A randomized, double-blind trial of the effect of treatment with montelukast on bronchial hyperresponsiveness and serum eosinophilic cationic protein (ECP), soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion molecule 1 (sICAM-1) in children with asthma

BACKGROUND: Anti-inflammatory properties of leukotriene modifiers and their effect on bronchial hyperresponsiveness have not been studied in children with asthma. OBJECTIVE: The primary objective of this study was to determine the changes in serum levels of inflammatory mediators, clinical efficacy, and bronchial hyperresponsiveness after treatment with montelukast. METHODS: In this double-blind, randomized, placebo-controlled trial, 39 children with mild-to-moderate atopic asthma were randomly allocated to receive montelukast or placebo for 6 weeks. Main outcome measures were changes in serum concentrations of soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion molecule 1 (sICAM-1); peripheral blood eosinophil count; and eosinophilic cationic protein (ECP). Asthma severity score, FEV(1), and bronchial hyperreactivity (BHR) for histamine were secondary end points. RESULTS: Compared to placebo, serum concentrations of IL-4, sICAM-1, and ECP and eosinophil blood counts significantly decreased after 6 weeks of treatment with montelukast. Montelukast significantly improved asthma control and FEV(1). Montelukast resulted in within-group significant decrease in levels of serum sIL-2R (611 vs. 483 pg/mL), IL-4 (0.123 vs 0.102 pg/mL), sICAM-1 (280 vs. 244 ng/mL), and ECP (74 vs. 59 microg/mL) and in eosinophil blood counts (349 vs. 310 cells/mm(3)). Mean FEV(1) value changed from 85% of predicted to 95% (P <.001) and for histamine (PC(20)H) from 2.8 mg/mL to 3.8 mg/mL (P <.001) after treatment with montelukast. There was no significant difference between montelukast and placebo recipients in the serum concentrations of sIL-2R and PC(20)H after treatment. CONCLUSION: Montelukast provides clinical benefit to patients with chronic asthma and decreases bronchial hyperresponsiveness. Montelukast caused a statistically significant decrease of serum concentrations in cytokine, ICAM-1, and ECP and peripheral blood eosinophil counts over the 6-week treatment period. This observation raises the possibility that leukotriene receptor antagonists, such as montelukast, may have effects on parameters of asthmatic inflammation.     

Soluble intercellular adhesion molecule-1 in sera of children with bronchial asthma exacerbation.

Previous studies have suggested that intercellular adhesion molecule-1 (ICAM-1; CD54) may be involved in the pathogenesis of asthma. In addition, a soluble form of intercellular adhesion molecule-1 (sICAM-1) has been detected in increased concentrations in the sera from adult patients with certain inflammatory, immune, or malignant diseases. To determine whether bronchial asthma exacerbation in children is associated with increased levels of serum sICAM-1 and to investigate the effect of the severity of exacerbation on these levels, the concentrations of sICAM-1 were measured in sera of 20 healthy control children and 45 asthmatic children (15 with mild, 15 with moderate, and 15 with severe asthma exacerbation) using an immunoenzymatic assay. Assessment of the severity of asthma exacerbation was based on clinical and physiological parameters. The mean (+/- SD) level of serum sICAM-1 for asthmatic children (390.0+/-108.3 ng/ml) was significantly higher than that for healthy (193.2+/-33.95 ng/ml; p = 0.000). We have also found a differential rise of serum sICAM-1 level which correlates well with the severity of asthma exacerbation. The elevated concentrations of serum sICAM-1 in acute bronchial asthma may reflect the extensive inflammatory response occurring in the airways during acute exacerbation of the disease with airway obstruction. The results of this study suggest that serum sICAM-1 is a promising serological marker of the severity of inflammation in bronchial asthma in children and it would not only facilitate staging of inflammation but also allow the monitoring of therapy and intervention.     

Elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and sE-selectin levels in bronchial asthma.

