TY  - JOUR
AB  - BACKGROUND: Mucus plugging has been identified as an important feature of severe asthma contributing to airway obstruction and disease severity. Recently, improvement of mucus plugging has been found upon treatment with several biologic therapies. OBJECTIVE: We aimed to analyze associations of baseline characteristic with mucus plugging score (MPS) and asked whether MPS at baseline predicts the clinical and functional response to biologic treatment in patients with severe asthma. METHODS: We retrospectively analyzed biologic-naïve patients with a suitable CT scan available at baseline. We calculated the MPS and analyzed correlations with baseline parameters and improvements of biomarkers, pulmonary function and clinical parameters after 4 months of biologic therapy. RESULTS: We included n=113 patients in the baseline cohort, hereof n=101 patients with sufficient data after 4-months of biologic therapy for the follow-up analysis. CT showed mucus plugging in 77% of patients with a median MPS of 4. Multivariate regression analysis showed correlation of MPS with lower FEV1 (rho= -0.24, p=0.009) and DLCO (rho=-0.26 , p= 0.01), and higher FeNO (rho=0.36 p=0.0003) at baseline. Patients received treatment with anti-IgE (8.8%), anti-IL5 (27.4%), anti-IL5R (37.2%), anti-IL4R (25.7%) and anti-TSLP (0,9%) in clinical routine. Baseline MPS correlated with improvements of FEV1 (beta=0.72; p=0.01) and ACT (beta= 0.24; p= 0.001) in multivariate regression analysis. CONCLUSION: Our study suggests that higher MPS correlates with worse pulmonary function at baseline, but also predicts a larger clinical and pulmonary function response to biologic therapies in severe asthma.
AU  - Götschke, J.*
AU  - Walter, J.*
AU  - Leuschner, G.*
AU  - Gerckens, M.
AU  - Götschke, M.*
AU  - Mertsch, P.*
AU  - Mümmler, C.
AU  - Lenoir, A.*
AU  - Barnikel, M.*
AU  - Dinkel, J.*
AU  - Behr, J.*
AU  - Kneidinger, N.*
AU  - Spiro, J.*
AU  - Milger, K.*
C1  - 73144
C2  - 56926
SP  - 1110-1122.e1
TI  - Mucus plug score predicts clinical and pulmonary function response to biologic therapy in patients with severe asthma.
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 13
IS  - 5
PY  - 2025
SN  - 2213-2198
ER  - 

TY  - JOUR
AB  - Accurate identification of the allergy-eliciting stinging insect(s) is essential to insuring effective management of Hymenoptera venom-allergic individuals with venom-specific immunotherapy (VIT). Diagnostic testing using whole venom extracts with skin tests and serological-based analyses remains the first level of discrimination for honeybee versus vespid venom sensitization in clinical history-positive patients. As a second-level evaluation, serological testing using molecular venom allergens can further discriminate genuine sensitization (honeybee venom: Api m 1, 3, 4, and 10 versus yellow jacket venom/Polistes dominula venom Ves v 1/Pol d 1 and Ves v 5/Pol d 5) from inter-species cross-reactivity [hyaluronidases (Api m 2, Ves v 2, Pol d 2) and dipeptidyl peptidases IV (Api m 5, Ves v 3, Pol d 3)]. Clinical laboratories use a number of singleplex, oligoplex, and multiplex immunoassays that employ both extracted whole venom and molecular venom allergens (highlighted above) for confirmation of allergic venom sensitization. Established quantitative singleplex autoanalyzers have general governmental regulatory clearance worldwide for venom allergic patient testing with maximally achievable analytical sensitivity (0.1 kUA/L) and confirmed reproducibility (inter-assay CVs<10%). Emerging oligo- and multiplex (fixed panel) assays conserve on serum and are more cost-effective, but they need regulatory clearance in some countries and are prone to higher rates of detecting asymptomatic sensitization. Ultimately, the patient's clinical history, combined with the proof of sensitization, is the final arbiter in the diagnosis of Hymenoptera venom allergy.
AU  - Blank, S.
AU  - Korosec, P.*
AU  - Slusarenko, B.O.
AU  - Ollert, M.*
AU  - Hamilton, R.G.*
C1  - 71418
C2  - 56159
TI  - Venom component allergen IgE measurement in the diagnosis and management of insect sting allergy.
JO  - J. Allergy Clin. Immunol. Pract.
PY  - 2024
SN  - 2213-2198
ER  - 

