Malgorzata Gorska-Ciebiada

Montelukast with desloratadine or levocetirizine for the treatment of persistent allergic rhinitis

BACKGROUND Montelukast sodium is approved as a treatment for intermittent and persistent allergic rhinitis (AR), but it has not been evaluated as combined therapy with antihistamines for persistent AR. OBJECTIVE To investigate the effects of 6 weeks of treatment of persistent AR with desloratadine, levocetirizine, or montelukast alone or in combination. METHODS A randomized, double-blind, placebo-controlled crossover study was performed. Patients were assigned to 2 arms: 20 received montelukast, 10 mg/d, desloratadine, 5 mg/d, or both or placebo and 20 received montelukast, levocetirizine, or both, 5 mg/d, or placebo. The treatment periods were separated by 2-week washout periods. Symptom scoring, skin prick tests, spirometry, rhinometry, and nasal lavage were performed the day before and the last days of the treatment periods. Eosinophil cationic protein levels were evaluated by means of nasal lavage. RESULTS The mean +/- SD total baseline nasal symptom score was 7.7 +/- 0.49 before treatment, 3.74 +/- 0.54 after desloratadine use, 3.6 +/- 0.48 after montelukast use, and 3.04 +/- 0.4 after montelukast-desloratadine use. The mean +/- SD baseline nasal symptom score was 7.95 +/- 0.68 before treatment, 3.02 +/- 0.64 after levocetirizine use, 3.44 +/- 0.55 after montelukast use, and 2.14 +/- 0.39 after montelukast-levocetirizine use. The greatest improvement in nasal symptoms occurred after combination treatment. Decreases in the level of eosinophil cationic protein were greater after the combined use of montelukast and antihistamine than after each agent given alone. CONCLUSIONS For persistent AR, the combination of montelukast and either desloratadine or levocetirizine is more effective than monotherapy with these agents.

Intercellular adhesion molecule 1 and tumor necrosis factor α in asthma and persistent allergic rhinitis: relationship with disease severity

BACKGROUND Tumor necrosis factor alpha (TNF-alpha) is involved in the up-regulation of intercellular adhesion molecule 1 (ICAM-1). Allergic rhinitis is often associated with bronchial hyperresponsiveness. OBJECTIVE We investigated the relationship between allergic airway disease severity and serum concentrations of soluble ICAM-1 (sICAM-1) and TNF-alpha and nasal expression of ICAM-1. METHODS Serum concentrations of TNF-alpha and sICAM-1 were investigated in 85 adults with persistent rhinitis and 90 patients with asthma. Seventy patients with rhinitis were challenged with methacholine. Nasal biopsy for ICAM-1 expression was performed in 6 patients with moderate-severe rhinitis and in 6 patients with mild rhinitis. RESULTS In patients with rhinitis, serum sICAM-1 concentrations were as follows: group without bronchial hyperresponsiveness (n = 29), 206.85 ng/mL; group with bronchial hyperresponsiveness but without asthma symptoms (n = 20), 233.39 ng/mL; and group with newly recognized asthma (n = 21), 260.06 ng/mL. The sICAM-1 level was significantly lower in patients with mild rhinitis (216.21 ng/mL) than in patients with moderate-severe rhinitis (244.08 ng/mL). Nasal ICAM-1 expression was significantly higher in the moderate-severe rhinitis group than in the mild rhinitis group. In patients with asthma, serum concentrations of sICAM-1 were as follows: patients with mild asthma, 272.8 ng/mL; patients with moderate asthma, 340.16 ng/mL; patients with severe asthma without oral corticosteroids therapy, 426.74 ng/mL; and patients with severe asthma with oral corticosteroids therapy, 314 ng/mL. The serum TNF-alphaa concentration differed between patients with rhinitis (n = 15) (1.065 pg/mL) and patients with asthma (n = 12) (3.46 pg/mL). Among patients with asthma, TNF-alpha concentrations were similar in all groups classified according to the disease severity. CONCLUSIONS sICAM and ICAM-1 expression correlates with airways diseases severity.

Mild cognitive impairment and depressive symptoms in elderly patients with diabetes: prevalence, risk factors, and comorbidity.

