Current Opinion in Pulmonary Medicine最新文献

Purpose of review: To provide an overview of current indications for lung transplantation (LTx) in COPD patients, to describe the different transplantation options, to compare the outcome of COPD and alpha1-antitrypsin deficiency (AATD) patients versus non-AATD COPD patients and to discuss the possible complications, also specifically related to COPD, AATD patients and the transplantation procedure.

Recent findings: Some 30-50% of all lung LTx worldwide are performed in COPD patients, with the majority being operated via double lung transplantation (DLTx). Unilateral lung transplantation (SLTx) remains an option, depending on the donor availability and the center's experience. The mean survival after LTx for COPD remains somewhat lower compared to other underlying diseases, especially after SLTx, which may lead to specific complications such as native lung hyperinflation and development of a native lung cancer.

Summary: LTx for end-stage COPD remains an accepted treatment modality in selected patients, which increases the QOL and the survival. The global 5-year survival is around 60%; somewhat better for AATD, compared to non-AATD COPD and after DLTx compared to SLTx. The best procedure of choice remains a matter for further discussion, although most centers prefer to perform DLTx, certainly in patients with underlying AATD.

Purpose of review: To update the reader on recent evidence relating to symptoms, diagnostic strategies and management options for small-fibre neuropathy (SFN) in sarcoidosis. Learning points from recent studies are presented in the context of previous research forming the basis of our knowledge of SFN in patients with sarcoidosis.

Recent findings: Recent studies have shown overlap of SFN and other symptoms beyond pain in patients with sarcoidosis. Where SFN exists, determining the optimal diagnostic modalities is challenging; there have been developments in how forms of temperature threshold testing should be performed, as well as whether this test may miss patchy involvement by SFN in sarcoidosis. To aid identification of SFN in sarcoidosis, questionnaires has been developed specifically looking at sarcoidosis-associated SFN, attempting to capture the patients with patchy or intermittent SFN symptoms. Standard systemic management for sarcoidosis is ineffective for SFN, though infliximab shows promise and is increasingly being utilised as a treatment option.

Summary: Few studies have been published in the last two years but there have been developments that have progressed our knowledge. This review collates the latest research alongside prior work, aiming to help summarise diagnosis and management strategies for this problematic manifestation of sarcoidosis.

Purpose of review: This review describes the properties and examines available evidence supporting LUS as a screening tool for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). ILD is a common and serious complication of RA, associated with high mortality rates, especially when diagnosed late. Despite its high prevalence and significant prognostic impact, the need for and approach to systematic screening for lung involvement in RA remain unclear and are not recommended in current guidelines. While high-resolution computed tomography (HRCT) is the gold standard for diagnosing ILD, it cannot be frequently repeated due to limitations in the availability, cost, and radiation exposure.

Recent findings: Lung ultrasound (LUS) has emerged as a potential noninvasive, accurate, low-cost, and nonionizing alternative for detecting ILD, offering high sensitivity and negative-predictive value (NPV) compared to HRCT. Key LUS findings indicative of ILD include B-line artefacts (BLA) and pleural irregularity. Evidence supporting the performance and applicability of LUS in diagnosing RA-ILD continues to grow.

Summary: LUS has shown a good performance in ILD detection. Further research and standardization efforts are needed to fully integrate LUS into routine RA screening protocols.

Purpose of review: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) leads to poor survival, on average only 3-5 years from time of diagnosis. Despite its clinical impact, evidence-based treatment approaches remain limited, creating urgent clinical uncertainty about optimal management strategies. This review examines emerging precision medicine approaches that may guide more effective, individualized treatment decisions.

Recent findings: Current treatment paradigms based on radiologic patterns lack empirical validation, with recent evidence suggesting radiologic features poorly predict immunomodulatory response. Advances in RA joint precision medicine using synovial biopsy and RNA sequencing have identified molecular endotypes predicting differential treatment response, establishing a framework that could be applied to RA-ILD. Emerging biomarkers including leukocyte telomere length, circulating proteomics, and lung-based systems biology show promise for identifying RA-ILD molecular heterogeneity and guiding treatment selection.

Summary: Progress in RA-ILD precision medicine requires multimodal approaches integrating molecular phenotyping with targeted therapeutic trials. Lessons from RA joint precision medicine suggest accessing the disease compartment directly through bronchoscopy may provide crucial information beyond peripheral biomarkers. Prospective biomarker-stratified trials are urgently needed to overcome clinical equipoise and improve outcomes for this challenging condition.

Purpose of review: Lymphangioleiomyomatosis (LAM) is a systemic, low-grade, metastasizing neoplasm that predominantly affects women. This review demonstrates recent progression in this rare disease, from improved understanding of pathogenesis, to novel treatments. We provide an overview of recent advances that are shaping the future of LAM diagnostic and treatment approaches.

Recent findings: Understanding the role of hormonal pathways, immune system interactions, mechanistic target of rapamycin (mTOR) signalling inhibition and the LAM microenvironment is creating opportunities for combination therapies with curative potential. Evidence supporting the uterine origin of LAM cells has renewed interest in hormonal signalling pathways, while potential immune evasion mechanisms of LAM cells are under investigation. More complete blockade of mTOR pathways by newer generation agents, as well as research into the crosstalk between LAM cells and their surroundings is informing development of novel combination therapies with disease modifying potential. Biomarker identification beyond vascular endothelial growth factor D (VEGF-D) is essential for diagnostic, prognostic and treatment decision making. Cellular mapping using single-cell RNA sequencing and spatial transcriptomics, as well as integration of artificial intelligence into diagnostic and therapeutic development pathways, has the potential to significantly advance our understanding of this rare disease.

