Phase 3 evidence for antifibrotic-directed therapies in idiopathic pulmonary fibrosis (IPF) has expanded, but direct head-to-head trials are lacking. Forced vital capacity (FVC) decline remains the principal trial outcome, although it may not fully capture clinically relevant differences among therapies. We systematically reviewed phase 3 randomized placebo-controlled trials of antifibrotic-directed therapies in IPF. FVC effects versus placebo were descriptively summarized using standardized 48–52-week estimates. All-cause treatment discontinuation and all-cause mortality were analyzed using placebo-controlled odds ratios. Sensitivity analyses assessed follow-up duration, background antifibrotic therapy, and trial-level consistency. Ten trials including 5,386 randomized participants were included. Pirfenidone and nintedanib showed consistent reductions in FVC decline versus placebo. Inhaled treprostinil showed a favorable FVC signal in the combined TETON-1/2 evidence, largely as add-on therapy with background antifibrotic treatment. Without background antifibrotic therapy, several therapies showed directionally favorable but imprecise FVC effects, without evidence of equivalence. Nintedanib and inhaled treprostinil were associated with higher odds of all-cause treatment discontinuation versus placebo: OR 1.39 (95
Virtual-assisted lung mapping (VAL-MAP) is a safe and useful procedure for identifying suitable lines for sublobar lung resections. Nonetheless, the current VAL-MAP technique using a thin bronchoscope limits access to peripheral lung regions, including the upper lobes or the S6 region. To overcome this limitation, we developed a new technique utilizing an ultrathin bronchoscope (UTB), termed ‘UTB VAL-MAP’, enabling precise dye marking of the visceral pleura which is difficult to access with a thin bronchoscope. We retrospectively evaluated the efficacy and safety of UTB VAL-MAP with those of conventional VAL-MAP at our institution. Overall, 178 preoperative markings (75 patients) were included: 74 markings in 35 patients in the UTB VAL-MAP group and 104 markings in 40 patients in the conventional VAL-MAP group. The overall detection rate in the UTB VAL-MAP group was significantly higher than that in the conventional VAL-MAP group [97.3
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disorder strongly mediated by genetic susceptibility and aberrant epithelial repair mechanisms. Among the identified genetic factors, the MUC5B promoter polymorphism rs35705950 represents the most significant and frequently replicated risk variant associated with both familial and sporadic IPF. This review focuses on the mechanistic role of MUC5B dysregulation in promoting epithelial dysfunction and profibrotic signalling, with particular emphasis on its interaction with transforming growth factor-beta (TGF-β) signalling and KL-6-associated epithelial injury. Excessive MUC5B expression within distal airways disrupts mucociliary homeostasis, prolongs epithelial exposure to inhaled toxic stimuli, and enhances persistent alveolar stress, thereby facilitating chronic epithelial injury and aberrant tissue repair. Sustained epithelial damage subsequently activates TGF-β-mediated SMAD signalling pathways, promoting fibroblast activation, myofibroblast differentiation, and extracellular matrix deposition. Emerging evidence further suggests a close relationship between MUC5B-associated epithelial dysfunction and elevated KL-6 expression, indicating that KL-6 may function as a downstream biomarker indicating ongoing epithelial injury and fibrotic progression. The proposed MUC5B/TGF-β/KL-6 mechanistic signaling provides an integrated molecular network linking genetic susceptibility, epithelial dysfunction, biomarker elevation, and progressive fibrosis in IPF. In addition, telomere-related and surfactant-associated gene mutations further lead to epithelial instability and impaired regenerative capacity. Together, these interconnected molecular mechanisms provide significant insights into IPF progression and may support the development of biomarker-driven prognostic approaches and targeted precision therapies for improved disease management.
Pulmonary vascular involvement is a determinant of worse outcomes in fibrotic lung diseases. Its prevalence and prognostic relevance in patients with progressive pulmonary fibrosis (PPF) is unknown. The aim of this study was to assess the prevalence of indirect echocardiographic abnormalities in progressive pulmonary fibrosis before antifibrotic therapy, characterize a baseline high-risk cardiopulmonary functional profile, and assess 12-month clinical trajectories. Observational, retrospective, multicentre study. 158 patients (median (IQR) age of 71 (65.2–77.0) years) with PPF were enrolled. Thirty (19.0
Routine assessment of programmed death-ligand 1 (PD-L1) expression and comprehensive next-generation sequencing (NGS) is recommended to guide treatment selection in patients with non-small cell lung cancer (NSCLC). Obtaining adequate tissue for biomarker and molecular analyses is therefore essential. This study compared sample adequacy for PD-L1 and NGS testing between shape-sensing robotic-assisted bronchoscopy (ssRAB) and computed tomography-guided transthoracic lung biopsy (CTTB) in patients with NSCLC. We conducted a single-center retrospective study of patients with NSCLC who underwent biopsy of PPL by ssRAB or CTTB between June 2020 and December 2025. Demographic, procedural, pathological, biomarker and molecular data were extracted from electronic medical records, and descriptive statistics analysis and multivariable logistic regression were performed. A total of 402 patients were included, comprising 198 in the ssRAB cohort and 204 in the CTTB cohort. ssRAB demonstrated significantly higher sample adequacy rates than CTTB for both PD-L1 (98.8
