Current Opinion in Pulmonary Medicine最新文献

Purpose of review: This review aims to provide an updated overview of the diagnosis, risk factors, and treatment strategies for immune checkpoint inhibitor (ICI) pneumonitis, with a particular emphasis on its underlying pathophysiology.

Recent findings: Recent advances, such as single-cell RNA sequencing of bronchoalveolar lavage fluid and the identification of biomarkers, including autoantibodies, are enhancing our understanding of ICI-related pneumonitis. These findings suggest that both cell-mediated and humoral mechanisms contribute to the pathophysiology of the condition.

Summary: Pneumonitis can significantly limit the efficacy of life-saving cancer treatments, such as ICIs. Although corticosteroids are the first-line treatment according to guidelines, steroid-refractory pneumonitis remains common and is associated with high mortality. Emerging data is providing a more detailed understanding of the dysregulated immune response responsible for pneumonitis, which may guide the development of targeted therapies and direct future research efforts.

Purpose of review: Lung transplantation is a common treatment for end-stage lung disease (ESLD). Patients present to lung transplantation evaluation on various medications that could impact their candidacy and posttransplant course. In this review, we will discuss pretransplant optimization of pharmacotherapy to minimize complications while waiting for transplant and increase posttransplant success. We will also discuss important considerations for posttransplant immunosuppression, antimicrobial prophylaxis, and complex drug interactions.

Recent findings: Prior to lung transplantation, several medications should be optimized to promote posttransplant success including minimization of corticosteroids, opioids, and benzodiazepines. Lung transplantation candidates should be up to date on vaccinations. Most medications for ESLD are well tolerated to continue up until the point of transplant including antifibrotics, CFTR modulators, and pulmonary vasodilators. Mammalian target of rapamycin inhibitors and other immunosuppressants may need to be stopped or minimized before lung transplantation to minimize posttransplant infection and would healing complications. Medications that increase risk of posttransplant bleeding, thrombosis, or aspiration should be stopped prior to listing.

Summary: In this article, we discuss management of pharmacotherapy for lung transplantation candidates to minimize posttransplant complications. Changes in medications for ESLD should be done cautiously to prevent worsening of native disease while waiting for lung transplantation.

Purpose of review: Lung transplantation is a critical and evolving therapy for patients with end-stage lung disease. As the need for lung transplantation increases, careful candidate selection is vital to maximizing outcomes and ensuring appropriate organ allocation. A key challenge in lung transplant candidates is the colonization or infection of the lungs by environmental and upper airway pathogens. These lung pathogens, along with other chronic infections, can lead to posttransplant complications with high mortality and an increased risk of graft failure.

Recent findings: Major infectious considerations for lung transplantation include colonization or infection by multidrug-resistant bacteria (including Burkholderia cepacia complex), nontuberculous mycobacteria, molds, and chronic viral infections. By recognizing the epidemiology, diagnosis, and management of these infections in the peri-transplant period, transplant providers can better mitigate infectious risks and improve transplant success. Similarly, advancements in diagnostics and therapeutics offer novel approaches to managing previously challenging infections.

Summary: As experience grows in treating these difficult infectious syndromes, more candidates are becoming eligible for transplantation. A thorough understanding of infectious considerations in lung transplant candidates is essential for improving candidate selection, reducing posttransplant complications, and expanding transplant eligibility.

Purpose of review: Advances in radiation delivery have expanded the scope of stereotactic body radiation therapy (SBRT) in lung cancer treatment, as it offers better local control, shorter treatments, and enhanced immunostimulation. This review summarizes recent literature regarding SBRT's role in nonoperable and operable early-stage, locally advanced, central, and oligometastatic nonsmall cell lung cancer (NSCLC), and its mixed results with immunotherapy.

Recent findings: Recent studies demonstrate SBRT achieves excellent local control in inoperable early-stage NSCLC and is being explored as an alternative to surgery for operable cases. Additionally, SBRT can be done safely in central tumors if strict dose limits to normal structures are observed. SBRT shows promise in locally advanced disease, as consolidative local therapy for oligoprogressive and oligometastatic disease and in combination with immune checkpoint inhibitors. Advances in adaptive radiation therapy and novel fractionation schedules, including ultra-hypofractionation and personalized approaches, further refine SBRT's role in lung cancer management, with more practice changing clinical trials on the horizon.