The aim of the study was to estimate the prevalence of mild cognitive impairment (MCI), depressive syndrome cases, and its comorbidity, and to identify predictors of these conditions. Methods. 276 diabetics elders were screened for MCI and depressive symptoms. Detailed information of history of diabetes, and data of BMI, HbA1c, and blood lipids were collected. Results. The prevalence of MCI was 31.5%, depressive syndrome was 29.7%, and MCI with coexisting depressive mood was 9.1%. The logistic regression analysis revealed that variables which increased the likelihood of having been diagnosed with MCI were: higher HbA1c level, previous CVD, hypertension, retinopathy, increased number of comorbidities, and less years of formal education. Significant predictors of having a depressive mood included female gender, single marital status, current and past smoking status, lack of physical activity, higher BMI and total cholesterol level, increased number of comorbidities, history of hypoglycemia, and insulin treatment. Factors associated with both MCI and depressive syndrome were female gender, single marital status, past smoking status, retinopathy, previous CVD or stroke, increased number of comorbidities, and insulin treatment. Conclusions. Depressive symptoms, MCI, and its comorbidity are common in elderly subjects with type 2 diabetes. Systematic screening could result in the identification of high-risk patients.

Serum Levels of Inflammatory Markers in Depressed Elderly Patients with Diabetes and Mild Cognitive Impairment

Objective The aim of the study was to determine the serum levels of CRP, IL-6 and TNF-α in elderly diabetic patients with depressive syndrome alone or with coexisting mild cognitive impairment (MCI). Methods 276 diabetics elders were screened for depressive symptoms (using Geriatric Depression Scale: GDS-30) and MCI (using the Montreal Cognitive Assessment: MoCA score). Data of HbA1c, blood lipids and inflammatory markers levels were collected. Results In all groups of patients levels of CRP, IL-6 and TNF-α were significantly higher as compared to controls. The highest level of inflammatory markers was detected in group with depressive mood and coexisting MCI, however IL-6 level didn’t significantly differ as compared to MCI group. We founded correlations between all inflammatory markers in group of patients with depressive mood and in group of subjects with depressive symptoms and coexisting MCI. GDS-30 score was correlated with levels of inflammatory markers in group with depressive mood, and with levels of CRP and TNF-α in group with depressive mood and coexisting MCI. In the group with depressive mood and coexisting MCI we founded that MoCA score was negatively correlated with CRP and TNF-α levels; and HbA1c level was positively correlated with all inflammatory markers. The univariate logistic regression models revealed that variables which increased the likelihood of having been diagnosed with MCI in depressed patients were: higher levels of HbA1c, CRP, IL-6 and TNF-α, previous CVD or stroke, increased number of co-morbidities and microvascular complications, older age, less years of formal education. The multivariable model showed that previous CVD, higher HbA1c and IL-6 levels are significant factors. Conclusions We demonstrated that the presence of depressive syndrome is associated with higher levels of inflammatory markers in elderly patients with diabetes. The presence of MCI in these depressed subjects has additive effect on levels of inflammatory mediators.

Use of Montelukast Alone or in Combination with Desloratadine or Levocetirizine in Patients with Persistent Allergic Rhinitis

Background We assessed the course of treatment in patients with persistent allergic rhinitis (AR) treated with montelukast, levocetirizine, or desloratadine alone or combinations of antihistamine and montelukast. Methods A 32-week randomized, double-blind, placebo-controlled, crossover, double-armed study in 40 adult patients with history of persistent AR, clinical allergy to house-dust mites, and a total nasal symptom score of at least 5 (congestion of at least 2) has been performed. Patients with asthma, chronic obstructive pulmonary disease, nonallergic rhinitis with clinical allergy associated with seasonal allergens, and other serious diseases were excluded. There were four 6-week treatment periods separated by 2-week washout periods. Twenty patients received either montelukast or antihistamine, a combination of montelukast and antihistamine, or placebo. The sequence of treatment was randomly assigned. Nasal symptoms were assessed using a 4-point scale at baseline, daily during the 1st week and on days 14, 21, 28, 35, and 42 of treatment. Results Montelukast alone, levocetirizine alone, desloratadine alone, and the montelukast/antihistamine combinations significantly improved nasal symptoms during the first 24 hours. Improvement gradually increased during the 6 weeks of treatment, especially in patients receiving montelukast alone or in combination therapy with the antihistamine in both arms. Improvement at 42 days of treatment was significantly greater than that achieved on the 1st day of therapy in patients treated with the combination of montelukast and levocetirizine. Conclusion Montelukast alone or in combination with antihistamines gave a gradual increase in nasal symptom improvement within 6 weeks of treatment in patients with persistent AR.

