and tissue re-modelling in bronchial biopsies from children with early respiratory symptoms before a clear clinical diagnosis of bronchial asthma could be made. We examined bronchial biopsies performed in 27 children between the ages of 1.2 and 11.7 yr who were bronchoscoped for a clinical indication because of recurrent or chronic respiratory symptoms. The patients were re-evaluated 22-80 months after the original bronchoscopy to determine whether or not they had subsequently developed bronchial asthma. There were more eosinophils in the bronchial mucosa (129.4 vs. 19.1 cells/mm2 of lamina propria, p <0.001) and the thickness of the subepithelial lamina reticularis was greater (4.65 vs. 3.72 microm, p=0.044) in children with bronchial asthma diagnosed at follow-up, compared with the children who did not progress to asthma. Eosinophilic inflammation and airway re-modelling occur early in the natural history of bronchial asthma and are present even before asthma would be diagnosed based on clinical symptoms. Recognition of these changes and their significance for clinical disease should emphasize the need for timely detection and diagnosis of asthma in children to facilitate the early introduction of anti-asthma therapy.     

慢性咳嗽患儿呼吸道高反应的危险因素

目的 探讨慢性咳嗽患儿呼吸道高反应的危险因素,为儿童慢性咳嗽的诊治提供依据.方法 选择2008年9月- 2009年10月就诊于本院呼吸科 门诊的慢性咳嗽患儿141例.男68例,女73例；年龄(6.56±1.89)岁.予问卷调查及采用Astograph法测定其呼吸道高反应性,对有关变量进行单因素分析,再将单因素分析有意义的变量进一步行Logistic逐步回归分析,应用STATA7.0统计软件进行统计学分析.结果 慢性咳嗽呼吸道反应性测定结果:呼吸道高反应106例,呼吸道反应正常35例.单因素分析有统计学意义的因素:直系亲属哮喘史、特应性皮炎史和被动吸烟.Logistic逐步回归分析显示,慢性咳嗽呼吸道高反应的独立危险因素有直系亲属哮喘史(OR=4.91；95％ CI:1.326 ～18.192)和特应性皮炎史(OR=0.26,95％CI:0.116～0.623).结论 直系亲属有哮喘史和患儿有特应性皮炎史是儿童慢性咳嗽呼吸道高反应的独立危险因素.     

Natural history of asthma

For some children, asthma is a disease whose symptoms seem to remit with time. Numerous children, however, develop disease that is persistent throughout their lifetimes and is associated with more severe symptoms, increased airway reactivity, and loss of lung function. These children typically have a family history of asthma and demonstrate increased airways reactivity and atopy in childhood. A clearer picture of the natural history of asthma in the developing child has been derived from the results of several longitudinal studies. Although some questions have been clarified, several questions still remain. Now that the incidence and severity of asthma seem to be increasing, children born in the last 10 years may experience more severe disease or a different pathophysiology than those born 30 to 40 years ago. New cohort studies are needed to assess this possibility. Additional investigations into the genetics of asthma causation will help elucidate the different phenotypic expressions of this complex disease. Once these different phenotypic groups can be identified early in life, further studies can be performed to explore the impact of therapeutic intervention on the severity of asthma symptoms and loss of lung function.     

Inflammatory phenotypes in stable and acute childhood asthma

Asthma is a complex disease with a significant inflammatory component characterized by repeated episodes of exacerbation and inflammatory changes in both large and peripheral airways. The clinical course of childhood asthma varies substantially among individuals. The reasons why the clinical course of asthma displays persistence and even progression in some children but is intermittent in others remains unclear. Children with asthma are different from adults with asthma. Inflammatory involvement in children with asthma appears to be localised more in peripheral than central airways, and the inflammatory phenotype displays differences from adults. Children with acute asthma display a dominant eosinophilic inflammatory phenotype instead of the neutrophilic phenotype that is seen in adults with acute asthma. Corticosteroids do not alter the natural history of the disease and may not prevent progressive decline of lung function in the subset of severe asthma. The underlying inflammatory mechanisms involved in the decline of lung function remains to be elucidated. Non-invasive biomarkers for monitoring lung function and inflammation are needed in children to track and monitor pathological changes in the distal airways, as is the development of therapeutic strategies that effective to peripheral airway in this vulnerable population. This review summarises our present understanding of airway inflammatory phenotypes in children with asthma and factors determining disease severity in exacerbations of asthma, and focuses on studies evaluating relationships between clinical features and the dominant inflammatory phenotypes in disease prognosis in a variety of asthma populations. This presents the crucial steps for describing the strategies associated with improvements for paediatric asthma care.     

