Real-world data show sustained therapeutic effects of dupilumab in chronic rhinosinusitis with nasal polyps (CRSwNP) over 3 years.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent chronic inflammatory condition affecting the nose and paranasal sinuses, posing a significant socio-economic impact with substantial challenges in management. Biologics targeting type 2 inflammation such as dupilumab, have emerged as promising options. This study addresses a critical knowledge gap by comprehensively evaluating the 3-year impact of sustained dupilumab therapy in CRSwNP. METHODS: A multicentric, retrospective collection of real-world data from five tertiary referral centers in Germany was conducted, enrolling 150 adult patients. The study investigated patient-reported outcomes, disease-specific indices and clinical measures, focusing on therapeutic response persistence, adverse events, and factors influencing treatment continuity. RESULTS: Results indicate significant improvements in clinical parameters from baseline (n = 150) with sustained effectiveness after 36 months (n = 138) as indicated in mean score ± standard deviation. Dupilumab treatment significantly improved overall disease-related impairment (VAS score: 7.5 ± 2.5 to 1.6 ± 1.3) and rhinosinusitis symptoms (SNOT-22: 59.4 ± 19.4 to 18.0 ± 15.0). Nasal Polyp Scores (NPS) decreased (5.3 ± 1.8 to 0.7 ± 1.1), and olfactory function improved (3.2 ± 2.5 to 8.4 ± 2.8), with three out of four patients achieving normosmia or hyposmia after 36 months. An "Excellent" treatment response according to EUFOREA23 criteria was observed in 76.5% of patients after 36 months. Sixteen patients discontinued Dupilumab, 12 permanently. Adverse events totaled 69 in 48 patients, commonly self-limiting. CONCLUSION: The study highlights the enduring effectiveness and lack of habituation to dupilumab after a sustained therapy of 3 years, providing valuable insights into its long-term therapeutic implications for CRSwNP patients.

Serological Cross-Reactivity of Various Aspergillus spp. with Aspergillus fumigatus: A Diagnostic Blind Spot.

INTRODUCTION: Aspergillus fumigatus is the most common airborne allergen of the Aspergillus family. However, allergies to Aspergillus spp. are increasing, and subsequently, allergies to Aspergillus species other than fumigatus are also on the rise. Commercial diagnostic tools are still limited to Aspergillus fumigatus. Hence, there is a need for improved tests. We decided to investigate the correlation between serological sensitization to A. fumigatus and other Aspergillus species. METHODS: Hundred and seven patients with positive skin prick tests to A. fumigatus were included in this study. Immunoglobulin E (IgE) concentrations against A. fumigatus, A. terreus, A. niger, A. flavus, and A. versicolor were measured from specimens by fluorescent enzyme-linked immunoassays. RESULTS: Patients showed considerably higher IgE concentrations against A. fumigatus (6.00 ± 15.05 kUA/L) than A. versicolor (0.30 ± 1.01 kUA/L), A. niger (0.62 ± 1.59 kUA/L), A. terreus (0.45 ± 1.12 kUA/L), or A. flavus (0.41 ± 0.97 kUA/L). Regression analysis yielded weak positive correlations for all Aspergillus spp., but low r2 values and heteroscedastic distribution indicate an overall poor fit of the calculated models. CONCLUSION: Serological sensitization against A. fumigatus does not correlate with sensitization against other Aspergillus spp. To detect sensitization against these, other diagnostic tools like a skin prick test solution of different Aspergillus spp. are needed.

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.

Diagnostics of allergic rhinitis under dupilumab therapy.

BACKGROUND: Allergic rhinits is a prevalent condition, affecting a substantial proportion of the population. This study investigates the impact of ongoing biologic therapy, specifically with Dupilumab, on allergy diagnostics in patients with allergic rhinits. METHODS: Various tests, including the Skin Prick Test, serum IgE levels and Allergy Screening Panels, were examined for their effectiveness in detecting sensitizations during biologic treatment. RESULTS: The results indicate a significant decline in total IgE levels following biologic therapy initiation, aligning with previous findings on Dupilumab's inhibitory effects on IL-4 and IL-13. However, the specific IgE to total IgE ratio for major allergens was not significantly reduced. Comparing diagnostic tools, the Skin Prick Test demonstrates an impressive retention rate of sensitizations (98%) during Dupilumab treatment, outperforming the Allergy Screening Panel, which shows a 75% detection rate. Notably, the panel displays limitations in capturing lower sensitization levels. CONCLUSION: In summary, this study underscores that, despite the influence of biologic therapy on certain markers, standard allergy tests remain viable while emphasizing the importance of considering specific IgE levels rather than relying solely on CAP classes. The Skin Prick Test in particular proves to be a reliable tool for identifying sensitizations during Dupilumab treatment. The results offer valuable guidance for the diagnostic management of Allergic rhinits in individuals subjected to Dupilumab treatment.

The use of biologics in patients suffering from chronic rhinosinusitis with nasal polyps - a 4-year real life observation.

