Prof. Dr. Claudia Traidl-Hoffmann

2024 Allergy

Makra L, Coviello L, Gobbi A, Jurman G, Furlanello C, Brunato M, et al.

Forecasting daily total pollen concentrations on a global scale

Background There is evidence that global anthropogenic climate change may be impacting floral phenology and the temporal and spatial characteristics of aero-allergenic pollen. Given the extent of current and future climate uncertainty, there is a need to strengthen predictive pollen forecasts. Methods The study aims to use CatBoost (CB) and deep learning (DL) models for predicting the daily total pollen concentration up to 14 days in advance for 23 cities, covering all five continents. The model includes the projected environmental parameters, recent concentrations (1, 2 and 4 weeks), and the past environmental explanatory variables, and their future values. Results The best pollen forecasts include Mexico City (R2(DL_7) ≈ .7), and Santiago (R2(DL_7) ≈ .8) for the 7th forecast day, respectively; while the weakest pollen forecasts are made for Brisbane (R2(DL_7) ≈ .4) and Seoul (R2(DL_7) ≈ .1) for the 7th forecast day. The global order of the five most important environmental variables in determining the daily total pollen concentrations is, in decreasing order: the past daily total pollen concentration, future 2 m temperature, past 2 m temperature, past soil temperature in 28–100 cm depth, and past soil temperature in 0–7 cm depth. City-related clusters of the most similar distribution of feature importance values of the environmental variables only slightly change on consecutive forecast days for Caxias do Sul, Cape Town, Brisbane, and Mexico City, while they often change for Sydney, Santiago, and Busan. Conclusions This new knowledge of the ecological relationships of the most remarkable variables importance for pollen forecast models according to clusters, cities and forecast days is important for developing and improving the accuracy of airborne pollen forecasts.

2024 JAMA Oncology

Hulpusch C, Neumann AU, Reiger M, Fischer JC, de Tomassi A, Hammel G, et al.

Association of Skin Microbiome Dynamics With Radiodermatitis in Patients With Breast Cancer

Importance The interindividual differences in severity of acute radiation dermatitis are not well understood. To date, the pathomechanism and interplay of microbiome and radiodermatitis before and during treatment remain largely unknown. Objective To assess the association of skin microbiome baseline composition and dynamics with severity of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer. Design, Setting, and Participants A longitudinal prospective pilot observational study was conducted between January 2017 and January 2019. Sequencing results were received in March 2021, and the data were analyzed from August 2021 to March 2023. This study was performed at an urban academic university cancer center. A total of 21 female patients with breast cancer after surgery were consecutively approached, of which 1 patient withdrew consent before the study started. Exposure Adjuvant radiotherapy for breast cancer for 7 weeks. Main Outcomes and Measures The main outcome was the association of baseline skin microbiome composition and its dynamics with the severity of radiodermatitis. A total of 360 skin microbiome samples from patients were analyzed, taken before, during, and after radiotherapy, from both the treated and contralateral healthy sides. The skin microbiome samples were analyzed using 16S (V1-V3) amplicon sequencing and quantitative polymerase chain reaction bacterial enumeration. Results Twenty female patients with breast cancer after surgery who underwent radiotherapy enrolled in the study had a median (range) age of 61 (37-81) years. The median (range) body mass index of the patients was 24.2 (17.6-38.4). The 16S sequencing revealed that low (<5%) relative abundance of commensal skin bacteria (Staphylococcus epidermidis, Staphylococcus hominis, Cutibacterium acnes) at baseline composition was associated with the development of severe radiodermatitis with an accuracy of 100% (sensitivity and specificity of 100%, P < .001). Furthermore, in patients with severe radiodermatitis, quantitative polymerase chain reaction bacterial enumeration revealed a general non–species-specific overgrowth of skin bacterial load before the onset of severe symptoms. Subsequently, the abundance of commensal bacteria increased in severe radiodermatitis, coinciding with a decline in total bacterial load. Conclusions and Relevance The findings of this observational study indicated a potential mechanism associated with the skin microbiome for the pathogenesis of severe radiodermatitis, which may be a useful biomarker for personalized prevention of radiodermatitis in patients undergoing adjuvant radiotherapy for breast cancer.

