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Biomedical subjects

P Kuna

Publications and source records attributed to P Kuna.

At least 19 recordsLinked to original sources
PubMed2006

Tacrolimus ointment does not affect the immediate response to vaccination, the generation of immune memory, or humoral and cell-mediated immunity in children.

BACKGROUND: Concern exists that the prolonged application of immunomodulators to treat atopic dermatitis may cause systemic immunosuppression. AIMS: In a 7-month, multicentre, randomised, controlled trial, we investigated the equivalence of response to vaccination against meningococcal serogroup C disease with a protein-conjugate vaccine in children (2-11 years) with moderate to severe atopic dermatitis, by applying either 0.03% tacrolimus ointment (TAC-O; n = 121[corrected]) or a hydrocortisone ointment regimen (HC-O; n = 111). METHODS: TAC-O was applied twice daily (bid) for 3 weeks, and thereafter daily until clearance. 1% hydrocortisone acetate (HA) for head/neck and 0.1% hydrocortisone butyrate ointment for trunk/limbs was applied bid for 2 weeks; thereafter HA was applied bid to all affected areas. At week 1, patients were vaccinated with protein-conjugate vaccine against meningococcal serogroup C, and challenged at month 6 with low dose meningococcal polysaccharide vaccine. The control group (44 non-atopic dermatitis children) received the primary vaccination and challenge dose. Assessments were made at baseline, weeks 1 and 5, and months 6 and 7. The primary end point was the percentage of patients with a serum bactericidal antibody (SBA) titre > or = 8 at the week 5 visit. RESULTS: The response rate (patients with SBA titre > or = 8) was 97.5% (confidence interval (CI) approximately 97.3 to 100), 99.1% (94.8 to 100) and 97.7% (93.3 to 100) in the TAC-O, HC-O and control groups, respectively. CONCLUSIONS: The immune response to vaccination against meningococcal serogroup C in children with atopic dermatitis applying either 0.03% TAC-O or HC is equivalent. Ointment application does not affect the immediate response to vaccination, generation of immune memory or humoral and cell-mediated immunity.

Administration, Topical↗
PubMed2006

Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma.

Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.

Administration, Inhalation↗
PubMed2005

The effect of treatment with montelukast on in vitro interleukin-10 production of mononuclear cells of children with asthma.

BACKGROUND: The effects of leukotriene modifiers on IL-10 production have not been studied in children with asthma. OBJECTIVE: The primary objective of this study was to determine the changes in IL-10 concentrations, clinical efficacy and peripheral blood eosinophil counts after treatment with montelukast. METHODS: The study was conducted on 27 patients: 13 patients monoallergic to grass pollen during the pollen season (GPs group) and out of the pollen season (GPos group), and on 14 patients monoallergic to house dust mite (HDM) from May to September (HDM group). Main outcome measures were changes in concentrations of IL-10 in the supernatant after a 4-week treatment with montelukast. Measurements of asthma severity score, forced expiratory volume in 1 s (FEV1) and peripheral blood eosinophil counts were the secondary end-points. RESULTS: Montelukast resulted in a within-group significant increase in IL-10 concentration in the supernatant in the GPs (54.0 vs. 125.5 pg/mL) and in the HDM (51.2 vs. 77.1 pg/mL) group. Montelukast had no effect on changes of IL-10 concentration in the supernatant from peripheral blood mononuclear cell (PBMC) culture after non-sensitizing allergen stimulation. Montelukast significantly improved asthma control and FEV1, and significantly decreased eosinophil blood count in the GPs and in the HDM group after a 4-week treatment. Montelukast did not lead to changes of all measured parameters within the GPos group. CONCLUSION: Montelukast increased IL-10 concentration in supernatants from sensitizing allergen-stimulated PBMC culture obtained from children with asthma monoallergic to grass pollen during the pollen season, and from children with asthma monoallergic to HDM.

Acetates↗
PubMed2004

Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic rhinitis: influence on clinical symptoms and nasal allergic inflammation.

