Seminars in respiratory and critical care medicine最新文献

{"title":"Update on Drug-Induced Pneumonitis in Lung Cancer.","authors":"Kathleen A McAvoy, Jennifer D Possick","doi":"10.1055/a-2666-7519","DOIUrl":"10.1055/a-2666-7519","url":null,"abstract":"<p><p>Drug-induced pneumonitis is a significant and potentially life-threatening complication associated with multiple lung cancer therapies. As novel therapies are introduced and incorporated into updated treatment algorithms, it is crucial to anticipate, recognize, and manage these events readily and comprehensively. As experience with these agents accumulates in real-world settings, so too does our appreciation for patient risk factors, the need for personalized monitoring strategies, the heterogeneity of both clinical and radiographic presentations, and the persistent importance of a systematic approach to diagnosis and management. Novel therapies are responsible for significant improvements in lung cancer survival, but enthusiasm for this progress must be tempered by mitigation and management of inherent risks to avoid undue morbidity and mortality for our patients. Challenging clinical scenarios such as steroid-refractory pneumonitis highlight the importance of thorough evaluation, confident attribution, and aggressive early management. Future elucidation of the pathophysiology of these reactions will hopefully refine future diagnostic and therapeutic options. A collaborative, multidisciplinary approach is essential to optimize patient safety and outcomes in lung cancer care. In this study, we describe approaches to pretreatment assessment, evaluation of suspected pneumonitis, and management of pneumonitis on a drug-specific basis. We emphasize emerging data and drug classes, while also highlighting remaining areas of uncertainty.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reimagining Fibrosis Research, Outcomes, and Therapeutics Through the Lens of Resolution.","authors":"Sean M Fortier, Elizabeth F Redente, Marc Peters-Golden","doi":"10.1055/a-2666-7479","DOIUrl":"10.1055/a-2666-7479","url":null,"abstract":"<p><p>Tissue fibrosis contributes to progressive organ dysfunction in a multitude of chronic human diseases. Despite decades of ongoing research dedicated to determining the cellular and molecular origins of fibrosis across multiple organs, we continue to lack truly impactful therapies that halt or reverse scarring. This unmet need is especially evident among individuals with fibrotic lung disease, such as idiopathic pulmonary fibrosis (IPF), who frequently succumb to progressive respiratory failure a few years after diagnosis. Current therapies approved for IPF and progressive fibrotic lung diseases emerged from a longstanding drug development paradigm focused on the inhibition of pro-fibrotic drivers of fibrosis. Given that the vast majority of patients with fibrotic lung disease present with already established scarring, the relative paucity of research focused on fibrosis resolution pathways represents a glaring and critical gap in our knowledge. In contrast to the progressive pathologic fibrosis emblematic of IPF, fibrosis evolved as a self-limited wound-healing response to tissue injury, and spontaneous resolution of lung fibrosis is observed in various experimental animal models. These naturally resolving animal models of fibrosis provide an opportunity to define endogenous anti-fibrotic mediators that inhibit multiple drivers of fibrosis and can orchestrate the return of tissue homeostasis. Therapeutic restoration of these endogenous \"resolvers\"-which are ostensibly disabled in states of pathologic fibrosis-has immense therapeutic potential. In this perspective, we contend that a paradigm shift in our approach toward fibrosis research is needed. Specifically, we propose that pulmonary fibrosis research be reprioritized to collectively focus on mechanisms of fibrosis resolution using rigorous methods designed to unveil, validate, and explore the therapeutic implications of endogenous resolvers.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Markers in the Era of Precision Care in Lung Cancer.","authors":"Ishan Paranjpe, Alexander I Salter, Kenneth Chen, Millie Das","doi":"10.1055/a-2649-9199","DOIUrl":"10.1055/a-2649-9199","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. The past two decades have brought advances in molecular profiling and the advent of therapies that specifically target genetic and/or molecular alterations in NSCLC. There are now many FDA-approved targeted therapies for patients with metastatic lung cancer who harbor oncogenic driver alterations, including those in epidermal growth factor receptor, ALK receptor tyrosine kinase, KRAS proto-oncogene, GTPase, and others. These advances epitomize personalized medicine and improve patient outcomes compared with conventional cytotoxic chemotherapy. This review highlights the current and evolving landscape of targeted therapies in NSCLC, emphasizing key targets, resistance mechanisms, and new approaches poised to improve patient outcomes in the era of precision oncology. The next decade will likely be marked by further improvements in the specificity, duration of action, and toxicity profiles of targeted therapies, allowing patients to live longer and better lives.