Does remodelling of the airway wall precede asthma?

Bronchial asthma is very common in childhood but the occurrence of wheeze with viral infections makes asthma difficult to diagnose in the pre-school child. Longitudinal studies suggest that there is a loss of airway function associated with early childhood asthma. Extrapolating from adult disease and the few tissue-based studies of children, this would appear to be related to abnormal postnatal development or remodelling of the airway walls. This appears to be associated with persistent airway inflammation without clinical evidence of airways obstruction. Abnormally thickened airways may be the mechanism underlying both bronchial hyper-responsiveness and fixed loss of respiratory function. The challenges for the future are to identify those children among the pre-school wheezers who will become asthmatic and to construct trials of therapies that may potentially prevent the development of clinical asthma or ameliorate the associated loss of airway function.     

Virus infections,wheeze and asthma

Viral infections are the most frequent triggers of wheeze and asthma and yet their role in the development of symptoms remains controversial. Pre-existing airway abnormalities contribute to early virus-induced symptoms which usually remit in early childhood, whereas an interaction with airway inflammation causes exacerbations in asthma. However, the distinction between these two groups and the reason why some but not other children wheeze with viral infections is still debated. The effect of early infections on the developing immune system is also complex. The successful maturation of the T-cell response from a predominantly type 2 (atopic predisposition) at birth to a predominantly type 1 (optimal viral immunity) response, is influenced by genetic factors and the number of infections, as both are known to affect outcome. The relative parts played by predisposition and immunomodulation by early infections in later development of asthma are still controversial. These contentions are gradually being resolved by detailed prospective studies.     

儿童不同呼吸系统疾病气道反应性特点及其临床价值

目的探讨儿童支气管哮喘、咳嗽变异性哮喘(CVA)和支气管炎等不同呼吸系统疾病气道反应性特点及其临床价值。方法应用Astograph法气道反应性测定技术,对42例哮喘患儿、38例咳嗽变异性哮喘(CVA)患儿、36例支气管炎患儿及30例健康儿童进行气道反应性测定;分别对反映气道敏感性和气道反应性的Dmin、SGrs、PD35等各指标进行统计学分析和评估。结果哮喘组、CVA组和支气管炎组患儿的Dmin、SGrs、PD35等指标均低于健康对照组,差异有统计学意义(P<0.05),哮喘组、CVA组与支气管炎组患儿之间比较,差异也有统计学意义(P<0.05),而哮喘组与CVA组患儿比较,差异无统计学意义(P>0.05)。结论哮喘病、CVA和支气管炎等不同呼吸系统疾病患儿的气道反应性及气道敏感性均高于健康儿童,而不同呼吸系统疾病患儿的气道反应性、气道敏感性变化也各不相同,以此可为鉴别诊断提供依据。     

T细胞凋亡与哮喘发生关系的研究进展

支气管哮喘是一种复杂的多病因的疾病,是由环境因素和遗传因素共同决定的,是多种炎症细胞参与引起的气道的慢性炎症.目前国内外的研究已经证明T细胞是参与气道炎症的主要免疫调节细胞及效应细胞,近年来有研究证明T细胞活化诱导凋亡机制参与哮喘的发病.该文从对T细胞凋亡参与支气管哮喘发病过程进行总结,为进一步阐明哮喘的发病机制提供依据.     

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??Excessive mucus produced by airway glands and goblet cells can cause airway mucus hypersecretion??long term of mucus secretions can blocking the airway and cause severe airflow limitation and ventilation dysfunction. Meanwhile??excessive mucus can reduce mucociliary clearance and local defense function??and foreign bodies and pathogens may remain in the lungs and airway??leading to recurrent respiratory infections. Airway mucus hypersecretion is closely related to bronchial asthma??bronchiectasis??low respiratory tract infection and other diseases. Airway mucus hypersecretion is an important factor influencing the occurrence??development and prognosis of bronchial asthma??bronchiectasis??lower respiratory tract infection and other diseases??so pediatricians should pay high attention to them.     

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.     

气道平滑肌细胞在哮喘气道重塑中的作用

气道重塑是气道慢性炎症的结果,包括气道壁增厚和基质沉积、胶原沉积、上皮下纤维化、平滑肌增生和肥大、肌成纤维细胞增殖及黏液腺、杯状细胞化生及增生、上皮下网状层增厚、微血管生成等病理改变.在这些病理变化中,气道平滑肌的改变被认为是导致气道高反应性和哮喘加重的重要因素.有很多因素导致气道平滑肌增生及肥大,如炎症介质、生长因子、细胞因子、细胞外基质蛋白和遗传因子等.最近的研究揭示气道平滑肌也是炎症介质的重要来源.建议在哮喘发病早期应用激素吸入治疗.     

