How to hit the allergy target: A critical appraisal of intralymphatic immunotherapy with practical recommendations on ultrasound-guided injections.

BACKGROUND: Intralymphatic immunotherapy (ILIT) represents a promising novel approach treating allergic diseases. However, no standardized procedures or recommendations have been established or reported, despite the recognized fact that treatment efficacy relies on the ability to inject the allergen intranodally. OBJECTIVE: We aim to provide a critical appraisal of ILIT as a method of allergen immunotherapy and to deliver practical recommendations for accurate ILIT. METHODS: One hundred and seventy-three ILIT injections were performed in 28 (47%) women and 32 (53%) men with median age of 29 years (21-59). The injections were ultrasound-guided and recorded for retrospective analysis with respect to injection location, needle visibility, medication release, and patient characteristics. RESULTS: The results show that the correct positioning of the needle within the lymph node (LN) was most critical. If the whole length of the needle bevel was not inserted into the LN, substance backflush into the interstitium was observed. Selecting a more superficial LN and inserting the needle at a smaller angle towards the LN significantly improved needle visibility in the ultrasound. Longitudinal results showed that continuous practice significantly correlated with improved needle visibility and more accurate ILIT injections. CONCLUSION: Based on our results and practical experience, we propose several recommendations for LN selection and the correct handling of ultrasound probe and needle. We are confident that ILIT standardization and training will be important as to meet the goals of good safety and efficacy of ILIT.

Effects of Chronic Inflammatory Activation of Murine and Human Arterial Endothelial Cells at Normal Lipoprotein and Cholesterol Levels In Vivo and In Vitro.

The activation of endothelial cells is crucial for immune defense mechanisms but also plays a role in the development of atherosclerosis. We have previously shown that inflammatory stimulation of endothelial cells on top of elevated lipoprotein/cholesterol levels accelerates atherogenesis. The aim of the current study was to investigate how chronic endothelial inflammation changes the aortic transcriptome of mice at normal lipoprotein levels and to compare this to the inflammatory response of isolated endothelial cells in vitro. We applied a mouse model expressing constitutive active IκB kinase 2 (caIKK2)-the key activator of the inflammatory NF-κB pathway-specifically in arterial endothelial cells and analyzed transcriptomic changes in whole aortas, followed by pathway and network analyses. We found an upregulation of cell death and mitochondrial beta-oxidation pathways with a predicted increase in endothelial apoptosis and necrosis and a simultaneous reduction in protein synthesis genes. The highest upregulated gene was ACE2, the SARS-CoV-2 receptor, which is also an important regulator of blood pressure. Analysis of isolated human arterial and venous endothelial cells supported these findings and also revealed a reduction in DNA replication, as well as repair mechanisms, in line with the notion that chronic inflammation contributes to endothelial dysfunction.

Prevalence and prognostic impact of bone disease in chronic heart failure with reduced ejection fraction.

AIMS: Chronic heart failure is associated with a bone-catabolic state and increases the risk of osteoporosis and fractures. Prospective studies investigating the clinical relevance of bone disease in heart failure are lacking. We aimed to assess the prevalence and prognostic impact of osteoporosis and vertebral fractures (VFs) in chronic heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Symptomatic outpatients with chronic heart failure and a previous diagnosis of overtly reduced left ventricular ejection fraction < 40% on stable, optimal HFrEF therapy and left ventricular ejection fraction < 50% at enrolment were included into a prospective single-centre study. Osteoporosis was determined with dual-energy X-ray absorptiometry and defined as a T-score ≤ 2.5 at any site. VFs were assessed using X-ray of both thoracic and lumbar spine applying the semiquantitative Genant score. We enrolled 205 patients (22% women), with a median age of 66 (IQR 58-74) years. Median left ventricular ejection fraction was 37 (IQR 30-43) % and median N-terminal pro B-type natriuretic peptide was 964 (IQR 363-2173) pg/mL. Osteoporosis, as defined by bone mineral density, and at least one VF were prevalent in 31 (15%) and 29 patients (14%). Osteoporosis or VF were present in 55 patients (27%) and 5 patients (2%) had both osteoporosis and a VF. During a median follow-up of 4.7 (IQR 4.0-5.3) years, 18 patients (9%) died due to cardiovascular (CV) cause, and 46 patients (22%) had a worsening heart failure (WHF) hospitalization. In multivariate Cox regression analyses, presence of VF independently predicted CV death (HR 2.82, 95% CI 1.04-7.65, P = 0.042), WHF hospitalizations (HR 2.39, 95% CI 1.18-4.82, P = 0.015), and a composite endpoint of CV death and WHF hospitalizations (HR 2.44, 95% CI 1.23-4.82, P = 0.011). Osteoporosis was not significantly associated with CV events. CONCLUSIONS: In a prospective study, bone disease affected every fourth patient with HFrEF, and patients with VF at baseline had a two-fold risk of subsequent CV death or WHF hospitalization. Prevalent bone disease, particularly VF, should be considered as a clinically relevant comorbidity in HFrEF.

