Dilşad Mungan

Comparison of the efficacy of subcutaneous and sublingual immunotherapy in mite-sensitive patients with rhinitis and asthma—a placebo controlled study

BACKGROUND The efficacy of therapy with sublingual allergen extracts is unproven. OBJECTIVE To evaluate the clinical and immunologic outcome of sublingual immunotherapy and to compare the results with subcutaneous immunotherapy and placebo in 36 patients with rhinitis and asthma due to mite allergy. METHOD Thirty-six patients with rhinitis and asthma due to mite allergy were randomly divided into three groups in order to receive subcutaneous injections with allergenic extracts, sublingual drops with solutions of purified standardized allergen preparations, or sublingual placebo for a period of 1 year. Assessment of clinical and immunologic efficacy included symptom and medication scores, methacholine provocation tests, skin prick tests, and specific IgE and IgG4 antibody concentrations. RESULTS Subcutaneous immunotherapy for both rhinitis and asthma was clinically effective. Patients treated with sublingual immunotherapy had decreased rhinitis symptoms (P < .01) but no change in asthma scores. Medication scores significantly decreased in both actively treated groups (P < .01) at the first year compared with baseline. When skin prick tests were evaluated, the subcutaneously treated group had a significant decrease in the wheal diameter of D. pteronyssinus (P < .01), D. farinae (P < .05), and histamine (P < .05) while other two groups showed no difference. There was no significant change in methacholine PC20 values in all groups at the end of the first year when compared with baseline. No change in D. pteronyssinus and D. farinae specific IgE levels were observed; however, specific IgG4 concentrations were significantly higher than baseline both in sublingual and subcutaneous immunotherapy groups (P < .05) after 1 year immunotherapy. No significant difference was obtained in any of these parameters in the placebo group. CONCLUSION Sublingual immunotherapy may be effective in patients with allergic rhinitis. Further, we believe it is a potential therapy for allergic asthmatic patients. The clinical usefulness of this form of immunotherapy (when administered to larger study groups for a longer time) and the mechanisms underlying its immunologic effect deserve additional studies.

Safety of Selective COX‐2 Inhibitors in Aspirin/Nonsteroidal Anti‐inflammatory Drug‐Intolerant Patients: Comparison of Nimesulide, Meloxicam, and Rofecoxib

Background. Intolerance to acetylsalicylic acid (ASA) and other nonsteroidal anti‐inflammatory drugs (NSAIDs) is a crucial problem in clinical practice. There is, therefore, a need for safer NSAIDs in patients with analgesic intolerance. Objective. To assess the safety of nimesulide, meloxicam, and rofecoxib, selective COX‐2 inhibitors, in a group of ASA/NSAIDs‐intolerant patients. Method. Tolerances to nimesulide, meloxicam, and rofecoxib were assessed by single‐blind placebo‐controlled oral challenges. One hundred twenty‐seven subjects with history of adverse reaction to ASA/NSAIDs received oral challenges with nimesulide, 61 subjects were challenged with meloxicam, 51 subjects were challenged with rofecoxib, and 37 subjects were challenged with all three drugs. Placebos were given to all patients on the first day of the study. On the second day, one‐fourth and three‐fourths of the therapeutic doses of the active drugs (nimesulide 100 mg, meloxicam 7.5 mg, or rofecoxib 25 mg) were given at 60‐minute intervals. There was at least a 3‐day interval between challenge tests. Erythema, pruritus accompanied by erythema, urticaria/angioedema, rhinorrhea, nasal obstruction, sneezing, dyspnea, or cough associated with a decrease of at least 20% in the forced expiratory volume (FEV1) and hypotension were considered as positive reactions. Results. Positive reactions to the nimesulide, meloxicam, and rofecoxib challenges were observed in 18/127 (14.3%), 5/61 (8.1%), and 1/51 (2.0%) patients, respectively. In each group of nine patients, there were two patients with asthma and four who developed skin type reactions and asthmatic reactions, respectively, to the nimesulide challenge. Among five patients who reacted to the meloxicam challenge, asthmatic type reactions were detected in two asthmatics. Only one urticarial type reaction was observed with rofecoxib challenge in one patient who presented with anaphylaxis to ASA/NSAIDs. All patients with asthma tolerated rofecoxib without any adverse effects. None of the patients reacted to the placebo. Among 37 patients challenged with all three drugs, 11 reacted to nimesulide, and one patient reacted only to meloxicam. Three patients reacted to more than one of the drugs tested, and one of them reacted to all drugs. Conclusion. This is the first placebo‐controlled report comparing these three drugs. The results indicate that among these alternative drugs for ASA/NSAIDs‐intolerant patients, rofecoxib seems to have the most favorable tolerability.

