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Safety and pharmacoeconomics of a cluster administration of mite immunotherapy compared to the traditional one.

Accelerated schedules of administration of immunotherapy (rush or clustered) allow to reach the maintenance dosage in shorter times with respect to traditional schedules. Nowadays formal assessments of the safety and economic aspects of those schedule lack for inhalant allergens. We compared in a prospective randomized open study a cluster and a traditional immunotherapy with standardized mite extracts. Thirty eight adult patients with persistent allergic rhinitis due to mites were randomized to receive either a traditional (N= 19) or a cluster (N=19) up-dosing scheme, lasting 13 and 3 weeks respectively. Side effects were carefully evaluated and recorded by physician and costs were calculated as well. In the cluster and traditional updosing 148 and 241 injections were given respectively. With the cluster up-dosing there were 8 local reactions (15.9% of patients and 5.4% of injections). With the traditional schedule 6 local reactions (31.5 % of patients and 2.4% of injections) occurred. There was no difference between the two treatments in occurrence of side effects per patient and per injection (chi-square 1.31 and 2.23, p= NS). No systemic reaction was recorded. Considering the cost of the extract, the cost of injections and the time spent, the cluster regimen resulted in a global spare of 244.95 euros per patient in the build-up phase. The cluster up-dosing is as safe as the traditional one and allows a significant economical save.

Adolescent↗

Immunological parameters in the sera of patients with atopic dermatitis and airborne allergy treated with allergy vaccines.

Patients with atopic disorders present an increased production of IgE, which is usually limited to specific antibodies against various environmental allergens. It has also been suggested that the production of these antibodies may be influenced by effective specific immunotherapy (SIT). Of course, a decline of serum antigen specific IgE in the course of such a treatment cannot explain the clinical efficacy of SIT and is probably not a key mechanism. However, SIT may at least participate in the final clinical result. In this study, 37 patients with atopic dermatitis were treated with allergy vaccines (Novo-Helisen Depot) for a time period of 48 months. The control group consisted of 29 patients with atopic dermatitis who were treated with classical methods. The clinical score (W-AZS), total IgE and antigen specific IgE (asIgE) in the sera of patients were assessed before treatment and after 24 and 48 months of therapy (FEIA CAP System, Pharmacia). There was a significant difference between the two investigated groups from both the clinical and immunological standpoints after 2 and 4 years of observation. There was a significant decrease of serum total IgE and asIgE (directed against airborne allergens) in the course of specific immunotherapy. In the control group, the total IgE level tended to increase, and this tendency was also recorded in case of asIgE measurements. We also evaluated the influence of specific immunotherapy on the serum level of IFN-G, sIL-2R, IL-4, IL-5 and IL-10 before treatment and after 4 years of therapy with the quantitative 2-step colorimetric sandwich ELISA method (R and D Systems). In the group of patients treated with allergy vaccines, a significant decrease of the serum sIL-2R level was observed after 48 months of therapy (p<0.01). In the control group, a significant increase of serum IL-4 (p<0.01) as well as IL-5 (p<0.05) was registered at the end of the observation period. There was no significant correlation between the clinical score and serum level of any of the investigated cytokines in either group of patients before the treatment or after 48 months of therapy.

Adolescent↗

Present situation of house dust mites in Dakahlia Governorate, Egypt.

House dust mites are common inhalant allergens, which can precipitate atopic disease episodes. The present study revealed presence of four mites. These are Dermatophagoides farinae, D. pteronyssinus, Acheles gracilis and Ornithonyssus bacoti. Population densities of different live adult mites were investigated in different house habitats. In urban houses, pyroglyphid mites were the predominant in bedrooms and D. farinae was the most abundant. A. gracilis was more abundant in living rooms followed by D. farinae then D. pteronyssinus. A. gracilis was the most prevalent in kitchens. While in rural houses, O. bacoti was the most abundant species followed by pyroglyphid mites. Since Dermatophagoides species and A. gracilis were present in numbers high enough to allow their ecological consideration, their seasonal abundance in urban bed-rooms was investigated and revealed that both D. farinae and D. pteronyssinus have two peaks of abundance, one slightly higher in spring and the second in autumn. A. gracilis has two peaks but the higher occurred in autumn and the second in spring.