BACKGROUND: The aim of our study was to investigate effects of 6-week pretreatment of seasonal allergic rhinitis (AR) with cetirizine, and montelukast, alone and in combination. Antihistamine/antileukotriene treatment is effective in AR. Antihistamines may prevent AR symptoms while prophylactic activity of antileukotrienes remains unclear. METHODS: Sixty AR patients, aged 18-35 years, were randomized to receive placebo, montelukast only, cetirizine only, or montelukast plus cetirizine, 6 weeks prior and 6 weeks after the beginning of grass pollen season. Mean self-recorded in-season symptom scores and mean weekly all-symptom scores were analyzed. In 31 patients, nasal lavages were performed before treatment, and at the end of the study, i.e. 12 weeks after the treatment initiation. Eosinophil and basophil counts, eosinophil cationic protein (ECP), and mast cell tryptase (MCT) levels were evaluated in lavage samples. RESULTS: Combined montelukast/cetirizine pretreatment significantly reduced in-season symptom score for sneezing, eye itching, nasal itching, rhinorrhea, and congestion. Montelukast plus cetirizine were more effective than cetirizine alone in preventing eye itching, rhinorrhea, and nasal itching. Moreover, combined pretreatment with montelukast and cetirizine delayed appearance of AR symptoms. Eosinophil nasal lavage fluid counts were significantly increased during pollen season in placebo and montelukast-only groups. No differences were observed in basophil counts. The in-season ECP level was significantly increased in all groups except montelukast-plus-cetirizine group. In-season MCT levels were not increased. CONCLUSION: Combined antihistamine and antileukotriene treatment started 6 weeks before the pollen season is effective in preventing AR symptoms and reduces allergic inflammation in nasal mucosa during natural allergen exposure.

Acetates↗
PubMed2003

Efficacy and safety of inhaled budesonide delivered once or twice daily via HFA-134a in mild to moderate persistent asthma in adult patients. Comparison with budesonide CFC.

This study was undertaken to investigate whether budesonide 4001 microg twice daily (Chiesi Farmaceutici S.p.A.) given with the HFA-134a propellant is equivalent in efficacy and safety to the same dose regimen delivered with the marketed CFC product in adult asthmatics with mild to moderate persistent asthma; the effects of budesonide HFA 800 microg once daily were also studied. After a 2-week run-in, a total number of 98, 103 and 97 patients were assigned to the 12-week treatment with budesonide given with HFA or CFC twice daily (morning and evening), or HFA once daily (morning), respectively. The main outcome variable morning PEFR, as well as evening PEFR and clinical symptoms (day-time and night-time asthma attacks, number of asthma-induced night-time awakenings and overall symptoms' scores) were measured daily by patients. Other standard pulmonary function testing were measured at clinic visits. A blood sample for morning serum dosing (8.00-10.00 AM) was taken at baseline and at endpoint. Adverse events and vital signs were also recorded. Significant improvements at endpoint in morning and evening PEFR, as well as in clinic PEFR and MEF50, were observed in both the twice daily groups only. An exact proof of equivalence between HFA and CFC given twice daily was demonstrated for the primary parameters, morning PEFR (equivalence pre-defined limits were +/- 40.27 l/min, difference between means = 4.0 l/min and 95% CI -6.9-14.9) and secondary parameters as evening PEFR: (limits +/- 40.19 l/min, difference between means = 2.1 l/min and 95% Confidence interval (CI) -9.4-13.5) and FEV1 (limits +/- 0.27 l, difference between means = 0.0 l and 95% CI -0.11-0.10). Less evident (but within limits) proofs of equivalence were shown in the comparisons with the once daily group. No substantial differences between the three groups were observed for the other efficacy variables, including symptoms and use of rescue salbutamol, which significantly improved over the run-in values in all groups. Minimal and non-significant decreases over pre-treatment values were observed in the three groups for morning serum cortisol levels: the analysis of individual data has shown a better outcome in the HFA twice daily regimen, compared with the other two groups. Again, a similar amount of patients in both the twice daily groups reported drug-related adverse events, which were more frequent in the once daily HFA group. Therefore, the results of this study have shown that inhaled budesonide given with new HFA-134a propellant can replace microgram-equivalent doses of the corresponding marketed CFC product when given twice daily. An overall maintainment and an unchanged risk-benefit ratio has emerged for budesonide HFA given once daily, which was however slightly inferior compared with the standard twice daily regimens.

