Sodium Chloride versus Lactose as a Carrier for House Dust Mite Allergen in Allergen Chamber Studies: A Clinical Study to Assess Noninferiority.

INTRODUCTION: In the Fraunhofer allergen challenge chamber (ACC), a standardized, universal, good manufacturing practice-conforming technology using a spray dried solution of lactose (L) and allergen extract has been established. In this study, we investigated the noninferiority of hypertonic sodium chloride (S) versus L as a carrier for house dust mite (HDM) allergen to simplify manufacturing, reduce costs, and allow for wider use. METHODS: Using a participant-blinded, sham exposure-controlled, single-arm, sequential intervention study, we challenged adults with HDM allergic rhinitis five times in the ACC. Participants were first exposed to S, L, and clean air (block 1), followed by S + HDM and L + HDM (block 2). Primary endpoints were mean total nasal symptom score (TNSS) and mean nasal secretion weight. RESULTS: 19 participants were enrolled in the study (10 females; mean age 32 years [22-49], 4 with mild allergic asthma). The safety profile of S + HDM and L + HDM was similar; eight participants experienced mild procedure-related adverse events including tiredness, cough, and dyspnea. Due to dropouts, 13 participants completed the study and were evaluated. Mean TNSS and nasal secretion were as follows: S 0.98, 0.28 g; L 1.1, 0.20 g; clean air 1.1, 0.23 g; S + HDM 5.7, 4.8 g; L + HDM 5.1, 5.1 g. Separate block 1/block 2 MANOVAs with TNSS and nasal secretion as dependent variables revealed no significant differences between the carriers, neither alone and compared with clean air (p = 0.2059, Wilk's λ = 0.78) nor combined with HDM (p = 0.3474, Wilk's λ = 0.89). Noninferiority of S was established using a meta-analysis-based minimal clinical important difference of -0.55: mean TNSS difference between S + HDM and L + HDM was 0.62 (90% CI: -0.51 to 1.74). CONCLUSION: S as an HDM carrier was safe and well tolerated. It was noninferior to L which makes it an adequate and easy-to-use carrier substitute.

[ADHS - Disorder concepts and the beginnings of pharmacotherapy in the Federal Republic of Germany and the German Democratic Republic]. / ADHS ­ Störungskonzepte und Anfänge der Pharmakotherapie in Bundesrepublik und DDR.

ADHS - Disorder concepts and the beginnings of pharmacotherapy in the Federal Republic of Germany and the German Democratic Republic Abstract. After sporadic references before 1900, the concept of attention deficit/hyperactivity disorder became established in the 20th century. The hyperactive and inattentive child then became the focus of neuropediatrics in the wake of the encephalitis lethargica epidemic by clinical presentations of postencephalitic residual conditions. From these patients, physicians distilled a subgroup with an blank neurological history but impressive clinical symptoms. Child psychiatry, which emerged in the middle of the last century, studied these minimally brain-damaged patients, searching for both causes and therapies. The disorder concepts of Reinhart Lempp and Gerhard Göllnitz are significant contributions from the Federal Republic of Germany and the GDR, respectively, which provide revealing insights into the establishment of pharmacotherapy with stimulants in the 1970s.

The Effect of a Thixotropic Nasal Gel on Nasal Symptoms and Inflammatory Biomarkers in Seasonal Allergic Rhinitis.

BACKGROUND: Drug-free viscous nasal applications have been shown to reduce nasal symptoms in individuals with seasonal allergic rhinitis (SAR). Nascum®-Plus (NP), a commercially available thixotropic gel, has been designed to reduce dryness and soreness of the nasal mucosa and prevent the absorption of small particles. OBJECTIVES: The aim of this study was to assess the efficacy of single-dose NP in treating nasal symptoms and secretion during challenge in an allergen challenge chamber (ACC). Furthermore, the effect of this treatment on biomarkers and immune cells of the allergic cascade were measured. METHODS: This open-label, cross-over, sequence-randomized, monocentric trial randomized 18 adults with SAR and a positive skin prick test reaction to Dactylis glomerata pollen to receive NP or no treatment during two 4-h ACC sessions 3 weeks apart. On Day 1, 9 subjects were challenged for 4 h with treatment, the other 9 without treatment, and vice versa on Day 22. Nasal lavage fluid and nasal filter eluate samples were obtained pre, 2, and 18 h post challenge in the ACC. RESULTS: NP significantly reduced nasal symptoms, assessed by total nasal symptom score (p < 0.001), and minimized nasal secretion (p = 0.047), while no significant effect on biomarkers and immune cells in the nasal fluid was observed. The treatment was safe and well-tolerated. CONCLUSIONS: The physical barrier built by NP nasal gel can be safely applied in patients with allergic rhinitis. It reduces allergic nasal symptoms and secretion, but application of a single dose does not affect local inflammatory biomarkers.

Quantifying Exhaled Particles in Healthy Humans During Various Respiratory Activities Under Realistic Conditions.

Background: Quantitatively collecting and characterizing exhaled aerosols is vital for infection risk assessment, but the entire droplet size spectrum has often been neglected. We analyzed particle number and size distribution of healthy participants in various respiratory activities, considering inter-individual variability, and deployed a simplified far-field model to inform on infection risks. Methods: Participants repeated the same respiratory activities on two visits. Particles were collected using an airtight extraction helmet supplied with High Efficiency Particulate Air (HEPA) filtered air. The sampling volume flow was transported to two particle counters covering the small and large particle spectrum. The applied simple mass balance model included respiratory activity, viral load, room size, and air exchange rates. Results: Thirty participants completed the study. The major fraction of the number-based size distribution was <5 µm in all respiratory activities. In contrast, the major fraction of the volume-based size distribution was 2-12 µm in tidal breathing, but >60 µm in all other activities. Aerosol volume flow was lowest in tidal breathing, 10-fold higher in quiet/normal speaking, deep breathing, coughing, and 100-fold higher in loud speaking/singing. Intra-individual reproducibility was high. Between participants, aerosol volume flow varied by two orders of magnitude in droplets <80 µm, and three orders of magnitude in droplets >80 µm. Simple model calculations not accounting for potential particle size-dependent differences in viral load and infection-related differences were used to model airborne pathogen concentrations. Conclusions: Quantitative analysis of exhaled aerosols for the entire droplet size spectrum as well as the variability in aerosol emission between individuals provides information that can support infection research. Clinical Trial Registration number: NCT04771585.

Biologics in asthma management - Are we out of breath yet?

The biologics authorized for the add-on therapy of severe asthma are monoclonal antibodies (mAbs). Before they are considered for therapy intensification, the patient's asthma endotype is determined on the basis of phenotypic characteristics. So far, 5 biologics are available that target the signaling pathways of the "TH2-high" asthma endotype, in which cytokines of the inflammation cascade mediated by type 2 T-helper cells are upregulated. The corresponding phenotype of this inflammatory endotype is severe eosinophilic asthma, with elevated eosinophils, immunoglobulin E, and fractional exhaled nitric oxide (FeNO). In contrast, the heterogeneous "TH2-low" endotype is not yet sufficiently understood. Frequently described in this variant is an increase of sputum neutrophils and an increased expression of the TH17-mediated interleukin-17 signaling pathway. There are numerous biologics currently in clinical trials, the thymic stromal lymphopoietin (TSLP) mAbs in particular have shown promising results independent of the asthma phenotype.