The clinically beneficial effects of AD on nasal and bronchial symptoms occurred only in the patients with AIA.

In 35 asthmatic patients with acetylsalicylic acid (aspirin; ASA) intolerance (AIA) and 15 asthmatics tolerating ASA well, the authors compared the diagnostic value of the placebo-controlled oral ASA versus inhaled L-lysine (L) ASA challenges.All AIA subjects gave a history of asthmatic attacks following ingestion of ASA and in all of them the intolerance was confirmed by oral challenge test over the past 10 yrs. Doses of ASA increasing in geometric progression were used in oral tests 10±312 mg (cumulative dose 500 mg); in bronchial tests 0.18±115 mg (cumulative dose 182 mg). Either challenge was considered as positive, if forced expiratory volume in one second (FEV1) dropped at least 20% from the baseline value and/or strong extrabronchial symptoms of intolerance occurred. Urinary leukotriene E 4 excretion was determined at baseline and following the challenges.In 24 out of 35 patients the oral test was positive, based on a 20% decrease in FEV1. When including extrabronchial symptoms this was positive in 31 cases. Bronchial L-ASA challenge led to $20% fall FEV1 in 21 out of 35 cases, and in 27 cases when including extrabronchial symptoms. No correlation was observed between ASA provocative dose causing a 20% fall in FEV1, determined by the oral route compared to the inhalation route. Urinary LTE 4 increased after both challenges the rise being higher following oral as compared to inhalation provocation (p=0.0001).It is concluded that both tests had similar specificity whilst the oral test showed a tendency to higher sensitivity for the clinical diagnosis of acetylsalicylic acid intolerance. The inclusion of extrabronchial symptoms into the criteria of test positivity enhanced the diagnostic value of both procedures. In both tests the highest leukotriene E 4 increases were found in the presence of extrabronchial symptoms, suggesting the participation of tissues other than the lung in aspirin induced leukotriene E 4 release to urine. Eur Respir J 2000; 15: 863±869.

Objectives: This prospective study aimed to assess the diagnostic yield of the combined approach -endobronchial (EBUS) and endoscopic (EUS) ultrasound-guided needle aspiration (combined ultrasound-needle aspiration (CUS-NA)) in the radiologically normal mediastinum in non-small-cell lung cancer (NSCLC) staging. Methods: CUS-NA was performed simultaneously under local anaesthesia and sedation in consecutive NSCLC patients with mediastinal nodes that were not enlarged on CT (stage IA-IIB). All patients with negative CUS-NA subsequently underwent the transcervical extended bilateral mediastinal lymphadenectomy (TEMLA) as a confirmatory test. Results: A total of 120 NSCLC patients underwent CUS-NA between 1 January 2008 and 31 December 2008. There were 318 mediastinal nodes biopsied (158 EBUS-NA -stations: 2R -2, 2L -1, 4R -34, 4L -33 and 7 -88 and 160 EUS-NA -stations: 4L -57, 7 -101 and 9 -2). CUS-NA revealed metastatic lymph node involvement in 19 of 120 patients (16%) and in 31 of 318 biopsies (10%). The prevalence was 22%. In 99 patients with negative CUS-NA, who underwent subsequent TEMLA, metastatic nodes were diagnosed in nine patients (8%) in 11 stations: 2R -2, 4R -4, 4L -1, 5 -3 and 7 -1. In all but one patient there were 'minimal N2' only. Diagnostic sensitivity, specificity, total accuracy, positive predictive value (PPV) and negative predictive value (NPV) of CUS-NA for normal mediastinum was 68% (95% confidence interval (CI): 48-84), 98% (95% CI: 92-100), 91% (95% CI: 86-96), 91% (95% CI: 70-99) and 91% (95% CI: 83-96), respectively. The sensitivity of CUS-NA was significantly higher than with EBUS-NA alone ( p = 0.04) and higher, close to the level of significance than with EUS-NA alone ( p = 0.07). The NPV of all techniques was high and that of CUS-NA was significantly higher than EBUS-NA alone and EUS-NA alone ( p = 0.01, p = 0.03). No complications of CUS-NAwere observed. Conclusions: In the radiologically normal mediastinum, CUS-NA is a highly effective and safe technique in NSCLC staging and, if negative, a surgical diagnostic exploration of the mediastinum may be omitted. #

