Pre-seasonal immunotherapy is effective in both monosensitized and polysensitized patients with allergic rhinitis.

Summary: Background. The effectiveness of pre-seasonal allergoid immunotherapy in polysensitized patients are not well-known. The aim of the present study was to compare the clinical efficacy and immunological changes of pre-seasonal allergoid immunotherapy in mono and polysensitized patients with grass pollen allergy. Methods. Fourty six patients with seasonal allergic rhinitis undergoing pre-seasonal grass pollen immunotherapy and 28 cases followed by conventional drug treatment were included. These groups were divided into monosensitized and polysensitized ones. All patients were followed between March-September with symptom-medication scores, and visual analogue scale (VAS). The quality of life was assessed using the Mini-RQLQ questionnaire. Phleum pratense (Phl p) specific IgE and IgG4 (UNI-CAP 100, Phadia) measurements were performed before and after 7 weeks of immunotherapy. Results. In the immunotherapy group, 15th weekly symptom-medication scores and VAS scores between May and August were found to be significantly lower than those in the control group (p < 0.05). Phl p specific IgE and IgG4 levels were significantly higher after immunotherapy compared to those before immunotherapy (p = 0.001). Furthermore, Phl p specific IgG4 levels after immunotherapy were also significantly higher than in the control group (p = 0.001). Improvements in activities-practical problems and non-nose/eye symptoms quality of life scores were significantly different between two groups (p < 0.05). There was no difference in terms of clinical and immunological parameters in mono- and polysensitized patients (p > 0.05). Conclusions. This study indicates that clinical improvement with pre-seasonal grass pollen immunotherapy is accompanied by important increase in specific IgG4 blocking antibodies. Furthermore, a single-allergen immunotherapy can lead to similar clinical efficacy and immunological changes in polysensitized as well as monosensitized patients with grass pollen allergy.

Economic burden of severe asthma in Turkey: a cost of illness study from payer perspective.

Summary: Objective. To estimate economic burden of severe asthma in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice. Methods. This cost of illness study was based on identification of per patient annual direct medical costs for the management of sever easthma in Turkey from payer perspective. Average per patient direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations and interventions, drug treatment and equipment, and co-morbidities/complications. Results. Based on total annual per patient costs calculated for outpatient admission ($ 177.91), laboratory and radiological tests ($ 82.32), hospitalizations/interventions ($ 1,154.55), drug treatment/equipment ($ 2,289.63) and co-morbidities ($ 665.39) cost items, total per patient annual direct medical costrelated to management of severe asthma was calculated to be $ 4,369.76 from payer perspective. Drug treatment/equipment (52.4%) was the main cost driver in the management of severe asthma in Turkey, as followed by hospitalizations/interventions (26.4%) and co-morbidities (15.2%). Conclusions. In conclusion, our findings indicate that managing patients with severe asthma pose a considerable burden to health economics in Turkey, with medications as the main cost driver.

Evaluation of vascular endothelial growth factor-A and Endostatin levels in induced sputum and relationship to bronchial hyperreactivity in patients with persistent allergic rhinitis monosensitized to house dust.

BACKGROUND: Studies about the pathogenesis of bronchial hyperreactivity (BHR) in patients with persistent allergic rhinitis (PAR) and its relationship with lower airway remodeling are extremely limited. OBJECTIVE: This study evaluated bronchial vascular remodeling via the measurement of angiogenic factor, vascular endothelial growth factor-A (VEGF-A), and anti-angiogenic factor, Endostatin, and evaluated their relationship with BHR in patients with PAR. METHODS: The study group consisted of 30 patients with PAR monosensitized to house dust mites and 14 non-allergic healthy controls. All subjects underwent induced sputum and methacholine (M) bronchial provocation tests. VEGF-A and Endostatin levels were measured by ELISA in induced sputum supernatants. RESULTS: The percentages of eosinophils in induced sputum were significantly increased in patients with PAR compared with healthy controls. There were no significant differences between patients with PAR and healthy controls in terms of levels of VEGF (37.9pg/ml, min-max: 5-373pg/ml vs. 24.9, min-max: 8-67pg/ml, p=0.8 respectively), Endostatin (532.5pg/ml, min-max: 150-2125pg/ml vs. 644, min-max: 223-1123pg/ml, p=0.2 respectively) and VEGF/Endostatin ratio (0.057 vs. 0.045, p=0.8 respectively). In addition, there were no significant differences between patients who are BHR positive (n=8), or negative to M (n=22) in terms of levels of VEGF, Endostatin and VEGF/Endostatin ratio and no correlations among value of PD20 to M and levels of VEGF, Endostatin and VEGF/Endostatin ratio. CONCLUSION: We conclude that VEGF-A and Endostatin did not differ between patients with PAR and healthy controls regardless of BHR to M.