Administration, Inhalation↗
PubMed2003

The effect of recombinant interleukin-8 on eosinophils' and neutrophils' migration in vivo and in vitro.

BACKGROUND: Interleukin-8 (IL-8) is a chemokine that causes chemotaxis of neutrophils, eosinophils and lymphocytes in vitro; however, its role as a chemoattractant in allergic inflammation is unclear. The objective of this study was to investigate the effect of nasal instillation of IL-8 on the influx of inflammatory cells. METHODS: Twelve patients suffering from seasonal allergic rhinitis hypersensitive to grass pollens, with average age 30.1 +/- 2.67 years were challenged both with diluent for IL-8 and IL-8 on a subsequent day, in two phases: before the pollen season (unprimed mucosa) and during the season (primed mucosa). The number of neutrophils, eosinophils and myeloperoxydase (MPO) levels in the nasal fluid collected after IL-8 or placebo challenge were determined. RESULTS: Challenge with IL-8 of primed nasal mucosa induced a significant influx of neutrophils (29 x 10(4) cells/ml at 0.5 h, 251 x 10(4) at 2 h and 334 x 10(4) at 3 h). Number of eosinophils in comparison with diluent challenge was not significant. There was no difference in MPO levels in the nasal lavage between IL-8 and diluent challenge of unprimed and primed mucosa. We did not find the relationship between MPO levels and the neutrophils number in the lavage (rank Spearman factor, RS = 0.258, P = 0.42). CONCLUSION: We have demonstrated that IL-8 causes influx of neutrophils but not eosinophils into nasal mucosa in vivo. MPO level seems to be of little value as a marker of neutrophil influx into nasal mucosa.

Administration, Intranasal↗
PubMed2003

Comparison of standard and modified SPT method.

BACKGROUND: The aim of our study was to compare clinical significance and economical factors of commonly used standard skin prick tests (SPT) method with new, modified and more handy way of performing SPT. METHODS: Twenty-one subjects [with an average age of 23 years (SD +/- 2.72)] with known sensitivity to examined allergen extracts were tested with histamine, negative control solution and standard allergen extracts (Allergopharma, Reinbeck, Germany). SPT were applied to the volar surface of randomly assigned forearm with two methods: standard technique using lancet needle to prick the epidermis under small drop of extract and tested method using lancet needle which was dipped in extract before prick. In this method all extracts were placed in marked, small, plastic chambers. RESULTS: Mean wheal to histamine was 5.49 (standard method) and 5.01 (modified method). There was no statistical difference between the standard and modified method for size of wheal to histamine (P = 0.654) and to allergen extracts (n = 36, P = 0.824, Wilcoxon test). Economical analysis revealed that examined SPT technique is cheaper than standard method. CONCLUSION: Examined method may be considered to be an alternative for performing SPT as it is safe, cheaper and more convenient than standard technique. SUMMARY STATEMENT: Comparison of standard and modified SPT method revealed the new method to be more economical.

Adult↗
PubMed2002

Eotaxin but not MCP-3 induces eosinophil influx into nasal fluid in allergic patients.

BACKGROUND: Eotaxin and MCP-3 (CC chemokines), owing to their preferential action on eosinophils, seem to be the very importance in the patophysiology of allergic rhinitis and asthma. The purpose of this study was to examine the effect of intranasally administered eotaxin and MCP-3 after specific allergen priming on the influx of inflammatory cells and their soluble mediators into the nasal mucosa. METHODS: Eotaxin and MCP-3 have been applied intranasally at the increasing doses of 1, 5 and 10 microg to allergic patients after allergen priming. The 'nasal pool' technique was used. The cell count and biochemical parameters in nasal lavage were evaluated before 30 min, and 4 and 24 h after the challenge with chemokines. RESULTS: Both eotaxin and MCP-3 induced the increase in clinical 'score' lasting till 24 h. Eosinophil influx into nasal mucosa after provocation with eotaxin was also observed. The challenge with MCP-3 did not induce any significant changes in nasal lavage fluid. CONCLUSIONS: Eotaxin is likely to play an important role in the pathogenesis of allergic conditions in humans. MCP-3 did not induce inflammatory cell influx into nasal mucosa. The role of this chemokine in the pathogenesis of allergic inflammation is difficult to assess and requires further studies.

