Semin Respir Crit Care Med [JOURNAL]
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200 papers
Monographic Issue on New Concepts in Acute Exacerbations of COPD.
Crisafulli E, Torres A
Semin Respir Crit Care Med · 2026 Jun · PMID 41990839 · Publisher ↗
Abstract loading — click title to view on PubMed.
Bidirectional Clinical Interactions among Exacerbations and Comorbidities in COPD: A Narrative Review.
Peerlings DEM, Houben-Wilke S, Simons SO … +3 more , Ioannides AE, Quint JK, Franssen FME
Semin Respir Crit Care Med · 2026 Jun · PMID 41962550 · Full text
Acute deteriorations of respiratory symptoms in people with chronic obstructive pulmonary disease (COPD), known as exacerbations, worsen COPD severity (e.g., speed up lung function decline), and increase hospital admissi...
Acute deteriorations of respiratory symptoms in people with chronic obstructive pulmonary disease (COPD), known as exacerbations, worsen COPD severity (e.g., speed up lung function decline), and increase hospital admissions, healthcare costs, and mortality risk. The prevention, diagnosis, and treatment of exacerbations remain challenging due to the heterogeneous nature of these events. This complexity is further compounded by the high prevalence of multiple comorbidities and incompletely understood underlying mechanisms. Exacerbations of COPD and comorbidities are linked through bidirectional relationships, characterized by mutual adverse impacts, overlapping clinical manifestations, and increased susceptibility to the other condition. The identification and management of comorbidities are pivotal for effective disease management. Although current clinical frameworks, that is, models that integrate clinical features and biomarker-based identification of exacerbations to guide risk stratification and management, represent promising approaches to improve patient outcomes, multimorbidity is insufficiently incorporated. This narrative review provides an overview of the complex clinical associations of comorbidities in COPD, with a particular focus on exacerbations. It highlights differences in comorbidity prevalence among exacerbators, explores clinical interrelationships, and underscores the importance of multimorbidity-oriented management.
Radiological Approach to Severe Respiratory Infections and Pulmonary Complications in Immunocompromised Patients.
Meredith S, Kaltsas A, Machnicki S … +4 more , Stover D, Saez K, Gruden J, Raoof S
Semin Respir Crit Care Med · 2026 Apr · PMID 41946459 · Publisher ↗
Immunocompromised patients include those with innate T or B cell suppression, acquired immunodeficiency states such as those caused by human immunodeficiency virus infection, and those with medication-induced immunosuppr...
Immunocompromised patients include those with innate T or B cell suppression, acquired immunodeficiency states such as those caused by human immunodeficiency virus infection, and those with medication-induced immunosuppression (chemotherapy or immunotherapy, solid organ transplant recipients). Any of these entities can place patients at increased risk of severe respiratory infection. We propose an algorithmic approach to the diagnosis of pulmonary complications that can arise in the immunocompromised patient. The first step is to gather all relevant clinical data to understand the history leading up to presentation, as well as the specific underlying immunosuppressive state. Following this, the clinician must identify the predominant imaging pattern of disease to help narrow the differential diagnosis and guide clinical management. Third, the time course of the clinical and imaging findings should be classified as acute, subacute, or chronic. We define the distinction between acute/subacute and chronic disorders as before or after 12 weeks. At the conclusion of these steps, it is hoped that a tailored differential diagnosis will allow for a rapid and precise management plan of these challenging patients.
Two Sides of the Same Smoke: Decoding Respiratory Bronchiolitis-Associated Interstitial Lung Disease and Alveolar Macrophage Pneumonia.
Alarcon-Calderon A, Yi ES, Koo CW … +1 more , Vassallo R
Semin Respir Crit Care Med · 2026 Apr · PMID 41916427 · Publisher ↗
Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and alveolar macrophage pneumonia (AMP) are two rare but closely related conditions within the spectrum of smoking-related interstitial pneumonias....
Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and alveolar macrophage pneumonia (AMP) are two rare but closely related conditions within the spectrum of smoking-related interstitial pneumonias. Both share characteristic histopathologic features, including the accumulation of pigmented alveolar macrophages alongside varying degrees of interstitial inflammation and fibrosis. RB-ILD is typically a localized, bronchiolocentric process often found in smokers, whereas AMP represents a more diffuse and clinically significant disease that may arise not only from tobacco smoke but also from other causes such as occupational exposures, autoimmune diseases, and drug reactions. This review highlights the clinical presentation, imaging findings, histopathology, and treatment of both entities, emphasizing their overlapping features as well as key distinctions. We further discuss the pathogenic mechanisms driven by cigarette smoke-including oxidative stress, immune activation, and fibrosis-that underlie these diseases. A clear understanding of the similarities and differences between RB-ILD and AMP is essential for accurate diagnosis, effective management, and prognostication, particularly in patients with a history of smoking and diffuse parenchymal lung involvement.
Role of Vaccination in the Prevention of ECOPD.
Sartori F, Crisafulli E, Cariqueo M … +4 more , Di Chiara C, Sartori G, Fantin A, Torres A
Semin Respir Crit Care Med · 2026 Jun · PMID 41871621 · Publisher ↗
Exacerbations of chronic obstructive pulmonary disease (ECOPD) represent key events in the natural history of COPD and are associated with several adverse outcomes. Respiratory infections are major and potentially modifi...
Exacerbations of chronic obstructive pulmonary disease (ECOPD) represent key events in the natural history of COPD and are associated with several adverse outcomes. Respiratory infections are major and potentially modifiable triggers of ECOPD, with viral pathogens such as the influenza virus, respiratory syncytial virus (RSV), and SARS-CoV-2, as well as bacterial infections caused by , playing a central role. This narrative review examines the current evidence supporting vaccination as a preventive strategy for ECOPD and discusses its translation into clinical practice. The biological rationale for vaccination in COPD is reviewed, including disease-related immune dysregulation, impaired mucociliary clearance, and increased susceptibility to respiratory pathogens. Evidence from randomized clinical trials, observational studies, meta-analyses, and real-world data is summarized for pneumococcal, influenza, SARS-CoV-2, and RSV vaccines. Pneumococcal vaccination has been shown to reduce the burden of community-acquired pneumonia and invasive pneumococcal disease, with conjugate and higher-valent vaccines providing enhanced immunogenicity in older and high-risk adults. Influenza vaccination consistently reduces severe exacerbations, hospitalizations, and mortality, with additional cardioprotective effects of relevance in COPD. SARS-CoV-2 vaccination markedly lowers the risk of severe COVID-19 and related respiratory deterioration in COPD, while recently licensed RSV vaccines offer a novel opportunity to prevent RSV-associated lower respiratory tract disease and potentially reduce exacerbation risk. Patient populations most likely to benefit from vaccination include frequent exacerbators, older adults, individuals with severe airflow limitation, multimorbidity, immune dysfunction, infection-prone phenotypes, and socially vulnerable groups. Future perspectives include precision vaccination strategies, novel vaccine platforms, coadministration approaches, and interventions to improve vaccine uptake. Vaccination emerges as a cornerstone of ECOPD prevention, with substantial potential to reduce exacerbation burden and improve long-term outcomes in COPD.
Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Pharmacological Treatment of AECOPD New Perspectives.
Calvello J, Avaricio M, Ruggeri P … +2 more , Esquinas AM, Mina B
Semin Respir Crit Care Med · 2026 Jun · PMID 41844237 · Publisher ↗
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are major drivers of morbidity, mortality, disease progression, and healthcare utilization worldwide. Evolving definitions of COPD and exacerbations,...