TY  - JOUR
AB  - BACKGROUND: In Hymenoptera venom allergy serologically double-sensitized patients, it is often difficult to identify the culprit insect for venom immunotherapy (VIT). OBJECTIVES: To evaluate if basophil activation tests (BATs) performed not only with venom extracts but additionally with single component-resolved diagnostics could differentiate between sensitized and allergic individuals and how the test results influenced the physicians' decision regarding VIT. METHODS: BATs were performed with bee and wasp venom extracts and with single components (Api m 1, Api m 10, Ves v 1, and Ves v 5) in 31 serologically double-sensitized patients. RESULTS: In 28 finally included individuals, 9 BATs were positive and 4 negative for both venoms. Fourteen of 28 BATs showed positive results for wasp venom alone. Two of 10 BATs positive for bee venom were only positive to Api m 1 and 1 of 28 BATs only to Api m 10, but not for whole bee venom extract. Five of 23 BATs positive for wasp venom were only positive for Ves v 5 but negative for wasp venom extract and Ves v 1. Finally, VIT with both insect venoms was recommended in 4 of 28 individuals, with wasp venom alone in 21 of 28 patients and with bee venom alone in 1 of 28. In 2 cases no VIT was recommended. CONCLUSIONS: BATs with Ves v 5, followed by Api m 1 and Api m 10, were helpful for the decision for VIT with the clinically relevant insect in 8 of 28 (28.6%) patients. A BAT with components should therefore be additionally carried out in cases with equivocal results.
AU  - Schmidle, P.*
AU  - Blank, S.
AU  - Altrichter, S.*
AU  - Hoetzenecker, W.*
AU  - Brockow, K.*
AU  - Darsow, U.*
AU  - Biedermann, T.*
AU  - Eberlein, B.*
C1  - 67831
C2  - 54309
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
SP  - 2890-2899.e2
TI  - Basophil activation test in double-sensitized patients with hymenoptera venom allergy: Additional benefit of component-resolved diagnostics.
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 11
IS  - 9
PB  - Elsevier
PY  - 2023
SN  - 2213-2198
ER  - 

TY  - JOUR
AB  - BACKGROUND: Little is known about the relationship between airway inflammatory phenotypes and some important asthma features such as small airway dysfunction (SAD). OBJECTIVE: To describe the longitudinal impact of airway inflammatory phenotypes on SAD and asthma outcomes METHODS: We measured eosinophil and neutrophil counts in induced sputum at baseline and one year later to stratify 197 adult asthma patients into four inflammatory phenotypes. We conducted a comprehensive assessment of lung function using spirometry, body plethysmography, impulse oscillometry, inert gas single and multiple breath washouts. We compared lung function, asthma severity, exacerbation frequency and symptom control between the phenotypes. We studied the longitudinal impact of persistent sputum inflammatory phenotypes and the change of sputum cell counts on lung function. RESULTS: Patients were stratified into eosinophilic (23%, n=45), neutrophilic (33%, n=62), mixed granulocytic (22%, n=43), and paucigranulocytic (24%, n=47) phenotypes. Eosinophilic and mixed granulocytic asthma patients had higher rates of airflow obstruction and severe exacerbation as well as poorer symptom control than paucigranulocytic asthma patients. All SAD measures were worse in eosinophilic and mixed than in paucigranulocytic asthma patients (all p-values <0.05). Eosinophilic asthma also indicated worse distal airflow obstruction, increased ventilation inhomogeneity (all p-values <0.05), and higher tendency for severe exacerbation (p= 0.07) than neutrophilic asthma. Longitudinally, persistent mixed granulocytic asthma was associated with the worst follow-up measures of SAD compared to persistent neutrophilic, persistent paucigranulocytic or non-persistent asthma phenotypes. In patients with stable FEV1, the mean increase in small airway resistance (R5-20) was greater in persistent mixed granulocytic patients (+103%) than in patients with persistent neutrophilic (+26%), p=0.040, or persistent paucigranulocytic asthma (-41%), p=0.028. Multivariate models adjusted for confounders and treatment with inhaled or oral corticosteroids or anti-eosinophilic biologics indicated that the change of sputum eosinophil rather than neutrophil counts is an independent predictor for the longitudinal change in FEV1, FEF25-75, sReff, RV and LCI. CONCLUSION: In asthma, airway eosinophilic inflammation is the main driver of lung function impairment and poor disease outcomes, which might also be aggravated by the coexistence of airway neutrophilia to confer a severe mixed asthma phenotype. Persistent airway eosinophilia might be associated with dynamic SAD even in patients with stable FEV1.
AU  - Abdo, M.*
AU  - Pedersen, F.*
AU  - Kirsten, A.M.*
AU  - Veith, V.*
AU  - Biller, H.*
AU  - Trinkmann, F.*
AU  - von Mutius, E.
AU  - Kopp, M.*
AU  - Hansen, G.*
AU  - Rabe, K.F.*
AU  - Bahmer, T.*
AU  - Watz, H.*
C1  - 64505
C2  - 52241
SP  - 1545-1553.e2
TI  - Longitudinal impact of sputum inflammatory phenotypes on small airway dysfunction and disease outcomes in asthma.
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 10
IS  - 6
PY  - 2022
SN  - 2213-2198
ER  - 

