Browsing by Author "Degirmenci, PB"

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    Analysis of the association of chronic spontaneous urticaria with interlekin-4,-10, transforming growth factor-β1, interferon-γ, interleukin-17A and-23 by autologous serum skin test
    Degirmenci, PB; Kirmaz, C; Vatansever, S; Onur, E; Nal, E; Erdin, S; Ozyurt, B
    Aim: To contribute to the understanding of the pathogenesis of chronic spontaneous urticaria (CSU) by identifying its relationship with autoimmunity and cytokines using the autologous serum skin test (ASST) and peripheral blood mononuclear cell culture (PBMC) method. Material and methods: Interleukins (IL)-4, IL-10, transforming growth factor (TGF-(31), interferon (IFN)-gamma, IL-17A, and IL-23 levels in cell supernatants obtained by the PBMC method were measured using ELISA. Disease activity was assessed by determining the urticaria activity score (UAS). Results: A total of 40 patients diagnosed with CSU participated in this study. Twenty patients had positive ASST results, and 20 had negative results. The control group included 20 healthy volunteers. We found that the IL-23 (p = 0.01), IL-10 (p = 0.04) and IL-4 (p = 0.04) levels of the patient groups were significantly lower compared with those of the control group. The IL-23 (p = 0.009), IL-10 (p = 0.009), IL-4 (p = 0.001), and IL-17 (p = 0.05) levels of the ASST(-) patient group were significantly lower compared with those of the control group. In addition, the IL-4 (p = 0.03) and IFN-gamma (p = 0.05) levels of the ASST(+) patient group were significantly lower compared with those of the control group, and the ASST(+) patients had a significantly higher UAS than the ASST(-) patients (p = 0.021). Conclusions: These results, when considered together with current reports in the literature, indicate that immune dysregulation occurs in the pathogenesis of CSU, causing cytokine imbalance.
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    Down-regulation of the auto-aggressive processes in patients with hypothyroid Hashimoto's thyroiditis following substitutive treatment with L-thyroxine
    Guclu, F; Ozmen, B; Kirmaz, C; Kafesciler, SO; Degirmenci, PB; Taneli, F; Hekimsoy, Z
    Background. Hashimoto's thyroiditis is a chronic, organ-specific autoimmune disease. It is the most common cause of primary hypothyroidism during the adolescent period, via autoimmune thyroid tissue destruction, affecting 2% of the population. The pathogenesis of Hashimoto's thyroiditis involves a complex interaction between predisposing genetic and environmental factors. Objective. In this study, we wanted to investigate the role of cytokines such as IL-2, IL-4, IL-12 and IFN-gamma in the pathogenesis of the disease, and the changes to cytokine levels brought about by treatment with L-thyroxine. Methods. Sixty five female patients, aged 18-73 years with Hashimoto's thyroiditis, referred to the Celal Bayar University Medical Faculty Endocrinology out-patients clinic, were included in this study. After a 10-12 week period of L-thyroxine treatment, all patients were restored to the euthyroid state. At the beginning and end of the treatment period, serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), autoantibodies against thyroid peroxidase (anti-TPO), autoantibodies against thyroglobulin (anti-Tg) levels were measured using a chemiluminecent, immunometric method, and cytokine levels were measured using ELISA. Results. There was a statistically significant decrease in the serum levels of TSH (p < 0.0001) and a concomitant increase in FT4 serum levels (p < 0.0001). Also, during the post-treatment period, serum levels of anti-Tg (p < 0.01) and anti-TPO (p < 0.001) were significantly lower than during the pre-treatment period. A statistically significant decrease was shown for interleukin (IL)-12 serum levels during the post-treatment period (p < 0.001). However, the decrease in interferon (IFN)-gamma serum levels was not statistically significant (p = 0.276). On the other hand, no change was demonstrated in serum IL-2 and IL-4 levels (p = 0.953 and p = 0.313, respectively) after treatment with L-thyroxine. Conclusion. Considering that our study involved a 10-12 week period of treatment, the statistically significant decrease in serum IL-12 levels, and the statistically non-significant decrease in IFN-gamma levels, might indicate that a T helper type 1 inflammatory process had been halted or slowed down.
