Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in ISAAC Phase II.

The association between breastfeeding and wheezing, lung function and atopy was evaluated in the International Study of Asthma and Allergy in Childhood (ISAAC) Phase II. Cross-sectional studies were performed in 27 centres in 20 countries. Information on disease and exposure factors was collected by parental questionnaires. Data from 54,000 randomly selected school children (aged 8-12 yrs, 31,759 with skin prick testing) and a stratified subsample (n = 4,888) were used for testing the correlation of breastfeeding with bronchial hyperreactivity and lung function. Random effect models for meta-analysis were applied to calculate combined odds ratios (ORs). Any breastfeeding was associated with less wheeze both in affluent (adjusted OR (OR(adj)) 0.87, 95% confidence interval (CI) 0.78-0.97) and nonaffluent countries (OR(adj) 0.80, 95% CI 0.68-0.94). Further analyses revealed that this was true only for nonatopic wheeze in nonaffluent countries (OR(adj) 0.69, 95% CI 0.53-0.90). Breastfeeding was not associated with atopic wheeze and objective measures of allergy in both affluent and nonaffluent countries. In contrast, breastfeeding was associated with higher predicted forced expiratory volume in one second in affluent countries only (mean ratio 1.11, 95% CI 1.02-1.20). Breastfeeding is associated with protection against nonatopic wheeze, which becomes particularly evident in nonaffluent countries. Overall, breastfeeding was not related to any measure of allergy. These findings may explain some of the controversy regarding breastfeeding, since the direction of the association with breastfeeding depends on the predominating wheeze phenotype (e.g. atopic, nonatopic).

A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2.

BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. RESULTS: Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. CONCLUSIONS: Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.

Childhood asthma perception in Turkey under real-life environment (CAPTURE) study.

Successful management of asthma requires good communication between patients and the healthcare team. The background and expectations of a patient inevitably influence the success of any partnership. A questionnaire-based survey was performed to obtain data on the perception of the impact of asthma in daily life among children (age-range 6-14 years) and adolescents (age-range 15-20 years). A total of 756 patients (384 children, 372 adolescents) were randomly selected from 11 Turkish cities and interviewed face-to-face. Of the total study population, 71.3% received regular follow-up and 75.9% currently took asthma medication. Almost 50% reported that asthma affected their lives significantly. Even though half of the patients had symptoms at least once a week, one-third were not receiving regular prophylactic treatment. Exercise produced asthma symptoms in 45.5% of children and 27.4% of adolescents. The finding that asthma continues to be a major health problem clearly indicates an urgent need for further management programs in Turkey.

Prevalence of asthma and other allergic disorders among schoolchildren in Diyarbakir, Turkey.

This study was performed to describe the prevalence rates of allergic diseases among children in southeast Anatolia. A questionnaire survey of children six to 15 years old was conducted using a modified version of the Turkish translated ISAAC protocol, with additional questions concerning sociodemographic and environmental characteristics of children that could be potential risk factors for allergic disorders. Questionnaires were distributed to parents of all children aged below 11 years and to children themselves aged over 11 for completion. A total of 3,040 children returned the questionnaires. The lifetime prevalence rates of asthma, wheezing, allergic rhinitis and atopic dermatitis were 14.1%, 22.4%, 12.9%, and 7.8%, respectively. The prevalence of wheezing, rhinitis and chronic rash in the last 12 months were 14.7%, 39.9%, and 11.8%, respectively. The prevalence rates of symptoms and diagnoses of allergic disorders were similar in boys and girls. Passive smoking, pet ownership, number of household and socioeconomic status were not significant risk factors for allergic diseases. Family history of atopy was the most prominent risk factor for all types of allergic diseases, high prevalence rates of asthma, rhinitis and eczema exist among schoolchildren in southeast Anatolia.

Serum levels of eosinophilic cationic protein (ECP), myeloperoxidase (MPO), lipid peroxidation products, interleukin (IL)-5 and interferon (IFN)-gamma in children with bronchial asthma at acute asthma attack and remission.

We determined serum levels of myeloperoxidase (MPO), eosinophilic cationic protein (ECP), reactive oxygen species measured as thiobarbituric acid reactive substances (TBARS), interleukin (IL)-5, and interferon (IFN)-gamma in 14 asthmatic children during an asthma attack and remission. Twelve healthy children served as controls. In atopic asthmatics, asthma attack resulted insignificant elevations of ECP, MPO, and TBARS compared to remission. TBARS levels were also higher at remission compared to controls. However, there was a great deal of overlap in the values of asthmatics and controls. IL-5 and IFN-gamma were detectable at low levels and only in a few patients. These results provide further evidence for participation of eosinophils, neutrophils and reactive oxygen species in the pathogenesis of acute asthma, and suggest that their products may be used in monitoring asthma attack. Serum IL-5 and IFN-gamma levels are not appropriate for use in the follow-up of asthmatic children.

