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.

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 (AU)

Evaluation of Interleukin-6, Leukotriene B-4, and Nitric Oxide Levels in Exhaled Breath Condensate of Asymptomatic Obese Individuals: Are Obese Patients Under Risk of Developing Asthma?

OBJECTIVE: If systemic inflammation in relation with obesity causes asthma, the detection of increased airway inflammation among obese individuals who do not have any respiratory symptoms can be also beneficial in indentifying obese patients who are at risk of developing asthma. The aim of this study was to evaluate the systemic and airway inflammation of asymptomatic obese and non-obese individuals. MATERIALS AND METHODS: Obese and non-obese individuals with no respiratory symptoms were included. Inflammatory biomarkers such as C-reactive protein (CRP), exhaled breath condensate (EBC) interleukin-6 (IL-6), EBC leukotriene B-4 (LTB-4), and EBC nitric oxide (NO) levels of obese and non-obese individuals were determined. RESULTS: Forty-five obese individuals (body mass index [BMI]≥30) and 31 non-obese individuals (BMI≤25) as a control group were included in this study. The mean age of the obese group (38.7±11.4 years) was significantly higher than the one of the non-obese group (29.5±8.6 years; p<0.001). There was no significant relationship between gender and BMI (χ2 =1.471, p=0.225). CRP levels were significantly higher in the obese group (6.94±8.28) than the non-obese group (3.29±0.39; p<0.001). The levels of EBC IL-6 in obese and non-obese group were found as 22.61±12.53 and 21.08±14.39, respectively (p=0.624). There was no significant difference between EBC NO levels of the obese group and non-obese group (24.35±10.9 vs. 21.56±7.83; p=0.226). No significant difference was found between the EBC LTB-4 level in the obese group and the non-obese group (36.39±89.82 vs. 16.64±17.45; p=0.231). CONCLUSION: Increased systemic inflammation in obese individuals who had no respiratory symptoms might indicate the tendency of asthma. However, airway inflammation was not significantly different between groups. Therefore the relationship between obesity and asthma should be investigated in future large-scale studies determining the direct effects of adipokines on airways.

Pulmonary involvement in ankylosing spondylitis assessed by multidetector computed tomography.

BACKGROUND: Ankylosing spondylitis (AS) may present with extra-articular involvement in the lungs. We aimed to evaluate the abnormal pulmonary multidetector computed tomography findings of patients with AS and compare them with the clinical symptoms, duration of illness, laboratory results and pulmonary function tests (PFT). MATERIAL/METHODS: We evaluated the chest multidetector computed tomography (MDCT) findings of 41 patients with ankylosing spondylitis (AS) and compared them with pulmonary function test (PFT) results, demographic characteristics, duration of illness and laboratory findings that we were able to obtain. RESULTS: The most common abnormalities were nodules, peribronchial thickening, pleural thickening and bronchiectasis. Abnormalities occurred in 96.87% of patients in the early AS group and 77.8% of patients in the late AS group. Patients with early AS included asymptomatic individuals with normal PFT results and abnormal MDCT findings. CONCLUSIONS: The use of MDCT in AS patients may be beneficial for the evaluation of pulmonary disease, even in asymptomatic patients without any PFT abnormalities and those in the early stages of the disease.

Use of nasal inspiratory flow rates in the measurement of aspirin-induced respiratory reactions.

BACKGROUND: Nasal ketorolac challenge with modified oral aspirin challenge is a safe and effective alternative for desensitizing patients with aspirin-exacerbated respiratory disease. In addition to clinical judgment, objective tests assessing nasal flow may help in diagnosing nasal reactions. OBJECTIVE: To evaluate the feasibility of peak nasal inspiratory flow (PNIF) as an objective measurement in the assessment of a reaction to nasal ketorolac and to determine changes in PNIF that have adequate sensitivity and specificity. METHODS: One hundred fifty-one patients referred to the Scripps Clinic for aspirin challenge and desensitization and 14 healthy controls participated in the study. Percentages of decrease in PNIF during reactions were compared with the nonreactors' measurements. A receiver operating characteristic curve was constructed to assess the diagnostic performance of PNIF measurement during a clinically positive nasal challenge. RESULTS: A total of 165 subjects participated in the study. One hundred fourteen patients (69.1%) clinically reacted to the nasal ketorolac challenge. There was no statistical difference between nasal reactors and nonreactors regarding sex, baseline forced expiratory volume in 1 second, and use of systemic steroid before challenge. The mean percentage of decrease in PNIF was significantly higher in the reactor group (-0.30 ± 0.29 vs -0.07 ± 0.16, P < .001). A cutoff value of 25% decrease in PNIF had the maximum sensitivity and specificity (56.1% and 94.1%). CONCLUSION: The high specificity of a 25% decrease in PNIF found in receiver operating characteristic curve analysis indicated that PNIF measurements can be useful for assessing nasal reactions during nasal ketorolac challenges in the diagnosis of aspirin-exacerbated respiratory disease.

