Urinary LTE4 is higher after nasal provocation test with L-ASA in bronchial than in only nasal responders

Aspirin induced asthma (AIA) is a syndrome characterised by intolerance to acetylsalycilic acid (ASA), nasal polyps and bronchial asthma, being the metabolic shift of arachidonic acid toward the lipoxygenase pathway and hyper-production of cysteinyl-leukotrienes (cys-LTs) the current pathogenetic hypothesis. The research for both sensitive indicators and safe diagnostic tests is still attracting. Aim of the study was to compare the levels of urinary LTE4 in baseline and after Nasal Provocation Test (NPT) with L-ASA from subjects affected by aspirinin-Intolerance and characterized by only a nasal response to ASA to those from subjects with both a nasal and a bronchial response to the same challenge.

After their written consent, 74 subjects with mill to moderate AIA (16 male, mean age 45.3 years +/- 12.3 sd, mean basal FEV1 = 78.1% pred. +/- 6.2.4sd, FEV1 reversibility = 14.3% bsln +/- 2.1 ds after salbutamol 200 mcg) performed a NPT with L-ASA (total maximal dose 25 mg). Spirometry (FEV1), acoustic rinometry (nasal volume--VOL; nasal Resistance--Req; AR; TM Hood Lab., USA), and urinary LTE4 (Cayman Chemical, MI, USA, via Triturus System, Grifols, Spain) were checked in all subjects in basal conditions and 90' after NPT.

t test between means +/- sd, assuming p < 0.05, and linear regression between all variables considered.

In 69 ASA-intolerant-asthmatics, mean FEV1 did not change significantly following NPT (78.7% pred. +/- 5.1 sd in baseline; 78.5% pred. +/- 4.1 sd after NPT, p = ns) even though in the presence of a significant decrease of VOL. (12.6 cm3 +/- 4.1 sd in baseline; 6.2 cm3 +/- 4.6 sd after NPT, p = 0.003); of a substantial increase in Req (0.9 cm H2O/l/min +/- 0.1 ds in baseline; 2.4 cmH2O/l/min +/- 0.2 after NPT, p = 0.04), and of urinary LTE4 excretion (333.0 pg/mg +/- 161.7 in bsln; 558.0 pg/mg +/- 171.690' after NPT with L-SA, p = 0.02). In only 5 subjects, the nasal response occurred concomitantly to a significant bronco-constriction after the NPT: mean FEV, changed from 77.9% pred. +/- 3.9 in bsln to 46.6% pred. +/- 4.3 after NPT (p < 0.001); mean VOL from 13.9 cm3 +/- 4.7 sd to 5.6 cm3 +/- 2.8 sd (p < 0.001); mean Req from 1.1 cmH2O/l/min +/- 0.2 in bsln to 2.5 cmH2O/l/min +/- 0.4 after NPT (p = 0.02) in these subjects. In ASA-intolerant bronchial responders, the severity of respiratory reactions proved related to the extent of urinary LTE4 response, which on the other hand, proved significantly higher than that observed in ASA-intolerant subjects with only nasal response and in ASA-tolerant subjects (LTE4 from 333.0 pg/mg +/- 161.7 in baseline up to 558.0 pg/mg +/- 171.6 90 min. following the NPT with L-ASA the nasal-responders, p = 0.04, but from 412.0 pg/mg +/- 102.8 in baseline up to 978.0 pg/mg +/- 108.7 after NPT in bronchial responders, p < 0.001 from baseline).

Nasal challenge with ASA affects significantly both nasal VOL and Req, and LTE4 excretion in all ASA-intolerant subjects. During the nasal challenge, severity of respiratory reactions proves associated with the highest basal LTE4 synthesis. This feature reflects a spectrum of respiratory tract reactions where cysteinil-LTs can play a specific diagnostic role.