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    Allergic rhinitis and its relationship with autoimmune thyroid diseases
    Degirmenci, PB; Kirmaz, C; Oz, D; Bilgir, F; Ozmen, B; Degirmenci, M; Colak, H; Yilmaz, H; Ozyurt, B
    Background: Autoimmune thyroid diseases are the most common of all autoimmune diseases. In the literature, Hashimoto thyroiditis (HT) is considered to be a T-helper (Th) type 1 dominant condition, and Graves disease is considered a Th2-dominant condition. Objective: The aim of this study was to highlight a new aspect of the relationships among Th cell subgroups by determining the incidence of autoimmune thyroid disease in patients with allergic rhinitis (AR). Methods: Patients were diagnosed with AR based on their medical histories, physical examinations, and skin-prick test results in an outpatient clinic. The levels of free triiodothyronine, free thyroxine, thyroid-stimulating hormone, thyroid peroxidase antibodies, and thyroglobulin antibodies were measured in peripheral blood samples from all study subjects. Results: A total of 1239 patients with AR and 700 consecutive, age- and sex-matched healthy subjects were included in the study. Thyroid function tests showed that 1037 patients with AR (83.7%) had normal thyroid function, 171 (13.8%) had euthyroid HT, and 31 (2.5%) had hypothyroid HT. Among the control subjects, thyroid function test results showed that 688 subjects (98.2%) had normal thyroid function, 10 subjects (1.4%) had euthyroid HT, and 2 subjects(0.4%) had hypothyroid HT. Conclusion: The incidence of HT in the general population is 1.5%; in contrast, it was observed in 16.3% of our patients with AR, which represented a much higher rate than that in the overall population. Graves disease was not detected in our study subjects. A high incidence of HT in patients with AR, in which Th2 responses are dominant, indicates that further studies of the relationships among atopy, autoimmune diseases, and Th cell subgroups are needed.
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    Increased expression of tissue vascular endothelial growth factor and foetal liver kinase-1 receptor in seasonal allergic rhinitis and relevance to asthma component
    Yuksel, H; Kose, C; Yilmaz, O; Ozbilgin, K; Degirmenci, PB; Pinar, E; Kirmaz, C
    There is a difference in the extent of remodelling in allergic rhinitis (AR) and asthma. This may be attributed to the difference in local tissue response to these mediators. The aim of this study was to compare vascular endothelial growth factor (VEGF) and its receptor foetal liver kinase (Flk)-1 expression between seasonal AR patients with or without asthma and non-allergic controls as well as that between AR patients with and without asthma. Thirteen subjects with seasonal AR and six non-allergic controls were included in the study. Allergic sensitization was demonstrated by a skin prick test. Inferior turbinate thiny biopsies were obtained from both groups. Monoclonal mouse antibodies were used to demonstrate VEGF and Flk-1. Nasal mucosal endothelial cells' staining intensity was graded semi-quantitatively and the histochemical score (HSCORE) was calculated. In all samples, VEGF- and Flk-1-labelled vessels were counted for the assessment of vascular surface density (VSD). The mean HSCORE for VEGF and anti-VEGF-based VSD were significantly higher in the patient group (P=0.001 and 0.002, respectively). The mean HSCORE for Flk-1 and anti-Flk-1-based VSD in the patient group were significantly higher than those in the control group (P=0.016 and 0.028, respectively). Differences between the mean HSCORE for VEGF and anti-VEGF-based VSD in patients with pure AR and AR and asthma were insignificant (P=0.16 and 0.39, respectively). The mean HSCORE for Flk-1 and anti-Flk-1-based VSD in patients with pure AR were significantly lower than those in patients with AR and asthma (P=0.004 and 0.018, respectively). Angiogenic factor VEGF and its receptor Flk-1 is increased in AR. A similar increase in VEGF in AR with and without asthma despite a higher Flk-1 in AR patients with asthma may be a possible explanation for the presence of angiogenesis in the airway wall in patients with asthma but not in those with pure AR.
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    Lower respiratory tract complications during nasal provocation: nonspecific stimulant or specific allergen?