C-Reactive Protein, Advanced Glycation End Products, and Their Receptor in Type 2 Diabetic, Elderly Patients with Mild Cognitive Impairment

Objective The aim of the study was to evaluate serum levels of advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE), and C-reactive protein (CRP) in elderly patients with type 2 diabetes mellitus with and without mild cognitive impairment (MCI) and to determine the predictors (including AGEs, RAGE, and CRP levels) of having MCI in elderly patients with type 2 diabetes. Methods Two hundred seventy-six diabetics elders were screened for MCI (using the Montreal Cognitive Assessment: MoCA score). Data of biochemical parameters and biomarkers were collected. Results Serum AGEs, RAGE, and CRP levels were significantly increased in MCI patients compared to controls. In group of patients with MCI, serum RAGE level was positively correlated with AGEs level and with CRP level. RAGE, AGEs, and CRP concentrations were positively correlated with HbA1c levels and negatively correlated with MoCA score. The univariate logistic regression models revealed that variables, which increased the likelihood of diagnosis of MCI in elderly patients with type 2 diabetes were higher levels of HbA1c, RAGE, AGEs, CRP, TG, lower level of HDL cholesterol, previous CVD, HA, or use of HA drugs, hyperlipidemia, retinopathy, nephropathy, increased number of co-morbidities, older age, and less years of formal education. HA or use of HA drugs, previous CVD, higher level of RAGE and CRP, older age and less years of formal education are the factors increasing the likelihood of having MCI in elderly patients with type 2 diabetes in multivariable model. Conclusion In summary, serum AGEs, RAGE, and CRP are increased in the circulation of MCI elderly diabetic patients compared to controls. A larger population-based prospective study needs to be performed to further confirm the relationship between AGEs, RAGE, and the cognitive decline or progress to dementia.

sICAM-1 and TNF-α in Asthma and Rhinitis: Relationship with the Presence of Atopy

Background. A genetically determined overproduction of specific immunoglobulin E (IgE) underlies many diseases like asthma or allergic rhinitis. IgE as well as tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) play a critical role in the induction and maintenance of inflammation. While the correlation between IgE and atopy is inseparable, little is known about the correlation of atopy with markers of inflammation. Objective. We investigated the relationship between the serum concentrations of TNF-α, soluble ICAM-1 (sICAM-1), and the presence of atopy in patients with persistent rhinitis or asthma. Methods. Serum concentrations of sICAM-1, TNF-α, and total IgE were investigated in 64 adults with persistent allergic rhinitis, 17 subjects with nonatopic rhinitis, 90 patients with asthma, and 21 healthy individuals. Atopy was diagnosed on the basis of positive family history, skin prick tests, and serum IgE concentration. Results. Total IgE concentration was significantly higher in patients with atopic rhinitis or asthma when compared with nonatopic patients and healthy individuals and was the highest in patients suffering from severe atopic asthma who were not treated with systemic glucocorticosteroids. Although there were marked alterations in IgE in atopic and nonatopic patients, there were no significant differences between atopic and corresponding groups of nonatopic rhinitic and asthmatic patients in sICAM-1 and TNF-α concentrations. (sICAM-1 in rhinitis: atopic vs. nonatopic patients: 224.02 and 221.08 ng/ml, respectively, p > .05; in mild/moderate asthma: atopic vs. nonatopic: 306.22 and 326.39 ng/ml, respectively, p > .05; severe asthma without oral corticosteroids therapy: atopic vs. nonatopic: 418.03 and 468.09 ng/ml, respectively, p > .05; and severe asthma with oral corticosteroids therapy: atopic vs. nonatopic: 320.66 and 308.09 ng/ml, respectively, p > .05). Conclusions. Concentrations of sICAM-1 and TNF-α are significantly higher in patients with asthma compared with those observed in patients with rhinitis, but they are independent of the presence of atopy.

