Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in adults: Beyond current classification.

BACKGROUND: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting. METHODS: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines. RESULTS: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs. CONCLUSIONS: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

Validity and Reliability of the Assessment Tool for Asthma (ATA) Questionnaire: the ATA Study.

OBJECTIVES: A multicenter trial was designed to validate the "Assessment Tools for Asthma (ATA)" questionnaire, a newly developed questionnaire, which evaluates both asthma control and risk factors associated with asthma control with a single instrument. MATERIALS AND METHODS: This cross-sectional study involved 810 cases from 14 clinics in 9 Turkish cities. The ATA questionnaire and Asthma Control Test (ACT) were administered. The Visual Analog Scale (VAS) was used to evaluate the control status of 100 randomized cases. ATA is an eight-item physician-administered questionnaire. It comprises the following two sections-ATA1, assesses symptomatic control criteria, and the remaining section, queries the flare-up of asthma, control of comorbidities, treatment adherence, and inhaler technique. RESULTS: The mean scores for ATA1, ATA total, VAS, and ACT were 24.7±14.8, 53.8±19, 7.1±3, and 18.8±5.5, respectively. According to the ATA questionnaire, among all patients, 34.3% had controlled, 18.8% had partly controlled, and 46.9% had uncontrolled asthma. Furthermore, 16.6% patients had flare-ups between visits, 96.4% patients had uncontrolled comorbidity, 17% patients had irregular asthma treatment, and only 8.4% patients used the incorrect inhaler technique. The ATA questionnaire showed internal consistency (Cronbach's alpha coefficient=0.683). ACT, ATA1, and two specialists' evaluations using VAS correlated strongly with the ATA total scores (Spearman correlation coefficient (r) values: 0.776, 0.783, and 0.909, respectively; p-values: p<0.001, p<0.001, and p<0.001, respectively). According to Receiver Operating Characteristic analysis, the cut-off value of ATA was 50 (sensitivity=84.4%, specificity=82.40%). CONCLUSION: The validated ATA questionnaire may be a practical tool for physicians in asthma management.

Demographic, Clinical and Management Characteristics of Newly Diagnosed COPD Patients in Turkey: A Real-Life Study.

Purpose: In order to determine the clinical and sociodemographic characteristics of newly diagnosed treatment-naïve asthma and COPD patients in Turkey, a multicenter study in 2012 was initiated . We aimed to investigate the characteristics and therapies of COPD patients in the original study in more detail. Patients and Methods: This nation-wide, multicentric, non-interventional, prospective, real-life observational cohort study was conducted in 122 centers. The newly diagnosed patients were not receiving any treatment before the recruitment. Their general characteristics, the combined GOLD 2011 COPD categories and exacerbation histories were noted. The patients were followed up with 3 voluntary visits for 1 year. Their adherence to the inhaled treatment according to GOLD 2011 was evaluated during follow-up visits. Results: The study included 776 COPD patients. Their mean age was 59.4±9.1 years, and 11.9% of the patients were female. 35.1% of the patients were in the GOLD 2011 C and D category. 12.6% are frequent exacerbators, and 52.8% had at least one comorbid condition. 71.8% overtreatment rate was detected. Their attendance rates for three follow-up visits became 55.9%, 32.9% and 18.7%, respectively. The adherence rate to the treatment was measured as 81.9%. Conclusion: Although these patients were diagnosed for the first time, the GOLD C and D categories and frequent exacerbator phenotype were found at a high rate. They were usually prescribed an overtreatment regimen. We think that newly diagnosed COPD patients should be evaluated carefully, and best effort should be made to treat these patients in accordance with the recommendations of the major COPD guidelines.

Asthma control and adherence in newly diagnosed young and elderly adult patients with asthma in Turkey.

OBJECTIVE: This study aimed to evaluate the factors that affect asthma control and adherence to treatment in newly diagnosed elderly asthmatics in Turkey compared with younger patients. METHODS: This real-life prospective observational cohort study was conducted at 136 centers. A web-based questionnaire was administered to the patients who were followed up for 12 months. RESULTS: Analysis included 1037 young adult asthma patients (age <65 years) and 79 elderly asthma patients (age ≥65 years). The percentage of patients with total control in the elderly and young groups were 33.9% and 37.1% at visit 1, 20.0% and 42.1% (p = 0.012) at visit 2, and 50.0% and 49.8% at visit 3, respectively. Adherence to treatment was similar for both groups. Visit compliance was better in the elderly group than in the young group at visit 1 (72.2% vs. 60.8%, p = 0.045), visit 2 (51.9% vs. 34.9%, p = 0.002), and visit 3 (32.9% vs. 19.4%, p = 0.004). Adherence to treatment increased with asthma control in both groups (both p < 0.001) but decreased with the presence of gastritis/ulcer, gastroesophageal reflux, and coronary artery disease in the elderly. CONCLUSIONS: Asthma control and adherence to treatment were similar for the elderly and young asthma patients, though the follow-up rate was lower in young patients. The presence of gastritis/ulcer, gastroesophageal reflux and coronary artery disease had negative impacts on the adherence to treatment in elderly adult patients.

