运动-组胺激发试验对提高支气管哮喘诊断价值的研究

目的　探讨运动 -组胺激发试验 (EHIA)对支气管哮喘的诊断价值 .方法　对 2 0例健康者、118例支气管哮喘、2 2例过敏性鼻炎、2 4例慢性支气管炎患者进行运动 -组胺激发试验 ,并与单纯运动激发试验及组胺激发试验进行比较 .结果　显示运动 -组胺激发试验对哮喘患者的诊断阳性率达 97.4%、特异性 10 0 % ,且EHIA阳性所吸入的组胺量也反映了哮喘患者非特异性气道高反应性 .结论　运动 -组胺激发试验对提高早期及非典型支气管哮喘的确诊具有实用价值     

Occurrence of atopy in asthmatic children

Asthma is one of the most common chronic diseases among children. The prevalence of asthma among adult and children has systematically increased for the last thirty years. It was hypothesized that atopy was a strong background predisposing to asthma. The aim of the study was to assess the occurrence of atopy in children suffering from asthma. Two groups of children were examined. The study group consisted of 24 children aged 3-7 suffering from asthma and 26 children with bronchitis. Data about each patient's personal and family allergic history were collected. Each child had skin prick tests with common allergens made, total and specific IgE level was measured and blood eosinophil count and spirometry were performed. The result showed that asthma in 88% of the children had an atopic background. Above 70% of the children had allergic diseases other than asthma--the most common was allergic rhinitis (54%) and atopic dermatitis (37.5%). Skin tests revealed that the examined children were mostly sensitized to the allergens of house dust (85.7%), house dust mite (66.6%), and grass pollen (33.3%). Atopic features were also found in children suffering from recurrent bronchitis.     

Prevalence of asthmatic phenotypes and bronchial hyperresponsiveness in Turkish schoolchildren: an International Study of Asthma and Allergies in Childhood (ISAAC) phase 2 study.

BACKGROUND: Numerous epidemiologic studies have revealed that bronchial asthma affects populations without regard to frontiers. However, standardized methodological approaches are necessary to compare these populations. OBJECTIVE: To investigate objective markers of childhood asthma on an epidemiologic basis and to include Turkish children in international comparisons. METHODS: Parental questionnaires were collected and skin prick tests performed on fourth grade primary schoolchildren, aged 8 to 11 years, residing in Ankara, Turkey. Pulmonary function tests and bronchial challenge with hypertonic saline (HS) were conducted in children selected from this cohort with a stratified random sampling according to the presence of current wheezing. RESULTS: A total of 3,041 questionnaires were included in the evaluation. Skin prick tests were performed on 2,774 children (97.1%). A total of 347 children from this cohort underwent pulmonary function and bronchial challenge tests. In 18 (5.1%) of the 347 children, bronchial challenge tests could not be successfully completed. The prevalence values were 11.5% for current wheezing, 6.9% for physician-diagnosed asthma, and 7.7% for physician-diagnosed recurrent bronchitis. Population-based weighted prevalence of bronchial hyperresponsiveness (BHR) was 21.8%. Frequency of responses to HS was 38.6% among physician-diagnosed asthma cases and 30.5% among patients with current wheezing. Skin test positivity was present in 38.7% of the children with a diagnosis of asthma or asthmatic bronchitis, 35.0% of current asthmatic patients, and 19.2% of patients with current wheezing. CONCLUSIONS: Objective markers, in addition to the questionnaire-based prevalence figures, need to be used in epidemiologic surveys for asthma, especially in countries with inadequate health care facilities or problems with interpretation of the wheeze concept.     

