The relation between paracetamol use and asthma:a GA2LEN European case-control study

Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking. As part of a multicentric case-control study organised by the Global Allergy and Asthma European Network (GA(2)LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (2045 yrs) and place of residence. In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma. These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations

Treatment of nocturnal airway obstruction improves daytime cognitive performance in asthmatics

It has been shown that asthmatics have nocturnal symptoms associated with impaired cognitive performance. We explored more carefully different therapeutic approaches on this performance in relation to lung function in 46 atopics with mild to moderate asthma and with a circadian variation in peak expiratory flow (PEF) greater than or equal to 15%, In a double-blind, parallel study they inhaled salmeterol 50 mu g or fluticasone 250 mu g or a combination of both twice daily for 6 wk, The psychometric tests used informed about. focused attention, mental flexibility, concentration, and attention, The results of the psychometric tests were compared with those in healthy control subjects, The PASAT score and the finishing time of the color-word chart subtest were significantly lower in these asthmatics than in the control subjects, Circadian PEF variation was the only Independent factor significantly associated with impaired cognitive performance before the treatment period. The three treatment groups were equally effective in reducing circadian PEF variation below 10% and in improving FEV1 and bronchial hyperresponsiveness to methacholine (MCh) both day and night, After 6 wk of therapy, the daytime cognitive performance was improved to levels comparable to those of the healthy control subjects no matter which drug was inhaled, We conclude that a high level of circadian PEF variation (greater than or equal to 20%) has been associated with lower daytime cognitive performance in asthmatics, Reduction of circadian PEF variation to below 10% is an important goal of treatment in asthmatics

DEFECT IN POTENTIATION OF ADENYLYL-CYCLASE CORRELATES WITH BRONCHIAL HYPERREACTIVITY

Background: Adenylyl cyclase is a transmembrane signaling system involved in the inhibition of cellular responses. Recently, we showed that the activity of adenylyl cyclase may be potentiated by stimuli that induce an increase of cellular responses but that do not activate adenylyl cyclase. This is probably an important physiologic feedback mechanism that prevents cells from becoming ''overstimulated.'' Objective: Because increased cellular activities are frequently observed in persons with asthma, we hypothesized that a defect in potentiation of adenylyl cyclase might be involved. Methods: Potentiation of isoprenaline-induced adenosine cyclic monophosphate (cAMP) production with the mitogen phytohemagglutinin (PHA; 45 mu g/ml) or the calcium ionophore A23187 (1 mu mol/L) was studied in peripheral blood mononuclear cells taken from patients with asthma (n = 8) and healthy control subjects (n = 11). Results: Isoprenaline-induced cAMP production was potentiated significantly in the healthy control subjects (PHA, 110% +/- 15%; A23187, 92% +/- 25%). In contrast, potentiation was not seen with PHA ol A23187 in the total group of patients with asthma. However; some patients showed weak potentiation, whereas in others PHA decreased isoprenaline-induced CAMP production. Moreover, the effect of PHA isoprenaline-induced cAMP production correlated significantly with the degree of bronchial hyperreactivity in patients with asthma (r = 0.96; p = 0.0001). Conclusions: The observed defect in signal transduction could play an important part in bronchial hyperresponsiveness