We performed a double-blind, two-phase study on protective and bronchodilator effects of prostaglandins E2 and E1 (PGE2, PGE1) and salbutamol in patients with aspirin-induced asthma (AIA). In phase 1 we assessed the effects of pretreatment with PGE2, salbutamol, or the PGE1-analogue, misoprostol, on bronchoconstriction precipitated by inhalation of L-lysine aspirin in 11 patients with AIA. PGE2 and salbutamol were inhaled at equimolar concentrations of 0.25 mumol, 5 min before the aspirin challenge, while 400 micrograms misoprostol was administered orally 1 h before challenge. PGE2 attenuated the bronchoconstrictive reactions in 10 patients, salbutamol in eight, and misoprostol in seven. The mean provocative dose of aspirin causing a 20% fall in FEV1 (PD20) decreased after PGE2 (p = 0.04) and salbutamol (p = 0.06), but only marginally after misoprostol (p = 0.25). There was a positive correlation between magnitude of the protection offered by the three compounds in individual subjects. In phase 2, we examined bronchial response to inhaled PGE2, PGE1, salbutamol, and 2% ethanol in 12 AIA patients compared with 10 aspirin-tolerant patients with asthma. AIA subjects were characterized by less pronounced and shorter bronchodilator responses. There was no correlation between the protective and bronchodilator actions of the compounds used in individual patients. Thus, inhaled PGE2 and salbutamol protect against aspirin-induced attacks of asthma through mechanisms unrelated to their bronchodilator properties. Airways of aspirin-sensitive patients with asthma demonstrate distinct bronchial reactivity.

Background: A special regulatory role for prostaglandin E 2 has been postulated in aspirin-induced asthma. A study was undertaken to investigate the effects of aspirin on the systemic production of prostaglandin E 2 and cysteinyl leucotrienes in patients with asthma. Methods: The urinary concentrations were determined of two main prostaglandin E 2 metabolites (13,14-dihydro15keto-PGE 2 using a commercial enzyme immunoassay and 9,15-dioxo-11a-hydroxy-2,3,4,5-tetranor-prostane-1,20-dioic acid by gas chromatography/mass spectrometry) and leucotriene E 4 using an immunoassay. Determinations were performed at baseline and following oral aspirin and celecoxib challenges in two well-defined asthma phenotypes: aspirin-sensitive and aspirin-tolerant patients.Results: Aspirin precipitated bronchial reactions in all aspirin-sensitive patients but in none of the aspirintolerant patients. Celecoxib 400 mg was well tolerated by all patients except for one with aspirin-induced asthma. At baseline, the mean levels of prostaglandin E 2 metabolites did not differ between the groups. Following different aspirin provocation doses, the mean levels of the two main prostaglandin E 2 metabolites were decreased in the aspirin-tolerant group but remained unchanged in the aspirin-sensitive group. The dose of aspirin had no effect on the magnitude of the response on the prostaglandin E 2 metabolites and its duration. In both groups, urinary prostaglandin E 2 metabolites decreased following celecoxib challenge. No correlation was found between prostaglandin E 2 metabolites and leucotriene E 4 . Conclusions: Aspirin-precipitated asthmatic attacks are not associated with changes in the systemic production of prostaglandin E 2 . In contrast, the systemic production of prostaglandin E 2 becomes depressed by aspirin in nonsensitive patients. This different response might indicate COX-1-dependent prostaglandin E 2 control of inflammatory cells in aspirin-induced asthma. Thus, PGE 2 is released during the clinical reactions to aspirin through an alternative COX-2 pathway. The clinical implications of this finding are in line with current observations of good tolerance of the selective COX-2 inhibitors in aspirinsensitive patients.Prostaglandin E 2 (PGE 2 ) is a bioactive compound formed by actions of cyclooxygenase (COX) and specific PGE synthases.1 In human airways PGE 2 is produced by many cells including epithelium, smooth muscle, alveolar cells, macrophages, phagocytes and lymphocytes.1 2 In vitro, PGE 2 relaxes smooth muscle and displays a number of inhibitory effects on mast cell degranulation, synthesis of leucotriene B 4 , activation of granulocytes and T cells.3-5 PGE 2 elicits a large number of biological effects acting through four receptors: EP1, EP2, EP3 and EP4. [6][7][8] The response of target cells to PGE 2 varies according to the spectrum of receptors they express.PGE 2 might be of special importance in aspirininduced asthma. This is a distinct clinical syndrome affecting 5-10% of adults with asthma. Asthma attacks trigge...