Neonatal hearing screening - does failure in TEOAE screening matter when the AABR test is passed?

PURPOSE: Newborns who fail the transient evoked otoacoustic emissions (TEOAE) but pass the automatic auditory brainstem response (AABR) in universal newborn hearing screening (UNHS), frequently have no further diagnostic test or follow-up. The present study aimed to investigate whether hearing loss might be missed by ignoring neonatal TEOAE failure in the presence of normal AABR. METHODS: A retrospective analysis was conducted in newborns presenting between 2017 and 2021 to a tertiary referral centre due to failure in the initial UNHS. The main focus was on infants who failed TEOAE tests, but passed AABR screening. The clinical characteristics and audiometric outcomes were analysed and compared with those of other neonates. RESULTS: Among 1,095 referred newborns, 253 (23%) failed TEOAE despite passing AABR screening. Of the 253 affected infants, 154 returned for follow-up. At 1-year follow-up, 46 (28%) achieved normal audiometric results. 32 (21%) infants had permanent hearing loss (HL) confirmed by diagnostic ABR, 58 (38%) infants had HL solely due to middle ear effusion (MEE), and for 18 (12%) infants HL was suspected without further differentiation. The majority of permanent HL was mild (78% mild vs. 13% moderate vs. 9% profound). The rate of spontaneous MEE clearance was rather low (29%) leading to early surgical intervention in 36 children. The profile of the risk factors for hearing impairment was similar to that of newborns with failure in both, TEOAE and AABR; however, there was a stronger association between the presence of risk factors and the incidence of HL (relative risk 1.55 vs. 1.06; odds ratio 3.61 vs. 1.80). CONCLUSION: In newborns, the discordance between a "refer" in TEOAE and a "pass" in AABR screening is associated with a substantial prevalence of hearing impairment at follow-up, especially in the presence of risk factors.

Clinical Relevance of Profilin Sensitization Concerning Oral Allergy Syndrome in Birch Pollen Sensitized Patients.

PURPOSE: Many plant food allergens contain homologs to the major birch allergen Bet v 1; therefore, the majority of patients with birch pollen allergy suffer from oral allergy syndrome. We studied the relevance of sensitization of Bet v 1 and co-sensitization with profilin concerning the clinical manifestations of an oral allergy syndrome. PATIENTS AND METHODS: A total of 1119 patients with a positive skin prick test to birch and diagnostic for specific IgE to the allergen components Bet v 1 and profilin were analyzed retrospectively regarding complaints in the upper and lower airways, with demographic data as well as oral and gastrointestinal allergy symptoms. RESULTS: Patients with simultaneous specific IgE to the allergen components Bet v 1 and profilin have to deal more often with an oral allergy syndrome and intestinal reactions. They also suffer more frequently and severely from rhinitis symptoms and show a higher tendency for asthma. No increased number of systemic reactions was seen. CONCLUSION: Patients with birch allergy recognizing both allergens have more probabilities of suffering from an oral allergy syndrome, and allergologists should be aware of this in order to give better advice to their patients.

Comparison of ABR and ASSR using narrow-band-chirp-stimuli in children with cochlear malformation and/or cochlear nerve hypoplasia suffering from severe/profound hearing loss.

OBJECTIVES: In pediatric audiology, objective techniques for hearing threshold estimation in infants and children with profound or severe hearing loss play a key role. Auditory brainstem responses (ABR) and auditory steady-state responses (ASSR) are available for frequency-dependent hearing threshold estimations and both techniques show strong correlations but sometimes with considerable differences. The aim of the study was to compare hearing threshold estimations in children with and without cochlear and cochlear nerve malformations. METHODS: Two groups with profound or severe hearing loss were retrospectively compared. In 20 ears (15 children) with malformation of the inner ear and/or cochlear nerve hypoplasia and a control group of 20 ears (11 children) without malformation, ABR were measured with the Interacoustics Eclipse EP25 ABR system® (Denmark) with narrow-band CE-chirps® at 500, 1000, 2000 and 4000 Hz and compared to ASSR at the same center frequencies under similar conditions. RESULTS: ABR and ASSR correlated significantly in both groups (r = 0.413 in malformation group, r = 0.82 in control group). The malformation group showed a significantly lower percentage of "equal" hearing threshold estimations than the control group. In detail, patients with isolated cochlear malformation did not differ significantly from the control group, whereas patients with cochlear nerve hypoplasia showed significantly greater differences. CONCLUSION: ABR and ASSR should be used jointly in the diagnostic approach in children with suspected profound or severe hearing loss. A great difference in hearing threshold estimation between these techniques could hint at the involvement of cochlear nerve or cochlear nerve hypoplasia itself.

