Anti-inflammatory properties of montelukast, a leukotriene receptor antagonist in patients with asthma and nasal polyposis.

BACKGROUND: Leukotrienes, especially LTC4, are important inflammatory mediators in allergic and nonallergic inflammation of the entire airways. Of particular interest are numerous theories regarding the pathogenesis of aspirin intolerance with subsequent hyperproduction of leukotrienes and inhibition of cyclooxygenase. OBJECTIVE: To examine the influence of the cysteinyl-leukotriene receptor antagonist montelukast on clinical symptoms and inflammatory markers in nasal lavage fluid in patients with bronchial asthma and nasal polyps, and determine its dependency on aspirin sensitization. METHODS: Twenty-four patients (7 women, 17 men; median age, 55.5 years) with nasal polyps and controlled asthma (n=12 with aspirin intolerance) were treated with 10 mg montelukast once daily for 6 weeks in a blinded, placebo-controlled fashion. The placebo phase was randomly assigned 4 weeks before (n=12) or after treatment (n=12). Symptom score, rhinoendoscopy, rhinomanometry, smears for eosinophils, and nasal lavages for the determination of different mediators were performed. RESULTS: Compared to placebo, there were significant improvements in the nasal symptom score and airflow limitation as well as a reduction in the inflammatory mediators in nasal lavage fluid after treatment. Furthermore, reduced eosinophils in nasal smears and peripheral blood were observed 2 and 6 weeks after treatment. CONCLUSION: Leukotriene 1 receptor blockade led to a significant decrease in eosinophil inflammation accompanied by a reduction in other mediators such as neurokinin A and substance P in the nasal lavage fluid of patients with nasal polyps and asthma, with or without aspirin intolerance.

Effect of fluticasone on neuropeptides in nasal lavage in persistent allergic rhinitis.

OBJECTIVE: Recent guidelines reveal that allergic rhinitis impairs quality of life. Neuropeptides play a central role in allergy-related nasal inflammation. The objective of this study was to analyze the release of neuropeptides (substance P, neurokinin A, and vasoactive intestinal peptide) in nasal lavage and their modification by intranasal fluticasone propionate as an established therapy in patients with allergic rhinitis. METHODS: Eleven patients with proven allergic rhinitis induced by house dust mite were challenged before and after administration of fluticasone propionate nasal spray. Nasal lavage samples were collected after allergen challenge, and neuropeptides were measured using enzyme-linked immunosorbent assay. Values for histamine, protein, and human serum albumin were also recorded. Eight healthy individuals were included as nonatopic controls. RESULTS: The neuropeptides investigated were detectable in nasal lavage fluid in both patients and controls. Treatment with fluticasone propionate significantly decreased clinical response to allergen challenge (P < .01) compared with the controls and led to a decrease in values for substance P, neurokinin A, vasoactive intestinal peptide, histamine release, human serum albumin, and total protein after allergen challenge (P < .01). CONCLUSIONS: The demonstration of proinflammatory neuropeptides in NAL and suppression of their release after allergen challenge caused by a topical corticosteroid suggest a role for neuropeptides in allergic inflammation. Diminished release of neuropeptides induced b fluticasone propionate was accompanied by an improvement in the clinical symptoms of patients with persistent allergic rhinitis.

Effects of fexofenadine on inflammatory mediators in nasal lavage fluid in intermittent allergic rhinitis.

OBJECTIVE: Allergic rhinitis, a disease that impairs quality of life, is characterized by inflammation due to an allergic reaction. Fexofenadine is a second-generation histamine receptor blocker well known for its potent interaction with this inflammatory process. The main aim of this study was to further clarify the anti-inflammatory effects exerted by fexofenadine in patients with intermittent allergic rhinitis. METHODS: Twenty patients with intermittent allergic rhinitis due to birch and mugwort pollen were enrolled. Fexofenadine was administered once a day at a dose of 120 mg. Clinical improvement was assessed by a symptom score, and nasal airway flows were measured by anterior rhinomanometry at baseline and after 2 weeks of treatment with fexofenadine. Nasal smears were tested for eosinophils and nasal lavage fluid were examined for histamine, cysteinyl leukotrienes, soluble intercellular adhesion molecule-1, eosinophil cationic protein, and albumin by enzyme-linked immunosorbent assay. All the tests were performed during the pollen season. RESULTS: Fexofenadine induced a significant improvement in nasal and ocular symptoms (P < .001), nasal edema and secretion (P < .001), and nasal airway flow (P < .001). The clinical improvement was related to a significant reduction in all inflammatory mediators (P < .01 in all cases). CONCLUSION: This study demonstrates that fexofenadine is able to mediate significant changes in different nasal lavage markers from patients with intermittent allergic rhinitis. The changes observed in the markers analyzed in both nasal secretions and serum are attributable to the anti-inflammatory effects of fexofenadine in vivo.

Efficacy and safety of formoterol delivered through the Novolizer, a novel dry powder inhaler (DPI) compared with a standard DPI in patients with moderate to severe asthma.

