House dust mite SCIT reduces asthma risk and significantly improves long-term rhinitis and asthma control-A RWE study.

BACKGROUND: The German Therapy Allergen Ordinance (TAO) triggered an ongoing upheaval in the market for house dust mite (HDM) allergen immunotherapy (AIT) products. Three HDM subcutaneous AIT (SCIT) products hold approval in Germany and therefore will be available after the scheduled completion of the TAO procedure in 2026. In general, data from clinical trials on the long-term effectiveness of HDM AIT are rare. We evaluated real-world data (RWD) in a retrospective, observational cohort study based on a longitudinal claims database including 60% of all German statutory healthcare prescriptions to show the long-term effectiveness of one of these products in daily life. Aim of this analysis was to provide a per product analysis on effectiveness of mite AIT as it is demanded by international guidelines on AIT. METHODS: Subjects between 5 and 70 years receiving their first (index) prescription of SCIT with a native HDM product (SCIT group) between 2009 and 2013 were included. The exactly 3:1 matched control group received prescriptions for only symptomatic AR medication (non-AIT group); the evaluation period for up to 6 years of follow-up ended in February 2017. Study endpoints were the progression of allergic rhinitis (AR) and asthma, asthma occurrence and time to the onset of asthma after at least 2 treatment years. RESULTS: In total, 892 subjects (608 adults and 284 children/adolescents) were included in the SCIT group and 2676 subjects (1824 adults and 852 children/adolescents) in the non-AIT group. During the follow-up period after at least 2 years of SCIT, the number of prescriptions in the SCIT group was reduced by 62.8% (p < .0001) for AR medication and by 42.4% for asthma medication (p = .0003). New-onset asthma risk was significantly reduced in the SCIT vs non-AIT group by 27.0% (p = .0212). The asthma-preventive effect of SCIT occurred 15 months after start of the treatment. In the SCIT group, the time to onset of asthma was prolonged compared to the non-AIT group (p = .0010). CONCLUSION: In this first product based RWD analysis on SCIT with a native HDM product, patients aged 5 to 70 years benefited from AIT in the long term in terms of reduced progression of AR and asthma after at least 2 years of treatment. The effects seemed to last for up to 6 years after treatment termination. A significantly reduced risk of asthma onset was observed, starting after 15 months of treatment.

Long-term effects of pollen allergoid tyrosine-adsorbed subcutaneous immunotherapy on allergic rhinitis and asthma.

BACKGROUND: Allergen immunotherapy (AIT) may have a long-term disease-modifying effect. The aim of this study was to demonstrate the long-term effects of pollen allergoid tyrosine-adsorbed subcutaneous AIT on allergic rhinitis (AR) and asthma (AA) in clinical practice. METHODS: This retrospective study, funded by an AIT manufacturer, analysed the impact of AIT on AR progression and onset of need for AA medication, using a German database covering ~35% of national prescriptions during 2008-2020. Anonymized prescription data of AR patients aged 5-65 years treated with grass or tree pollen AIT between 2009 and 2013 and followed for at least 2 years after AIT cessation were compared with matched control patients with seasonal AR. RESULTS: 181,496 patients received AIT prescriptions. 5959 fulfilled the inclusion criteria. The median AIT treatment duration was 1092 days and the follow-up duration was 6.4 years. Less patients treated with AIT received prescriptions for symptomatic AR medication in the follow-up versus controls (AIT: OR: 0.37; 95% Confidence Interval (CI) 0.34, 0.40; p < .001, tyrosine-adsorbed AIT: OR: 0.27; 95% CI 0.20, 0.35 p < .001). Less asthmatic patients under AIT received prescriptions for AA medications versus controls (AIT: OR: 0.48; 95% CI 0.41, 0.55; p < .001, tyrosine-adsorbed AIT: OR: 0.48; 95% CI 0.29, 0.79; p = .004). AR and AA medication prescriptions for AIT patients were reduced in the follow-up versus baseline and controls (AIT: AR: 20.0%; 1.5 vs. 0.2 prescriptions; AA: 29.1%; 2.0 vs. 0.6 prescriptions, p < .001; tyrosine-adsorbed AIT: AR: 24.2%, 1.4 vs. 0.2 prescriptions; AA: 35.6%, 2.1 vs. 0.6 prescriptions, p < .001). The probability of AA medication onset in non-asthmatic patients during follow-up was reduced for AIT patients compared to controls (OR: 0.77, 95% CI 0.66, 0.90; p = .001). All endpoints were significant for children/adolescents and adults in stratified analyses. CONCLUSIONS: We found evidence for long-term effects up to 9.5 years for tyrosine-adsorbed AIT.