Adult↗
PubMed2002

Cockroach allergy and exposure to cockroach allergen in Polish children with asthma.

BACKGROUND: Asthma morbidity increases every year, especially among children, and exposure to high levels of indoor allergens is a very important factor. We evaluated the prevalence and exposure to cockroach (CR) allergen in asthmatic children in Poland, and also tested the hypothesis that asthma with allergy to CR is more severe than with allergy to other antigens. METHODS: One hundred and sixty children with asthma were examined, had skin prick tests (SPT) with common and CR allergens, underwent spirometry, and provocation tests to histamine. Children with positive SPT to CR had measured specific IgE levels to this antigen and Bla g 2 concentrations were measured in their homes. RESULTS: The most common allergen, was dust mite 51.3%, followed by pollen 48.8% and CR allergen 24.3%. In children with CR sensitivity, 13% had mild asthma, 26% moderate and 61% had severe asthma. Their levels for forced expiratory volume in one second (FEV1), and the provocative concentration of histamine that caused a 20% fall in FEV1 (PC20), were statistically lower than in the group of children with other than CR allergies. Bla g 2 antigen was detected in 55.13% samples. The highest levels of Bla g 2 were found in old houses, without central heating, and in houses with lower income. CONCLUSION: In Polish children, CR allergen is a very important factor of sensitivity. Concentrations of Bla g 2 in homes are higher than previously reported in other European countries, and are strongly related to the houses' characteristics. Also, children with CR hypersensitivity have severe asthma more often than children with other allergies.

Adolescent↗
PubMed2002

A randomized, double-blind trial of the effect of glucocorticoid, antileukotriene and beta-agonist treatment on IL-10 serum levels in children with asthma.

BACKGROUND: Levels of an immunoregulatory and anti-inflammatory cytokine IL-10 are reduced in asthmatic airways, potentially contributing to more intense inflammation. Triamcinolone has anti-inflammatory properties and the anti-inflammatory effects of montelukast and formoterol have been discussed. OBJECTIVE: The purpose of this study was to define the effect of treatment with triamcinolone, montelukast and formoterol on the serum level of IL-10, eosinophil blood counts, eosinophil cationic response (ECP) and clinical parameters (symptom score, FEV1 and PC20H) in children with moderate asthma. METHODS: An 8-week, placebo-controlled and randomized, double-blind trial was carried out. The subjects were 91 children with moderate atopic asthma who were allergic to dust mite. Patients were randomly allocated to receive 400 microg triamcinolone (n = 19), 5 or 10 mg (according to age) montelukast (n = 18), 24 microg formoterol (n = 18) or placebo (n = 36). RESULTS: Seventy-nine children completed the study. After treatment with triamcinolone and montelukast the level of IL-10 in blood serum significantly increased, eosinophil blood counts and ECP levels significantly decreased and all clinical parameters improved; treatment with formoterol had no effect on IL-10 level, eosinophil blood counts in serum and bronchial hyper-reactivity; ECP level significantly decreased after treatment and asthma symptoms and FEV1 improved significantly. Mean IL-10 levels in serum before and after treatment with triamcinolone were 7.23 pg/mL with 95% CI, 6.74 -7.72% and 14.24 pg/mL with 95% CI, 11.6-16.88%, respectively (P < 0.001); with montelukast they were 6.59 pg/mL with 95% CI, 6.26-7.23% and 10.94 pg/mL with 95% CI, 8.24-12.65%, respectively (P < 0.002); with formoterol they were 7.06 pg/mL with 95% CI, 6.61-7.52% and 7.04 pg/mL with 95% CI, 6.15-7.93%. We found statistically significant correlations between serum level of IL-10 and serum level of ECP after treatment with triamcinolone and montelukast. CONCLUSION: This study demonstrates that one possible way by which triamcinolone and montelukast contribute to inhibition of inflammation is by increasing IL-10 levels.