How reliable is anamnestic data in predicting the clinical relevance of house dust mite sensitization?

PURPOSE: For perennial inhalant allergens such as house dust mite (HDM), the German guideline on allergen-specific immunotherapy explicitly recommends provocation testing. This procedure is time-consuming, expensive, and potentially dangerous for the patient. Recently it has been discussed whether provocation tests are really necessary for diagnosing allergy to Dermatophagoides species. Thus, our study aimed to analyze the concordance between nasal provocation tests with Dermatophagoides species and anamnestic data. METHODS: We retrospectively analyzed the concordance between patients' histories including self-reported symptom scores and the results of provocation testing in 471 individuals with proven sensitization to Dermatophagoides species. RESULTS: 248 patients had a positive nasal provocation test (NPT) result to Dermatophagoides species and 223 individuals a negative NPT result. Patients allergic to HSM suffered significantly more often from atopic dermatitis (14% vs. 7%, p = 0.046) and more from asthma (20% vs. 19%, p = 0.851). Moreover, individuals with clinically silent sensitization complained less about nasal secretion (37% vs. 45%, p = 0.244) but significantly more about nasal dryness (46% vs. 34%, p = 0.046) whereas rates of nasal airway obstruction, ocular complaints and sleep quality were comparable in both groups. Allergic patients reported more often perennial (34% vs. 30%, p = 0.374) and location-dependent (39% vs. 31%, p = 0.090) symptoms. However, the discrepant prevalence of atopic dermatitis was the only statistically significant difference between both groups. CONCLUSION: Despite slight differences between both patient groups, clinical data are not sufficient to distinguish between silent sensitization and clinically relevant allergic rhinitis to HDM. Therefore, nasal provocation testing remains the gold standard for assessing clinical relevance in patients sensitized to Dermatophagoides species.

Value of Component Resolved Diagnostics to Aspergillus fumigatus in Patients with Upper Airway Complaints.

INTRODUCTION: Sensitization to Aspergillus fumigatus is a risk factor for severe asthma. However, little is known about its presence, appearance, and impact on allergic rhinitis. Herein, we investigated the usefulness of component resolved diagnostics in patients sensitized to Aspergillus fumigatus protein extract. METHODS: Seventy-eight patients with suspected allergic rhinitis and elevated IgE levels toward Aspergillus fumigatus protein extract were retrospectively evaluated regarding their total and Aspergillus-specific IgE levels and their skin prick test. Furthermore, they were tested for specific IgE antibodies against Asp f 1, 2, 3, 4, and 6. RESULTS: Skin prick test missed 6 patients (7.7%) with elevated IgE toward Aspergillus fumigatus protein extract. Fifty percent of patients (n = 39) were sensitized to at least one component. Even though monosensitization affected all components, all patients with positivity toward more than one component were sensitized to Asp f 1. There was a statistically significant increase of Aspergillus-specific IgE with increasing number of components affected by sensitization. Many patients were oligo- (34.6%) or polysensitized (51.3%). There was a high prevalence of sinusitis (61.8%). CONCLUSIONS: Component resolved diagnostic testing toward the major allergen Asp f 1 was less sensitive than skin prick test and serology to Aspergillus fumigatus protein extract. However, sensitivity of component resolved diagnostics might be underestimated. Diagnostics of the species-specific allergens Asp f 1, 2, and 4 might allow to differentiate between genuine and cross-reactive sensitization. In the clinical routine, skin prick test and serology to crude extract remain the methods of choice.

Does the principle of homologous groups allow a reduction of allergens in the skin prick test panel?