AIT in pediatric allergology: Opportunities and difficulties on the home stretch of the Therapy Allergen Ordinance.

Allergen immunotherapy (AIT) is the only causal therapy for allergic diseases and therefore particularly important. Allergen preparations have been classified as medicinal products since 1989 (Directive 89/342/EEC) and were taken over into Directive 2001/83/EC in 2001. In addition, in 2008 the Therapy Allergen Ordinance (TAO) came into force to stricter regulate the exception for named patient products (NPP) by exclusion of common therapy allergens from the exception to be marketed as NPP. The TAO regulates the requirements for testing safety and efficacy for these common therapy allergens. Due to the long transitional provisions, the last deadlines for solving clinical shortcomings will end in 2026. The advantage of this regulation is that the market for common allergens has been cleared of products without proof of efficacy, and new preparations with an optimal dose range are developed through dose-finding studies. The demand for long-term pediatric studies has been outlined by the standard Pediatric Investigation Plan (PIP) on allergen products from the Pediatric Committee of the EMA (PDCO). This is particularly problematic, as it is foreseeable that recruitment of patients will be limited and ethical problems arise from the prolonged use of placebo. Furthermore, many newly approved preparations will not be used in pediatrics for the foreseeable future, as no marketing authorization has yet been granted for this age group. This will result in a serious supply gap for children.

Ivy leaf dry extract EA 575 for the treatment of acute and chronic cough in pediatric patients: review and expert survey.

OBJECTIVES: EA 575 (Prospan) is a herbal medicine containing a dried extract of ivy leaves (drug extract ratio 5-7.5:1; extraction solvent, 30% ethanol). Although widely used for the treatment of cough, there remains a lack of clarity on the effects of EA 575 in children. This study aimed to evaluate the efficacy and tolerability of EA 575 in pediatric patients with cough, via a literature review and expert survey. METHODS: A MEDLINE/PubMed database search was performed to identify articles evaluating the efficacy and tolerability of EA 575 in pediatric patients with cough. An online survey of international pediatric cough experts was conducted to gather expert opinion regarding the use of EA 575 for pediatric cough. RESULTS: Ten controlled clinical trials and nine observational studies were identified. Controlled trials reported improvements in lung function and subjective cough symptoms with EA 575, while observational studies indicated overall favorable efficacy. EA 575 was generally well tolerated, with a low incidence of adverse events in children of all ages, including those aged <1 year. Survey responses from ten experts aligned with findings from the reviewed studies. Most experts agreed that EA 575 may improve quality of life, and highlighted its potential benefits on sleep. CONCLUSIONS: EA 575 has minimal side effects in pediatric patients with cough, as demonstrated by large, real-world studies. EA 575 may provide clinical benefits in pediatric patients; however, more robust clinical trials are needed to confirm its efficacy.

EA 575 (Prospan) is a medicine containing a dried extract of ivy leaves that is used to treat coughs. The aim of this review was to evaluate the available published information on the health benefits and side effects of EA 575 in children with coughs. We also conducted a survey of doctors who treat children with coughs. We found information from ten research trials that compared EA 575 with another cough medicine or a "dummy medicine". Although these studies included only a small number of children, the results suggested that children's breathing and cough symptoms may improve with EA 575 treatment. We also found nine studies that included children being treated in normal clinical situations and not in a research setting. Most of the children included in these studies and their doctors thought that EA 575 treatment was beneficial. A low number of side effects was reported in children of all ages, including in infants aged <1 year. Survey responses from ten doctors generally agreed with the findings from the research studies. Most of the doctors thought that EA 575 may improve quality of life. Improved sleep was commonly mentioned by doctors. Overall, our findings indicate that EA 575 has minimal side effects in children; we call for more research on the benefits of EA 575 on cough symptoms in children.

[Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023 - published by the German Respiratory Society (DGP) e. V.] / S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023.

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.

Pathogen spectra in hospitalised and nonhospitalised children with community-acquired pneumonia.