Bronchial hyperresponsiveness in children with atopic rhinitis: a 7-year follow-up

BACKGROUND: A high prevalence of bronchial hyperresponsiveness (BHR) was found in atopic subjects with rhinitis. Those subjects may be at higher risk for developing bronchial asthma. We evaluated, in a 7-year follow-up, BHR and atopy in a homogeneous population of nonasthmatic children with allergic rhinitis (AR), and their role in asthma development. METHODS: Twenty-eight children (6-15 years) with AR were studied. At enrollment (T(0)), skin tests, total serum IgE assay, peak expiratory flow (PEF) monitoring and methacholine (Mch) bronchial challenge were performed. BHR was computed as the Mch dose causing a 20% forced expiratory volume (FEV)(1) fall (PD(20)FEV(1)) and as dose-response slope (D(RS)). Subjects were reassessed after 7 years (T(1)) using the same criteria. RESULTS: At T(0), 13 children (46%), showing a PD(20)FEV(1) <1526 microg of Mch, had BHR (Mch+), although PEF variability (PEFv) was within normal limits. None of the children with negative methacholine test developed bronchial asthma after 7 years. Of the 13 Mch+, only two reported asthma symptoms after 7 years. No significant change was seen in the other parameters of atopy considered. CONCLUSION: Children with allergic rhinitis present a high prevalence of BHR. Nevertheless, their PEFv is normal and the rate of asthma development low.     

Skin sensitization to common allergens in Turkish wheezy children less than 3 years of age

Infants and small children with asthma are not commonly skin tested, as allergy is not considered to be a major cause of infantile asthma. The aim of this study was to determine the frequency of skin test positivity to various allergens in wheezy children less than 3 years of age. We evaluated 161 patients with infantile asthma (median age 20 months) and 100 healthy controls (median age 18 months). Infantile asthma was defined as three or more episodes of wheezing in a child less than 3 years of age, whose symptoms improved on treatment with beta-agonist and anti-inflammatory agents. All children were skin tested to house dust mites (HDM), pollens, molds, and cow milk extracts using prick technique. One hundred and eighteen (73.3%) children In the patient group tested positive to HDM, 84 (52.1%) to pollens, 37 (22.9%) to molds, and 16 (10%) to cow milk. Sensitization rates to HDM were significantly higher in the patient group than In the healthy controls. Sensitization rates to pollens were not statistically different between the two groups. There was no association between family history of atopy and frequency of sensitization to allergens in the wheezy and control groups. We concluded that skin sensitization to allergens was common In wheezy infants. The prevalence of sensitization to indoor allergens was higher than to outdoor or food allergens.     

Recurrent acute bronchitis: the association with undiagnosed bronchial asthma

Forty-six consecutive patients with a history of recurrent acute bronchitis (chest colds) referred from primary care clinics were studied prospectively to determine if hyperreactive airways (mild bronchial asthma) was a concomitant entity. Mild bronchial asthma was diagnosed in 30/46 (65%) patients by history, physical examination, and routine spirometry, or by methacholine bronchial provocation. The incidence of mild bronchial asthma was markedly increased in patients with a history of recurrent acute bronchitis over that seen in the general population. These results emphasize a need to investigate an underlying cause in patients with recurrent acute bronchitis.     

Preferential transmission and association of the -403 G --> A promoter RANTES polymorphism with atopic asthma

Asthma is a complex inherited disease. The study was undertaken to identify the association of RANTES promoter polymorphisms with atopy and asthma using family-based association tests (FBATs) and generation-specific case-control analyses. We identified 154 nuclear families (453 individuals) in whom we established RANTES promoter status using the RFLP-PCR method. Of the two known promoter polymorphisms -403G/A and -28C/G, only the former appeared with a clinically relevant frequency. A total of 61 families were eligible for assessment of transmission of the allele with asthma and atopy by the pedigree disequilibrium test (PDT). Overall, allele frequency for -403A was 38.3% and 84 of 89 (94.3%) alleles were transmitted with physician diagnosed asthma (PDA) (P=0.001). All 89 children with atopy received the mutant allele, which was more than expected following Mendelian Laws of transmission (P=0.0001). In 303 unrelated parents, significant associations of the mutant allele were for atopy with or without asthma (P=0.001). In 150 unrelated children, significant associations were for atopy alone (P=0.001) and asthma (P=0.001). No associations were found for bronchial hyper-responsiveness (BHR). The -403 G --> A is transmitted with atopy and atopic asthma, although its contribution appears to relate more to atopy than asthma and BHR.     

