The effect of regular versus on-demand desloratadine treatment in children with allergic rhinitis.

OBJECTIVE: Desloratadine is a potent antihistamine. Whether regular or on-demand use of desloratadine influences its therapeutic efficacy in allergic rhinitis is unknown. The aim of the study was to compare the clinical efficacy and the anti-inflammatory activity of regularly administered desloratadine to its on-demand use in children with allergic rhinitis due to pollen allergy. METHODS: Thirty-seven patients with allergic rhinitis with or without mild intermittent asthma were enrolled in a prospective parallel group study. Patients were treated with desloratadine regularly or on-demand during pollen season. Rescue medications and symptom scores were recorded on a diary card. Nasal flow rate and inflammatory markers were recorded, and methacholine (Mch) challenge test was administered before and within the pollen season. RESULTS: Though symptoms were lower in the evening than in the morning (p<0.001), there was no difference between the two groups. There was no difference between the groups with respect to medication score except that the salbutamol use was lower in the regular treatment group during the fourth week (p=0.032) in the pollen season. Nasal flow rate and inflammatory markers failed to show any difference between the groups. A significant reduction in PC20 values (provocative concentration of Mch causing a 20% fall in FEV(1)) was observed in regular (p=0.016) and on-demand (p=0.005) treatment groups compared to the pre-season measurements. The number of children with a PC20 below 8 mg/ml increased significantly in the on-demand group. CONCLUSION: Our study demonstrates that on-demand use of desloratadine during the pollen season is clinically as effective as regular treatment. However, regular treatment may provide better control of lower airway symptoms and airway reactivity.

Are risk factors of childhood asthma predicting disease persistence in early adulthood different in the developing world?

BACKGROUND: Predictive factors of childhood asthma for favorable prognosis may differ between populations where a variety of genetic and environmental factors are present. OBJECTIVES: To document the factors predicting disease persistence in early adulthood in Turkey. METHODS: An outpatient cohort (n = 115) with a mean follow-up duration of 11.4 +/- 0.2 years was evaluated. Complete remission was defined as no asthma symptoms, no use of controller medication, no airflow limitation and no airway hyper-responsiveness, and clinical remission as no symptoms and no use of controller medication, within the past year. RESULTS: The mean ages during referral and at the final visit were 5.8 +/- 0.2 and 17.1 +/- 0.2 years, respectively. Thirty-one (27%) were in complete remission, and a further 30 (26%) in clinical remission. In multivariate logistic models, diminished airflow [forced expiratory volume in 1 s (FEV1) < 80% vs > or = 80%] at the initial lung function test predicted current diminished airflow (8.422; 2.202-32.206) (odds ratio; 95% confidence interval), and presence of obstructive pattern (FEV1/forced vital capacity (FVC) < 80% vs > or = 80%) predicted current obstructive pattern (29.333; 3.022-284.724). Furthermore, female gender appeared to predict persistence of asthma symptoms (3.330; 1.250-8.333) and absence of clinical remission (2.398; 1.038-5.254); eosinophilia predicted persistence of symptoms (4.271; 1.080-16.889) and presence of airway hyper-responsiveness (3.723; 1.129-12.278). CONCLUSIONS: Diminished airflow, female gender and eosinophilia appear to predict an adverse outcome of childhood asthma, supporting the concept that variability may exist between populations.

ALOX5 promoter genotype, asthma severity and LTC production by eosinophils.

BACKGROUND: The number of Sp1-Egr1 binding tandem repeats at the ALOX5 promoter influences gene transcription and may modify the response to anti-leukotriene treatment. The relationship of ALOX5 variants to asthma severity and leukotriene production by eosinophils is unknown. OBJECTIVE: To characterize ALOX5 mRNA expression and cysteinyl-leukotriene production by eosinophils from individuals bearing ALOX5 promoter deletional variants and their association with the severity of childhood asthma. METHODS: Eosinophils from adult asthmatics bearing only variant alleles (with other than five tandem repeats on both chromosomes, non5/non5) or no variant alleles (5/5) were cultured in vitro and ALOX5 expression and leukotriene secretion were measured. A total of 621 children with mild or moderate-severe asthma were genotyped at the ALOX5 core promoter. RESULTS: Asthmatics with non5/non5 genotype expressed less ALOX5 mRNA and produced less LTC4 into culture supernatants than 5/5 individuals (6.4 +/- 2.0 and 20.0 +/- 5.0 pg/ml, n = 5; P < 0.05). More asthmatic children bearing non5/non5 genotype had moderate-severe asthma than children with the 5/5 genotype (5.3% vs. 1.4%, P = 0.008). Multivariate logistic regression identified ALOX5 promoter genotype as a significant predictor of disease severity (OR = 3.647, 95% CI: 1.146-11.608, P = 0.03). Consistent with these findings, children bearing the non5/non5 genotype had greater bronchomotor response to exercise as measured by the maximum fall after exercise and the area under the exercise curve (P < 0.05 for both). CONCLUSION: Our results suggest that children who express the asthma phenotype despite having a genetic variant that impairs their ability to express ALOX5 have more severe disease and thus are more likely to have asthma symptoms.