TY  - JOUR
AU  - Banzon, T.M.*
AU  - von Mutius, E.
AU  - Phipatanakul, W.*
C1  - 66075
C2  - 53084
SP  - 2252-2253
TI  - The microbiome in clinical allergy and immunology: Emerging role as friend and foe.
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 10
IS  - 9
PY  - 2022
SN  - 2213-2198
ER  - 

TY  - JOUR
AB  - BACKGROUND: Positive bronchodilator responsiveness (BDR) (ΔFEV1≥+200ml and ≥+12%) after inhalation of short-acting beta-agonist (SABA) has been an inclusion criterion in licensing trials of anti-IL5/anti-IL5Rα biologics in severe asthma. However, in clinical practice patients with severe uncontrolled asthma frequently show a negative BDR. OBJECTIVE: To investigate whether the response to anti-IL5/anti-IL5Rα therapies differs between patients with positive and negative BDR at baseline. METHODS: Retrospective multicenter analysis of treatment outcomes in patients with severe asthma receiving anti-IL5/anti-IL5Rα stratified for baseline BDR. RESULTS: Of 133 patients included, 37 had a positive and 96 had a negative BDR at baseline. Following anti-IL5/anti-IL5Rα treatment FEV1 improved significantly in both groups compared to baseline (p<0.0001), with no significant difference between patients with positive and negative BDR (ΔFEV1 +493ml vs +306ml, p=0.06). FVC increased (ΔFVC: +85ml vs +650ml, p<0.01) and RV decreased (ΔRV +113ml vs -307ml, p<0.01) significantly in patients with negative BDR. Median annualized exacerbations (0 vs 0; p=0.7), reduction of exacerbation rate (Δexacerbations: 0 vs -2, p=0.07), continuous oral corticosteroid (OCS) use (Δpatients on OCS: -35% vs -39%, p=0.99) and improvement of asthma control test (ACT) score (ΔACT: 6 vs 5, p=0.7) were similar in both groups. Multivariate logistic regression analysis showed no significant correlations of positive vs negative BDR with response parameters. CONCLUSIONS: Both groups improved following treatment with similar responses concerning reduction of OCS therapy, exacerbations and improvement of symptom control. Pulmonary function also improved in both groups during anti-IL5/anti-IL5Rα treatment, with differences in response patterns noted.
AU  - Mümmler, C.
AU  - Suhling, H.*
AU  - Walter, J.*
AU  - Kneidinger, N.
AU  - Buhl, R.*
AU  - Kayser, M.Z.*
AU  - Drick, N.*
AU  - Behr, J.*
AU  - Welte, T.*
AU  - Korn, S.*
AU  - Milger, K.
C1  - 65756
C2  - 52899
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
SP  - 3174-3183
TI  - Overall response to anti-IL5/anti-IL5Rα treatment in severe asthma does not depend on initial bronchodilator responsiveness.
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 10
IS  - 12
PB  - Elsevier
PY  - 2022
SN  - 2213-2198
ER  - 