Adhesion molecules such as ICAM-1 and E-selectin have been shown to play important roles in the production of allergic inflammation. In the present study, we measured serum soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-selectin) levels by ELISA in 42 patients with bronchial asthma (22 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of ICAM-1 and E-selectin in allergic inflammation. Both serum sICAM-1 levels and serum sE-selectin levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels, serum tumour necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. There was a correlation between the nature of change in serum TNF-alpha levels and the nature of change in serum sICAM-1 levels or serum sE-selectin levels, though serum TNF-alpha levels did not correlate with serum sICAM-1 levels or serum sE-selectin levels. These results suggest that higher levels of sICAM-1 and sE-selectin during asthma attacks may reflect the up-regulation of ICAM-1 and E-selectin expression in allergic inflammation, and that the soluble form of these adhesion molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of ICAM-1 and E-selectin in vitro, however; the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels remains to be clarified.     

The effect of immunotherapy on nonspecific bronchial hyperresponsiveness in bronchial asthma and allergic rhinitis

Allergen injection therapy may improve nonallergic bronchial hyperresponsiveness, but results at the moment are less than convincing. The present study was conducted to evaluate the effect of immunotherapy on the degree of nonspecific bronchial hyperresponsiveness in patients with allergic bronchial asthma (BA) and/or allergic rhinitis (AR). Methacholine challenge bronchial provocation test, allergic skin test, serum IgE and peripheral blood eosinophil counts were performed before and after 12 months or more of immunotherapy. The improved group, as determined by a shift of at least two doubling concentrations of methacholine, was 75% of AR (n=16), 41.7% of BA (n=24) and 53.8% of BA+ AR (n=13). The geometric mean of the methacholine provocational concentration (PC20) changed from 3.40 to 14.36 mg/ml (P <0.05) in AR, from 0.73 to 1.04 mg/ml in BA (not significant), and from 1.43 to 5.07 mg/ml (P <0.05) in BA+ AR. In conclusion, nonspecific bronchial hyperresponsiveness was improved by immunotherapy in three quarters of the allergic rhinitis cases and in about a half of the allergic bronchial asthma patients, which suggests that immunotherapy might be helpful at preventing the development of bronchial hyperresponsiveness in allergic rhinitis patients, and that it does not improve bronchial hyperresponsiveness in about a half of allergic bronchial asthma patients.     

Bronchial hyperresponsiveness in young children with allergic rhinitis and its risk factors

BACKGROUND: Subjects with allergic rhinitis but no clinical evidence of asthma have greater bronchial hyperresponsiveness (BHR), and several factors have been implicated as its determinants. However, studies in young children are lacking. The aims of this study were to evaluate the prevalence of BHR in young children with allergic rhinitis and to investigate its risk factors. METHODS: Methacholine bronchial challenges were performed in 4- to 6-year-old nonasthmatic children with allergic rhinitis (n = 83) and in healthy nonatopic controls (n = 32), using a modified auscultation method. The end-point was defined as the appearance of wheezing and/or oxygen desaturation. Subjects were considered to have BHR when they had end-point concentrations of methacholine 相似文献   

Serum concentrations of interferon-γ and intercellular adhesion molecule-1 eight years after an early respiratory syncytial virus infection

BACKGROUND: Respiratory syncytial virus (RSV) infection may influence the development of recurrent wheezing and atopy, but the mechanisms are unclear. OBJECTIVE: The purpose was to evaluate serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), CD14, IgE, IL-5 and IFN-gamma in children 6-10 years after an RSV infection and their correlation with subsequent asthma and atopy. METHODS: Fifty-one subjects admitted to hospital for RSV infection during the first year of life and controls matched for birth date and sex underwent clinical examinations including lung function, skin prick and blood tests. RESULTS: The RSV subjects had significantly higher serum concentrations of IFN-gamma and sICAM-1 than the controls (for IFN-gamma 224.9 pg/mL (standard deviation (SD) 271.3) vs. 187.1 pg/mL (372.9), difference 37.8 pg/mL, 95% confidence interval (CI) -90.3 to 166.0, P = 0.05; for sICAM-1 170.2 ng/mL (SD 63) vs. 147.8 ng/mL (SD 57), difference 22.4 ng/mL, 95% CI -1.4 to 46.1, P = 0.04). The RSV subjects with asthma had significantly higher concentrations of IFN-gamma than the controls with asthma, and the RSV subjects with wheezing during the previous 12 months had significantly higher concentrations of both IFN-gamma and sICAM-1 than the controls with wheezing. CONCLUSIONS: Children hospitalized for RSV infection in infancy still differ in IFN-gamma and sICAM-1 production 6-10 years after the infection. The data suggest that the pathomechanism of asthma and wheezing after an early RSV infection may be different from that of children without an early RSV infection.     

Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing

BACKGROUND: Eosinophilic airway inflammation is the hallmark of asthma, but it has also been reported in other conditions such as allergic rhinitis. We have tested whether the analysis of cells and chemicals in sputum can distinguish between patients with mild allergic asthma, those with allergic rhinitis, and healthy controls. The relationship between inflammation markers in sputum and nonspecific bronchial hyperresponsiveness to methacholine (BHR) (PD20 and maximal response plateau [MRP] values) was also evaluated. METHODS: We selected 31 mild asthmatics and 15 rhinitis patients sensitized to house-dust mite. As a control group, we studied 10 healthy subjects. Every subject underwent the methacholine bronchial provocation test (M-BPT) and sputum induction. Blood eosinophils and serum ECP levels were measured. Sputum cell differentials were assessed, and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin (IL)-5 levels were measured in the entire sputum supernatant. RESULTS: Blood eosinophils and serum ECP levels were higher in asthma patients and rhinitis than in healthy controls, but no difference between asthma patients and rhinitis patients was found. Asthmatics had higher eosinophil counts and higher ECP and tryptase levels in sputum than rhinitis patients or control subjects. Sputum albumin levels were higher in asthmatics than in controls. Rhinitis patients exhibited higher sputum eosinophils than healthy controls. An association between sputum eosinophil numbers and MPR values (r= -0.57) was detected, and a trend toward correlation between sputum ECP levels and PD20 values (r= -0.47) was found in the rhinitis group, but not in asthmatics. No correlation between blood eosinophilic inflammation and lung functional indices was found. CONCLUSIONS: Induced sputum is an accurate method to study bronchial inflammation, allowing one to distinguish between rhinitis patients and mildly asthmatic patients. The fact that no relationship was detected between sputum inflammation and BHR suggests that other factors, such as airway remodeling, may be at least partly responsible for BHR in asthma.     

Soluble endothelium-associated adhesion molecules in patients with Graves' disease.

The targeting and recruitment of inflammatory cells to vascular endothelium in Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1), soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n = 21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels of sICAM-1 were markedly elevated in patients with GD before treatment with thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition, elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml, respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and sVCAM-1 dropped significantly after initiation of therapy and were within the normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM-1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM-1 correlated with the serum concentrations of anti-thyroid-stimulating hormone (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810, respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673 and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab, TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found. In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM-1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease activity.     

Effect of glucocorticosteroids on tumour necrosis factor-α-induced intercellular adhesion molecule-1 expression in cultured primary human nasal epithelial cells

