Biomedical subjects

G Kunkel

Publications and source records attributed to G Kunkel.

At least 19 recordsLinked to original sources

PubMed2006

Omalizumab decreased IgE-release and induced changes in cellular immunity in patients with allergic asthma.

BACKGROUND: Omalizumab, a recombinant monoclonal anti-immunoglobulin E (IgE) antibody, shows proven efficacy in the treatment of allergic diseases. A little is known about the immunological pathways affected by the decrease of circulating free IgE during omalizumab treatment. AIM OF THE STUDY: To investigate the immunological consequence of IgE withdrawal, we studied the influence of omalizumab on stimulated IgE-release of cultured peripheral blood mononuclear cells (PBMC) and on the relative number of lymphocytes in the peripheral blood (cellular immune status) in patients with allergic asthma. METHODS: Nineteen patients were enrolled and received omalizumab at a dose of at least 0.016 mg/kg/IgE (IU/ml) every 4 weeks. PBMC were isolated from peripheral blood. Cells were cultured and stimulated with IL-4 (5 ng/ml) and CD40 ligand (1 microg/ml) for 10 days. IgE release was detected in cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Cellular immune status was investigated by fluorescence-activated cell sorting. RESULTS: Omalizumab treatment induced significant inhibition of stimulated IgE release (median 1.38-0 ng/ml vs. 1.64-2.0 ng/ml in placebo group, P<0.05). B-lymphocyte counts were also significantly lower in the omalizumab group compared with placebo after 12 weeks of treatment (median 18.2-15.6% lymphocytes vs 12.7-13.7% lymphocytes after placebo, P<0.01). There were no significant differences in the other lymphocyte subpopulations between the groups. CONCLUSIONS: These findings provide evidence of immunological influences of omalizumab treatment, leading to a downregulation of IgE secretion and decrease of lymphocyte subpopulations (B-cells) indicating their anti-inflammatory potency.

Adult↗

PubMed2005

Use of CD34+ autologous stem cell transplantation in the treatment of children with refractory systemic lupus erythematosus.

We report on the unique effects and benefits of autologous stem cell transplantation in childhood systemic lupus erythematosus (SLE) and describe this procedure in two young girls with severe and refractory disease. The patients' stem cells were mobilized with granulocyte colony-stimulating factor (G-CSF) and collected by CS-3000 Blood Cell Separator (Baxter Healthcare, Round Lake, Ill., USA), and the CliniMACS CD34+ cell selection device (Miltenyi Biotech, Bergisch Gladbach, Germany) was used to obtain CD34+ cells. A total of 1.7x10(6) and 1.0x10(6)/kg CD34+ cells were obtained, with 2.0x10(5) and 1.0x10(4)/kg of CD3+ cells remaining, respectively. The conditioning regimen consisted of cyclophosphamide (50 mg/kg per day for 4 days) plus antithymocyte globulin (ATG-Fresenius, 5 mg/kg per day for 3 days). Neutrophil counts recovered within 9 days in both cases. Within 15 days, the platelet counts recovered and were sustained over 100x10(9)/l. Cushingoid features disappeared completely 3 months after transplantation because of the removal of corticosteroid medication. One 13-year-old child increased her height by 5 cm in 6 months after stopping steroids. She had not increased her height in her previous 7 years of disease. As of the time of this report, the first patient remains in clinical and laboratory remission for nearly 4 years, while the second suffered a relapse of thrombocytopenia 9 months post-transplantation. One residual effect of their treatment is that their CD4+ cell counts remained in the lower range after one year of transplant. The effect of this conditioning regimen plus CD34+ autologous stem cell transplantation on these two children with refractory SLE was beneficial, but long-term follow-up data and additional experience with this procedure are required. Autologous stem cell transplantation may limit the long-term toxicity of therapy in childhood SLE.

Adolescent↗

PubMed2004

Omalizumab inhibits allergen challenge-induced nasal response.