Chlamydia pneumoniae infection in patients with acute bronchitis and bronchial asthma]

In this study, a total of 60 patients with acute bronchitis, 71 patients with bronchial asthma and 20 healthy volunteers were serologically and bacteriologically analyzed to investigate whether Chlamydia pneumoniae infection is associated with the onset and the exacerbation with acute bronchitis and bronchial asthma. Antibody titers to Chlamydia pneumoniae were also measured and compared by ELISA method. The antibody-positive rate in the patients with acute bronchitis (88.4%) was significantly higher than that in the patients with bronchial asthma (73.3%) or that in the healthy volunteers (60%). And the levels of the IgA antibody in the patients with acute bronchitis were significantly higher than those in the patients with bronchial asthma or those in the healthy volunteers. The rate of acute C. pneumoniae infection in the patients with acute bronchitis (20%) did not show significantly differences compared with that in the patients with bronchial asthma (15.5%) or that in the healthy volunteers (10%). The cases of acute C. pneumoniae infection had both as a single etiologic agent and as a mixed infection, most often with Streptococcus pneumoniae. Therefore, we demonstrated that the acute C. pneumoniae infection may be associated with the onset and the exacerbation in acute bronchitis and bronchial asthma.     

Relationship between recurrent croup and airway hyperreactivity

The relationship between recurrent croup and bronchial asthma was evaluated by measuring bronchial hyperreactivity (methacholine challenge), physiologic parameters of upper airway obstruction, and skin response to environmental allergens. Patients with recurrent croup (n = 10) had a significantly higher degree of airway hyperreactivity and atopy than healthy children (n = 15), but significantly less than the patients with bronchial asthma (n = 30). No physiologic signs of upper airway obstruction could be detected at rest or following methacholine. It is suggested that bronchial asthma and recurrent croup share a few characteristics.     

Exercise-induced asthma in Nepalese children

Three hundred and one children between 5 and 15 years old in the hills of east Nepal were studied to determine the prevalence and the main causes of asthma and atopy. Asthma was diagnosed on the basis of history, clinical examination and the results of a 6-min exercise test (step test). Asthma was diagnosed in six children, none of whom was skin prick test positive. We present here normal values of baseline peak expiratory flow rate (PEFR), and the exercise-induced changes in PEFR in normals, asthmatics, other wheezy children and others with atopic histories. The results of the skin prick tests are presented with the atopic histories in another paper.     

IL-5, IL-8 and GM-CSF immunostaining of sputum cells in bronchial asthma and chronic bronchitis

Background: Granulocyte-macrophage colony stimulating factor (GM-CSF) and inlerleukin (IL)-5 or IL-8 have been .suggested to play an important role in the pathogenesis of eosinophilic airway inflammation in bronchial asthma or neutrophilic airway inflammation in chronic bronchitis, respectively, However, GM-CSF and IL-8 have biological activities to either eosinophils or neutrophils. Objective: To investigate the contribution of these cytokines to airway inflammation, we compared the cellular differential and immunolocalization of GM-CSF, IL-5 and IL-8 in sputum cells from patients with bronchial asthma and chronic bronchitis. Methods: Cytospins of sputum cells from 12 patients with bronchial asthma and 12 with chronic bronchitis were subjected to cellular differential counting and immunocytochemistry with antihuman GM-CSF, IL-5 and IL-8 antibody. Results: The predominant cells in bronchial asthma were eosinophils and lymphocytes, while those in chronic bronchitis were neutrophils. All cytokines examined were detected in either bronchial asthma or chronic bronchitis, although the percentage of GM-CSF and IL-5 positive cells in bronchial asthma (53.4 ± 6.0 [mean±sfm ]% and 9.7 ± 2.8%, respectively) was significantly higher than that in chronic bronchitis (11.4±2.5%; P < 0.001 and 1.7plusmn;0.3%; P < 0.007. respectively). In contrast, the percentage of IL-8 positive cells in chronic bronchitis (23.8 ± 7.0%) was significantly higher than that in bronchial asthma (7.7 ± 1.9%; P < 0.04). The cells positive for IL-5 were lymphocytes in bronchial asthma and chronic bronchitis. The cells positive for GM-CSF in bronchial asthma were predominantly eosinophils. while those in chronic bronchitis were monocytes/macrophages and neutrophils. In contrast, neutrophils are mainly positive for IL-8 in chronic bronchitis, while monocytes/macrophages and bronchial epithelial cells are positive for IL-8 in bronchial asthma. Conclusion: The immunochcmical comparison of GM-CSF and IL-8 localization in sputum cells between bronchial asthma chronic bronchitis suggests the differential regulation and roles of these cytokines in eosinophilic vs neutrophilic airway inflammation, resulting in the development of different types of airway inflammation.     

