Betül Ayşe Sin

Pathophysiology of Allergic and Nonallergic Rhinitis

Allergic and nonallergic rhinitis affect approximately 30% of the U.S. population. Although allergic rhinitis has a clear definition and its pathophysiology has been thoroughly investigated, nonallergic rhinitis remains poorly defined and understood. There is consensus, however, that nonallergic rhinitis consists of a variety of heterogeneous conditions. In allergic rhinitis, the process of allergen sensitization involves the participation of antigen-presenting cells, T lymphocytes, and B lymphocytes and depends on environmental allergen exposure. Sensitization results in the generation of allergen-specific IgE that circulates in the peripheral blood and attaches itself on the surface of all mast cells and basophils including those that home to the nasal mucosa. Subsequent nasal exposure to allergen activates these cells and, through the release of the classic mediators of the allergic reaction, produces acute nasal symptoms. Over a short period of time, these symptoms become indolent, whereas inflammatory and immune cell infiltrate, including eosinophils, basophils, neutrophils, T lymphocytes, and monocytes, characterizes the late stages of the allergic response. In parallel, and probably as a result of the development of mucosal inflammation, the nose becomes primed to allergen and reacts more vigorously to subsequent allergen exposure but also becomes hyperresponsive to irritants and to changes in atmospheric conditions. In nonallergic rhinitis, several conditions may have been identified that are of interest for further research and phenotyping. These include a group of patients with apparent hyperresponsiveness of the C-fiber sensory nerves with no inflammatory changes in the nasal mucosa and a group with mucosal eosinophilia who may have allergic sensitization to common aeroallergens that is, however, manifested only in the nasal mucosa.

The antioxidative defense in asthma

Asthma is a disease characterized by chronic airway inflammation. Generation of oxygen free radicals by activated inflammatory cells produces many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. However, the activities of antioxidant enzymes and their relation with asthma have not been well defined. This study was performed to examine the activities of major intracellular antioxidants in mild asthmatic patients. Twelve asymptomatic mild asthmatic patients who never used any antiasthma medication and 13 age- and sex-matched healthy control subjects were selected. The activities of erythrocyte antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GSH-Px) were measured spectrophotometrically. The mean SOD activity of asthmatic patients was found to be significantly lower than that of the controls (p < 0.05). There was no significant difference in CAT and GSH-Px activities between patients and controls (p > 0.05). Although the mechanisms underlying the association between asthma and antioxidant system are unclear, according to our findings, decreased antioxidant protection may contribute to the pathogenesis of mild asthma.

The prevalence of allergic diseases and atopy in Ankara, Turkey: a two-step population-based epidemiological study.

To assess the prevalence of allergic diseases and atopy in adults, a two-step population-based epidemiological study was undertaken in Ankara, the capital city of Turkey. In step 1, a screening questionnaire adapted from the European Community Respiratory Health Survey (ECRHS) was applied in a cross-sectional manner. In step 2, a nested case-controlled design study was conducted and subjects were evaluated in the clinical setting for history, physical examination, skin prick tests (SPTs), and serum total IgE and phadiotop measurements. According to the results, self-reported current asthma prevalence in step 1 was lower compared with that in step 2 (3% vs. 7%, p < 0.05). The prevalences of food and drug allergy were 6.2% and 3.9%, respectively, in step 1, but were not demonstrated in any of the subjects in step 2. The overall prevalence of atopy was 25% after step 2 evaluation. In conclusion, allergic disorders are not uncommon in our adult population; however, sole application of a screening questionnaire appeared to be ineffective in revealing the accurate figures of asthma, and food or drug allergy.