Elevated serum levels of antigen-specific immunoglobulin (Ig)E are often associated with allergic respiratory diseases. This parallel-group, randomised, double-blind, placebo-controlled trial was designed to study the influence of omalizumab on the early nasal response to allergen challenge reflected by symptom score and inflammatory marker levels in nasal lavage fluid (NAL). A total of 23 patients with allergic rhinitis took part in the study, 11 were given placebo and omalizumab was administered subcutaneously in 12. Omalizumab or placebo were given at 2- or 4-week intervals based on a patient's body weight and IgE levels to a total dose of 0.016 mg x kg(-1) x IgE(-1) (IU x mL(-1)) every 4 weeks. Compared to placebo, 16 weeks of treatment with omalizumab significantly inhibited allergen challenge-induced nasal symptoms (median symptom score 7.0-0.5 versus 7.0-7.0) and inhibited the increase of human serum albumin (median 15.3-0.12 mg x mL(-1) versus 8.2-19.7 mg x mL(-1)) in the NAL after allergen challenge. Treatment with omalizumab induced a significant decrease in tumour necrosis factor-alpha levels in basal NAL, but no change was seen for histamine. These results indicate that subcutaneously administered monoclonal anti-immunoglobulin-E antibody, omalizumab, inhibits the nasal responses to allergen challenge of patients with allergic rhinitis. Omalizumab may provide a new strategy for the treatment of allergic rhinitis.

Adult↗

PubMed2003

Antioxidative enzymes in human nasal mucosa after exposure to ozone. Possible role of GSTM1 deficiency.

OBJECTIVE AND DESIGN: Epithelial antioxidative enzymes (AOEs) are thought to be a first line of defense against reactive oxygen species as they are upregulated after exposure to ozone according to animal studies. We analysed the activities of the AOEs catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD) and glutathione-S-transferase (GST) in a tissue culture of human nasal mucosa and analysed the influence of GSTM1 polymorphism on AOE regulation. METHODS: Tissue biopsies of 20 subjects were incubated for 24 h with and without 120 ppb ozone. Activities were assayed to determine what enzymatic changes had taken place, both overall and in regard to GSTM1 status. RESULTS: Activities for GPX (p = 0.272) and SOD (p = 0.291) were found increased after ozone exposure. GSTM1-deficient patients showed a significantly enhanced upregulation of SOD activity (p = 0.011) compared to GSTM1 carriers. CONCLUSION: Our findings suggest that GSTM1-deficiency has an impact on AOE-regulation after ozone exposure.

Genotype↗

PubMed2003

The production, storage and release of the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 by human peripheral eosinophils in allergics and non-allergics.

BACKGROUND: Recent studies have shown that neurotrophins are produced by and can act on several immune-inflammatory cells. The origin of circulating as well as local neurotrophins is unknown. OBJECTIVES: The aim of this study was to assess whether eosinophils of allergic and non-allergic donors produce, store and release the neurotrophic factors NGF, BDNF and NT-3. METHODS: Eosinophils were purified by negative immunoselection (purity > 96%) from allergic asthmatics and non-allergic donors (25 to 53 years). The presence of mRNA for neurotrophic factors was evaluated by reverse transcription PCR. Specificity was demonstrated by cloning products and sequencing. Stored NGF, BDNF and NT-3 was demonstrated by Western-blotting and flow cytometry. Eosinophils were incubated and supernatants were collected for measurement of neurotrophic factors after cell stimulation with PAF. Neurotrophin content in eosinophil lysates was determined by ELISA. RESULTS: Eosinophils demonstrate mRNA for neurotrophins. Proteins were detectable by Western blot and FACS analysis. Neurotrophins were found in the eosinophil lysates at different amounts comparing allergic and non-allergic donors. Cell stimulation with PAF (10-8-10-5 M) after priming with GM-CSF leads to a dose-dependant release of NGF and BDNF. CONCLUSIONS: Eosinophils store, produce and release NGF, BDNF and NT-3. They are a possible source of elevated neurotrophin levels found in allergy and asthma.