Adiponectin, leptin and IL-1 β in elderly diabetic patients with mild cognitive impairment

The aim of the study was to determine the serum levels of adiponectin, leptin and IL-1 β in elderly diabetic patients with and without mild cognitive impairment (MCI) and to examine the associations of these markers with clinical and cognitive parameters. A biochemical evaluation was performed of 62 seniors with type 2 diabetes (T2DM) and MCI, and 132 seniors with T2DM but without MCI (controls). Serum leptin and IL-1 β levels were higher and adiponectin concentration was lower in MCI patients than controls. In MCI subjects, adiponectin level was negatively correlated with leptin, IL-1 β levels and BMI. Leptin concentration was correlated with IL-1 β level. Univariate logistic regression models revealed that the factors which increased the likelihood of diagnosis of MCI in elderly patients with T2DM were higher levels of HbA1c, leptin, IL-1 β and triglycerides, as well as lower levels of adiponectin and HDL cholesterol. Similarly, previous CVD, hypertension, hyperlipidemia, retinopathy, nephropathy, hypoglycemia, longer duration of diabetes, increased number of co-morbidities, older age, fewer years of formal education were found to be associated with MCI. The multivariable model indicated fewer years of formal education, previous CVD, hypertension, increased number of co-morbidities, higher HbA1c and IL-1 β levels and lower adiponectin level. Elderly diabetic patients with MCI have higher levels of leptin and IL-1 β and lower levels of adiponectin. Further prospective studies are needed to determine the role of these markers in the progression to dementia.

Expression of IL-7 receptor in human peripheral regulatory T cells.

Introduction Regulatory T cells (Tregs, CD4 + CD25high Foxp3+) play a crucial role in allergy and other inflammatory diseases. However, the isolation of viable Tregs on the basis of intracellular expression of specific Forkhead Box Protein P3 (Foxp3) is difficult. In this study we checked if the expression of IL-7 receptor (CD127) on the Tregs could be a useful marker for isolation of viable Treg Foxp3+ cells. Material and methods Twenty-five patients sensitized to grass pollen with allergic rhinitis (AR) and ten healthy subjects were included. We compared Foxp3 expression in different CD4+ T cell subsets by flow cytometry and we assessed the relationship between the expression of Foxp3 and CD127 within regulatory T cells. Results Within the CD4+ lymphocytes 3.68 ±2.0% showed expression of Foxp3, 51.82 ±8.03% of CD4+CD25high were Foxp3 positive (Foxp3+), whereas 82.12 ±5.4% of CD4+CD25highCD127low were Foxp3+. High intracellular expression of Foxp3 correlated with low superficial CD127 expression (r = 0.42, p = 0.017). There were no significant differences regarding the analysed markers between AR patients and healthy controls. Conclusions Regulatory T cells may be purified from the fresh peripheral blood as viable regulatory Foxp3 bright cells using CD4, high expression of CD25 and low expression of CD127 antigen.

Orally exhaled nitric oxide in patients with seasonal allergic rhinitis during natural pollen season.

Background Nitric oxide (NO) is the endogenous molecule involved in regulatory, protective, and defensive mechanisms. Although exhaled NO (ENO) has been used to monitor patients with asthma, possible usage of ENO in allergic rhinitis (AR) still needs to be evaluated. The authors wanted to determine the levels of NO exhaled orally both out of the pollen season and during the natural pollen exposure in patients with AR without asthma. Methods Forty-six patients without asthma, with seasonal AR (SAR) and 15 healthy, nonreactive, nonatopic subjects as a control group were investigated. ENO, congestion score, and peak nasal inspiratory flows (PNIFs) were measured in all subjects 6 weeks before the pollen season, at the height of the pollen season, and 6 weeks after the end of the pollen season. Results Patients with SAR had significantly higher basal ENO values compared with healthy control. The number of parts of NO increased in both groups during the pollen season but only in AR patients was the increase significant compared with the levels before the pollen season. Those with SAR and high levels of NO in exhaled air at the height of the pollen season had significantly lower PNIF rates and higher obstruction scores than out of the pollen season and in the healthy group. Conclusion Natural exposure may lead to an elevation of ENO in the patients with SAR without asthma. We estimate that the increased ENO may result from subclinical allergic inflammation present within the lower airways of nonasthmatic patients with SAR.