Bronchial overproduction of leukotrienes and inhibition of prostaglandin synthesis are involved in the pathogenesis of aspirin-induced asthma. We investigated whether inhaled prostaglandin E2 (PGE2) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinary leukotriene E4 (u-LTE4) in seven aspirin-sensitive subjects with asthma. Each subject performed two challenges with a single dose of LASA that caused a decrease in FEV1 of 20% or more in a preliminary test, immediately after inhaling 100 micrograms PGE2 in 4 ml saline or placebo, according to a randomized double-blind protocol. FEV1 was recorded at 30-min intervals for 4 h. u-LTE4 was measured by combined high-performance liquid chromatography enzyme immunoassay at 2-h intervals. After placebo, LASA caused an obstructive reaction in all patients, with a maximum decrease in FEV1 of 35 +/- 5% with respect to baseline. u-LTE4 rose from 911 +/- 261 picograms (pg)/mg creatinine at baseline to a maximum value of 2249 +/- 748 after challenge. Inhaled PGE2 provided almost complete protection in all patients. Baseline u-LTE4 was 883 +/- 243 pg/mg creatinine and did not change significantly during the test, reaching a maximum value of 864 +/- 290 (p < 0.05 versus placebo). These results confirm that PGE2 is highly effective in preventing aspirin-induced asthma and suggest that this effect is mediated by inhibition of sulfidopeptide leukotriene production.
Many different inhalers are available for delivering aerosol therapy in respiratory medicine. As a consequence, the prescribing physicians may have some difficulty tailoring the most suitable inhaler to each patient. This multicenter, observational study using a self-administered questionnaire analyzed the characteristics of a large sample of patients (n ؍ 1,305; 55% females; mean age 57.4, with a range of 15-88 years; most suffering from asthma or chronic obstructive pulmonary disease [COPD]) familiar with several different types of inhalers in relation to their most commonly used delivery device. Data on the inhalation technique for 2,057 observations of 1,126 patients using device-specific checklists and factors associated to misuse were also evaluated. Prevalent usage of newer dry powder inhalers (DPIs) was significantly associated with male sex, higher education, better respiratory function, and prescription from a respiratory physician. Patients using DPIs had received less instruction by health caregivers and were more likely to have read the instruction leaflet than users of metered dose inhalers (MDIs). Under these conditions, inhaler misuse was common and similar for both pressurized metered dose inhalers (pMDIs) and DPIs. For both types of inhalers, misuse was significantly and equally associated to increased age, less education, and less in-127
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