Adult↗

PubMed2003

Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions.

Influx of eosinophils in airway mucosa and airway lumen is a hallmark of bronchial asthma. In-vitro data and animal studies indicate that the T-helper (Th) type-2 cell cytokine, interleukin (IL)-5, plays an important role in eosinophil maturation, differentiation, recruitment, and survival. The objective of this study was to determine whether intravenous treatment with monoclonal anti-IL-5 would affect the number of peripheral blood eosinophils, their activation status, T-cell activation or the pattern of Th1 and Th2 cytokine production. Over a period of 6 months, 19 asthmatics were investigated in a double-blind, placebo-controlled, multicentre study with mepolizumab (SB 240563) anti-IL-5 antibody administered three times. Before each infusion and 12 weeks after the last infusion, peripheral blood leukocytes were examined, qualitative and quantitative distribution of eosinophils and lymphocyte subpopulations, frequencies of IL-2, -3, -4, -5, -10, -13, interferon-gamma-producing CD4 T-cells and serum eosinophil cationic protein (ECP) levels were determined. Treatment with mepolizumab resulted in a marked, rapid and sustained decrease of eosinophil numbers (median values from 300 to 45 per microL) paralleled by decreased levels of serum ECP (median values from 15 to 5 microg x L(-1)). Distribution of T-cell subsets and T-cell cytokine production were not altered during antibody treatment. In conclusion, administration of mepolizumab to asthmatic patients markedly reduces peripheral blood eosinophils without altering the distribution and activation status of lymphocytes.

Adult↗

PubMed2002

Effects of beta-endorphin on nasal allergic inflammation.

BACKGROUND: Beta-endorphin is a derivative of pro-opiomelanocortin. Cells of the immune system can also synthesize and secrete beta-endorphin. Its concentration is increased during the allergic reaction and during stress. Increased reactivity during psychological stress of allergic subjects is also well known. OBJECTIVE: Is beta-endorphin one physiological link between stress and an exacerbation of the allergic reaction? METHODS: First, intranasal beta-endorphin challenges with subsequent lavages to determine histamine and albumin levels and measurements of nasal flow and resistance in dose-response and time course experiments were performed. Secondly, we examined whether beta-endorphin pre-treatment increased the antigen-induced release of histamine and albumin in nasal lavages and the clinical symptoms. RESULTS: Exogenous beta-endorphin (100 pM-10 microM/mL) induced a dose-dependent increase in nasal symptoms in asymptomatic allergic subjects with rhinitis (n = 14) as well as in non-allergic controls (n = 10), but did not release any mediators into nasal secretion. However, comparing the antigen-evoked release of mediators into nasal secretions with that of a beta-endorphin pre-treated antigen challenge we could note a significant enhancement of human serum albumin influx (P < 0.05) and histamine liberation (P < 0.05) 10 min after antigen challenge compared with the allergen challenge alone, with also a correlation with the more pronounced decrease in nasal flow (P < 0.05). CONCLUSION: These results suggest that beta-endorphin-induced increase in nasal congestion is mediated through direct neuroendocrine receptor activation independent of mast cell activation and that during the allergic reaction there is a beta-endorphin/mast cell interaction that enhances the mediator response to nasal allergen challenge.

Administration, Inhalation↗

PubMed2002

Activation of the specific neurotrophin receptors TrkA, TrkB and TrkC influences the function of eosinophils.