OBJECTIVE: In order to confirm the direct effect of glucocorticosteroids on epithelial intercellular adhesion molecule-1 (ICAM-1) expression, we examined ICAM-1 expression on primary cultured human nasal epithelial cells (HNECs) at both protein and mRNA levels. MATERIAL AND METHODS: HNECs were stimulated with recombinant human TNF-alpha (20 pg/mL-20 ng/mL) for specified time periods (0, 12, 24, and 48 h) and ICAM-1 mRNA and the soluble ICAM-1 (sICAM-1) concentrations were measured by quantitative RT-PCR and ELISA, respectively. We also evaluated surface expression of ICAM-1 by flow cytometry 48 h after stimulation and determined the effect of dexamethasone (DEX) on TNF-alpha-induced ICAM-1 expression. RESULTS: Significant increases in ICAM-1 gene expression in HNECs were initially detected at 24 h, peaking at 48 h after the stimulation. The TNF-mediated-ICAM-1 mRNA and ICAM-1 surface expression at 48 h was significantly inhibited by co-incubation with human recombinant soluble TNF receptor I. Similarly, TNF-alpha-induced release sICAM-1 occurred in a time- and concentration-dependent manner. DEX 10(-6) M attenuated the TNF-alpha-induced ICAM-1 expression at mRNA and protein levels. CONCLUSIONS: Our finding suggests a potential role for topical steroids in allergic rhinitis in suppressing inflammatory reactions in the nasal mucosa by regulating ICAM-1 expression on nasal epithelium.     

Relationship between nasal and bronchial responsiveness in perennial allergic rhinitic patients with asthma

BACKGROUND: The nasal and bronchial mucosa present similarities and most patients with asthma also have rhinitis, suggesting the concept of 'one airway one disease'. Although many studies may suggest the relationship between nasal and bronchial responsiveness in patients with allergic rhinitis and asthma, few studies have been published which address this question directly. The aim of this study is to investigate whether the relationship between nonspecific nasal and bronchial responsiveness exists in perennial allergic rhinitic patients with asthma. METHODS: Fifty-one perennial allergic rhinitic patients with the definitive or suspected asthma underwent methacholine bronchial provocation tests and nasal histamine challenge tests. A slope of the absolute changes in nasal symptoms score/log concentrations of histamine was calculated by linear regression analysis. A ratio of the final absolute change in nasal symptoms score to the sum of all the doses of histamine given to the subject was also calculated. The degree of bronchial responsiveness to methacholine was categorized as positive bronchial hyperresponsiveness (BHR) if PC(20) (provocative concentration of methacholine resulting in 20% fall in FEV(1)) was <4 mg/ml, borderline BHR if PC(20) was >or=4 but 16 mg/ml. Another index of bronchial responsiveness (BRindex) was calculated as the log [(% decline in FEV(1)/log final methacholine concentration as mg/dl) + 10]. RESULTS: The geometric means of the slope (4.47 vs. 2.95, p < 0.05) and the ratio (1.68 vs. 0.54, p < 0.01) were higher in patients with positive BHR (n = 23) than in patients with negative BHR (n = 19), respectively. The geometric means of the slope (3.50) and the ratio (1.13) in patients with borderline BHR (n = 9) were between the two groups, respectively. In all patients, the log-slope (r = 0.48, p < 0.001) and the log-ratio (r = 0.51, p < 0.001) were correlated well with the BRindex, respectively. Even in allergic rhinitic patients with definitive asthma, the log-slope was correlated with the BRindex (r = 0.39, p < 0.05) or log-PC(20) (r = -0.36, p < 0.05). CONCLUSIONS: The nonspecific nasal responsiveness may be related to the nonspecific bronchial responsiveness in patients with allergic rhinitis and asthma, which may support the viewpoint that allergic rhinitis and asthma represent a continuum of inflammation involving one common airway.     

The role of patient training in the management of seasonal rhinitis and asthma: clinical implications

BACKGROUND: Allergic rhinitis is an inflammatory disease often associated with bronchial asthma. Intranasal corticosteroids and oral antihistamines are the first-choice drugs. Patient training is relevant to asthma management, but little is known about its impact on rhinitis. We evaluated the role of patient training in the treatment of allergic rhinitis and its effects on nasal and bronchial symptoms. METHODS: One hundred and one patients (M/F = 62/39, age range 12-62 years) with pollen-induced rhinitis (32 with concomitant mild asthma) were enrolled. They were randomized into three groups: A (n = 30) with drug therapy alone, B (n = 35) with drug therapy plus training on the use of nasal spray, and C (n = 36) the same as B plus a lesson on rhinitis and asthma. All patients received mometasone furoate nasal spray for 8 weeks as regular therapy, plus rescue medications on demand. Symptoms and drug consumption were evaluated during the pollen season. RESULTS: The rate of noncompliance/dropout was highest in the untrained patients (P = 0.001). No difference in nasal symptoms was seen among the three groups. On the other hand, group C had significantly fewer asthma symptoms (P = 0.02) and less albuterol use (P = 0.005) than group A. Moreover, the trained group globally used less rescue medication than the other groups (P = 0.02). CONCLUSIONS: Detailed training of patients seems to improve compliance with treatment, reduce concomitant asthma symptoms, and reduce the use of symptomatic drugs.     