Characteristic features of cockroach hypersensitivity in Turkish asthmatic patients

Exposure to cockroach has been reported to cause asthma in many parts of the world. Although house‐dust‐mite is known to be the most important indoor allergen in Turkey, there are few data on the prevalence of allergy t o cockroaches. Therefore, we evaluated the prevalence of cockroach sensitivity in asthmatic TUrkish patients to see whether it is also an important source of asthma in addition to house‐dust mites. A total of 206 patients demonstrating the characteristic features of asthma were included in the study. Sixty‐three percent of the patients were considered atopic, and 37% were found to be nonatopic by skin prick tests. Mite allergens were the most common cause of indoor allergy (50%), while cockroach sensitivity was detected in 25.7% of all the asthmatics. Among all cockroach‐sensitive patients, 70% were also positive for mites. A female predominance was observed in cockroach‐sensitive patients, as 44% of atopic women and 34% of atopic men had positive skin tests with cockroach allergen. The average duration of asthma was 7.1+5.6 years in cockroach‐sensitive asthmatics, and there was no difference between groups in average duration of asthma (P>0.05). Mild, moderate, and severe asthmatics constituted 73.6%, 20.7%. and 5.7% of the cockroach‐sensitive patients, respectively. These data indicate that cockroach is also an important source of domestic infestation n i Tlirkey. Thus, it seems reasonable to suggest the need for cockroach allergen in the routine battery of inhalant skin tests in this geographic location. However, possible cross‐reactivity with mites has to be taken into consideration during the clinical evaluation of subjects with cockroach sensitivity, especially in our patient population with such high rates of house‐dust‐mite allergy.

EAACI Guidelines on Allergen Immunotherapy: Hymenoptera venom allergy

Hymenoptera venom allergy is a potentially life‐threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic‐allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life‐threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1‐antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunologys (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom‐allergic children and adults to prevent further moderate‐to‐severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence‐based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

Severity and associated risk factors in adult asthma patients in Turkey

BACKGROUND The prevalence of asthma of varying severity and associated risk factors are unknown in Turkey. OBJECTIVE The study investigated the distribution of asthma severity, the factors having roles in asthma severity, and the relationship between serum eosinophil cationic protein (ECP) levels and disease severity. METHODS Three hundred patients with asthma (73 male, 227 female) were enrolled in the study. The patients were surveyed for their smoking habits, educational levels, household incomes, asthma duration, occupations, and accompanying diseases. ECP levels were also determined in certain patients representing different disease severities (n: 76) and in a control group (n: 9). RESULTS Patients were classified as mild intermittent (n: 14, 5%), mild persistent (n: 220, 73%), moderate (n: 44, 15%), and severe asthma (n: 22, 7%). Cigarette consumption and educational status were similar in all groups. A longer duration of disease and an older population predominated in patients with moderate and severe asthma. Analgesic sensitivity was seen in 7%, 10%, 6%, and 31% of mild intermittent, mild persistent, moderate and severe asthma patients, respectively, with the highest ratio in severe asthma (P < .05). Nasal polyps were significantly higher in severe asthmatics. Atopy was diagnosed in 85%, 57%, 56% and 10% of mild intermittent, mild persistent, moderate and severe asthma patients, respectively. ECP levels were significantly higher in moderate and severe asthma patients. CONCLUSIONS Mild asthma was the most common clinical presentation and was associated with atopy. The factors associated with severe asthma included prolonged asthma duration, advanced age, nonatopy, analgesic intolerance and nasal polyps. ECP levels also reflected disease severity.

Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis.

The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost‐effectiveness and safety of AIT in the management of insect venom allergy.