Background: Paediatric community-acquired pneumonia (CAP) is a leading cause of paediatric morbidity. However, particularly for outpatients with paediatric CAP, data on aetiology and management are scarce. Methods: The prospective pedCAPNETZ study multicentrically enrols children and adolescents with outpatient-treated or hospitalised paediatric CAP in Germany. Blood and respiratory specimens were collected systematically, and comprehensive analyses of pathogen spectra were conducted. Follow-up evaluations were performed until day 90 after enrolment. Results: Between December 2014 and August 2020, we enrolled 486 children with paediatric CAP at eight study sites, 437 (89.9%) of whom had radiographic evidence of paediatric CAP. Median (interquartile range) age was 4.5 (1.6-6.6) years, and 345 (78.9%) children were hospitalised. The most prevalent symptoms at enrolment were cough (91.8%), fever (89.2%) and tachypnoea (62.0%). Outpatients were significantly older, displayed significantly lower C-reactive protein levels and were significantly more likely to be symptom-free at follow-up days 14 and 90. Pathogens were detected in 90.3% of all patients (one or more viral pathogens in 68.1%; one or more bacterial strains in 18.7%; combined bacterial/viral pathogens in 4.1%). Parainfluenza virus and Mycoplasma pneumoniae were significantly more frequent in outpatients. The proportion of patients with antibiotic therapy was comparably high in both groups (92.4% of outpatients versus 86.2% of hospitalised patients). Conclusion: We present first data on paediatric CAP with comprehensive analyses in outpatients and hospitalised cases and demonstrate high detection rates of viral pathogens in both groups. Particularly in young paediatric CAP patients with outpatient care, antibiotic therapy needs to be critically debated.

Post hoc analysis examining symptom severity reduction and symptom absence during food challenges in individuals who underwent oral immunotherapy for peanut allergy: results from three trials.

PURPOSE: Peanut allergy and its current management, involving peanut avoidance and use of rescue medication during instances of accidental exposure, are burdensome to patients and their caregivers and can be a source of stress, uncertainty, and restriction. Physicians may also be frustrated with a lack of effective and safe treatments other than avoidance in the current management of peanut allergy. Efficacy, determined using double-blind, placebo-controlled food challenges (DBPCFCs), of oral immunotherapy with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Palforzia®) was demonstrated versus placebo in children and adolescents aged 4 to 17 years in multiple phase 3 trials; continued benefit of PTAH was shown in a follow-on trial. The DBPCFC is a reproducible, rigorous, and clinically meaningful assessment accepted by regulatory authorities to evaluate the level of tolerance as an endpoint for accidental exposures to peanut in real life. It also provides useful clinical and patient-relevant information, including the amount of peanut protein an individual with peanut allergy can consume without experiencing dose-limiting symptoms, severity of symptoms, and organs affected upon ingestion of peanut protein. We explored symptoms of peanut exposure during DBPCFCs from phase 3 and follow-on trials of PTAH to further characterize treatment efficacy from a perspective relevant to patients, caregivers, and clinicians. METHODS: Symptom data recorded during screening and/or exit DBPCFCs from participants aged 4 to 17 years receiving PTAH or placebo were examined post hoc across three PTAH trials (PALISADE [ARC003], ARC004 [PALISADE follow-on], and ARTEMIS [ARC010]). The maximum peanut protein administered as a single dose during DBPCFCs was 1000 mg (PALISADE and ARTEMIS) and 2000 mg (ARC004). Symptoms were classified by system organ class (SOC) and maximum severity. Endpoints were changes in symptom severity and freedom from symptoms (ie, asymptomatic) during DBPCFC. Relative risk (RR) was calculated for symptom severity by SOC and freedom from symptoms between groups; descriptive statistics were used to summarize all other data. RESULTS: The risk of any respiratory (RR 0.42 [0.30-0.60], P < 0.0001), gastrointestinal (RR 0.34 [0.26-0.44], P < 0.0001), cardiovascular/neurological (RR 0.17 [0.08-0.39], P < 0.001), or dermatological (RR 0.33 [0.22-0.50], P < 0.0001) symptoms was significantly lower in participants treated with PTAH versus placebo upon exposure to peanut at the end of the PALISADE trial (ie, exit DBPCFC). Compared with placebo-treated participants (23.4%), the majority (76.3%) of PTAH-treated participants had no symptoms at the exit DBPCFC when tested at the peanut protein dose not tolerated (ie, reactive dose) during the screening DBPCFC. Significantly higher proportions of PTAH-treated participants were asymptomatic at doses ≤ 100 mg in the exit DBPCFC compared with placebo-treated participants (PALISADE: 69.35% vs 12.10%, RR 5.73 [95% confidence interval (CI) 3.55-9.26]; P < 0.0001; ARTEMIS: 67.42% vs 13.95%, RR 4.83 [95% CI 2.28-10.25]; P < 0.0001); findings were similar at peanut protein doses ≤ 1000 mg (PALISADE: RR 15.56 [95% CI 5.05-47.94]; P < 0.0001; ARTEMIS: RR 34.74 [95% CI 2.19-551.03]; P < 0.0001). In ARC004, as the period of PTAH maintenance became longer, greater proportions of participants were asymptomatic at doses of peanut protein ≤ 1000 mg in the exit DBPCFC (from 37.63% after ~ 6 months of maintenance treatment [exit DBPCFC of PALISADE] to 45.54% after ~ 13 months and 58.06% after ~ 20 months of overall PTAH maintenance treatment). CONCLUSIONS: PTAH significantly reduced symptom severity due to exposure to peanut, which is clinically relevant. When exposed to peanut, participants with peanut allergy treated with PTAH rarely had moderate or severe respiratory or cardiovascular/neurological symptoms. Oral immunotherapy with PTAH appears to reduce frequency and severity of allergic reactions in individuals with peanut allergy after accidental exposure to peanut and may enable them and their families to have an improved quality of life. Trial registration ClinicalTrials.gov, NCT02635776, registered 17 December 2015, https://clinicaltrials.gov/ct2/show/NCT02635776?term=AR101&draw=2&rank=7 ; ClinicalTrials.gov, NCT02993107, registered 08 December 2016, https://clinicaltrials.gov/ct2/show/NCT02993107?term=AR101&draw=2&rank=6 ; ClinicalTrials.gov, NCT03201003, registered 22 June 2017, https://clinicaltrials.gov/ct2/show/NCT03201003 ? term = AR101&draw = 2&rank = 9.