Animals↗

House dust mites and allergic manifestations among some children in Dammam, Saudi Arabia.

The house dust mites is (=HDM) still one of the many causes of allergy, particularly atopic dermatitis. In the houses of children who were suffering allergic manifestations as atopic dermatitis, respiratory allergy, bronchitis, skin rash and fever. Double manifestations with fever were reported in four children. In the present study, two types of mites were recovered, Dermatophagoides farinae and Ornithonyssus bacoti. The immunoglobulins (G., M., A. & E) as well as complements (C3 & C4) were measured in the patients and cross-matched controls. The complements did not show any significant difference among patients and controls. Elevation was detected in IgG and IgM, but not in IgA. However, high significant elevation was in IgE. The results were discussed on the light of regional work.

Adolescent↗

Does a multifaceted environmental intervention alter the impact of asthma on inner-city children?

OBJECTIVE: To evaluate the impact of a multifaceted environmental and educational intervention on the indoor environment and health in 5-12-year-old children with asthma living in urban environments. DESIGN: Changes in indoor allergen levels and asthma severity measurements were compared between children who were randomized to intervention and delayed intervention groups in a 14-month prospective field trial. Intervention group households received dust mite covers, a professional house cleaning, and had roach bait and trays placed in their houses. RESULTS: Of 981 eligible children, 410 (42%) were enrolled; 161 (40%) completed baseline activities and were randomized: 84 to intervention and 77 to delayed intervention groups. At the study's end, dust mite levels were 163% higher than at baseline for the delayed intervention group. Overall asthma severity scores did not change. However, the median functional severity score (FSS) component of the severity score improved more in the intervention group (33% vs. 20%) than in the delayed intervention group. At the study's end, the median FSSs for the intervention group improved 25% compared with the delayed intervention group, (p<0.01). Differences between groups for medication use, emergency department (ED) visits or hospitalization were not significant. CONCLUSIONS: Despite low retention, the intervention resulted in decreased dust mite allergen levels and increased FSSs among the intervention group. The interventions probably contributed to the improvements, especially among the more severely affected children. This study highlights the complexities of designing and assessing the outcomes from a multifaceted asthma intervention.

Allergens↗

Analysis of the positivity rate in IgE positive patients to inhalant allergens in Verona Hospital Laboratory during 2002-2003.

BACKGROUND: At present test tube allergy diagnosis is becoming increasingly more comparable to skin prick tests and is therefore increasingly more reliable, not only from an analytical point of view but also from a clinical one. The cost of test tube allergens has decreased over the years and the specific IgE dosage can quickly give a good diagnostic indication. OBJECTIVE: To study the percentage of positive subjects for each individual allergen in cases of suspected allergy, the laboratory can easily identify, also by age bracket, the positivity for those well known allergens that are more commonly responsible for allergic pathologies by using the skin prick test. Our laboratory has studied the test tube diagnostic activity of 2002 and 2003. The inhaled allergens used to identify the positivity percentage were selected from those in our Allergy Unit and which literature identifies as those more commonly positive at skin prick tests. METHODS: The positivity rate of specific IgEs (UniCAP100- Phamarcia) were analyses for two age brackets before and after the age of 12. The younger than 12 group was then subdivided further into pre-school age (3-5 years) and school age (6-12). RESULTS: It can be stated that in the grass group, the seasonal allergens, the most commonly positive were cereals and pellitory, the latter increasing in adult age (above 12 years). In the tree group of seasonal allergens, positivity was found to increase in adult age for olive and cypress trees. The more commonly positive perennial allergens in the adult age (above 12) are dermathophagoides and cat. Below 12, there is a strong positivity to alternaria. CONCLUSIONS: Such test tube studies on IgE positivity are not only useful for better defining diagnostic patterns to give an initial idea of suspected allergy, but also to highlight any changes in the IgE antibody count within different age brackets, with the possibility of documenting the progress of the pathology which is characteristic of the allergy in question.