Expression of ICAM-1 on conjunctival epithelium and ECP in tears and serum from children with allergic conjunctivitis.

BACKGROUND: Conjunctival eosinophilia may be considered to be an indicator of conjunctival allergic disease. The absence of eosinophils on conjunctival scraping, however, cannot rule out the diagnosis of allergic conjunctivitis because eosinophil infiltration may be deeper in conjunctival tissue. Eosinophil cationic protein (ECP) is a toxic product secreted by activated eosinophil as a marker of eosinophil activation. Eosinophil cationic protein concentrations in body fluids correlate with the severity of some allergic diseases. ICAM-1 promotes adhesion of leukocytes to epithelium, endothelium, and upregulates inflammation. Expression of adhesion can be modified by many extracellular and intracellular variables such as proinflammatory cytokines, extracellular matrix proteins, and viral infection. OBJECTIVE: We investigated whether local eosinophils are only activated in conjunctival epithelium or circulating activated eosinophils are involved in peripheral blood during allergic reaction of the eye. We also demonstrated the possible expression of ICAM-1 on epithelial cells from conjunctival scraping and compared them with soluble ICAM-1 values of serum and tears in children with allergic conjunctivitis and healthy children. METHODS: Seventeen subjects were selected on the basis of clinical manifestations, history, skin prick test, and total serum IgE. A microcapillary tube was used to collect the tears from the inner canthus. Conjunctival epithelia were obtained by scraping the upper tarsal conjunctiva. The level of ECP was measured by the CAP system, soluble ICAM-1 was measured by ELISA, and ICAM-1 on conjunctival epithelial cells were expressed by the avidine-biotin peroxide complex procedure. RESULTS: Serum IgE and the eosinophil count were increased in 10 out of 17 patients, positive skin prick tests were positive in 11 patients (Dermatophagoides pternyssinus; 9, Dermatophagoides farinae: 8), and eosinophilia in conjunctival epithelium was in 11 patients (4 patients: >3/HPF, 7 patients: 1-3/HPF). The ECP levels in tears were significantly increased in the patient group (12.0+/-8.0 versus 3.9+/-3.8 microg/mL, P = .01), but not in serum (52.5+/-43.1 versus 28.3+/-25.9 microg/mL). There is significant correlation between the eosinophil count in peripheral blood and on conjunctival epithelium (P = .007, r = .62; n = 25). The ICAM-1 expression score on conjunctival epithelial cells was significantly different between the patient group and controls (patient group: 1.77+/-1.25 versus control: 0.13+/-0.35 ng/mL, P = .002). There was a significant correlation between ICAM-1 expression on conjunctival epithelial cells and the ECP levels of tears (P = .01, r = .58; n = 25). Soluble ICAM-1 levels in serum and tears showed no significant difference between the patient group and controls, and also, there was no correlation between sICAM-1 levels in the serum and tears. CONCLUSION: Eosinophil cationic protein in tears and ICAM-1 expression scores on conjunctival epithelium showed a significant difference between children with allergic conjunctivitis and the healthy controls, but circulating ECP and sICAM-1 in serum were not significantly different between the two groups. These results may suggest that ICAM-1 is locally upregulated in inflammation, mediating eosinophil activation and migration to conjunctival epithelium, but is not involved as inflammatory mediators in peripheral blood during allergic response in children with allergic conjunctivitis.     