Serum levels of antioxidant vitamins (alpha tocopherol, beta carotene, and ascorbic acid) in children with bronchial asthma.

We determined serum levels of alpha tocopherol, beta carotene, and ascorbic acid and lipid peroxidation products (thiobarbituric acid reactive substances--TBARS) in 14 children during an asthma attack and remission. Twelve healthy children served as controls. All antioxidant vitamins were significantly lower in asthmatics at remission compared to controls. Comparison of attack and remission periods in asthmatic patients failed to reveal any difference except in beta carotene (p = 0.03). The levels of all three vitamins correlated very significantly with each other (r = 0.89-0.95). TBARS levels were significantly higher at asthma attack compared to remission (p = 0.001). No correlation was observed between the antioxidant vitamins and lipid peroxidation products. This study shows that antioxidant vitamins are decreased in sera of asthmatic patients even during the asymptomatic periods of the disease, and that this decrease is not totally dependent on the increased oxidative stress as reflected by lipid peroxidation products. The role of antioxidant vitamins in prevention and/or treatment of asthma remains to be determined.

Comparison of two different dose regimens of nedocromil sodium with placebo in the management of childhood asthma.

According to the recent guidelines, persistent asthma requires daily antiinflammatory treatment with either nedocromil sodium, cromolyn sodium or inhaled corticosteroids. In choosing the most appropriate drug, it is wise to weigh the therapeutic advantages against possible side effects, particularly in patients at the milder end of disease spectrum and in children. Cromolyn sodium and nedocromil sodium both have strong safety profiles, and nedocromil sodium has been reported to have a broader spectrum of efficacy than cromolyn sodium. In an attempt to provide data for the efficacy of two different dose regimens of inhaled nedocromil sodium in childhood asthma, a placebo-controlled, randomized, double-blind, double-dummy, parallel group study was conducted in 38 subjects with mild to moderate persistent asthma. After a 2-week run-in period, patients were randomly allocated into one of the three study groups and treated with either placebo or with two times daily (4 mg b.i.d.) or four times daily (4 mg q.i.d.) regimens of inhaled nedocromil sodium for 8 weeks. Symptom scores, bronchodilator requirements, FEV1, daily PEFs and methacholine hyperreactivity were evaluated at study entry, before randomization and at weeks 4 and 8 of treatment. In the four times daily treatment group, slight but significant increases were observed in FEV1, peak expiratory flows and symptom scores (p < 0.05 for each). However, there was no significant change in methacholine hyperreactivity and bronchodilator requirement. In the two times dose regimen and placebo groups, there were no improvements in any of the variables. The compliance, measured as the reduced weight of the canisters, was low, but was not different between the two nedocromil sodium treatment groups. The four times daily regimen of nedocromil sodium was effective in improving control of mild to moderate persistent asthma in children, whereas the two times daily regimen failed.

Evaluation of immunotherapy by nasal antigen challenge.

BACKGROUND: Nasal antigen challenge test is used to evaluate the allergic conditions within different diagnostic procedures. OBJECTIVE: This study was conducted to evaluate the efficacy of immunotherapy (IT) in an objective and simple way in children with perennial allergic rhinitis. METHOD: This study was a double-blind, placebo-controlled procedure. Nineteen patients (mean age 10 +/- 6 years) were treated only with IT and 17 patients (mean age 11 +/- 5 years) constituted the control group without any treatment. The patients were evaluated at the beginning and at 3 and 6 months of IT. Nasal provocation reactions were evaluated and scored at 5-, 10-, and 30-minute intervals. RESULTS: In the IT group, mean clinical scores and mean nasal provocation scores decreased significantly between the initial value and at 3 and 6 months of IT, whereas there was no significant change in the value for the control group. There were no significant differences among the 5-, 10-, 15-, and 30-minute evaluations within both the IT and control groups. CONCLUSION: The efficacy of IT in perennial allergic rhinitis may be assessed by the nasal antigen challenge test in a simple and objective way within a 5-minute period.

Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial.

