COVID-19 and chronic rhinosinusitis: management and comorbidity - what have we learned?

INTRODUCTION: Approximately 5%-12% of the population worldwide suffer from chronic rhinosinusitis (CRS). CRS is defined as a chronic respiratory disease and is considered to be a risk factor for COVID-19 patients. AREAS COVERED: A non-systematic literature research was conducted on COVID-19 and treatment options for CRSwNP. The latest international publications in medical databases, international guidelines, and the internet were reviewed. Since there were no publications on all aspects of this topic during the pandemic, we included our own experience in this report. Based on the conducted literature research in addition to our previously reported experience, we discuss the treatment of CRSwNP during the COVID-19 pandemic and what can be taken for future pandemics. EXPERT OPINION: Intranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Indications for surgical treatment of CRS should be critically evaluated and reserved for patients with complications and those with no other treatment options. For this purpose, COVID-19 status should be known if possible and, in case of unclear status (emergency), using appropriate personal protective equipment. Systemic corticosteroids should be avoided were possible. Biological treatment should be continued under careful monitoring in uninfected patients and should be temporarily interrupted during COVID-19 infection.

[Neuroimmunology of allergic rhinitis part 2 : Interactions of neurons and immune cells and neuroimmunological units]. / Neuroimmunologie der allergischen Rhinitis Teil 2 : Interaktionen von Neuronen und Immunzellen und neuroimmunologische Einheiten.

Allergic rhinitis is an IgE-mediated, type­2 inflammatory disease. neuropeptides are released by neurons and interact with immune cells. Via colocalization, neuroimmune cell units such as nerve-mast cell units, nerve-type 2 innate lymphoid cell (ILC2) units, nerve-eosinophil units, and nerve-basophil units are formed. Markedly elevated tryptase levels were found in nasal lavage fluid and were strongly associated with neuropeptide levels. A close anatomical connection allows bidirectional communication between immune and neuronal cells. Transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin repeat 1 (TRPA1) are critically involved in immunological reactions in the setting of allergic rhinitis. Neuroimmunological communication plays an important role in the inflammatory process, so that allergic rhinitis can no longer be considered a purely immunological disease, but rather a combined neuroimmunological disease.

[Neuroimmunology of allergic rhinitis : Part 1: Cellular and humoral basic principles]. / Neuroimmunologie der allergischen Rhinitis : Teil 1: Zelluläre und humorale Grundlagen.

Allergic rhinitis (AR) is a very common disease with a high prevalence worldwide. It is an IgE-mediated type 2 inflammatory disease following exposure to inhalant allergens. A multitude of different neuropeptides including substance P, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), and neuromedin U (NMU) can be released via peripheral axon or central reflexes, interact with immune cells, and thus contribute to neurogenic inflammation which causes the nasal hyperreactivity (NHR) characteristic of AR. Independent production of neuroendocrine hormones and neuropeptides by immune cells has also been demonstrated. Neuro-immune cell units arise when immune and neuronal cells colocalize, for which typical anatomic regions are, e.g., the mast cell-nerve functional unit. The focus of this review is the elucidation of neuroimmune communication mechanisms in AR.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Protein quality as a complementary functional unit in life cycle assessment (LCA).

