Background: Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, has demonstrated efficacy for severe asthma in clinical trials, but real-world evidence remains limited. We aimed to evaluate the characteristics and outcomes of patients initiating tezepelumab in a real-world setting. Methods: We conducted a retrospective, multicentre cohort study across four tertiary care centres to evaluate the real-world effectiveness of tezepelumab in patients with severe asthma. Eligible patients were adults with a confirmed diagnosis of severe asthma, treated with tezepelumab. Data on exacerbation rates, pulmonary function and corticosteroid use were collected and analysed at baseline and 1-year follow-up. Results: The study included 103 patients treated with tezepelumab with a median (interquartile range) duration of 323 (267–359) days. Overall, 39% had prior biologic therapy and 32% had an eosinophil count <300 cells·μL⁻¹. At follow-up, there was a 66.7% relative reduction in annual exacerbations. The most pronounced reduction was observed in biologic-naïve patients with peripheral eosinophil counts ≥300 cells·μL⁻¹ (78% reduction). A 62% relative reduction was found among patients with eosinophil counts <150 cells·μL⁻¹. There were significant improvements in forced expiratory volume in 1 s, with 51% of patients demonstrating a ≥10% relative increase. Of patients using maintenance oral corticosteroid (mOCS), 45% discontinued mOCS and 23% reduced their dose by more than 50%. Conclusions: In this real-world cohort, treatment with tezepelumab for a median of 46 weeks was associated with improved asthma control, reductions in exacerbations, mOCS and inhaled corticosteroid doses, and a low symptom burden. These findings were consistent in biologic-experienced or low-eosinophil patients.

Pulmonary alveolar proteinosis (PAP) presents a significant challenge due to its progressive and potentially fatal nature. Whole lung lavage (WLL) is a key treatment for primary PAP with respiratory failure. Despite its efficacy, the lack of standardised protocols has led to diverse practice techniques across different institutions. Our study introduces a novel approach, employing a cardiopulmonary bypass (CPB) system for infusing lavage fluid, a method not previously utilised. This paper will share our pioneering experience with this technique at a tertiary referral centre, focusing on its implementation and safety profile. This retrospective study included patients aged ≥ 18 who underwent WLL for PAP or silicosis. Pre-lavage preparations included chest X-rays and pulmonary function tests (PFT). Preprocedural empiric antibiotics were administered. During lavage, warm saline was infused using a CPB, with cycles of normal saline infusion and degassing until fluid clarity was reached. Positioning techniques facilitated saline drainage. The procedure concluded with intravenous furosemide administration. Fifty-two WLLs were identified between 2010 and 2024; complete data was available for 33 procedures. Of these, 91% were due to PAP, and 9% to silicosis. Almost half of the patients did not require additional WLL, while 43% needed sequential contralateral WLL. Median operative and mechanical ventilation times were 65 [58.5, 67.5] and 118 [97, 195] minutes, respectively. The median length of hospital stay was two days [2, 3]. Although not statistically significant, O2 saturation and a 6-minute walk distance increase were observed after the WLL. This study outlines our novel approach to WLL, which incorporates rapid saline infusion via a CPB system. Our findings indicate reduced procedure time while maintaining safety and efficacy for treating PAP and silicosis. Despite promising results, the retrospective design and small sample size limit generalizability. Further high-quality studies are warranted to validate and refine this technique.

The diagnosis of adult-onset Still disease (AOSD) is challenging with ambiguous clinical presentation and no specific serological markers. We aim to evaluate the diagnostic utility of clinical, laboratory and serum ferritin features in established AOSD patients. We included all patients >18 years who were admitted to 2 tertiary medical centers (2003–2019) with serum ferritin above 1000 ng/mL. AOSD patients and non-AOSD controls were matched in 1:4 ratio for age and sex. The primary outcomes were sensitivity, specificity, positive/negative likelihood ratio and area under the curve (AUC) using clinical and laboratory characteristics based on the Yamaguchi classification criteria, in addition to serum ferritin. We identified 2658 patients with serum ferritin above 1000 ng/m, of whom 36 diagnosed with AOSD and 144 non-AOSD matched controls. Presence of arthralgia/arthritis showed the highest sensitivity (0.74), specificity (0.93), positive likelihood ratio (10.69), negative likelihood ratio (0.27) and AUC (0.83, 95% confidence interval 0.74–0.92) to the diagnosis of AOSD. On the other hand, serum ferritin showed variation and poorer results, depends on the chosen ferritin cutoff. Joint involvement showed the best diagnostic utility to establish the diagnosis of AOSD. Although clinicians use often elevated ferritin levels as an anchor to AOSD, the final diagnosis should be based on thorough clinical evaluation.

