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Asthma is not a homogenous disease but a bundle of different phenotypes producing common symptoms due to swelling of bronchial mucosa and constriction of the airway smooth muscle. Beyond the treatment with a combination of topical steroids and long-acting beta agonists, new therapeutic options arise with the knowledge of different phenotypes. One option, specifically in allergic asthma, is the long known allergen immunotherapy. To identify the individual phenotype a diagnostic work up is warranted when asthma is diagnosed and whenever asthma control cannot be maintained. [ABSTRACT FROM AUTHOR]

According to the international guidelines of COPD (GOLD) and asthma (GINA) diagnosis and treatment of both diseases necessitate spirometry in the private practice as well as in hospital setting. However today, spirometry is not sufficiently used in Switzerland. This paper intends to give an easy overview how spirometry is performed and spirometric values can be interpreted. [ABSTRACT FROM AUTHOR]

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Background: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. B cells have a central role in the pathogenesis of systemic sclerosis. We present a detailed analysis of the effects of CD19-targeting CAR T-cell therapy in patients with systemic sclerosis., Methods: Six patients with severe diffuse systemic sclerosis with an insufficient response to at least two treatments were consecutively recruited at the Department of Internal Medicine 3, University Hospital Erlangen (Erlangen, Germany) to receive CD19-targeting CAR T-cell treatment (1 × 10 6 CAR T cells per kg bodyweight). Events were predefined by progression of interstitial lung disease, onset of congestive heart failure, onset of renal failure, onset of arterial hypertension, or initiation of new immunosuppressive or antifibrotic therapy. Event-free time or treatment intensification after study entry was the primary outcome. Key secondary outcomes included changes in the modified Rodnan Skin Score (mRSS), imaging (a component of the assessment of lung fibrosis), laboratory assessments, patient-reported outcomes, and a modified version of the American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline, 3 months, 6 months, 9 months, and 12 months., Findings: Between April 20, 2022, and Nov 8, 2023, six patients with severe diffuse systemic sclerosis (median age 42 years [IQR 36-53]; four men and two women; all White European) were recruited and received CD19-targeted CAR T-cell therapy. The median follow-up time was 487 days (IQR 342-585). No events occurred within the observational period. Probability of improvement in the ACR-CRISS score increased to a median of 100% (IQR 100-100) at 6 months. Median mRSS decreased by 31% (IQR 29-38), corresponding to a median of 8 points (IQR 7-13) within 100 days. The extent of disease on CT scan decreased by a median of 4% (IQR 3-4) due to reduction of ground-glass opacities while the reticular pattern remained stable. Forced vital capacity improved by a median of 195 mL (IQR 18-275) at the latest observational timepoint., Interpretation: We provide the first evidence that CD19-targeting CAR T-cell therapy might intercept with the progression of fibrotic organ manifestations in patients with systemic sclerosis., Funding: Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN-Foundation Erlangen, IZKF Erlangen, and Bundesministerium für Bildung und Forschung., Competing Interests: Declaration of interests JA and ChB received a travel grant from Kyverna therapeutics. ChB received a research grant from Boehringer Ingelheim and speaker fees from Novartis. CaB received consulting fees from Almirall, Delcath, BMS, Immunocore, Pierre Fabre, MSD, Novartis, Regeneron, and Sanofi; honoraria from Almirall, Leo Pharma, BMS, Pierre Fabre, and MSD; travel support from Pierre Fabre; and participates on the data safety monitoring or advisory board of Miltenyi Biotech and InflaRx. FM received a research grant from Kite/Gilead and consulting fees from AbbVie, ArgoBio, AstraZeneca, BMS, Crispr Therapeutics, Janssen, Kite, and Novartis; honoraria from AbbVie, ArgoBio, AstraZeneca, BMS, Crispr Therapeutics, Janssen, Kite, Kyverna, Miltenyi, Novartis, and Sobi; and participates on the BMS and Biontech data safety monitoring or advisory board. TKr received grants, consulting fees, honoraria, and travel support from Novartis and Pfizer, as well as consulting fees and honoraria from Kiowa Kirin, payment for expert testimony from Novartis, and travel support from AbbVie. GS received honoraria from Cabaletta, Novartis, Janssen, and Kyverna. SoK received honoraria from BMS and Sobi, as well as travel support from Janssen, BMS, Sobi, Novartis, and Kite/Gilead. JHWD has consultancy relationships with and is part of the speaker or advisory board of AbbVie, Active Biotech, Anamar, ARXX, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Calliditas Therapeutics, Celgene, Galapagos, Genentech, GSK, Inventiva, Janssen, Novartis, Pfizer, Roche, and UCB; has received research funding from Anamar, Argenx, ARXX, BMS, Bayer Pharma, Boehringer Ingelheim, Cantargia, Celgene, CSL Behring, Galapagos, GSK, Inventiva, Kiniksa, Lassen, Sanofi-Aventis, RedX, and UCB; travel support from AbbVie and SOBI; and is Chief Executive Officer of 4D Science and Scientific Lead of FibroCure. AM received grants from Miltenyi Biomedicine and Kyverna, and consulting fees from BMS/Celgene, KITE/Gilead, Novartis, BioNTech, Miltenyi Biomedicine, and Century Therapeutics. AM received honoraria from BMS/Celgene, KITE/Gilead, Novartis, BioNTech, Miltenyi Biomedicine, and Century Therapeutics, and travel support from AbbVie and Janssen. RGB received grants from Kyverna and travel support from BMS and Novartis. MA received grants, honoraria, payment for expert testimony, travel support and equipment from Miltenyi Biotec; and received consulting fees, honoraria and travel support from Miltenyi Biomedicine. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Measurement of reference speech-recognition curves for a specific speech test in typical clinical testing environments and for different loudspeaker configurations., Design: Speech-recognition scores were measured at four signal-to-noise ratios for five loudspeaker configurations in two anechoic rooms, and in four audiometric test rooms with low reverberation times., Study Sample: 240 young participants (aged 18-25 years) without hearing impairment participated in the measurements., Results: Reference speech-recognition curves for speech and noise from the front (S 0 N 0 ) were similar across rooms. Compared to S 0 N 0 , lower speech-recognition thresholds (SRTs) were observed for all other loudspeaker configurations in which speech and noise were spatially separated. This spatial release from masking was significantly reduced for the audiometric test rooms compared to the anechoic rooms. A binaural speech-intelligibility model was used to verify the influence of room acoustic properties and loudspeaker configuration on SRT., Conclusions: Speech-recognition curves for spatially separated loudspeaker configurations depend on the room acoustic properties, even in audiometric test rooms with low reverberation times. This makes it more difficult to compare clinical measurements with reference speech-recognition curves, or even with data measured in a different test room. It is thus recommended to document the loudspeaker configuration and test room for each clinical measurement.