气道平滑肌细胞在哮喘气道重塑中的作用

气道重塑是气道慢性炎症的结果,包括气道壁增厚和基质沉积、胶原沉积、上皮下纤维化、平滑肌增生和肥大、肌成纤维细胞增殖及黏液腺、杯状细胞化生及增生、上皮下网状层增厚、微血管生成等病理改变.在这些病理变化中,气道平滑肌的改变被认为是导致气道高反应性和哮喘加重的重要因素.有很多因素导致气道平滑肌增生及肥大,如炎症介质、生长因子、细胞因子、细胞外基质蛋白和遗传因子等.最近的研究揭示气道平滑肌也是炎症介质的重要来源.建议在哮喘发病早期应用激素吸入治疗.     

核因子-κB在哮喘患儿支气管上皮细胞的活化及意义

目的　探讨核因子 κB(nuclearfactor κB ,NF κB)在哮喘患儿气道炎症中的作用。　方法选取 9例哮喘患儿及 6例非哮喘对照患儿的支气管粘膜 ,进行普通病理检查 ,观察是否存在气道炎症 ;进行免疫组化及凝胶电泳迁移率检查 ,分别观察NF κB在支气管上皮细胞核的表达及NF κB与DNA的结合活性。结果　 9例哮喘患儿均存在气道炎症 ,NF κB在其支气管上皮细胞核均有表达 ;对6例哮喘患儿进行了凝胶电泳迁移率检查 ,其中 4例观察到NF κB与DNA结合 ,2例未见NF κB与DNA结合。 6例非哮喘对照患儿无气道炎症 ,在其支气管上皮细胞核均未见NF κB表达 ,也未见NF κB与DNA结合。结论　NF κB在哮喘患儿支气管上皮细胞活化 ,可能通过调控多种炎性蛋白的表达 ,导致气道炎症发生。     

Characteristics of asthma and airway hyper-responsiveness after premature birth

Asthma-like symptoms and airway hyper-responsiveness (AHR) are frequently reported in children subsequent to premature birth and bronchopulmonary dysplasia (BPD). There is limited knowledge on the mechanisms underlying these respiratory manifestations. Generally, childhood asthma and AHR is described within a context of inheritance, allergy and eosinophilic airway inflammation, and often in relation to cigarette exposures. We investigated these factors in relation to current asthma and AHR in a population-based cohort of 81 young people, born with gestational age < or = 28 wk or birth weight < or = 1000 g, and in a matched term-born control population. In the pre-term population, asthma and AHR were additionally studied in relation to neonatal respiratory morbidity. At follow up, more pre-term than control subjects had asthma. Forced expiratory volume in first second (FEV1) was reduced, AHR was substantially increased, and the level of the urinary leukotriene metabolite E4 (U-LTE4) was increased in the pre-term population compared to the term-born. In control subjects, asthma and AHR was associated with a pattern consistent with inheritance, allergy, airway inflammation, and cigarette exposures. In the pre-terms, asthma and AHR was either unrelated or less related to these factors. Instead, AHR was strongly related to a neonatal history of BPD and prolonged requirement for oxygen treatment. In conclusion, asthma and AHR subsequent to extremely premature birth differed from typical childhood asthma with respect to important features, and AHR was best explained by neonatal variables. These respiratory manifestations thus seem to represent a separate clinical entity.     

Parental and neonatal risk factors for atopy, airway hyper-responsiveness, and asthma

BACKGROUND: Previous studies have not resolved the importance of several potential risk factors for the development of childhood atopy, airway hyperresponsiveness, and wheezing, which would allow the rational selection of interventions to reduce morbidity from asthma. Risk factors for these disorders were examined in a birth cohort of 1037 New Zealand children. METHODS: Responses to questions on respiratory symptoms and measurements of lung function and airway responsiveness were obtained every two to three years throughout childhood and adolescence, with over 85% cohort retention at age 18 years. Atopy was determined by skin prick tests at age 13 years. Relations between parental and neonatal factors, the development of atopy, and features of asthma were determined by comparison of proportions and logistic regression. RESULTS: Male sex was a significant independent predictor for atopy, airway hyper-responsiveness, hay fever, and asthma. A positive family history, especially maternal, of asthma strongly predicted childhood atopy, airway hyperresponsiveness, asthma, and hay fever. Maternal smoking in the last trimester was correlated with the onset of childhood asthma by the age of 1 year. Birth in the winter season increased the risk of sensitisation to cats. Among those with a parental history of asthma or hay fever, birth in autumn and winter also increased the risk of sensitisation to house dust mites. The number of siblings, position in the family, socioeconomic status, and birth weight were not consistently predictive of any characteristic of asthma. CONCLUSIONS: Male sex, parental atopy, and maternal smoking during pregnancy are risk factors for asthma in young children. Children born in winter exhibit a greater prevalence of sensitisation to cats and house dust mites. These data suggest possible areas for intervention in children at risk because of parental atopy.     