The effect of polymorphisms at the CD14 promoter and the TLR4 gene on asthma phenotypes in Turkish children with asthma.

BACKGROUND: Endotoxin, with its potential to enhance type 1 immunity, is a significant player in the hygiene hypothesis. The combined effects of the genetic variants of various molecules in the endotoxin response pathway on asthma related phenotypes are largely unknown. OBJECTIVE: To investigate the effects of the genetic variants of CD14 and TLR4 genes on asthma phenotypes in a large number of asthmatic children. METHODS: 613 asthmatic children were genotyped at the CD14-C159T, TLR4-A896G and TLR4-C1196T loci. IgE, eosinophil numbers and FEV1 were compared in 327 children who were not on any controller medications and were symptom free. Multivariate logistic regression was used to determine the factors associated with total IgE. RESULTS: Among children with atopic asthma, total IgE levels were significantly different among the three genotypes in the co-dominant model [CC: 435 kU/l (interquartile range: 146-820); CT: 361 (140-710); TT 204 (98-435), P = 0.035]. TT genotype was significantly and independently associated with lower IgE levels (OR: 0.5 95%; CI = 0.28-0.90, P = 0.021). Both TLR4-A896G and TLR4-C1196T polymorphisms were more frequent in the mild asthma group with atopy (P = 0.032, 0.018, respectively). The combined effects of the genetic variants in CD14 and TLR4 genes did not improve the observed associations. CONCLUSION: Our study demonstrates that the CD14-C159T promoter variant influences total IgE levels and also indicates that the T allele has a more profound effect on total IgE in children with atopic asthma. Polymorphisms in the TLR4 gene may be associated with milder forms of disease in atopic asthmatics in the population studied.

Burden of rhinitis in children with asthma.

Although the clinical association of allergic rhinitis and asthma has been recognized for centuries, in recent years the association appears to be stronger than was reported previously. However, data for children are less clear, and some studies indicate that results observed in developing countries may differ from those observed in Western populations. We therefore intended to document the association of rhinitis with pediatric asthma in terms of caregivers' perception, physician practice, and file records. Asthmatic children aged 3-16 years with at least 1-year follow-up in an allergy-asthma outpatient clinic were invited to participate in the study during a 10-month interval. In addition to a face-to-face questionnaire-based interview, file records were evaluated retrospectively to obtain information relating to asthma and rhinitis. Of 396 patients included in the study, 369 with consistent replies were included in the analyses. The mean age of the study group was 10.6 +/- 0.2 (mean +/- SEM) years, and a greater proportion of the respondents were male (63.7%), atopic (78.3%), and mildly asthmatic (50.7%). House dust mite and grass pollens were the most commonly sensitized allergens (50.7% and 46.9%, respectively). Although only 5.4% of our study population regarded themselves as rhinitic and 23.8% had been diagnosed with allergic rhinitis according to the file records, almost 57.7% of patients had required medications for rhinitis within the last year, and 68.8% had findings consistent with allergic rhinitis. Furthermore, 41.2% and 58.8% reported that their rhinitis symptoms caused a significant burden in their daily life and exacerbated their asthma, respectively, and almost 50% felt that their rhinitis had not been given significant consideration by their physician. In conclusion, although we report a large discrepancy between caregivers' perception of rhinitis, documentation in file records, and treatments for rhinitis, the allergic rhinitis prevalence determined in the survey and the medication use for rhinitis appeared to be in agreement. We recommend a greater effort be made to identify, label, and educate children with rhinitis and their families in asthma outpatient clinics.

Decreased prevalence of atopy in paediatric patients with familial Mediterranean fever.