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are major drivers of morbidity, mortality, disease progression, and healthcare utilization worldwide. Evolving definitions of COPD and exacerbations, along with emerging evidence on risk stratification and treatment optimization, have prompted updates in clinical practice, most recently reflected in the 2026 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. This review summarizes contemporary perspectives on AECOPD, with a focus on updated definitions, epidemiology, predictors, clinical impact, and current pharmacological and nonpharmacological management strategies, including emerging preventive therapies. A narrative review of published literature, international guidelines, and major clinical trials was conducted, emphasizing evidence relevant to the assessment, treatment, and prevention of AECOPD. Particular attention was given to severity classification and guideline-directed therapeutic approaches. AECOPD is associated with substantial short- and long-term mortality, accelerated lung function decline, increased cardiovascular risk, and high readmission rates. The 2026 GOLD guidelines lower the threshold for high-risk classification, recognizing that even a single moderate exacerbation increases future risk. Acute management remains centered on short-acting bronchodilators, short courses of systemic corticosteroids, and antibiotics when indicated, with treatment of intensity guided by clinical severity and physiological derangements. Adjunctive supportive measures and early postdischarge interventions are critical to improving outcomes. While biologics, macrolides, Roflumilast, and Ensifentrine have no established role in the acute setting, they play an important role in exacerbation prevention as part of individualized, biomarker-informed maintenance strategies. AECOPD should be viewed as a sentinel event that necessitates both effective acute management and reassessment of long-term therapy. Early intervention, severity-based treatment, and postexacerbation optimization of maintenance therapy are essential to reduce recurrence, limit disease progression, and improve survival and quality of life in patients with COPD.
Nonpharmacological Strategies to Improve Stability and Prevent Exacerbations of COPD.
Vitacca M, Ambrosino N
Semin Respir Crit Care Med · 2026 Jun · PMID 41786312 · Publisher ↗
Exacerbations of chronic obstructive pulmonary disease (ECOPD) are the main cause of hospitalization, mortality, and progressive worsening in health-related quality of life (HRQL). Each ECOPD speeds functional decline, m...
Exacerbations of chronic obstructive pulmonary disease (ECOPD) are the main cause of hospitalization, mortality, and progressive worsening in health-related quality of life (HRQL). Each ECOPD speeds functional decline, making these individuals increasingly susceptible to further infections. Therefore, we need strategies to prevent ECOPD and maintain disease stability as long as possible. In addition to medications, lifestyle interventions aimed at promoting vaccinations and avoiding smoking, minimizing exposure to environmental pollutants, encouraging physical activity, addressing obesity and malnutrition, along with empowering individuals through disease awareness and self-management, may improve stability and HRQL and reduce ECOPD rate. Although long-term oxygen therapy is known to enhance survival, its broader utility in curtailing healthcare utilization requires further clarification. Home noninvasive ventilation (NIV) and the more recently introduced high-flow nasal cannula may reduce the need for hospitalization and mortality in individuals with stable chronic hypercapnia. Long-term NIV should be initiated after ECOPD is successfully treated and set to reduce hypercapnia. Telemedicine programs may be potentially useful, but their effectiveness and safety in real life have to be confirmed.
Microbiologic Diagnosis of Respiratory Infections in Critically Ill Immunocompromised Patients.
Liu Y, Pickens C
Semin Respir Crit Care Med · 2026 Apr · PMID 41763193 · Publisher ↗
Critically ill, immunocompromised individuals are vulnerable to both common and uncommon etiologies of respiratory infection. Identifying the etiology of infection has therapeutic, prognostic, and public health implicati...
Critically ill, immunocompromised individuals are vulnerable to both common and uncommon etiologies of respiratory infection. Identifying the etiology of infection has therapeutic, prognostic, and public health implications. In some circumstances, immunocompromised patients may be empirically treated with excessively broad antibiotics but ultimately be diagnosed with a common cause of pneumonia. In other circumstances, immunocompromised patients may have a non-specific clinical presentation for severe respiratory failure and be diagnosed with a rare etiology of infection. Because this patient population is at risk for a broad array of infections, it is important to understand the advantages and limitations of sampling and diagnostic techniques. Furthermore, the last decades of research have produced novel methods to enhance diagnostic accuracy. Many of these tests are molecular diagnostics that have high sensitivity, but their clinical impact is unknown, particularly in immunocompromised individuals. In this article we discuss various approaches to sampling and microbiologic diagnosis in immunocompromised individuals with severe respiratory failure.