Prevalence and risk factors of allergies in Turkey: Results of a multicentric cross-sectional study in children

The Prevalence And Risk Factors of Allergies in Turkey (PARFAIT) study was planned to evaluate prevalence and risk factors of asthma and allergic diseases and also to find out which geographical variables and/or climatic conditions play a role determining the prevalence of allergic diseases in Turkish school children. Study was planned as cross‐sectional questionnaire‐based. About 25,843 questionnaires from 14 centers were appropriate for analysis. Parental history of allergy, having an atopic sibling and other atopic disease in index case was significant risk factors for all allergic diseases. Breast feeding decreased the risk of current asthma (OR: 0.92, CI: 0.86–0.99) and wheezing (OR: 0.93, CI: 0.87–0.99) but not allergic rhinitis and eczema. Respiratory infection in the past was an important risk factor for the occurrence of allergic diseases especially for asthma which was increased 4.53‐fold. Children exposed to household smoke were significantly at higher risk of asthma, wheezing, and allergic rhinitis (OR: 1.20, CI: 1.08–1.33; OR: 1.21, CI: 1.09–1.34; and OR: 1.32, CI: 1.21–1.43, respectively). All allergic diseases were increased in those children living in areas which have altitude of below 1000 m and mean yearly atmospheric pressure above 1000 mb. The study has suggested that household and country‐specific environmental factors are associated with asthma, wheezing, allergic rhinitis, and eczema risk during childhood in Turkey.

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.

Prevalence and Risk Factors of Allergies in Turkey (PARFAIT): results of a multicentre cross-sectional study in adults

The Prevalence and Risk Factors of Allergies in Turkey (PARFAIT) study was planned to evaluate the prevalence of and risk factors for asthma and allergic diseases in Turkey. The present analysis used data from 25,843 parents of primary school children, obtained from a cross-sectional questionnaire-based study. A total of 25,843 questionnaires from 14 centres were evaluated. In rural areas, the prevalences asthma, wheezing, allergic rhinitis and eczema in males were: 8.5% (95% confidence interval (CI) 7.9–9.1%), 13.5% (95% CI 12.8–14.2%), 17.5% (95% CI 16.7–18.2%) and 10.8% (95% CI 10.2–11.4%), respectively; and in females were: 11.2% (95% CI 10.9–11.8%), 14.7% (95% CI 14.3–15.1%), 21.2% (95% CI 20.4–22.0%) and 13.1% (95% CI 12.4–13.8%), respectively. In urban areas, the corresponding prevalences in males were: 6.2% (95% CI 5.8–6.6%), 10.8% (95% CI 10.3–11.3%), 11.7% (95% CI 11.4–12.0%) and 6.6% (95% CI 6.2–7.0%), respectively; and in females were: 7.5 % (95% CI 7.9–7.1%), 12.0% (95% CI 11.7–12.3%), 17.0% (95% CI 16.4–17.6%) and 7.3% (95% CI 6.9–7.7%), respectively. Having an atopic first-degree relative or any other atopic diseases had significant effects on the prevalence of allergic diseases. Housing conditions, such as living in a shanty-type house, visible moulds at home and use of wood or biomass as heating or cooking material were associated with one or more allergic diseases. Although genetic susceptibility is strongly associated, country- and population-based environmental factors may contribute to increased prevalence rates of allergic diseases.