PURPOSE: Regulatory and economic conditions drive the application of the concept of homologous groups on therapeutic and diagnostic formulations. In this context, a possible reduction of allergens in the skin prick test panel in the clinical routine should be investigated for the grass, birch and Dermatophagoides homologous group. METHODS: Grass and cultivated rye skin prick test results of 1101 patients, birch/hazel/alder skin prick test results of 1131 patients and 1068 Dermatophagoides pteronyssinus and farinae skin prick tests were retrospectively evaluated with regard to sensitivity and false-negative rate detecting sensitization against cultivated rye with grass skin prick test, sensitization against hazel and/or alder with birch skin prick test and sensitization towards Dermatophagoides farinae with Dermatophagoides pteronyssinus skin prick test. RESULTS: Skin prick test results in all groups highly correlated in Spearman Rank Order correlation. Sensitivity of grass skin prick test detecting sensitization against cultivated rye was highest with 98.9%, sensitivity of birch skin prick test detecting sensitization toward hazel and alder was 95.6 and 90.0%, respectively. Sensitivity of skin prick test with Dermatophagoides pteronyssinus detecting sensitization towards Dermatophagoides farinae was 93.6%. Only 26 patients with positive rye, hazel, alder or Dermatophagoides farinae skin prick test that were overlooked by grass, birch or Dermatophagoides pteronyssinus skin prick test reported allergic symptoms. CONCLUSION: In routine clinical practice, sensitization against cultivated rye can safely be detected by skin prick test with grass allergen. In addition, the sensitivity of birch skin prick test is high in terms of sensitization towards hazel, but lower for alder. Sensitivity of Dermatophagoides pteronyssinus skin prick test also is high to detect sensitization towards Dermatophagoides farinae. Further research will indicate if several skin prick test allergens will disappear and be completely replaced by a single skin prick test based on the principle of homologous groups.

The Role of Der p 23 Sensitization: An Analysis of 474 Patients Sensitized to Mite.

INTRODUCTION: House dust mite contains several allergen components and causes perennial allergy. Lately, a new major allergen, Der p 23, was described with relatively high sensitization rates in different European Countries. In addition, Der p 23 is supposed to cause asthmatic disease. OBJECTIVE: We would like to question the prevalence and clinical impact of specific immunoglobulin E to Der p 23 in a large patient sample in southern Bavaria, Germany. METHODS: 474 patients from southern Bavaria, who visited the allergy department within the Department of Oto-Rhino-Laryngology of a university hospital, with sensitization to Dermatophagoides pteronyssinus were retrospectively compared regarding their sensitization profile to Der p 1, Der p 2, and Der p 23 and their clinical characteristics. RESULTS: Among D. pteronyssinus-sensitized patients, the overall sensitization rate to Der p 23 was 42% in southern Bavaria. Most likely, patients were simultaneously sensitized to Der p 1, Der p 2, and Der p 23. Der p 23-sensitized patients reported more frequently asthma and showed higher prevalence of poly-sensitization towards 3 additional allergen groups and higher prevalence of double-sensitization to Der p 1 and Der p 2 compared to patients with missing sensitization to Der p 23. Considering the results of allergen provocation tests, neither IgE sensitization against Der p 23 nor levels of specific immunoglobulin E to Der p 23 allow a clear prediction of the clinical relevance of the sensitization. CONCLUSION: With a sensitization rate of 42%, Der p 23 closely misses the criterion of a major allergen in our southern Bavarian patient collective. A higher prevalence of polysensitization and self-reported asthma was the only clinical feature found in Der p 23-sensitized patients.

De novo sensitization during subcutaneous allergen specific immunotherapy - an analysis of 51 cases of SCIT and 33 symptomatically treated controls.

Since the beneficial implementation of allergen specific subcutaneous immunotherapy (SCIT), there are only a few studies on the risk of SCIT-induced neosensitizations. In 51 patients, we retrospectively analyzed sIgE and sIgG patterns by a multiplex ELISA as well as demographic and clinical features before and after SCIT. 33 allergic patients, who only received symptomatic treatment, served as controls. In 12 of 51 SCIT-treated patients (24%), we found new sIgE against allergen components of the allergen source treated by SCIT; eight of them were adults. Among controls, no adult patient showed neosensitization to components of the primarily affected allergen source. Only two children of the control group were affected by neosensitization, which was limited to major allergen components and rarely accompanied by sIgG. In the SCIT-treated group, neosensitization affected major and minor allergen components, and was accompanied by a strong induction of sIgG against major components. A clear clinical predictor of neosensitization during SCIT was not found. Comparing symptom scores, patients seem to profit more from SCIT, if neosensitization remained absent. Patients undergoing SCIT might carry an enhanced risk of neosensitization towards formerly unrecognized allergen components. According to anamnestic data, these neosensitizations might be of clinical relevance - supporting attempts towards personalized recombinant vaccines.