Nonpharmacological Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease.
Panzuti G, Zanaboni T, Pisani L
Semin Respir Crit Care Med · 2026 Jun · PMID 41734791 · Publisher ↗
Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are acute events characterized by rapid worsening of dyspnea, cough, and sputum production, often leading to gas exchange impairment, ventilatory fai...
Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are acute events characterized by rapid worsening of dyspnea, cough, and sputum production, often leading to gas exchange impairment, ventilatory failure, and hospitalization. While pharmacological therapy remains central for managing the acute phase, nonpharmacological interventions play a crucial role in stabilizing patients, reducing complications, and promoting functional recovery. Respiratory strategies-including conventional oxygen therapy, high-flow nasal cannula, noninvasive ventilation, and invasive mechanical ventilation-are tailored to disease severity and underlying pathophysiology, aiming to unload respiratory muscles, improve ventilation, and optimize gas exchange. Pulmonary rehabilitation (PR) is essential to counteract skeletal and respiratory muscle dysfunction, sarcopenia, and exercise intolerance, thereby enhancing quality of life (QoL) and physical performance. Nutritional management addresses malnutrition, negative energy balance, and micronutrient deficiencies, supporting muscle preservation, immune function, and overall recovery. Home-based care models, including hospital-at-home programs and telerehabilitation, reduce hospital stays, facilitate early discharge, and improve access to structured PR programs. Structured self-management strategies and individualized exacerbation action plans empower patients, enhance symptom control, and reduce hospital readmissions, although their effectiveness may vary according to patient health literacy. Integrating these interventions into a comprehensive, multidisciplinary care pathway addresses both acute physiological derangements and long-term functional decline. Emerging digital health solutions-including telemonitoring, wearable sensors, and artificial intelligence-based predictive models-offer opportunities for early detection, personalized interventions, and enhanced patient engagement. This review synthesizes current evidence on nonpharmacological management of AECOPD, highlighting practical strategies to optimize respiratory support, rehabilitation, nutritional interventions, and self-management, ultimately aiming to accelerate recovery, prevent relapse, and improve QoL in this high-risk patient population.
The Impact of Acute Exacerbations of COPD on Patient Outcomes.
Fantin A, Castaldo N, Sartori G … +4 more , Chiara CD, Morana G, Patruno V, Crisafulli E
Semin Respir Crit Care Med · 2026 Jun · PMID 41734785 · Publisher ↗
Acute exacerbations of chronic obstructive pulmonary disease (ECOPD) represent major inflection points in the natural history of the disease, driving accelerated functional decline, reduced autonomy, and increased cardio...
Acute exacerbations of chronic obstructive pulmonary disease (ECOPD) represent major inflection points in the natural history of the disease, driving accelerated functional decline, reduced autonomy, and increased cardiovascular and mortality risk. This narrative review synthesizes current evidence on the multidimensional impact of ECOPD on patient outcomes, spanning respiratory physiology, muscle function, exercise capacity, inflammation, cardiovascular vulnerability, survival, and performance status. Across physiological domains, ECOPD induces sustained functional impairments that may take weeks to months to normalize. Muscular and functional consequences are similarly profound: Skeletal and diaphragmatic muscle dysfunction, reduced mobility, and long-lasting decrements in exercise tolerance contribute to prolonged disability and reduced quality of life. Systemic and airway inflammation often persists long after the acute phase, promoting recurrent exacerbations, progressive lung injury, and cardiometabolic complications. Cardiovascular instability is a defining feature of the post-ECOPD period, with markedly elevated short- and medium-term risks of myocardial infarction, stroke, arrhythmias, and acute heart failure. Mortality remains substantial post-ECOPD, and recurrent readmissions reflect ongoing physiological fragility. Autonomy, performance status, and health-related quality of life frequently remain impaired months after discharge, emphasizing the long-term functional burden of ECOPD. ECOPD recovery is therefore a subacute, high-risk phase of multisystem instability that requires integrated respiratory, cardiovascular, functional, and rehabilitative strategies. Future directions should prioritize personalized post-ECOPD care, guided by treatable traits, performance-based assessments, biomarkers, and digital monitoring. The development of ECOPD-specific functional endpoints and patient-centered outcomes represents a critical unmet need to advance research and improve long-term prognosis.