Real life profile of asthma and chronic obstructive pulmonary disease patients in Turkey.

INTRODUCTION: Despite the presentation of similar symptoms, the airway diseases have different underlying pathophysiological processes and must be distinguished to enable the administration of appropriate treatment. In several studies the clinician- and patient-related causes of poor compliance to treatment in asthma/chronic obstructive pulmonary disease (COPD) patients have been evaluated. This study aimed to determine the clinical and sociodemographic characteristics of newly diagnosed treatment-naïve asthma and COPD patients in Turkey. MATERIALS AND METHODS: This national, multicentre, prospective, observational study was conducted in 122 centres. A questionnaire including items related to demographic, clinical, laboratory parameters was applied. All patients were intended to be followed-up for 12 months. RESULT: 1892 adult patients (1116 asthma and 776 COPD) from 122 centres were enrolled. Overall 95%, 86% and 65% of intermittent, mild persistent and moderate persistent asthma patients were over-treated. Among COPD patients, the percentages of over-treated patients were 66%, 79% and 82% for those with GOLD stage A, B and C. Physicians' adherence to guidelines was appropriate in 93% of severe persistent asthma patients and 89% of GOLD stage D COPD patients. Among patients with high compliance to treatment, proportion of asthma patients with total control was 44% and that of COPD patients at GOLD stage A was 41%. In consecutive two visits, this figure increased to 52% and 63% in asthma patients and 54% and 50% in COPD patients. CONCLUSIONS: The main findings are: (a) patients are frequently over-treated and (b) patients do not adhere to visits as expected, in both asthma and COPD.

Tiotropium may improve asthma symptoms and lung function in asthmatic patients with irreversible airway obstruction: the real-life data.

BACKGROUND AND AIMS: Some patients with asthma have poorly controlled disease despite the use of high-dose inhaled corticosteroids (ICS), long-acting ß2 agonists (LABAs) and antileukotrienes. The aim of the study was to assess the effectiveness of tiotropium as an add-on therapy to the standard treatment with high-dose ICS/LABA on asthma control and lung function in patients with severe asthma. METHODS: Of the 633 asthmatic patients, 64 (10.1%) patients with severe asthma who were add-on treated at least for 3 months were evaluated. Number of exacerbations, emergency department visits, hospitalizations and lung functions of patients belonging to 12 months before starting add-on treatment were compared with those of 12 months after starting add-on treatment. RESULTS: The mean duration of add-on tiotropium treatment was 8.3 ± 0.5 months. For patients with severe asthma that was poorly controlled with standard combination therapy, tiotropium improved asthma control in 42.2%, decreased the number of emergency department visits in 46.9% and decreased the number of hospitalizations in 50.0% of them. The mean baseline forced expiratory volume in 1 s before add-on tiotropium was 57.5 ± 1.9% and forced vital capacity was 74.3 ± 15.6%. However, after 12 months of add-on tiotropium treatment, these rates became 65.5 ± 1.9% and 82.5 ± 15.1%, respectively. The addition of tiotropium significantly improved the percentages of the number of emergency department visits, the number of hospitalizations (P < 0.05). CONCLUSION: Our study has suggested that, for patients with poorly controlled asthma despite of the use of ICS/LABA, the addition of tiotropium to standard care may be beneficial.

The frequency of chronic rhinosinusitis/nasal polyp in COPD and its effect on the severity of COPD.

This study aimed to investigate the effect of chronic rhinosinusitis/nasal polyposis on the severity of COPD and to find out whether the 'united airway disease' hypothesis is valid for COPD. The study enrolled 90 patients diagnosed and staged according to criteria of an international guideline for diagnosis and management of COPD. The patients in stages I and II were classified as Group 1 and the patients in stages III and IV as Group 2. All the patients were questioned about the presence of major and minor criteria of sinusitis, underwent paranasal sinus computed tomography (PNS-CT) scans, and answered a questionnaire based on a quality of life test for sinusitis (SNOT-20). Sinusitis was present in 48 (53%) patients according to criteria of major and minor symptoms, and in 58 (64%) patients according to Lund-Mackay scoring system of PNS-CT. There was no significant difference in CT score between Group 1 and Group 2 (2.3 +/- 0.5 vs. 2.1 +/- 0.4, p > 0.05). However, the frequency of minor symptoms was greater in Group 2. SNOT-20 score was significantly higher in Group 2 than in Group 1 (28.7 +/- 1.7 and 22.2 +/- 1.9, respectively, p = 0.014). A significant correlation was determined between Lund-Mackay and SNOT-20 scores. The presence of CRS should be assessed in COPD patients, especially in those with severe disease. Further research is needed to disclose possible common immunopathological mechanisms in the pathogeneses of COPD and CRS.

Leukotriene receptor antagonists: a good choice in the treatment of premenstrual asthma?