BACKGROUND: Recent studies have shown that nerve growth factor (NGF) can act on several immune cells as well as residential cells. But little is known about their role in modulating eosinophil function via activation of high-affinity receptors. OBJECTIVES: The aim of this study was to assess whether eosinophils express functional receptors and if their function is influenced by NGF, brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3). METHODS: Eosinophils were purified by negative immunoselection (purity > 96%). High-affinity neurotrophin receptors were demonstrated by reverse transcription polymerase chain reaction, western blotting and flow-cytometry analysis. Functionality of receptors was demonstrated by receptor phosphorylation after ligand binding. Eosinophils were incubated with NGF, BDNF and NT-3, and cells and supernatants were collected for measurement of the mediators IL-4, IL-5, IL-8, transforming growth factor (TGF)-beta1, eosinophil cationic protein (ECP), eosinophil protein X (EPX) as well as eosinophil viability. RESULTS: Eosinophils expressed mRNA for neurotrophin receptors. Proteins were detectable by western blot and fluorescent-activated cell sorter analysis. The receptors were phosphorylated after stimulation with neurotrophins. After NGF stimulation, a significant increase in IL-4 was detectable. BDNF and NT-3 stimulation led to a significant increase in EPX. Eosinophil viability was not influenced. CONCLUSIONS: Eosinophils express the functionally active receptors TrkA, TrkB and TrkC. Receptor activation stimulates eosinophils. This might be an additional pathway regulating inflammatory responses in allergic reactions.

Blotting, Western↗

PubMed2001

Correlation between neutral endopetidase (NEP) 3.4.24.11 in serum and the degree of the bronchial hyperreactivity.

Neutral endopeptidase (NEP) is described in airways as the major degrading enzyme of tachykinins such as neurokinin A (NKA) and substance P (SP). Due to its localization and mode of action NEP may play a role in the pathophysiology of bronchial reactivity (BR) especially under the aspect of neurogenic inflammation. Serum NEP concentrations were measured by ELISA to investigate if there is a correlation between serum NEP and the degree of bronchial reactivity expressed by PC20-FEV1 histamine(.). PC20-FEV1 histamine was determined in 31 asthmatic patients [age 31.9+/-1.3 years (mean+/-SEM) FEV1=92.1+/-2.4% (mean+/-SEM) 16 females/15 males]. Prior to the histamine challenge blood samples were obtained and stored at -70 degrees C until determination using ELISA. A significant correlation between serum NEP and the PC20-FEV1 (n=31, r=0.49, P<0.01) was found. The results suggest that serum NEP is modulating neuropeptide-induced effects in the pathophysiology of airway responsiveness.

Adult↗

PubMed2001

The influence of inhalative corticosteroids on circulating Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Neurotrophin-3 in allergic asthmatics.

BACKGROUND: The neurotrophins Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin (NT)-3 are produced, stored and released by various immunological cells. The influence of NTs upon the function of these cells is described. Elevated plasma levels were found in inflammatory, autoimmune and allergic diseases with the highest levels in allergic asthma. A connection between bronchial hyper-responsiveness and serum levels has been reported. OBJECTIVE: Little is known about the influence of treatment with inhaled corticosteroids (ICS) on serum NT levels and their influence on the asthmatic state. METHODS: Eighty-seven volunteers were studied. Thirty-eight were stable allergic asthmatics with constant ICS doses, 29 were asthmatics not receiving anti-asthmatic treatment and 20 were age- and sex-matched healthy controls. Demographic and lung function data were evaluated. NT serum levels were determined by ELISA. RESULTS: NGF and BDNF levels were significantly increased in untreated asthmatics compared to the control and the treated group, while NT-3 demonstrated significantly higher levels in treated asthmatics compared to healthy controls. After stabilization of untreated subjects with ICS, the NT levels decreased significantly. CONCLUSIONS: These results suggest that NTs participate in allergic inflammation and asthma. Effective treatment leads to a decrease of circulating neurotrophic factors.

Adrenal Cortex Hormones↗

PubMed2001

Therapeutic equivalence of the Sofotec Novolizer to established standard devices in COPD and asthma.