Trends in aeroallergen sensitization in Germany - An analysis of 2919 serological data sets of a university ENT department.

Background: Recently, population-based birth-cohort studies provided an insight into the allergic march during childhood.Aims: Our study aimed to investigate sensitization pattern until advanced age.Patients and methods: Demographic, clinical and serological characteristics of 2919 patients with positive allergen-specific IgE between 1999 and 2019 were analyzed. We performed subgroup analysis of various age-groups and different years of birth to distinguish between age-dependent changes and birth-cohort-effects.Results: Since 1999, the proportion of sensitized children has significantly increased. The prevalence of sIgE towards most allergens reached its peak in adolescence or young adulthood. Only to mites, the highest rate of sensitization was found in childhood. With further aging, the prevalence of sIgE significantly decreased in most sensitizations. Only to Fagales, the highest rate of sensitization was observed among patients >65 years. The year-of-birth analysis proved the above-mentioned changes to be age-dependent. Further, it revealed various sensitization trends from older to younger generations.Conclusions and significance: The increased proportion of children with sensitization during the last 20 years outlines the allergy epidemic. Probably due to immunosenescence, the aeroallergen sensitization rates decreased with aging, except for Fagales. Over time, different aeroallergens gained or lost relevance, potentially due to environmental and life-style changes.

Comparison of ABR and ASSR using NB-chirp-stimuli in children with severe and profound hearing loss.

INTRODUCTION: Objective techniques for hearing threshold estimation in infants and children with profound or severe hearing loss play a key role in pediatric audiology to prevent speech acquisition disorders by choosing the adequate therapy. Auditory brainstem responses and auditory steady-state responses are available for frequency-dependent hearing threshold estimations and both techniques show strong correlations. However, various systems and stimuli are available, which is one reason why comparison is challenging, and, so far, no single "gold standard" could be established for hearing threshold estimation in children suffering from profound or severe hearing loss. The aim of the study was to compare hearing threshold estimations in children with profound or severe hearing loss derived with narrow-band CE-chirps evoked auditory brainstem responses and auditory steady-state response. SUBJECTS: and Methods: 71 children (121 ears) with an age from 3 month to 15 years were measured with the Interacoustics Eclipse EP25 ABR system® (Denmark) with narrow-band CE-chirps® at 500, 1000, 2000 and 4000 Hz under identical conditions. RESULTS: Auditory brainstem responses and auditory steady-state responses highly correlate (r = 0.694, p < 0.001). Correlation coefficients differ depending on the center frequency and patient age. Generally, auditory steady-state responses show a better hearing threshold than auditory brainstem responses or a remaining hearing threshold when auditory brainstem responses could not be obtained. In approximately 15% of cases this would have affected the therapeutic strategy when only taking one technique into account. CONCLUSION: Auditory brainstem responses and auditory steady-state responses should be jointly used in the diagnostic approach in children with suspected profound or severe hearing loss.

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.

Randomized controlled single-blinded clinical trial of functional voice outcome after vascular targeting KTP laser microsurgery of early laryngeal cancer.

BACKGROUND: Local control rate (LCR) of early glottic cancer is high after radiation therapy or transoral laser microsurgery (TLM). The aim of this study was to investigate functional voice outcome after TLM using a microvessel-ablative potassium-titanyl-phosphate (KTP) laser in comparison with a gold standard cutting CO2 laser. METHODS: The primary end point of this prospective, randomized, single-blinded, clinical phase II study with control group was voice outcome during a follow-up of 6 months assayed by Voice Handicap Index (VHI-30)-questionnaires in patients with unilateral high-grade dysplasia, carcinoma in situ or early glottic cancer undergoing TLM-KTP (n = 8) or TLM-CO2 (n = 12). The secondary end point was LCR. RESULTS: Starting from the 9-week-follow-up visit, TLM-KTP yielded significantly reduced VHI scores compared to TLM-CO2 . No relapse occurred after TLM-KTP in contrast to one recurrence after TLM-CO2 within 6 months. CONCLUSION: Multicenter phase II or III studies on voice outcome or local control rate after TLM-KTP in early glottic cancer are warranted enrolling larger patient cohorts.

Component resolved analysis of ash pollen allergy in Bavaria.