Summary: SBRT provides durable and well tolerated treatment for patients with localized and metastatic lung cancer. With ongoing trials exploring its synergy with immunotherapy and its applicability in operable patients and large tumors, SBRT is poised to play an even greater role in personalized lung cancer treatment.

Purpose of review: Over the past decade, increased knowledge has contributed to improved medical and technical treatments across the spectrum of respiratory diseases. As a result, timing for transplant evaluation might be more challenging. In this review, the focus is on timing of lung transplant evaluation of patients from the main respiratory diseases referred. Disease-specific predictors of survival in relation to timing of transplant evaluation and alternative treatments will be reviewed.

Recent findings: Treatment options have evolved for respiratory diseases like chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis and pulmonary arterial hypertension. These treatments have led to improved quality of life, exercise tolerance, lung function and outcome. However, the effect of these alternative treatments on transplant candidacy and knowledge on timing of lung transplant evaluation are lacking.

Summary: This article reviews the current best evidence to guide clinicians regarding the optimum timing for transplant referral and highlights considerations to optimize transplant candidacy and outcomes.

Purpose of review: Median survival after lung transplantation is 5.7 years, which lags behind other solid organ transplants, such as heart, liver, and kidney. The major barrier to long-term survival in lung transplant recipients is chronic lung allograft dysfunction (CLAD). This review discusses the challenge of CLAD as a barrier to tolerance and identifies key areas in the field that require further development.

Recent findings: CLAD is a heterogenous disease in its kinetics of onset and severity and remains a clinical diagnosis of exclusion, based on a decline in allograft function. While acute cellular rejection and antibody-mediated rejection are major risk-factors for CLAD, other barriers to long-term allograft acceptance are aspiration and primary graft dysfunction. However infections, particularly respiratory viral infections and Cytomegalovirus (CMV) remain the most significant risks for CLAD. Additionally, the lung transplant field is limited by a lack of molecular diagnostic assays for CLAD. Further, new targets are needed for precision immunosuppression, and more studies are needed to develop novel interventions to extend allograft acceptance.

Summary: This review discusses new lines of study to address important unmet needs necessary to extend lung allograft acceptance. Other studies, such as tandem lung transplant and bone marrow transplant in select patients with primary immunodeficiency may provide additional lessons on how to potentially establish tolerance. However, tolerance in lung transplant is extremely rare, and further studies are needed to pursue this ultimate goal.

Purpose of review: This review examines the current understanding of telomere biology disorders (TBDs) in advanced lung disease, with particular focus on their implications for lung transplantation outcomes and management.

Recent findings: Recent studies have revealed that TBDs are enriched in lung transplant populations, with many idiopathic pulmonary fibrosis transplant recipients having short telomeres and/or carrying variants in telomere-related genes. While survival outcomes remain debated, recipients with short telomeres consistently show increased susceptibility to cytopenias, cytomegalovirus (CMV) infection, and may require modified immunosuppression regimens. New evidence suggests potential protection against acute cellular rejection in some cases, and novel approaches using letermovir for CMV prophylaxis show promise in managing these complex patients.

Summary: Management of lung transplant recipients with TBDs requires careful consideration of multiorgan manifestations and individualized management strategies. A multidisciplinary approach incorporating genetics, haematology, and hepatology expertise is increasingly essential for optimal outcomes in this unique population.

Purpose of review: To explore the current applications of artificial intelligence and machine learning in lung transplantation, including outcome prediction, drug dosing, and the potential future uses and risks as the technology continues to evolve.

Recent findings: While the use of artificial intelligence (AI) and machine learning (ML) in lung transplantation is relatively new, several groups have developed models to predict short-term outcomes, such as primary graft dysfunction and time-to-extubation, as well as long-term outcomes related to survival and chronic lung allograft dysfunction. Additionally, drug dosing models for Tacrolimus levels have been designed, demonstrating proof of concept for modelling treatment as a time-series problem.

Summary: The integration of ML models with clinical decision-making has shown promise in improving post-transplant survival and optimizing donor lung utilization. As technology advances, the field will continue to evolve, with enhanced datasets supporting more sophisticated ML models, particularly through real-time monitoring of biological, biochemical, and physiological data.