Cow's milk and hen's egg anaphylaxis: A comprehensive data analysis from the European Anaphylaxis Registry.

BACKGROUND: Cow's milk (CM) and hen's egg (HE) are leading triggers of anaphylaxis in early childhood. The aim of this study was to identify clinical phenotypes and therapeutic measures for CM anaphylaxis (CMA) compared to HE anaphylaxis (HEA) in children up to 12 years of age, based on a large pan-European dataset from the European Anaphylaxis Registry. METHODS: Data from 2007 to 2020 on clinical phenotypes and treatment from 10 European countries, as well as Brazil, were analysed. The two-step cluster analysis was used to identify the most frequent phenotypes. For each trigger, three clusters were extracted based on sex, age, and existence of symptoms in four vitally important systems. RESULTS: Altogether 284 children with CMA and 200 children with HEA were identified. They were characterised as male (69% vs. 64%), infants (65% vs. 61%), with a most frequent grade III of Ring&Messmer classification (62% vs. 64%), in CMA versus HEA, respectively. Respiratory symptoms occurred more often in CMA (91% vs. 83%, p = 0.010), especially in infants (89% vs. 79%, p = 0.008). Cardiovascular symptoms were less frequent in CMA (30% vs. 44%, p = 0.002), in both infants (33% vs. 46%, p = 0.027), and older children (25% vs. 42%, p = 0.021). The clusters extracted in the CMA group were characterised as: (1) mild dermal infants with severe GI (40%), 2. severe dermal (35%), 3. respiratory (25%). While in HEA group: 1. infants with severe GI and/or reduction of alertness (40%), (2) conjunctival (16%), (3) mild GI without conjunctivitis (44%). The severity of the reaction was independent from the amount of ingested allergen protein, regardless of trigger. The first-line adrenaline application differed between the countries (0%-92%, as well as the reasons for not administering adrenaline, p < 0.001). CONCLUSIONS: Despite the similarity of their age, sex, and severity grade, the clinical profiles differed between the CMA and HEA children. Adrenaline was underused, and its administration was country dependent. Further studies are needed to assess to what extent the differences in the clinical profiles are related to matrix and/or absorption effects, and/or the allergen itself.

Food-Induced Anaphylaxis: Data From the European Anaphylaxis Registry.