BACKGROUND: Sensitization to ash pollen is underestimated in various regions. The prevalence in Germany is about 10%. However, allergy to ash pollen is widely overlooked by allergists, since the pollination period of ash and birch in central Europe closely overlap and rhinoconjunctival symptoms during April/May are often assigned to birch pollen. Component resolved analysis of the different ash allergens is not routinely available. Therefore, we would like to question the usefulness of component resolved diagnostic via olive components, as ash and olive are both part of the Oleaceae family. METHODS: 113 patients with nasal provocation and skin prick test to ash were retrospectively compared regarding their specific immunoglobulin E antibody profiles with response to native ash extract, rOle e 1, nOle e 7 and rOle e 9. RESULTS: In nasal provocation testing 58% of 113 patients sensitized to ash were allergic, 42% were only sensitized without showing symptoms. Skin prick testing and serology against native ash extract detected most patients sensitized to ash pollen, whereas rOle e 1 was less sensitive. However, the value of measurements of skin prick test, serology to native ash extract and rOle e 1 did not allow a differentiation between an allergy and clinically silent sensitization. Specific antibodies to nOle e 7 and rOle e 9 were only seen in individual patients and were all positive for native ash extract and rOle e 1. CONCLUSION: Skin prick testing and serology to native extract of ash pollen are the most reliable tools to diagnose a sensitization to ash pollen for patients living in Germany. Component resolved diagnostic to the major allergen rOle e 1 as representative of the Oleaceae family is possible but was less sensitive. Diagnostic of nOle e 7 and rOle e 9 did not show any additional benefit. Regarding differentiation between allergy and clinically silent sensitization to ash pollen, provocation is the leading diagnostic tool. Concluding, in routine clinical practice the standard methods-skin prick test, serology to native ash extract and provocation testing-remain crucial in the diagnosis and differentiation of ash sensitization and allergy.

The Clinical Impact of Bet v 6 in Birch Pollen-Sensitized Patients.

BACKGROUND: Bet v 6, a minor birch pollen allergen, is commercially available for allergen-specific IgE antibody testing. However, there is hardly any literature on the clinical impact of Bet v 6. The aim of the present study was to analyze if testing specific IgE against Bet v 6 can add valuable benefit to the standard diagnostics of birch pollen-sensitized patients, especially in patients with unknown sensitization-eliciting allergens. METHODS: Birch pollen-sensitized patients with missing IgE reactivity against Bet v 1, 2, and 4 were tested for specific IgE antibodies against Bet v 6. For comparison, an equal number of randomly selected patients with birch pollen sensitization, regardless of their individual sensitization patterns, were tested for specific anti-Bet v 6. RESULTS: Of 57 cases with missing reactivity against the standard birch pollen allergens, 2 patients were positive for Bet v 6. In the representative sample, 3 patients showed specific IgE against Bet v 6 - resulting in a total prevalence of 5%. None of the Bet v 6-positive patients showed allergic symptoms after exposure to birch pollen or an oral allergy syndrome. An increased prevalence of asthma and a higher degree of sensitization were the only distinctive clinical features in Bet v 6-positive patients. CONCLUSIONS: Among birch pollen-sensitized patients, the prevalence of specific IgE against Bet v 6 is low. Further, sensitization to Bet v 6, which shows characteristics of a panallergen, remains clinically silent. Therefore, determination of anti-Bet v 6 is not considered useful in the clinical routine.

Usefulness of component resolved analysis of cat allergy in routine clinical practice.

BACKGROUND: Cat allergy is of great importance, and its prevalence is increasing worldwide. Cat allergens and house dust mite allergens represent the major indoor allergens; however, they are ubiquitous. Cat sensitization and allergy are known risk factors for rhinitis, bronchial hyperreactivity and asthma. Thus, the diagnosis of sensitization to cats is important for any allergist. METHODS: 70 patients with positive skin prick tests for cats were retrospectively compared regarding their skin prick test results, as well as their specific immunoglobulin E antibody profiles with regard to their responses to the native cat extract, rFel d 1, nFel d 2 and rFel d 4. 35 patients were allergic to cats, as determined by positive anamnesis and/or nasal provocation with cat allergens, and 35 patients exhibited clinically non-relevant sensitization, as indicated by negative anamnesis and/or a negative nasal allergen challenge. RESULTS: Native cat extract serology testing detected 100% of patients who were allergic to cats but missed eight patients who showed sensitization in the skin prick test and did not have allergic symptoms. The median values of the skin prick test, as well as those of the specific immunoglobulin E antibodies against the native cat extract, were significantly higher for allergic patients than for patients with clinically non-relevant sensitization. Component based diagnostic testing to rFel d 1 was not as reliable. Sensitization to nFel d 2 and rFel d 4 was seen only in individual patients. CONCLUSION: Extract based diagnostic methods for identifying cat allergy and sensitization, such as the skin prick test and native cat extract serology, remain crucial in routine clinical practice. In our study, component based diagnostic testing could not replace these methods with regard to the detection of sensitization to cats and differentiation between allergy and sensitization without clinical relevance. However, component resolved allergy diagnostic tools have individual implications, and future studies may facilitate a better understanding of its use and subsequently may improve the clinical management of allergic patients.