Atopy and house dust mite sensitization as risk factors for asthma in children

BACKGROUND: Recent evidence suggests that asthma is not invariably related to atopy. The aim of this study was to evaluate the frequency of atopy, asthma and sensitization to eight common allergens in a large group of children with allergic symptoms. METHODS: 1426 children referred to our Paediatric Asthma and Allergy Center because of allergic symptoms were examined. Bronchial asthma, allergic rhino-conjunctivitis, food allergy and atopic dermatitis were diagnosed with standardized methods. Atopy was diagnosed if at least one skin test was positive. RESULTS: Of the 1426 children examined, 629 (44%) were atopic and 769 (56%) were non-atopic. Asthma was diagnosed in the same proportion (i.e., 64%) of atopic and non-atopic children. However, after division into age groups, non-atopic asthma was significantly more prevalent (chi2 = 8.46) in children between 0 and 3 years old (group 1). On the other hand, atopy was significantly associated with asthma only in group 3 (odds ratio 1.85). Furthermore, a significant association with asthma symptoms was found for house dust mite (HDM) in group 3 (odds ratio 4.8). CONCLUSIONS: Asthma is related to atopy in pre-selected children only from the age of 7 years. House dust mite sensitization seems to be an important determinant of asthma in these "older" children.     

Bronchodilating effect of ipratropium bromide inhalation powder and aerosol in children and adolescents with stable bronchial asthma

Ulrik CS, Backer V, Bach-Mortensen N. Bronchodilating effect of ipratropium bromide inhalation powder and aerosol in children and adolescents with stable bronchial asthma. The purpose of this study was to compare the bronchodilating effect of ipratropium bromide (IB) administered by a conventional Ingelheim powder device system (IPI) and by a metered dose inhaler (MDI) in children and adolescents with stable bronchial asthma. Seventy patients, aged 7 to 16 years, with stable bronchial asthma from our outpatient clinic were tested for bronchial responsiveness to inhaled IB. Fifteen (21%) of the 70 subjects were found to have a substantial bronchial response to inhalation of 40 γg IB, i.e. at least 15% increase in FEV₁ 30 min after inhalation; the remaining 55 subjects had <15% increase in FEV₁. No relationship between severity of asthma, age or sex and bronchial responsiveness to inhaled IB was found. Among the 15 subjects who had substantial bronchial response to IB, the increase in FEV₁ after inhalation of fenoterol tended to be greater than the response to inhaled IB, although this did not reach statistical significance. Responders, i.e. subjects who had at least 15% increase in FEV₁ after inhalation of IB, took part in a double-blind, cross-over study of the bronchodilating effect of 40 γg IB delivered by IPI and MDI. We found no significant differences in the bronchodilating effect during a 6-h follow-up. Maximum bronchodilating effect of IB was reached after 30 min and the maximum response lasted for 90 min. No side or adverse effects were observed following inhalation of IB. We conclude that before starting treatment with ipratropium bromide for bronchial asthma in children and adolescents, the patients should be tested for bronchial responsiveness to inhaled IB to find out whether they are responders or nonresponders; and further that, among responders, inhalation of powder is as effective as inhalation from a dosis-aerosol.     