Airway function and nasal inflammation in seasonal allergic rhinitis and asthma

BACKGROUND: Allergic rhinitis (AR) and asthma are frequently associated and characterized by a Th2-dependent inflammation. Nasal and bronchial obstruction may be objectively measured. OBJECTIVE: The aim of this study was to evaluate the relationships among upper and lower airway function and nasal inflammation in subjects with seasonal allergic rhinitis (SAR) and asthma. METHODS: Twenty out-patients (12 males and eight females, mean age: 23.4+3.6 years) with SAR and asthma were evaluated during the pollen season. All of them showed a moderate-severe grade of nasal obstruction. Total symptom score, rhinomanometry, spirometry, nasal lavage, and nasal scraping were obtained in all subjects. Eosinophils were counted by conventional staining; IL-4 and IFN-gamma were measured by immunoassay on fluids recovered from nasal lavage. RESULTS: Functional parameters, i.e. nasal airflow and forced expiratory volume in 1 s (FEV(1)), were correlated with nasal eosinophils (R(2)>0.83, P<0.001). Inflammatory parameters, i.e. eosinophils were correlated with immunological parameters, i.e. IL-4 and IFN-gamma levels (R(2)=0.93, P<0.001). Nasal symptoms were correlated with nasal airflow (rho=-0.71, P< or =0.01) and eosinophils (rho=0.72, P<0.01). Nasal airflow was correlated with FEV(1) (r=0.89, P<0.0001). CONCLUSIONS: This study demonstrates the close connection between Th2 cytokines and eosinophil infiltration in the nose. There is also clear evidence concerning the relationships between eosinophils infiltration and cytokines levels. Nasal eosinophils can be regarded as the most important predictors of upper and lower airway functions. These findings constitute first evidence of a relationship among nasal Th2-related inflammation and nasal and bronchial airflow in patients with SAR and asthma.     

Comparison of deltaFVC between patients with allergic rhinitis with airway hypersensitivity and patients with mild asthma.

BACKGROUND: In asthmatic individuals, airway sensitivity and maximal airway response are increased. Airway sensitivity is usually evaluated by measuring the provocation concentration of inhaled methacholine or histamine that causes a decrease in forced expiratory volume in 1 second of 20% (PC20). The percentage decrease in forced vital capacity at the PC20 (deltaFVC) has been proposed as a surrogate marker for maximal airway response. Individuals with allergic rhinitis and no clinical evidence of asthma frequently exhibit airway hypersensitivity. OBJECTIVE: To compare the deltaFVC between patients with allergic rhinitis and mild asthmatic patients with a similar degree of airway hypersensitivity. METHODS: A retrospective analysis of methacholine challenge test data from 72 children with allergic rhinitis and airway hypersensitivity (methacholine PC20 < 16 mg/mL) (rhinitis group) and from 72 children with mild atopic asthma matched to the rhinitis group regarding the methacholine PC20 (asthma group). The deltaFVC was calculated on the concentration-response curve to methacholine. RESULTS: The mean +/- SD deltaFVC was significantly lower in the rhinitis group (15.0% +/- 3.6%) vs the asthma group (17.4% +/- 5.3%) (P = .002). There was no significant correlation between the deltaFVC and PC20 in the rhinitis (r = -0.101; P = .41) and asthma (r = -0.023; P = .85) groups when 2 patients with PC20 less than 1 mg/mL were excluded from each group. CONCLUSIONS: Patients with allergic rhinitis and airway hypersensitivity had a significantly lower deltaFVC than methacholine PC20-matched mild asthmatic patients, suggesting that the level of maximal airway response in patients with allergic rhinitis is lower than that in mild asthmatic patients with a similar degree of airway hypersensitivity.     

