May the Force be with antileukotriene drugs

W 1979 roku na Kongresie Prostaglandynowym w Waszyngtonie, Bengt Samuelsson przedstawił budowę chemiczną i drogi powstawania leukotrienów [...

Prevalence of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in the population of adult asthmatics in Poland based on an epidemiological questionnaire

Introduction: Hypersensitivity reactions to drugs account for 25% of all side effects related to drugs, affecting more than 7% of the population. One in four such reactions is caused by acetylic acid and other non-steroidal anti-inflammatory drugs. Material and methods: Between 1998 and 2000 epidemiological research was carried out in various centers, with the aim of estimating the frequency of allergy-based diseases in Poland. The objective of the study was to evaluate the frequency of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), based on an epidemiological questionnaire, in the Polish adult population. Results: Bronchial asthma was diagnosed in 582 patients (5.4%). Of that group, 75 patients (12.9%) additionally reported symptoms of hypersensitivity to NSAIDs. Aspirin-induced asthma was diagnosed in 11 patients (14.7%) with clinical manifestations of hypersensitivity responses. Frequency of aspirin-induced asthma with clinical symptoms amounted to 1.9% of asthmatics. In the assessment of severity of the disease, aspirin intolerance was the only statistically significant factor (p = 0.0003; odds ratio 28.6 with assumed 95% confidence interval). Conclusions: In the population of adults in Poland, the frequency of aspirin-induced asthma amounted to 0.1%. Hypersensitivity to NSAIDs was observed in 12.9% of asthmatics. In asthmatics with symptoms of hypersensitivity to non-steroidal anti-inflammatory drugs, which takes the course of clinically demonstrable aspirin-induced asthma, the risk of severe asthma is 30-fold higher

Prevalence of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in the population of adult asthmatics in Poland based on an epidemiological questionnaire

Wstęp: Reakcje nadwrażliwości na leki stanowią około 25% działań niepożądanych leków i dotyczą ponad 7% ogólnej populacji. Kwas acetylosalicylowy i inne niesteroidowe leki przeciwzapalne (NLPZ) w jednej czwartej przypadków odpowiadają za te reakcje. Materiał i metody: W latach 1998–2000 przeprowadzono wieloośrodkowe badanie epidemiologiczne, mające oszacować częstość występowania schorzeń alergicznych w Polsce. Celem autorów pracy była próba oceny częstości występowania reakcji nadwrażliwości na NLPZ w populacji dorosłych cierpiących na astmę w Polsce, na podstawie prowadzonych badań epidemiologicznych. Wyniki: Badanie objęło grupę 10 684 dorosłych osób w Polsce. Astmę oskrzelową rozpoznano u 582 (5,4%) badanej populacji. W grupie tej 75 chorych (12,9%) zgłaszało objawy nadwrażliwości na NLPZ. Częstość występowania astmy aspirynowej wyniosła 1,9% wśród wszystkich chorych na astmę. W grupie z nadwrażliwością na NLPZ astmę przewlekłą umiarkowaną choi ciężką rozpoznano u 21,3% chorych. W ocenie ciężkości astmy wśród populacji badanej istotność statystyczną uzyskano w tylko w przypadku nietolerancji na aspirynę (p = 0,0003; iloraz szans 28,6 przy założonym 95-procentowym przedziale ufności). Wnioski: Częstość występowania astmy aspirynowej w populacji osób dorosłych w Polsce wynosi 0,1%, natomiast wśród dorosłych chorych na astmę oskrzelową stanowi 1,9%. Reakcje nadwrażliwości na NLPZ występują u 12,9% dorosłych chorych na astmę w Polsce. Chorych na astmę aspirynową charakteryzuje statystycznie znamiennie cięższy przebieg choroby w porównaniu do chorych na astmę tolerujących aspirynę. Ryzyko wystąpienia u nich ciężkiego przebiegu astmy jest zwiększone blisko 30-krotnie.Introduction: Hypersensitivity reactions to drugs account for 25% of all side effects related to drugs, affecting more than 7% of the population. One in four such reactions is caused by acetylic acid and other non-steroidal anti-inflammatory drugs. Material and methods: Between 1998 and 2000 epidemiological research was carried out in various centers, with the aim of estimating the frequency of allergy-based diseases in Poland. The objective of the study was to evaluate the frequency of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), based on an epidemiological questionnaire, in the Polish adult population. Results: Bronchial asthma was diagnosed in 582 patients (5.4%). Of that group, 75 patients (12.9%) additionally reported symptoms of hypersensitivity to NSAIDs. Aspirin-induced asthma was diagnosed in 11 patients (14.7%) with clinical manifestations of hypersensitivity responses. Frequency of aspirin-induced asthma with clinical symptoms amounted to 1.9% of asthmatics. In the assessment of severity of the disease, aspirin intolerance was the only statistically significant factor (p = 0.0003; odds ratio 28.6 with assumed 95% confidence interval). Conclusions: In the population of adults in Poland, the frequency of aspirin-induced asthma amounted to 0.1%. Hypersensitivity to NSAIDs was observed in 12.9% of asthmatics. In asthmatics with symptoms of hypersensitivity to non-steroidal anti-inflammatory drugs, which takes the course of clinically demonstrable aspirin-induced asthma, the risk of severe asthma is 30-fold higher