Acetates↗
PubMed2002

Symbicort Turbuhaler: a new concept in asthma management.

Symbicort is a novel asthma product containing both budesonide and formoterol in a single inhaler, Turbuhaler. Budesonide is a corticosteroid that treats underlying airway inflammation in asthma; formoterol is a rapid- and long-acting beta2-agonist that prevents and reverses airway obstruction. Budesonide and formoterol therefore have complementary effects, treating two different components of asthma. Clinical studies have shown that Symbicort is more effective in the treatment of asthma than double-dose corticosteroid, and clinical experience to date indicates that Symbicort is at least as effective and well tolerated as budesonide and formoterol given in separate inhalers. Symbicort has a fast onset of effect, which may help patients feel more in control of their condition and improve adherence to their medication, and a long duration of effect that allows twice-daily or even once-daily dosing during periods of good control. More convenient treatment represents another important benefit for patients with asthma, as ease of use can also result in improved adherence, leading to better disease control.

Administration, Inhalation↗
PubMed2001

Markers of allergic inflammation in peripheral blood of children with asthma after treatment with inhaled triamcinolone acetonide.

BACKGROUND: It is important to monitor inflammation regularly in asthma in addition to clinical symptoms, and there is a great need for noninvasive tests that could routinely be used in clinical practice. OBJECTIVE: Our hypothesis was that the improvement of clinical parameters, together with decreased airway responsiveness, could be correlated with changes in the levels of serum markers of inflammation after a 4-week treatment with triamcinolone. METHODS: In this double-blind, randomized, placebo-controlled trial, 48 children, aged 6 to 18 years, with mild to moderate atopic asthma, were randomly allocated to receive triamcinolone or matching placebo for 4 weeks. The following parameters were measured: the symptom score, forced expiratory volume in 1 second (FEV1), provocative concentration of histamine causing a 20% fall in FEV1 (PC20) for histamine and peripheral blood eosinophil count, serum levels of the inflammatory markers eosinophil cationic protein (ECP), soluble receptor of interleukin-2 (sIL-2R), interleukin-4, soluble intercellular adhesion molecule-1 before and after treatment. RESULTS: The clinical parameters significantly improved after treatment with triamcinolone; the mean value of FEV1 changed from 74% of predicted value before, to 90% of predicted after treatment (P < 0.001). PC20 for histamine after treatment with triamcinolone increased significantly from the mean value 2.5 mg/mL to 4.7 mg/mL (P < 0.001). Treatment with triamcinolone significantly (P < 0.05) decreased serum levels of all the measured inflammatory markers. The mean concentration of eosinophil blood count was 380 and 261 cells/mm3; ECP, 83 and 58 ng/mL; serum sIL-2R, 734 and 487 pg/mL; soluble intercellular adhesion molecule-1, 266 and 210 ng/mL, before and after treatment, respectively. The values of interleukin-4 were low and close to the sensitivity of the assay. A significant correlation was found between ECP and sIL-2R levels before and after treatment with triamcinolone. CONCLUSIONS: A significant decrease of all the measured serum parameters was observed after treatment with triamcinolone; however, no significant correlation was found among any of those parameters and clinical markers of disease severity (such as FEV1 or PC20H).

Administration, Inhalation↗
PubMed2001

Double-blind, randomized, placebo-controlled trial of effect of nedocromil sodium on clinical and inflammatory parameters of asthma in children allergic to dust mite.