The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma.

The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia.

Tobacco Exposure and Efficacy of Biologic Therapy in Patients With Severe Asthma: A Nationwide Study From the Danish Severe Asthma Register.

BACKGROUND: Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important. OBJECTIVE: To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma. METHODS: We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment. RESULTS: A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years. CONCLUSION: Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma.

Clinical Response and Remission in Patients With Severe Asthma Treated With Biologic Therapies.

BACKGROUND: The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal. RESEARCH QUESTION: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment? STUDY DESIGN AND METHODS: The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined "clinical response" to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. "Clinical remission" was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV1 > 80%) and a six-question Asthma Control Questionnaire score ≤ 1.5 following 12 months of treatment. RESULTS: Following 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled the study criteria of clinical remission, corresponding to 19% of the entire population. Remission was predicted by shorter duration of disease and lower BMI in the entire population of patients treated with biologic therapy. INTERPRETATION: Clinical response was achieved in most adult patients initiating biologic therapy, and clinical remission was observed in 19% of the patients following 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission with biologic therapy.

Gallstone as a cause of intestinal obstruction (Bouveret syndrome).

Gallstone ileus is a rare cause of bowel obstruction. Here we report about two cases with clinical findings and therapy options. Both patients were presented with typical ileus-like symptoms, although the surgical treatment differs due to the CT scan and intraoperative findings. There are many methods for treating patients with Bouveret syndrome. Endoscopy should be the first treatment option for young patients with no significant diseases in the medical history, depending on the size of the stone. Surgical approach is the next possible option. Combination of these two methods is associated with higher mortality. In case there is no extraluminal gas or intraperitoneal fluid in CT-scan, there is no need for an acute surgery. Conservative therapy prior to the intervention enables a precise planning of whether the endoscopic approach or open surgery would be beneficial for the patient.

Realistic prediction and engineering of high-Q modes to implement stable Fano resonances in acoustic devices.

Quasi-bound states in the continuum (QBICs) coupling into the propagating spectrum manifest themselves as high-quality factor (Q) modes susceptible to perturbations. This poses a challenge in predicting stable Fano resonances for realistic applications. Besides, where and when the maximum field enhancement occurs in real acoustic devices remains elusive. In this work, we theoretically predict and experimentally demonstrate the existence of a Friedrich-Wintgen BIC in an open acoustic cavity. We provide direct evidence for a QBIC by mapping the pressure field inside the cavity using a Laser Doppler Vibrometer (LDV), which provides the missing field enhancement data. Furthermore, we design a symmetry-reduced BIC and achieve field enhancement by a factor of about three compared to the original cavity. LDV measurements are a promising technique for obtaining high-Q modes' missing field enhancement data. The presented results facilitate the future applications of BICs in acoustics as high-intensity sound sources, filters, and sensors.

Domperidone Protects Cells from Intoxication with Clostridioides difficile Toxins by Inhibiting Hsp70-Assisted Membrane Translocation.

Clostridioides difficile infections cause severe symptoms ranging from diarrhea to pseudomembranous colitis due to the secretion of AB-toxins, TcdA and TcdB. Both toxins are taken up into cells through receptor-mediated endocytosis, autoproteolytic processing and translocation of their enzyme domains from acidified endosomes into the cytosol. The enzyme domains glucosylate small GTPases such as Rac1, thereby inhibiting processes such as actin cytoskeleton regulation. Here, we demonstrate that specific pharmacological inhibition of Hsp70 activity protected cells from TcdB intoxication. In particular, the established inhibitor VER-155008 and the antiemetic drug domperidone, which was found to be an Hsp70 inhibitor, reduced the number of cells with TcdB-induced intoxication morphology in HeLa, Vero and intestinal CaCo-2 cells. These drugs also decreased the intracellular glucosylation of Rac1 by TcdB. Domperidone did not inhibit TcdB binding to cells or enzymatic activity but did prevent membrane translocation of TcdB's glucosyltransferase domain into the cytosol. Domperidone also protected cells from intoxication with TcdA as well as CDT toxin produced by hypervirulent strains of Clostridioides difficile. Our results reveal Hsp70 requirement as a new aspect of the cellular uptake mechanism of TcdB and identified Hsp70 as a novel drug target for potential therapeutic strategies required to combat severe Clostridioides difficile infections.