Cat and dog sensitization in pet shop workers.

BACKGROUND: Sensitivity and symptoms related to animal proteins have been investigated in various occupational groups. However, data from pet shops are limited. AIMS: To investigate rates of sensitivity to cats and dogs among pet shop workers, to assess the relationship between sensitivity, allergen levels and symptoms and to investigate whether passive transport from pet shops to homes is possible. METHODS: Pet shop workers underwent interviews with a questionnaire adapted from the European Community Respiratory Health Survey. Dust samples for allergen detection were collected from pet shops using a vacuum cleaner. Skin tests were performed with common allergens. Dust samples were also obtained from the houses of 7 workers and 12 control subjects. RESULTS: Fifty-one workers from 20 pet shops were included in the study. Thirteen (25%) workers reported work-related symptoms. Four workers had sensitivity to animal allergens. The mean cat/dog allergen levels from pet shops were 15.7 and 3.2 µg/g, respectively. There was no significant relationship between cat/dog allergen levels and work-related symptoms and sensitivity to pets. None of the dust samples collected from the homes of pet shop workers contained cat allergens. Dog allergen was detected in only one house (0.58 µg/g). Neither cat nor dog allergens were found in the homes of the 12 control subjects. CONCLUSIONS: Although a quarter of pet shop workers reported work-related symptoms, sensitivity to cat and dog was low. These findings suggest that work-related symptoms may be due to other factors than cat and dog sensitivity.

Immediate-type hypersensitivity reactions to proton pump inhibitors: usefulness of skin tests in the diagnosis and assessment of cross-reactivity.

BACKGROUND: Data are limited about the value of skin tests in the diagnosis of proton pump inhibitor (PPI)-induced hypersensitivity reactions and the cross-reactivity between PPIs. We aimed to assess the role of skin testing in the diagnosis of PPI-related immediate hypersensitivity reactions and the cross-reactivity patterns among PPIs. METHODS: The study was designed in a prospective, national, multicentre nature. Sixty-five patients with a suggestive history of a PPI-induced immediate hypersensitivity reaction and 30 control subjects were included. Standardized skin prick and intradermal tests were carried out with a panel of PPIs. Single-blind, placebo-controlled oral provocation tests (OPTs) with the PPIs other than the culprit PPI that displayed negative results in skin tests (n = 61) and diagnostic OPTs with the suspected PPI (n = 12) were performed. RESULTS: The suspected PPIs were lansoprazole (n = 52), esomeprazole (n = 11), pantoprazole (n = 9), rabeprazole (n = 2), and omeprazole (n = 1). The sensitivity, specificity, and negative and positive predictive values of the skin tests with PPIs were 58.8%, 100%, 70.8%, and 100%, respectively. Fifteen of the 31 patients with a hypersensitivity reaction to lansoprazole had a positive OPT or skin test result with at least one of the alternative PPIs (8/52 pantoprazole, 6/52 omeprazole, 5/52 esomeprazole, 3/52 rabeprazole). CONCLUSION: Considering the high specificity, skin testing seems to be a useful method for the diagnosis of immediate-type hypersensitivity reactions to PPIs and for the evaluation of cross-reactivity among PPIs. However, OPT should be performed in case of negativity on skin tests.

Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity?

