Semin Respir Crit Care Med
· 2024 Jun · PMID 38547917
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Connective tissue diseases (CTD) are heterogeneous, immune-mediated inflammatory disorders often presenting with multiorgan involvement. With the advent of high-resolution computed tomography, CTD-related pleuritis-pleur...Connective tissue diseases (CTD) are heterogeneous, immune-mediated inflammatory disorders often presenting with multiorgan involvement. With the advent of high-resolution computed tomography, CTD-related pleuritis-pleural thickening and effusion-is now increasingly recognized early in the disease trajectory. The natural history of CTD-related pleural effusions varies from spontaneous resolution to progressive fibrothorax with ventilatory impairment. Treatment of the underlying CTD is necessary to manage the pleural disease. Depending on the degree of symptom burden and physiological insult, specific treatment of pleural disease can include monitoring, repeated aspirations, systemic anti-inflammatory medication, and surgical decortication.
Semin Respir Crit Care Med
· 2024 Jun · PMID 38547916
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The assessment of pulmonary nodules is a common and often challenging clinical scenario. This evaluation becomes even more complex in patients with connective tissue diseases (CTDs), as a range of disease-related factors...The assessment of pulmonary nodules is a common and often challenging clinical scenario. This evaluation becomes even more complex in patients with connective tissue diseases (CTDs), as a range of disease-related factors must also be taken into account. These diseases are characterized by immune-mediated chronic inflammation, leading to tissue damage, collagen deposition, and subsequent organ dysfunction. A thorough examination of nodule features in these patients is required, incorporating anatomic and functional information, along with patient demographics, clinical factors, and disease-specific knowledge. This integrated approach is vital for effective risk stratification and precise diagnosis. This review article addresses specific CTD-related factors that should be taken into account when evaluating pulmonary nodules in this patient group.
Semin Respir Crit Care Med
· 2024 Jun · PMID 38547915
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Systemic Lupus Erythematosus (SLE) is a multifaceted, multisystem autoimmune disorder with diverse clinical expressions. While prevalence reports vary widely, pulmonary involvement accounts for significant morbidity and...Systemic Lupus Erythematosus (SLE) is a multifaceted, multisystem autoimmune disorder with diverse clinical expressions. While prevalence reports vary widely, pulmonary involvement accounts for significant morbidity and mortality in SLE. This comprehensive review explores the spectrum of pulmonary disease in SLE, including upper airway manifestations (e.g., laryngeal affection), lower airway conditions (e.g., bronchitis, bronchiolitis, bronchiectasis), parenchymal diseases (e.g., interstitial lung disease, acute lupus pneumonitis, diffuse alveolar hemorrhage), pleural diseases (e.g., serositis, shrinking lung syndrome), and vascular diseases (e.g., pulmonary arterial hypertension, pulmonary embolism, acute reversible hypoxemia syndrome). We discuss diagnostic modalities, treatment strategies, and prognosis for each pulmonary manifestation. With diagnostics remaining a challenge and with the absence of standardized treatment guidelines, we emphasize the need for evidence-based guidelines to optimize patient care and improve outcomes in this complex disease.
Semin Respir Crit Care Med
· 2024 Jun · PMID 38531379
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Systemic sclerosis is a multisystem connective tissue disease that is associated with substantial morbidity and mortality. Visceral organ involvement is common in patients with systemic sclerosis and occurs independently...Systemic sclerosis is a multisystem connective tissue disease that is associated with substantial morbidity and mortality. Visceral organ involvement is common in patients with systemic sclerosis and occurs independently of skin manifestations. Pulmonary hypertension (PH) is an important and prevalent complication of systemic sclerosis. The clinical classification of PH cohorts conditions with similar pathophysiological mechanisms into one of five groups. While patients with systemic sclerosis can manifest with a spectrum of pulmonary vascular disease, notable clinical groups include group 1 pulmonary arterial hypertension (PAH) associated with connective tissues disease, PAH with features of capillary/venous involvement, group 2 PH associated with left heart disease, and group 3 PH associated with interstitial lung disease. Considerable efforts have been made to advance screening methods for PH in systemic sclerosis including the DETECT and ASIG (Australian Scleroderma Interest Group) composite algorithms. Current guidelines recommend annual assessment of the risk of PAH as early recognition may result in attenuated hemodynamic impairment and improved survival. The treatment of PAH associated with systemic sclerosis requires a multidisciplinary team including a PH specialist and a rheumatologist to optimize immunomodulatory and PAH-specific therapies. Several potential biomarkers have been identified and there are several promising PAH therapies on the horizon such as the novel fusion protein sotatercept. This chapter provides an overview of PH in systemic sclerosis, with a specific focus on group 1 PAH.