Administration, Inhalation↗

Dust-mites: effect on lipid peroxidation.

BACKGROUND: Dust-mites are present in our homes, feed on dead exfoliated skin and other organic material. It is also known that oxidative stress may lead to cellular damage that can be confirmed by markers of cellular disruption. Oxidative stress in various infective processes has been documented. We investigated whether house dust-mites cause oxidative stress in patients. METHODS: Products of lipid peroxidation in erythrocytes and lymphocytes were assessed by measuring malondialdehyde concentration. RESULTS: Our results showed that patients who had a positive skin test for dust-mite antigens and had dust-mites present in their houses (dust-mite positive) had increased erythrocyte malondialdehyde levels (62.39 [18.56] nmol/g-Hb) compared with those who were skin test positive, dust-mite negative (45.45 [10.82]) or skin test negative, dust-mite negative (42.20 [5.68]). They also had significantly higher levels of lymphocyte malondialdehyde (4.22 [0.55] nmol/g-protein) compared with those who were skin test positive, dust-mite negative (3.46 [0.29]) or skin test negative, dust-mite negative (1.25 [0.31]; p <0.05). However, there was no statistically significant difference between the malondialdehyde levels of dust-mite negative/skin test positive and dust-mite negative/skin test negative patients. CONCLUSION: Increased malondialdehyde activity in lymphocytes and erythrocytes in the dust-mite positive/skin test positive group shows the presence of the oxidative stress in patients with dust-mite infestation.

Adolescent↗

[Asthma in the elderly--estimation of natural disease course].

UNLABELLED: Bronchial asthma in the elderly is the significant medical problem because it is often underdiagnosed and insufficiently treated. The aim of the study was the assessment of natural course of bronchial asthma and its diagnostic procedures and treatment in patients after 65 yrs. The study group consisted of 181 patients suffering from asthma, at mean age 69 +/- 2.1 yrs. Apart from retrospective analysis, spirometry, skin tests and serum IgE concentration were performed. RESULTS: The mean duration of asthma was 23 +/- 7.2 yrs and in most cases time of proper diagnosis was prolonged. 49% of elderly patients bad a positive history to atopy. In spirometry the mean value of FEV1 was 2.78 +/- 1.3 l/s. House dust mites were the most common allergen confirmed by skin prick tests and specific serum IgE level. CONCLUSION: The observations proved underdiagnosis and insufficient treatment of asthma in the elderly. Positive skin test and specific IgE observed in a large group of elderly objects can indicate atopic mechanism in these cases.

Aged↗

Mycobacterium bovis BCG mycobacteria--new application.

The polarized response of T helper-2 (Th2) lymphocytes to an allergen is considered to be the main cause of the pathogenesis of asthma. In this study, we asked a question whether M. bovis BCG mycobacteria which are known for the preferential stimulation of T helper-1 (Th1) immunity, diminish the effector functions of Th2 cells from allergic patients upon stimulation with a common house dust mite Der p-1 allergen. Our results allow a positive answer to this question. We demonstrate that BCG modulates the dendritic cell-dependent allergen presentation process and switches naive T lymphocytes towards an anti-allergic Th1 profile.

Animals↗

[Safety of immunotherapy and skin tests with allergens in children younger than five years].

