Cengiz Kirmaz

Sexual dysfunction in patients with allergic rhinoconjunctivitis

BACKGROUND Sexual dysfunction in chronic diseases has recently attracted attention owing to its impact on quality of life (QoL). Allergic rhinoconjunctivitis (ARC) affects QoL, causing limitations in many areas. However, there has not been research on changes in sexual function in patients with ARC. OBJECTIVE To report the effect of ARC and its treatment on sexual function in men and women. METHODS Forty-three sexually active patients with seasonal ARC aged 22 to 49 years were included in the study. The control group was composed of 40 healthy individuals aged 22 to 46 years. Conjunctival symptom scores (CSSs) and nasal symptom scores (NSSs) of patients with symptomatic ARC were determined, as were sexual function scores (SFSs) using the Female Sexual Function Index and the International Index of Erectile Function during allergen exposure in the pollination period and after treatment with oral desloratadine, 5 mg/d, for 30 days. The SFSs were evaluated in the control group. RESULTS The CSSs and NSSs significantly improved in treated ARC (P < .001). In women, Female Sexual Function Index results in symptomatic ARC were significantly lower than in treated ARC and controls (P = .003). In men, International Index of Erectile Function results in treated ARC (P = .001) and controls (P < .001) were significantly higher than in symptomatic ARC. Furthermore, correlation between improvement in CSSs and NSSs and that of SFSs was determined (P = .007 for women; P = .001 for men). CONCLUSION Improvement in sexual function as a variable of QoL may accompany the treatment of symptoms in patients with ARC.

Nasal mucosal expression of nitric oxide synthases in patients with allergic rhinitis and its relation to asthma

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.

Sensitization to cat allergens in non–cat owner patients with respiratory allergy

BACKGROUND Cats represent one of the most important sources of indoor allergens. The sensitization rate can reach up to 60% in western countries. Keeping cats indoors is uncommon in big cities in Turkey, but cats living in the streets are common. OBJECTIVE To investigate the prevalence of sensitization to cats in patients with respiratory allergy from Izmir, Turkey, and its relationship to home cat allergen levels. METHODS A total of 387 patients (70.8% female; mean age, 34.3 years) with respiratory allergic diseases (rhinitis and/or asthma) were included in this study. Skin prick test to cat was performed. House dust samples were collected from the living room of 25 patients and 14 healthy subjects. The major cat allergen (Fel d 1) levels were measured by Dustscreen. Fel d 1 levels given by the manufacturer were as follows: 0.05, 0.13, 0.40, 1.1, and 6.2 mU/mL. RESULTS The prevalence of cat sensitivity was 44.7% (n = 173). Only 6 patients (1.6%) had a history of feeding a cat in their houses. Thirty-six (92%) of 39 houses had detectable levels of cat allergen (mean Fel d 1 level, 2.24 +/- 2.69 mU/mL). The mean Fel d 1 levels were 1.58 +/- 2.51 mU/mL in the healthy group, 1.91 +/- 2.61 mU/mL in the asthmatic group, and 3.26 +/- 2.85 mU/mL in the group with allergic rhinitis (P = 0.12). The prevalence of cat sensitivity in patients who had 1.1 mU/mL of Fel d 1 in their homes was 57.1%. This rate was five times lower (11.1%) in patients who had the highest Fel d 1 level (6.2 mU/mL) in their homes. CONCLUSIONS The prevalence of cat sensitivity in Izmir, where cats are generally not kept within homes, is as high as in western countries. The sampled houses have measurable levels of Fel d 1 even in the absence of indoor cats. High prevalence of cat sensitivity in Izmir is probably due to indirect exposure.

Increased expression of tissue vascular endothelial growth factor and foetal liver kinase‐1 receptor in seasonal allergic rhinitis and relevance to asthma component

Background 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.

Regulatory-T, T-helper 1, and T-helper 2 cell differentiation in nasal mucosa of allergic rhinitis with olive pollen sensitivity.