The aim of this study was to investigate the effects of leukotriene receptor antagonists (LTRAs) on the premenstrual exacerbation of asthma (PMA). Twenty-four female patients with mild asthma were enrolled in the study. Patients were followed for three menstrual cycles and separated into two groups based on whether they exhibit premenstrual worsening of asthma symptoms (n = 11) or not (n = 13). During the first month all were treated with only inhaled steroids (IS) (run-in period); during the second month they received IS plus placebo; and during the third month they were given IS plus montelukast. Furthermore, they were advised to use beta(2)-agonists as needed. Peak expiratory flow rate (PEFR) and symptom scores were recorded during the 3 months. Pulmonary function tests (PFT) and the levels of oestrogen, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured a week before the beginning of the menstrual period. At the end of the 3-month period, it was observed that following therapy with montelukast, the patients with PMA showed significant improvement in PEFR variability and symptom scores when compared with the placebo group. Baseline FSH levels were higher, but FSH and other hormone levels and PFTs did not change in these groups. However, in the group without PMA there was no difference between the montelukast or placebo groups in PEFR variability, symptom scores, PFTs, and hormone levels. Based on the data in hand, it could be stated that LTRAs have ensured the control of symptoms and improved PEFR variability in patients with PMA by suppressing inflammation. We are of the view that LTRAs would be a right choice in the treatment of patients with PMA.

Psychological status of patients with chronic urticaria.

Although chronic urticaria is the most common cutaneous disorder seen in our outpatient allergy clinics, to our knowledge, no study of psychiatric morbidity in allergy departments has been carried out in our country. For the present study, we used the Minnesota Multiphasic Personality Inventory (MMPI) to evaluate the personality traits and psychological status of patients with chronic idiopathic urticaria (CIU). Fifty-nine outpatients with CIU and 59 healthy control subjects were enrolled in the study. Patients were included if no specific cause for their urticaria could be identified by detailed history and appropriate investigations. Psychiatric evaluation for all patients and controls was conducted at the Department of Psychiatry by using MMPI. Analysis of the MMPI profile showed that the scores for hypochondriasis, depression, hysteria, psychopathic deviance, paranoia, psychasthenia, schizophrenia, and social introversion were higher in patients with CIU compared to the control group (P < 0.05). The mean score of hysteria was significantly higher in women. There were no significant correlations between the scores of MMPI and duration of the disease. These data indicate that our patients with CIU seem to have more depressive, hysteric, touchy and suspicious personality traits with hypochondriac tendencies and in more conflict with their social environment. Attitudes such as perfectionism, need for approval, external control and need to be loved were also characteristics of the patient group. We believe that psychological status should be considered for effective management of patients with CIU.

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, 1/4 and 3/4 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.

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.

Direct cost assessments in subjects with seasonal allergic rhinitis living in Ankara, Turkey.

The characteristics of seasonal allergic rhinitis (SAR) including the severity at initial presentation and cost estimates are not established for Turkey. The aim of this study was to document the clinical features and direct cost of subjects with SAR when diagnosed and followed according to international treatment guidelines and to determine the effectiveness of treatment in relation to the regional pollen count in our country. The clinical features of SAR were determined cross-sectionally in 175 patients living in Ankara, Turkey. The direct medical cost analysis obtained by a symptom-medication score method was performed prospectively in a subgroup of patients evaluated at the beginning of the pollen season (n = 37). Airborne Gramineae pollen grains were counted also in the same period. SAR was mild in 12.6% of cases, moderate in 51.4% of cases, and severe in 36% of cases. Regional pollen counts were correlated with the number of patient visits and the initial severity of SAR. Mean cost of SAR per person without a comorbid disorder during a Gramineae pollen season for Ankara was 79.0 +/- 3.3 dollars, where it reached a mean of 138.60 +/- 0.5 dollars in the presence of asthma and/or conjunctivitis. No difference was observed among disease severity groups by means of total direct cost (p > 0.05). Regional pollen counts influence the initial severity of SAR in our country. Appropriate treatment seemed to induce effective symptom control. Hence, education of both public and primary care physicians about the international guidelines might provide better cost-effective management of SAR.

Direct medical cost of asthma in Ankara, Turkey.

BACKGROUND: There has been no documented data regarding the cost of asthma in our country. OBJECTIVE: In this 1-year prospective study, we aimed to determine the annual cost of asthma in Ankara, Turkey. METHODS: Direct medical cost analysis was performed in 118 patients. RESULTS: Mean annual direct medical costs of asthma were USD 1,465.7 +/- 111.8 per capita. Medication cost comprised the majority (81%) of the total direct cost. Mean direct medical costs according to the stage of disease were USD 172.5 +/- 51.7, 860.7 +/- 70.2, 1,671.6 +/- 141.8 and 3,491.9 +/- 417.6 for stage 1 (n = 4), 2 (n = 54), 3 (n = 46) and 4 (n = 14) patients, respectively. CONCLUSIONS: In this first study to document the cost of asthma for our region, direct cost of asthma was found to be increased with the severity of the illness. Considering the fact that medication cost comprises the major fraction of the direct cost, cost-effectiveness trials to determine the effective treatment with optimal cost for different asthma stages should be the next step.