Real-world data on tezepelumab in patients with severe asthma in Germany.

BACKGROUND: Tezepelumab is a novel biologic blocking thymic stromal lymphopoetin (TSLP), approved for severe asthma irrespective of biomarker levels or phenotype. OBJECTIVE: To characterize a real-world tezepelumab patient cohort and the efficacy among various asthma phenotypes. METHODS: We performed a retrospective, multi-center study on patients with severe asthma initiating tezepelumab. Clinical response was evaluated at 3 and 6 months. RESULTS: We included 129 patients with an average age of 52.5 ± 13.1 years, 59.7% were female. The majority (86.0%) had increased T2 biomarkers, 68.2% an allergic and 31.8% an eosinophilic phenotype. 23.3% of patients were biologic-naïve. 22 (18.2%) patients discontinued tezepelumab therapy due to suspected side-effects or insufficient efficacy. At 6 months follow-up, median reduction in annualized exacerbation rate (AE) was -1 [-2.9;0.0], the reduction of oral corticosteroid (OCS) dose among patients with long term OCS therapy was -5 mg [-10;0] and asthma control test (ACT) improved by 2 [0;5] points. 80.8% demonstrated a treatment response according to Biologic Asthma Response Score. There were no significant differences in treatment response between T2-high vs. T2 low, early vs. adult onset and eosinophilic vs. non-eosinophilic asthma. Prior treatment with other biologics was associated with inferior treatment response. CONCLUSION: In this real-life cohort, including a large proportion of patients with history of previous biologic use and encompassing various subgroups, the majority responded to tezepelumab. Our data further suggest a steroid-sparing effect of tezepelumab.

As-needed low-dose inhaled corticosteroid/formoterol therapy in patients with severe asthma included in the German Asthma Net cohort.

After the GINA update in 2019, the proportion of SMART therapy increased with evidence for better disease control in SMART patients compared to SABA alone https://bit.ly/3SSPX1C.

Factors influencing voriconazole plasma level in intensive care patients.

Background: In clinical routine, voriconazole plasma trough levels (Cmin) out of target range are often observed with little knowledge about predisposing influences. Objectives: To determine the distribution and influencing factors on voriconazole blood levels of patients treated on intensive- or intermediate care units (ICU/IMC). Patients and methods: Data were collected retrospectively from patients with at least one voriconazole trough plasma level on ICU/IMC (n = 153) to determine the proportion of sub-, supra- or therapeutic plasma levels. Ordinal logistic regression analysis was used to assess factors hindering patients to reach voriconazole target range. Results: Of 153 patients, only 71 (46%) reached the target range at the first therapeutic drug monitoring, whereas 66 (43%) patients experienced too-low and 16 (10%) too-high plasma levels. Ordinal logistic regression analysis identified the use of extra corporeal membrane oxygenation (ECMO), low international normalized ratio (INR) and aspartate-aminotransferase (AST) serum levels as predictors for too-low plasma levels. Conclusion: Our data highlight an association of ECMO, INR and AST levels with voriconazole plasma levels, which should be considered in the care of critically ill patients to optimize antifungal therapy with voriconazole.

["Crack lung" - atypical bilateral pneumonia]. / "Crack lung" ­ atypische bilaterale Pneumonie.

Inhalation of crack and freebase results in alveolar hemorrhage. In severe courses of the disease, progressive respiratory insufficiency may lead to respiratory failure and acute respiratory distress syndrome (ARDS). Computed tomography of the thorax reveals bilateral consolidation and ground-glass pattern leaving a subpleural gap. This case report of a 48-year-old male patient highlights the importance of a thorough medical history while ruling out infectious causes.

Association of respiratory infections and the impact of vaccinations on cardiovascular diseases.

Influenza, pneumococcal, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus infections are important causes of high morbidity and mortality in the elderly. Beyond the burden of infectious diseases, they are also associated with several non-infectious complications like cardiovascular events. A growing body of evidence in prospective studies and meta-analyses has shown the impact of influenza and pneumococcal vaccines on types of cardiovascular outcomes in the general population. Influenza vaccination showed a potential benefit for primary and secondary prevention of cardiovascular diseases across all ages. A reduced risk of cardiovascular events for individuals aged 65 years and older was associated with pneumococcal vaccination. Despite scientific evidence on the effectiveness, safety, and benefits of the vaccines and recommendations to vaccinate elderly patients and those with risk factors, vaccination rates remain sub-optimal in this population. Doubts about vaccine necessity or efficacy and concerns about possible adverse events in patients and physicians refer to delayed acceptance. Vaccination campaigns targeting increasing professional recommendations and public perceptions should be implemented in the coming years. The aim of this review paper is to summarize the effect of vaccination in the field of cardiovascular disease to achieve a higher vaccination rate in this patient population.

Adverse Effects Under Th2 Biologics (Dupilumab and Tezepelumab) in a Patient with Severe Asthma and Atopic Dermatitis.

INTRODUCTION: This is the first report of a patient with severe asthma and atopic dermatitis that developed local perioral skin infection which onset coincided with the patient's treatment with dupilumab (candida albicans) and later with tezepelumab (microscopic detection of yeast). CASE PRESENTATION: Besides moderate headache, macular exanthema was found after administration of tezepelumab, which was subsequently accompanied by a worsening of symptoms upon reexposure to the treatment. Both sensations needed multidisciplinary treatment and both antibody therapies were stopped.

Relationship Between the Response to Antibody Therapy and Symptoms of Depression and Anxiety Disorders in Patients with Severe Asthma.

Purpose: Asthma is associated with a high prevalence of psychopathological disorders, especially depressive disorders or anxiety. In patients with uncontrolled severe asthma, monoclonal antibody (mAb)-therapy positively influenced control of mental disorders. Therefore, we evaluated the impact of antibody therapy on the burden of these mental diseases depending on responder status. Patients and Methods: Data were collected retrospectively in patients with uncontrolled severe asthma (n = 82) prior to mAb-therapy ("baseline") (omalizumab, dupilumab, benralizumab or mepolizumab). Symptoms of Major Depressive Disorder (MDD) or General Anxiety Disorder (GAD) were detected at baseline using the Hospital Anxiety and Depression Scale (HADS), as well as general sociodemographic data and lung function parameters. At 6-month (±3 month) follow-up, the burden of psychopathological symptoms under mAb-therapy was assessed using the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder Scale-2 (GAD-2). Response status was classified using the Biologics Asthma Response Score (BARS), assessing exacerbations, oral corticosteroid usage and asthma control test (ACT) score. Predictors for non-response to mAb-therapy were identified using linear regression analysis. Results: Patients with severe asthma suffered from symptoms of MDD/GAD more often compared to the general population, with a higher prevalence among mAb therapy non-responders. mAb-responders exhibited a declining burden of MDD, better quality of life (QoL), less exacerbations, better lung function and better disease control compared to non-responders. A history of symptoms of depression was identified as a predictor for non-response to mAb-therapy. Conclusion: Asthma symptoms and psychological problems are linked and more prevalent in our cohort of severe asthma patients than in the general population. Patients with signs of MDD/GAD before mAb-therapy show less mAb therapy response suggesting a negative impact of prior psychological problems on treatment response. In some patients, the score on MDD/GAD was caused by severe asthma - here symptoms decreased after effective treatment.