Background: Allergic rhinitis (AR) is a disease in which T-helper (Th)2 response is predominant and its pathogenic mechanism is still poorly understood. Aim: To evaluate the possible role of Th1, Th2 and regulatory-T (Treg) cells in the pathogenesis of AR. Methods: This case-control study enrolled 41 patients with seasonal AR (10–62 years old), sensitive to olive pollens, and 15 healthy controls (18–60 years old). Nasal biopsy was performed and specimens of nasal lavage fluid were obtained from all participants. The levels of interleukin (IL)-4, IL-10, interferon (IFN)-γ and transforming growth factor-β (TGF-β) were measured in nasal lavage fluid specimens. The expression of FOXP3, GATA-3 and T-bet was measured by immunohistochemical methods in the nasal biopsy specimens. Results: The levels of IFN-γ in the group with AR were significantly lower than those in the control group (p = 0.008). The levels of IL-4, IL-10 and TGF-β did not differ between the two groups. The expression of FOXP3 and T-bet in patients with AR was significantly lower than that in the control group (both p = 0.001). Expression of GATA-3 in the nasal mucosa was similar between the groups (p = 0.2). The ratios of T-bet/GATA-3 and FOXP3/GATA-3 in the AR group were significantly lower than those in the control group (p = 0.001). Conclusion: Insufficient Treg and Th1 cells may be associated with the allergic inflammation that may be attributed to the Th2 immune response in patients suffering from AR who are sensitive to olive pollen.

Down-regulation of the auto-aggressive processes in patients with hypothyroid Hashimoto's thyroiditis following substitutive treatment with L-thyroxine.

BACKGROUND Hashimotos 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 Hashimotos 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 Hashimotos 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.

Effects of allergen-specific immunotherapy on functions of helper and regulatory T cells in patients with seasonal allergic rhinitis.

BACKGROUND Seasonal allergic rhinitis (SAR) is characterized by a helper T (Th)2 cell-mediated immune response at the target site. There is a relative Th1 and/or regulatory T (Treg) cell insufficiency in patients with SAR. It has been demonstrated that there is a change in the balance between these cells after allergen-specific immunotherapy (SIT), which is a curative treatment modality for this disease. However, there are few studies that evaluate the number and function of these cells in the inflammatory area after SIT treatment. OBJECTIVE We aimed to investigate the distribution of Th1, Th2 and Treg cells in nasal biopsies and lavage fluid (NLF) specimens from patients with SAR, before and after SIT. METHODS Twenty-four, symptomatic SAR patients sensitized to Olea europeae, were enrolled in the study prior to treatment. Fifteen, non-allergic subjects with nasal septum deviation, who needed surgical treatment, served as the control group. NLF and inferior turbinate biopsies were obtained from both groups during the pollen season. Conventional, subcutaneous SIT with Olea europeae extract was initiated in patients with SAR. One year after the first biopsy, biopsies and NLF specimens were again obtained for reevaluation. All biopsies were evaluated for Th1, Th2 and Treg cell counts by means of their transcription factors (T-bet, GATA-3 and FoxP3) using an immunohistochemical analysis method. Additionally, all NLF specimens were evaluated for the functions of these cells, by means of their specific cytokines, using an ELISA method. RESULTS When the basal status of those patients with SAR was evaluated based on transcription factors, prior to treatment, Th1 and Treg cells were found to be fewer than in non-allergic controls (p=0.001 for both T-bet and FoxP3). It was demonstrated that numbers of GATA-3-carrying cells, which are a marker for Th2, were not significantly different between the groups (p=0.276), but evaluation of the Th1/Th2 ratio revealed a relative Th2 dominance in patients with SAR prior to treatment. When evaluated on the basis of cytokine levels, it was observed that Th1-originated IFN-γ was lower in patients with SAR compared to the control group, both before and after treatment (p=0.012 for both comparisons), Th2-originated IL-4 levels were not significantly different between the groups either before or after treatment (p=0.649, p=0.855; respectively). Th2- and Treg cell-originated IL-10 levels were higher in patients with SAR before treatment (p=0.033), but this difference was not statistically signifant following treatment compared with controls (p=0.174). Treg cell-originated TGF-β levels were slightly lower in patients with SAR compared to the controls, although the difference was not statistically significant (p=0.178, p=0.296; respectively). None of the above mentioned cytokine levels changed significantly as a result of SIT. CONCLUSION The results of our study indicate that although clinical findings improve after one year of SIT, this duration may not be sufficient to detect changes in cytokine patterns and transcription factors. Further studies that evaluate outcome over a longer duration of treatment would provide valuable information.