    Kirmaz, C; Degirmenci, PB; Tunali, D; Yuksel, H
    Background: Allergic rhinitis (AR) is an allergic inflammatory disease in which allergen exposure leads to the appearance of symptoms in sensitized individuals because of histamine liberation from nasal mucosal mast cells. Comorbidity of this disease with allergic asthma is common. Therefore, the one airway one disease theory has been put forward. Lower respiratory tract provocation tests with both nonspecific (methacholine) and specific stimulants (allergen) have yielded positive results in nonasthmatic patients with AR. However, not enough research is available to demonstrate whether there is a response in the lower respiratory tract during nasal provocation tests (NPTs) performed to evaluate only nasal airway in these patients. Objectives: To determine if the lower respiratory tract was affected as a result of NPTs with nonspecific and specific stimulants in nonasthmatic patients with AR and to determine the frequency of lower respiratory tract obstruction due to NPT with nonspecific and specific stimulants. Methods: Thirty-six participants were enrolled in the study between November 2005 and January 2006 (18 AR patients and 18 healthy control subjects). Patients underwent 2 sessions of NPT. The first session was performed with nasal methacholine as a nonspecific stimulant, and the second session was performed with nasal Olea europaea extract as a specific stimulant. The control group underwent only nonspecific nasal provocation with methacholine. Basal nasal opening and nasal pressures were evaluated spirometrically by rhinomanometric measurements and basal respiratory function tests in both groups before methacholine nasal provocation. Whether or not nasal provocation was achieved, spirometric measurements were performed in all patients and controls after NPTs. Results: NPTs with methacholine resulted in a similar frequency of nasal provocation in the patient and control groups (P = .63). However, the mean methacholine dose was lower in patients with AR (P = .049). There was a decrease in parameters of asthma, including the ratio of forced expiratory volume in I second to forced vital capacity (P = .04), peak expiratory flow (P = .01), and forced expiratory flow between 25% and 75% (P = .004), as a result of NPTs with methacholine in the patient group. However, NPTs with allergen did not cause a change in lower respiratory tract obstruction criteria. Conclusions: Lower respiratory tract obstruction can occur after NPTs with nonspecific stimulants; therefore, tests performed with specific allergens can be regarded as safer.
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    Validity and reliability of Turkish version of rhinitis and mini-rhinitis quality of life questionnaires
    Yuksel, H; Yilmaz, O; Alkan, S; Degirmenci, PB; Kirmaz, C
    Background: The aim of the present study was to develop the Turkish version of Rhinitis Quality of Life Questionnaire (RQLQ) and mini-RQLQ for clinical and research purposes. Methods: Study included 55 patients with Allergic Rhinitis (AR), aged 18-69. Demographic characteristics and symptom score (T4SS) were recorded. All patients filled in the Turkish RQLQ and mini-RQLQ. Reliability analysis included internal consistency and item-total score correlations. Construct validity analysis was performed by Known Group method by correlation of RQLQ and mini-RQLQ scores with T4SS and SF36. Results: Mean age of patients was 36.4 +/- 10.6. Mean T4SS was 4.7 +/- 4.1. Cronbach's alpha. scores of all RQLQ domains were above 0.90 and those of mini-RQLQ were above 0.80. All items were significantly correlated with their domains. All correlation coefficients for item versus domain score were above 0.75 for RQLQ and above 0.84 for mini-RQLQ. Total RQLQ score was correlated with SF36 domains except physical functioning domain. Total mini-RQLQ score was significantly correlated with all SF36 domains (all r>-0.46). T4SS revealed significant correlation with RQLQ practical score (r=0.38). On the other hand, T4SS was correlated significantly with practical, nose and total scores of mini-RQLQ (r=0.33, 0.48, 0.34 respectively). Conclusions: Health is the complete state of well-being and AR has major impact on quality of life (QoL), therefore it seems essential to include QoL measures in clinical evaluation along with traditional parameters. This study has demonstrated that RQLQ and mini-RQLQ are valid measures for use in Turkish patients with AR. (C) 2009 SEICAP. Published by Elsevier Espana, S.L. All rights reserved.
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    Nasal mucosal expression of nitric oxide synthases in patients with allergic relation to asthma rhinitis and its
    Yuksel, H; Kirmaz, C; Yilmaz, O; Pinar, E; Vatansever, S; Degirmenci, PB; Ozbilgin, K
    Background: Nitric oxide (NO) has contradictory roles in the pathophysiology of allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large amounts produced by inducible NOS (iNOS) are proinflammatory. Objective: To investigate the difference in constitutive endothelial NOS (eNOS) and iNOS expression in nonallergic and allergic mucosa and the possible relation of this to the coexistence of asthma in seasonal AR. Methods: Seventeen patients (10 women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy specimens were obtained in all. Levels of eNOS and iNOS expressed as immunohistochemical scores (HSCOREs) were determined immunohistochemically from the specimens. Results: The mean +/- SD HSCOREs for eNOS in patients with seasonal AR were not significantly different from those of the nonallergic controls (1.85 +/- 0.78 vs 1.63 +/- 0.54; P =.12). On the other hand, the mean SD HSCOREs for iNOS were significantly higher in patients with seasonal AR (1.75 +/- 0.75 vs 0.71 +/- 0.6; P =.004). Furthermore, although eNOS expression was not different between seasonal AR patients with and without asthma, the mean +/- SD HSCOREs for iNOS were significantly higher in the patients with asthma (1.93 +/- 0.78 vs 1.65 +/- 0.55; P =.01). Conclusion: Increased expression of iNOS might have a role in the development of allergic inflammation in upper and lower airways and in comorbidity of AR and asthma.
