Deyun Wang

Correlations between complaints, inflammatory cells and mediator concentrations in nasal secretions after nasal allergen challenge and during natural allergen exposure

A quantitative determination of the inflammatory mediators was performed and correlated with complaints and the measurement of the inflammatory cells in nasal secretions of 18 seasonal allergic rhinitis patients (group 1) outside the pollen season and 40 symptomatic patients (group 2) with seasonal allergic rhinitis during the pollen season. Ten nonallergic subjects (group 3) were also studied as a normal control group. In group 1, 17 (94%) out of 18 patients had an immediate response of nasal symptoms accompanied by a significant increase of histamine, leukotriene C4 (LTC4), and tryptase 5 min after nasal allergen challenge (NAC). One hour later, a simultaneous increase was seen both in the percentage of the eosinophils and in the eosinophil cationic protein (ECP) concentration. The eosinophil count reached a peak 2 h after NAC with a duration of 8 h, while the highest ECP level was reached only after 24 h with no clear-cut plateau. In group 2, a high percentage of eosinophils was observed. Mostly one observed significantly (p < 0.01) higher concentrations of ECP, LTC4 and histamine but not of tryptase than the baseline values of group 1. The authors concluded that during the pollen season allergic rhinitis reflects mainly a chronic state of allergic inflammation of the nasal mucosa involving various inflammatory components induced by one or more episodes of early-phase type allergic reaction. Infiltration of eosinophils and consequently release of the various late-phase inflammatory mediators into the nasal secretions are certainly believed to be the predominant pathophysiologic condition in the patients.

Fiberoptic examination of the nasal cavity and nasopharynx in children

In this prospective study, a flexible fiberoptic nasolaryngoscope with color video camera was used to examine the nasal cavity and nasopharynx in 180 pediatric patients. The relative size of the adenoid tissue was judged by endoscopy, which lead to a classification into 3 types according to the distance from the vomer to the adenoid tissue. The condition of the nasopharyngeal orifice of the Eustachian tube was also described and differentiated into 3 types relating to the condition of adenoid tissue. Assessment was performed by correlating these measurements with the tympanogram, lateral X-ray and clinical complaints. The authors conclude that: (1) fiberoptic examination allows direct visualization of the size and condition of the adenoid tissue, as well as of the condition of the nasopharyngeal orifice of the Eustachian tube. (2) The size of the adenoid tissue correlates very well with the nasal obstruction complaints as well as with the type of tympanogram. (3) The condition of the nasopharyngeal orifice of the Eustachian tube significantly corresponds with the type of tympanogram. (4) For the indication of adenoidectomy, fiberscopy gives more accurate information than standard X-ray. (5) With a correct choice of premedication and local anesthesia, it is a minor invasive technique which is very well tolerated by children. It is possible in all cases, provided it is performed by a skilled endoscopist and preceded by careful explanation to the child. (6) Finally, thanks to the possibility of direct visualization of the fiberscopic image via a monitor, it allows a better explanation of the indication for adenoidectomy to the childs parents.

An approach to the understanding of the nasal early‐phase reaction induced by nasal allergen challenge

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 μU/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.

Pathogenic mechanisms underlying the clinical symptoms of allergic rhinitis.

This paper reviews our previous studies on an objective evaluation of nasal symptoms, a quantitative determination of biochemical mediators, and inflammatory cells in nasal secretions of atopic patients after nasal allergen challenge (NAC) and during natural allergen exposure. The use of the micro-suction technique has proved to be a useful and reliable nasal sampling method permitting quantitative analysis of important mediators in nasal secretions. This has provided accurate data on the activity of some important inflammatory cells such as mast cells, basophils, and eosinophils in allergic rhinitis. Our studies demonstrate that a significant increase in the concentrations of histamine, tryptase, and LTC4 in nasal secretions occurs within seconds or minutes after NAC, and this is accompanied by itching, sneezing, rhinorrhea, and nasal obstruction. The infiltration and activation of eosinophils are found to be the predominant condition during the late-phase reaction (LPR), which is mainly characterized by unilateral and/or bilateral nasal obstruction with little sneezing and rhinorrhea. The latter condition is found to be very much similar to the pathophysiology of patients with ongoing allergic rhinitis. In conclusion, our studies demonstrate that patients with ongoing allergic rhinitis seem to be in a continuous late phase state of eosinophil and increased mediator release, a condition that can explain priming and nonspecific hyperreactivity of the nasal mucous membrane.

Effect of Topical Applications of Budesonide and Azelastine on Nasal Symptoms, Eosinophil Count and Mediator Release in Atopic Patients after Nasal Allergen Challenge during the Pollen Season

We studied the activity of a topical form of a corticosteroid (budesonide) and an antihistamine (azelastine) in the treatment of seasonal allergic rhinitis by including an assessment of mediator concentrations and the percentage of eosinophils in the nasal secretions before and after the treatment. Nasal allergen challenge (NAC) during the season was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction. The study compared in a randomized way (2 parallel groups) the effect of budesonide (Rhinocort Aqua) and azelastine (Allergodil nasal spray) in a group of 14 patients during the pollen season. The study showed that azelastine significantly reduced sneezing, total nasal resistance and increased nasal airflow even when significant increases in histamine, tryptase and leukotriene C4 (LTC4) concentrations in nasal secretions were evidenced immediately after NAC. Budesonide showed a strong (p<0.05) decrease in infiltration and activation of eosinophils, and on tryptase and LTC4 release after NAC. These effects (not for LTC4) lasted at least for 1 week after therapy. Azelastine is a powerful topical antihistamine, while budesonide appears to be a potent long-acting anti-inflammatory agent.