Screening for impaired pulmonary function using peak expiratory flow: Performance of different interpretation strategies.

BACKGROUND: Spirometry is the gold standard for diagnosis of impaired pulmonary function, but is often unavailable in resource-constrained settings. Some authors have suggested using peak expiratory flow (PEF) to screen for impaired pulmonary function when spirometry is unavailable, but with no consensus on how to define abnormally low PEF. Strategies have included cutoffs based on absolute value of PEF, PEF in percent predicted, PEF Z-score, PEF × height-2, and gender-specific cutoffs of absolute PEF. The objective of this paper is to determine the PEF interpretation strategy with the highest predictive ability for low pulmonary function, with spirometry as the gold standard. METHODS: We analyzed data on individuals aged 40-79 years in the United States National Health and Nutrition Examination Survey 2007-2012. 6,144 individuals fulfilled inclusion criteria for the main analysis. For each PEF interpretation strategy, we calculated the area under the receiver operating curve (AUC) for the detection of low pulmonary function (defined by FEV1 Z-score < -1.645, < -2, < -2.5 or < -3). RESULTS: The AUC was substantially and statistically significantly higher for PEF in percent predicted and PEF Z-score than for absolute value and PEF × height-2, including after stratification by gender. There was no difference in AUC between PEF in percent predicted and PEF Z-score. CONCLUSION: If using PEF to screen adults aged 40 years or older for impaired pulmonary function defined by low FEV1 Z-score, basing cutoffs on PEF in percent predicted or PEF Z-score may result in improved predictive ability. As percent predicted is a mathematically simpler term than Z-score, it may be preferable to use cutoffs based on PEF in percent predicted.

NF-κB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells.

Nuclear factor κB (NF-κB) is a dimeric transcription factor constituted by two of five protein family members. It plays an essential role in inflammation and immunity by regulating the expression of numerous chemokines, cytokines, transcription factors, and regulatory proteins. Since NF-κB is expressed in almost all human cells, it is important to understand its cell type-, tissue-, and stimulus-specific roles as well as its temporal dynamics and disease-specific context. Although NF-κB was discovered more than 35 years ago, many questions are still unanswered, and with the availability of novel technologies such as single-cell sequencing and cell fate-mapping, new fascinating questions arose. In this review, we will summarize current findings on the role of NF-κB in monocytes and macrophages. These innate immune cells show high plasticity and dynamically adjust their effector functions against invading pathogens and environmental cues. Their versatile functions can range from antimicrobial defense and antitumor immune responses to foam cell formation and wound healing. NF-κB is crucial for their activation and balances their phenotypes by finely coordinating transcriptional and epigenomic programs. Thereby, NF-κB is critically involved in inflammasome activation, cytokine release, and cell survival. Macrophage-specific NF-κB activation has far-reaching implications in the development and progression of numerous inflammatory diseases. Moreover, recent findings highlighted the temporal dynamics of myeloid NF-κB activation and underlined the complexity of this inflammatory master regulator. This review will provide an overview of the complex roles of NF-κB in macrophage signal transduction, polarization, inflammasome activation, and cell survival.

Estimating the Interaction Strength Between PTS1-Peptides and Their Receptor PEX5 in Living Cells Using Flow-Cytometer-Based FRET (flowFRET) Measurements.

The import of many peroxisomal matrix proteins is initiated by the interaction of type-1 peroxisomal targeting signals (PTS1) residing at the extreme C-terminus of cargo proteins and their receptor protein PEX5. This interaction has been amply investigated by biophysical methods using isolated proteins and peptides or heterologous systems such as two-hybrid assays. However, a recently developed novel application of Fluorescence resonance energy transfer (FRET) allows a quantifying measurement of this interaction in living cells. This method combines the systematic measurement of FRET-efficiency in a high number of cells with a well-suited normalization protocol and a fitting algorithm, which together allow the estimation of numerical values for the apparent interaction strength that correlates with other measures of binding strength but can be obtained under rather physiological conditions.

Twelve-month follow-up after hospitalization for SARS-COV-2: Physiology improves, symptoms remain.

