The time course of nasal cytokine secretion in patients with aspirin-exacerbated respiratory disease (AERD) undergoing aspirin desensitization: preliminary data.

PURPOSE: Aspirin-exacerbated respiratory disease (AERD) is a severe form of chronic rhinosinusitis with nasal polyps (CRSwNP) accompanied by asthma and an aspirin intolerance. The underlying pathomechanism of AERD still remains unclear, recent data suggest a complex inflammatory imbalance. In the present study, we investigated the cytokine patterns in AERD, CRSwNP and healthy control patients. Furthermore, we describe the change in cytokine level in the course of aspirin desensitization (AD) with continuous intake of aspirin. METHODS: The study included a total of 104 participants, 48 healthy controls, 45 patients with nasal polyps and 11 patients with AERD undergoing AD. Nasal secretions were analyzed for IL-1ß, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, THF-α, IFN-γ, eotaxin and ECP using Bio-Plex Human Cytokine Assay and Uni-CAP FEIA. Baseline measurements of cytokine levels were performed in all 104 patients; in patients with AERD, follow-up was performed 1-6 and 6-24 months after the initiation of AD. RESULTS: Our preliminary results show a TH2 dominated, eosinophilic milieu in AERD patients, which decreased in the first weeks of AD. However, after 6 months of AD, proinflammatory cytokines show a tendency to increase again. Also, TH1 as well as Treg associated cytokine seem to increase over time. CONCLUSIONS: For the first time, the present work shows the cytokine pattern in nasal secretions of AERD patients before and during AD. Further investigation of the complex interaction of inflammatory cytokines during AD might reveal important insights into the disease entity of AERD and open up new horizons for a targeted therapy.

Eosinophils and mast cells: a comparison of nasal mucosa histology and cytology to markers in nasal discharge in patients with chronic sino-nasal diseases.

Allergic rhinitis (AR), nasal polyps (NP) as well as chronic rhinosinusitis (CRS) are all known to be associated with eosinophilic infiltration and elevated numbers of mast cells (MC) within the mucosa. Both cell types and their markers eosinophilic cationic protein (ECP) and tryptase are utilized in the diagnosis and management of chronic sino-nasal diseases. Mucosal cytology samples were gathered by cytobrush, histological samples were obtained from the inferior turbinate. In both sample sets, the number of eosinophils and MC was determined. Their corresponding markers ECP and tryptase were quantified from nasal discharge. Patients were grouped with reference to their main diagnosis: AR (n = 34), NP (n = 25), CRS (n = 27) and controls (n = 34). Eosinophil counts from cytobrush and ECP levels were significantly elevated in NP compared to all other groups-31- and 13-fold over control, respectively. However, histologic review did not reveal any difference in eosinophil count among groups. Tryptase was significantly elevated threefold in AR versus CRS and controls. No correlation to cytological and histological MC counts could be found. ECP levels in nasal discharge as well as eosinophil counts can provide useful information with regard to the diagnosis. Likewise, tryptase concentrations can do. The presented data show that the measurement of markers in nasal discharge is superior in differentiating among diagnosis groups. Given that the collection of nasal secretions is more comfortable for patients than the more invasive techniques, we recommend first line ECP and tryptase testing performed on nasal secretions.

Mediators and cytokines in persistent allergic rhinitis and nonallergic rhinitis with eosinophilia syndrome.

BACKGROUND: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES) show typical symptoms of persistent allergic rhinitis (PAR). The aim of the present study was to compare nasal cytokine patterns between NARES and PAR. METHODS: Nasal secretions of 31 patients suffering from NARES, 20 patients with PAR to house dust mite and 21 healthy controls were collected using the cotton wool method and analyzed for interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1ß (MIP-1ß) by Bio-Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by UniCAP-FEIA. RESULTS: NARES and PAR presented elevated levels of tryptase, while ECP was markedly increased solely in NARES compared to both the controls and PAR. Elevated levels of IL-1ß, IL-17, IFN-γ, TNF-α and MCP-1 were found in NARES compared to the controls as well as PAR. MIP-1ß was elevated in NARES and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL- 5 was elevated in PAR only. CONCLUSIONS: In patients with NARES and PAR, eosinophils and mast cells appear to be the pivotal cells of inflammation, reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as factors for eosinophil migration and survival. The elevated levels of proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating process of inflammation in NARES which seems to be more pronounced than in PAR. IL-17 might be a factor for neutrophilic infiltration or be responsible for remodeling processes in NARES.

Tropomyosin sensitization in house dust mite allergic patients.

The growing popularity and frequency of consumption of seafood is accompanied by an increasing number of adverse reactions reported in literature. Allergic reactions to seafood can generate a variety of symptoms ranging from a mild oral allergy syndrome to keen anaphylactic reactions. Tropomyosin, the major shellfish allergen is regarded to be responsible for clinical cross-reactivity to inhaled house dust mites. The aim of the study was to investigate the prevalence of sensitization to tropomyosin in house dust mite allergic patients in southern Bavaria and to compare the results with allergic symptoms. Sera of house dust mite allergic patients (positive skin prick test, allergen-specific IgE and intranasal provocation) were screened for IgE antibodies to tropomyosin (Der p 10). Patients were contacted by phone to evaluate allergic symptoms when consuming seafood. IgE antibodies to house dust mite tropomyosin (Der p 10) could be found in 4 out of 93 sera (4.3%). Two of these four patients (50%) showed itching and swelling of oral mucosa accompanied by bronchial obstruction after consumption of shrimp. Two patients had no problems when eating seafood. None of the seronegative patients complained about any health problems during or after consumption of seafood. In conclusion, cross-reactivity to tropomyosin in house dust mite allergic patients in southern Bavaria, Germany is rarer than suspected. Beside the direct allergic reactions, a further part of reactions to seafood must therefore be ascribed to other mechanisms such as intoxication or intolerance to, e.g. additives in the food product.