BACKGROUND: Food is one of the most common elicitors of anaphylaxis, with an increasing incidence over recent years. OBJECTIVES: To characterize elicitor-specific phenotypes and identify factors enhancing the risk or severity of food-induced anaphylaxis (FIA). METHODS: We analyzed data from the European Anaphylaxis Registry applying an age- and sex-matched analysis of associations (Cramer's V) for single food triggers and calculated odds ratios (ORs) for severe FIA. RESULTS: We identified 3,427 cases of confirmed FIA showing an age-dependent elicitor ranking (for children: peanut, cow's milk, cashew, and hen's egg; and for adults: wheat flour, shellfish, hazelnut, and soy). The age- and sex-matched analysis revealed defined symptom patterns for wheat and cashew. Wheat-induced anaphylaxis was more frequently associated with cardiovascular symptoms (75.7%; Cramer's V = 0.28) and cashew-induced anaphylaxis with gastrointestinal symptoms (73.9%; Cramer's V = 0.20). Furthermore, concomitant atopic dermatitis was slightly associated with anaphylaxis to hen's egg (Cramer's V = 0.19) and exercise was strongly associated with anaphylaxis to wheat (Cramer's V = 0.56). Additional factors influencing the severity were alcohol intake in wheat anaphylaxis (OR = 3.23; CI, 1.31-8.83) and exercise in peanut anaphylaxis (OR = 1.78; CI, 1.09-2.95). CONCLUSIONS: Our data show that FIA is age-dependent. In adults, the range of elicitors inducing FIA is broader. For some elicitors, the severity of FIA seems to be related to the elicitor. These data require confirmation in future studies considering a clear differentiation between augmentation and risk factors in FIA.

Pathogenic variants in CLXN encoding the outer dynein arm docking-associated calcium-binding protein calaxin cause primary ciliary dyskinesia.

PURPOSE: Primary ciliary dyskinesia (PCD) is a heterogeneous disorder that includes respiratory symptoms, laterality defects, and infertility caused by dysfunction of motile cilia. Most PCD-causing variants result in abnormal outer dynein arms (ODAs), which provide the generative force for respiratory ciliary beating and proper mucociliary clearance. METHODS: In addition to studies in mouse and planaria, clinical exome sequencing and functional analyses in human were performed. RESULTS: In this study, we identified homozygous pathogenic variants in CLXN (EFCAB1/ODAD5) in 3 individuals with laterality defects and respiratory symptoms. Consistently, we found that Clxn is expressed in mice left-right organizer. Transmission electron microscopy depicted ODA defects in distal ciliary axonemes. Immunofluorescence microscopy revealed absence of CLXN from the ciliary axonemes, absence of the ODA components DNAH5, DNAI1, and DNAI2 from the distal axonemes, and mislocalization or absence of DNAH9. In addition, CLXN was undetectable in ciliary axonemes of individuals with defects in the ODA-docking machinery: ODAD1, ODAD2, ODAD3, and ODAD4. Furthermore, SMED-EFCAB1-deficient planaria displayed ciliary dysmotility. CONCLUSION: Our results revealed that pathogenic variants in CLXN cause PCD with defects in the assembly of distal ODAs in the respiratory cilia. CLXN should be referred to as ODA-docking complex-associated protein ODAD5.

Therapeutic principles and unmet needs in the treatment of cough in pediatric patients: review and expert survey.

BACKGROUND: There are evidence gaps in the management of pediatric cough, particularly for acute pediatric cough. This study had two aims: to identify therapeutic principles and unmet needs in the treatment of cough in pediatric patients (internationally), and to consider the evidence required to address these unmet needs. METHODS: A MEDLINE/PubMed database search was performed to identify articles describing therapeutic principles in the treatment of pediatric cough. An online survey of international pediatric cough experts was conducted, with questions on the definitions, diagnosis, treatment, and unmet needs in pediatric cough management. RESULTS: Cough guidelines have differing definitions of pediatric patients (≤12-18 years), acute pediatric cough (< 2-3 weeks), and chronic pediatric cough (> 4-8 weeks). Similarly, among 18 experts surveyed, definitions varied for pediatric patients (≤10-21 years), acute pediatric cough (< 3-5 days to < 6 weeks), and chronic pediatric cough (> 2-8 weeks). Guidelines generally do not recommend over-the-counter or prescription cough medicines in acute pediatric cough, due to lack of evidence. In the expert survey, participants had differing opinions on which medicines were most suitable for treating acute pediatric cough, and noted that effective treatments are lacking for cough-related pain and sleep disruption. Overall, guidelines and experts agreed that chronic pediatric cough requires diagnostic investigations to identify the underlying cough-causing disease and thereby to guide treatment. There are unmet needs for new effective and safe treatments for acute pediatric cough, and for randomized controlled trials of existing treatments. Safety is a particular concern in this vulnerable patient population. There is also a need for better understanding of the causes, phenotypes, and prevalence of pediatric cough, and how this relates to its diagnosis and treatment. CONCLUSIONS: Whereas pediatric cough guidelines largely align with regard to the diagnosis and treatment of chronic cough, there is limited evidence-based guidance for the management of acute cough. There is a need for harmonization of pediatric cough management, and the development of standard guidelines suitable for all regions and patient circumstances.