BACKGROUND: The purpose of this study was to determine the clinical effect of nedocromil sodium and its relationship with serum levels of inflammatory mediators by monitoring lung function and noninvasive markers of airway inflammation, such as eosinophil blood counts; serum ECP, sIL-2R, IL-4 and sICAM; and total IgE. Anti-inflammatory medications cause a reduction in the markers of airway inflammation, decrease the intensity of airway hyperresponsiveness, and improve clinical symptoms of asthma. Among the available choices is nedocromil sodium, which is favored in the treatment of asthmatic children due to its very mild side-effects. It has been previously shown to improve the clinical parameters of asthma, but there are limited data on its effect on inflammatory mediators in the serum of asthmatic children. METHODS: In this double-blind, randomized, placebo-controlled 8-week trial, 39 children, aged 9-16 years, with moderate atopic asthma were randomly allocated to receive either nedocromil sodium, two puffs twice daily, 0.002 g/puff, or placebo, two puffs twice daily. The primary end points were the clinical parameters of asthma measured by asthma symptom score, FEV1, and PC20H. Other end points included the serum levels of various inflammatory markers - ECP, sIL-2R, IL-4, sICAM, and IgE. RESULTS: Clinical and inflammatory parameters improved with the use of nedocromil sodium, compared with placebo. Nedocromil significantly decreased serum levels of inflammatory markers, as shown in the following table. No correlation was found between any of the measured parameters. CONCLUSION: Nedocromil sodium provided effective anti-inflammatory treatment for children with moderate atopic asthma.

Adolescent↗
PubMed2001

[The effect of triamcinolone, montelukast and formoterol on serum levels of il-4, IgE and clinical parameters in children with asthma].

Levels of pro-allergic cytokine IL-4 are increased in asthmatic airways, contributing to allergic inflammation. The purpose of this study was to define the effect of treatment with triamcinolon, montelukast, and formoterol on serum level of IL-4 and IgE, clinical parameters (symptom score, FEV1) and bronchial hyperreactivity (BHR) in children with moderate asthma. It was 8 week, placebo-controlled and randomized, double blind trial of 99 children with moderate atopic asthma allergic to dust mite. Patients were randomly allocated to receive 400 mg triamcinolon (n = 20), 5 or 10 mg (according to age) montelukast (n = 18), 24 mg formoterol (n = 19), or placebo (n = 42). 80 children completed the study. After treatment with triamcinolon, montelukast, and formoterol the level of IL-4 in blood serum in all study groups significantly decreased, and all clinical parameters improved; treatment with triamcinolon, formoterol, and montelukast had no effect on IgE level in serum. Mean IL-4 levels in serum before and after treatment with triamcinolon were 0.129 pg/ml with 95% Cl, 0.1-0.145 pg/ml and 0.086 pg/ml with 95% Cl, 0.023-0.109 pg/ml respectively (p = 0.02); with montelukast were 0.123 pg/ml with 95% Cl, 0.57-0.82 pg/ml and 0.102 pg/ml with 95% Cl, 0.62-0.82 pg/ml respectively (p < 0.001); with formoterol were 0.128 pg/ml with 95% Cl, 0.108-0.164 pg/ml and 0.113 pg/ml with 95% Cl, 0.096-0.146 pg/ml respectively (p = 0.002). No correlations have been found between changes in serum IL-4 and any other clinical parameters after treatment. This study demonstrates that one of the possible ways by which triamcinolon, montelukast, and formoterol contribute to inhibition of allergic inflammation is by decreasing IL-4 levels.

Acetates↗
PubMed2001

[The effect of inhaled heparin on airway responsiveness to metacholine in asthmatic children].