The Novolizer is a breath-actuated multidose dry powder inhaler that was developed as an alternative to the pressurized metered dose inhalers. The efficacy, safety and tolerability of the Novolizer has been compared with those of established inhalational devices for the delivery of salbutamol (Sultanol) in patients with chronic obstructive pulmonary disease and for the administration of budesonide (Pulmicort Turbuhaler) to patients with asthma. In both studies, improvement in forced expiratory volume in 1 s in patients who were randomly assigned to use the Novolizer was comparable with that in patients who used the established devices. Furthermore, no differences in tolerability or safety between the Novolizer and the control devices were observed. Finally, patient acceptance of the Novolizer was high, with the majority of patients who used it stating that they would use the device again.

Albuterol↗

PubMed2001

Immunoblot studies in birch pollen-allergic patients with and without fruit hypersensitivity: part I: antibody pattern for birch pollen extract.

About 40-70% of birch pollen allergic patients show allergic symptoms after ingesting or handling raw fruits. Several investigations have indicated a partial immunological identity between birch pollen and stone fruit. To further clarify this association, we investigated 59 patients with allergic symptoms (conjunctivitis, rhinitis, and asthma during the birch pollen season) and 18 nonatopic controls by skin prick test (SPT) and RAST with birch pollen, fresh apple, cherry, and peach as well as freshly prepared fruit extracts. According to a questionnaire dealing with symptoms after ingestion of raw fruits, the subjects were divided into groups with (35 FH+) and without (24 FH-) fruit hypersensitivity. IgE, IgG, IgG1, IgG4, IgA, and IgM binding patterns to birch pollen extracts were performed with 33 sera (12 FH+, 11 FH-, and 10 nonatopic controls) using the immunoblot-technique. Patients with FH+ expressed a significantly stronger sensitization to birch pollen than patients without FH-, as measured by RAST and SPT. Native fruits induced stronger SPT reactions than fruit extracts, and patients with FH+ showed a significantly higher skin index with all fruits and fruit extracts tested. Specific IgE, IgG, IgG1, IgG4, IgM and IgA to birch pollen extracts could be detected by immunoblot in all groups, albeit with different frequencies and intensities. From this data we conclude that fruit hypersensitivity is related more to the 17 kd and 67-85 kd than to the 26-28 kd or 36 kd protein bands of the birch pollen extract. The relationship of specific IgE > IgG > IgM to a single protein band seems to be associated with the development of symptomatic type I allergy.

Adolescent↗

PubMed2001

Immunoblot studies in birch pollen-allergic patients with and without fruit hypersensitivity: part II: antibody pattern for fruit extracts.

Patients allergic to birch pollen also exhibit more hypersensitivity reactions to fresh fruits and vegetables than do patients allergic to other pollens. Several investigations have indicated a possible partial immunological identity between birch pollen and fruits. To study this, 23 birch pollen-allergic patients 12 with (FH+) and 11 without (FH-) fruit hypersensitivity and 10 nonatopic controls were examined with self-prepared apple-peel, cherry, and peach extracts by immunoblotting. The self-prepared extracts were characterized by histamine release studies with 20 FH+ birch pollen-allergic patients. Specific IgE, IgG, IgG1, IgG4, IgA, and IgM binding patterns of the fruit extracts presented an individual distribution with at least 1-3 IgE bands at varying molecular weight locations. The FH+ group expressed intense IgE binding to the different extracts compared to the FH- group, and even the control group showed all immunoglobulin classes, though different frequencies and intensities compared to the allergic groups. It seemed that the specific IgE > IgG > IgM relation to a single antigen is important for distinguishing between symptomatic and asymptomatic persons. With this hypothesis we found most IgE with less IgG binding to apple-peel in the region of 22-28 kd and 43-56 kd, cherry: 15-25 kd and 72- > 90 kd and peach 35-41 kd and 66-76 kd, suggesting that these proteins might be important for cross-reactivity with birch pollen and developing fruit hypersensitivity.

Antibodies↗

PubMed2000

Substance P induced histamine release from nasal mucosa of subjects with and without allergic rhinitis.

