Allergen immunotherapy in polysensitized patient.

Specific allergen immunotherapy (AIT) is the only therapeutic method with positive impact on natural course of allergic disease - affecting clinical development (including the progression of rhinitis to asthma) and new sensitisations. The actual problem is the increasing number of patients manifesting poly-sensitivity in allergy skin tests and / or in specific IgE tests. Usually, AIT is not recommended in such individuals. The objective we are facing is that in many patients tested as poly-reactive, we have to distinguish in which cases it is a true polysensitization, and when it is due to cross-reactivity of specific IgE antibodies induced by panallergens. This may really determine when AIT may be an appropriate course of action. The article focuses on this problem in more detail, applying the long time Czech and Slovak experience with allergy testing and allergen immunotherapy.

Evidence for clinical safety, efficacy, and parent and physician perceptions of levocetirizine for the treatment of children with allergic disease.

Allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) are highly burdensome diseases, which are increasing in prevalence, especially in the paediatric population. Despite the availability of a large number of medications for treatment of AR and CIU, their use in children has primarily been based on data obtained from a limited number of clinical trials in children and/or testing in adults. The H(1)-antihistamines have traditionally been used as first-line treatment for the relief of both AR and CIU symptoms in children. The first-generation H(1)-antihistamines are associated with marked adverse effects such as sedation, sleepiness/drowsiness as well as difficulties in learning and cognitive processing; thus, they are recommended for limited or discontinued use in children with AR or CIU. In contrast, second-generation H(1)-antihistamines are more adapted for the use in children with AR and CIU due to better safety profiles. However, only a limited number of trials with these agents have been conducted and generally, data from well-designed trials in children are lacking. Levocetirizine is one of the most extensively investigated H(1)-antihistamines for its pharmacologic properties, safety, efficacy as well as overall global satisfaction in children aged 2-12 years. Levocetirizine is the only H(1)-antihistamine launched in the 21st century shown to lack clinically relevant adverse effects on physical and psychomotor development or routine laboratory tests over a long-term period of 18 months in 1- to 3-year-old children predisposed to development of allergic disease. Available data suggest that levocetirizine is a suitable treatment option for AR and CIU in children aged 6 months to 12 years.

Pharmacokinetics and pharmacodynamics of cetirizine in infants and toddlers.

The pharmacokinetics of the second generation H1-receptor antagonist cetirizine were studied in 15 infants and toddlers (mean +/- SD age, 12.3 +/- 5.4 months) who were treated with a single 0.25 mg/kg dose of cetirizine solution. The infants and toddlers were hospitalized for recurrent respiratory infections or other hypersensitivity-related diseases. Blood samples were collected at 1/2, 1, 11/2, 2, 4, 6, 8, 12, and 24 hours, and a 24-hour urine sample was obtained. A peak plasma level of 390 +/- 135 ng/ml was observed after 2.0 +/- 1.3 hours. The elimination half-life was 3.1 +/- 1.8 hours, the apparent oral body clearance was 2.13 +/- 1.15 ml/min/kg, and the apparent volume of distribution was 0.44 +/- 0.19 L/kg. The excretion of unchanged cetirizine in six complete urinary collections was 62.7% +/- 13.2% of the administered dose. An additional pharmacodynamic study (inhibition of the histamine-induced wheal and flare) was performed in 10 of these infants and toddlers, after the intake of 0.25 mg/kg cetirizine twice a day for at least 4 days. A 90% +/- 12% inhibition of the wheal and a 87% +/- 17% inhibition of the flare were still observed 12 hours after the last intake. The duration of the H1-inhibition by cetirizine at the cutaneous level is thus longer in infants and toddlers than could be inferred from its pharmacokinetics; the level of inhibition at 12 hours was the same as in older age groups.

Living & learning with allergy: a European perception study on respiratory allergic disorders.