PURPOSE: Antibody therapy for chronic rhinosinusitis with nasal polyps (CRSwNP) has been established in Germany since 2019. With limited long-term data on biologic treatment for CRSwNP, we conducted a comprehensive evaluation of our 4-year data. This monocentric study aims to assess the real-world effects of this treatment on clinical course, quality of life, treatment adherence, biologic switching, dual therapy, and comorbidities. METHODS: We retrospectively analysed biologic therapy data in patients with severe chronic rhinosinusitis with nasal polyps. 191 patients with CRSwNP treated with Dupilumab, Mepolizumab, or Omalizumab were observed for up to 4 years in a real-life setting. RESULTS: We observed clear symptom improvements with few side effects. No loss of efficacy or tolerability was noted during the 4-year period. Patients reported high satisfaction compared to previous therapies, with overall improved quality of life. Revision surgery or oral steroid use during biologic therapy was rare. Some patients prolonged injection intervals or discontinued steroid nasal spray. Biologic switching occurred infrequently due to side effects or inadequate response and was generally well tolerated. Many patients reported additional positive effects such as asthma or allergy symptom improvement and reduced medication intake. CONCLUSION: In summary, this study confirms the potency and tolerability of biologics for CRSwNP treatment, with sustained efficacy over 4 years. Biologic switching is a viable option for inadequate response or intolerable side effects. Therapy positively impacts Th2 comorbidities, corticosteroid requirements, surgery need, and overall compliance remains high. CLINICAL TRIAL REGISTRATION: Project No.: 22-0802. Registry name: Biologika bei Patient*innen mit chronischer Sinusitis mit Nasenpolypen.

[Biologic therapy in patients with severe NSAID-exacerbated respiratory disease and previous aspirin desensitization : Results of a multicentric study]. / Biologikatherapie bei schwer erkrankten Patienten mit "NSAID-exacerbated respiratory disease" und stattgehabter ASS­Desaktivierung : Ergebnisse einer multizentrischen Studie.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type­2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. METHODS: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. RESULTS: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B­SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. CONCLUSION: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.

Efficacy of human C1 esterase inhibitor concentrate for treatment of ACE-inhibitor induced angioedema.

BACKGROUND: ACE inhibitor (ACEi) induced angioedema predominantly affects the upper aerodigestive tract. As ACEi induced angioedema is mediated by bradykinin, therapeutic response to antihistamines and glucocorticoids remains unsatisfactory. In bradykinin mediated hereditary angioedema, C1-esterase inhibitor (C1INH) is an effective and approved treatment since many years. Our aim was to evaluate the therapeutic effect of C1INH in ACEi induced angioedema. METHODS: We performed a double-blind, parallel-group, multicentre randomised placebo-controlled trial between December 2013 and September 2018. Eligible were adults with ACEi induced angioedema with airway obstruction. Participants were randomised 1:1 to single doses of either C1INH (20 IU/kg) or placebo (0.9% NaCl) i.v in addition to standard care (i.v. 500 mg prednisolone and 2.68 mg clemastine) i.v. Composite symptom scores were assessed at baseline and up to 48 h, at discharge and 1 week after discharge. Physician assessed time to complete oedema resolution (TCER) and time to onset of relief (TOR). RESULTS: 30 patients (16 C1INH, 14 placebo) were randomised and dosed. 25 (9 C1INH, 12 placebo) completed the study. TCER was 29.63 h ± 15.56 h in the C1INH and 17.29 h ± 10.40 h in the placebo arm (p = 0.0457). TORs were 4.13 h ± 3.38 h and 2.86 h ± 1.29 h for C1INH and placebo, respectively (p = 0.4443). There were no adverse events related to study medication. CONCLUSIONS: In the context of baseline application of steroids and antihistamines C1INH was inferior in the treatment of ACEi induced angioedema when compared to placebo with respect to time to complete resolution of symptoms. Eudra-CT Number: 2012-001670-28.

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.

Acupuncture and its effect on cytokine and chemokine profiles in seasonal allergic rhinitis: a preliminary three-armed, randomized, controlled trial.

PURPOSE: Numerous studies have demonstrated effectiveness for acupuncture in the treatment of seasonal allergic rhinitis (SAR). However, the underlying mechanism remains still unclear. METHODS: 29 SAR patients were recruited from a large randomized, controlled trial investigating the efficacy of acupuncture in SAR. 16 patients were treated by acupuncture plus rescue medication (RM, cetirizine), 6 patients received sham acupuncture plus RM and 8 patients RM alone over 8 weeks. Patients were blinded to the allocation to real or sham acupuncture. At baseline and different time-points during intervention, plasma and nasal concentration of mediators of various biological functions were determined in addition to validated disease-specific questionnaires. RESULTS: The concentration of biomarkers related to the Th1-, Th2-, and Treg-cluster was not changed in patients who received acupuncture, in neither plasma nor nasal fluid. However, with respect to eotaxin and some unspecific pro-inflammatory cytokines (IL-1b, IL-8, IP-10, MIP-1b, MCP-1), acupuncture led to a, partially significantly, lower nasal concentration than sham acupuncture or RM. Furthermore, the nasal symptom score was significantly reduced in patients only after real acupuncture. CONCLUSION: In SAR, acupuncture reduces the intranasal unspecific inflammation, but does not seem to act immunologically on the Th1-Th2-imbalance.