BACKGROUND: COX-2 inhibitors are safe alternatives in patients with cross-reactive non-steroidal anti-inflammatory drug (NSAID) hypersensitivity. These drugs are recommended to these patients after negative drug provocation tests (DPTs). However, cumulative data on encouraging results about the safety of COX-2 inhibitors in the majority of these patients bring the idea as to whether a DPT is always mandatory for introducing these drugs in all patients with cross-reactive NSAID hypersensitivity. OBJECTIVE: To document the safety of COX-2 inhibitors currently available and to check whether or not any factor predicts a positive response. METHODS: This study included the retrospective analysis of cases with cross-reactive NSAID hypersensitivity who underwent DPTs with COX-2 inhibitors in order to find safe alternatives. DPTs were single-blinded and placebo controlled. RESULTS: The study group consisted of 309 patients. COX-2 inhibitors were well tolerated in the majority of the patients [nimesulide: 91.9%; meloxicam: 90.2%; rofecoxib: 94.9%; and celecoxib: 94.9%)]. Twenty-five patients (30 provocations) reacted to COX-2 inhibitors. None of the factors were found be associated with positive response. CONCLUSION: Our results suggest to follow the traditional DPT method to introduce COX-2 inhibitors for finding safe alternatives in all patients with cross-reactive NSAID hypersensitivity before prescription as uncertainty of any predictive factor for a positive response continues. However, these tests should be performed in hospital settings in which emergency equipment and experienced personnel are available.

Prevalence of aspirin-exacerbated respiratory disease in patients with asthma in Turkey: a cross-sectional survey.

BACKGROUND: There are no country-based data focused on aspirin (ASA)-exacerbated respiratory disease (AERD) in Turkey. OBJECTIVE: To assess the prevalence of AERD in adult patients with asthma. METHODS: A structured questionnaire was administered via face-to-face interview by a specialist in pulmonology/allergy at seven centres across Turkey. RESULTS: A total of 1344 asthma patients (F/M: 1081/263: 80.5%/19.5%, mean age: 45.7 ± 14.2 years) were enrolled. Atopy rate was 47%. Prevalence of allergic rhinitis, chronic rhinosinusitis/rhinitis, and nasal polyposis (NP) were 49%, 69% and 20%, respectively. Of 270 patients with NP, 171 (63.3%) reported previous nasal polypectomy and 40 (25%) had a history of more than three nasal polypectomies. Aspirin hypersensitivity was diagnosed in 180 (13.6%) asthmatic patients, with a reliable history in 145 (80.5%), and oral ASA provocation test in 35 (19.5%) patients. Clinical presentations of ASA hypersensitivity were respiratory in 76% (n=137), respiratory/cutaneous in 15% (n=27), and systemic in 9% (n=16) of the patients. Multivariate analysis indicated that a family history of ASA hypersensitivity (p: 0.001, OR: 3.746, 95% CI: 1.769-7.929), history of chronic rhinosinusitis/rhinitis (p: 0.025, OR: 1.713, 95% CI: 1.069-2.746) and presence of NP (p<0.001, OR: 7.036, 95% CI: 4.831-10.247) were independent predictors for AERD. CONCLUSION: This cross-sectional survey showed that AERD is highly prevalent among adult asthmatics and its prevalence seems to be affected by family history of ASA hypersensitivity, history of rhinosinusitis and presence of NP.

Allergy to hazelnut in adults: a two-step study.

BACKGROUND: Although hazelnut consumption is very high in Turkey, the prevalence of hazelnut allergy is still unknown. This study's objective was to investigate the prevalence of hazelnut sensitisation and to verify its clinical importance using double-blind, placebo-controlled challenge (DBPCFC) in an adult population. METHODS: Prick-to-prick skin tests were performed with fresh hazelnut in 904 patients admitted to the allergy department. Among the 904 subjects, 20 patients with a history of allergic reactions to hazelnut and/or positive skin tests were recalled for further evaluation. Specific IgE was measured in these subjects. Eleven (11/20) patients accepted to undergo DBPCFC with hazelnut. RESULTS: Among the 904 individuals, the history of reactions to hazelnut was positive in 16 subjects (1.8%); prick-to-prick skin tests were positive in 13 (1.4%); prick tests with the commercial product were positive in nine (0.9%); and history plus skin tests were positive in 16 (1.8%). Specific IgE to hazelnut was positive in only three patients. DBPCFC was conducted in 11 subjects with a positivity rate of 63.6% (7/11). We observed six mild and one moderate systemic reactions during the DBPCFC. Among seven subjects with a positive DBPCFC, six (85.7%) had a history of hazelnut allergy, and five (71.4%) had both history and skin test positivity. CONCLUSION: Skin test sensitisation to hazelnut was found to be 1.76% (16/904) which is similar to the sensitisation rate in previous reports. However, DBPCFC was positive in 63% of cases with a history of hazelnut allergy and/or positive skin tests in this study. These results indicate that the presence of history with a positive skin test can be suggestive of hazelnut allergy; however an oral food challenge is needed to confirm the diagnosis.