Adipokines in cord blood and risk of wheezing disorders within the first two years of life

BACKGROUND: Adipokines are involved in the regulation of many inflammatory processes and are present at very high concentrations in cord blood of term infants. OBJECTIVE: We analysed data of a large prospective birth cohort study to examine whether adiponectin and leptin concentration in cord blood are determinants of wheezing disorders in children within the first 2 years of life. METHODS: Seven hundred and forty mothers and their newborns were included in this analysis. Adiponectin and leptin concentrations were measured in cord blood. The cumulative incidence of physician-reported asthma or obstructive bronchitis was recorded during a 2-year follow-up. RESULTS: During the first 2 years of life, asthma or obstructive bronchitis was reported by the caring paediatricians for 157 (19.6%) of the children. We found a strong interaction of cord blood adiponectin and history of atopic disease in the mother with respect to the risk of physician-reported asthma or obstructive bronchitis (P=0.006). Compared with children with cord blood levels in the middle quintile (reference category), the odds ratios for physician-reported asthma or obstructive bronchitis in the bottom quintile and top quintile were 0.14 [95% confidence interval (CI) 0.02-0.90] and 2.12 (95% CI 0.67-6.66), respectively (P for trend=0.0003), among children of mothers with a history of atopy. This association was independent of other established risk factors. Leptin levels in cord blood were not associated with risk of asthma or obstructive bronchitis. CONCLUSIONS: In children of mothers with a history of atopy, concentrations of adiponectin in cord blood could play an important role in determining risk of wheezing disorders in early childhood.     

Bronchial hyperresponsiveness in two populations of Australian schoolchildren. I. Relation to respiratory symptoms and diagnosed asthma

In order to explore the relationship between bronchial hyperresponsiveness (BHR) to inhaled histamine, respiratory symptoms and diagnosed asthma in children, we undertook a cross-sectional study of 2363 Australian schoolchildren aged 8–11 years. The methods used included a self-administered questionnaire to parents, which was shown to have a high degree of repeatability, and a histamine inhalation test to measure bronchial responsiveness (BR). The study showed that 17.9% of children had BHR, defined as a 20% fall in FEV₁ at a provoking dose of histamine (PD₂₀ FEV₁) of less than 7.8 μmol. The distribution of PD₂₀ FEV₁ appeared to be continuous. Most children with PD₂₀ FEV₁ values < 1.0μmol had symptoms of asthma. However, 6.7% of children had BHR without symptoms or a previous diagnosis of asthma and 5.6% had had a diagnosis of asthma but had no BHR. Although there was a good association between BHR and respiratory symptoms, questionnaire data of wheeze and diagnosed asthma do not reflect accurately the level of BHR in the community. We conclude that cross-sectional studies of BR to identify children with BHR probably do not reflect the prevalence of asthma in populations of children. However, the strong association between BHR and symptoms, particularly in children with severe and moderate BHR, suggests that measurements of BR in populations are useful for defining a group of children whose airways behave differently from those of the majority. Prospective studies are needed to define the level of BHR that is associated with important sequelae.     

Clinical evaluation of eosinophils in the sputum.

The sputum differential eosinophil/neutrophil count was done in 384 patients using Leishman staining. The patients were distributed in four groups: bronchial asthma (197 patients); chronic bronchitis with wheezing (45 patients); chronic bronchitis and/or emphysema without wheezing (73 patients); other pulmonary diseases (64 patients). Eosinophils were present in patients from all groups but more frequently (P less than 0.001) in asthma: 142 (72%) of 197 patients. In bronchial asthma and chronic bronchitis with wheezing the percentages of eosinophils were more frequently (P less than 0.001) above 80%: 57% and 58% of the patients respectively. The other two groups had more cases with 19% or less eosinophils. There is no percentage level specific for asthma but levels above 80% of eosinophils are strongly suggestive of asthma or of chronic bronchitis with wheezing.     

Relationships of allergic sensitization, total immunoglobulin E and blood eosinophils to asthma severity in children of the EGEA Study