Semin Respir Crit Care Med
· 2024 Jun · PMID 38499196
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Pulmonary hypertension (PH) is a known complication of certain connective tissue diseases (CTDs), with systemic sclerosis (SSc) being the most common in the Western world. However, PH in association with non-SSc CTD such...Pulmonary hypertension (PH) is a known complication of certain connective tissue diseases (CTDs), with systemic sclerosis (SSc) being the most common in the Western world. However, PH in association with non-SSc CTD such as systemic lupus erythematous, mixed connective tissue disease, and primary Sjögren's syndrome constitutes a distinct subset of patients with inherently different epidemiologic profiles, pathophysiologic mechanisms, clinical features, therapeutic options, and prognostic implications. The purpose of this review is to inform a practical approach for clinicians evaluating patients with non-SSc CTD-associated PH.The development of PH in these patients involves a complex interplay between genetic factors, immune-mediated mechanisms, and endothelial cell dysfunction. Furthermore, the broad spectrum of CTD manifestations can contribute to the development of PH through various pathophysiologic mechanisms, including intrinsic pulmonary arteriolar vasculopathy (pulmonary arterial hypertension, Group 1 PH), left-heart disease (Group 2), chronic lung disease (Group 3), chronic pulmonary artery obstruction (Group 4), and unclear and/or multifactorial mechanisms (Group 5). The importance of diagnosing PH early in symptomatic patients with non-SSc CTD is highlighted, with a review of the relevant biomarkers, imaging, and diagnostic procedures required to establish a diagnosis.Therapeutic strategies for non-SSc PH associated with CTD are explored with an in-depth review of the medical, interventional, and surgical options available to these patients, emphasizing the CTD-specific considerations that guide treatment and aid in prognosis. By identifying gaps in the current literature, we offer insights into future research priorities that may prove valuable for patients with PH associated with non-SSc CTD.
Semin Respir Crit Care Med
· 2024 Jun · PMID 38484788
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Interstitial lung disease (ILD) is a common pulmonary complication of rheumatoid arthritis (RA), causing significant morbidity and mortality. Optimal treatment for RA-ILD is not yet well defined. Reliable prognostic indi...Interstitial lung disease (ILD) is a common pulmonary complication of rheumatoid arthritis (RA), causing significant morbidity and mortality. Optimal treatment for RA-ILD is not yet well defined. Reliable prognostic indicators are largely byproducts of prior ILD progression, including low or decreasing forced vital capacity and extensive or worsening fibrosis on imaging. In the absence of validated tools to predict treatment response, decisions about whether to initiate or augment treatment are instead based on clinical judgment. In general, treatment should be initiated in patients who are symptomatic, progressing, or at high risk of poor outcomes. Retrospective data suggest that mycophenolate mofetil, azathioprine, and rituximab are likely effective therapies for RA-ILD. Abatacept is also emerging as a potential first-line treatment option for patients with RA-ILD. Further, recent data demonstrate that immunosuppression may be beneficial even in patients with a usual interstitial pneumonia (UIP) pattern on imaging, suggesting that immunosuppression should be considered irrespective of imaging pattern. Recent randomized controlled trials have shown that antifibrotic medications, such as nintedanib and likely pirfenidone, slow forced vital capacity decline in RA-ILD. Consideration can be given to antifibrotic initiation in patients progressing despite immunosuppression, particularly in patients with a UIP pattern. Future research directions include developing tools to predict which patients will remain stable from patients who will progress, discriminating patients who will respond to treatment from nonresponders, and developing algorithms for starting immunosuppression, antifibrotics, or both as first-line therapies.
Semin Respir Crit Care Med
· 2024 Apr · PMID 38428839
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In 2023, the new European guidelines on severe community-acquired pneumonia, providing clinical practice recommendations for the management of this life-threatening infection, characterized by a high burden of mortality,...In 2023, the new European guidelines on severe community-acquired pneumonia, providing clinical practice recommendations for the management of this life-threatening infection, characterized by a high burden of mortality, morbidity, and costs for the society. This review article aims to summarize the principal evidence related to eight different questions covered in the guidelines, by also highlighting the future perspectives for research activity.