OBJECTIVE AND DESIGN: There is evidence that substance P (SP) is involved in events related to allergic and nonallergic rhinitis. Furthermore, some effects of SP seem to be greater in subjects suffering from allergic rhinitis than in nonallergic subjects. To investigate if these effects may be partly mediated by histamine release (HR) we studied the influence of SP on HR from nasal mucosa of subjects with and without allergic rhinitis using an in vitro organ culture system. SUBJECTS: Nasal mucosa of the inferior turbinate was obtained from ten patients suffering from allergic rhinitis and eighteen non-allergic subjects receiving surgical therapy for nasal obstruction. METHODS: Tissue samples of nasal mucosa were stimulated with 10(-5) M SP or with 10(-5) M Ca-ionophore A23187 for 120 minutes, and the histamine content was determined in the culture supernatant. RESULTS: Both SP and Ca-ionophore A23187, caused a significantly higher HR from the samples of the non-allergic group (p < 0.01) compared to baseline controls (spontaneous release). The same effect was seen in the allergic group (p < 0.01 and p = 0.036). Comparing the increase in HR from allergic and non-allergic mucosa, in allergics the HR stimulated by SP was significantly higher (p = 0.031), whereas Ca-ionophore A23187 did not show this effect. CONCLUSION: These findings suggest a role of SP in inducing release of histamine from human nasal mucosa, thereby influencing physiologic and pathophysiologic nasal conditions, especially in allergic inflammatory processes.

Adult↗

PubMed2000

Allergen inhalation challenge induces decrease of serum neutral endopeptidase (NEP) in asthmatics.

There is accumulating evidence that tachykinins are implicated in inflammation, including asthma. Therefore, we hypothesized that the neutral endopeptidase (NEP), under challenge conditions, could be affected. Serum from 21 asthmatics and six healthy volunteers was sampled before, 30, and 120 min after allergen challenge. NEP-IR was determined using an ELISA and was found in all subjects. Compared to prechallenge, no difference was seen between asthmatics and controls; however, under challenge conditions, NEP-IR in asthmatics was significantly lower (30 min, P = 0.058; 120 min, P = 0.0017, respectively). This finding supports indirectly the hypothesis that tachykinins are released during allergen exposure, and suggests a regulatory role of NEP.

Administration, Inhalation↗

PubMed2000

Respimat (a new soft mist inhaler) delivering fenoterol plus ipratropium bromide provides equivalent bronchodilation at half the cumulative dose compared with a conventional metered dose inhaler in asthmatic patients.

BACKGROUND: Respimat, a possible alternative to the conventional metered dose inhaler (MDI), is a novel, reusable, propellant-free, multidose soft mist inhaler. Respimat slowly releases a metered dose of active substance as a soft mist with a high proportion of the dose in the fine particle fraction, leading to improved lung deposition following inhalation when compared with the conventional MDI. OBJECTIVES AND METHODS: The equipotent bronchodilating efficacy and safety of a combination of fenoterol hydrobromide and ipratropium bromide (F/I) in cumulative doses delivered by either Respimat or pressurised MDI was assessed in a randomised, controlled, double-blind (within device) 4-way crossover study. Forty-three patients with stable asthma (mean FEV(1) 62% predicted) responsive to F/I inhaled cumulatively 16 puffs on each of 4 test days (1 + 1 + 2 + 4 + 8 puffs at 50-min intervals) via Respimat delivering 50/20, 25/20 or 25/10 microg F/I per puff or via MDI delivering 50/20 microg F/I per puff. RESULTS: Cumulative doses of 400/160 and 400/320 microg F/I via Respimat produced bronchodilation (evaluated by average increase in FEV(1) 45-245 min after first inhalation) equivalent to that achieved with a cumulative 800/320 microg F/I via MDI (mean increase in FEV(1) above baseline 0.76, 0.73 and 0.71 litres, respectively). The tolerability of the F/I combination via Respimat was also comparable to that of twice the dose delivered via MDI. CONCLUSION: Therefore, a fenoterol hydrobromide/ipratropium bromide combination delivered by Respimat is as safe and effective as the MDI at half the cumulative dose, on acute administration to patients with asthma.