AIMS: To determine the role of formoterol in the treatment of children with bronchial asthma who are symptomatic despite regular use of inhaled corticosteroids. METHODS: A randomised, double blind, parallel group, placebo controlled study to investigate the effects of inhaled formoterol (12 microg twice a day) in 32 children with moderate to severe bronchial asthma. The study consisted of two week run in periods and six week treatment periods, during both of which the patients continued their regular anti-inflammatory drugs. The efficacy parameters were symptom scores, bronchodilator use, daily peak expiratory flow rates (PEFR), methacholine hyper-reactivity, forced expiratory volume in one second (FEV1), lung volumes, and airway conductance. RESULTS: Formoterol treatment for six weeks decreased symptom scores, PEFR variability, and the number of rescue salbutamol doses, and increased morning and evening PEFR significantly. No adverse reactions were seen. CONCLUSION: These findings suggest that inhaled formoterol is effective in controlling chronic asthma symptoms in children who are symptomatic despite regular use of inhaled corticosteroids.

Prevalence of asthma symptoms among Turkish Cypriot schoolchildren.

We assessed the prevalence of symptoms suggestive of asthma in Turkish Cypriot schoolchildren and the associated risk factors using a slightly modified version of the ISAAC (International Study of Asthma and Allergies in Childhood) questionnaire. The questionnaire and questions regarding risk factors were issued to the parents of 2,822 children aged six to 14 years. The response rate was 89.6 percent. The cumulative and 12-month prevalence of wheezing were 14.7 and 4.8 percent, respectively. The prevalence of physician-diagnosed asthma was 11.4 percent. Family history of atopy was the strongest risk factor for "ever wheezing" (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.52-1.92) and physician-diagnosed asthma (OR 1.71, CI 1.53-1.93). This study demonstrates that symptoms suggestive of asthma are quite common and constitute a major health problem in Northern Cyprus.

Latex sensitivity among hospital employees and atopic children.

Allergic reactions to latex products are an important health problem for health care workers and children. To investigate the prevalence of latex and latex-associated food sensitivities among hospital employees and atopic children, 61 hospital employees (44 nurses, 13 cleaning staff, 4 technicians) and 40 atopic children were evaluated by in vivo and in vitro testing methods. All subjects were also skin prick tested with common inhalant allergens and some cross-reactive food allergens to latex. In addition, all subjects were evaluated using an enzyme-linked immunometric assay for detection of specific IgE to inhalant allergens and to the known food latex cross-reactant food allergens (banana, chestnut, peanut and kiwi fruit). Latex challenges were performed in 12 history-negative and anti-latex IgE positive atopic children. Seven of the 61 hospital staff (11.4%) and four of the 40 atopic children (10%) showed skin reactivity to latex. By serologic testing, hypersensitivity to latex was found in 30 subjects, to banana in 23, to chestnut in 37, to peanut in 32 and to kiwi fruit in 22 subjects. Latex challenges were negative in all of the children who were tested. Total IgE was higher than expected in 32 subjects and 50 individuals tested positive for specific IgE to common inhalant allergens (AlaTOP). These results indicate that latex allergy may be a health problem for our hospital staff and atopic children. In vitro testing may detect latex-specific IgE in atopic children even when no history of an adverse reaction to latex is present.

The effect of house dust mite specific immunotherapy on cysteinyl leukotriene production by blood leukocytes in subjects with perennial allergic rhinitis and asthma.

Specific immunotherapy has been successfully used in the treatment of allergic diseases for years. In this study, we examined the clinical efficacy of specific immunotherapy and its effect on cysteinyl leukotriene releasability by blood leukocytes in house dust mite allergic subjects with asthma and allergic rhinitis. In an open, parallel study, 13 subjects were treated with specific immunotherapy for 12 months and five patients served as the control group. Before specific immunotherapy treatment, and 1 and 12 months after, patients were evaluated with respect to total immunoglobulin (Ig) E levels, Dermatophagoides pteronyssinus specific IgE levels, symptom scores, usage of rescue medicines, lung function tests, nasal challenge scores, skin reactivity to D. pteronyssinus and cysteinyl leukotriene releasability by blood leukocytes. At the 12th month of specific immunotherapy, total asthma symptom scores, bronchodilator requirement, number of sneezes following nasal challenge and immediate skin reactivity to D. pteronyssinus was decreased, while FEV1 increased compared to the pretreatment values (p < 0.05 for each). These parameters remained unchanged in the control group. In vitro cysteinyl leukotriene releasability by blood leukocytes in response to D. pteronyssinus antigen and anti-IgE antibody remained unchanged both in the specific immunotherapy group and the control group. However, in the treated group, there were six patients who showed at least a 50% reduction in their symptoms after specific immunotherapy. In five of these, cysteinyl leukotriene release induced by both HACM buffer and D. pteronyssinus were decreased by more than 50% of the baseline values. The other patient demonstrated only a marked decrease (more than 50%) in background. Our results suggest that specific immunotherapy is effective in the treatment of allergic rhinitis and bronchial asthma due to house dust mite allergy and that the clinical response to specific immunotherapy may be associated with decreased cysteinyl leukotriene releasibility by blood leukocytes in some patients.

