Seminars in respiratory and critical care medicine最新文献

{"title":"Cryptogenic Organizing Pneumonia.","authors":"Michael Z Root, Joyce S Lee","doi":"10.1055/a-2703-4537","DOIUrl":"https://doi.org/10.1055/a-2703-4537","url":null,"abstract":"<p><p>Cryptogenic organizing pneumonia (COP), formerly called bronchiolitis obliterans organizing pneumonia (BOOP), was first described in the 1980s and is classified as a rare idiopathic interstitial pneumonia (IIP). COP classically presents in a subacute fashion following a flu-like illness with fever, non-productive cough, and fatigue. Imaging often reveals diffuse, bilateral, peribronchovascular and peripheral consolidative and ground glass opacities although various imaging subtypes also exist. Physical exam may be normal or reveal inspiratory crackles. Hypoxemia, when present, is commonly identified with exertion but can also occur at rest. Diagnostic evaluation relies on excluding secondary causes of organizing pneumonia and includes a thorough history including medications, exposures, and signs or symptoms of underlying rheumatologic disease. Invasive diagnostic testing including tissue sampling allows for histopathologic confirmation of COP while excluding secondary causes including infection and malignancy. While video-assisted thorascopic surgery (VATS) lung biopsy is often the preferred method of obtaining sufficient tissue, less invasive means may be employed based on patient-specific factors. A defining feature of COP is steroid-responsiveness, and most experts recommend prolonged corticosteroid courses (6-12 months). Response to corticosteroids and prognosis is typically excellent. Relapse rates range from 25-50% and occur most often during steroid taper or complete withdrawal necessitating additional therapy. Steroid-sparing immunosuppression may be used in select circumstances. Further study is needed to define optimal corticosteroid dose and duration.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087130","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":"The Evaluation of the Oncologic Patient for Drug-Induced Pneumonitis.","authors":"Terra C Swanson, Brent W Kinder, Joshua M Clark","doi":"10.1055/a-2703-4574","DOIUrl":"https://doi.org/10.1055/a-2703-4574","url":null,"abstract":"<p><p>The National Cancer Institute (NCI) estimates that over 2 million Americans will be diagnosed with cancer in 2025. A significant proportion of these patients will receive chemotherapeutics, radiation, molecularly targeted therapies, or immunotherapies-many of which are associated with pulmonary toxicity. Drug-induced interstitial lung disease (D-ILD) is a growing and well-recognized complication of cancer-related therapies, carrying substantial morbidity and mortality. In addition to its direct health impact, D-ILD often necessitates modification or discontinuation of cancer treatment, further complicating oncologic care. As such, pulmonologists must be proficient in the evaluation and management of suspected D-ILD. In this review, we propose a structured approach to assessing patients with malignancy who present with diffuse parenchymal lung disease. We also summarize commonly implicated cancer therapies and their associated pulmonary toxicities.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087352","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":"Glucocorticoid Treatment in Community-Acquired Pneumonia.","authors":"Pierre-François Dequin, Marco Confalonieri","doi":"10.1055/a-2704-6851","DOIUrl":"https://doi.org/10.1055/a-2704-6851","url":null,"abstract":"<p><p>Despite a fairly large number of comparative trials (which are, however, very heterogeneous), the role of corticosteroids in the adjuvant treatment of community-acquired pneumonia remains controversial. Nevertheless, recent randomized trials with adequate power in ICU patients, albeit with conflicting results, have contributed to clarifying our understanding of this issue. More accurate phenotyping of patients likely to benefit from corticosteroid treatment must now be carried out. In COVID-19 pneumonia, their benefit is not in question. For certain specific pathogens, including viral pathogens, their indications must be refined. They are still not recommended for influenza. They appear generally safe for short-term use in select populations.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087170","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":"The Glucocorticoid System: A Multifaceted Regulator of Mitochondrial Function, Endothelial Homeostasis, and Intestinal Barrier Integrity.","authors":"G Umberto Meduri, Anna-Maria G Psarra","doi":"10.1055/a-2684-3689","DOIUrl":"https://doi.org/10.1055/a-2684-3689","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Critical illness initiates a cascade of systemic disturbances-including energy deficits, oxidative stress, endothelial injury, and intestinal barrier dysfunction. Mitochondria, the vascular endothelium, and the intestinal barrier are three critical interfaces that facilitate the restoration of homeostasis. These processes are regulated by the glucocorticoid (GC) signaling system, specifically through the glucocorticoid receptor