Work-related stress and atopic dermatitis: Results from the study on occupational allergy risks.

Chronic stress at work is ubiquitous in modern societies. However, its influence on atopic dermatitis (AD) has hardly been investigated. This study aimed to elucidate the association between work-related stress and AD via a longitudinal study. The analysis comprised data from three phases (2002-2003, 2007-2009, 2017-2018) of the prospective Study on Occupational Allergy Risks (SOLAR), including 1,240 young adults aged 16 to 18 years at baseline (61% female) who were originally recruited for the International Study of Asthma and Allergies in Childhood Phase II in 1995-1996. AD was assessed at all three phases based on self-reports of a physician's diagnosis and symptoms. Work-related stress was measured at all three periods using the work discontent and work overload scales from the Trier Inventory for the Assessment of Chronic Stress with adaptions to school and university. Generalized estimating equations were used to analyze the association between stress and AD, treating work discontent and work overload first as continuous and then as categorical exposure variables. We observed 50 AD cases (4%) at SOLAR I, 48 (4%) at SOLAR II, and 42 (3%) at SOLAR III. A one-point increase in the work discontent score was associated with an odds ratio (OR) for AD of 1.05 (95% confidence interval [CI], 1.00-1.10). The respective increase in the work overload score led to an OR of 1.03 (95% CI, 0.99-1.06). In the categorical analysis, there was no clear indication of elevated odds of AD in the highest vs. lowest exposure group (4th vs. 1st quartile: OR, 1.53; 95% CI, 0.92-2.53 for work discontent; OR, 1.38, 95% CI, 0.83-2.27 for work overload). Altogether, we observed limited to no evidence for an association between work-related stress and AD. Our study's ability to detect stronger evidence may have been compromised by shortcomings such as nondifferential misclassification of the outcome or insufficient statistical precision due to small numbers of AD cases. Another explanation could be that AD predominantly becomes evident in childhood, not in adulthood.

Parental occupational exposures prior to conception and offspring wheeze and eczema during first year of life.

PURPOSE: Parental exposures prior to conception might influence asthma and allergy risk in offspring. As occupational exposures are established risk factors for asthma and allergies, we investigated if parental occupational exposures prior to conception cause wheeze and eczema in offspring during the first year of life. METHODS: We analysed data of 436 families from an offspring cohort based on a follow-up study of German participants of the International Study of Asthma and Allergies in Childhood (ISAAC). Offspring cohort data was collected between 2009 and 2019. Occupational exposures were based on participants' work histories and measured by a Job-Exposure-Matrix. We used Bayesian logistic regression models for analysis. Inference and confounder selection were based on directed acyclic graphs. RESULTS: In mothers, for both allergic and irritative occupational exposures prior to conception suggestive effects on offspring eczema during the first year of life were found (allergens: odds ratio (OR) 1.22, 95% compatibility interval (CI) 0.92-1.57; irritants: OR 1.36, 95% CI 0.99-1.77), while no relation with wheeze was suggested. CONCLUSIONS: Our results suggest that reduction of asthma-related occupational exposures might not only reduce the burden of disease for occupationally induced or aggravated asthma and allergies in employees but also in their children.

Real-world evidence for the long-term effect of allergen immunotherapy: Current status on database-derived European studies.

Randomized controlled trials (RCTs) are the gold-standard for benefit-risk assessments during drug approval processes. Real-word data (RWD) and the resulting real-world evidence (RWE) are becoming increasingly important for assessing the effectiveness of drug products after marketing authorization showing how RCT results are transferred into real life care. The effectiveness of allergen immunotherapy (AIT) has been assessed in several RWE studies based on large prescription databases. We performed a literature search for retrospective cohort assessments of prescription databases in Europe to provide an overview on the methodology, long-term effectiveness outcomes, and adherence to AIT. Thirteen respective publications were selected. AIT was more effective in reducing the progression of allergic rhinitis (AR) compared to a non-AIT control group receiving only symptomatic treatment for AR for up to 6 years. The development and progression of asthma were hampered for most endpoints in patients treated with most preparations compared to the non-AIT group, receiving only anti-asthmatic medication. The results for "time to onset" of asthma were inconsistent. Adherence to AIT decreased during the recommended 3-year treatment period, however, in most studies higher adherence to subcutaneous than to sublingual AIT was shown. The analysis of long-term effectiveness outcomes of the RWE studies based on prescription databases confirms the long-term efficacy of AIT demonstrated in RCTs. Progression of rhinitis and asthma symptoms as well as delayed onset of asthma triggered by different allergens, real life adherence to the treatment shows differences in particular application routes.