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Trends in Global Lung Cancer Burden.","authors":"Lynn Y-W Shong, David C-L Lam","doi":"10.1055/a-2651-0612","DOIUrl":"https://doi.org/10.1055/a-2651-0612","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related deaths worldwide, with its burden shaped by evolving risk factors, demographic changes, and healthcare disparities. Over the past decades, while age-standardized incidence and mortality rates have declined, the absolute number of cases has risen due to population growth and aging. Tobacco smoking remains the most common risk factor, accounting for approximately 60% of cases globally, though its contribution has declined in high-income regions due to effective tobacco control. Conversely, countries with lower socioeconomic development, particularly in East and South Asia, face rising incidence and mortality driven by increasing smoking prevalence, air pollution, and limited access to healthcare. Emerging risk factors, such as ambient air pollution and genetic predisposition, are increasingly significant, particularly in regions with lower Human Development Index scores. Sex disparities are evident, with lung cancer rates declining among men in many high-income countries but rising among women globally. Early-onset lung cancer is also an emerging concern, especially in middle socio-demographic index regions, driven by smoking, environmental exposures, and genetic factors. By 2035, it is predicted that lung cancer deaths could reach 3 million annually. To address the impact of the growing lung cancer burden, a multifaceted approach is needed, including strengthened tobacco control, improved air quality, promotion of clean cooking fuels, and expanded low-dose computed tomography screening, particularly in resource-constrained regions.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peeling Back the Layers of the Bleomycin Model of Lung Fibrosis: Lessons Learned, Factors to Consider, and Future Directions.","authors":"Patricia Brazee, Nancy Allen, Rachel Knipe, Elizabeth F Redente, Claude Jourdan Le Saux","doi":"10.1055/a-2649-9402","DOIUrl":"https://doi.org/10.1055/a-2649-9402","url":null,"abstract":"<p><p>Bleomycin-induced lung injury remains the most widely used and well-characterized experimental model for studying pulmonary fibrosis, particularly idiopathic pulmonary fibrosis (IPF). This review provides a comprehensive analysis of the bleomycin model's utility, phases, variability, and translational relevance. Bleomycin administration in rodents induces acute epithelial injury followed by inflammation, fibroblast activation, extracellular matrix deposition, and eventual fibrosis. The model progresses through defined stages, acute inflammation (days 1-7), fibrogenesis (days 7-28), and in most cases, spontaneous resolution (days 42-63), making it suitable for understanding temporal aspects of fibrosis and repair, the cell populations involved, and the signaling mechanisms involved. Despite its advantages, the single-dose model lacks key features of human IPF, including persistent fibrosis, honeycomb cysts, and fibroblastic foci. Repetitive dosing and the use of aged mice have improved chronicity and recapitulation of progressive disease and observation of the expansion of aberrant epithelial cell populations in simple cyst structures. This review discusses route-specific effects, strain and sex susceptibilities, and the growing role of microbiome and genetic background in influencing fibrosis outcomes. It also highlights cellular responses across epithelial cell populations, fibroblasts, endothelial cells, and immune cell populations. Although limitations exist in this model-such as reversibility and incomplete modeling of human pathology-bleomycin remains invaluable for mechanistic studies and preclinical drug screening. Importantly, all FDA-approved antifibrotic drugs demonstrated efficacy in bleomycin models prior to clinical success. The review advocates for careful model selection, incorporation of persistent fibrosis models, and parallel use of human-relevant systems to enhance translational relevance in pulmonary fibrosis research.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144848985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Concepts in Therapeutic Interventions for Idiopathic Pulmonary Fibrosis.","authors":"Cody A Schott, Michael P Mohning, Joseph C Cooley","doi":"10.1055/a-2651-1937","DOIUrl":"10.1055/a-2651-1937","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a rare but devastating diagnosis for patients with only two approved drug therapies. Extensive preclinical studies have identified and characterized novel pathways driving IPF pathogenesis, and researchers have identified several new promising therapeutic targets to help treat IPF. However, translating these preclinical models into viable treatment modalities has proven challenging. This review will address the evolving nature of IPF research, examine the preclinical studies and their target pathways that have advanced to clinical trials, and address the translational gap that has limited the success of novel therapeutic trials for IPF.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Concepts in Fibroblast Biology and Progressive Pulmonary Fibrosis.","authors":"Priyanka Singh, Shanda Edjah, Wei Shi, Satish K Madala","doi":"10.1055/a-2649-9359","DOIUrl":"10.1055/a-2649-9359","url":null,"abstract":"<p><p>Pulmonary fibrosis is characterized by scarring and thickening of the lung parenchyma due to excessive deposition of collagen and other extracellular matrix (ECM) proteins. This leads to disruption of gas exchange areas and ultimately respiratory failure, a pathology shared across multiple interstitial lung diseases (ILDs). Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive ILD characterized by exertional dyspnea, dry cough, and restrictive lung defects. Clinical progression is marked by worsening lung function, declining exercise tolerance, and hypoxemia. High-resolution computed tomography in IPF typically shows reticular opacities and honeycombing, predominantly distributed in the subpleural regions and lower lobes of the lungs. The disease course is variable, with episodes of acute exacerbation associated with high mortality. Myofibroblasts and fibroblasts are central drivers of fibrogenesis through uncontrolled proliferation, migration, survival, senescence, myofibroblast differentiation, and ECM production. Myofibroblasts represent a heterogeneous population in both origin and function, arising from diverse precursor cells, including lung resident fibroblasts, endothelial cells, and mesothelial cells, and are shaped by tissue-specific niches. Persistent activation of (myo)fibroblasts is sustained by a complex network of profibrotic growth factors and their downstream transcriptional regulators. In this review, we comprehensively examine the cellular origins and molecular pathways underlying fibroblast activation, with an emphasis on mechanistic insights that may inform the development of targeted antifibrotic therapies to attenuate disease progression and improve patient outcomes.