2024 European Heart Journal

He C, Breitner S, Zhang S, Huber V, Naumann M, Traidl-Hoffmann C

Nocturnal heat exposure and stroke risk

Background and Aims In recent decades, nighttime temperatures have increased faster than daytime temperatures. The increasing prevalence of nocturnal heat exposure may pose a significant risk to cardiovascular health. This study investigated the association between nighttime heat exposure and stroke risk in the region of Augsburg, Germany, and examined its temporal variations over 15 years. Methods Hourly meteorological parameters, including mean temperature, relative humidity, and barometric pressure, were acquired from a local meteorological station. A data set was obtained consisting of 11 037 clinical stroke cases diagnosed during warmer months (May to October) between the years 2006 and 2020. The average age of cases was 71.3 years. Among these cases, 642 were identified as haemorrhagic strokes, 7430 were classified as ischaemic strokes, and 2947 were transient ischaemic attacks. A time-stratified case-crossover analysis with a distributed lag non-linear model was used to estimate the stroke risk associated with extreme nighttime heat, as measured by the hot night excess (HNE) index after controlling for the potential confounding effects of daily maximum temperature and other climatic variables. Subgroup analyses by age group, sex, stroke subtype, and stroke severity were performed to identify variations in susceptibility to nighttime heat. Results Results suggested a significant increase in stroke risk on days with extreme nighttime heat (97.5% percentile of HNE) (odds ratio 1.07, 95% confidence interval 1.01–1.15) during the full study period. When comparing the results for 2013–20 with the results for 2006–12, there was a significant increase (P < .05) in HNE-related risk for all strokes and specifically for ischaemic strokes during the more recent period. Furthermore, older individuals, females, and patients with mild stroke symptoms exhibited a significantly increased vulnerability to nighttime heat. Conclusions This study found nocturnal heat exposure to be related to elevated stroke risk after controlling for maximum daytime temperature, with increasing susceptibility between 2006 and 2020. These results underscore the importance of considering nocturnal heat as a critical trigger of stroke events in a warming climate.

2023 BMC Biology

Hulpusch C, Rauer L, Nussbaumer T, Schwierzeck V, Bhattacharyya M, Erhart V, et al.

Benchmarking MicrobIEM – a user-friendly tool for decontamination of microbiome sequencing data

Background Microbiome analysis is becoming a standard component in many scientific studies, but also requires extensive quality control of the 16S rRNA gene sequencing data prior to analysis. In particular, when investigating low-biomass microbial environments such as human skin, contaminants distort the true microbiome sample composition and need to be removed bioinformatically. We introduce MicrobIEM, a novel tool to bioinformatically remove contaminants using negative controls. Results We benchmarked MicrobIEM against five established decontamination approaches in four 16S rRNA amplicon sequencing datasets: three serially diluted mock communities (108–103 cells, 0.4–80% contamination) with even or staggered taxon compositions and a skin microbiome dataset. Results depended strongly on user-selected algorithm parameters. Overall, sample-based algorithms separated mock and contaminant sequences best in the even mock, whereas control-based algorithms performed better in the two staggered mocks, particularly in low-biomass samples (≤ 106 cells). We show that a correct decontamination benchmarking requires realistic staggered mock communities and unbiased evaluation measures such as Youden’s index. In the skin dataset, the Decontam prevalence filter and MicrobIEM’s ratio filter effectively reduced common contaminants while keeping skin-associated genera. Conclusions MicrobIEM’s ratio filter for decontamination performs better or as good as established bioinformatic decontamination tools. In contrast to established tools, MicrobIEM additionally provides interactive plots and supports selecting appropriate filtering parameters via a user-friendly graphical user interface. Therefore, MicrobIEM is the first quality control tool for microbiome experts without coding experience.

2022 The Lancet Planetary Health

Herrmann A, Lenzer B, Muller BS, Danquah I, Nadeau KC, Muche-Borowski C, et al.