BACKGROUND: Although allergy is highly associated with childhood asthma, it is not well known if there is a relationship between the intensity of allergic sensitization and asthma severity. OBJECTIVE: The objectives of the study were to examine the relationships between several markers of allergy and asthma severity in asthmatic children included in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyper-responsiveness and atopy (EGEA). METHODS: The population comprised 216 asthmatic children below 16 years of age. Total IgE and blood eosinophil counts were measured and skin prick tests to 11 aeroallergens were performed. The intensity of the allergic sensitization was assessed by the number of positive skin prick tests and by skin weal sizes. Asthma severity was measured with four criteria: a clinical severity score, history of hospitalization for asthma, FEV1% predicted and inhaled steroid use in the last 12 months. RESULTS: Most of the children were sensitized to at least one aeroallergen (88.2%). Atopy was not related to the severity of asthma, except for a tendency for a more severe clinical score in non-atopic children. The type and intensity of the allergic sensitization were not associated with any criteria of asthma severity. Total IgE was significantly increased in children treated with inhaled corticosteroids and in children ever hospitalized for asthma (P-values 0.009 and 0.04, respectively). Eosinophil counts were not related to asthma severity. CONCLUSION: Our results suggest that severe childhood asthma may be related to a high level of total IgE but not to blood eosinophil counts. The lack of positive relationships between both atopy and the intensity of allergic sensitization with asthma severity supports the hypothesis of different risk factors being associated with asthma and with the severity of asthma.     

Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide

BACKGROUND: Children with severe asthma have persistent symptoms despite treatment with inhaled corticosteroids (ICSs). The differentiating features of severe asthma in children are poorly defined. OBJECTIVE: To identify features of severe versus mild-to-moderate asthma in school-age children using noninvasive assessments of lung function, atopy, and airway inflammation. METHODS: A total of 75 children (median age, 10 years) with asthma underwent baseline characterization including spirometry and lung volume testing, methacholine bronchoprovocation, allergy evaluation, and offline measurement of exhaled nitric oxide (F(ENO)). Twenty-eight were followed longitudinally over 6 months. Participants were assigned to the severe asthma subgroup if they required high-dose ICS plus 2 or more minor criteria. RESULTS: Children with severe versus mild-to-moderate asthma had more symptoms, greater airway obstruction, more gas trapping, and increased bronchial responsiveness to methacholine. Subjects with severe asthma also had higher concentrations of F(ENO) and significantly greater sensitization to aeroallergens. With long-term study, both the reduction in FEV(1) and increase in F(ENO) persisted in the severe versus mild-to-moderate group. Furthermore, despite adjustments in ICS doses, the frequency of exacerbations was significantly higher in subjects with severe (83%) versus mild-to-moderate asthma (43%). CONCLUSION: Severe asthma in childhood is characterized by poor symptom control despite high-dose ICS treatment and can be differentiated from mild-to-moderate asthma by measurement of lung function and F(ENO). CLINICAL IMPLICATIONS: Clinicians should suspect severe asthma in children with poor response to ICS, airway obstruction, and high F(ENO).     

Association between body mass index and allergy in teenage girls in Taiwan

BACKGROUND: The prevalence of atopy and asthma is affected by age, sex and lifestyle factors. Obesity was reported to be a risk factor for asthmatic symptoms in children and adults. OBJECTIVE: To examine the relation between body mass index (BMI) and the prevalence of atopy, rhinitis, wheezing and bronchial responsiveness in adolescents. METHODS: BMI (kg/m2), skin-prick test, bronchial hyperresponsiveness (BHR) to methacholine, and self-reported rhinitis and airway symptoms were assessed in a cross-sectional survey in 1459 eighth-grade students (age 13.2 to 15.5, mean 13.6 years) of seven junior high schools in northern Taiwan. RESULTS: The prevalence of atopy was 42% in boys and 27% in girls. The study population was grouped into quintiles of BMI by sex. Girls in the highest BMI quintile had higher prevalence of atopy and rhinitis symptoms. Compared with the middle three quintiles, they had increased risk of atopy in multivariate analyses adjusted for area of living, sibling number, parent education level and family history of asthma (odds ratio = 1.77, 95% confidence interval = 1.15-2.73). Girls with the lowest BMI quintile had lower prevalence of BHR and wheezing. Compared with the middle three quintiles, they had reduced risk of BHR in multivariate analyses adjusted for area of living, atopy, family history of asthma, and baseline pulmonary function (odds ratio = 0.40, 95% confidence interval = 0.20-0.81). No association between BMI and atopy or BHR was seen in boys. CONCLUSION: BMI was a significant predictor of atopy, allergic symptoms and BHR in teenage girls.