Inflammatory Response in Exacerbations of COPD: Clinical and Predictive Roles of C-Reactive Protein.
Sartori G, Fantin A, Sartori F … +1 more , Crisafulli E
Semin Respir Crit Care Med · 2026 Jun · PMID 41730300 · Publisher ↗
Acute exacerbations of chronic obstructive pulmonary disease (ECOPD) are pivotal events that accelerate lung function decline, impair quality of life, and increase the risk of hospitalization and mortality. Beyond episod...
Acute exacerbations of chronic obstructive pulmonary disease (ECOPD) are pivotal events that accelerate lung function decline, impair quality of life, and increase the risk of hospitalization and mortality. Beyond episodic airway deterioration, ECOPD should be conceptualized as a systemic inflammatory syndrome driven by dysregulated responses to infectious or environmental triggers. Among inflammatory biomarkers, C-reactive protein (CRP) is the most extensively studied in ECOPD because of its rapid kinetics, wide availability, and clinical accessibility. This narrative review aims to summarize the diagnostic, therapeutic, and prognostic role of CRP in ECOPD. CRP levels rise sharply during exacerbations, particularly in pneumonic events, supporting diagnostic stratification and differentiation from non-bacterial or eosinophilic phenotypes. When integrated with clinical assessment, CRP improves diagnostic accuracy and informs antibiotic stewardship; CRP-guided strategies have been shown to reduce unnecessary antibiotic use without compromising clinical outcomes. Elevated CRP at presentation is associated with greater exacerbation severity, increased need for ventilatory support, and longer hospital stay. Persistently elevated CRP at discharge is linked to early relapse and readmission, while higher levels have also been associated with thromboembolic and cardiovascular risk, highlighting the systemic consequences of ECOPD. Despite these advantages, CRP is inherently nonspecific, influenced by comorbidities and timing of measurement, and optimal thresholds vary across clinical settings. CRP is a robust and accessible biomarker that provides valuable diagnostic, therapeutic, and prognostic information in ECOPD. Its incorporation into routine clinical practice can improve patient stratification, support antibiotic stewardship, and enhance monitoring of individuals at high risk of adverse outcomes. Future advances are likely to rely on longitudinal interpretation of CRP and its integration into multimarker panels and predictive models, combined with clinical variables and digital health data, to enable phenotype-driven management and precision medicine approaches in ECOPD.
Epidemiology of COPD Exacerbations.
Lopez-Campos JL, Jiménez Ruiz JA, Quintana-Gallego E
Semin Respir Crit Care Med · 2026 Jun · PMID 41730299 · Publisher ↗
Chronic obstructive pulmonary disease (COPD) exacerbations represent the most common acute event and the one with the greatest medium- to long-term clinical and prognostic impact, acting as a key driver of functional dec...
Chronic obstructive pulmonary disease (COPD) exacerbations represent the most common acute event and the one with the greatest medium- to long-term clinical and prognostic impact, acting as a key driver of functional decline, deterioration in quality of life, and constituting a substantial share of the morbidity, mortality, and healthcare costs attributable to the disease. This review synthesizes the most relevant epidemiological evidence on the frequency, distribution, and environmental determinants of exacerbations, with particular emphasis on longitudinal trends, seasonal patterns, and economic burden. Overall, the last decades have seen a decline in exacerbation rates within the context of clinical trials; however, analyses based on hospital registries are constrained by methodological limitations, notably reliance on International Classification of Diseases-coded case identification and a predominant focus on severe events. Temporal trajectories also vary by region: in Spain, decrease followed by subsequent rebounds have been described, with a more pronounced increase among women, while other European and non-European settings report divergent patterns. Seasonality emerges as a robust feature in temperate climates, with winter peaks and a consistent association between low temperatures (and thermal variability) and higher admission rates and exacerbation severity. Ambient air pollution (PM/PM, NO, SO, O) is linked to an increased risk of exacerbation, potentially with lagged effects, through biologically plausible pathways mediated by oxidative stress and inflammation. Finally, we discuss the impact of exposures arising from environmental disasters (wildfires, volcanic eruptions, and oil spills), illustrated by recent events in Spain, and integrate the economic dimension, underscoring that exacerbations account for a large proportion of the total cost of COPD.