Desloratadine reduces systemic allergic inflammation following nasal provocation in allergic rhinitis and asthma patients

BACKGROUND: Preclinical studies have demonstrated that some second-generation antihistamines have anti-inflammatory effects. It is not known whether these effects are also demonstrable in vivo. In this study we investigated the effect of treatment with desloratadine (DL) on systemic inflammation and on nasal and bronchial mucosal inflammation after nasal allergen provocation (NP) in subjects with grass-pollen-allergic rhinitis and asthma. METHODS: Twenty-six subjects with grass-pollen-allergic rhinitis and asthma were randomly allocated to 8 days of treatment with DL (n = 13) or placebo (n = 13) outside the grass pollen season. On day 7 they underwent nasal provocation with grass pollen allergen. Nasal and bronchial biopsies were taken for immunohistochemical evaluation, and blood samples were analysed. Rhinitis and asthma symptoms, peak nasal inspiratory flow and peak expiratory flow, were also measured at specified times. RESULTS: The number of circulating eosinophils decreased during DL treatment, and there was a reduced increase in circulating eosinophils after NP in these subjects. There was also a significant reduction in early bronchial clinical response. There was no significant lessening in the severity of the nasal symptoms. Nasal and bronchial mucosal inflammation parameters did not alter under DL treatment. CONCLUSION: These data suggest that treatment with DL reduces systemic eosinophilia and prevents the increase in circulating eosinophils after NP. DL also significantly reduces the early bronchial clinical response to NP. However, airway mucosal inflammation is not altered by 1 week of treatment.     

Relationship between cytokine concentrations (FGF, sICAM-1 and SCF) in serum, follicular fluid and ICSI outcome

OBJECTIVE: The aim of this study was (i) to investigate the existence of fibroblast growth factor (FGF), soluble intracellular adhesion molecule-1 (sICAM-1), and stem cell factor (SCF) in serum and human follicular fluid (FF) of intracytoplasmic sperm injection (ICSI) patients, and (ii) to determine the relationship between these parameters and ICSI outcome. MATERIAL AND METHOD: Seventy-five patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropin (hMG) after down-regulation with GnRHa were included in this study. The concentrations of FGF, SCF, and sICAM-1 were measured by using commercially available enzyme-linked immunosorbent assay test kits. RESULTS: The FGF, sICAM-1, and SCF concentrations in the serum of women who become pregnant (group I) were 8.5 +/- 1.5 pg/mL, 235.8 +/- 81.1 ng/mL, and 597.7 +/- 139.9 pg/mL, and the corresponding concentrations of women who did not (group II) were 6.4 +/- 3.6 pg/mL, 230.6 +/- 66.5 ng/mL, and 569.6 +/- 91.4 pg/mL respectively. No significant difference was observed between the two investigated groups with regard to the number of hMG ampoules administered for controlled ovarian hyperstimulation, estradiol concentration on the day of human chorionic gonadotropin (hCG) injection, number of retrieved oocytes and fertilization rate. CONCLUSION: The concentration of FGF, sICAM-1, and SCF did not differ significantly between the two groups in serum or in FF. Besides, the ICSI outcome was not related to their concentrations in serum or FF. Therefore, these parameters could not be used as a prognostic factor in ICSI program.     

Different serum soluble Fas levels in patients with allergic rhinitis and bronchial asthma

BACKGROUND: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy-inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis-regulating molecules. METHODS: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase. CONCLUSIONS: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis-linked step.     

Blood serum levels of vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) in diabetic retinopathy