OBJECTIVES: Persistent symptoms on short-term follow-up after infection with COVID-19 are common, but long-term consequences have been insufficiently studied. The aim of this study was to characterize pulmonary function and ongoing symptoms 12 months after hospitalization with COVID-19. METHODS: This prospective multicenter study included 222 patients hospitalized with PCR-confirmed COVID-19 in the Central Denmark Region. Disease severity was stratified using WHO Clinical Progression Scale. Clinical characteristics, pulmonary function test (PFT), 6-minute walk test (6MWT), and patient-reported outcome measures were collected at follow-up 3 and 12 months after discharge. Outcome measures from follow-up 3 months after discharge have previously been published. RESULTS: A total of 179 (81%) patients completed the 12-month follow-up. Median age was 60 years (IQR 51, 69) and 58% were male patients. At 12-month follow-up 49.7% had a normal diffusion capacity for carbon monoxide (DLCO), while 39.4% had DLCO < 80%. The 6MWT distance increased significantly (29 m 95% CI 19, 40; p < 0.01). An mMRC score of 0 was reported by 51% and an mMRC ≥ 2 by 20%. The frequency and severity of fatigue, depression, and anxiety did not improve over time. CONCLUSIONS: The study found that impaired DLCO percentage is common 12 months after hospitalization with SARS-CoV-2 and reduction in DLCO percentage is associated to dyspnea.

Antagonistic Functions of Androgen Receptor and NF-κB in Prostate Cancer-Experimental and Computational Analyses.

Prostate cancer is very frequent and is, in many countries, the third-leading cause of cancer related death in men. While early diagnosis and treatment by surgical removal is often curative, metastasizing prostate cancer has a very bad prognosis. Based on the androgen-dependence of prostate epithelial cells, the standard treatment is blockade of the androgen receptor (AR). However, nearly all patients suffer from a tumor relapse as the metastasizing cells become AR-independent. In our study we show a counter-regulatory link between AR and NF-κB both in human cells and in mouse models of prostate cancer, implying that inhibition of AR signaling results in induction of NF-κB-dependent inflammatory pathways, which may even foster the survival of metastasizing cells. This could be shown by reporter gene assays, DNA-binding measurements, and immune-fluorescence microscopy, and furthermore by a whole set of computational methods using a variety of datasets. Interestingly, loss of PTEN, a frequent genetic alteration in prostate cancer, also causes an upregulation of NF-κB and inflammatory activity. Finally, we present a mathematical model of a dynamic network between AR, NF-κB/IκB, PI3K/PTEN, and the oncogene c-Myc, which indicates that AR blockade may upregulate c-Myc together with NF-κB, and that combined anti-AR/anti-NF-κB and anti-PI3K treatment might be beneficial.

Effects of Hyperoxia and Hyperoxic Oscillations on the Proteome of Murine Lung Microvascular Endothelium.

Patients presenting with insufficient tissue oxygenation and impaired lung function as in acute respiratory distress syndrome (ARDS) frequently require mechanical ventilation with supplemental oxygen. Despite the lung being used to experiencing the highest partial pressure of oxygen during healthy breathing, the organ is susceptible to oxygen-induced injury at supraphysiological concentrations. Hyperoxia-induced lung injury (HALI) has been regarded as a second hit to pre-existing lung injury and ventilator-induced lung injury (VILI) attributed to oxidative stress. The injured lung has a tendency to form atelectasis, a cyclic collapse and reopening of alveoli. The affected lung areas experience oxygen conditions that oscillate between hyperoxia and hypoxia rather than remaining in a constant hyperoxic state. Mechanisms of HALI have been investigated in many animal models previously. These studies provided insights into the effects of hyperoxia on the whole organism. However, cell type-specific responses have not been dissected in detail, but are necessary for a complete mechanistic understanding of ongoing pathological processes. In our study, we investigated the effects of constant and intermittent hyperoxia on the lung endothelium from a mouse by an in vitro proteomic approach. We demonstrate that these oxygen conditions have characteristic effects on the pulmonary endothelial proteome that underlie the physiological (patho)mechanisms.

Studying the interaction between PEX5 and its full-length cargo proteins in living cells by a novel Försters resonance energy transfer-based competition assay.

