Tolerance to alternative cyclooxygenase-2 inhibitors in nonsteroidal anti-inflammatory drug hypersensitive patients

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently cause adverse drug reactions. Many studies have shown that drugs which selectively inhibit the cyclooxygenase-2 enzyme (COX-2) are safe alternatives in the majority of patients. However, hypersensitivity reactions to COX-2 inhibitors have been published. Hardly any data are available regarding the safety of alternatives in case of COX-2 inhibitor hypersensitivity. We aimed to investigate the tolerance to COX-2 inhibitors in patients with non-selective NSAID hypersensitivity. Furthermore, in COX-2 hypersensitive patients tolerance of a second COX-2 inhibitor was investigated. Methods: We retrospectively analyzed 91 patients with proven non-selective NSAID hypersensitivity that underwent oral challenges with a COX-2 inhibitor. Patients with intolerance to the first challenged COX-2 inhibitor received a second challenge with a different COX-2 inhibitor. Results: 19 out of 91 (21%) patients had a positive reaction to the first oral challenge with a COX-2 inhibitor. 14 of them underwent a second challenge with a different COX-2 inhibitor and 12 (86%) did not react. Conclusions: A relatively high percentage (21%) of the non-selective NSAID hypersensitive patients did not tolerate a COX-2 inhibitor and oral challenge is advised prior to prescription of a COX-2 inhibitor. For the majority of patients reacting to a COX-2 inhibitor an alternative can be found

T lymphocytes and cytokines in graft-versus-host disease : a study in mice with emphasis on prevention and treatment.

This thesis describes the results of experiments aimed to improve the insight into this complex disease using a murine model. Based on previous work from our laboratory we investigated the possibilities to prevent GVHD in a specific manner, namely by pretreatment of prospective donors with a recipient-specific blood transfusion. Furthermore, we assessed the role of (subsets of) T lymphocytes and of cytokines in GVHD. Cytokines are factors that can be produced a.o. by T cells and play a central role in immune and inflammatory reactions. Recent data from the literature indicate that cytokines might be involved in the development of GVHD. We studied the therapeutic effect of in vivo administration of anti-T cell (subset), anti-cytokine and anti-cytokine receptor monoclonal antibodies (mAb) on GVH

Fecal microbiome and food allergy in pediatric atopic dermatitis: A cross-sectional pilot study

Background: Exposure to microbes may be important in the development of atopic disease. Atopic diseases have been associated with specific characteristics of the intestinal microbiome. The link between intestinal microbiota and food allergy has rarely been studied, and the gold standard for diagnosing food allergy (double-blind placebo-controlled food challenge [DBPCFC]) has seldom been used. We aimed to distinguish fecal microbial signatures for food allergy in children with atopic dermatitis (AD). Methods: Pediatric patients with AD, with and without food allergy, were included in this cross-sectional observational pilot study. AD was diagnosed according to the UK Working Party criteria. Food allergy was defined as a positive DBPCFC or a convincing clinical history, in combination with sensitization to the relevant food allergen. Fecal samples were analyzed using 16S rRNA microbial analysis. Microbial signature species, discriminating between the presence and absence food allergy, were selected by elastic net regression. Results: Eighty-two children with AD (39 girls) with a median age of 2.5 years, and 20 of whom were diagnosed with food allergy, provided fecal samples. Food allergy to peanut and cow's milk was the most common. Six bacterial species from the fecal microbiome were identified, that, when combined, distinguished between children with and without food allergy: Bifidobacterium breve, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Escherichia coli, Faecalibacterium prausnitzii, and Akkermansia muciniphila (AUC 0.83, sensitivity 0.77, specificity 0.80). Conclusions: In this pilot study, we identified a microbial signature in children with AD that discriminates between the absence and presence of food allergy. Future studies are needed to confirm our findings

Pretransplant helper T-lymphocyte determination in bone marrow donors: acute graft-versus-host disease prediction and relation with long-term survival

Helper T-lymphocyte precursor (HTLp) frequency from 19 allogeneic bone marrow donors was tested to detect weak antigenic differences with the recipient, and then compared to the outcome. HTLp frequency was estimated in limiting dilution cultures, and HLA-DR and CD 80 expression by stimulating cells was measured by flow cytometry. 12/19 patients experienced acute graft-versus-host disease (aGVHD) grade II–IV. A good correlation was found between high pretransplant HTLp frequency and grade II–IV aGVHD (median: 1/55848 PBMNC for II–IV GVHD versus 1/ 184346 for 0–I GVHD; P¼0·008). Sensitivity was 82%, specificity 63%, negative predictive value 71% and positive predictive value 75%. Long-term survivors also had a lower HTLp median frequency (1/143354) when compared with patients who died as a result of the transplant procedure (1/22100, P < 0·001). No correlation was found between HTLp frequency and HLA-DR or CD80 expression by patient’s cells. We conclude that HTLp frequency estimation can predict, although poorly, acute GVHD risk and long-term survival