TY  - JOUR
AB  - BACKGROUND: An important 'window of opportunity' for early life exposures has been proposed for the development of atopic eczema and asthma. OBJECTIVE: However it is, unknown whether hay fever with a peak incidence around late school age to adolescence is similarly determined very early in life. METHODS: In the PASTURE birth cohort potentially relevant exposures such as farm milk consumption and exposure to animal sheds were assessed at multiple time points from infancy to age 10.5 years and classified by repeated measure latent class analyses (N=769). Fecal samples at age 2 and 12 months were sequenced by 16S rRNA. Hay fever was defined by parental reported symptoms and/or physician's diagnosis of hay fever in the last 12 months using questionnaires at age 10.5 years. RESULTS: Farm children had half the risk of hay fever at age 10.5 years (adjusted odds-ratio (aOR) [95% CI]=0.50 [0.31; 0.79]) compared to non-farm children. While early life events such as gut microbiome richness at age 12 months (aOR=0.66 [0.46; 0.96]) and exposure to animal sheds in the first three years of life (aOR=0.26 [0.06; 1.15]) were determinants of hay fever, the continuous consumption of farm milk from infancy up-to school age was necessary to exert the protective effect (aOR=0.35 [0.17; 0.72]). CONCLUSION: While early life events determine the risk of subsequent hay fever, continuous exposure is necessary to achieve protection. These findings argue against the notion that only early life exposures set long-lasting trajectories.
AU  - Pechlivanis, S.
AU  - Depner, M.
AU  - Kirjavainen, P.V.*
AU  - Roduit, C.*
AU  - Täubel, M.*
AU  - Frei, R.*
AU  - Skevaki, C.*
AU  - Hose, A.*
AU  - Barnig, C.*
AU  - Schmaußer-Hechfellner, E.
AU  - Ege, M.J.
AU  - Schaub, B.*
AU  - Divaret-Chauveau, A.*
AU  - Lauener, R.*
AU  - Karvonen, A.M.*
AU  - Pekkanen, J.*
AU  - Riedler, J.*
AU  - Illi, S.
AU  - von Mutius, E.
C1  - 66680
C2  - 53275
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
SP  - 591-601
TI  - Continuous rather than solely early farm exposure protect from hay fever development.
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 11
IS  - 2
PB  - Elsevier
PY  - 2022
SN  - 2213-2198
ER  - 

TY  - JOUR
AU  - Briegel, I.
AU  - Felicio-Briegel, A.*
AU  - Mertsch, P.
AU  - Kneidinger, N.
AU  - Haubner, F.*
AU  - Milger, K.
C1  - 62908
C2  - 51164
CY  - Radarweg 29, 1043 Nx Amsterdam, Netherlands
SP  - 4477-4479
TI  - Hypereosinophilia with systemic manifestations under dupilumab and possibility of dual benralizumab and dupilumab therapy in patients with asthma and CRSwNP.
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 9
IS  - 12
PB  - Elsevier
PY  - 2021
SN  - 2213-2198
ER  - 

TY  - JOUR
AB  - Background: Biological treatments directed against IgE and IL-5 have largely improved outcomes for patients with severe type 2–high asthma. However, a fraction of patients with severe asthma show insufficient treatment outcome under anti-IgE and anti–IL-5/IL-5 receptor α antibodies. Objective: To evaluate whether switching to dupilumab was of benefit in patients with insufficient outcome under previous anti-IgE or anti–IL-5/IL-5 receptor α therapy. Methods: We retrospectively analyzed 38 patients who were switched to dupilumab from a previous anti-IgE or anti–IL-5/IL-5 receptor α medication because of insufficient outcome. We defined response criteria after 3 to 6 months as an improvement in at least 1 of the following criteria without deterioration in the other criteria, comparing values under dupilumab with values under previous antibody therapy: (1) increase of 3 or more in Asthma Control Test score, (2) 50% or more reduction in oral corticosteroid dose, and (3) FEV1 improvement greater than or equal to 150 mL, and classified patients as responders and nonresponders. Results: Switch to dupilumab led to a response in 76% of patients. In the total cohort, Asthma Control Test score increased by a mean of 2.9 (P < .0001), whereas exacerbations decreased significantly (P < .0001) and number of oral corticosteroid–dependent patients decreased from 15 to 12. Mean FEV1 improved by 305 mL (P < .0001). Median fractional exhaled nitric oxide decreased by −30 ppb (P < .0001), whereas eosinophil counts increased by 0.17 G/L (P < .01). There were no significant differences in clinical characteristics between responders and nonresponders to dupilumab. However, patients with increased fractional exhaled nitric oxide (≥25 ppb) during previous antibody therapy were more often responders than patients with low fractional exhaled nitric oxide (<25 ppb) (P < .05). Conclusions: Altogether, we show that a switch to dupilumab in patients with insufficient outcome under previous biological therapy was effective in most patients.
AU  - Mümmler, C.
AU  - Munker, D.
AU  - Barnikel, M.
AU  - Veit, T.
AU  - Kayser, M.*
AU  - Welte, T.*
AU  - Behr, J.
AU  - Kneidinger, N.
AU  - Suhling, H.*
AU  - Milger, K.
C1  - 60329
C2  - 49235
SP  - 1177-1185.e4
TI  - Dupilumab improves asthma control and lung function in patients with insufficient outcome during previous antibody therapy.
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 9
IS  - 3
PY  - 2020
SN  - 2213-2198
ER  - 