Goal and theoretical commentary: A number of recent life cycle assessment (LCA) studies have concluded that animal-sourced foods should be restricted-or even avoided-within the human diet due to their relatively high environmental impacts (particularly those from ruminants) compared with other protein-rich foods (mainly protein-rich plant foods). From a nutritional point of view, however, issues such as broad nutrient bioavailability, amino acid balances, digestibility and even non-protein nutrient density (e.g., micronutrients) need to be accounted for before making such recommendations to the global population. This is especially important given the contribution of animal sourced foods to nutrient adequacy in the global South and vulnerable populations of high-income countries (e.g., children, women of reproductive age and elderly). Often, however, LCAs simplify this reality by using 'protein' as a functional unit in their models and basing their analyses on generic nutritional requirements. Even if a 'nutritional functional unit' (nFU) is utilised, it is unlikely to consider the complexities of amino acid composition and subsequent protein accretion. The discussion herein focuses on nutritional LCA (nLCA), particularly on the usefulness of nFUs such as 'protein,' and whether protein quality should be considered when adopting the nutrient as an (n)FU. Further, a novel and informative case study is provided to demonstrate the strengths and weaknesses of protein-quality adjustment. Case study methods: To complement current discussions, we present an exploratory virtual experiment to determine how Digestible Indispensable Amino Acid Scores (DIAAS) might play a role in nLCA development by correcting for amino acid quality and digestibility. DIAAS is a scoring mechanism which considers the limiting indispensable amino acids (IAAs) within an IAA balance of a given food (or meal) and provides a percentage contribution relative to recommended daily intakes for IAA and subsequent protein anabolism; for clarity, we focus only on single food items (4 × animal-based products and 4 × plant-based products) in the current case exemplar. Further, we take beef as a sensitivity analysis example (which we particularly recommend when considering IAA complementarity at the meal-level) to elucidate how various cuts of the same intermediary product could affect the interpretation of nLCA results of the end-product(s). Recommendations: First, we provide a list of suggestions which are intended to (a) assist with deciding whether protein-quality correction is necessary for a specific research question and (b) acknowledge additional uncertainties by providing mitigating opportunities to avoid misinterpretation (or worse, dis-interpretation) of protein-focused nLCA studies. We conclude that as relevant (primary) data availability from supply chain 'gatekeepers' (e.g., international agri-food distributors and processors) becomes more prevalent, detailed consideration of IAA provision of contrasting protein sources needs to be acknowledged-ideally quantitatively with DIAAS being one example-in nLCA studies utilising protein as a nFU. We also contend that future nLCA studies should discuss the complementarity of amino acid balances at the meal-level, as a minimum, rather than the product level when assessing protein metabolic responses of consumers. Additionally, a broader set of nutrients should ideally be included when evaluating "protein-rich foods" which provide nutrients that extend beyond amino acids, which is of particular importance when exploring dietary-level nLCA.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System. METHODS: A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included. RESULTS: Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

Positionspapier: Empfehlungen zur Anwendung von Mepolizumab bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

The toll of noninfected CRS patients to the COVID-19 pandemic.

Social distancing with the aim of avoiding infections and pre-serve critical care capacities during the COVID-19 pandemic has been implemented in Germany according to World Health Organization (WHO) recommendations from early March onwards. Limitations of physical contacts to reduce exposure to SARS-CoV-2 infected individuals were handled strictly, particularly in medical centers dealing with airway diseases, like rhinology and pneumology clinics. Such measures and reluctance to visit out- and inpatient services resulted in a 82% decrease in consultations to the 12 German oto-rhino-laryngological (ORL) centres forming our database during the 50 days following March 09 in 2020 if compared to the same period in 2019. Our data on CRS care underline reports on undertreatment of non-COVID-19 individuals with several different diseases during the current pandemic. We should try to reduce the toll these patients have to pay as much as possible. We established telemedicine, e-Health and artificial intelligence-supported triage for selecting the right patients for onsite-consultations and to advise patients in several demands.

Genome-wide association study for αS1- and αS2-casein phosphorylation in Dutch Holstein Friesian.