BACKGROUND: A number of inflammatory diseases, including familial Mediterranean fever (FMF), have been shown to be driven by a strongly dominated Th1 response, whereas the pathogenesis of atopic diseases is associated with a Th2 response. OBJECTIVE: Because dominance of interferon gamma has the potential of inhibiting Th2 type responses-that is, development of allergic disorders, to investigate whether FMF, or mutations of the MEFV gene, have an effect on allergic diseases and atopy that are associated with an increased Th2 activity. METHOD: Sixty children with FMF were questioned about allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis, as were first degree relatives, using the ISAAC Study phase II questionnaire. The ISAAC Study phase II was performed in a similar ethnic group recruited from central Anatolia among 3041 children. The same skin prick test panel used for the ISAAC Study was used to investigate the presence of atopy in patients with FMF and included common allergens. RESULTS: The prevalences of doctor diagnosed asthma, allergic rhinitis, and eczema were 3.3, 1.7, and 3.3%, respectively, in children with FMF, whereas the corresponding prevalences in the ISAAC study were 6.9, 8.2, and 2.2%, respectively. Only the prevalence of allergic rhinitis was significantly different between the two groups (p<0.001). The prevalence of atopy in these patients with FMF (4/60 (7%)) was significantly lower than in the children of the population based study (20.6%) (p<0.001). CONCLUSION: Family Mediterranean fever seems to be protective against development of atopic sensitisation and allergic rhinitis.

Hidden fish substance triggers allergy.

Food allergy (hypersensitivity) is a form of adverse food reaction caused by an immunological response to a particular food. IgE-mediated food allergy is responsible for most immediate-type food-induced hypersensitivity reactions. The prevalence of food allergy in the general population, not including oral allergy syndrome, is about 1-2%. While adults might tend to be allergic to fish, crustaceans, peanuts, and tree nuts, children, on the other hand, tend to be allergic to cow's milk, egg white, wheat, and soy. Food is the most common eliciting factor of anaphylaxis (45%), followed by drugs (29%), and insect stings (21%). Our study describes a 3 1/2-year-old boy who is allergic to fish consumed via ingestion and inhalation. This case is a good example of how easily people with food allergies can unintentionally consume foods to which they allergic, and is a clear demonstration of the dangers of such effects.

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.

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.

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.

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.

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.

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.

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.

IgG subclasses in children with recurrent respiratory tract infections in an allergy practice.

Isolated or combined deficiencies of immunoglobulin G (IgG) subclasses have been recognized in children with recurrent infections. In our allergy practice, there are a subset of children with recurrent respiratory tract infections. To investigate the presence of immunoglobulin G subclass deficiency (IgGSD), 60 children with atopy and 14 children without atopy suffering from recurrent respiratory tract infections were studied in an attempt to determine whether atopy is associated with a certain IgG subclass pattern. Ten atopic children were found to have isolated or combined IgG subclass deficiencies: one with IgG1, two with IgG2, four with IgG3 and three children had IgG2-IgG3. Neither IgG subclass concentration nor the frequency of children with high or low IgG subclasses showed any difference between atopic and non-atopic groups. Except for a week correlation with IgG3, no correlation existed between IgE and other IgG subclasses. It was concluded that childhood respiratory diseases complicated by recurrent respiratory tract infections may be associated with IgG subclass deficiencies. Although there have been reports noting some IgG subclass patterns in atopic disorders, in the present study, no distinctive feature between atopics and non-atopics with respect to IgG subclass concentrations and patterns was observed.

The effect of cetirizine on sulfidoleukotriene production by blood leukocytes in children with allergic rhinitis.

Twelve children with allergic rhinitis due to monosensitivity to Dermatophagoides pteronyssinus (Dp) took part in a placebo-controlled, double-blind, crossover study to evaluate the effect of cetirizine, a second-generation, nonsedating H1-blocker-type antihistamine, on sulfidoleukotriene releasability by blood leukocytes and to determine its correlation with clinical findings and nasal challenge scores. Sulfidoleukotriene release by blood leukocytes was determined by the cellular allergen stimulation test (CAST), which measures leukotriene (LT)C4, LTD4, and LTE4, all in one assay. Compared to placebo, cetirizine significantly (P < 0.05) decreased daily symptom scores of nasal discharge, nasal itching, and sneezing, as well as the number of sneezings after nasal challenge with the antigen, without alleviating nasal obstruction (P > 0.05). It also suppressed both early (P < 0.05) and late skin reactions to intradermal tests. Although cetirizine did not influence in vitro sulfidoleukotriene production by blood leukocytes with buffer or anti-IgE (P > 0.05), it substantially reduced the release of these mediators upon challenge with Dp antigen. Furthermore, there was a high correlation between the number of sneezes after challenge and the amount of sulfidoleukotriene released in nine patients (r = 0.78; P < 0.01). It is concluded that the amount of sulfidoleukotrienes produced by blood leukocytes in vitro may reflect the nasal hyperreactivity of the patient, and that cetirizine, which is highly effective in the treatment of allergic rhinitis, owes part of its effect to inhibition of sulfidoleukotriene releasability by blood leukocytes in children.