Clinical Relevance of IgE to Profilin and/or Polcalcin in Pollen-Sensitized Patients.

BACKGROUND: Component-resolved diagnostics is gaining importance in allergy diagnostics. Allergen extracts contain components with different rates of prevalence and clinical relevance, which can be subdivided at molecular level into major and minor allergens. Clinical complaints are usually triggered by major allergens, while the role of sensitization to the panallergens profilin and polcalcin still remains unclear. METHODS: Eighty-six patients from southern Bavaria with sensitization to the panallergens profilin (Bet v 2/Phl p 12) and/or polcalcin (Bet v 4/Phl p 7) were examined in regard to their sensitization to the 4 main botanic denominations Betulaceae, Oleaceae, Poaceae and Asteraceae by skin prick test and measurement of specific immunoglobulin E antibodies to natural allergen extracts as well as major allergen components rPhl p 1/5, rBet v 1, rOle e 1 and nArt v 1. Sensitization was rated as clinically relevant or irrelevant depending on anamnesis or intranasal allergen challenge. RESULTS: Regarding the 4 botanic denominations, there was no significant difference in the incidence of sensitization to the panallergens profilin, polcalcin or both. The sensitization pattern does not alter when subdividing the cohort into clinically relevant and silent sensitization. We did not find clinically symptomatic sensitization to panallergens without cosensitization to a major allergen. CONCLUSIONS: Our results suggest that sole sensitization to panallergens seems to have no clinical relevance in allergic rhinoconjunctivitis. Clinical complaints seem to be triggered manly by major allergens. Thus, component-resolved allergy diagnostics is crucial in the diagnosis and treatment of polysensitized patients.

Non-allergic rhinitis with eosinophilia syndrome is not associated with local production of specific IgE in nasal mucosa.

Non-allergic rhinitis with eosinophilia syndrome (NARES) is an eosinophilic inflammation of the nasal mucosa without evidence of an allergy or other nasal pathologies. Patients complain about perennial symptoms like nasal obstruction, rhinorrhea, itchiness and sneezing of the nose sometimes accompanied by hyposmia. The aim of the study was to better characterize NARES patients using immunoassay-biochip technology to examine serum and nasal secretion. Sera and nasal secretion of patients with NARES (perennial nasal symptoms, no evidence of acute or chronic rhinosinusitis with or without polyps, negative SX1-Screening test and/or negative skin prick test, eosinophilic cationic protein in nasal secretion >200 ng/ml) were tested by immunoassay-biochip technology (ImmunoCAP(®) ISAC, Phadia). 112 different allergen components from 51 allergen sources were tested on the chip. Furthermore, serum and nasal secretion were tested for specific IgE to Staphylococcus aureus enterotoxin TSST-1 by fluorescence-enzyme-immunoassay (UniCAP(®), Phadia). Unrecognized systemic sensitization could be ruled out by negative ISAC results in sera of all patients. Testing of nasal secretion for allergen-specific IgE by ISAC chip technology was negative as well in all cases. In one patient, a systemic sensitization to Staphylococcus aureus superantigen TSST-1 was detectable but no allergen-specific IgE to TSST-1 was measurable in nasal secretion of any patient. The results demonstrate that NARES is not associated with local allergy (entopy) nor with a local inflammation driven by Staphylococcus aureus enterotoxin TSST-1. Further studies are necessary to better understand the underlying mechanisms of NARES.

Cytokine profiles in nasal fluid of patients with seasonal or persistent allergic rhinitis.