α (GRα), which coordinates cellular metabolism, immune modulation, and vascular integrity. This integrated signaling network offers therapeutic targets to prevent or reduce organ dysfunction and damage. Mitochondria function as metabolic hubs, transforming substrates mobilized by GC-GRα into adenosine triphosphate (ATP) via oxidative phosphorylation (OXPHOS), while also regulating calcium homeostasis, reactive oxygen species (ROS) signaling, and apoptosis. However, excessive ROS generation during critical illness can disrupt cellular energetics, leading to systemic inflammation and critical illness-related corticosteroid insufficiency (CIRCI). GC-GRα signaling helps mitigate mitochondrial dysfunction by promoting mitochondrial biogenesis, enhancing antioxidant defenses, and maintaining redox balance, which is essential for metabolic recovery and survival. The vascular endothelium and the intestinal barrier are the two most extensive and vulnerable surfaces affected during critical illness, and their preservation or restoration is vital for recovery. These active interfaces are essential for maintaining vascular integrity, immune balance, and metabolic stability-functions that are often severely impaired in critical illness. The vascular endothelium, which lines the entire circulatory system, plays a crucial role in regulating vascular tone, permeability, and immune cell recruitment through mediators like nitric oxide and prostacyclin. In conditions such as sepsis and acute respiratory distress syndrome (ARDS), inflammatory injury damages the endothelial glycocalyx and tight junctions, leading to microvascular leakage and widespread inflammation. Activation of GC-GRα pathways helps restore endothelial integrity by inhibiting nuclear factor-κB (NF-κB), lowering proinflammatory cytokine production, increasing tight junction proteins, and boosting endothelial nitric oxide synthase (eNOS) activity-mechanisms that collectively prevent thrombosis and edema. The intestinal barrier, maintained by tight junctions and gut microbiota, is essential for nutrient absorption and mucosal immune defense. During critical illness, gut dysbiosis-marked by a depletion of beneficial commensals and overgrowth of pathogenic species-compromises barrier integrity, increases intestinal permeability, and promotes bacterial translocation. GC-GRα signaling plays a key role in preserving the intestinal barrier by regulating tight junctions, lowering permeability, and affecting microbiota composition. Combining GC therapy with microbiota-focused int","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081518","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":"Updates in Lung Cancer Screening: A Decade of Evidence.","authors":"Lori Sakoda, Louise Henderson","doi":"10.1055/a-2701-9312","DOIUrl":"https://doi.org/10.1055/a-2701-9312","url":null,"abstract":"<p><p>To be addedIn this review, we summarize recent evidence from approximately the last five years across the lung cancer screening (LCS) care continuum. First, we review the results from the NELSON trial, from the extended follow-up of other LCS randomized controlled trials (RCTs), and from a meta-analysis of RCTs. Together, these RCTs reported a 16% relative reduction in lung cancer mortality for LDCT LCS versus non-LDCT controls. Next, we summarize updates to clinical guidelines and recommendations around LCS in the United States, noting the current debate around the use of time since quit as an eligibility criterion. We also discuss the implementation of LCS focusing on the following areas: (i) global landscape, (ii) selection criteria and approach, (iii) LCS program structure, (iv) shared decision making, (v) smoking cessation, (vi) LCS uptake, (vii) American College of Radiology Lung Reporting and Data System (Lung-RADS), (viii) annual LCS adherence, (ix) screen-detected findings and management, (x) incidental findings and management, and (xi) disparities. Lastly, we highlight emerging data and considerations for personalized LCS and new technologies, with an emphasis on risk prediction models, biomarkers, and artificial intelligence. This review highlights the latest changes to LCS and the ongoing need to monitor and evaluate LCS as it diffuses into clinical practice across various real-world settings.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076038","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":"Glucocorticoids and GRα Signaling in Critical Illness: Phase-Specific Homeostatic Corrections Across Systems.","authors":"G Umberto Meduri","doi":"10.1055/a-2691-6148","DOIUrl":"https://doi.org/10.1055/a-2691-6148","url":null,"abstract":"<p><p>Glucocorticoid (GC)-activated glucocorticoid receptor α (GRα) signaling-underpins survival and recovery during severe physiological stress. Rooted in evolution, these adjustments are not mere damage control; they constitute a coordinated, dynamic, phase-specific program that integrates metabolic, immune (innate and adaptive), cardiovascular, neuroendocrine, and organ functions. By boosting mitochondrial energy production and regulating inflammatory and hemostatic pathways, the GC-GRα axis enables adaptation to the demands of