Guideline on allergen immunotherapy in IgE-mediated allergic diseases: S2K Guideline of the German Society of Allergology and Clinical Immunology (DGAKI), Society of Pediatric Allergology and Environmental Medicine (GPA), Medical Association of German Allergologists (AeDA), Austrian Society of Allergology and Immunology (ÖGAI), Swiss Society for Allergology and Immunology (SSAI), German Dermatological Society (DDG), German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), German Society of Pediatrics and Adolescent Medicine (DGKJ), Society of Pediatric Pulmonology (GPP), German Respiratory Society (DGP), German Professional Association of Otolaryngologists (BVHNO), German Association of Paediatric and Adolescent Care Specialists (BVKJ), Federal Association of Pneumologists, Sleep and Respiratory Physicians (BdP), Professional Association of German Dermatologists (BVDD).

Not available.

Allergen immunotherapy during the COVID-19 pandemic-A survey of the German Society for Allergy and Clinical Immunology.

BACKGROUND: When the coronavirus pandemic 2019 (COVID-19) emerged, concerns were also raised regarding the safety of allergen immunotherapy (AIT). The German Society for Allergology and Clinical Immunology (DGAKI) conducted a survey to collect real-world data on the daily routine of administering subcutaneous AIT (SCIT) and sublingual AIT (SLIT) during the COVID-19 pandemic. METHODS: A web-based retrospective survey using the online platform survio with 26 standardized questions was used to survey physicians treating allergic patients during the pandemic. RESULTS: Three hundred and forty-five physicians who regularly offer and perform AIT in German-speaking countries responded to the questions. 70.4% of the respondents stated that they regularly initiated and dosed up SCIT for inhalant allergies (41.4% venom-SCIT, 73.6% SLIT), and 85.2% of the respondents stated that they continued SCIT for inhalant allergies during the maintenance phase in a regular way (59.1% venom-SCIT, 90.4% SLIT) in healthy patients without current symptoms indicating an infection with COVID-19. With regard to tolerability, there was no evidence for increased occurrence of adverse events in patients without current symptoms of COVID-19 infection during the pandemic. CONCLUSIONS: This retrospective study demonstrated adherence to national and international position papers of AIT during the COVID-19 pandemic in German-speaking countries. Besides, the survey has confirmed a good tolerability of AIT for both SCIT and SLIT.

S3 guideline Allergy Prevention.