A breath for health: an exploratory study in severe asthma patients in Turkey.

BACKGROUND: Severe asthma puts enormous burden on patients. To evaluate asthma-related restrictions on patients' daily lives along with their expectations about future asthma care. METHODS: A structured questionnaire was administered to severe asthma patients at 25 centers across Turkey. The patients were divided into; uncontrolled (n: 274) and controlled asthma (n: 177) according to the existence of symptoms despite the GINA step 4 or 5 treatment. RESULTS: A total of 451 patients (F/M: 337/114, mean age: 47.6 +/- 13.2 years) were included; 93% were nonsmokers and 51.2% were atopic. Chronic rhino-sinusitis, ASA/NSAID sensitivity, and osteoporosis were significantly higher in uncontrolled patients. Nearly 70% of the uncontrolled asthmatics defined asthma as disturbing with significant restrictions in daily life. The most important role for medication was symptom relief. One inhaler or one tablet a month was the most preferred form of drug usage. In addition, 30.6% of the patients had tried alternative treatment with herbal remedies. Although patients were willing to become members of an asthma association, they expected the Turkish government to provide special asthma clinics and fund research into new treatments. Controlled patients achieved or were close to achieving asthma control goals. Uncontrolled patients seemed to be more pessimistic in this respect, but they reserved significant levels of hope for the future. Two-thirds of all the patients thought that they would receive better treatment in the next 5 years. CONCLUSIONS: In this study group, severe asthma patients face significant limitations in their daily lives, but they are optimistic about better asthma control and treatment options in the future.

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.

Lipoxin A4 levels in asthma: relation with disease severity and aspirin sensitivity.

BACKGROUND: Lipoxin (LX) A4, an endogenous anti-inflammatory eicosanoid, has been found to be low in patients with severe asthma. However, few studies also suggested more diminished LX A4 levels in aspirin-exacerbated respiratory disease (AERD) when compared with aspirin-tolerant asthma (ATA). It is, therefore, currently not clear whether the asthma severity or the presence of AERD has a primary role in the disturbed LX metabolism. OBJECTIVE: To detect LX A4 and 15-epi-LX A4 levels in asthma patients with and without AERD of comparable severity. METHODS: The study groups consisted of 22 subjects with AERD, 22 subjects with ATA and 10 volunteers without asthma and aspirin sensitivity. Whole-blood samples were stimulated with calcium ionophore, A23187 (5 x 10(-5) m) and A23187 (5 x 10(-5) m)+aspirin (10(-4) m). LX A4 and 15-epi-LX A4 levels were analysed by the enzyme immune assay method. RESULTS: Severe asthma patients in both AERD [0.5 (0.8)] ng/mL and ATA [0.5 (0.45) ng/mL] groups showed diminished generation for LX A4 to stimulation with A23187 in comparison with other severity degrees in their groups (P=0.02 and 0.046, respectively). LX A4 generation in both severe groups was comparable with each other (P>0.05). Although severe cases with AERD showed a diminished capacity to generate 15-epi-LX A4, this did not reach statistical significance. CONCLUSION: This study indicated that diminished LX A4 generation was unique to severe asthma phenotype regardless of comorbid aspirin sensitivity. Clinical Implications Lower LX A4 levels in severe asthma would suggest a possibility for LX analogues as future treatment options in these patients.

Dipyrone improves small airway function in asthmatic patients with moderate obstruction.