Phosphorylation of caseins (CN) is a crucial post-translational modification that allows caseins to form colloid particles known as casein micelles. Both αS1- and αS2-CN show varying degrees of phosphorylation (isoforms) in cow milk and were suggested to be more relevant for stabilizing internal micellar structure than ß- and κ-CN. However, little is known about the genetic background of individual αS2-CN phosphorylation isoforms and the phosphorylation degrees of αS1- and αS2-CN (αS1-CN PD and αS2-CN PD), defined as the proportion of isoforms with higher degrees of phosphorylation in total αS1- and αS2-CN, respectively. We aimed to identify genomic regions associated with these traits using 50K single nucleotide polymorphisms for 1,857 Dutch Holstein Friesian cows. A total of 10 quantitative trait loci (QTL) regions were identified for all studied traits on 10 Bos taurus autosomes (BTA1, 2, 6, 9, 11, 14, 15, 18, 24, and 28). Regions associated with multiple traits were found on BTA1, 6, 11, and 14. We showed 2 QTL regions on BTA1, one affecting αS2-CN production and the other harboring the SLC37A1 gene, which encodes a phosphorus antiporter and affects αS1- and αS2-CN PD. The QTL on BTA6 harbors the casein gene cluster and affects individual αS2-CN phosphorylation isoforms. The QTL on BTA11 harbors the PAEP gene that encodes for ß-lactoglobulin and affects relative concentrations of αS2-CN-10P and αS2-CN-11P as well as αS1-CN PD and αS2-CN PD. The QTL on BTA14 harbors the DGAT1 gene and affects relative concentrations of αS2-CN-10P and αS2-CN-11P as well as αS1-CN PD and αS2-CN PD. Our results suggest that effects of identified genomic regions on phosphorylation of αS1- and αS2-CN are related to changes in milk synthesis and phosphorus secretion in milk. The actual roles of SLC37A1, PAEP, and DGAT1 in αS1- and αS2-CN phosphorylation in Dutch Holstein Friesian require further investigation.

Influence of partially demineralized milk proteins on rheological properties and microstructure of acid gels.

Innovative clean label processes employed in the manufacture of acid gels are targeted to modify the structure of proteins that contribute to rheological properties. In the present study, CO2-treated milk protein concentrate powder with 80% protein in dry matter (TMPC80) was mixed with nonfat dry milk (NDM) in different ratios for the manufacture of acid gels. Dispersions of NDM and TMPC80 that provided 100, 90, 70, and 40% of protein from NDM were reconstituted to 4.0% (wt/wt) protein and 12.0% (wt/wt) total solids. Dispersions were adjusted to pH 6.5, followed by heat treatment at 90°C for 10 min. Glucono-δ-lactone was added and samples were incubated at 30°C, reaching pH 4.5 ± 0.05 after 4 h of incubation. Glucono-δ-lactone levels were adjusted to compensate for the lower buffering capacity of samples with higher proportions of TMPC80, which is attributable to the depletion of buffering minerals from both the serum and micellar phase during preparation of TMPC80. Sodium dodecyl sulfate-PAGE analysis indicated a higher amount of caseins in the supernatant of unheated suspensions with increasing proportions of CO2-treated TMPC80, attributable to the partial disruption of casein micelles in TMPC80. Heat treatment reduced the level of whey proteins in the supernatant due to the heat-induced association of whey proteins with casein micelles, the extent of which was larger in samples containing more micellar casein (i.e., samples with a lower proportion of TMPC80). Particle size analysis showed only small differences between nonheated and heated dispersions. Gelation pH increased from ˜5.1 to ˜5.3, and the storage modulus of the gels at pH 4.5 increased from ˜300 to ˜420 Pa when the proportion of protein contributed by TMPC80 increased from 0 to 60%. Water-holding capacity also increased and gel porosity decreased with increasing proportion of protein contributed by TMPC80. The observed gel properties were in line with microstructural observations by confocal microscopy, wherein sample gels containing increasing levels of TMPC80 exhibited smaller, well-connected aggregates with uniform, homogeneous pore sizes. We concluded that TMPC80 can be used to partially replace NDM as a protein source to improve rheological and water-holding properties in acid gels. The resultant gels also exhibited decreased buffering, which can improve the productive capacity of yogurt manufacturing plants. Overall, the process can be leveraged to reduce the amount of hydrocolloids added to improve yogurt consistency and water-holding capacity, thus providing a path to meet consumer expectations of clean label products.