Bispecific T cell engagers (BiTEs) kill B cells by engaging T cells. BiTEs are highly effective in acute lymphoblastic leukemia. Here we treated six patients with multidrug-resistant rheumatoid arthritis (RA) with the CD19xCD3 BiTE blinatumomab under compassionate use. Low doses of blinatumomab led to B cell depletion and concomitant decrease of T cells, documenting their engager function. Treatment was safe, with brief increase in body temperature and acute phase proteins during first infusion but no signs of clinically relevant cytokine-release syndrome. Blinatumomab led to a rapid decline in RA clinical disease activity in all patients, improved synovitis in ultrasound and FAPI-PET-CT and reduced autoantibodies. High-dimensional flow cytometry analysis of B cells documented an immune reset with depletion of activated memory B cells, which were replaced by nonclass-switched IgD-positive naïve B cells. Together, these data suggest the feasibility and potential for BiTEs to treat RA. This approach warrants further exploration on other B-cell-mediated autoimmune diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID intolerance (Widal's disease) behaves under biologicals. We therefore describe the case of a patient with both clinical conditions who reacted with a severe intolerance reaction under perioperative metamizole administration., Competing Interests: Es bestehen keine Interessenkonflikte, (© 2024 Aerzteverlag medinfo AG.)

Background: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission., Methods: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology-European League against Rheumatism (ACR-EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded., Results: The median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR-EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell-associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization., Conclusions: In this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.)., (Copyright © 2024 Massachusetts Medical Society.)