Introduction: Recombinant human deoxyribonuclease I (rhDNase) cleaves DNA in mucus, facilitating increased mucociliary clearance of purulent sputum. In cystic fibrosis (CF), rhDNase improves pulmonary function and decreases exacerbations. Conversely, rhDNase use in non-CF bronchiectasis (NCFB) patients has not yielded similarly effective results. We explored the safety and feasibility of rhDNase in patients with bronchiectasis due to primary ciliary dyskinesia (PCD). Methods: In this real-life pilot study, patients with PCD received rhDNase to treat viscous mucus. We compared pulmonary function tests and pulmonary exacerbations for these patients over six months of use of rhDNase. Results: Eight PCD patients with symptomatic bronchiectasis commenced use of rhDNase at variable dosing (ranging from at least twice weekly to a full 2.5 mg dose daily). Over a six-month period, pulmonary function tests, as measured by mean FVC and FEV₁, remained relatively stable compared to prior to commencing rhDNase. Mean pulmonary exacerbations decreased from 3.1 to 2.3 in the six-month period after commencing rhDNase, as compared to the six-month period prior to rhDNase. Conclusions: Use of rhDNase in PCD patients was safe and did not adversely impact lung function or increase pulmonary exacerbations, in contrast to earlier trial results in NCFB patients with heterogeneous etiologies. Further clinical data is required to identify the population of PCD patients who can benefit from rhDNase, as well as the appropriate dosing and timing.

Background: Computed tomography (CT)-guided lung biopsy plays a pivotal role in diagnosing thoracic lesions. However, its diagnostic yield may be compromised in large, necrotic, or heterogeneous tumours due to inadvertent sampling of non-viable tissue. Dual-energy CT (DECT) iodine mapping provides functional imaging by identifying iodine-avid, perfused areas, thereby offering the potential to improve biopsy targeting. Methods: This single-centre retrospective study evaluated the clinical feasibility and diagnostic performance of DECT-guided biopsy. Adult patients with suspected necrotic lung or mediastinal lesions who underwent DECT iodine mapping prior to CT-guided biopsy between April 2021 and December 2022 were evaluated. DECT iodine maps were generated using dual-source CT and used to identify viable tumour regions for targeted biopsy. The primary outcome was diagnostic yield, defined as obtaining a definitive histopathological diagnosis. Secondary outcomes included safety and adequacy of samples for molecular testing. Results: Twenty patients were included. A definitive diagnosis was obtained in 18/20 biopsies (90%). Diagnostic yield was 9/11 (81.8%) for pulmonary lesions and 9/9 (100%) for mediastinal/pleural lesions. Diagnoses included non-small-cell lung cancer (n = 8), Hodgkin lymphoma (n = 4), thymoma (n = 3), and other malignancies (n = 3). Biopsy material was sufficient for additional molecular testing in 13/20 cases (65%). Complications were minor (one pneumothorax not requiring drainage and two self-limited bleeding events). Conclusions: DECT iodine map-guided targeting was feasible in this retrospective cohort and was associated with high diagnostic yield, low complication rates, and frequent acquisition of tissue suitable for molecular analyses. Prospective controlled studies are needed to quantify benefit over conventional CT guidance.

Hospital-at-home programs have shown clinical and economic benefits globally but are still in the early stages in Israel for acute care. This study evaluated hospital-at-home units’ clinical, safety, and economic outcomes compared to internal wards. The study assesses hospital-at-home units’ clinical, safety, and economic outcomes versus internal wards for acutely ill patients. This retrospective matched cohort study assessed the impact of at-home hospitalization on patient survival. Patients admitted from the emergency room to at-home hospitalization were matched 2:1 with patients admitted to internal wards based on demographic and clinical characteristics using propensity score matching. The primary outcome was the rate of readmissions at 30 days. After matching, 645 individuals were included: 215 in the hospital-at-home group and 430 in the control group. Baseline characteristics were well-balanced. After 30 days, 6 individuals in the study group and 38 in the control group had died. The study group’s overall mortality rate was significantly lower (2.79% vs 8.84%, p = .0043). The hazard ratio for the control group compared to the study group was 1.907 (95% CI 1.227-2.963), indicating a 90% increased risk of death. The primary outcome of readmissions at 30 days did not differ significantly between groups. Secondary outcomes showed substantially lower healthcare resource use in the study group. Hospital-at-home units are a safe alternative to internal wards, offering significant mortality risk reduction and lower healthcare resource use. These findings support the feasibility of implementing hospital-at-home units for acute care in Israel.