Parental and neonatal risk factors for atopy,airway hyper-responsiveness,and asthma.

BACKGROUND: Previous studies have not resolved the importance of several potential risk factors for the development of childhood atopy, airway hyperresponsiveness, and wheezing, which would allow the rational selection of interventions to reduce morbidity from asthma. Risk factors for these disorders were examined in a birth cohort of 1037 New Zealand children. METHODS: Responses to questions on respiratory symptoms and measurements of lung function and airway responsiveness were obtained every two to three years throughout childhood and adolescence, with over 85% cohort retention at age 18 years. Atopy was determined by skin prick tests at age 13 years. Relations between parental and neonatal factors, the development of atopy, and features of asthma were determined by comparison of proportions and logistic regression. RESULTS: Male sex was a significant independent predictor for atopy, airway hyper-responsiveness, hay fever, and asthma. A positive family history, especially maternal, of asthma strongly predicted childhood atopy, airway hyperresponsiveness, asthma, and hay fever. Maternal smoking in the last trimester was correlated with the onset of childhood asthma by the age of 1 year. Birth in the winter season increased the risk of sensitisation to cats. Among those with a parental history of asthma or hay fever, birth in autumn and winter also increased the risk of sensitisation to house dust mites. The number of siblings, position in the family, socioeconomic status, and birth weight were not consistently predictive of any characteristic of asthma. CONCLUSIONS: Male sex, parental atopy, and maternal smoking during pregnancy are risk factors for asthma in young children. Children born in winter exhibit a greater prevalence of sensitisation to cats and house dust mites. These data suggest possible areas for intervention in children at risk because of parental atopy.     

Chronic inflammation and airway remodeling in asthma. Importance of an early treatment

Chronic inflammation in asthma stimulates complex repair mechanisms which ultimately lead to deep structural changes in the bronchial tree, defined as airway remodeling, consisting principally in the thickening of the bronchial wall. These processes contribute to progressive airway narrowing with incomplete responsiveness to bronchodilating agents: clinical conditions of patients are irreversibly impaired. There is evidence that remodeling is a process that begins in early childhood and continues into adult life. These observations provide the rationale for early intervention with antiinflammatory drugs like inhaled corticosteroids, which effectively reduce airway inflammation and possibly prevent the progression to lung damage. Several clinical and pharmacological studies have demonstrated that these drugs inhibit cellular processes involved remodeling.     

儿童气道黏液高分泌的管理

气道黏液通常是呼吸道的第一道防线,是先天免疫的重要组成部分.分泌出现异常时可导致气道黏液高分泌,黏液聚集并阻塞气道,可引起通气功能障碍;同时过量黏液可降低黏液纤毛清除功能和局部防御功能,导致出现反复呼吸道感染.气道黏液高分泌与支气管哮喘、囊性纤维化、支气管扩张、下呼吸道感染等多种疾病密切相关,是影响这些疾病发生、发展及...     

Cold air challenge and specific airway resistance in preschool children

Important asthma outcomes such as lung function and bronchial hyperresponsiveness are probably determined in early childhood. Early and longitudinal objective assessment of lung function and bronchial hyperresponsiveness is necessary to enable early diagnosis, monitor intervention and improve prognosis in preschool children. Cold air challenge and plethysmographic measurement of specific airway resistance (sRaw) are feasible candidate methods for diagnosis, clinical monitoring and research during this critical period of lung growth and development. Methodology and practical aspects of cold air challenge and assessment of sRaw in preschool children are reviewed. Reference values are provided for sRaw and have allowed discrimination between health and respiratory disease, both in cross-sectional and longitudinal studies. Bronchial hyperresponsiveness can be determined with acceptable repeatability and provides good discrimination between asthmatics and healthy. The effects of classic anti-asthmatic therapies have also been documented with these techniques. The need for further standardisation and improvement of these methods and future perspectives are outlined.