critical illness. These mechanisms operate across tissues and time to sustain systemic stability. This program unfolds in three phases. In the priming phase, innate immunity is rapidly mobilized, bioenergetic reserves are secured, and cardiovascular function is enhanced to build resilience. With the immediate threat contained, the modulatory phase suppresses excessive inflammation and oxidative stress and restores and preserves vascular integrity. In the restorative phase, resolution of injury enables structural and functional repair, re-establishing tissue architecture and function for long-term recovery. Failure to enter or complete the modulatory phase prolongs dysregulated responses that impede recovery. GRα is central: beyond anti-inflammatory actions, it shapes pro-inflammatory and metabolic programs. Through context-dependent co-regulation with nuclear factor-κB and activator protein-1, GRα directs cell-specific responses, drives chromatin remodeling, and orchestrates phase-specific gene expression to maintain a dynamic balance essential for survival. When transition to the modulatory phase fails, persistent stress signaling depletes neuroendocrine reserves, impairs bioenergetics, and exhausts key micronutrients, increasing allostatic load and mortality risk. Clinical modifiers-including critical illness-related corticosteroid insufficiency (CIRCI), mitochondrial dysfunction, hypovitaminosis, and oxidative stress-accelerate metabolic strain and decline toward organ failure. Mechanism-aligned care targeting GRα and synchronizing therapy with recovery phases enables individualized CIRCI correction, tempering of dysregulated inflammation, and organ recovery. Recognizing GC-GRα as the coordinator of homeostatic corrections highlights its evolutionary importance and guides strategies that complement the body's capacity to restore homeostasis.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075993","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":"Factors Influencing Glucocorticoid Treatment Response: Mechanism-Based Strategies to Overcome Glucocorticoid Resistance and Restore GRα Function.","authors":"G Umberto Meduri","doi":"10.1055/a-2691-6206","DOIUrl":"10.1055/a-2691-6206","url":null,"abstract":"<p><p>Glucocorticoids (GCs) remain central to managing dysregulated systemic inflammation in critical illness, yet therapeutic response varies widely due to multifactorial glucocorticoid resistance (GCR). This chapter provides a translational framework to guide clinicians in identifying and overcoming GCR, with a central emphasis on restoring glucocorticoid receptor α (GRα) function. Mechanisms of resistance include reduced GRα expression, GRβ dominance, impaired nuclear translocation, oxidative stress, mitochondrial dysfunction, micronutrient depletion, and epigenetic suppression. Pharmacokinetic and pharmacodynamic barriers-such as suboptimal dosing, impaired tissue penetration, accelerated clearance, erratic dosing schedules, and premature tapering-further compromise GRα engagement and treatment efficacy. In addition, interindividual variability in GR responsiveness is shaped by genetic polymorphisms, isoform balance, and local tissue conditions, compounded by up to 10-fold variability in circulating drug levels within the same patient. This chapter outlines evidence-based strategies to optimize GC therapy, including dose refinement, continuous infusion protocols, biomarker-guided escalation, and structured tapering. Adjunctive therapies-such as antioxidants, micronutrients, probiotics, and melatonin-are also highlighted for their role in enhancing mitochondrial resilience, redox stability, and GRα signaling across key regulatory phases. Importantly, many of these disruptions-whether arising from mitochondrial dysfunction, epigenetic changes, or intestinal dysbiosis-converge on shared molecular pathways such as nuclear factor kappa-B (NF-κB) activation, mitogen-activated protein kinase (MAPK) signaling, histone deacetylase 2 (HDAC2) inhibition, and oxidative stress, all of which compromise GRα function across systems. Recognizing this mechanistic convergence helps explain the multisystem nature of steroid resistance. It supports a unified therapeutic approach that targets oxidative stress, restores mitochondrial function, modulates the microbiome, and reinforces epigenetic regulation-working together to preserve GRα signaling across affected systems. While this framework is grounded in mechanistic and translational evidence, its application in clinical practice-including tapering strategies, biomarker thresholds, and adjunctive therapies-requires validation in randomized controlled trials.