Mediators and cytokines in allergic and viral-triggered rhinitis.

Intermittent allergic rhinitis and common cold constitute frequent conditions and show similar clinical symptoms. The purpose of this study was to investigate the pattern of cytokines in the nasal fluid of patients with acute symptoms caused by allergic and viral rhinitis. Nasal secretions were analyzed by immunosorbent assay techniques using a cytokine panel assay and routine ELISA. Allergic patients had significantly higher levels of eosinophil cationic protein (ECP), interleukin (IL)-5, and tryptase. Significantly elevated concentrations of proinflammatory cytokines (IL-1b, IL-6, IL-7, IL-17, interferon [IFN] gamma, and tumor necrosis factor [TNF]-alpha) as well as chemokines for cellular infiltration (IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1beta), factors for cellular proliferation (granulocyte colony-stimulating factor [G-CSF] and granulocyte macrophage colony-stimulating factor [GM-CSF]), and elastase were found in viral rhinitis. IL-10 was only detectable in viral rhinitis. IL-4 was significantly higher in patients with viral rhinitis than allergic rhinitis, and IL-5 was significantly elevated in viral rhinitis compared with controls. In viral-triggered rhinitis, we detected a predominantly Th1-type cytokine pattern with potent proinflammatory mediators. Factors reflecting a neutrophil and eosinophil immune response, due to IL-5, IL-8, GM-CSF, ECP, and elastase were shown. Nasal secretions of patients with allergic rhinitis showed highest concentrations of tryptase, IL-5, and ECP, reflecting a mast cell and eosinophil immune response. Nasal secretion levels of IL-4 did not show highest levels in allergic rhinitis but did in viral rhinitis. IL-4 also may play a role in limiting inflammatory processes by inhibiting the production of inflammatory cytokines.

Latex allergy, a special risk for patients of otorhinolaryngology and head and neck surgery?

A total of 206 patients of the otorhinolaryngology (ORL) department and 204 of the visceral surgery department of the Ludwig Maximilians University of Munich were preoperatively evaluated for latex-specific sensitization. A prick test, a questionnaire, and an enzyme-linked immunosorbent assay immunoprecipitation for IgE antibodies were performed. Latex is a widely spread allergen, and it does not only concern healthcare populations. Within the ORL surgery group, 43 (20.9%) patients were sensitized against latex allergen, and 2 of them were reported to manifest symptoms in consorting with latex. In the cohort of visceral surgery patients, we detected only 23 patients (11.3%) with sensitization against latex. Moreover, most patients were positively detected with the skin prick test (86.4%), whereas the enzyme-linked immunosorbent assay method was less sensitive (18.3%). Patients of the ORL department were considerably more frequently exposed to latex protein particles than patients of the visceral surgery department. This difference attributes to their significant difference in mean age: 44 years in the ORL patients group versus 58 years in the visceral patients cohort. Furthermore, we did not find any correlation to the number of past operations--although undergoing any surgical procedures is a well-known risk factor in other studies about latex sensitization in surgical patients.

Factors contributing to nasal 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 eotaxin; of the adhesion molecule sVCAM-1; and of the leukotriene LTC4 for the allergic late phase eosinophilia.

An approach of immunoneurological aspects in nasal allergic late phase.

This examination is an approach of the allergic early phase reaction (EPR) and late-phase reaction (LPR) via quality of life (QoL), acoustic rhinometry, and eosinophilic cationic protein (ECP), interleukin (IL)-5, and leukotriene C4 (LTC4). Results are discussed under consideration of a possible neurological participation in the occurrence and persistence of the allergic inflammatory process. Thirteen patients suffering from seasonal allergic rhinitis were challenged intranasally by their specific allergen. In a time window of 8 hours after provocation, patients completed QoL questionnaires, and underwent acoustic rhinometry. Nasal secretions were analyzed for total protein, ECP, IL-5, and LTC4 The need to sneeze and a runny nose were the strongest symptoms during the EPR and LPR. Restriction of overall QoL persisted much longer than any other symptom. Evaluation of acoustic rhinometry revealed an EPR in 100% and a LPR in 92%. The EPR was marked by increases in volume of nasal secretions, total protein, and elevations in LTC4. Allergic LPR was marked by increases in nasal secretions, total protein, ECP, IL-5, and LTC4. Both the need to sneeze as strongest and announcing symptom of the allergic LPR and the persisting restriction in overall QoL seem to propose a possible neurological participation in the development of the allergic late-phase inflammation and consequent hyperresponsiveness of the nasal mucosa. In addition, the persistence and enhancement of the nasal cycle during the allergic LPR can be interpreted in favor of a hypothetical activation of the autonomous nervous system. LTC4 enters this discussion as a promising link at the immunoneurological interface.