BACKGROUND:This examination focused on the allergic early and late phase reaction via nasal symptom scores, acoustic rhinometry, and the determination of mediators possibly involved in late phase eosinophilia. We examined nasal secretions for IL-5; the chemokines IL-8, MCP-1, and Eotaxin; the adhesion molecule sVCAM-1, and the leukotriene LTC4 for their suggested impacts on tissue eosinophilia.METHODS:13 patients suffering from seasonal allergic rhinitis were challenged intranasally out of the natural pollen season by their specific allergen. In a time window of 8 h following the provocation, patients completed symptom questionnaires, and underwent acoustic rhinometry. Nasal secretions were gained by the cotton wool method over a time period of 8 h. Nasal secretions were analyzed for the above mentioned mediators.RESULTS:Individual evaluation of the acoustic rhinometry measurements revealed an early phase reaction in 100 % of the cases and a late phase reaction in 92 %. The need to sneeze and a runny nose were the strongest symptoms during the allergic early and late phase reaction. A typical late phase kinetic was observed for IL-5, MCP-1, Eotaxin, sVCAM-1, and LTC4. IL-8 was characteristic for early phase reaction but increased in late phase as well.CONCLUSIONS:The need to sneeze, a runny nose, and the overall quality of life were most apt to evaluate the allergic early and late phase reaction. Highly significant correlations between nasal obstruction and acoustic rhinometry measurements indicate a high sensitivity of visual analogue scales in the representation of minimal changes in nasal symptom scores during the allergic reaction. Our data point to a relevant role of the TH2 cytokine IL-5; of the chemokines IL-8, MCP-1, and Eotaxin; of the adhesion molecule sVCAM-1, and of the leukotriene LTC4 for the allergic late phase eosinophilia.

RATIONALE: Patients with NARES (non-allergic rhinitis with eosinophilia syndrome) complain about typical symptoms of persistent allergic rhinitis, mainly nasal congestion and rhinorrhea. Nevertheless, the underlying pathophysiology of NARES still remains unknown. The objective of the study was to investigate cytokines and chemokines in nasal secretions of patients with NARES and persistent allergic rhinitis to further elucidate the pathophysiology of NARES.METHODS: Nasal secretions of 31 patients suffering from NARES, 21 patients with persistent allergic rhinitis (PAR) and 20 healthy controls were gained by the cotton wool method and analyzed for IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, GM-CSF, G-CSF, IFN-γ, TNF-α, MCP-1, and MIP-1β (Bio-Plex Cytokine Assay). ECP and Tryptase as mediators for cellular activation were analyzed by ELISA.RESULTS: We found high and significantly elevated levels of pro- inflammatory cytokines IL-1b, IL-6, IFN-γ and TNF-α as well as of IL-4, IL-17 and MCP-1 in nasal secretions of patients with NARES compared to healthy controls and PAR. Concentrations of IL-7, G-CSF and GM-CSF were higher in NARES than in controls, while there was no significant elevation of GM-CSF in patients with PAR. IL-5 and MIP-1b showed likewise elevated levels in PAR and NARES compared to controls.CONCLUSIONS: The elevated levels of pro-inflammatory cytokines in NARES are an indicator for the chronic process of inflammation in NARES. IL-4, IL-5 and GM-CSF may be released by eosinophils to sustain eosinophilic migration and retention in the inflamed mucosa. IL-17 may play a role in remodeling processes of the nasal mucosa in patients with NARES. RATIONALE: Patients with NARES (non-allergic rhinitis with eosinophilia syndrome) complain about typical symptoms of persistent allergic rhinitis, mainly nasal congestion and rhinorrhea. Nevertheless, the underlying pathophysiology of NARES still remains unknown. The objective of the study was to investigate cytokines and chemokines in nasal secretions of patients with NARES and persistent allergic rhinitis to further elucidate the pathophysiology of NARES. METHODS: Nasal secretions of 31 patients suffering from NARES, 21 patients with persistent allergic rhinitis (PAR) and 20 healthy controls were gained by the cotton wool method and analyzed for IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, GM-CSF, G-CSF, IFN-γ, TNF-α, MCP-1, and MIP-1β (Bio-Plex Cytokine Assay). ECP and Tryptase as mediators for cellular activation were analyzed by ELISA. RESULTS: We found high and significantly elevated levels of pro- inflammatory cytokines IL-1b, IL-6, IFN-γ and TNF-α as well as of IL-4, IL-17 and MCP-1 in nasal secretions of patients with NARES compared to healthy controls and PAR. Concentrations of IL-7, G-CSF and GM-CSF were higher in NARES than in controls, while there was no significant elevation of GM-CSF in patients with PAR. IL-5 and MIP-1b showed likewise elevated levels in PAR and NARES compared to controls. CONCLUSIONS: The elevated levels of pro-inflammatory cytokines in NARES are an indicator for the chronic process of inflammation in NARES. IL-4, IL-5 and GM-CSF may be released by eosinophils to sustain eosinophilic migration and retention in the inflamed mucosa. IL-17 may play a role in remodeling processes of the nasal mucosa in patients with NARES.