BACKGROUND: It has been demonstrated that specific immunotherapy, in addition to its preventive properties, is an effective and safe therapeutic resource for allergic asthma, allergic rhinitis and allergy to insect's venom; however, its use in patients younger than five years has been limited due to the risk of systemic reactions. OBJECTIVES: To know the frequency and severity of systemic reactions in children younger than five years and to know if a greater risk of systemic reactions in this group of age is real. PATIENTS AND METHODS: We included 239 patients from one to five years of age with diagnosis of allergic disease and verified its specific sensitivity with skin tests or RAST and were treated with specific immunotherapy. A detailed registry of the application of specific immunotherapy was kept from every patient, with special attention to any symptom present during the first 30 minutes post application of specific immunotherapy or skin test. RESULTS: From January 1996 to June 2005, 6,689 injections were applied to 239 patients. Only one patient of 36 months of age presented with a delayed systemic reactions characterized by generalized hives, itching, runny nose, water eyes, 90 minutes post injection. The patient was under treatment with Dermatophagoides farinae and pteronissinus (house dust mites) with a dose of 1AU for allergic rhinitis. The systemic reactions were treated easily and without complications with a single dose of intramuscular epinephrine (0.15cc, 1:1000) and oral antihistamine. CONCLUSION: Patients younger than five years are not in greater risk of systemic reactions from specific immunotherapy or skin tests than the older children or adults and the treatment of those systemic reactions does not imply greater difficulty. Because of its preventive properties, safety and effectiveness in lowering the severity of symptoms of allergic diseases, we concluded that specific immunotherapy should be considered at early age, prescribed and administered only by specialist in pediatric allergy and in optimal conditions of safety.

Allergens↗

House dust-mites: effect on antioxidant enzyme activities.

BACKGROUND: House dust-mites are potent allergens of the indoor environment and are common inhabitants of houses worldwide. Free radicals are constantly produced by cells, mostly as reactive oxygen species. Once produced, free radicals are removed by antioxidant defenses, including the enzymes SOD, GPx, and CAT. MATERIAL/METHODS: The aim was to describe the importance of the antioxidant enzymes SOD, GPx, and CAT co-acting in hunan cells against toxic reactive oxygen species and their relationship with pathophysiological processes in stubjects who have dust-mites in their homes. RESULTS: The activities of erythrocyte GPx and SOD in skin-test-positive (dust-mite-positive/negative) patients were significantly lower than those in dust-mite- and skin-test-negative controls (p < 0.05). Among the skin-test-positive patients, SOD activity was found to be lower in dust-mite-positive than in dust-mite-negative patients (p < 0.05). There was not a statistically significant difference between the CAT levels of skin-test-positive (dust-mite-positive/negative) patients and dust-mite- and skin-test-negative controls (p > 0.05). CONCLUSIONS: This study clearly shows that dust-mite depresses the activities of SOD, GPx, and, to a small extent, CAT; which influence cellular reducing capacity and consequently may increase asthma risk more than other allergens.

Adolescent↗

Risk factors and characteristics of early-onset asthma in Taiwanese children.

BACKGROUND AND PURPOSE: Early-onset asthma has been reported to be associated with a family history of allergy and exposure to environmental factors. This study was designed to evaluate the relationship between age of onset of asthma and genetic and environmental factors with asthma severity in Taiwanese children. METHODS: A group of 352 children with asthma (220 males and 132 females), ranging in age from 5 to 15 years, were enrolled in this study. The subjects were divided into 2 groups: early-onset asthma (up to and including age 3) and late-onset asthma. General characteristics including family history of allergies and exposure to domestic pets and tobacco smoke were recorded. The subjects underwent pulmonary function testing and analysis of serum immunoglobulin E (IgE), eosinophil counts, and specific IgE for common allergens. RESULTS: Early-onset asthma was present in 149 subjects and late-onset asthma in 203. Family history of allergies included a sibling with asthma or urticaria predisposed to early-onset asthma (asthma, p=0.034; urticaria, p=0.024). Food and milk allergen sensitization were more common in early-onset asthma (food allergens, p=0.025; milk, p=0.034). Children with early-onset asthma had higher eosinophil counts (p=0.041). However, there was no correlation between age at onset and pulmonary function testing, the levels of total IgE and IgE specific for Dermatophagoides pteronyssinus or Dermatophagoides farinae. CONCLUSIONS: A history of asthma or urticaria in a sibling is a risk factor for early-onset asthma. A greater prevalence of food allergen sensitization and high eosinophil counts are characteristic of early-onset disease.