BACKGROUND: The persistently high prevalence of allergic diseases in Western industrial nations and the limited possibilities of causal therapy make evidence-based recommendations for primary prevention necessary. METHODS: The recommendations of the S3 guideline Allergy Prevention, published in its last version in 2014, were revised and consulted on the basis of a current systematic literature search. The evidence search was conducted for the period 06/2013 - 11/2020 in the electronic databases Cochrane and MEDLINE, as well as in the reference lists of current reviews and through references from experts. The literature found was screened in two filtering processes, first by title and abstract, and the remaining papers were screened in the full text for relevance. The studies included after this were sorted by level of evidence, and the study quality was indicated in terms of potential bias (low/high). The revised recommendations were formally agreed and consented upon with the participation of representatives of the relevant professional societies and (self-help) organizations (nominal group process). Of 5,681 hits, 286 studies were included and assessed. RESULTS: Recommendations on maternal nutrition during pregnancy and breastfeeding as well as on infant nutrition in the first months of life again play an important role in the updated guideline: Many of the previous recommendations were confirmed by the current data. It was specified that breastfeeding should be exclusive for the first 4 - 6 months after birth, if possible, and that breastfeeding should continue with the introduction of complementary foods. A new recommendation is that supplementary feeding of cow's milk-based formula should be avoided in the first days of life if the mother wishes to breastfeed. Furthermore, it was determined that the evidence for a clear recommendation for hydrolyzed infant formula in non-breastfed infants at risk is currently no longer sufficient. It is therefore currently recommended to check whether an infant formula with proven efficacy in allergy prevention studies is available until the introduction of complementary feeding. Finally, based on the EAACI guideline, recommendations were made for the prevention of chicken egg allergy by introducing and regularly giving thoroughly heated (e.g., baked or hard-boiled) but not "raw" chicken egg (also no scrambled egg) with the complementary food. The recommendation to introduce peanut in complementary feeding was formulated cautiously for the German-speaking countries: In families who usually consume peanut, the regular administration of peanut-containing foods in age-appropriate form (e.g., peanut butter) with the complementary diet can be considered for the primary prevention of peanut allergy in infants with atopic dermatitis (AD). Before introduction, a clinically relevant peanut allergy must be ruled out, especially in infants with moderate to severe AD. There is still insufficient evidence for an allergy-preventive efficacy of prebiotics or probiotics, vitamin D, or other vitamins in the form of supplements so that recommendations against their supplementation were adopted for the first time in the current guideline. Biodiversity plays an important role in the development of immunological tolerance to environmental and food allergens: there is clear evidence that growing up on a farm is associated with a lower risk of developing asthma and allergic diseases. This is associated with early non-specific immune stimulation due to, among other things, the greater microbial biodiversity of house dust in this habitat. This aspect is also reflected in the recommendations on animal husbandry, on which a differentiated statement was made: In families without a recognizable increased allergy risk, pet keeping with cats or dogs should not generally be restricted. Families with an increased allergy risk or with children with already existing AD should not acquire a new cat - in contrast, however, dog ownership should not be discouraged. Interventions to reduce exposure to dust mite allergens in the home, such as the use of mite allergen-proof mattress covers ("encasings"), should be restricted to patients with already proven specific sensitization against house dust mite allergen. Children born by caesarean section have a slightly increased risk of asthma - this should be taken into account when advising on mode of delivery outside of emergency situations. Recent work also supports the recommendations on air pollutants: Active and passive exposure to tobacco smoke increase the risk of allergies, especially asthma, and should therefore be avoided. Exposure to nitrogen oxides, ozone, and small particles (PM 2.5) is associated with an increased risk, especially for asthma. Therefore, exposure to emissions of nitrogen oxides, ozone, and small particles (PM 2.5) should be kept low. The authors of this guideline are unanimously in favor of enacting appropriate regulations to minimize these air pollutants. There is no evidence that vaccinations increase the risk of allergies, but conversely there is evidence that vaccinations can reduce the risk of allergies. All children, including children at risk, should be vaccinated according to the current recommendations of the national public health institutes, also for reasons of allergy prevention. CONCLUSION: The consensus of recommendations in this guideline is based on an extensive evidence base. The update of the guideline enables evidence-based and up-to-date recommendations for the prevention of allergic diseases including asthma and atopic dermatitis.

Trajectories of asthma and allergy symptoms from childhood to adulthood.

BACKGROUND: Phenotypes of asthma and allergic diseases are mainly studied separately for children and adults. To explore the role of adolescence and young adulthood, we investigated symptom trajectories at the transition from childhood into adulthood. METHODS: Latent class analysis (LCA) was conducted in a population initially recruited for the German arm of Phase II of the International Study of Asthma and Allergies in Childhood and followed-up three times until their early 30s (N=2267). Indicators included in LCA were 12-month prevalences of symptoms of wheeze, rhinoconjunctivitis, and eczema. Latent classes were further characterised regarding important traits such as skin prick tests. Logistic regression models were used to investigate associations with environmental determinants such as smoking and occupational exposures. RESULTS: Six latent classes were identified: an asymptomatic one as well as three with single and two with co-occurring symptoms. All trajectories essentially established between baseline assessment at around 10 years and the first follow-up at around 17 years. Probabilities for symptoms increased from childhood to adolescence, especially for wheeze-related latent classes, while they remained constant in adulthood. Wheeze-related latent classes were also positively associated with exposures during adolescence (e.g. active smoking). CONCLUSION: Distinct trajectories of asthma and allergy symptoms establish from childhood through adolescence and stabilize during early adulthood. This pattern was most notable in wheeze-related latent classes which also showed the strongest positive associations with environmental exposures in adolescence/young adulthood. Therefore, not only childhood but also adolescence is relevant for disease development and offers considerable potential for prevention and health promotion.