Background: This examination focused on the allergic early and late phase reaction via nasal symptom scores, acoustic rhinometry, and the determination of mediators possibly involved in late phase eosinophilia. We examined nasal secretions for IL-5; the chemokines IL-8, MCP-1, and Eotaxin; the adhesion molecule sVCAM-1, and the leukotriene LTC4 for their suggested impacts on tissue eosinophilia. Methods: 13 patients suffering from seasonal allergic rhinitis were challenged intranasally out of the natural pollen season by their specific allergen. In a time window of 8 h following the provocation, patients completed symptom questionnaires, and underwent acoustic rhinometry. Nasal secretions were gained by the cotton wool method over a time period of 8 h. Nasal secretions were analyzed for the above mentioned mediators. Results: Individual evaluation of the acoustic rhinometry measurements revealed an early phase reaction in 100% of the cases and a late phase reaction in 92%. The need to sneeze and a runny nose were the strongest symptoms during the allergic early and late phase reaction. A typical late phase kinetic was observed for IL-5, MCP-1, Eotaxin, sVCAM-1, and LTC4. IL-8 was characteristic for early phase reaction but increased in late phase as well. Conclusions: The need to sneeze, a runny nose, and the overall quality of life were most apt to evaluate the allergic early and late phase reaction. Highly significant correlations between nasal obstruction and acoustic rhinometry measurements indicate a high sensitivity of visual analogue scales in the representation of minimal changes in nasal symptom scores during the allergic reaction. Our data point to a relevant role of the TH2 cytokine IL-5; of the chemokines IL-8, MCP-1, and Eotaxin; of the adhesion molecule sVCAM-1, and of the leukotriene LTC4 for the allergic late phase eosinophilia.

Objective: This study focused on factors contributing to eosinophilia after intranasal allergen challenge.Methods: Nasal secretions of 13 allergic individuals were gained over a period of 8 hours after nasal allergen challenge. Early and late phase reactions were determined by acoustic rhinometry and changes of volume and total protein in nasal secretions. Eosinophilia was demonstrated by nasal eosinophilic cationic protein. Interleukin (IL)-5; the chemokines IL-8, monocyte chemotactic protein (MCP)-1 and MCP-3, and eotaxin; soluble vascular cell adhesion molecule 1 (sVCAM-1); and the leukotriene C4 (LTC4) were analyzed by enzyme-linked immunosorbent assay for their Suggested impacts on tissue eosinophilia.Results: By means of rhinometry, we observed in 69% an alternating type of late phase response, followed by a bilateral (15%) or unilateral (8%) type. A biphasic kinetic could be demonstrated by changes in nasal volume and total protein of nasal secretions, reflecting the early and late phase responses. A typical late phase kinetic was observed for IL-5. MCP-1, eotaxin, sVCAM-1, and LTC4. Interleukin 8 was characteristic for early phase reaction but increased in late phase as well. We could not detect any MCP-3 in our samples.Conclusions: Our data point to a relevant role of the T(H)2 cytokine IL-5; of the chemokines IL-8, MCP-1, and cotaxin; of the adhesion molecule sVCAM-1; and of the leukotriene LTC4 for the allergic late phase eosinophilia. (C) 2006 Elsevier Inc. All rights reserved.

RESULTS:Human healthy conjunctiva expresses TLR-2, -4 and -9 mRNA's and proteins.VKC conjunctiva expresses significant higher amounts of TLR-4mRNA/protein, and a significant decrease of TLR-9mRNA/protein.TLR-4 mRNA and protein was also found to be overexpressed in VKC-derived fibroblasts, while TLR-2 and -9mRNAs and proteins were slightly down-regulated.CONCLUSIONS: This is the first report of TLR-2, -4 and -9 expression in the human healthy conjunctiva.The up-regulation of TLR-4 and downregulation of TLR-9, in VKC both at molecular and biochemical level, might suggest a role of the innate and adaptive response to microbial antigens in modulating the ocular allergic inflammatory response.