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    The frequency of autoimmune thyroid disease in our allergic rhinitis patients
    Degirmenci, PB; Kyrmaz, C; Oz, D; Gungor, G; Kurt, H; Hekimsoy, Z
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    Allergic Rhinitis and Its Relationship with IL-10, IL-17, TGF-β, IFN-γ, IL 22, and IL-35
    Degirmenci, PB; Aksun, S; Altin, Z; Bilgir, F; Arslan, IB; Colak, H; Ural, B; Kahraman, DS; Diniz, G; Ozdemir, B; Kirmaz, C
    Background. We aimed in our study to research the role of new cytokines such as IL-35, IL-22, and IL-17 that may form a target for novel treatment approaches. Methods. IL-10, IL-17, TGF-beta, IFN-gamma, IL-22, and IL-35 serum levels of allergic rhinitis (AR) patients were measured using ELISA method. Allergic sensitization was demonstrated by the skin prick test. Patients only with olive tree sensitivity were evaluated for seasonal AR (SAR). Patients only with mite sensitivity were included in the study for perennial AR (PAR). AR clinic severity was demonstrated by the nasal symptom scores (NSS). Results. In total, 65 AR patients (patient group), having 31 PAR and 34 SAR patients, and 31 healthy individuals (control group) participated in the study. Cytokine levels between the patient group and the control group were compared; IL-17 (p = 0 038), IL-22 (p = 0 001), and TGF-beta (p = 0 031) were detected as high in the patient group, and IFN-gamma (p < 0 001) was detected as low in the patient group. When correlation analysis was made between age, gender, prick test result, NSS, AR duration, and cytokine levels in the patient group, a negative correlation was detected only between IFN-gamma (p = 0 032/r = -0 266) level and NSS. Conclusions. Accompanied by the literature information, these results made us think that T cell subgroups and cytokines have an important role in AR immunopathogenesis. It is thought that future studies to be conducted relating to this subject will form new targets in treatment.
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    Long-Term Omalizumab Treatment: A Multicenter, Real-Life, 5-Year Trial
    Yorgancioglu, A; Erkekol, FÖ; Mungan, D; Erdinç, M; Gemicioglu, B; Özseker, ZF; Degirmenci, PB; Nayci, S; Çilli, A; Erdenen, F; Kirmaz, C; Ediger, D; Yalçin, AD; Büyüköztürk, S; Öztürk, S; Güleç, M; Isik, SR; Kalyoncu, AF; Göksel, Ö; Aydin, O; Havlucu, Y; Ar, IB; Erdogdu, A
    Background: Omalizumab has demonstrated therapeutic benefits both in controlled clinical trials and real-life studies. However, research concerning the long-term effects and tolerability of omalizumab is needed. The main objective of this study was to evaluate the effectiveness and tolerability of treatment with omalizumab for up to 5 years. Methods: A multicenter, retrospective, chart-based study was carried out to compare documented exacerbations, hospitalizations, systemic steroid requirement, FEV1, and asthma control test (ACT) results during 1 year prior to omalizumab treatment versus at 1, 3, and 5 years of treatment. Adverse events and reasons for discontinuation were also recorded at each time point. Results: Four hundred and sixty-five patients were enrolled in the study. Outcome variables had improved after the 1st year and were sustained after the 3rd and 5th years of treatment with omalizumab. Omalizumab treatment reduced the asthma exacerbation rate by 71.3% (p < 0.001) at 1 year, 64.3% (p < 0.001) at 3 years, and 54.8% (p = 0.002) at 5 years. The hospitalization rate also decreased; by the 5th year of the treatment no patients were hospitalized. ACT results had also improved significantly: 12 (p < 0.001) at 1 year, 12 (p < 0.001) at 3 years, and 12 (p = 0.002) at 5 years. Overall, 12.7% of patients reported adverse events (most of these were mild-to-moderate) and the overall dropout rate was 9.0%. Conclusion: Omalizumab had a significant effect on asthma outcomes and this effect was maintained over 5 years. The drug was found to be generally safe and treatment compliance was good. (C) 2018 S. Karger AG, Basel