BACKGROUND & OBJECTIVE: Because of environmental concerns CFC-containing pressurised metered dose inhalers (pMDI) had to be replaced by dry powder inhalers (DPI). The Novolizer, a novel DPI has previously been shown to be as effective as the Turbuhaler in delivering budesonide. The objective of this study was to show non-inferiority of inhaled formoterol therapy delivered through the Novolizer compared to formoterol delivered through the Aerolizer in patients suffering from moderate to severe asthma. METHODS: In this double-blind, double-dummy, multicentre study 392 patients were randomised and received a dose of 12 microg formoterol twice daily for 4 weeks either through the Aerolizer or the Novolizer. FEV1 after 4 weeks of treatment was the primary variable. Secondary variables were FVC, PEF, consumption of short-acting; 2 adrenoceptor agonists, asthma symptoms, tolerability and safety. RESULTS: After 4 weeks of treatment, the mean trough FEV1 (95% CI) was 2.34 L (2.24-2.45) for the Novolizer and 2.31 L (2.21-2.41) for the Aerolizer. Non-inferiority was proven (p<0.0001, pre-defined; of 0.25 L). All secondary variables (incl. PEF) confirmed these findings. Treatment with both devices was safe and well tolerated. CONCLUSION: Inhalation of 12 microg formoterol twice daily via Novolizer was shown to be equally therapeutically effective compared to the inhalation via Aerolizer in the treatment of moderate to severe persistent asthma. Treatment via both inhalers was safe and well tolerated.

Turbulent flow in smooth and rough pipes.

Recent experiments at Princeton University have revealed aspects of smooth pipe flow behaviour that suggest a more complex scaling than previously noted. In particular, the pressure gradient results yield a new friction factor relationship for smooth pipes, and the velocity profiles indicate the presence of a power-law region near the wall and, for Reynolds numbers greater than about 400x103 (R+>9x103), a logarithmic region further out. New experiments on a rough pipe with a honed surface finish with krms/D=19.4x10-6, over a Reynolds number range of 57x103-21x106, show that in the transitionally rough regime this surface follows an inflectional friction factor relationship rather than the monotonic relationship given in the Moody diagram. Outer-layer scaling of the mean velocity data and streamwise turbulence intensities for the rough pipe show excellent collapse and provide strong support for Townsend's outer-layer similarity hypothesis for rough-walled flows. The streamwise rough-wall spectra also agree well with the corresponding smooth-wall data. The pipe exhibited smooth behaviour for ks+ < or =3.5, which supports the suggestion that the original smooth pipe was indeed hydraulically smooth for ReD< or =24x106. The relationship between the velocity shift, DeltaU/utau, and the roughness Reynolds number, ks+, has been used to generalize the form of the transition from smooth to fully rough flow for an arbitrary relative roughness krms/D. These predictions apply for honed pipes when the separation of pipe diameter to roughness height is large, and they differ significantly from the traditional Moody curves.

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.

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.

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.

Direct detection of bacterial genomic DNA using gold nanoparticle probes.

The molecular probes and associated instrumentation necessary to perform genetic analyses are typically expensive, complex, and prone to error. While techniques such as real-time polymerase chain reaction (PCR) and gene expression analysis have provided a wealth of information previously unattainable, their utility in clinical diagnostics has yet to be realized due to the aforementioned limitations. Nanosphere Inc. has developed a gold nanoparticle-based platform for sequence specific DNA detection that is well-suited for clinical diagnostics due to its cost-effectiveness, simplicity, and accuracy. Thirteen nanometer gold nanoparticle probes, stabilized by a shell of oligonucleotides using proprietary attachment chemistries, enable highly sensitive and specific detection of bacterial genomic DNA sequences without synthetic amplification techniques on a glass array. After silver staining, light scattered by the nanoparticle probes is collected with robust, cost-effective instrumentation. It is the unique features of Nanosphere's detection methodology that provide the necessary steps forward to allow for genetic analyses to become part of routine clinical diagnostics.

Efficacy, safety, and acceptance of beclomethasone dipropionate administered via a new dry powder Inhaler or a standard CFC metered-dose inhaler in asthma patients.

BACKGROUND/OBJECTIVES: The mechanical aerosol generator, MAGhaler, is a new chlorofluorocarbon-free inhalation device. The objective of this trial was to show equivalent efficacy and safety of beclomethasone dipropionate (BDP) delivered via the MAGhaler and the metered-dose inhaler (MDI) in patients with mild to moderate bronchial asthma. Moreover, user-friendliness and acceptance of the two devices were compared. METHODS: This was a double-blind, reference-controlled, 12-week trial in 171 patients with asthma receiving BDP (1,000 microg/day) delivered via either the MAGhaler or the conventional MDI. Respiratory function parameters, clinical symptoms, concomitant intake of salbutamol or fenoterol, adverse events (AEs), laboratory values, and concomitant medications and diseases were recorded. The primary efficacy parameter was mean forced expiratory volume in 1 s (FEV1), measured after 4, 8, and 12 weeks of therapy. RESULTS: The equivalence of the two devices was confirmed (p = 0.003) on the basis of the ratios of the mean FEV1 in weeks 4 to 12. Mean (+/- SD) FEV1 (MAGhaler was 2.24 +/- 0.60 l (baseline), 2.61 +/- 0.90 litres (week 4), and 2.62 +/- 0.87 litres (weeks 4-12). Mean FEV1 (MDI) was 2.28 +/- 0.59 litres (baseline), 2.53 +/- 0.82 litres (week 4), and 2.56 +/- 0.77 litres (weeks 4-12). In total, 33 AEs occurred in 26 (30.2%) patients (MAGhaler) and 51 AEs in 36 (42.4%) patients (MDI). Most of the AEs were of mild or moderate intensity. The relationship to treatment could not be excluded for 11 AEs in 11 patients (MAGhaler) and 23 AEs in 18 patients (MDI). Three serious AEs, all unrelated to treatment, occurred in 3 patients (MAGhaler: 2, MDI: 1). There were no clinically relevant changes in other safety parameters. Most patients either preferred the MAGhaler or rated the two devices as equally acceptable. CONCLUSION: The new MAGhaler was equivalent to the standard MDI in terms of the safety and efficacy of BDP. The improved user-friendliness and acceptance of the MAGhaler over the conventional MDI represent an important advance in the clinical management of bronchial asthma.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.