Background: Mucosa-immunologic aspects are gaining an increasing awareness in the pathophysiology of type I allergies. Humoral mucosal immune responses are dominated by secretory IgA, but there is evidence for a relevant role of IgG in nasal mucosa-associated lymphoid tissue.Objective: was to measure allergen-specific immunoglobulins (IgA and IgG) in nasal secretions as an expression of a humoral mucosal immune response in allergic rhinitis. For tissue eosinophilia we studied nasal Eosinophilic Cationic Protein (ECP) and for mast cell activation nasal tryptase.Methods: Nasal secretions of 40 patients suffering from allergic rhinitis were analyzed for allergen-specific IgA, IgG, and IgE, and for ECP and tryptase. Patients were highly sensitized against the major allergens of house dust mites, timothy, and birch pollen. 43 non-atopic individuals served as controls. In order to study possible effects of the actual pollen season on the studied parameter we secondly compared patients allergic to seasonal allergens co- (n = 28) and extra-seasonally (n = 41). In order to determine a possible influence of allergen-specific IgA in eosinophilic degranulation we additionally studied 5 patients after nasal allergen challenge.Results: In allergic rhinitis we found significantly increased levels of allergen-specific immunoglobulins of all studied subclasses and allergens in nasal secretions. Comparison of nasal ECP and tryptase showed significantly increased concentrations in allergic individuals as well. Co-seasonally we found elevated allergen-specific IgE, ECP, and tryptase but lower concentrations of allergen-specific IgA and IgG. There was no association between late phase eosinophilia and IgA concentrations after local allergen challenge.Conclusions: The occurrence of allergen-specific immunoglobutins in nasal secretions is interpreted as a local humoral mucosal immune response. The physiologic role of local allergen-specific immunoglobulins is not clear to date. Involvement in degranulation of eosinophils or mast cells, like suggested before, seems unlikely.

Hintergrund: Die Differentialdiagnose chronisch entzündlicher Erkrankungen der Nase und Nasennebenhöhlen (NNH) ist trotz Einsatz von Endoskopie und bildgebenden Verfahren schwierig. Viele Patienten klagen über eine ähnliche Beschwerdesymptomatik. Ziel der vorliegenden Studie war der Vergleich pathophysiologisch relevanter in-vitro Parameter im Nasensekret.

Background Differential diagnosis of chronic nasal inflammation is insufficient when based solely on clinical examination and radiography of paranasal sinuses. Patients complain about more or less similar symptoms. Activation of mast cells and eosinophils is pivotal in nasal inflammation.Objective To compare tryptase and eosinophilic cationic protein (ECP) in nasal secretions in different forms of chronic nasal inflammation and to establish norm values.Methods The study included 1710 patients presenting with nasal complaints. Nasal secretions were gained by the cotton wool method and analysed for tryptase, as a marker of mast cell activation, and for ECP, as a marker of tissue eosinophilia and activation. Patients were grouped according to their diagnosis: chronic, non-allergic rhinosinusitis (sinusitis, n = 194), non-allergic nasal polyposis (polyposis, n = 138), non-allergic rhinitis with eosinophilia syndrome (NARES, n = 198), isolated perennial allergic rhinitis (AR) (n = 126), isolated seasonal AR (n = 132), and patients allergic to both, seasonal and perennial allergens (n = 193). Seven hundred and twenty-nine patients with nasal complaints due to a deviated septum and without any nasal inflammation served as controls.Results Nasal tryptase was highly significantly (P < 0.001) elevated in polyposis, NARES, and in AR. ECP was highly significantly (P < 0.001) elevated in all groups of patients suffering from chronic nasal inflammation. Based on our data and method we established norm values (95% confidence interval of mean value) for nasal tryptase in healthy adults, ranging from 12.0 to 18.7 ng/mL and for ECP ranging from 84.4 to 102.6 ng/mL.Conclusion Mast cells and eosinophils are involved in non-allergic and allergic forms of chronic nasal inflammation. We established an in vitro assay for tryptase and ECP in nasal secretions and defined norm values based on our data and method. In vitro measurement of biological markers in nasal secretions provides important information for differential diagnosis and therapeutic strategies of chronic nasal inflammation.

Late-phase response in allergic rhinitis is characterized by tissue eosinophilia and influx of CD4+ T-cells. IL-16 and MIP-1 alpha are highly chemotactic on T-cells and on eosinophils. Both IL-16 and MIP-1 alpha have been demonstrated to be up-regulated after challenge in the late-phase response in various atopic conditions other than allergic rhinitis. The aim of our study was to determine the expression of IL-16 and MIP-1 alpha in nasal secretions following allergen challenge in allergic rhinitis, and to compare these with characteristic late-phase mediators such as IL-5 and ECP. Nasal secretions of 14 allergic volunteers challenged intranasally by their specific allergen were studied from 20 minutes to 8 hours after allergen challenge. Nasal secretions were analyzed by routine ELISA for IL-16, MIP-1 alpha, IL-5, and ECP. IL-16 and MIP-1 alpha increased significantly in nasal secretions of challenged allergic patients in the late-phase response. IL-16 revealed highest amounts 5 hours after challenge, whereas MIP-1 alpha peaked at 7 hours. Both correlated significantly (r = 0.917, p < 0.05) at 6 hours. IL-5 and ECP peaked between 6 and 8 hours and correlated significantly (r = 0.951, p < 0.01) at 6 hours as well. Our data demonstrate that IL-16 and MIP-1 alpha are expressed in the late-phase response in allergic rhinitis in a more or less similar kinetic like IL-5 and ECP. They are suggested to be responsible for the observed influx of eosinophils (IL-5, IL-16, and MIP-1 alpha) and CD4+ T-cells (IL-16 and MIP-1 alpha) into the challenged allergic mucosa.