BACKGROUND: Dipyrone is an analgesic and antipyretic agent with a distinctive spasmolytic effect on smooth muscles. We recently showed that dipyrone significantly relaxed precontracted tracheal smooth muscle in guinea pig. OBJECTIVE: To investigate whether this in vitro observation could be observed in vivo in the respiratory function parameters of asthma patients. METHOD: Twenty-two patients, aged 18 to 75 years and diagnosed with asthma according to the American Thoracic Society criteria were enrolled at the time they had any indication for dipyrone use. Pulmonary function tests were performed before and 30, 60, 90, and 120 minutes after oral intake of 1 g of dipyrone. The tests were repeated without dipyrone intake in a situation of spontaneous recovery after a minimum washout period of 2 days. RESULTS: Patients were classified according to their baseline forced expiratory volume in 1 second (FEV1) as having mild obstruction (FEV > or =80% predicted) or moderate obstruction (FEV1 60%-80% predicted). Significant improvement with dipyrone was seen in FEV1 and peak expiratory flow rates at 25%, 50% and 75%) of forced vital capacity and in maximum midexpiratory flow rate only in patients with moderate asthma. No significant change was observed on the spontaneous recovery day except in FEV1. CONCLUSION: Dipyrone had a significant effect leading to an improved small airway function in asthmatic patients with moderate airway obstruction, confirming our recent in vitro findings.

Meloxicam-associated anaphylactic reaction.

Anaphylactic reaction to meloxicam has never been reported to date. We report 2 cases of meloxicam-induced anaphylactic reaction with no sensitivity to another selective cyclooxygenase 2 inhibitor. A thorough drug allergy work-up should be done before other cyclooxygenase inhibitors are prescribed.

Rush hymenoptera venom immunotherapy is efficacious and safe.

BACKGROUND: Although rapid venom immunotherapy (VIT) protocols have been shown to be safe and effective, this issue has not yet been clarified in Turkey. OBJECTIVE: The aim of this study was to evaluate the side effects of rush VIT as well as early clinical and immunological responses in patients with a venom allergy. METHODS: Eighteen patients who had a history of severe systemic reactions after Hymenoptera sting were included in the study. The diagnosis was made on the basis of positive skin test reactivity and the presence of specific IgE in serum to either bee or vespid venoms. Fourteen patients underwent an average 7-day rush VIT regimen under careful monitoring in our clinic. Among them 7 patients were treated with Vespula species and 7 with Apis mellifera venom extracts. Four patients were followed up as a control group. Skin test response, specific IgE and IgG4 levels were determined before and after a year of VIT. Local and systemic reactions due to injections were monitored during the induction and maintenance phases of VIT. RESULTS: Specific IgG4 levels significantly increased after 1 year compared with levels before VIT (mean concentration before and after; 13.04 vs 21.85 mg/L, respectively; P < .05) whereas specific IgE levels did not change (11.54 vs. 13.32 kU/L). No significant differences were observed before and after one year of VIT in skin prick (2.34 vs 3.66 mm) and intradermal (0.12-0.11 microg/mL) test reactivities (P > .05). A single patient treated with bee venom developed 4 mild systemic reactions (4/469 injections, 0.85%) during the course of VIT. More local reactions occurred in patients receiving bee venom extract (3.33%) than in those receiving yellow jacket venom (1.33%). Two patients tolerated field stings without reactions. CONCLUSION: Our experience confirms that rush VIT is safe and has a low systemic reaction. It can be considered for patients requiring rapid protection.

The safety of allergen immunotherapy (IT) in Turkey.

Allergen immunotherapy (IT) has encouraging therapeutic outcomes but its safety is still being questioned because of possible severe systemic reactions. The aim of this study was to determine the frequency of systemic reactions (SR), and to identify their correlation with the characteristics of therapy, such as allergen composition and IT schedule, and diagnosis. We analyzed the data of 126 patients who received IT between 2000-2003, and suffered from respiratory allergy or hymenoptera venom anaphylaxis. IT was given by rush, clustered or conventional schedules. The standardized allergen extracts used were grass pollen, house dust mite and hymenoptera venom in 88, 18 and 20 patients, respectively. None of the patients received premedication. A total 4705 injections were administered. One hundred and twenty-three adverse events (AE) (2.6% per injection) were documented in 46 patients. Sixty-one of them were SRs (1.3% SRs per injection) and they were seen in 28 patients. Asthmatics had more tendency to SRs (p=0.05). Rush (1.8%) and clustered (2.8%) IT protocols were associated with a higher rate of SRs (per injection) when compared to conventional schedule (0.9%) (rush vs conventional; p=0.013, clustered vs conventional; p=0.001). The majority of SRs corresponded to grade 3 (49%). Forty-nine (80%) of the 61 SRs were observed during the build-up phase, and mostly with pollen extracts (75.5%). Patients showed more severe SRs during the build-up phase (p<0.05). Twenty-six (42.6%) of the SRs were immediate, whereas 35 (57.4%) SRs appeared within 2 hours. Delayed SRs were significantly more frequent in polysensitized patients when compared to monosensitized subjects (p=0.018). Our data indicate that rapid IT regimens and the presence of asthma represent a greater risk for SR development. Since the late SRs occur as frequently as the early ones, we suggest a longer waiting period beyond 30 minutes, especially in polysensitized and asthmatic patients.