Effect of H1 and H2 Antagonists on Nasal Symptoms and Mediator Release in Atopic Patients after Nasal Allergen Challenge during the Pollen Season

During the pollen season, quantitative determination of the chemical mediators and eosinophil count was performed in 16 patients with hay fever after nasal allergen challenge (NAC). The aim of this study was objectively to assess the effect of H1 and of a combination of H1 and H2 antagonists on nasal symptoms, mediator release, and eosinophil count during an allergic reaction. NAC was performed at baseline (V1), 2 weeks after treatment with cetirizine 10 mg/day (V2), and after a combined therapy with cetirizine 10 mg and cimetidine 800 mg a day during the following week (V3). Results showed a significant (p < 0.05 or p < 0.01) relief of nasal symptoms such as: itching, sneezing, rhinorrhea and congestion, and of objective parameter such as: reduction of the number of sneezes after NAC at V2 and V3. Neither H1 antagonist nor a combination of H1 and H2 antagonists showed any effect on eosinophilia and ECP concentration caused by natural allergen exposure, nor on histamine and tryptase release immediately after NAC. When a combination of H1 and H2 antagonists was administered significant reduction of the nasal airway resistance and increase of the nasal air flow were demonstrated.

Concentrations of chemical mediators in nasal secretions after nasal allergen challenges in atopic patients

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 μU/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.

Concentrations of chemical mediators in nasal secretions of patients with hay fever during natural allergen exposure

By using the microsuction technique, quantitative determination of the chemical mediators in nasal secretions was performed in 40 patients with seasonal allergic rhinitis during the pollen season. The aim of this study was to investigate the actual concentrations of these important mediators in nasal secretions during natural allergen exposure so as to better understand the pathophysiology of allergic rhinitis. The median concentrations of four mediators, were histamine: 51.5 ng/g (range: 4-146 ng/g); tryptase: 0 (range: 0-84 microU/g); leukotriene C4 (LTC4): 23 ng/g (range: 11-77 ng/g); and eosinophil cationic protein (ECP): 410 ng/g (range: 6-2380 ng/g). The authors compared these concentrations with those of the same mediator found in a previous study of seasonal allergic rhinitis patients after nasal challenge outside the pollen season. The present study demonstrates that during the season allergic rhinitis reflects a chronic state of allergic inflammation of the nasal mucosa involving various inflammatory mediators induced by one or more episodes of early type allergic reaction.

Concentrations of myeloperoxidase in nasal secretions of atopic patients after nasal allergen challenge and during natural allergen exposure

A quantitative determination of myeloperoxidase (MPO) concentration was performed in the nasal secretions of atopic patients (challenged group, n = 17) after nasal allergen challenge outside the pollen season, and of patients with ongoing seasonal (seasonal group, n = 40) and with perennial (perennial group, n = 30) allergic rhinitis. The concentrations of MPO obtained from 10 nonallergic healthy volunteers (control group) were used as a normal control. Results showed that there was no statistical difference between the normal controls (median: 2.0 micrograms/g) and the atopic patients (median: 1.7 micrograms/g) outside the pollen season. After nasal allergen challenge (challenged group), there was no significant difference of MPO at 5 min (median: 1.0 microgram/G), 8 h (median: 1.7 micrograms/g), and 24 h (median: 3.1 micrograms/g) after challenge as compared to the baseline values. Also, there was no significant difference between patients with ongoing seasonal (median: 1.3 micrograms/g) or perennial (median: 1.8 micrograms/g) rhinitis, and atopic patients outside the pollen season. In conclusion, this study showed that MPO is not locally elaborated in measurable quantities in nasal secretions after nasal allergen challenge and during natural allergen exposure. Further studies will be needed to elucidate the role of neutrophils in the pathophysiological processes of allergic rhinitis.

Inflammatory Cells and Mediator Concentrations in Nasal Secretions of Patients with Cystic Fibrosis

In this study, cytological examination of nasal secretions of 17 patients with cystic fibrosis (CF) was combined with quantitative determination of common inflammatory mediators. Results showed a normal cytogram in these patients. However, obvious mucosal inflammation is evidenced by significantly higher concentrations of leukotriene C4 (LTC4) and eosinophil cationic protein (ECP). The activation of other common inflammatory cells such as mast cells (or basophils) and neutrophils could not be demonstrated since their mediators (histamine, tryptase and myeloperoxidase) are not raised. Increased concentrations of LTC4 and ECP indicate the active participation of eosinophils, and can contribute to the new concept of non-infectious inflammatory involvement of the nasal epithelium of patients with CF.