Cysteinyl leukotrienes in exhaled breath condensate of smoking asthmatics.

BACKGROUND: Cysteinyl leukotrienes (CysLTs) are among important inflammatory mediators in asthma pathogenesis. In this study, we aimed to determine leukotriene D4 (LTD4) and leukotriene E4 (LTE4) levels in exhaled breath condensate (EBC) in asthmatics and to evaluate the effect of smoking upon CysLTs levels and to speculate the importance of adding leukotriene receptor antagonists in smoking asthmatics. METHODS: A total of 88 participants were included in the study. Of them, 59 were asthmatics; 30 of the 59 asthmatics were smokers (Group I) and the others were non-smokers (Group II). As a control group (Group III), 29 healthy non-smokers were enrolled. EBC samples were collected (EcoScreen, Jaeger, Hoechberg, Germany) and pulmonary function tests (PFTs) were performed in each case, and an asthma control questionnaire (ACQ) was completed by the asthmatics. LTD4 and LTE4 levels in EBC samples were analyzed by using ELISA. RESULTS: LTD4 levels were found to be higher in Group I than other groups and similar in Group II and Group III. LTE4 levels were lower in Group III than other groups and similar in Group I and Group II. PFTs were different between Group I and Group III and there was a significant negative correlation between LTE4 levels and forced expiratory volume in one second and forced vital capacity ratio in Group I. CONCLUSIONS: LTD4, but not LTE4, concentrations in EBC were higher in asthmatic smokers than asthmatic nonsmokers. LTE4 concentrations in EBC were higher in asthmatics than healthy non-smokers. In smoking asthmatics usage of agents that block the effects of LTD4 can be beneficial; however, new clinical studies are required.

Procalcitonin: Is it a predictor of noninvasive positive pressure ventilation necessity in acute chronic obstructive pulmonary disease exacerbation?

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AeCOPD) are important causes of morbidity and mortality. In this study, we analyzed procalcitonin (PCT) levels in AeCOPD and stable period of COPD in order to evaluate usage of PCT in the prediction of the severity of AeCOPD, and its value on the planing of noninvasive positive pressure ventilation (NPPV). MATERIALS AND METHODS: In this cross sectional study (2009-2010) 118 COPD patients were enrolled, 68 of them (58%) were in acute exacerbations (case group). The others had stabile COPD and they were defined as control group. RESULTS: In case group the mean levels of PCT (0.19 ± 0.02) C-Reactive Protein (44.7 ± 5.92), erythrocyte sedimentation rate (28.4 ± 2.65), white blood cell (9.4 ± 0.43) and %neutrophils (69.9 ± 1.22) were significantly higher than controls (P = 0.0001). There was no difference between PCT levels based on stages of COPD. There were significiant differences in mean PCT levels according to type and severity of AeCOPD. Mean PCT level in hospitalized patients receiving NPPV was 0.36 ng/ml, while it was 0.15 ng/ml for those treated without NPPV (P = 0.0001). PCT cut-off value for NPPV indication was determined to be 0.10 ng/ml. CONCLUSIONS: PCT levels were found to be higher in AeCOPD patients than in stable COPD patients, as expected. Also mean PCT levels increased especially in cases with severe AeCOPD and those receiving NPPV among them. In the present study, we determined a cut off value of PCT as 0.10 ng/ml as a predictor of necessity of NPPV in AeCOPD.

Oxidative stress levels in exhaled breath condensate associated with COPD and smoking.

