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.

Tumor seeding following CT- guided transthoracic needle biopsy in lung cancer. A case report.

As a result of advances in the treatment of lung cancer, the life expectancy of lung cancer patients has improved significantly, but it remains the leading cause of cancer death worldwide. For decades, most of the initial tumor biopsies have been obtained by bronchoscopy or computed tomography (CT)-guided transthoracic lung biopsy without concerning reports of cancer seeding following the latter. In this case report we discuss the patient history of a 56-year old women with low-differentiated squamous cell lung cancer who developed tumor seeding following a CT-guided transthoracic biopsy 11 months after the intervention. This is put into context reviewing former and current literature.

Association of coronary artery calcification with clinical and physiological characteristics in patients with COPD: Results from COSYCONET.

Chronic obstructive pulmonary disease (COPD) is frequently associated with coronary artery disease (CAD). When considering computed tomography (CT) for COPD phenotyping, coronary vessel wall calcification would be a potential marker of cardiac disease. However, non-ECG gated scans as used in COPD monitoring do not comply with established quantitative approaches using ECG-triggered CT and the Agatston score. We studied the diagnostic potential of Agatston scores from non-triggered scans for cardiac disease. The study population was a sub-group of the COPD cohort COSYCONET that underwent CT scanning in addition to comprehensive clinical assessments, echocardiographic data and physician-based diagnoses of comorbidities. Agatston scores from non-contrast enhanced, non-triggered CT were used to identify a cut-off value for CAD via ROC analysis. 399 patients were included (152 female, mean age 66.0 ± 8.2 y). In terms of CAD, an Agatston score ≥1500 AU performed best (AUC 0.765; 95% CI: 0.700, 0.831) and was superior to the conventional cut-off value (400 AU). Using this value for defining groups, there were differences (p < 0.05) in lung function, left atrial diameter and left ventricular end-systolic diameter as well as CT-determined central airway wall thickness pointing towards a bronchitis phenotype. In multivariate analysis, BMI, hyperlipidemia, arterial hypertension, GOLD D (p < 0.05) but particularly Agatston score ≥1500 AU (Odds ratio 10.5; 95% CI: 4.8; 22.6)) were predictors of CAD. We conclude that in COPD patients, Agatston scores derived from non-ECG gated CT showed a much higher cut-off value (1500 AU) for actionable coronary artery disease than the score derived from ECG-triggered CT in cardiology patients.

KRAS signaling in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.