Erdosteine enhances airway response to salbutamol in patients with mild-to-moderate COPD.

BACKGROUND: Oxidative stress is presumed to impair beta-adenoceptor function and airway patency. Erdosteine (E), a mucomodulatory compound, has shown important antioxidant properties. METHODS: The objective was to assess the effect of antioxidant interventions on short-term airway response to salbutamol in non-reversible mild-to-moderate COPD patients. Thirty COPD patients (GOLD class 1-2), current smoker (>or=10 pack/year), randomly received E 300 mg, N-acetylcysteine (NAC) 600 mg, or placebo, twice daily for ten days. Reversibility to salbutamol 200 microg was tested in baseline, after four and ten days of each treatment. ROS and 8-isoprostane blood levels were measured on the same days. Between-treatment comparison was performed by ANOVA and t-test or Wilcoxon test, and p<0.05 assumed. E enhanced FEV1 reversibility after four and ten days significantly (+5.1% and +5.0%; both p<0.01 vs. placebo), while NAC only showed a transient effect at day 4 (+3.0%, p<0.05), but not at day 10 (+1.3%, p = ns). RESULTS: E and NAC caused significant drops in ROS blood levels after four and ten days (p<0.001 and p<0.0001 vs. placebo). In contrast to NAC, E lowered 8-isoprostane levels substantially for ten days (p = 0.017 and p = 0.0004 vs. placebo, respectively). Only E restored significantly short-term reversibility in COPD patients previously unresponsive to beta(2)-adrenergics. CONCLUSIONS: This effect seems more related to the peculiar protection against lipid peroxidation rather than to the scavenging activity, which proves equal to that of NAC. E provides a sort of indirect bronchodilation through 're-sensitisation' of beta( 2)-adrenoceptors. Once confirmed in further controlled studies, it may be useful in long-term treatment of COPD.

Changes in urinary LTE4 and nasal functions following nasal provocation test with ASA in ASA-tolerant and -intolerant asthmatics.

UNLABELLED: Aspirin-induced asthma (AIA) is a syndrome characterized by intolerance to aspirin (ASA), nasal polyps and bronchial asthma, the metabolic shift of arachidonic acid towards the lipoxygenase pathway and hyper-production of cysteinyl-leukotrienes (cys-LTs) being the current pathogenetic hypothesis. The research for both sensitive indicators and safe diagnostic tests is still attracting. Aim of the study was to measure changes in urinary LTE4 excretion and in nasal function (Resistance-Req, and Volume-Vol, assessed by acoustic rhinomanometry (AR)) following a nasal provocation test (NPT) with ASA:LTE4 measurements have been never previously used to our knowledge for assessing nasal responsiveness to ASA. METHODS: After written consent, 118 mild-to-moderate asthmatics (48 males, mean age 41.8 years+/-11.9SD, range 25-70 years; basal FEV1=80.1% pred.+/-5.8SD) underwent NPT by nasal instillation of ASA (total maximal dose 25 mg). Spirometry, acoustic rhinomanometry (AR; TM Hood Lab., USA) and urinary LTE4 (pg/mg creatinine; Cayman Chemical, MI, USA) were measured in baseline and 2h after the ASA challenge. STATISTICS: t-Test between means+/-sd, assuming P<0.05, and linear regression between all variables considered. RESULTS: In 67 ASA-intolerant asthmatics, FEV1 did not change significantly following NPT (81.7% pred.+/-5.1SD in baseline, 80.5% pred.+/-4.1 after NPT, P=ns) even in the presence of a significant decrease of Vol (11.3 cm3+/-4.1SD in baseline, 5.9 cm3+/-4.2SD after NPT, P=0.003), a substantial increase of Req (0.88 cmH2O/l/min+/-0.11SD in baseline, 2.41 cmH2O/l/min+/-0.77 after NPT, P=0.002), and urinary LTE4 excretion (433.0 pg/mg+/-361.7 in bsln, 858.0 pg/mg+/-471.6 90 min after NPT with L-SA, P=0.04). NPT did not affect FEV1 also in 51 ASA-tolerant asthmatics (89.7% pred.+/-6.9 in bsln, 86.6% pred.+/-4.3 after NPT), but in these subjects also Vol (from 14.9 cm3+/-4.2sd to 14.6 cm3+/-3.8SD), Req (0.38 cmH2O/l/min+/-0.14 in bsln, 0.26 cmH2O/l/min+/-0.2 after NPT, P=ns), and urinary LTE4 (333.1 pg/mg+/-202.8 in bsln, 318.0 pg/mg+/-198.7 after NPT, P=ns) remained unchanged. Only pre-NPT LTE4 values proved related to pre-NPT Req and Vol values (r=0.54 and r=-0.71, respectively), but not to patients' age (R=-0.05), and basal FEV1 (r=0.01). CONCLUSIONS: In ASA-intolerant patients, NPT with lysine-aspirin (L-ASA) only induces a substantial nasal obstruction and enhances urinary LTE4 excretion in the absence of any significant bronchial obstruction. Nasal ASA challenge proves a test absolutely safe for asthma patients suspected of ASA intolerance. Measures of urinary LTE4 excretion contributed significantly to magnify the discriminant and the diagnostic value of NPT.