Review Article

Pathogenic Mechanisms and In Vitro Diagnosis of AERD

Figure 6

(a): FET and NSAID-triggered eicosanoid imbalance of individuals suffering from diseases with lower airway symptoms. The FET was performed and the FET values were calculated according to the total eicosanoid pattern score of [11] using PBLs. Patients suffering from NSAID-triggered bronchoconstrictive symptoms were confirmed and characterised by clinical and in vitro diagnosis. Allergy was ruled out by medical history, skin test, and in vitro test for total and specific immunoglobulin. The mean FET value (solid line) of controls, ATA, and AERD was 0.7, 1.4, and 2.1, respectively. FET values > 1.0 characterise patients with lower airway symptoms. FET values ≥ 1, 8 (dashed line, potential threshold) differentiate NSAID-tolerant asthmatics and patients with AERD; ATA: patients suffering from aspirin-tolerant asthma, AERD: patients suffering from aspirin exacerbated respiratory disease; ( for each group, * , ** ). (b): FET and functional metabolic differentiation of patients with and without NSAID-triggered eicosanoid of lower and upper airway symptoms. The functional metabolic differentiation (FMD) of subgroups of patient was achieved by in vitro provocation of PBLs and calculation of the FET value according to the total eicosanoid pattern score of [11], but by amending the FET value by subtracting the difference of the sum of the enzymatic capacity (EC) of PG- and LT-synthesis as well as the difference of the ASA- and neuropeptide-induced eicosanoid balances (EB) from the primary FET value (EC and EB were calculated according to [11]). The FET-FMD value takes into account two metabolites of the eicosanoid pathway and their in vitro modification by ASA and neuropeptide. The latter had been shown to be intimately implicated in hyperresponsiveness of airway ([11] and ref. therein). The FET-FMD value reveals the differentiation of ATA, NP, and AERD, but without discrimination of ATA and healthy controls. The mean value of FET-FMD (solid line) was 0.4, 0.4, 1.1, and 1.7, for controls, ATA, NP, and AERD, respectively. The threshold of FET-FMD was ≥1.0 (dashed line) for NSAID-triggered lower and upper symptoms of the airways. In conclusion, this approach confirmed and characterised NSAID-triggered symptoms by clinical and in vitro diagnosis. ATA: patients suffering from bronchial asthma, but tolerant to NSAIDs, NP: patients suffering from nasal polyposis, AERD: patients suffering from aspirin exacerbated respiratory disease with asthmatic symptoms; for each group, ns: not significant, * , ** . Allergy was ruled out by medical history, skin test and in vitro test of total an specific immunoglobulin.
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