Obstructive sleep apnea syndrome (OSAS) is a condition characterized by recurrent episodes of obstruction of the upper airway. The aim of this study was to evaluate whether nasal obstruction due to allergic rhinitis constitutes a risk factor for OSAS. Patients (n = 119) presenting typical symptoms of sleep apnea were tested for OSAS using polysomnography. Additionally all patients were tested in vivo and in vitro (including nasal eosinophilic cationic protein) for allergic rhinitis. Examination for allergic rhinitis revealed that 88.3% of all patients had no allergic rhinitis, whereas only 11.7% were diagnosed as allergic. No significant differences in sleeping parameters were observed between allergic and non-allergic patients. Comparison of parameters indicative of relevant OSAS (apnea-hypopnea index [AHI] > 10) revealed that 60% of non-allergic patients had relevant OSAS, compared to only 50% of allergic patients. Investigation of allergic subgroups revealed similar results: no significant differences in sleeping parameters or elevated rates of relevant OSAS parameters were observed, especially in perennial allergic rhinitis due to house dust mites. No elevated rates of allergic rhinitis were observed in the studied cohort of patients suffering from sleep apnea or OSAS. Furthermore, no significant differences in sleeping behavior or polysomnography parameters were found on comparing allergic and non-allergic patients. In summary, our data rule out allergic rhinitis as a major risk factor for OSAS.

OBJECTIVE:To compare concentrations of interleukin-5 (IL-5), immunoglobulin E (IgE), eosinophilic cationic protein (ECP), and soluble intercellular adhesion molecule-1 (sICAM-1) in nasal secretion and serum of patients with chronic nonallergic sinusitis, allergic rhinitis, and nonallergic nasal polyposis to obtain information about the pathogenesis of these diseases.METHODS:Nasal secretion and serum were analyzed by routine enzyme-linked immunosorbent assay techniques. Nineteen patients with chronic nonallergic sinusitis, 24 patients with seasonal allergic rhinitis, and 18 patients with nonallergic nasal polyposis were included in the study. Eight healthy, nonallergic probands served as control subjects.RESULTS:Significantly elevated concentrations of IL-5 (5-fold, P < .05) and IgE (15-fold, P < .01) were detected in nasal secretion of patients with allergic rhinitis (IL-5, 51.8 +/- 13.2 pg/mL; IgE, 41.9 +/- 20.9 kU/L) or nonallergic nasal polyposis (IL-5, 57.9 +/- 36.9 pg(mL; IgE, 40.5 +/- 20.2 kU/L) compared with controls (IL-5, 10.6 +/- 7.8 pg/mL; IgE, 2.8 +/- 0.5 kU/L) or with patients with chronic nonallergic sinusitis (IL-5, 16.5 +/- 13.2 pg/mL; IgE, 5.4 +/- 3.1 kU/L). There were no significant differences between patients with allergic rhinitis and those with nonallergic nasal polyposis. Concentrations of ECP were significantly elevated (sixfold, P < .01) in patients with allergic rhinitis (297.8 ng/mL +/- 173.1) compared with controls (52.4 +/- 28.0 ng/mL) or patients with chronic nonallergic sinusitis (44.8 +/- 40.1 ng/mL), whereas twofold higher concentrations (not significant) of ECP were observed in patients with nonallergic nasal polyposis (107.1 +/- 26.6 ng/mL). Significantly elevated concentrations of sICAM-1 in nasal secretion (threefold, P < .05) were detected only in patients with chronic nonallergic sinusitis (79.4 +/- 45.6 ng/mL). The elevated sICAM-1 nasal secretion values in this group correlated significantly (P < .05) to the serum values.CONCLUSIONS:Equally elevated concentrations of IL-5 and IgE in patients with allergic rhinitis and nonallergic nasal polyposis implicated similar pathogenic processes in both diseases. Whereas the pathogenesis of allergic rhinitis is IgE-specific, the pathogenesis of nasal polyps is not as clear. IL-5 was suggested to play a pivotal role in tissue eosinophilia, which was confirmed by data in the present study. Elevated concentrations of ECP were suggested to result from tissue eosinophilia--a characteristic of both diseases. Elevated concentrations of sICAM-1 in patients with chronic nonallergic sinusitis pointed to its key role in the recruitment of neutrophils into the inflamed tissue, whereas an important role in eosinophil recruitment was ruled out.