BACKGROUND: Interaction between cells via intimate cell-cell contact is facilitated by a cell surface molecules, termed adhesion molecules. The aim of the study was to evaluate the blood serum concentration of soluble forms of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) in patients with type 1 diabetes mellitus without and with diabetic retinopathy. MATERIALS AND METHODS: The study was performed in 75 patients with type 1 diabetes mellitus, 35 without retinopathy (group 1) and 40 with retinopathy (group 2). Soluble forms of VCAM-1, ICAM-1 and ELAM-1 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum concentration of sICAM-1 and sELAM-1 were significantly elevated and the concentration sVCAM-1 was elevated but not significantly in diabetic patients when compared with control subjects. There was a significant difference in VCAM-1 concentrations between the control group and group 2 (965.9 +/- 229.0 vs. 1283.7 +/- 387.6 ng/ml, p < 0.05) and between group 1 and group 2 (1115.0 +/- 285.5 vs. 1283.7 +/- 387.6 ng/ml, p < 0.05). There were significant differences in sICAM-1 concentrations between the control group and group 1 (p < 0.05) and between the control group and group 2 (p < 0.05). Where was no significant difference in sICAM-1 concentration between group 1 and 2 (405.2 +/- 135.9 vs. 443.1 +/- 112.7 ng/ml, p = 0.08). ELAM-1 concentration was significantly elevated in group 2 (120.5 +/- 49.3 ng/ml) when compared with the control group (51.7 +/- 18.1 ng/ml, p < 0.005) and with group 1 (81.2 +/- 27.7 ng/ml, p < 0.05). CONCLUSIONS: The correlations found between sVCAM-1, sICAM-1 and sELAM-1 and the presence of retinopathy suggest that cellular adhesion and neovascularization may be linked processes.     

Elevation of plasma transforming growth factor beta1 levels in stable nonatopic asthma.

BACKGROUND: Increased transforming growth factor beta1 (TGF-beta1) levels have been reported in bronchoalveolar lavage fluid and bronchial biopsy specimens from asthmatic patients. However, systemic TGF-beta1 levels have not been reported in asthma. OBJECTIVE: To evaluate the levels of plasma TGF-beta1 in asthmatic patients and matched, healthy controls to determine the associations with atopic status, disease severity, and duration. METHODS: Asthmatic patients and healthy controls were recruited prospectively from a university hospital outpatient department between January 2001 and May 2002. Plasma TGF-beta1 and serum IgE levels were estimated using established methods. Patients were classified as atopic or nonatopic based on the presence or absence of serum specific IgE directed to common allergens. RESULTS: Of the 56 patients recruited for the study, 32 were atopic and 24 nonatopic. The median value of plasma TGF-beta1 was significantly higher in nonatopic asthmatic patients (2.5 ng/mL) compared with controls (1.5 ng/mL, P = .002) and atopic asthmatic patients (1.4 ng/mL, P = .008). The median absolute neutrophil count in the nonatopic asthmatic patients (4.0 x 10(9)/L) was significantly higher compared with atopic asthmatic patients (3.0 x 10(9)/L) and healthy controls (3.5 x 10(9)/L) (P = .01 and P = .04). There was no significant correlation between the duration or severity of asthma and plasma TGF-beta1 levels. The distribution of moderate-persistent asthma cases was similar in atopic and nonatopic groups. CONCLUSION: Compared with atopic asthmatic patients and healthy controls, patients with nonatopic asthma have elevated plasma TGF-beta1 levels and leukocytosis. These data suggest that nonatopic asthmatic patients exhibit an altered inflammatory response, perhaps to a respiratory infection.     

Adhesion molecules (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) in sera from patients with Staphylococcus aureus bacteraemia with or without endocarditis

The aim of this prospective study was to evaluate if patients with endocarditis display a more extensive endothelial activation than those with bacteraemia but without endocarditis. Sixty-five patients with blood culture-verified Staphylococcus aureus bacteraemia were included and serum samples collected on admission were analysed by enzyme immunoassays. Elevated serum concentrations of adhesion molecules were found in most of the patients with S. aureus bacteraemia. Patients with endocarditis (n = 15) showed significantly higher serum E-selectin (median 156 ng/ml) and VCAM-1 (median 1745 ng/ml) concentrations compared with those with S. aureus bacteraemia but without endocarditis (80 ng/ml and 1172 ng/ml, respectively; P = 0.01 and P = 0.003). No significant difference was found between the groups concerning ICAM-1 (median 451 ng/ml versus 522 ng/ml). In addition, serum tumour necrosis factor-alpha (TNF-alpha) concentrations were significantly correlated (P < 0.002) to serum levels of E-selectin, ICAM-1 and VCAM-1.