Prevalence of asthma symptoms in school children in Ankara, Turkey.

The aim of this study was to determine the prevalence of symptoms suggestive of asthma in children aged 7-14 years in Ankara, Turkey. For this purpose, the recently developed ISAAC (International Study for Asthma and Allergies in Childhood) questionnaire supplemented with six additional questions was issued to parents of 3154 primary school children from 12 schools. A separate page with questions regarding risk factors was also added to the questionnaire. The response rate was 88.3%. The cumulative and 12-month prevalence of wheezing were 14.4 and 4.7% respectively. The prevalence of physician-diagnosed asthma was 8.1%. A family history of atopy was found to be the strongest risk factor for having ever had wheezing (odds ratio (OR) = 2.89, 95% confidence interval (CI) = 2.32-3.60), wheezing in the past 12 months (OR = 3.21, CI = 2.21-4.67), and severe attack (OR = 2.41, CI = 1.36-4.25). Passive smoking was a risk only for having ever had wheezing (OR = 1.33, CI = 1.03-1.76). Increasing age was associated with a lower risk of current wheezing (OR = 0.85, CI = 0.81-0.90) and severe attack (OR = 0.77, CI = 0.67-0.88). Gender, socio-economic level and pet ownership did not appear to be risk factors for asthma-related symptoms. This study, the first epidemiological survey in Ankara, Turkey, using the ISAAC protocol, clearly shows that symptoms suggestive of asthma, albeit lower than in most European countries, are quite common and constitute a major health problem in Turkey.

Comparison of four different measures of bronchial responsiveness in asthmatic children.

Although several tests are available to assess the presence and severity of bronchial hyperresponsiveness (BHR), there is no agreement on the most appropriate stimulus. The most commonly used stimuli are methacholine, histamine, and exercise. Daily peak expiratory flow (PEF) variation has been reported to correlate with the severity of BHR, and in recent years this has been widely used because of its noninvasiveness and ease of performance. This study was carried out to determine the relationship among these four commonly used measures of bronchial responsiveness in asthmatic children. For this purpose, 12 asthmatic children of varying disease severity were recruited. Subjects underwent three challenges on 3 separate days in 1 week. During the week preceding the challenges (methacholine, histamine, and exercise), patients recorded PEF three times a day. All patients had PC20 less than 8 mg/ml with methacholine and histamine. Patients with PC20 greater than 3.5 mg/ml for both methacholine or histamine had negative exercise challenges. The strongest correlation was between histamine and methacholine (r = 0.95). Exercise-induced bronchospasm had substantial and significant correlation with the other three measures. No significant correlation was observed between PEF variability and histamine or methacholine. The varying degrees of relationships among the four commonly used measures suggests that each method yields information on different but related phenomena. More than one measure may be required to detect the different aspects of asthmatic bronchial responsiveness.

Inhaled budesonide reduces lung hyperinflation in children with asthma.

Previous studies have shown that asthmatics have hyperinflation as defined by larger total lung capacity. The present study was set up in order to document changes in asthma clinic, airway calibre, airway reactivity and lung volumes after budesonide treatment. After a 2-week run-in period, 28 children with moderate persistent asthma were treated in a double-blind manner either with budesonide (0.4 mg/day) or placebo for 8 weeks and, thereafter, all patients were treated with open-label budesonide for a further 20 weeks. Symptoms, bronchodilator requirements and airway calibre improved significantly after 8 weeks of treatment (p < 0.05 for each) and prolonged treatment did not cause any further improvement. Reduction in hyperreactivity was apparent only after 20-28 weeks of treatment. Total lung capacity decreased along with budesonide treatment in both groups suggesting that early introduction of an inhaled corticosteroid may be useful in the prevention of asthma-related remodelling of the lung and thoracic cage.

The prevalence of self-reported asthma and respiratory symptoms in Ankara, Turkey.