TY  - JOUR
AU  - von Mutius, E.
AU  - Matsui, E.C.*
C1  - 58500
C2  - 48135
SP  - 890-891
TI  - Prevention is the best remedy: What can we do to stop allergic disease?
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 8
IS  - 3
PY  - 2020
SN  - 2213-2198
ER  - 

TY  - JOUR
AB  - BACKGROUND: It is unclear whether early life food sensitization (as opposed to aeroallergen sensitization) is associated with subsequent poor lung function.OBJECTIVES: We investigated the associations between food sensitization in the first 2 years of life and lung function at 12 to 18 years and whether these observed associations are mediated through aeroallergen sensitization or asthma.METHODS: We used data from a high-risk cohort (Melbourne Atopy Cohort Study [MACS]) and a population-based "Influence of life-style-related factors on the development of the Immune System and Allergies in East and West Germany plus the influence of traffic emissions and genetics" (LISAplus) cohort. Food sensitization was assessed at 6, 12, and 24 months in MACS and 24 months in LISAplus. Lung function was evaluated by spirometry at 12 and 18 years in MACS and 15 years in LISAplus. Linear regression models were used to estimate the association with sensitization (food and/or aeroallergen) while adjusting for potential confounders.RESULTS: Sensitization to food without aeroallergen at 6 months was associated with reduced forced expiratory volume in 1 second (FEV1) at both 12 years (-153 mL; 95% confidence interval [CI] = - 256 mL, - 51 mL) and 18 years (- 206 mL; 95% CI = -347 mL, - 65 mL) in MACS. Similar results were observed for sensitization measured at 12 months but not at 24 months. Early-life asthma (but not aeroallergen sensitization) partially mediated these associations. Both cohorts showed that only aeroallergen sensitization at 24 months but not food sensitization was associated with lower adolescent lung function.CONCLUSIONS: This study showed that food sensitization at 6 and 12 months was associated with reduced FEV1 in adolescence. Our finding that this link is not completely mediated by either subsequent asthma or aeroallergen sensitization is novel and suggests that early food sensitization itself can be used to identify high-risk groups for poor lung health. (C) 2019 American Academy of Allergy, Asthma & Immunology
AU  - Alduraywish, S.*
AU  - Luzak, A.
AU  - Lodge, C.*
AU  - Aldakheel, F.*
AU  - Erbas, B.*
AU  - Allen, K.*
AU  - Matheson, M.*
AU  - Gurrin, L.*
AU  - Heinrich, J.
AU  - Lehmann, I.*
AU  - von Berg, A.*
AU  - Standl, M.
AU  - Abramson, M.*
AU  - Schulz, H.
AU  - Lowe, A.*
AU  - Dharmage, S.*
C1  - 55512
C2  - 46313
CY  - Po Box 211, 1000 Ae Amsterdam, Netherlands
SP  - 1825-1834.e12
TI  - The role of early life food sensitization in adolescent lung function: Results from 2 birth cohort studies.
JO  - J. Allergy Clin. Immunol. Pract.
VL  - 7
IS  - 6
PB  - Elsevier Science Bv
PY  - 2019
SN  - 2213-2198
ER  -