UNLABELLED: Atopic asthma is a chronic inflammatory disorder of the airways associated with airway hyperresponsiveness to various bronchoconstrictor stimuli. There are several pharmacologic agents, involved in the inflammatory process, that can produce acute bronchoconstriction, such as metacholine. Heparin possesses multiple noncoagulant properties, including anti-inflammatory actions. OBJECTIVES: The purpose of the present study was to investigate the effect of inhaled heparin on the airway response to metacholine in children with asthma. METHODS: Fifteen children with mild atopic asthma participated in the study. It was randomized, double-blind, cross-over, placebo controlled study. There were three study visits. At the first visit patients were included into the study and beta-agonists were withheld for at least 12 hours before the next visit (second day). At the second visit provocation test with metacholine, inhalation with single dose of heparin or placebo followed by provocation test with metacholine were performed. After two weeks, tests were performed in the same manner except of that patients instead of heparin inhaled placebo or opposite. RESULTS: Fourteen children completed the study. Single dose of inhaled heparin significantly decreased bronchial hyperresponsiveness to metacholine when compared to placebo. CONCLUSION: The exact mechanism of anti-inflammatory role of heparin is still under investigation and needs to be studied further. The possible anti-inflammatory effect of heparin can be through effect on the neuronal M2 receptors or on receptor-protein G binding or direct effect on the smooth muscles, and in such mechanisms, heparin can decrease bronchial hyperreactivity to metacholine.

Administration, Inhalation↗
PubMed2000

[Non-specific immunotherapy for the treatment of allergic diseases].

IgE antibodies play a key role in the development of allergic reactions. Non-specific immunotherapy which enables to control the IgE dependent response at either the synthesis level or the effector phase can be an effective therapeutic agent for atopic diseases. To decrease the quantity of IgE anti-IgE molecules have been developed. Humanized monoclonal antibodies (mAbs) CGP 51901, CGP 56901 and rhuMAb E25 are currently under clinical studies. They bind to the C epsilon 3 domain of human free IgE and surface IgE of IgE expressing B cells but not to IgE bound to high affinity IgE receptors (Fc epsilon RI) on mast cells and basofils or low affinity IgE receptors (Fc epsilon RII) on other cells, and therefore they do not release the histamine and other mediators from these cells. Intravenous administration of anti-IgE mAb reduces circulating levels of IgE in atopic patients to low levels commonly seen in non-atopic individuals. Anti-IgE therapy offers protection against allergen-induced bronchoconstriction and reduces severity of symptoms of allergic rhinitis. Anti-IgE mAbs produce improvement in lung function and symptom control, they reduce the need for short acting inhaled beta 2-agonist and corticosteroids among asthmatic patients. Anti-IgE mAb are well tolerated. They do not induce anaphylaxis and the occurrence of antibodies against anti-IgE mAb is sporadic. The results of cited studies suggest that humanized anti-IgE monoclonal antibodies may have important immunotherapeutic benefit for treatment of allergic disorders.

Humans↗
PubMed2000

[The role of heparin in allergic inflammation].

Heparin is a glycosaminoglican used in prophylactic and treatment of thrombosis. Heparin possesses also non-anticoagulant properties, including modulation of various proteases, anticomplement activity, and anti-inflammatory actions. Inhaled heparin has been shown to reduce early phase of asthmatic reaction and suppress allergen induced rise in bronchial hyperreactivity. Heparin inhibits the acute cutaneous reaction due to allergens. Moreover, inhaled heparin prevents exercise-induced asthma. The exact mechanism of heparin action in bronchial asthma remains obscure. It has been observed that heparin acts as a specific blocker of IP3 receptors and inhibits IP3-mediated calcium release in various cell types, including vascular smooth muscle and airway smooth muscle. In this mechanism heparin inhibits allergen induced mast cell degranulation and prevents subsequent development of reaction cascade leading to inflammation, bronchial hyperreactivity and asthma. It also modulates migration of proinflammatory cells, eosinophils and neutrophils, into the site of allergic reaction. Furthermore, heparin inhibits the increased vascular permeability induced by a wide range of agonists acting via specific receptors located on the vascular endothelial cells. The cationic peroxidases, such as major basic protein and eosinophil peroxidase, are neutralized by the highly anionic heparin; thus heparin inhibits the epithelial damage induced by some of these cationic proteins. The mechanism involved in the control of bronchial hyperreactivity by heparin has been studied little and is yet poorly understood. Heparin deserves further investigations in large number of subjects to provide further insight into the pathophysiology of asthma. Heparin may also be of clinical importance and may form the basis of novel therapeutic approaches.

Anticoagulants↗