Atopic status of an adult population with active and inactive tuberculosis

The rise in allergic disorders over the past three decades has been suggested to be related to the decrease in infectious diseases. Recently, a negative association between tuberculin responses and atopic disorders has also been reported. We planned to investigate the effect of natural exposure to Mycobacterium tuberculosis on atopic status in patients with active tuberculosis and to compare the findings with the data of patients with inactive disease. A total of 97 subjects were divided into two groups. Group 1, patients with proven active pulmonary tuberculosis (n = 66); group 2, subjects who had a history of previous tuberculous disease, with negative bacteriologic studies and no clinical and/or roentgenographic evidence of current disease (n = 31). Current history of allergic diseases was recorded by a physician with the use of a questionnaire adapted from the European Community Respiratory Health Survey (ECRHS), and skin-prick tests (SPTs) were performed using a standardized panel. Total IgE and Phadiatop were measured by the Pharmacia uniCAP system. The rate of one or more positive SPTs was significantly lower in the patients with active tuberculosis than the inactive group (15% versus 48.4%, p < 0.001). The current history of atopic diseases was 7.6% and 29% in the active and inactive tuberculosis groups, respectively (p = 0.002). The rate of positive skin tests to inhalant allergens in patients with inactive disease was higher than the rate of healthy adult Turkish people (48.4% versus 25%, p = 0.001). Geometric mean of total IgE levels were lower in patients with inactive disease than patients with active pulmonary tuberculosis (74.97 kU/L versus 106.3 kU/L, p = 0.05). The ratios of Phadiatop positivity were 21% and 38.7% in the active and inactive tuberculosis groups, respectively (p = 0.008). We found lower atopy rates in patients with active pulmonary tuberculosis than subjects with inactive disease. Although our data support the hypothesis that M. tuberculosis may prevent the development of atopic disorders by inducing the production of cytokines antagonistic to Th2 development, we believe prospective and experimental studies are needed before attributing a direct cause-effect link to this association.

Short-Term Preseasonal Immunotherapy: Is Early Clinical Efficacy Related to the Basophil Response?

Background: An aluminum hydroxide-adsorbed depot allergoid preparation of six-grass pollen allergens has been developed for short-term preseasonal immunotherapy in pollinosis. However, only limited knowledge exists about its immunological and clinical effects. The aim of this study was to evaluate the basophil response, which can explain early clinical findings of short-term preseasonal allergoid immunotherapy in allergic rhinitis. Methods: In a double-blind, placebo-controlled study, 31 patients allergic to grass pollens received one course of short-term preseasonal allergoid immunotherapy or placebo. Immunogenicity was assessed by the levels of specific IgG4, IgE antibodies and an allergen-induced CD203c basophil activation test. The primary clinical end point was the combined symptom and medication score/average combined score (ACS). Results: There was a 52.9% difference in ACS between the treatment and placebo groups in favor of immunotherapy (p = 0.01). Active treatment induced Phleum pratense-specific IgG4 and IgE antibodies (p < 0.05). A decrease in allergen-induced basophil activation at submaximal allergen concentrations was demonstrated at the end of immunotherapy and at the peak of the grass pollen season after immunotherapy. Conclusions: This study shows that grass pollen-allergic patients treated with one course of short-term preseasonal allergoid immunotherapy exhibit a decrease in allergen-induced basophil activation, an increase in allergen-specific IgG4 antibodies and early clinical improvement.

Reliability of basophil activation test using CD203c expression in diagnosis of pollen allergy.

Background CD203c is a basophil surface marker and its expression is rapidly up-regulated after cross-linking of high-affinity immunoglobulin E (IgE) receptor (FcepsilonR1) by an allergen. CD203c basophil activation tests have been studied for the in vitro diagnosis of several allergic conditions. However, there is limited data about its diagnostic usefulness. The optimum allergen concentrations for stimulation and allergen specific cutoff values remain unknown for a number of allergens. This study was designed to investigate the efficacy of basophil activation test via CD203c in the diagnosis of pollen allergy. Methods The CD203c basophil activation was determined in 31 allergic rhinitis patients with pollen allergy and 9 healthy nonatopic controls during the off-season. CD203c expression was evaluated using three-color staining protocol by flow cytometry. Results After an in vitro stimulation with grass pollen extract, the CD203c assay clearly discriminated pollen-allergic patients from controls (p < 0.001). A dose-dependent increase in the percentages of CD203c-activated basophils was shown in rhinitis patients with pollen allergy (p < 0.001). The sensitivity and specificity was 100% and optimal cutoff values were 14.05 and 10.05% with 45.1 and 4.5 μg/mL Phl p 5 stimulation, respectively. Although the specificity was also 100%, the sensitivity was 93 and 87% and the cutoff values were 5.40 and 5.35% with 4.5 x 10–4 and 4.5 x 10–5 micrograms/mL Phl p 5 stimulation, respectively. Conclusion The CD203c basophil activation test seems to be a reliable tool in the diagnosis of grass pollen allergy. It could be used when conventional diagnostic tests fail or can not be performed.