Endophenotyping Oxaliplatin Hypersensitivity: Personalizing Desensitization to the Atypical Platin.

BACKGROUND: Oxaliplatin causes a wider variety of immediate hypersensitivity reactions than do other platin-based chemotherapeutics. Some resemble type 1 reactions that respond to desensitization. Others are atypical, possibly mast cell-independent cytokine release reactions refractory to desensitization. Given this variability, clinicians need an evidence-based strategy to personalize therapy for oxaliplatin-hypersensitive patients. OBJECTIVE: To develop a data-driven algorithm to optimize treatment of oxaliplatin-hypersensitive patients. METHODS: We retrospectively analyzed the baseline clinical characteristics, biomarkers, and reactions of 48 oxaliplatin-hypersensitive patients who received a total of 266 oxaliplatin desensitizations. RESULTS: We characterized 4 endophenotypes: type 1, cytokine release, mixed, and either. A mean 40-fold increase in serum concentration of IL-6 helped define the cytokine release endophenotype. Younger patients were more likely to have a cytokine release endophenotype, whereas older patients were more likely to have a type 1 reaction. Skin testing was not informative for determining endophenotype or risk of reaction during desensitization, and did not associate with initial or desensitization grade of reaction. Patients with a history of atopy and an initial type 1 reaction responded to desensitization with antihistamine premedications, whereas nonatopic patients with the same initial reaction phenotype were more likely to convert to a cytokine release or mixed reaction during desensitization. We combined these reaction patterns with biomarker data and desensitization outcomes to construct an algorithm that helps tailor desensitization protocol design to meet individual patient needs. CONCLUSIONS: Endophenotyping oxaliplatin hypersensitivity reactions may help forecast desensitization outcomes and personalize treatment plans.

[Inverse relation between atopic status and tuberculin response in adult asthmatics]. / Eriskin astimlilarda atopik durum ile tüberkülin yaniti arasindaki ters iliski.

INTRODUCTION: We aimed to examine the relation between tuberculosis infection and both atopic and nonatopic asthma. MATERIALS AND METHODS: Eighty six patients with asthma were included. These patients were divided into two groups according to atopic status. Seventy one patients with positive prick tests to at least one aeroallergen together with history of allergy were named as atopic asthma group, and the other 15 patients with negative prick tests, who do not have any history of allergy were named as nonatopic asthma group. Two different control groups similar in terms of age and gender were taken for each group. Tuberculin skin test was done. RESULTS: As a different from most of the previous studies, we included nonatopic asthmatics besides atopic asthma group. PPD value in atopic asthma group was significantly lower (p< 0.001) than the control group. In nonatopic asthmatics, PPD value was also lower than the control group, but it wasn't statistically significant. When we take all patients and controls, negative correlation was seen between mean PPD value and total IgE levels. CONCLUSION: PPD reactivity has been detected as remarkably suppressed in atopic asthma group while mildly suppressed in nonatopic asthmatics. The results may be affected by the fact that mycobacterium infection or BCG vaccination may have suppressive effect on atopic asthma development which comes out in early ages, but they don't have the same effect on nonatopic asthma development which comes out in elder ages.

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.

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

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

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.

Does the combination of inhaled steroids with long acting beta2 agonists decrease the risk for osteoporosis? A 1-year prospective follow-up study.

Combination of inhaled corticosteroids (ICS) with long acting beta2 agonists has been used increasingly in the treatment of moderate-severe asthma, however there is indefinitive data about their effect on bone loss. The aim of this study was to compare the effects of treatment with single ICS and combination of ICS with long acting beta2 agonists (combination therapy) on BMD and biomarkers of bone metabolism in adult patients with asthma over 1 year period. Forty-three patients with asthma were enrolled. Patients were separated into two groups according to their use of asthma drugs: single ICS or combination therapy (ICS plus long-acting inhaled beta2-agonist). Change in bone mineral density (BMD) and biochemical markers of bone metabolism were measured at baseline and at the end of 1 year. Mean ages and basal BMD of patients did not differ between the two groups (P > 0.05). The decrease in BMD was higher in the single ICS group than the combination therapy group, however there was no significant difference between them (P > 0.05). One year change (%) in BMD and biochemical markers of bone metabolism were not different between two groups (P > 0.05). In conclusion, use of ICS-in the range of doses used- does not seem to have an effect on the change of BMD. However, our data indicate a nonsignificant trend towards reducing bone loss with the use of combination therapy. Future studies are needed to provide definitive evidence for this trend to allow us suggesting combination therapy for minimizing bone loss.

Allergy to drugs: is there an association with mental ill-health?

Objectives. Hypersensitivity reactions to drugs are not infrequent. A certain of anxiety, aggression or depression should be expected in patients with drug allergies, as they could experience symptoms ranging from mild to life-threatening reactions following consumption of drug. However, a literature search resulted in very limited data. This study was designed to evaluate the psychological status of patients with drug allergy and to assess the relationships between psychological evaluations of the patients and, duration of drug allergy, type of allergic reaction, hypersensitivity reaction of the type of drug involved. Methods. The study group comprised 61 patients (43 F, 18 M), age ranging from 16 to 75 years, with reliable history of drug allergy. A total of 55 healthy subjects (39F, 16M) age ranging from 17 to 70 years served as control group. Assessment tools consisted of Beck Depression Inventory (BDI), and Speilberger's State-Trait Anxiety Inventory (STAI Tx-2). Results. The prevalence of depression and anxiety among patients with drug allergies was not greater than that of the controls. There were no associations between the scores of these psychological assessments and duration of drug allergy, type of allergic reaction, type of drug. Conclusions. Our data suggest that follow-up studies including high numbers of patients and patients with specific and potentially life-threatening clinical pictures of drug allergies are needed to detect clinically relevant associations.

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 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.