Physiopathology of Exacerbation of Chronic Obstructive Pulmonary Disease.
Tonelli R, Michelacci S, Verduri A … +1 more , Clini E
Semin Respir Crit Care Med · 2026 Jun · PMID 41679730 · Publisher ↗
Acute exacerbations of chronic obstructive pulmonary disease (ECOPD) represent crucial events in the natural history of the disease. These are mainly characterized by abrupt worsening of respiratory symptoms, that is, dy...
Acute exacerbations of chronic obstructive pulmonary disease (ECOPD) represent crucial events in the natural history of the disease. These are mainly characterized by abrupt worsening of respiratory symptoms, that is, dyspnea, cough, and sputum production. Defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as acute symptom deterioration requiring additional therapy, ECOPD markedly worsens lung function and has strong clinical outcomes for any patient involved. Pathobiology is multidimensional, arising from inflammatory, mechanical, and cardiovascular perturbations that are linked to each other and are likely to generate a self-reinforcing cycle of respiratory derangement and/or failure. Indeed, lung inflammation and injuries intensify airflow limitation, which in turn promotes air trapping and dynamic hyperinflation, increases elastic loads, and predisposes to respiratory muscle dysfunction. The resulting alterations of the blood gases may lead to even severe respiratory system failure and to an increased risk of death.
Limitations in the Design of Critical Care Studies and Suggestions for Future Research Directions.
Meduri GU, Lannini S, Smit JM
Semin Respir Crit Care Med · 2026 Feb · PMID 41539328 · Publisher ↗
Glucocorticoid (GC) therapy has been a cornerstone of critical care; however, its full potential has been constrained by fixed-dose regimens and trial designs that predate current insights into the dynamic, phase-specifi...
Glucocorticoid (GC) therapy has been a cornerstone of critical care; however, its full potential has been constrained by fixed-dose regimens and trial designs that predate current insights into the dynamic, phase-specific functions of glucocorticoid receptor α (GRα). This study shifts focus from mechanistic pathways to the clinical implications of phase-adaptive care, emphasizing how GC therapy can be optimized through individualized, response-guided strategies tailored to illness trajectory and biological variability. Rather than reiterating GRα's mechanistic role, which is discussed in Chapter 3, this work highlights its practical relevance in therapeutic decision-making across the three sequential phases of critical illness: priming, modulatory, and restorative. In this clinically oriented framework, phase-specific treatment adjustments are informed by real-time changes in systemic stress markers, immune dynamics, and metabolic indicators. Earlier randomized controlled trials were instrumental in establishing safety but often failed to account for evolving physiological demands or receptor variability, contributing to inconsistent outcomes. To bridge this translational gap, this study proposes the integration of response-guided protocols utilizing accessible clinical biomarkers-such as C-reactive protein, interleukin-6, D-dimer, and lactate-allowing for adaptive dosing and tapering strategies aligned with patient-specific recovery patterns. Moving beyond pharmacologic dosing, the study outlines adjunctive clinical strategies-including targeted micronutrient supplementation and microbiome-supportive therapies-not as theoretical possibilities but as practical co-interventions that can be incorporated into intensive care unit protocols. Furthermore, it explores how artificial intelligence-enabled clinical decision systems and adaptive trial designs can operationalize precision care by dynamically stratifying patients and tailoring interventions to shifting biological profiles. Together, these applied strategies support a transition from static treatment paradigms to a precision medicine model in critical care-one that aligns GC therapy with individualized recovery trajectories, maximizes therapeutic responsiveness, and reduces treatment-related risks through multimodal, phase-responsive interventions.