Differences between asthma and COPD in the elderly.

Asthma and chronic obstructive pulmonary disease (COPD) are both characterized by the presence of airflow obstruction. Both diseases are not rare in the elderly population. Distinguishing between these diseases is difficult and may be impossible in some older patients. The aim of the study was to investigate clinical and functional characteristics and the presence of atopic status in elderly subjects compared to COPD patients. Fifty-one patients over 60 years of age were selected for the study (27 patients with late-onset asthma, 24 patients with COPD). Atopy was defined by skin prick test and serum total IgE concentrations which were measured in all patients. Pulmonary function tests including airflow rates, lung volumes, airway resistance, diffusing capacity, and arterial blood gases analysis were performed in all patients. The rate of skin prick test positivity in asthmatics was significantly higher than that of the COPD patients. FEV1 was lower in COPD patients than in asthmatic patients. Bronchial reversibility in asthmatics became significantly higher than in COPD patients. While FRC and RV were increased in both groups showing same degree of pulmonary hyperinflation, patients with COPD demonstrated significantly decreased DLCO when compared to asthmatic patients. The level of both PO2 and PCO2 in patients with COPD significantly differed from asthmatics. In conclusion, a history of heavy smoking, decreased diffusing capacity for carbon monoxide, the presence of more prominent lung hyperinflation and chronic hypoxemia favour the diagnosis of COPD, whereas atopy and significant bronchodilator responsiveness favour the diagnosis of asthma.

Rofecoxib, as a safe alternative for acetyl salicylic acid/nonsteroidal anti-inflammatory drug-intolerant patients.

BACKGROUND: Intolerance to acetylsalicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) is a crucial problem in medical practice. There is therefore a need for safer NSAIDs in analgesic-intolerant patients. OBJECTIVE: To assess the safety of rofecoxib, a selective COX-2 inhibitor, in ASA/NSAID-intolerant patients. METHODS: A single blind, placebo-controlled oral challenge procedure was applied to 94 adult patients (M/F: 30/64, mean age: 39.2 +/- 11.9 yrs) with a reliable history of ASA/NSAID intolerance. 1/4 and 3/4 divided doses of placebo and rofecoxib were given with 2-hour intervals on consecutive days. During the challenge procedure, blood pressure, heart rate, nasoocular, pulmonary and cutaneous symptoms were monitored. Erythema, pruritus accompanied by erythema, urticaria/angioedema, rhinorrea, nasal obstruction, sneezing, dyspnea or cough associated with a decrease of at least 20% in the FEV1, and hypotension were considered as positive reactions. RESULTS: None of the patients reacted to placebo. Only one patient (1.1%) presented urticarial-type cutaneous reaction to rofecoxib challenge. The remaining patients (98.9%) perfectly tolerated the drug challenge. CONCLUSION: Rofecoxib can be used as a safe alternative drug for ASA/NSAID intolerant patients.

The effect of montelukast on eosinophil apoptosis: induced sputum findings of patients with mild persistent asthma.