Adolescent↗

[Evaluation of the prevalence of house dust mites in house dust sent to the Adnan Menderes University Medical Faculty Parasitology Laboratory].

House dust is composed of remnants and particles of many kinds of animate and inanimate materials. It has been reported that the most common allergens in house dust are mites that cause allergic rhinitis, asthma, atopic dermatitis, and seasonal keratoconjunctivitis. The aim of this study was to determine the prevalence of house dust mites in dust specimens sent to our laboratory from November 2002-May 2004. Specimens were evaluated using the flotation concentration method in the first, fourth and 24th hours. Out of 88 specimens, mites were detected in 20 (22.72%). In addition Enterobius vermicularis eggs were found in two specimens.

Allergens↗

[Effect of 1-year specific immunotherapy with standardized house dust mite vaccine on mild to moderate allergic asthmatic patients].

OBJECTIVE: To evaluate the clinical efficacy and safety of specific immunotherapy (SIT) with standardized house dust mite (HDM) vaccine on allergic asthmatic patients. METHODS: The investigation was a multicentre, randomized, double-blind, placebo-controlled clinical study. 132 patients with mild to moderate asthma who were allergic to HDM, recruited from three hospitals of China (The First Affiliated Hospital of Guangzhou Medical College, Shenyang General Military Hospital, Suzhou Children's Hospital), were randomly allocated to the active group (n = 66) or the control group (n = 66) respectively. The active group received SIT with a standardized depot Dermatophagoides pteronyssinus (Der p) extract absorbed to aluminium hydroxide (Alutard SQ, ALK-Abelló, Denmark), while the control group received a placebo containing histamine dihydrochloride by subcutaneous injections for 1 year. Treatment of each group was started from the initial concentration. Updosing was performed with weekly injections from four 10-fold dose-increase vials (active group: 100, 1,000, 10,000, 100,000 SQ-U/ml, control group: 0.01, 0.1, 1.0, 10 microg/ml. 100,000 SQ-U/ml of Der p extract contains 9.8 microg/ml of the majoy allergen Der p1). The single-dose was injected weekly with 0.2, 0.4, 0.8 ml of each concentration in turn from the preceding 3 vials, totally for 9 weeks. Subsequently, the dose with 0.1, 0.2, 0.4, 0.6, 0.8 ml of the highest concentration was injected weekly from the 10th-14th week and a maintenance dose with 1 ml was reached at the 15th week. The dosing interval was then gradually increased to 2, 4, 6 weeks until the end of the first 26-weeks updosing phase (phase I, H(1)). Thereafter, the dosing continued at 6-week intervals for maintenance phase (phase II, H(2)) till the end of the complete treatment. The patient was observed for at least 30 minutes in the clinic after each injection. RESULTS: A total of 132 subjects were randomized and 129 subjects (64 in the active group, 65 in the control group) completed the whole study. Dropouts included three females because of poor compliance, being afraid of the epidemic of Severe Acute Respiratory Syndrome (SARS) and emigration respectively. Both groups were comparable at baseline in all clinical and laboratory parameters. The mean daily symptom scores in 4-weekly began to diverge at the 29th-32nd week with the active group showing a significant lower scores (0.17 +/- 0.33) than the control group (0.39 +/- 0.74, Z = 2.031, P < 0.05) till the end of the study. Significant difference was found in average daily symptom scores between H(1) (0.29 +/- 0.39) and H(2) (0.19 +/- 0.27) in the active group (Z = 2.923, P < 0.01), while no significant difference was found between H(1) (0.45 +/- 0.62) and H(2) (0.40 +/- 0.68) in the placebo group (Z = 1.885, P > 0.05). There were significant differences in subjective judgement of the improvement about overall asthmatic symptoms, exacerbation severity and exacerbation frequency between the active group (96.9%, 95.3%, 95.4%) and the control group (80.0%, 75.4%, 83.1%) with the self-evaluation questionnaire (chi(2) = 13.246, 11.576, 16.204, all P < 0.01). The trend line of daily medication scores in weekly intervals showed a significant decline. The mean daily medication score of phase II (0.20 +/- 0.36) was significant lower than that of phase I (0.33 +/- 0.67, Z = 3.344, P < 0.01), whereas the control group did not show a significant difference between phase II (0.35 +/- 0.96) and phase I (0.32 +/- 0.95, Z = 0.744, P > 0.05). After 1-year treatment, no significant differences were found in morning and evening peak expiratory flow of predicted value (PEF%), forced expiratory volume in one second of predicted value (FEV(1)/FVC), forced vital capacity of predicted value (FVC%), forced expiratory volume in one second to forced vital capacity ratio (FEV(1)/FVC), provoking dose decreasing FEV(1) by 20% (PD(20)-FEV(1)) between the active group [(97 +/- 17)%, (98 +/- 18)%, (91 +/- 11)%, (98 +/- 9)%, (82 +/- 10)%, 2.35 (7.9) micromol] and the control group [(99 +/- 19)%, (100 +/- 19)%, (90 +/- 14)%, (99 +/- 13)%, (82 +/- 9)%, 1.80 (7.8) micromol] (t = 0.170 - 0.630, Z = 0.264, all P > 0.05). Skin index (SI) to Der p in the active group (1.2 +/- 0.5) was significantly lower than that of the control group (1.5 +/- 0.6) after treatment (t = 2.395, P < 0.05). There was no significant difference in the level of serum sIgE against Der p between groups, which was 76.80 (97.0) kU/L in active group and 66.50 (99.3) kU/L in the control group (Z = 0.232, P > 0.05). The frequency of systemic adverse reactions graded by guidelines based on the position paper of European Academy of Allergology and Clinical Immunology (EAACI), was 5.7% and 1.8% of the total injections in the active group and the control group, respectively. Although significant difference was found in adverse reactions between groups (chi(2) = 4.705, P < 0.05), all were mild or moderate. The majority occurred within 30 minute after injection and were controlled well with symptomatic therapy. No any severe systemic adverse reaction was shown in the study. CONCLUSION: One year specific immunotherapy with standardized house dust mite (HDM) vaccine significantly improved symptoms and reduced medication use in mild to moderate allergic asthmatic patients. SIT also reduced skin prick test reactivity to Der p. Complying with the EAACI immunotherapy guidelines, SIT with standardized HDM vaccine was a safe treatment.