Impact of Hymenoptera venom allergy and the effects of specific venom immunotherapy on mast cell metabolites in sensitized children

Introduction and objective. Mast cells (MC) are effector cells during severe systemic reactions (SR) to Hymenoptera stings. Venom specific immunotherapy (VIT) is the treatment of choice for prevention of SR to stings. Tryptase and prostaglandin D2 metabolites (PGD2 ) are the markers of MC activation. The study design was to 1. compare baseline values of serum tryptase concentration (BST) and PGD2 metabolites in children with/without venom sensitization, 2. to evaluate an influence of rush VIT on MC markers in treated children. Materials and methods. Sensitized group: 25 children with SR to Hymenoptera sting. Control group: 19 healthy children. Active treatment: 5-day-rush-VIT. BST was evaluated by ImmunoCAP, PGD2 metabolites in blood and urine by GC-NICI-MS. Results. The baseline blood levels of MC markers were significantly higher, while urinary concentration of 9α,11β-PGF2 was significantly lower in the whole group of venom-sensitized children compared to controls. Severity of SR showed negative correlation with urinary PGD2 metabolites, while positive with plasma 9α,11β-PGF2 and BST concentration The highest sensitivity was obtained for plasma 9α,11β-PGF2 whereas the highest specificity for urinary PGD-M. Conclusions. In children with IgE-mediated SR to Hymenoptera stings, elevation of baseline values of PGD2 metabolites in blood is accompanied by decreased excretion of its urinary metabolites. Assessment of stable PGD2 metabolites might serve as an independent MC marker to identify allergic children. There is an association between urinary PGD2 metabolites and severity of the SR to Hymenoptera stings

Inhibition of thrombin generation by simvastatin and lack of additive effects of aspirin in patients with marked hypercholesterolemia

AbstractOBJECTIVESTo assess the effects of aspirin compared with simvastatin on thrombin generation in hypercholesterolemic men, and to establish whether the reduction of elevated blood cholesterol by simvastatin would affect the action of aspirin on thrombin formation.BACKGROUNDAspirin inhibits thrombin formation, but its performance is blunted in hypercholesterolemia. By virtue of altering lipid profile, statins could be expected to influence thrombin generation.METHODSThirty-three men, aged 34 to 61 years, with minimal or no clinical symptoms, serum total cholesterol >6.5 mmol/liter and serum triglycerides <4.6 mmol/liter, completed the study consisting of three treatment phases. First, they received 300 mg of aspirin daily for two weeks (phase I), which was then replaced by simvastatin at the average dose of 24 mg/d for three months (phase II). In phase III, aspirin, 300 mg/day, was added for two weeks to simvastatin, the dose of which remained unchanged. Thrombin generation was assessed: 1) in vivo, by measuring levels of fibrinopeptide A (FPA) and prothrombin fragment 1+2 (F1+2) in venous blood; and 2) ex vivo, by monitoring the rates of increase of FPA and F1+2 in blood emerging from standardized skin incisions of a forearm. A mathematical model was used to describe the kinetics of thrombin formation at the site of microvascular injury.RESULTSTwo-week treatment with aspirin had no effect on thrombin markers in vivo, while ex vivo it depressed the total amount of thrombin formed, though not the reaction rate. After simvastatin treatment, serum cholesterol decreased by 31% and LDL cholesterol by 42%, while thrombin generation became markedly depressed. In venous blood, FPA was significantly reduced. Concomitantly, the initial thrombin concentration and total amount of thrombin generated decreased significantly. Addition of aspirin to simvastatin (phase III) had no further effect on any of these parameters.CONCLUSIONSIn men with hypercholesterolemia, lowering serum cholesterol level by a three-month simvastatin treatment is accompanied by a marked reduction of thrombin generation both at basal conditions in venous blood and after activation of hemostasis by microvascular injury. Once blood cholesterol became reduced, adding aspirin to simvastatin did not enhance dampening of thrombin formation