Tolerability of Selective Cyclooxygenase Inhibitor, Celecoxib, in Patients with Analgesic Intolerance

Intolerance reactions to acetyl salicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) are common and caused by inhibition of COX-1 enzyme. Therefore, drugs that selectively inhibit COX-2 enzyme may be safe in these subjects. In this study, we evaluated the tolerability of celecoxib, a selective COX-2 inhibitor, in patients with analgesic intolerance. The eligible study population consisted of patients with a history of urticaria/angioedema, naso-ocular symptoms, bronchospasm, and/or anaphylactoid reaction induced by ASA and/or NSAIDs. A single-blind, placebo-controlled oral challenge test was performed in the hospital setting. On 2 separate days, ¼ and ¾ divided doses of placebo and celecoxib (Celebrex 200 mg, Pfizer, Turkey) were given with 2-hour intervals. Seventy-five subjects (mean age: 38.2 ± 1.4 years; F:M: 55:20) were included in the study. Twenty-one subjects had asthma. No reaction was observed with placebo or celecoxib provocation. Although celecoxib seems to be a safe alternative drug in our study group, considering its serious adverse events reported in the literature, the drug should be recommended for patients with analgesic intolerance only after being tested by an experienced allergist.

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.

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.

Influenza Vaccination in Patients with Asthma: Effect on the Frequency of Upper Respiratory Tract Infections and Exacerbations

Influenza epidemics of variable extent and severity occur every winter and are frequently associated with exacerbations of asthma. Accordingly, annual vaccination against influenza is recommended for patients with asthma However, there are very limited data concerning its protective effect in this group of patients. The aim of this study was to assess the effect of influenza vaccination on the frequency of upper respiratory tract infections and also asthma‐related outcomes such as exacerbation rates, hospital admissions, and rescue courses of oral corticosteroids in patients with stable asthma. Between September 15 and November 7, 2001, a total of 128 patients with asthma were randomly assigned to receive (n = 86) and not to receive vaccine (n = 42). The primary outcome measures were frequency of upper respiratory tract infections and exacerbations of asthma during the winter following vaccination. Study subjects were asked to record the presence and duration of symptoms suggestive of an upper respiratory tract infection and call their physician in the presence of conditions suggestive of an exacerbation until March 2002. Among the vaccinated group, 48% of the patients reported that they had no upper respiratory tract infection during the winter following injection, whereas 57% of nonvaccinated participants were upper respiratory symptom free during the same period (p > 0.05). The frequency of upper respiratory tract infection was also not different between the two groups in all severity forms of asthma (p > 0.05). There was no significant difference in the frequency of exacerbations of asthma between the two groups during the study period (p > 0.05). None of the vaccinated group was hospitalized due to an asthma attack; however, two patients (4.8%) in the nonvaccinated group had to be hospitalized following an exacerbation (p > 0.05). In summary, our findings do not support the protective effect of influenza vaccination for patients with asthma. However, no firm conclusions on this effect of the vaccine can be made without the data on the rate of influenza epidemic in that season and without the knowledge of the cause of upper respiratory tract infections in those patients. Therefore, we believe randomized, double‐blind, placebo‐controlled studies, including larger subgroups of severe asthmatics, are needed to evaluate the protective effect of influenza vaccination in asthma.

Regional pollen load: effect on sensitisation and clinical presentation of seasonal allergic rhinitis in patients living in Ankara, Turkey.

BACKGROUND Although Gramineae pollens are the main reason for seasonal allergy in many parts of Europe, the influence of regional flora on sensitisation and symptoms has always been a topic of interest. The aim of this study was to document the sensitisation to pollens and to evaluate their clinical importance in patients with seasonal allergic rhinitis living in Ankara/central Anatolia. METHODS The study included those subjects with seasonal allergic rhinitis living in Ankara. Skin prick testing with a panel of common aeroallergens as well as grass, individual tree and weed pollens predominant in the region was performed. The patients were followed by symptom-medication scores during the same season in which regional pollens were also counted. RESULTS The final eligible study consisted of 54 subjects (F/M: 26/28; mean age: 29.4 years). Trees were the most common pollen source consisting of 95 % of the total amount, followed by grasses (3 %) and weeds (2 %). Sensitisation to Gramineae, to at least one weed; and to tree pollens were 100 %, 85.2 % and 94.4 %, respectively. The most common positive skin tests among tree pollens were to Oleaceae (59.2 %), Aesculus (57.4 %); and Tilia (42.5 %) despite low pollen counts. Chenopodiaceae (88 %) and Plantago (63 %) were the most sensitised weed pollens, with high pollen counts. All patients had significant symptoms during May and June. CONCLUSION Although Gramineae pollens seem to be major allergens for seasonal allergic rhinitis in Ankara, the particular role of tree pollens and weed pollens cannot be discarded on symptom development in sensitised patients.