Integrating planetary health into clinical guidelines to sustainably transform health care

Climate change and other ecological crises threaten the health of humans and the natural systems on which humans depend.1 However, such planetary health issues have not yet entered the core of evidence-based medicine—clinical guidelines. Globally, medical associations, research institutions, and universities have placed planetary health on their agenda and are starting to integrate it into medical education.2,3 The UK National Health Service (NHS) aims to be climate neutral by 2040,4 and more than 50 countries committed to climate-smart health care by 2030 at the 26th UN Climate Conference of the Parties in Glasgow, Scotland.5 Despite all this progress, planetary health principles have yet to be fully incorporated into clinical routines. To achieve this, we believe that clinical guidelines are crucial. We screened a sample of 49 clinical guidelines from British, Chinese, Indian, Brazilian, Australian, European, German, and US-American medical associations and organisations (appendix pp 1–8). We selected guidelines dealing with a range of topics, which have apparent associations with planetary health issues, such as allergies, asthma, chronic obstructive pulmonary disease, cardiovascular disease, obesity, diabetes, dermatology, renal diseases, heat stroke, and colorectal cancer. We used the QDA Miner Lite programme (version 2.0.7; Provalis Research) to scan the guidelines for 30 keywords related to planetary health (eg, climate change, air pollution, and emissions; appendix pp 8–10). Most of the keywords were found in fewer than 5% of the guidelines. As an exception, “air pollution” was mentioned in 20%, and “environmental protection” and “emissions” in 10% of the scanned guidelines. If any of the 30 keywords were mentioned, they were frequently used in the context of disease aetiology or epidemiology and less often with regards to sustainable health services. Notably, the scanned British clinical practice guidelines from the National Institute for Health and Care Excellence (NICE) include an introductory paragraph about responsibility to promote environmentally sustainable health care. The NICE guideline on the prevention of cardiovascular disease explicitly mentions the environmental cobenefits of physically active travel and reduced intakes of animal-based saturated fats.6 The NICE strategy for 2021 to 2026 aims to develop a framework that aids in including environmental impact data in their guidelines to reduce the environmental footprint of health care.7 We argue that all medical associations and organisations who publish medical guidelines should include a strategy that systematically addresses planetary health issues in their guidelines. WHO has developed recommendations on how to incorporate equity, human rights, gender, and social determinants of health as cross-cutting issues into each step of WHO guideline development.8 Similarly, planetary health should become a mandatory dimension of clinical guideline development. The panel shows in what areas of guidelines the planetary health dimension should be considered. Developing separate guidelines on specific sustainable health care topics could also be useful—eg, administration of climate-friendly anaesthesia.

2022 Allergy

Agache I, Sampath V, Aguilera J, Akdis CA, Akdis M, Barry M, et al.

Climate change and global health: A call to more research and more action

There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political, and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

2021 PNAS

Damialis A, Gilles S, Sofiev M, Sofieva V, Kolek F, Bayr D, Traidl-Hoffman C, et al.

Higher airborne pollen concentrations correlated with increased SARS-CoV-2 infection rates, as evidenced from 31 countries across the globe

Pollen exposure weakens the immunity against certain seasonal respiratory viruses by diminishing the antiviral interferon response. Here we investigate whether the same applies to the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is sensitive to antiviral interferons, if infection waves coincide with high airborne pollen concentrations. Our original hypothesis was that more airborne pollen would lead to increases in infection rates. To examine this, we performed a cross-sectional and longitudinal data analysis on SARS-CoV-2 infection, airborne pollen, and meteorological factors. Our dataset is the most comprehensive, largest possible worldwide from 130 stations, across 31 countries and five continents. To explicitly investigate the effects of social contact, we additionally considered population density of each study area, as well as lockdown effects, in all possible combinations: without any lockdown, with mixed lockdown-no lockdown regime, and under complete lockdown. We found that airborne pollen, sometimes in synergy with humidity and temperature, explained, on average, 44% of the infection rate variability. Infection rates increased after higher pollen concentrations most frequently during the four previous days. Without lockdown, an increase of pollen abundance by 100 pollen/m3 resulted in a 4% average increase of infection rates. Lockdown halved infection rates under similar pollen concentrations. As there can be no preventive measures against airborne pollen exposure, we suggest wide dissemination of pollen-virus coexposure dire effect information to encourage high-risk individuals to wear particle filter masks during high springtime pollen concentrations.