Pulmonary Infections in Patients Receiving Corticosteroids and Other Immunomodulators.
Hartman ES, Cavallazzi R
Semin Respir Crit Care Med · 2026 Apr · PMID 41475423 · Publisher ↗
The prevalence of immunosuppression in the general population has been increasing over time due to a combination of factors, including advances in health care and the emergence of new therapies. Population-based studies...
The prevalence of immunosuppression in the general population has been increasing over time due to a combination of factors, including advances in health care and the emergence of new therapies. Population-based studies show that approximately 3% of the population are prescribed systemic corticosteroid therapy at least once a year. Additionally, the number of immunomodulatory agents, such as biologics and small molecules, continues to grow. The chronic use of systemic corticosteroid and immunomodulating agents has an impact not only on the incidence of patients with pneumonia, but also on their microbiology, clinical presentation, and outcomes. Recent cohort studies show that chronic corticosteroid therapy is one of the leading causes of immunosuppression in patients with nosocomial pneumonia and community-acquired pneumonia requiring hospitalization. Different immunomodulating agents can have varying effects on the immune system; hence, each agent should be individually analyzed when assessing their impact on the immune system. Important factors to consider are the dose and duration of immunosuppressive medications, as well as their indication. Many of the conditions for which corticosteroids and immunomodulators are prescribed also lead to immunosuppression. In the study, we aim to assess the literature on the risk of pneumonia associated with the use of chronic systemic corticosteroid therapy and immunomodulating agents, particularly biologics and small molecules. We also discuss clinical manifestations and management of patients who develop pneumonia while on these therapies.
Monographic Issue on Glucocorticoid Therapy in Critical Illness and Respiratory Disease.
Meduri GU, Torres A
Semin Respir Crit Care Med · 2026 Feb · PMID 41418814 · Publisher ↗
Abstract loading — click title to view on PubMed.
Advances in Invasive Diagnostics in Lung Cancer.
Roy P, Shadchehr S, Gonzalez AV
Semin Respir Crit Care Med · 2025 Oct · PMID 41386288 · Publisher ↗
Lung cancer is the leading cause of cancer incidence and mortality worldwide. Pulmonologists play a central role in the timely, guideline-concordant diagnosis and staging of lung cancer. Minimally invasive procedures mus...
Lung cancer is the leading cause of cancer incidence and mortality worldwide. Pulmonologists play a central role in the timely, guideline-concordant diagnosis and staging of lung cancer. Minimally invasive procedures must also provide sufficient tissue for advanced molecular testing, particularly in light of the evolving landscape of lung cancer treatment. Advanced diagnostic bronchoscopy has developed at an accelerated pace over the last two decades, with a widening array of tools and technologies. Minimally invasive diagnostic sampling is typically guided by the suspected stage of disease. Linear endobronchial ultrasound has an established role in the diagnosis and staging of lung cancer. Novel technologies targeting the lung periphery aim to overcome the challenge of successfully reaching peripheral lung lesions and bridge the diagnostic gap by acquiring adequate samples. Advanced imaging modalities are combined with electromagnetic navigation, ultrathin bronchoscopy, and robotic-assisted bronchoscopy platforms. Herein, we review recent advances in invasive diagnostics in lung cancer, with a focus on interventional pulmonary procedures. The importance of strictly defined diagnostic outcomes in the advanced bronchoscopy literature is highlighted, as is the ongoing need for comparative effectiveness studies.
Advanced Pulmonary Sarcoidosis.
Spagnolo P, Dhanani Z, Cameli P … +2 more , Fiorentù G, Gupta R
Semin Respir Crit Care Med · 2025 Dec · PMID 41380740 · Publisher ↗
In sarcoidosis, pulmonary manifestations are almost universal; however, their severity ranges from asymptomatic to respiratory failure and death. Approximately 20% of patients progress to advanced pulmonary sarcoidosis (...