BACKGROUND: Knowledge of allergy patients' perception of own disease is inadequate, and understanding of the impact of local environment, including family and health-care system, on patients' management of disease is insufficient. We examined the potential of telephone-based survey techniques for establishing this knowledge in 10 European countries. METHODS: A two-phased questionnaire developed by use of focus groups in seven countries was translated into 10 languages. To ensure that the true values of the populations were restored in randomly selected populations, 75,343 telephone numbers selected for screening represented balanced national distributions of households. RESULTS: Eight thousand two hundred and sixty-eight respiratory allergy sufferers were identified by the telephone screening process. 85.4% accepted to participate in the survey and 89.6% completed both phases comprising 34 questions and rating of 49 statements. Data for each country were weighted in terms of age, sex and the recorded allergy prevalence within age intervals. CONCLUSIONS: The telephone survey technique allowed for establishment of random representative samples, and application of mathematical weighting procedures assured that the true national values were restored in the data set. As all interviews were performed in a standardised manner we conclude that the telephone-based survey methodology enables national representative data set to be established and compared.

Comparative pharmacokinetic analysis of theophylline in serum and saliva.

The kinetics of theophylline disposition in serum and saliva was evaluated after single and multiple circadian administration of a sustained-release theophylline formulation (Euphyllin CR) to 20 asthmatic children. Salivary concentrations were proportional to serum drug levels, with the significant correlation of r = 0.92. The kinetics of theophylline absorption and elimination and the mean residence time were identical in both saliva and serum estimations. In steady-state conditions after multiple drug administration, the area under the concentration-time curve and the magnitude of peak levels in saliva were reduced proportionally with decreased serum theophylline concentrations. The significantly higher volume of theophylline distribution in saliva confirmed that salivary concentrations represent the free, pharmacologically active fraction in plasma. The determination of theophylline salivary levels could therefore be of clinical importance. The values of the saliva/serum ratio determined in the elimination phase of concentration-time curves for individual patients were constant and stable over the treatment period of three weeks. Saliva appears to be a convenient and noninvasive alternative to blood for the assessment of the variable pharmacokinetic parameters of theophylline and for around-the-clock monitoring of individual dosage regimens, especially in paediatric patients.

The prophylactic treatment of bronchial asthma in children with ketotifen: a double-blind comparison with placebo.

Report on a double-blind parallel group comparison of ketotifen and placebo in two groups of twenty-five children with extrinsic bronchial asthma. Duration of treatment: 12 weeks, dosage adapted to body-weight, 0.5-1 mg b.i.d. Main parameters: Overall assessment of efficacy by the treating physician, total duration and frequency of asthmatic episodes per observation period. In all parameters ketotifen was far superior to placebo in spite of decreased concomitant bronchodilator therapy. The tolerance and acceptability of the compound was good.

Allergogenous mites (Acari: Pyroglyphidae) in private recreation houses.

The bed fauna of periodically inhabited dwellings markedly differs from the bed fauna in town apartments, both in quantity--a higher number of mites and quality--an important dominance of the species Euroglyphus maynei which makes up 70.4% of mites in country cottages, but only 28% in town apratments used by the owners of such recreation houses. In other apartments it is very rare. There differences are explained by the specific regime of humidity and temperature in the periodically inhabited rooms. The patients' worsening condition is apparently caused by quantitative changes.

Investigations on the fauna of beds in flats, children's sanatoria and old-age homes.

An analysis was carried of the fauna found in 338 beds from two old-age homes and from flats inhabited by asthmatic children. During hospitalization of these children the fauna in the flats was compared with that found in beds used by them in sanatoria. The most abundant species proved to be Dermatophagoides pteronyssinus that is also widely spread in other countries of Europe. The bed fauna in the sanatoria is very poor, corresponding to the improved state of health of patients during hospitalization. The authors assume that the low population density of fauna is influenced by constant airing of rooms and by strict separation of bedrooms from dining halls and other premises. Also the number of mites in different padding material used in mattresses was evaluated and an analysis of the general fauna per bed was carried out.

[Detection of specific antibodies to all classes, including IgE, against pollen allergens using the ELISA test]. / Prukaz specifických protilátek vsech tríd, vcetne IgE, proti pylovým alergenum testem ELISA.