BACKGROUND: COPD is characterized by chronic air-flow limitation. Smoking is the most important factor in the pathogenesis of COPD. Smoking is associated with increased oxidative stress in the lungs. In this study our aim was to evaluate the differences in the burden of oxidative stress in patients with COPD, smokers, and non-smokers by measuring hydrogen peroxide (H(2)O(2)), malondialdehyde (MDA), and 8-isoprostane levels in the exhaled breath condensate (EBC) samples. METHODS: Eighty subjects were included in the study. Group I (no. = 25) had COPD, Group II (no. = 26) was smokers, and Group III (no. = 29) was nonsmokers. The severity of the COPD and dyspnea was assessed according to the results of pulmonary function tests (PFTs) and Medical Research Council (MRC) scale. RESULTS: The mean age of the subjects was 58 ± 8.9 years. While 8-isoprostane and H(2)O(2) levels were significantly higher in subjects with COPD (44.8 ± 40.2 pg/mL and 1.9 ± 0.8 µmol/L) and smokers (41.3 ± 26 pg/mL and 1.7 ± 0.7 µmol/L) than non-smokers (15.8 ± 6.9 pg/mL and 0.8 ± 0.4 µmol/L), levels were similar between smokers and COPD subjects. MDA levels were similar between the 3 groups (P = .31). There was no correlation between 8-isoprostane and H(2)O(2) levels and PFT parameters. There was a significant positive correlation between dyspnea grade on the MRC scale and 8-isoprostane levels (r = 0.805, P < .001). CONCLUSIONS: Even if respiratory function tests are within normal limits, oxidant burden in lungs of smokers is equivalent to that in COPD patients. 8-isoprostane could be useful in assessing symptom severity and health status of COPD patients.

The effects of antidepressants on the results of skin prick tests used in the diagnosis of allergic diseases.

BACKGROUND: Some drugs may cause false negative results by suppressing the reactivity of the skin prick tests (SPTs). The aim of this survey was to show whether escitalopram, fluoxetine and sertraline had any effect on the reactivity of SPT. METHODS: Twenty-four patients who were admitted to the outpatient clinic of the Psychiatry Department at the Hacettepe University Hospital and planned to be treated by these antidepressants were included in the study between May and October 2008. SPTs with positive control (histamine), negative control and 3 common aeroallergens were performed in the beginning, at the first and fourth weeks. A questionnaire including 26 questions about respiratory symptoms and allergic diseases was filled in face to face by the fellow-in-training. The Visual Analog Scale (VAS) of current respiratory and nasal symptoms was recorded at all 3 visits. RESULTS: There were no statistically significant differences between the 3 mean diameters measured at 3 time points in addition to the mean diameters of the wheals between groups using escitalopram, sertraline and fluoxetine (p > 0.05). There was a statistically significant decrease between the VAS of nasal symptoms at the 3 visits (p < 0.05). CONCLUSIONS: Escitalopram, fluoxetine and sertraline do not seem to affect the reactivity of SPTs. Nasal symptoms might have been decreased due to both the allergic treatment suggested and the end of the pollen season.

Asthma and allergic diseases in school children from 1992 to 2007 with incidence data.

BACKGROUND: Information about change in the prevalence of asthma and allergic diseases and factors related with these diseases would be beneficial in decreasing the burden of these diseases. OBJECTIVE: To assess (i) change in prevalence of asthma and allergic diseases; (ii) factors associated with asthma and wheeze; and (iii) incidence of asthma and wheeze. METHODS: A questionnaire was administered to children aged 7-12 years in first five grades in the same primary school in 1992 (n: 1036), 1997 (n: 738), 2002 (n: 621), and 2007 (n: 422) and filled by the parents. A second survey in 2007 (n: 474, in eight grades) was conducted in the same schoolchildren, 6 months apart, to assess the incidence of asthma and wheeze and the associated factors. RESULTS: Comparison of 1992, 1997, 2002, and 2007 surveys revealed that prevalence of asthma (8.3%, 9.8%, 6.4%, 3.3%, respectively), wheeze (11.9%, 13.3%, 6.4%, 3.1%, respectively), hay fever (15.4%, 14.1%, 7.2%, 3.1%, respectively), and eczema (4.0%, 4.3%, 1.8%, 1.2%, respectively) were significantly lower in 2002 and 2007 compared with that in 1992. Percentage of passive smoking decreased after 1992 (74.0%, 64.0%, 64.1%, and 65.5%, respectively). Incidence of asthma and wheeze in 2007 surveys were 0.9/100 and 1.1/100, respectively. After the adjustment for age and gender, infection in the past, family atopy, and presence of atopic disease (eczema or hay fever) were associated with asthma and wheeze. Maternal smoking and lack of breast feeding were associated with asthma. Male gender, pet ownership in the past, lack of health insurance coverage, snoring, and wood or coal used as fuel were associated with wheeze. CONCLUSIONS: Decreased prevalence of asthma and allergic diseases in the last 10 years could be related to decreased rate of passive smoking. Lower socioeconomic status and lack of breast feeding could increase the risk of asthma in children.