In sarcoidosis, pulmonary manifestations are almost universal; however, their severity ranges from asymptomatic to respiratory failure and death. Approximately 20% of patients progress to advanced pulmonary sarcoidosis (APS), a disease phenotype that is driven mostly by pulmonary fibrosis and associated complications, including bronchiectasis, chronic pulmonary aspergillosis, and pulmonary hypertension, which may result from multiple mechanisms. APS may be burnt out but is often active as confirmed by F-fluorodeoxyglucose-PET. APS is a major cause of morbidity and mortality in patients with sarcoidosis, but its natural history is largely unknown and evidence-based treatment guidelines are lacking. Here, we review the major patterns of APS with emphasis on clinical manifestations, pathophysiology, and management, although this is based on expert opinion and may include, based on the predominant disease phenotype, anti-inflammatory/immunosuppressive treatment, antifibrotics, pulmonary rehabilitation, antibiotics, vasodilators, and, in highly selected patients, lung transplantation.
Neurosarcoidosis in Critical Care, Internal, and Pulmonary Medicine: A Practical Approach.
Queisi MM, Pardo CA
Semin Respir Crit Care Med · 2025 Dec · PMID 41371265 · Full text
Neurosarcoidosis is a rare but clinically significant manifestation of sarcoidosis, often presenting with diverse neurologic symptoms that can lead to permanent disability if left untreated. This review aims to provide i...
Neurosarcoidosis is a rare but clinically significant manifestation of sarcoidosis, often presenting with diverse neurologic symptoms that can lead to permanent disability if left untreated. This review aims to provide internists, pulmonologists, nonneurologist clinicians, and critical care specialists with a structured, pragmatic approach to the evaluation, diagnosis, and management of neurosarcoidosis in two distinct patient groups: those with a known diagnosis of systemic sarcoidosis and those with no prior history of sarcoidosis. We emphasize the recognition of key acute clinical syndromes such as seizures, stroke, neuroendocrinopathy, hydrocephalus, meningeal disease, myelopathy, and infectious complications that may be encountered in emergency and critical care scenarios. The management approach, which includes first-line therapies such as glucocorticoids and immunomodulatory treatments such as TNF inhibitors and IL-6 inhibitors, is now accepted in the critical care setting to minimize the development of long-standing neurological complications associated with neurosarcoidosis. Furthermore, there is a critical need for a safe and effective transition to steroid-sparing medications for long-term disease control, while closely monitoring the risk for infections, such as tuberculosis and opportunistic infections, metabolic disturbances, and other complications. Given the significance of neurosarcoidosis as a severe manifestation of systemic sarcoidosis, a multidisciplinary approach is essential to effectively manage both neurological and systemic manifestations.
Top 7 Diagnostic Dilemmas in Cardiac Sarcoidosis: Lessons from Clinical Practice.
Wagle AA, Kuzma I, Gilotra NA
Semin Respir Crit Care Med · 2025 Dec · PMID 41285391 · Publisher ↗
Cardiac sarcoidosis (CS) is a potentially fatal but often underrecognized manifestation of systemic sarcoidosis. Its diagnosis remains a major clinical challenge due to nonspecific symptoms, overlapping features with oth...
Cardiac sarcoidosis (CS) is a potentially fatal but often underrecognized manifestation of systemic sarcoidosis. Its diagnosis remains a major clinical challenge due to nonspecific symptoms, overlapping features with other cardiac and genetic diseases, and the lack of a universal diagnostic gold standard. This review outlines seven key diagnostic dilemmas frequently encountered in clinical practice: (1) failure to consider CS, (2) premature attribution of findings to CS, (3) limitations and misinterpretation of echocardiogram and cardiac magnetic resonance imaging, (4) limitations of F-FDG positron emission tomography, (5) mistaking mutation for granuloma, (6) biopsy paradox, and (7) navigating diagnostic definitions. Each dilemma highlights the need for careful clinical reasoning, multimodal imaging interpretation, integration of data, and expert multidisciplinary collaboration. Ultimately, a nuanced, patient-centered, and evidence-informed approach is essential to improve diagnosis and outcomes in patients with suspected CS.
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