Administration, Inhalation↗

PubMed1999

Bronchodilation using combined urodilatin - albuterol administration in asthma: a randomized, double-blind, placebo-controlled trial.

Urodilatin, the renal form of natriuretic peptide type A, induces bronchodilation, increasing intracellular cyclic guanosine monophosphate (cGMP), whereas the bronchorelaxant effect by b2-agonists is triggered by cyclic adenosine monophosphate (cAMP). The objective of this investigation is to demonstrate the efficacy of urodilatin in inducing bronchodilation, and to show this activity alone or in combination with albuterol. Therefore, a randomized, double-blind, placebo-controlled, dose-finding study with cross-over design was carried out including 12 stable, mild to severe (step 2 to 4, definition by NIH/NHLBI guideline 1997) asthmatics. 96 treatments were thus performed. The intervention was comprised of an intravenous infusion of urodilatin (0, 10, 30, or 60 ng/kg/min) combined with inhaled albuterol (0 or 200 microg). As primary objective, the increase in forced expiratory volume in one second (FEV subset1) was measured. - The trial shows that urodilatin at all applied doses or 200 microg albuterol significantly increases FEV subset1 (p < 0.05). Combination of urodilatin and albuterol treament significantly improves FEV subset1 (p < 0.05) compared to either monotherapy and results in maximum bronchodilation. - From the results, the following conclusions can be drawn. In stable asthmatics, the combined activation of cGMP- and cAMP-mediated pathways results in a significantly improved, maximal bronchodilation in comparison to either type of monotherapy. This shows that urodilatin combined with albuterol improves lung function and ameliorates the therapy in asthmatics.

Adult↗

PubMed1999

Serum eosinophil cationic protein (ECP) as a mediator of inflammation in acute asthma, during resolution and during the monitoring of stable asthmatic patients treated with inhaled steroids according to a dose reduction schedule.

OBJECTIVE AND DESIGN: The main objective was to establish the level of serum ECP in a group of adult asthmatic patients with acute exacerbation and the following resolution and in another group of adult, stable asthmatic patients during reduction of inhaled steroids. SUBJECTS AND TREATMENT: Acute group: Twenty-one asthmatic patients admitted to the asthma clinic with acute deterioration of their asthma were set on oral steroids which were reduced to 0 within one week. Reduction group: Forty-four stable asthmatic patients on maintenance inhaled steroids were included and, on the basis of their peak expiratory flow (PEF) values, adjustments in the doses of steroids were made. CONTROL GROUP: Twenty stable asthmatics on a constant dose of inhaled steroids were enrolled as controls. METHODS: All patients registered daily PEF measurements and spirometry was performed at each visit. Blood samples were drawn and analysed for eosinophil cationic protein (ECP), myeloperoxidase (MPO), eosinophils and neutrophils. RESULTS: ECP was low and within the normal range for all three groups at study entry. (Acute group = 8.4 microg/l, reduction group = 3.7 microg/l and control group = 4.6 microg/l). Nevertheless, the value in the acute group was significantly higher than in the control group (p=0.005). The levels in the acute group decreased significantly (p=0.004) after one week on oral steroids. No significant changes in ECP were observed in the reduction group or in the control group during the follow-up period. The lung function was low in the acute group at inclusion, forced expiratory volume in one second (FEV1)=47.1% of predicted, and increased significantly during the treatment period (p = 0.006). The patients in the reduction- and control group showed small variations in lung function during the whole study, FEV1 >70% and PEF > 80% of predicted, respectively. No correlation between atopy and ECP was found in the patients irrespective of the stage of disease. CONCLUSIONS: This study suggests that the resolution of acute asthma exacerbations during treatment could be followed using ECP determinations. In stable asthmatics on inhaled steroids and with normal ECP levels, a dose reduction could be indicated. A longer period after tapering off steroids is proposed to confirm the benefit of ECP measurements for controlling asthma.

Acute Disease↗