leukotriene-c4 and Nasal-Obstruction

We have found that acoustic rhinometry is a reliable means of assessing nasal airway caliber changes during the immediate reaction to nasal allergen challenge of sensitive subjects. Comparison of such changes with symptoms and patterns of mediator release could help in the understanding of mechanisms of immediate and late-phase reactions after allergen challenge and their clinical relevance.. Nasal minimal cross-sectional area (MCA) was assessed sequentially for 6 hours after two blinded challenges in random order with pollen antigens and buffer diluent in five sensitive human subjects. Comparisons were made with: (1) symptom scores; (2) olfaction changes; and (3) nasal secretion levels of histamine, tryptase, leukotriene C4, serum albumin (a marker of vascular permeability), lactoferrin (a marker of local glandular secretion), and inflammatory cells in nasal scrapings.. In four of five subjects there was a significantly greater decrease in MCA after antigen challenge than after diluent challenge, correlating with the degree of subjective nasal congestion. In two of these four subjects there was a prominent second late-phase decrease in MCA at 3 to 5 hours, whereas the MCA was persistently decreased in an additional subject with accompanying subjective congestion. No significant decrease in olfactory acuity occurred. Levels were significantly higher in nasal secretions obtained after antigen challenge than in those obtained after buffer challenge with histamine (9 +/- 2.7 ng/ml vs 1.2 +/- 0.5 ng/ml; p = 0.04); tryptase (95 +/- 83 ng/ml vs 3 +/- 0.9 ng/ml; p = 0.02), leukotriene C4 (5293 +/- 1385 ng/ml vs 578 +/- 183 ng/ml; p = 0.02), and albumin (123 +/- 9 ng/ml vs 19 +/- 1.6 ng/ml; p = 0.005) but not with lactoferrin (4.6 +/- 1.2 ng/ml vs 4.1 +/- 28 ng/ml; p = not significant). Granulocyte exudation was seen after antigen challenge but not after buffer diluent challenge. However, there was not a precise correlation between decreases in MCA with changes in levels of these mediators in individual subjects.. Acoustic rhinometry can quantitatively assess congestion during immediate and late-phase reactions after nasal challenge without significant correlation to the degree of individual inflammatory events assessed.

Topics: Acoustics; Adult; Albumins; Cerebrospinal Fluid Rhinorrhea; Chymases; Eosinophils; Granulocytes; Histamine Release; Humans; Lactoferrin; Leukotriene C4; Nasal Cavity; Nasal Mucosa; Nasal Obstruction; Nasal Provocation Tests; Serine Endopeptidases; Time Factors; Tryptases

Quantitative determinations of the inflammatory mediators in nasal secretions were performed and correlated with the objective nasal symptoms within 1 h after nasal allergen challenge (NAC). Twenty-six patients with seasonal allergic rhinitis were enrolled outside the pollen season. All measurements were performed before (as a baseline control) and at 1, 5, 10, 30, and 60 min after NAC. This study aimed to clarify the pathogenic mechanism of the early-phase reaction (EPR) by monitoring the evolution of early-phase mediators in nasal secretions and the presence of nasal symptoms during this period. The results showed that, after NAC, the maximal mediator concentration was already reached after 1 min for histamine (124 ng/g), 5 min for tryptase (56 microU/g), and 5-10 min for leukotriene C4 (40 ng/g). Itching and sneezing started as early as 20-30 s, and they were predominant symptoms within 5 min. Rhinorrhea and nasal obstruction started a few minutes after NAC and lasted until more than 1 h after NAC. There was no significant correlation between any single mediator and nasal symptoms during the sampling period. In conclusion, this study demonstrated that during the EPR the presence of nasal symptoms involves a complex mechanism, reflecting the interaction between the mediators released by inflammatory cells, and the receptors on different target organs. When evaluating symptoms during the EPR, one must consider not only the severity of these symptoms but also the time period within which these symptoms occur. For the symptoms of nasal obstruction and rhinorrhea, the early-phase reaction often lasted more than 1 h.

Topics: Adult; Allergens; Chymases; Female; Histamine; Humans; Leukotriene C4; Male; Nasal Mucosa; Nasal Obstruction; Nasal Provocation Tests; Pruritus; Serine Endopeptidases; Sneezing; Tryptases

By using a microsuction technique, a quantitative determination of chemical mediators in nasal secretions was performed in 18 hay-fever patients and in a control group of 10 healthy volunteers. The authors then compared these quantitative data for mediators with objective nasal findings counting the number of sneezes, passive anterior rhinomanometry (PAR) and nasal inspiratory peak flow. A sampling protocol was designed with a follow-up of 3 days after nasal allergen challenge (NAC) in order to investigate both early and late allergic reactions. Median baseline concentrations of five major mediators were obtained: histamine, 19 ng/g; leukotriene C4 (LTC4), 5.7 ng/g. tryptase, 0; prostaglandin D2 (PGD2), 477 pg/g; eosinophil cationic protein (ECP), 105 ng/g. Significant increases in histamine (214 ng/g), LTC4 (20 ng/g) and tryptase (28 microU/g) were found, but a significant decrease occurred in ECP (47 ng/g) and PGD (226 pg/g) immediately after NAC in the patients studied. Most ECP concentrations (94%) increased slowly 1 h after NAC and reached a significantly higher level 24 h later. In evaluating nasal symptoms, sneezes were present in a high percentage of cases (76%) during the early phase but were uncommon during the late phase (29%). Total nasal obstruction occurred in 94% during the early phase. In contrast, unilateral nasal obstruction presented in 82% during the late phase, whereas total nasal obstruction was present only in 41%. The most common type of late phase nasal obstruction shown by PAR was alternating nasal obstruction.

Topics: Adolescent; Adult; Allergens; Blood Proteins; Case-Control Studies; Chymases; Eosinophil Granule Proteins; Female; Follow-Up Studies; Histamine; Humans; Inflammation Mediators; Inhalation; Leukotriene C4; Male; Middle Aged; Nasal Mucosa; Nasal Obstruction; Nasal Provocation Tests; Prostaglandin D2; Rhinitis, Allergic, Seasonal; Ribonucleases; Serine Endopeptidases; Sneezing; Tryptases