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967670","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":"Glucocorticoid Treatment in Severe COPD Exacerbations: Biological Rationale, Clinical Effects, and Practical Advice.","authors":"Filippo Sartori, Giulia Sartori, Claudia Di Chiara, Alberto Fantin, Ernesto Crisafulli","doi":"10.1055/a-2693-0577","DOIUrl":"https://doi.org/10.1055/a-2693-0577","url":null,"abstract":"<p><p>Acute exacerbations of chronic obstructive pulmonary disease (AECOPD), particularly those requiring hospitalization or intensive care unit (ICU) admission, represent a significant clinical and prognostic burden. Systemic corticosteroids remain a cornerstone of AECOPD management, supporting their role in improving time to recovery, symptom relief, and hospital length of stay. These benefits are primarily attributed to corticosteroids' broad anti-inflammatory and immunomodulatory actions, including the downregulation of pro-inflammatory cytokines such as interleukin (IL)-6, IL-8, and tumor necrosis factor α, as well as the restoration of glucocorticoid receptor function impaired in severe disease. Randomized controlled trials and meta-analyses confirm that short-course, low-to-moderate corticosteroid regimens are as effective as prolonged or higher-dose treatments, minimizing adverse effects such as hyperglycemia and infections. Oral administration is equally effective as intravenous therapy in most hospitalized patients, streamlining care without compromising efficacy. In ICU settings, systemic corticosteroids have been shown to reduce the need for invasive ventilation and shorten ICU stay, although mortality benefits remain inconsistent. Emerging precision medicine approaches highlight the relevance of blood eosinophil counts in predicting corticosteroid responsiveness. Eosinophilic patients experience shorter hospital stays, faster clinical improvement, and fewer treatment failures, suggesting the utility of eosinophil-guided corticosteroid therapy. Conversely, patients with neutrophil-predominant or infectious exacerbations may derive less benefit and face a greater risk of steroid-related complications. This narrative review synthesizes current evidence on the pharmacological, clinical, and biomarker-guided use of corticosteroids in severe AECOPD, emphasizing individualized treatment strategies to optimize therapeutic outcomes. With limitations represented by heterogeneity in study populations, lack of standardized eosinophil thresholds, and sparse data in critically ill or comorbid patients, future directions should include defining optimal corticosteroid regimens, refining eosinophil thresholds, exploring adjunctive therapies, and expanding biomarker-based protocols in ICU populations. Corticosteroid stewardship, guided by inflammatory profiles, represents a critical step toward personalized care in high-risk patients with COPD.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076000","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":"Corticosteroid Treatment in Septic Shock.","authors":"Jiao Liu, Qian Xing, Xiaojun Pan, Sheng Zhang, Dechang Chen, Djillali Annane","doi":"10.1055/a-2694-4823","DOIUrl":"https://doi.org/10.1055/a-2694-4823","url":null,"abstract":"<p><p>Septic shock, the most severe manifestation of sepsis, is characterized by profound circulatory failure and carries the highest mortality risk among sepsis-related conditions. Current therapeutic strategies remain primarily supportive, emphasizing empirical antimicrobial therapy and advanced organ system support. The immunomodulatory properties of corticosteroids in sepsis pathophysiology have been extensively investigated since the 1970s, though current guidelines recommend corticosteroid therapy for sepsis patients, albeit with a weak evidence base. In this review, we explore the molecular underpinnings of corticosteroid activity in septic shock and clinical evidence from randomized controlled trials, with a special emphasis on the stabilization of hemodynamics and the impact on mortality outcomes. Furthermore, we analyze recent advances in pharmacodynamic understanding that may inform more targeted corticosteroid administration in septic shock.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076006","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":"Heterogeneity of Lung Phagocytes and Clearance of Apoptotic Cells in Lung Injury and Repair.","authors":"Stephanie M Bersie, Alexandra L McCubbrey","doi":"10.1055/a-2675-2564","DOIUrl":"https://doi.org/10.1055/a-2675-2564","url":null,"abstract":"<p><p>Poor repair following lung injury is a significant cause of morbidity and mortality. Clearance of apoptotic cells, termed efferocytosis, has emerged as a key process that can influence repair outcomes and facilitate successful repair. Although prior literature has focused on efferocytosis by macrophages, evidence is emerging that nonprofessional phagocytes, including fibroblasts and epithelial cells, may play critical roles in efferocytosis during tissue repair. This review summarizes existing knowledge of different lung phagocytes that can participate in efferocytosis, evidence linking efferocytosis to lung health and tissue repair, and discusses factors that may inhibit or redirect efferocytosis to promote mis-repair. A deeper understanding of how the integrated landscape of lung phagocytes participates in efferocytosis will likely provide significant insight into repair and mis-repair processes.</p>","PeriodicalId":21727,"journal":{"name":"Seminars in respiratory and critical care medicine","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001412","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}