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung Cancer in Special Populations.","authors":"Matthew Triplette, Melinda C Aldrich","doi":"10.1055/a-2657-9494","DOIUrl":"https://doi.org/10.1055/a-2657-9494","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer deaths worldwide, claiming more lives than other age-related and screen-detectable cancers. Cigarette smoking remains the most important risk factor. However, despite common perceptions, risk is not related solely to cigarette smoking. Several vulnerable and special populations experience a disproportionate burden of lung cancer, often complicated by overlapping medical issues, diagnostic challenges, and treatment limitations. This review highlights four populations (people with HIV, persons who are immunocompromised, lung cancer in nonsmoking women, and individuals with interstitial lung disease [ILD]) who experience unique risks that impact early detection, diagnosis, and management of lung cancer. Three of these populations are frequently underrepresented in clinical trials, yet they may be at elevated risk due to chronic inflammation, immune dysregulation, or previous medical therapies. Individuals with HIV have a significantly increased incidence of lung cancer, often presenting at younger ages and with more advanced disease. Similarly, patients who are immunocompromised following organ or stem cell transplantation are at heightened risk due to prolonged immune dysfunction and prior exposures to toxic therapies. Individuals with ILD, especially idiopathic pulmonary fibrosis (IPF), have an increased risk of developing lung cancer, which is challenging to detect with imaging given architectural distortion and even more challenging to treat given limited pulmonary reserve. We also highlight women, as there has been a striking trend of rising incidence of lung cancer among women worldwide, particularly among those who have never smoked. The intersection of these risks with traditional lung cancer risk factors like tobacco smoking highlights a critical need for increased awareness, improved risk stratification, and adapted screening strategies that take these complexities into account. In this review, we explore the epidemiology, clinical presentation, and early detection and management challenges unique to each population, underscoring the necessity of precision approaches to support individualized care.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-Cell Lung Cancer Updates.","authors":"Yunan Nie, Anne C Chiang","doi":"10.1055/a-2649-9240","DOIUrl":"https://doi.org/10.1055/a-2649-9240","url":null,"abstract":"<p><p>Small-cell lung cancer (SCLC) is a high-grade, aggressive neuroendocrine tumor with a particularly poor prognosis, characterized by early metastases and rapid development of therapy resistance. There have historically been few treatment options for advanced or extensive stage SCLC, which comprises 70% of patients at the time of diagnosis, and 5-year survival rates for these patients have been under 5% for decades. Treatment of SCLC is now undergoing rapid changes due to advances in the field and many promising clinical trials, with several new therapy approvals within the last year. Advanced SCLC treatment is now a combination of chemotherapy and immunotherapy in the first line, with multiple second and later-line options. Early-stage SCLC is treated with chemoradiation followed by consolidative immunotherapy, a change in practice based on a recent clinical trial demonstrating an improvement of almost 2 years in median overall survival. In the era of immunotherapy and novel agents, prognosis has improved for advanced-stage disease, with 3-year survival rates of 16 and 17% in clinical trials for chemoimmunotherapy combinations. Despite these advances, most patients will progress within 6 months of starting first-line chemoimmunotherapy; thus, this disease continues to represent an area of unmet need. This update will highlight current standard of care practices and updates of recent promising trials that have improved outcomes, including survival, for SCLC patients.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survivorship Challenges and Supportive Care in Lung Cancer.","authors":"Duc M Ha, Regina A Jacob, Brett C Bade","doi":"10.1055/a-2649-9311","DOIUrl":"10.1055/a-2649-9311","url":null,"abstract":"<p><p>The number of lung cancer survivors-anyone living with and beyond a lung cancer diagnosis-is increasing along with advances in screening, early detection, and treatment. Following diagnosis and treatment, however, many lung cancer survivors experience high symptom burden and functional challenges that culminate in poor health-related quality of life (HRQL). We incorporated the cancer life course endorsed by the United States National Academy of Medicine (formerly Institute of Medicine) and reviewed interventions to improve HRQL, starting from the time of diagnosis, during or following curative intent treatment, noncurative intent treatment, and continued until changes in disease status and/or goals of care. We reviewed clinical guidelines from the American College of Chest Physicians on HRQL following curative intent therapy, symptom management, and supportive care in lung cancer, as well as the role of exercise-based rehabilitation, complementary therapies, and integrative medicine. Moreover, we identified interventions evaluated in 19 randomized controlled trials (RCTs) or pilot RCTs in the past 10 years, involving 2,506 participants, to address HRQL challenges reported by ≥80% of lung cancer survivors as \"important\" or \"very important\": dyspnea, fatigue, sleep difficulties, fear/distress, anxiety, depressive symptoms, physical or role function/independence. This narrative review, which incorporates findings from physical exercise and rehabilitation, cognitive-behavioral and psychological therapies, mind-body therapies, mindfulness-based interventions, and other complementary therapies, has significant implications for enhancing the HRQL of the growing population of lung cancer survivors.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}