Respiratory Research最新文献

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbestos-induced lung fibrosis mice. Iron was partially co-localized with the fibroblast marker vimentin in IPF lungs. By using publicly available single cell RNA sequencing datasets, we identified SLC40A1, the only known gene involved in iron export, as a downregulated gene in alveolar fibroblasts of IPF. The downregulation of SLC40A1 was confirmed in the lung fibroblasts isolated from IPF patients and bleomycin-treated mice. The treatment of human lung fibroblasts with transforming growth factor-β1 (TGF-β1), a major cytokine elevated in IPF, reduced SLC40A1 mRNA and protein expression. TGF-β1 downregulated SLC40A1 expression via SMAD3 as determined by chromatin immunoprecipitation and luciferase promoter reporter assays. Knockdown of SLC40A1 using lentiviral shRNAs or TGF-β1 treatment induced iron accumulation in human lung fibroblasts as determined by live cell ferrous dye staining using a SiRhoNox-1 probe. Knockdown of SLC40A1 enhanced the iron-induced lung fibroblast activation. In summary, we conclude that the downregulation of SLC40A1 caused by TGF-β1 induces iron accumulation in lung fibroblasts, resulting in fibroblast activation.

Background: Shape-sensing robotic-assisted bronchoscopy (ssRAB) is an emerging technology in geographies outside the United States in use for complex pulmonary nodule biopsy. Geography specific data is needed to better understand outcomes in each population and health care system. The objective of this study is to assess the learning curve, diagnostic performance and safety of ssRAB in sampling peripheral pulmonary nodules (PPN) from an initial multicenter experience in China.

Methods: Consecutive patients with solid or part-solid nodules 8-30 mm in largest diameter were prospectively enrolled across three centers. Biopsy was performed using the ssRAB platform with 2D fluoroscopy and radial EBUS guidance only. Biopsy workflow was standardized across all centers. Subjects were followed through 30 days post-procedure. The primary endpoint was diagnostic yield per American Thoracic Society (ATS) and American College of Chest Physicians (ACCP) definition. Secondary outcomes included procedure characteristics and incidence of procedure or device-related complications. Learning curve based on procedure time and diagnostic yield for each proceduralist was assessed using the cumulative sum method.

Results: Ninety nodules from ninety subjects were biopsied with the ssRAB system. Average nodule size was (20.3 ± 4.9) mm. ATS/ACCP diagnostic yield was 90.0% (95% CI, 82.1%-94.7%). Multivariate analysis demonstrated no association with any nodule characteristic or imaging signal. Pneumothorax requiring chest tube was 1.1%. No severe airway bleeding was reported. Decreasing procedure time was observed through the case series with a suggested association to incremental procedure and bronchus sign presence. Two novice operators achieved diagnostic yield competency after 15 and 32 cases, respectively.

Conclusions: For PPN in China, ssRAB showed a strong diagnostic performance with high safety profile during first cases. Proficiency can be stably achieved among beginners at early stage of learning.

Trial registration: ClinicalTrials.gov (NCT06308120) 2024-04-03.