Relevance of Major Allergens in Weed Pollen Allergy.

INTRODUCTION: Weed pollen allergy is an important and in prevalence increasing cause of pollinosis in Europe and across the world. In this study we focus on the value of common diagnostic tools for detection of a sensitization to mugwort and English plantain, especially with regard to the clinical relevance of the sensitization. METHODS: Eighty weed pollen sensitized patients (41 to mugwort and 39 to English plantain) were assessed retrospectively regarding their clinical anamnesis, in-vivo tests (skin prick test [SPT] and allergen specific provocation) and in-vitro tests (immunoglobulin E [IgE] reactivity to purified natural allergen extract and specific allergen components in serum). RESULTS: 85% of mugwort and 83% of English plantain sensitizations could be diagnosed by SPT alone. Distinction between allergic and non-allergic patients could be made with clinical challenges solely. IgE serology revealed IgE antibodies against the native pollen extracts for mugwort in 98% and for English plantain in 90% of patients. Detection of major allergens nArt v 1, nArt v 3 and Pla l 1 did not add accuracy to the diagnosis. A vast majority of the weed pollen allergic patients was sensitized to >1 allergen. Minor allergens were found to be of less importance. CONCLUSION: The exact diagnosis of weed pollen allergy can be challenging due to confounding components in anamnesis and diagnostic tests. IgE-serology does not delineate allergic from sensitized patients. Component resolved diagnostics (CRD) can confirm, but not replace, extract based diagnostic methods, such as SPT, provocation tests or serology to native extracts. Hence, these are the gold standard diagnostic tools in weed pollen allergy up to now.

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.

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.

Milbenallergie im HNO-Bereich: Bedeutung, Diagnostik und Therapieoptionen.

Allergic rhinitis (AR) affects ca. 20% of the population. Approximately one third of patients affected by AR are suffering from perennial rhinitis due to mite allergy. Perennial rhinitis is the form of the disease that is most frequently associated with other allergy-related comorbidities such as asthma and atopic dermatitis, sleep disorders, chronic sinusitis, eustachian tube dysfunction and others.The often non-specific symptoms and the insidious course may lead to misinterpretations in diagnosing the disease.Therapeutic options include allergen avoidance with regard to environmental measures, encasings and personal actions. Drug therapy in mite-AR consists mainly in the administration of mast cell stabilizers, H1-antihistamines, glucocorticosteroids (GCS), leukotriene receptor antagonists and decongestants. It is particularly important to ensure a good antiinflammatory activity. Thus, a combination of H1-antihistamine and topical nasal GCS seems to be a rational approach. The only causal treatment form besides allergen avoidance is allergen-specific immunotherapy 1.

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.

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.

Real-Life Study for the Diagnosis of House Dust Mite Allergy - The Value of Recombinant Allergen-Based IgE Serology.

BACKGROUND: Dermatophagoides pteronyssinus is one of the most important perennial allergen sources worldwide. Molecular diagnostics using the commercially available major allergens (Der p 1 and Der p 2) in combination with Der p 10 do not detect house dust mite (HDM) sensitization in a number of cases when used alone. The objective was to evaluate the IgE reactivity profiles of these patients using an experimental immunoassay biochip. METHODS: Sera of HDM-allergic patients (positive skin prick test, CAP class ≥1 for allergen extract, and positive intranasal provocation) were tested for IgE antibodies against Der p 1, Der p 2, and Der p 10 by ImmunoCAP fluorescence enzyme immunoassay. Negatively tested sera were examined by an experimental chip containing 13 microarrayed HDM allergens. RESULTS: Of 97 patients tested, 16 showed negative results to Der p 1, Der p 2, and Der p 10. MeDALL chip evaluation revealed 5 patients monosensitized to Der p 23, and 11 patients were negative for all HDM MeDALL chip components. Seven sera were available for further testing, and 3 of them showed IgE reactivity to dot-blotted nDer p 1, and 2 reacted with high-molecular weight components (>100 kDa) in nitrocellulose-blotted HDM extract when tested with 125I-labeled anti-IgE in a RAST-based assay. The HDM extract-specific IgE levels of the 11 patients were <3.9 kU/l. CONCLUSIONS: Recombinant allergen-based IgE serology is of great value when conventional IgE diagnostics fails. Der p 23 is an important HDM allergen, especially when major allergens are negative. Therefore, it would be desirable to have Der p 23 commercially available. Further research concerning the prevalence and clinical significance of different HDM allergens is needed.

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.