2021 Global Change Biology

Rojo J, Oteros J, Picornell A, Maya-Manzano JM, Damialis A, Zink K, et al.

Effects of future climate change on birch abundance and their pollen load

Climate change impacts on the structure and function of ecosystems will worsen public health issues like allergic diseases. Birch trees (Betula spp.) are important sources of aeroallergens in Central and Northern Europe. Birches are vulnerable to climate change as these trees are sensitive to increased temperatures and summer droughts. This study aims to examine the effect of climate change on airborne birch pollen concentrations in Central Europe using Bavaria in Southern Germany as a case study. Pollen data from 28 monitoring stations in Bavaria were used in this study, with time series of up 30 years long. An integrative approach was used to model airborne birch pollen concentrations taking into account drivers influencing birch tree abundance and birch pollen production and projections made according to different climate change and socioeconomic scenarios. Birch tree abundance is projected to decrease in parts of Bavaria at different rates, depending on the climate scenario, particularly in current centres of the species distribution. Climate change is expected to result in initial increases in pollen load but, due to the reduction in birch trees, the amount of airborne birch pollen will decrease at lower altitudes. Conversely, higher altitude areas will experience expansions in birch tree distribution and subsequent increases in airborne birch pollen in the future. Even considering restrictions for migration rates, increases in pollen load are likely in Southwestern areas, where positive trends have already been detected during the last three decades. Integrating models for the distribution and abundance of pollen sources and the drivers that control birch pollen production allowed us to model airborne birch pollen concentrations in the future. The magnitude of changes depends on location and climate change scenario.

2021 The Lancet

Neumann AU, Goekkaya M, Dorgham K, Traidl-Hoffmann C, Gorochov G

Tocilizumab in COVID-19 therapy: who benefits, and how?

The RECOVERY Collaborative Group reported statistically significant improvement in survival of patients with COVID-19 who were receiving tocilizumab interleukin (IL)-6 inhibitor, albeit with very modest reduction of mortality (31% vs 35% with usual care, p=0·0028). This result adds to a number of studies with tocilizumab and other IL-6 antagonists, such as sarilumab, which showed only minor, or no, reduction in mortality. Given that IL-6 is associated with COVID-19 severity and mortality,3 the question arises as to why IL-6 antagonist therapy does not substantially improve survival. In April, 2021, we showed that IL-6 serum concentrations are indeed associated with COVID-19 severity (appendix); however, a better classification of severity is obtained when IL-6 is combined with other cytokine concentrations. Moreover, within each respiratory severity group, IL-6 is not significantly associated with mortality (appendix). It is rather distinct combinations of interferon α, inteferon β, IL-10, and tumour necrosis factor α that are better predictors of mortality in different severity groups. Nevertheless, mortality in the low IL-6 group of patients is significantly lower than in the high IL-6 group of patients (appendix), suggesting that IL-6 inhibitors should be given only to patients with high IL-6. Indeed, a retrospective analysis of tocilizumab therapy as a function of baseline IL-6 concentrations showed a large reduction in mortality (from 36% to 16%) in patients with high-baseline IL-6, but no reduction in mortality in low-baseline IL-6 patients. In conclusion, clinical trials of IL-6 antagonist therapy, such as RECOVERY1 and sarilumab COVID-19 global studies, should consider reanalysis of their results as a function of IL-6 baseline concentrations. More generally, clinical trials of personalised precision medicine, based on cytokine profiling, are needed for optimisation of COVID-19 therapy.

2021 Journal of Allergy and Clinical Immunology

Dorgham K, Quentric P, Gokkaya M, Marot S, Parizot C, Sauce D, et al.

Distinct cytokine profiles associated with COVID-19 severity and mortality

Background Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). Objective We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Methods Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). Results At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P < .0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. Conclusions Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.