The import of the majority of soluble peroxisomal proteins is initiated by the interaction between type-1 peroxisomal targeting signals (PTS1) and their receptor PEX5. PTS1 motifs reside at the extreme C-terminus of proteins and consist of a characteristic tripeptide and a modulatory upstream region. Various PTS1-PEX5 interactions have been studied by biophysical methods using isolated proteins or in heterologous systems such as two-hybrid assays, but a recently established approach based on Försters resonance energy transfer (FRET) allows a quantifying investigation in living cells. FRET is the radiation-free energy transfer between two fluorophores in close proximity and can be used to estimate the fraction of acceptor molecules bound to a donor molecule. For PTS1-PEX5 this method relies on the measurement of FRET-efficiency between the PTS1-binding TPR-domain of PEX5 tagged with mCherry and EGFP fused to a PTS1 peptide. However, this method is less suitable for binding partners with low affinity and protein complexes involving large proteins such as the interaction between full-length PTS1-carrying cargo proteins and PEX5. To overcome this limitation, we introduce a life-cell competition assay based on the same FRET approach but including a fusion protein of Cerulean with the protein of interest as a competitor. After implementing the mathematical description of competitive binding experiments into a fitting algorithm, we demonstrate the functionality of this approach using known interaction partners, its ability to circumvent previous limitations of FRET-measurements and its ability to study the interaction between PEX5 and its full-length cargo proteins. We find that some proteins (SCP2 and AGXT) bind PEX5 with higher affinity than their PTS1-peptides alone, but other proteins (ACOX3, DAO, PerCR-SRL) bind with lower but reasonable affinity, whereas GSTK1 binds with very low affinity. This binding strength was not increased upon elongating the PEX5 TPR-domain at its N-terminus, PEX5(N-TPR), although it interacts specifically with the N-terminal domain of PEX14. Finally, we demonstrate that the latter reduces the interaction strength between PEX5(N-TPR) and PTS1 by a dose-dependent but apparently non-competitive mechanism. Altogether, this demonstrates the power of this novel FRET-based competition approach for studying cargo recognition by PEX5 and protein complexes including large proteins in general.

A register-based study: cough - a frequent phenomenon in the adult population.

BACKGROUND: Chronic cough, more than 8 weeks, can either be without co-morbidity called unexplained chronic cough (UCC) or with co-morbidity called refractory chronic cough (RCC). Using datasets from the Danish National Prescription Registry (Prescription Registry) and Danish National Patient Registry (Patient Registry) we wanted to investigate the prevalence and factors of importance of cough in a Nationwide registry. MATERIAL AND METHODS: Inclusion criteria were patients 18-90 years with at least one final cough diagnosis (ICD-10 DR05/DR059) in Patient registry or patients who have redeemed ≥2 prescriptions for relevant cough-medication within a 90-day harvest in the Prescription registry from 2008 to 2017. To validate this study's chosen proxy on chronic cough an analysis of the Patient registry sub-population with a contact of ≥8 weeks and then final diagnosis code DR05/DR059 was also performed. The population was divided into UCC and RCC. RESULTS: Of the 104,216 patients from the Prescription registry, 52,727 were classified as having UCC and 51,489 were classified with RCC. From the Patient registry 34,260 were included, of whom 12,278 had UCC and 21,982 had RCC. Cough were frequently found among females (p < 0.0001). Both genders were around 2 years older in RCC than UCC (p < 0.0001) Spirometry was performed in 69 and 57%, X-ray in 73 and 58% and asthma challenge test performed in 13 and 5% (UCC and RCC, respectively, p < 0.0001). The frequency of co-morbidities such as heart failure, rheumatologic disease, pulmonary embolism, and diabetes was < 10%. CONCLUSION: Many patients suffer from chronic cough or cough requiring medications, with or without co-morbidity; frequently found among menopausal women. Most patients had a substantial work-up performed. The high frequency and the resources consuming work-up program call for systematic coding of disease, systematic patient evaluation and more specific treatment options. The study was approved (ID: no. P-2019-191).

Complete response to anti-interleukin-5 biologics in a real-life setting: results from the nationwide Danish Severe Asthma Register.

Background: Phase III regulatory trials show that anti-interleukin (IL)-5 biologics efficiently reduce exacerbations and the use of maintenance oral corticosteroids (mOCS) in patients with severe eosinophilic asthma. However, patients eligible for these trials differ significantly compared with real-life severe asthma populations. Therefore, our aim was to explore efficacy in a real-life setting. The Danish Severe Asthma Register (DSAR) is a complete, nationwide register that comprises all Danish patients on biological therapy for severe asthma. Methods: This prospective study identified patients in the DSAR who were complete responders to anti-IL-5 biologics after 1 year of treatment. A complete response was defined as resolution of the parameter setting the indication, i.e. recurrent exacerbations and/or use of mOCS. Results: A total of 289 out of 502 (58%) patients were complete responders to anti-IL-5 biologics after 12 months. Complete responders had greater improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire (ACQ) score compared with noncomplete responders (Δ 210 versus 30 mL; p<0.0001 and Δ -1.04 versus -0.68; p=0.016, respectively). A complete response was predicted by age at onset, less severe disease at baseline (i.e. no mOCS and lower ACQ score) and higher blood eosinophils. Conclusions: More than half of Danish patients treated with anti-IL-5 biologics for severe asthma achieve a complete response to treatment, thereby becoming free from asthma exacerbations and the need for mOCS. Complete responders also achieved superior effects on lung function and symptoms compared with noncomplete responders.