The authors describe a modification of the immunoenzymatic test suitable for estimation (sensitive dedection) of specific antibodies against pollen allergens of all classes of immunoglobulins, incl. specific IgE. When introducing the method, sera of experimental rabbits immunized with selected allergens were used. After elaboration of suitable conditions, the method was used to assess the presence of specific antibodies in sera of patients with the diagnosis of pollinosis. It was found that the most suitable concentration of pollen allergen combined with the solid phase for detection of specific IgE is 100 micrograms/ml, the optimal concentration of glutaraldehyde used to increase the amount of allergen combined with the solid phase by its polymerization and fixation is 0.25%. The use of the method does not call for special equipment and uses locally produced products. The method is useful for supplementing the diagnosis and its more accurate assessment under clinical conditions when biological tests cannot be used for diagnosis. The test makes monitoring during immunotherapy possible.

[Pharmacokinetics and chronotherapy of delayed action theophylline (Euphyllin CR)]. / Farmakokinetika a chronoterapie protrahovane pusobícím teofylinem (Euphyllin CR).

Monitoring of theophyllinaemia in the course of 24 h during treatment with theophylline anhydrate capsules (Euphyllin CR) was used in 20 children (9-15 years) and in 20 adults (18-61 years) with bronchial asthma. The doses used in children were 5.96 mg/kg at 7 a.m. and 10.2 mg/kg at 7 p.m., while in adults the morning and evening doses were similar (4.35 and 4.89 mg/kg). After the first dose in the morning the serum theophylline concentration (STC) did not differ in children and adults (10.4 and 10.5 mg/l). In adults the half-time of absorption was twice as high as in children (0.63 and 0.3 h), as well as the time when the peak theophylline concentration was reached (2.7 and 1.39 h). In children a double dose of the drug at night ensured a STC of 11.2 mg/l and a maximum theophyllinaemia (C max = 13.5 mg/l between 8 p.m. and 6 a.m. (measured by the EMIT method). In adults the values during the night were significantly lower than in day-time (STC: ANOVA test P less than 0.05, C max: T-test P less than 0.01). The percentage fluctuation in individual subjects was small (36-49) interindividual, fluctuations in children and adults were considerable (105 to 207). From the chronoprofile of the pharmacokinetics of Euphyllin CR ensues that at the age of 9-15 years the most important indicators are similar to those in adults and that both groups should be given at night a double dose, as compared with that administered in the morning.

[Use of the interruption method in the measurement of respiratory tract resistance in children]. / Vyuzití prerusovací metody pri merení odporu dýchacích cest u detí.

In a group of 50 children with a negative case- history as regards airways and lacking acute respiratory disease, the authors assessed the resistance of the airways on a whole-body plethysmograph and by using the interruptor method on a Bronchoscreen (Jaeger) apparatus. The authors found a satisfactory correlation of the two methods (r = 0.7). When relating the resulting values of resistance to height, greater differences were found between the two methods in younger children; with increasing height the differences disappear. For the relationship of the resistance assessed by the interruptor method and height in our group a Rint regression equation was calculated [kPa/(l/s)] = -0.00765 X height (cm) + 1,565.

[The further development of bronchial asthma which began in childhood]. / Pohled na dalsí vývoj astma bronchiale, které vzniklo v detství.

The paper evaluates the contemporary health status in 115 former child asthmatics, investigated in the past at the allergological department of the First Paediatric Clinic and Faculty Policlinic in Prague-Motol. The data were obtained by processing of a questionnaire and retrospective analysis of the patients' health records. The mean age of the investigated group is 26 years (21-37) incl. 77 men and 38 women. Of these 85, i.e. 74%, still suffer from asthma in adult age, incl. almost half (55 patients) who suffer from the milder form, only one quarter suffers from the more severe form (30 patients) and in one quarter the quiescent stage has been reached. In those where asthma persists there is concurrent eczema (26%), pollinosis (44%), other forms of allergy (43%). Where asthma is in the quiescent stage, eczema is present in 10%, pollinosis in 33% and other allergies in 27% of the investigated subjects. A greater probability of favourable development is in boys as compared with girls and in those without a family-history of allergy and where the disease developed only during late childhood and the patients themselves do not suffer from any other allergosis. A positive family-history of allergy, early onset of the disease and concurrent eczema signalize a poorer prognosis.