The prevalence of self-reported asthma was studied in a group of Turkish adults using the European Community Respiratory Health Survey (ECRHS) questionnaire distributed during 1994 local elections in Ankara, Turkey. A total of 2020 questionnaires were issued and 1820(90%) were returned. The mean age of the subjects was 34.5 +/- 10.2 years. The prevalence of wheezing at any time in the past was 39.1% which is much higher than has been reported in the literature. However, only 21.7% of the study population had wheezing in the year preceding the survey and 2.9% of them had severe asthma attacks. The prevlaences of nocturnal wheeze, nocturnal cough and morning tightness were higher in females (P = 0.05 for each). The results of this study showed a high rate of reported symptoms but a low rate of diagnosis and treatment of asthma among the adult population in Ankara.

Standardization of methacholine inhalation challenge.

Methacholine inhalation challenge has been shown to be an extremely useful diagnostic test. The purpose of this study was to document the reproducibility of methacholine inhalation challenge used in our clinic. In addition, we also examined the output of the delivery system, the stability of four-month-old methacholine solution, and the cumulative effect of methacholine. To document reproducibility, two identical challenges were performed in each of 19 asthmatic children. The influence of the previous doses of methacholine on bronchial response was examined by performing a third challenge with a single dose of methacholine in ten of these children. The remaining nine children were also tested for the third time with four-month-old methacholine solution to examine the stability of that solution. The output of the delivery system was assessed by measuring the change in weight of the nebulizer. Responses to methacholine were highly reproducible within one doubling dose interval. There was a small but significant cumulative effect of methacholine. Comparable results were obtained with newly prepared methacholine solution and four-month-old solution. The variability of the output of the same nebuliser was less than that of different nebulisers of the same model. The major clinical implication of our results is that our methacholine inhalation challenge procedure is standardized. This encourages more widespread use of this important diagnostic test for demonstration of airway hyper-responsiveness.

Effect of oral and inhaled salbutamol in infants with bronchiolitis.

The response of bronchiolitis to bronchodilator drugs is controversial. The present study was designed to evaluate the efficacy of oral or metered dose inhaler (MDI) salbutamol using a coffee cup as a spacer device in bronchiolitis. In the trial, 31 hospitalized patients between 6 and 24 months of age, who exhibited the first episode of acute bronchiolitis without any other predisposing illness such as cystic fibrosis, congenital heart disease etc., were randomly assigned to receive oral salbutamol (n = 11, 0.1 mg/kg per dose, four times a day), or MDI salbutamol (n = 12, 200 micrograms per dose, every 3 h) or formed the control group without any bronchodilator therapy (n = 8). All of the patients were given supplemental oxygen as needed and adequate hydration was maintained. The patients were evaluated with clinical symptom scores. There were no differences in the beneficial or side effects of salbutamol, or the number of days in hospital between the treatment groups and the control group. It was concluded that there is no beneficial effect in using bronchodilators in infants with bronchiolitis. Supplemental oxygen and maintenance of normal hydration may be adequate.

Prevalence of allergic diseases and influencing factors in primary-school children in the Ankara Region of Turkey.

We have studied the prevalence of atopic disease, by questionnaire, in 3024 primary-school children from three different socioeconomic levels in Ankara. Physical examinations were also performed on these children. The cumulative prevalence of asthma, allergic rhinitis, allergic conjunctivitis, and atopic eczema was 6.9%, 11.7%, 4.6%, and 2.6%, respectively. Allergic rhinitis was more common in children older than 10 years. Most of the symptoms of asthmatic patients began in the first 3 years of life. The cumulative prevalence of allergic diseases was 23.4%. This study has estimated the prevalence of allergic diseases, including asthma, allergic rhinitis, allergic conjunctivitis, and allergic dermatitis, in the Ankara region of Turkey.

Efficacy of salmeterol in the treatment of childhood asthma.

The aim of the clinical study reported here was to investigate the efficacy of salmeterol, a new long-acting selective beta 2-agonist, in patients with bronchial asthma. Twenty-four children with moderate asthma were enrolled in the longitudinal study, consisting of a run-in period of 2 weeks followed by a treatment period of 4 weeks. Maintenance treatment consisted of inhaled corticosteroid and disodium cromoglycate, or both, at the same daily dose throughout the study. During the run-in period, the patients continued to inhale salbutamol when needed and some of them (37%) also received theophylline. They were subsequently treated with salmeterol 50 micrograms twice daily and prn salbutamol for 4 weeks. Efficacy was evaluated using symptom scores and pulmonary function tests including forced vital capacity parameters, pulmonary volumes, airway resistance and specific airway conductance that were measured sensitively by a whole body plethysmograph. As a result, salmeterol produced significant improvement in morning and evening peak expiratory flow rates, vital capacity, airway resistance, conductance and asthma symptoms versus salbutamol and theophylline. Adverse reactions were judged to be mild and few.