BACKGROUND: New therapeutic approaches with biologic agents such as anti-cytokine antibodies are currently on trial for the treatment of asthma, rhinosinusitis or allergic diseases necessitating patient selection by biomarkers. Allergic rhinitis (AR), affecting about 20 % of the Canadian population, is an inflammatory disease characterised by a disequilibrium of T-lymphocytes and tissue eosinophilia. Aim of the present study was to describe distinct cytokine patterns in nasal secretion between seasonal and perennial AR (SAR/PAR), and healthy controls by comparing cytokines regulating T-cells or stimulating inflammatory cells, and chemokines. METHODS: Nasal secretions of 44 participants suffering from SAR, 45 participants with PAR and 48 healthy controls were gained using the cotton wool method, and analysed for IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, GM-CSF, G-CSF, IFN-γ, MCP-1, MIP-1α, MIP-1ß, eotaxin, and RANTES by Bio-Plex Cytokine Assay as well as for ECP and tryptase by UniCAP-FEIA. RESULTS: Participants with SAR or PAR presented elevated levels of tryptase, ECP, MCP-1, and MIP-1ß, while values of GM-CSF, G-CSF, IL-1ß, and IL-6 did not differ from the controls. Increased levels of IL-5, eotaxin, MIP-1α, and IL-17 and decreased levels of IFN-γ, IL-12 and IL-10 were found in SAR only. RANTES was elevated in SAR in comparison to PAR. Interestingly, we found reduced levels of IL-4 in PAR and of IL-13 in SAR. CONCLUSIONS: Elevated levels of proinflammatory cytokines were seen in both disease entities. They were, however, more pronounced in SAR, indicating a higher degree of inflammation. This study suggests a downregulation of TH1 and Treg-lymphocytes and an upregulation of TH17 in SAR. Moreover, the results display a prominent role of eosinophils and mast cells in AR. The observed distinct cytokine profiles in nasal secretion may prove useful as a diagnostic tool helping to match patients to antibody therapies.

A noninvasive procedure for early-stage discrimination of malignant and precancerous vocal fold lesions based on laryngeal dynamics analysis.

About two thirds of laryngeal cancers originate at the vocal cords. Early-stage detection of malignant vocal fold alterations, including a discrimination of premalignant lesions, represents a major challenge in laryngology as precancerous vocal fold lesions and small carcinomas are difficult to distinguish by means of regular endoscopy only. We report a procedure to discriminate between malignant and precancerous lesions by measuring the characteristics of vocal fold dynamics by means of a computerized analysis of laryngeal high-speed videos. Ten patients with squamous cell T1a carcinoma, ten with precancerous lesions with hyperkeratosis, and ten subjects without laryngeal disease underwent high-speed laryngoscopy yielding 4,000 images per second. By means of wavelet-based phonovibrographic analysis, a set of three clinically meaningful vibratory measures was extracted from the videos comprising a total number of 15,000 video frames. Statistical analysis (ANOVA with post hoc two-sided t tests, P < 0.05) revealed that vocal fold dynamics is significantly affected in the presence of precancerous lesions and T1a carcinoma. On the basis of the three measures, a discriminating pattern was extracted using a support vector machine-learning algorithm performing an individual classification in respect to the different clinical groups. By applying a leave-one-out cross-validation strategy, we could show that the proposed measures discriminate with a very high performance between precancerous lesions and T1a carcinoma (sensitivity, 100%; specificity, 100%). Although a large-scale study will be necessary to confirm clinical significance, the set of vibratory measures derived in this study may be applicable to improve the accuracy and reliability of noninvasive diagnostics of vocal fold lesions.

Rapid and non-enzymatic in vitro retrieval of tumour cells from surgical specimens.

The study of tumourigenesis commonly involves the use of established cell lines or single cell suspensions of primary tumours. Standard methods for the generation of short-term tumour cell cultures include the disintegration of tissue based on enzymatic and mechanical stress. Here, we describe a simple and rapid method for the preparation of single cells from primary carcinomas, which is independent of enzymatic treatment and feeder cells. Tumour biopsies are processed to 1 mm(3) cubes termed explants, which are cultured 1-3 days on agarose-coated well plates in specified medium. Through incisions generated in the explants, single cells are retrieved and collected from the culture supernatant and can be used for further analysis including in vitro and in vivo studies. Collected cells retain tumour-forming capacity in xenotransplantation assays, mimic the phenotype of the primary tumour, and facilitate the generation of cell lines.