Drug allergy in tertiary care in Turkey: Results of a national survey. The ADAPT study: Adult drug allergy perception in Turkey

BACKGROUND No data are available on the incidence of drug hypersensitivity (DH) reactions in outpatient settings of tertiary allergy/immunology clinics. Our aims were to document the frequency of outpatient hospital admissions due to DH reactions to allergy/immunology clinics in adults and the management of these reactions in real life. We also investigated whether drug allergy affected social and medical behaviours of the patients. METHODS This multi-centre study was performed for one year with the participation of 11 out of 16 tertiary allergy/clinical immunology clinics in Turkey. The study group consisted of the patients with DH reactions. Results of a questionnaire including drug reactions and management were recorded. RESULTS Among 54,863 patients, 1000 patients with DH were enrolled with a median of 2.1% of all admissions. In real life conditions, the majority of approaches were performed for finding safe alternatives (65.5%; 1102 out of 1683) with 11.7% positivity. Diagnostic procedures were positive in 27% (154/581) of the patients. The majority of the patients had higher VAS scores for anxiety. A total of 250 subjects (25%) reported that they delayed some medical procedures because of DH. CONCLUSION Our results documented the frequency of admissions due to DH reactions to allergy/clinical immunology clinics for the first time. Although physicians mostly preferred to perform drug tests in order to find safe alternatives, considering the fact that DH was confirmed in 27% of the patients, use of diagnostic tests should be encouraged, if no contraindication exists in order to avoid mislabelling patients as DH.

Validity and reliability of Turkish version of rhinitis and mini-rhinitis quality of life questionnaires

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. Cronbachs 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.

The paracrine immunomodulatory interactions between the human dental pulp derived mesenchymal stem cells and CD4 T cell subsets

Mesenchymal stem cells (MSCs) have strong immunomodulatory properties, however these properties may show some differences according to the tissue type of their isolate. In this study we investigated the paracrine interactions between human DP derived MSCs (hDP-MSCs) and the CD4+ T helper cell subsets to establish their immunomodulatory mechanisms. We found that the CD4+-Tbet+ (Th1) and CD4+-Gata3+ (Th2) cells were suppressed by the hDP-MSCs, but the CD4+-Stat3+ (Th17) and CD4+-CD25+-FoxP3+ (Treg) cells were stimulated. The expressions of T cell specific cytokines interferon gamma (IFN-g), interleukin (IL)-4 and IL-17a decreased, but IL-10 and transforming growth factor beta-1 (TGF-b1) increased with the hDP-MSCs. The expressions of indoleamine-pyrrole 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), soluble human leukocyte antigen G (sHLA-G) derived from hDP-MSCs slightly increased, but hepatocyte growth factor (HGF) significantly increased in the co-culture groups. According to our findings, the hDP-MSCs can suppress the Th1 and Th2 subsets but stimulate the Th17 and Treg subsets. The Stat3 expression of Th17 cells may have been stimulated by the HGF, and thus the pro-inflammatory Th17 cells may have altered into the immunosuppressive regulatory Th17 cells. Further prospective studies are needed to confirm our findings.