BACKGROUND: Apoptosis may be important in limiting airway eosinophilia. Treatment with leukotriene antagonists decreases the number of eosinophils in both peripheral blood and sputum. AIM: To assess the effect of montelukast on eosinophil apoptosis in a group of patients with mild persistent asthma (MPA) and to compare this effect with the apoptotic effect of fluticasone propionate (FP). METHODS: Randomly selected patients with MPA (n = 22) who had not taken anti-inflammatory therapy within the preceding 12 months were included in the study. The sputum induction procedure was performed and the patients were divided into two groups: group 1 (n = 10) received FP 250 microg/day and group 2 (n = 22) received montelukast 10 mg/day orally for 4 weeks. Sputum induction was repeated after the treatment period. The resulting cytospin slides were stained by Wright's stain and morphologic changes in apoptotic eosinophils were assessed by the use of light microscopy by two blinded expert pathologists. Serum soluble Fas ligand (sFasL) concentrations were measured by an ELISA method at baseline and after treatment in both groups, as well as in a group of healthy subjects. RESULTS: In within-group comparisons, the apoptotic ratio (AR) increased at the end of the study period in group 1 (p = 0.05). In the group treated with FP the ratio of sputum eosinophils significantly decreased (p = 0.02), and the AR significantly increased (p < 0.005). No differences were found in the two study groups in serum sFasL levels at the end of the treatment period compared with baseline values (p > 0.05). CONCLUSION: Our findings demonstrate that 4 weeks' treatment with a CysLT receptor antagonist (montelukast) resulted in an increase in eosinophil apoptosis comparable to that produced by FP, suggesting that induction of apoptosis may be a potential mechanism for the mode of action of CysLT receptor antagonists in asthma.

Airway inflammation in nasal polyposis: immunopathological aspects of relation to asthma.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disorder of the upper respiratory tract, which is often coexist with asthma. However, the pathogenesis of especially in patients with NP is still a matter of debate. OBJECTIVE: To better understand the immunopathologic mechanism involved in this relationship, we investigated the inflammatory cell profiles in bronchial and nasal tissues of patients with NP alone and with concomitant asthma. METHODS: Seventeen patients with NP (six male, 11 female, age range: 19-63, mean age: 38.29+/-13.27 years) were selected for the study. Subjects were divided into two groups based on the presence of asthma or bronchial hyper-responsiveness (BHR). NP without BHR (Group 1) (n=8), NP and asthma or BHR (Group 2) (n=9). All patients underwent atopy evaluation including detailed history, skin prick test (SPT), total and specific IgE determination in sera. None of the subjects had taken inhaled, nasal or oral corticosteroids for at least 1 month before the study. Respiratory symptoms of asthmatic patients were controlled with only short acting beta(2)-agonist inhaler drugs as needed. NP tissue, nasal and bronchial mucosa biopsies were taken from all patients using fiberoptic endoscopy. CD3, CD8, CD16, CD68, AA1 (mast cell tryptase), human leucocyte antigen-DR (HLA-DR) and eosinophil peroxidase (EPO) expressing cells in specimens were determined by immunohistochemical methods. Positively staining inflammatory cell types were counted. Subepithelial lamina propria and periglandular areas were separately evaluated. RESULTS: No significant difference was found in polyp tissue, nasal and bronchial CD3(+), CD8(+), CD16(+), CD68(+), AA1(+), HLA-DR(+) and EPO(+) positive cells between groups. There were significantly higher numbers of CD8(+), CD16(+), HLA-DR(+), EPO(+) cells in the polyp tissue and nasal mucosa vs. the bronchial mucosa in all groups (P<0.05). However, CD8(+) cells were significantly increased in the polyp tissue and bronchial mucosa of patients with NP alone when compared with the patients with both asthma and NP (P<0.05). CD3(+), CD68(+) and CD16(+) cell counts were tended to be higher within the nasal polyp tissue of patients with isolated NP compared with counts within nasal and bronchial mucosa of patients with NP and asthma. Also, patients with isolated NP showed more HLA-DR(+) cells in the nasal polyp tissue and nasal mucosa than those of patients with NP and asthma. Immunoreactivity for EPO(+) eosinophils within the nasal and bronchial mucosa was more prominent in patients with NP and asthma compared with patients with NP alone. The number of EPO(+) eosinophils within the polyp tissue, nasal and bronchial mucosa was higher in the skin prick test negative (SPT -ve) group than the SPT positive (SPT +ve) ones. CONCLUSIONS: Our results demonstrate that infiltration of inflammatory cells in the nasal and the lower airways do not remarkably differ between patients with NP alone who has no evidence of BHR and asthmatic patients with NP. However, patients with SPT-ve NP reveal more intense eosinophilic inflammation in the entire respiratory mucosa.