Adolescent↗

Evaluation of the nasal provocation test for its necessity in the diagnosis of nasal allergy to house dust mite.

The aim of this study was to evaluate rhinomanometric responses to nasal allergen provocation in children with allergic rhinitis sensitized to house dust mite. We studied 51 children, aged 6-16 years (mean: 11.5 +/- 2.6 years), with clinical symptoms of perennial allergic rhinitis without asthma and 20 non-atopic healthy controls in the same age range (mean: 11.8 +/- 3.8 years). All of the patients had positive skin prick test (SPT) results and serum specific IgE above 0.70 kU/l to Dermatophagoides pteronyssinus (Dp). Nasal provocation testing (NPT) was performed with increasing concentrations of Dp extracts and the nasal response was evaluated by active anterior rhinomanometry. A 100% increase of resistance in one or both nasal cavities was considered positive. There was a statistically significant difference of baseline nasal resistance (total, right and left sides) between the control and the patient groups (p < 0.001). A positive response to house dust mite allergens was recorded in 47/51 (92.2%) patients by rhinomanometry. The NPT presented no significant correlation with age, weight, height, SPT diameter, serum total and specific IgE levels to Dp and baseline nasal airway resistance values. This study suggests that a nasal provocation test with allergen is unnecessary in children with positive skin prick test and serum IgE specific to house dust mite. The rhinomanometric response to the allergen provocation does not correlate with the diameter of the skin prick test and the level of serum specific IgE.

Adolescent↗