Zeynep Misirligil

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.

The use of nimesulide in patients with acetylsalicylic acid and nonsteroidal anti-inflammatory drug intolerance

Intolerance or idiosyncrasy to acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) is a crucial problem because these drugs are frequently used in medical treatment. In this study, we tested whether nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, might be a valid alternative for patients with histories of adverse reaction to ASA or NSAIDs. A single-blind, placebo-controlled oral challenge procedure was applied to 60 adult patients (19 male, 41 female; with a mean age of 40.31 +/- 10.44 years, range 20-68 years) with a reliable history of ASA/NSAIDs-intolerance. According to history, the clinical presentations of intolerance were urticaria/angioedema in 32 patients, anaphylactoid reaction in 2 patients, respiratory reaction in 19 patients, and respiratory and cutaneous reaction in 7 patients. Atopy was confirmed by means of skin prick test with inhalant allergens. Oral challenge protocol was started with 25 mg of nimesulide and the remaining 75 mg was given 1 hr later. During the challenge procedure, blood pressure, pulse, nasoocular, pulmonary, and cutaneous symptoms were monitored. Of the 60 patients tested, 55 (91.7%) tolerated the drug with no adverse reaction. Only five (8.3%) patients demonstrated a positive response to oral challenge. The clinical presentations of intolerance to nimesulide were urticaria/angioedema in three patients, mild rhinitis in one patient, and mild dyspnea in one patient. The atopy prevalence was higher, with a ratio of 41.7%, in patients with ASA/NSAIDs intolerance than that of the healthy adult population in Turkey (p < 0.05). We believe that nimesulide can be used as an alternative drug for patients with ASA/NSAIDs intolerance.

Safety of Meloxicam in Aspirin-Hypersensitive Patients with Asthma and/or Nasal Polyps

Background: The anti-inflammatory actions of acetylsalicylic acid (ASA)/non-steroidal anti-inflammatory drugs (NSAIDs) are thought to be due to inhibition of COX-2, whereas the side effects such as gastric damage and aspirin-induced asthma are mediated through inhibition of COX-1. Therefore, a new class of drugs with COX-2 selectivity may be well tolerated by patients with ASA/NSAIDs hypersensitivity. Objective: We investigated whether subjects with asthma and/or nasal polyps (NP) and analgesic intolerance proven by oral ASA provocation test tolerated the selective COX-2 inhibitor, meloxicam. Methods: All subjects were first challenged with ASA using a 2-day, single-blind, placebo-controlled oral provocation test. Thereafter, the subjects showing positive response to ASA provocation underwent a single-blind, placebo-controlled challenge with a cumulative dose of 7.5 mg of meloxicam on 2 separate days. One and three fourths of the divided doses of placebo and the active drug were given at 1-hour intervals. Clinical symptoms, lung function, and blood pressure were monitored during these challenge protocols. Results: Twenty-one patients with asthma and/or NP (10 males and 11 females; mean age: 38.4 ± 2.9 years) who reacted to ASA challenges were enrolled in the study. Response to ASA provocation was rhinitis + bronchospasm in 13, and extrabronchial reactions in 8 (isolated rhinitis in 3) patients. Mean PD20 was 163.4 ± 39.9 mg ASA among patients who reacted with bronchospasm to ASA. Only 1 patient reacted to meloxicam challenge at a cumulative dose of 7.5 mg. Conclusion: This study indicates that 7.5 mg of meloxicam is a safe alternative treatment for ASA-hypersensitive asthma and/or NP patients with proven hypersensitivity via oral ASA challenges.

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.

Upregulation of CD63 or CD203c Alone or in Combination Is Not Sensitive in the Diagnosis of Nonsteroidal Anti-Inflammatory Drug Intolerance

Background: The oral aspirin (ASA) provocation test is considered to be the gold standard in the diagnosis of ASA sensitivity. However, since it may be associated with severe adverse reactions, safer alternatives would be highly desirable. The basophil activation test has been proposed as such an alternative, but there is limited information about its usefulness. Our aim was to evaluate the clinical usefulness of flow cytometric basophil activation in the diagnosis of ASA sensitivity. Methods: Patients with ASA sensitivity (n = 18), patients with ASA tolerance (n = 12) and healthy volunteers (n = 12) were included in the study. A 2-day single-blind placebo-controlled oral ASA provocation test was performed on all patients. Basophil activation after lysine-ASA and diclofenac stimulation was measured by Flow-CASTTM (Bühlmann Laboratories) for CD63 and an allergenicity kit (Beckman Coulter) for CD203c. The results of CD63 and CD203c were compared within groups, and sensitivity and specificity of the assay were measured against oral ASA provocation. Results: The highest sensitivity and specificity of CD63 were 33.3 and 79.2%, respectively, and of CD203c were 16.7 and 100%, respectively, for ASA. The highest sensitivity and specificity of CD63 were 16.7 and 91.7%, respectively, and of CD203c were 22.2 and 100%, respectively, fordiclofenac. Neither the addition of CD203c to CD63 nor the addition of diclofenac improves the overall sensitivity and specificity of CD63 to ASA. Conclusion: At present, basophil activation using CD63 and CD203c does not seem to be optimally sensitive for the diagnosis of ASA sensitivity.

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.

Hypersensitivity Reactions to Contrast Media: Prevalence, Risk Factors and the Role of Skin Tests in Diagnosis – A Cross-Sectional Survey

Background: Hypersensitivity to contrast media (CMs) may be common and serious. Aim: To evaluate the prevalence of CM hypersensitivity, risk factors associated with it and the role of skin testing in its diagnosis. Methods: A structured questionnaire was administered to patients who underwent computed tomography during a 1-year period. Skin tests with CMs, including skin prick tests (SPTs), intradermal tests (IDTs) and patch tests (PTs), were conducted on CM reactors (n = 24). Volunteers who tolerated CM exposure or had never been exposed to any CMs served as controls (n = 37). Results: A total of 1,131 patients (630 females and 501 males; mean age 55 ± 14.2 years) were enrolled in the study. The prevalence of historical and current CM reactors was 33/1,131 (2.92%) and 8/1,105 (0.72%), respectively. The skin was the most affected site, with mild to moderate reactions. Female gender, a history of doctor-diagnosed asthma, drug allergy, food allergy and psychiatric diseases were significant risk factors. The sensitivities of SPTs and early readings of IDTs in the diagnosis of immediate reactions were 0 and 20%, respectively, and the specificities were 94.6 and 91.4%, respectively. For early readings of IDTs, the positive predictive value (PPV) and negative predictive value (NPV) were 40 and 80%, respectively. For nonimmediate reactions, the sensitivities of delayed readings of IDTs and PTs were 14.3 and 25%, respectively; specificity was 100% for both tests. The PPV was 100% for both of these tests, and the NPVs were 85.4 and 82.4%, respectively. Conclusions: Our findings are comparable with the incidence, profile and risk factors associated with CM hypersensitivity reported previously. Skin testing with CMs has a high specificity, but its role in diagnosis is limited due to low sensitivity.