Summary: LAM research demonstrates how sustained investigation in rare disease can advance from preclinical mechanistic insights to targeted treatments. Understanding the role of hormonal pathways, immune system interactions, mTOR signalling inhibition and the microenvironment is creating opportunities for combination therapies with curative potential. Advancements in technology, including single cell analysis, spatial transcriptomics and artificial intelligence are accelerating the discover of biomarkers and therapeutic targets, positioning LAM for significant clinical advances in the coming years.

Purpose of review: Pulmonary hypertension (PH) is a significant complication of various lung diseases, including rare conditions such as lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). This review explores the pathophysiology, diagnostic challenges, and therapeutic strategies for managing PH in these conditions, emphasizing recent findings and gaps in knowledge.

Recent findings: In LAM, PH primarily results from parenchymal destruction and hypoxic vasoconstriction rather than direct vascular involvement, leading to its reclassification from Group 5 to Group 3 PH. Sirolimus, an mTOR inhibitor, has demonstrated benefits in stabilizing lung function and may indirectly reduce pulmonary pressures, though direct effects remain unproven. In PLCH, PH is often disproportionate to lung function impairment, suggesting a distinct pulmonary vasculopathy. Histopathologic studies reveal extensive vascular remodeling, including features of pulmonary veno-occlusive disease. Case reports suggest potential benefits of PH-specific therapies such as endothelin receptor antagonists and phosphodiesterase-5 inhibitors, but their use requires caution due to the risk of worsening gas exchange.

Summary: PH in LAM and PLCH is uncommon but clinically relevant, particularly in advanced disease. While emerging therapies show promise, further research is needed to optimize management and improve patient outcomes.

Purpose of review: The management of sarcoidosis has relied mainly on glucocorticoids for over 80 years. Innumerable review articles, as well as all current guidelines, position systemic steroids as first line therapy for moderate and severe sarcoidosis. Despite accumulating evidence of short term (mostly overt) and long term (often unrecognized) toxicities of steroids, and the example of specialists treating diseases like rheumatoid arthritis and inflammatory bowel disease, the treatment paradigm for sarcoidosis has remained stubbornly affixed to steroids.

Recent findings: In 2025, there is now compelling evidence to relegate steroids to a lesser role in the management of sarcoidosis. Nonsteroid agents, especially methotrexate, can be used as first line therapy for many patients.

Summary: As steroid use diminishes, the development and implementation of additional steroid-sparing agents will assume increased importance.

Purpose of review: The pathobiology of pulmonary arterial hypertension (PAH) is complex and has been characterized by aberrant signalling in diverse pathways, many of which have been explored in recent studies. While some of these studies have demonstrated negative results, nonetheless they provide valuable insights into these drugs and the disease.

Recent findings: The focus of this article is to provide an overview of recent negative trials in pulmonary hypertension, with a specific focus on PAH. These include recent studies exploring the use of tocilizumab, selonsertib, rodatristat ethyl, anastrazole and dry powder inhalation of imatinib (AV-101).

Summary: This article provides an overview of the key learning points from these studies and reinforces the importance of the publication of all trials, irrespective of outcome, so that we can learn from negative studies and prioritize promising therapies and treatment pathways.

Purpose of review: Left heart disease (LHD) is the commonest cause of pulmonary hypertension (PH). The differential diagnosis between PH associated with LHD (PH-LHD) and pulmonary arterial hypertension (PAH) may be difficult. PH associated with LHD is causally related to chronically increased pulmonary artery wedge pressure (PAWP). However, PAWP may be "falsely" normal or high-normal at the time of diagnostic right heart catheterization.

Recent findings: Updated guidelines for step-by-step diagnosis of PAH and LHD leave nevertheless a proportion of patients with PH and diagnostic uncertainty. In these patients, several studies have shown that a PAWP >18 mmHg after a rapid infusion of 500 ml saline is associated with a high likelihood of LHD. Evidence has been accumulated that patients with PH, cardiovascular risk factors and a high-normal PAWP should have LHD excluded by a fluid challenge. Preliminary studies suggest that the test may be performed noninvasively by combining Doppler echocardiography and lung ultrasound showing respectively a ratio of trans-mitral flow E wave to mitral annulus tissue velocity e' (E/e') ≥12 and ≥5 B-lines.

Summary: A fluid challenge has a place in the step-by-step diagnostic work-up of patients referred for PH for the differential diagnosis between PH-LHD and PAH.

Purpose of review: Pulmonary hypertension (PH) is a specific but heterogeneous disease defined foremost by elevated pulmonary artery pressure, typically occurring due to pulmonary vascular fibroproliferative, plexigenic, or thrombotic remodelling. The heterogenous clinical and pathobiological basis of PH poses challenges and opportunities for optimizing treatment alignment to individual patients.

Recent findings: Advancing precision medicine through personalized treatment pathways in PH is particularly timely owing to persistent morbidity and shortened lifespan reported for patients despite an expanding armamentarium of pharmacotherapeutics, particularly for pulmonary arterial hypertension. Accomplishing this goal successfully has benefited from efforts that optimize clinical phenotyping, establishing reticulotypes that represent the phenotypic consequences of functionally essential pathogenic molecular events, and build greater insight on treatment response variability observed in randomized clinical trials.

Summary: Although as a scientific field PH remains early in the precision medicine journey, wider availability and lower cost of high throughput -omics platforms, and increasingly sophisticated analytical methodologies introduces optimism that clinically actionable strategies that improve patient-treatment alignment can be realized in the near-term.