[The relation between nitric oxide levels in exhaled breath condensate and asthma control questionnaires in asthma patients]. / Astimli olgularda yogunlastirilmis soluk havasinda nitrik oksit seviyeleri ile astim kontrol ölçekleri arasindaki iliskinin degerlendirilmesi.

The goal of asthma treatment is to achieve clinical control. The aim of this study was to compare the role of measurement of nitric oxide and its products in exhaled breath condensate and asthma control questionnaire (ACQ), level of asthma control (LAC) according to GINA guidelines and bronchial provocation test (BPT) in assessing asthma control in cases with stable asthma. Thus, 47 patients with the diagnosis of stable asthma and 42 individuals in the control group were enrolled in the study. The mean ages of the patient and the control groups were 44 +/- 11 and 47 +/- 11 years, respectively. While there was no significant relation between LAC and levels of nitric oxide, nitrite and nitrate, there was a significant relation between ACQ and mini quality of life questionnaire (p< 0.001). In the group with positive BPT, ACQ scores and absolute serum eosinophil values were significantly higher (p< 0.05), and FEV(1)/FVC and PEF percentages were significantly lower than those of the group with negative BPT (p< 0.05). Reversibility was significantly higher in participants with positive BPT than in those with negative BPT (11.2 +/- 7.4 and 6.9 +/- 6.6, respectively; p< 0.05). There was no significant relationship between nitric oxide, nitrite, nitrate in the exhaled breath condensate and ACQ, LAC, BPT and pulmonary function tests (p> 0.05). In conclusion, it was found that the levels of exhaled breath condensate nitric oxide, nitrite and nitrate were not sufficient for determining the level of asthma control in patients with stable asthma. It was concluded that the currently available asthma control questionnaires may be adequate for assessing asthma control.

Smoking determinants in Turkish university students.

The aim was to explore the prevalence and the correlates of smoking in a group of Turkish university students. A sample of 1,870 students (21.2 +/- 2.0 years old) completed the Beck Depression Inventory, Beck Hopelessness Scale, Anxiety Sensitivity Index, 20-item Toronto Alexithymia Scale. Smoking was highly prevalent (35.9%) in this sample. Male gender (OR = 2.72, CI 2.15-3.44), and parental smoking (OR = 1.41, CI 1.13-1.78) were factors associated with increased likelihood of smoking. Higher depressive symptoms and hopelessness levels were significantly related to smoking behavior. Smoking behavior might initiate as a mild and transient habit and unfortunately could become more serious and lead to an actual dependence. The results of this study show that it is necessary to pay attention to levels of depression and hopelessness, as well as parental influence.

Risk factors for asthma and other allergic diseases in seasonal rhinitis.

BACKGROUND: Rhinitis and asthma are common comorbidities. The aim of this study was to determine the risk factors for asthma and other allergic diseases in seasonal rhinitis (SR) patients. METHODS: Records of 922 patients diagnosed as SR between 1991 and 2005 were evaluated retrospectively. Patients were grouped according to the results of our standard skin prick tests as follows: I-No sensitization: no sensitization to any allergen; II-Mono-pollen sensitization: sensitization to only one pollen allergen; III-Poly-pollen sensitization: sensitization to more than one pollen allergen; IV-Mite sensitization: sensitization to mite with or without any other allergen sensitization. RESULTS: The mean age of the patients was 29.5 +/- 9.6 and 587 patients (63.2%) were females. Age at onset of SR was median 21 years (16-29 years). Of the 922 patients, 99 had no sensitization, 335 had poly-pollen sensitization, 346 had mono-pollen sensitization, and 142 had mite sensitization. The most prevalent allergens were P. pratense (85.3%) and O. europae (31.5%). No sensitization group as compared to poly-pollen sensitization group had significantly higher prevalence of asthma as a single accompanying disease (14.1%, p < 0.05). Mono-pollen sensitization was significantly associated with lower risk of any accompanying allergic disease (OR: 0.7, 95% CI 0,5-0,9) while no sensitization group (OR: 2.8, 95% CI 1.3-5.9) and mite sensitization were associated with asthma (OR: 2.3, 95% CI 1.2-4.4). CONCLUSION: SR is a condition that presents with different phenotypes. The group with no sensitization and mite sensitization has the highest prevalence of asthma while SR patients with mono-pollen sensitization are unlikely to have an accompanying allergic disease, including asthma.