Carella F, Aliberti S, Stainer A
… +2 more, Voza A, Blasi F
Semin Respir Crit Care Med
· 2024 Apr · PMID 38395062
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Community-acquired pneumonia (CAP) is globally one of the major causes of hospitalization and mortality. Severe CAP (sCAP) presents great challenges and need a comprehensive understanding of its long-term outcomes. Cardi...Community-acquired pneumonia (CAP) is globally one of the major causes of hospitalization and mortality. Severe CAP (sCAP) presents great challenges and need a comprehensive understanding of its long-term outcomes. Cardiovascular events and neurological impairment, due to persistent inflammation and hypoxemia, contribute to long-term outcomes in CAP, including mortality. Very few data are available in the specific population of sCAP. Multiple studies have reported variable 1-year mortality rates for patients with CAP up to 40.7%, with a clear influence by age, comorbidities, and disease severity. In terms of treatment, the potential protective role of macrolides in reducing mortality emphasizes the importance of appropriate empiric antibiotic therapy. This narrative review explores the growing interest in the literature focusing on the long-term implications of sCAP. Improved understanding of long-term outcomes in sCAP can facilitate targeted interventions and enhance posthospitalization care protocols.
Semin Respir Crit Care Med
· 2024 Apr · PMID 38330995
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The clinical presentation of community-acquired pneumonia (CAP) can vary widely among patients. While many individuals with mild symptoms can be managed as outpatients with excellent outcomes, there is a distinct subgrou...The clinical presentation of community-acquired pneumonia (CAP) can vary widely among patients. While many individuals with mild symptoms can be managed as outpatients with excellent outcomes, there is a distinct subgroup of patients who present with severe CAP. In these cases, the mortality rate can reach approximately 25% within 30 days and even up to 50% within a year. It is crucial to focus attention on these patients who are at higher risk. Among the various definitions of severe CAP found in the literature, one commonly used criterion is the requirement for admission to intensive care unit. Notable epidemiological characteristics of these patients include the impact of acute cardiovascular diseases on clinical outcomes and the enduring, independent effect of pneumonia on long-term outcomes. Factors such as pathogen virulence, the presence of comorbidities, and the host response are important contributors to the pathogenesis of severe CAP. In these patients, the host response may be dysregulated and compartmentalized. Gaining a better understanding of the epidemiology and pathogenesis of severe CAP will provide a foundation for the development of new therapies for this condition. This manuscript aims to review the definition, epidemiology, and pathogenesis of severe CAP, shedding light on important aspects that can aid in the improvement of patient care and outcomes.
Campaña-Duel E, Camprubí-Rimblas M, Areny-Balagueró A
… +3 more, Quero S, Artigas A, Ceccato A
Semin Respir Crit Care Med
· 2024 Apr · PMID 38301713
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Severe community-acquired pneumonia (SCAP) is difficult to treat when caused by difficult-to-treat (DTR) pathogens because of limited treatment options and poorer clinical outcomes. Over time, several predictive scoring...Severe community-acquired pneumonia (SCAP) is difficult to treat when caused by difficult-to-treat (DTR) pathogens because of limited treatment options and poorer clinical outcomes. Over time, several predictive scoring systems based on risk factors for infection with multidrug resistant pathogens have been developed. We reviewed the available tools for identifying DTR pathogens as the cause of SCAP, both predictive scoring systems and rapid diagnostic methods, to develop management strategies aimed at early identification of DTR pathogens, reducing broad-spectrum antibiotic use and improving clinical outcomes. The scoring systems reviewed show considerable heterogeneity among them at the level of the region studied, the definition of risk factors, as well as which DTR pathogens are the target pathogens. The models described have shown limited effectiveness in reducing inappropriate antibiotic treatment or improving patient outcomes by themselves. However, predictive models could serve as a first step in identifying DTR pathogen infections as part of a larger detection algorithm. Rapid diagnostic tools, such as multiplex polymerase chain reaction, would be useful for the rapid identification of pneumonia-causing pathogens and their resistance mechanisms. In resource-limited settings, rapid tests should be limited to patients at high risk of developing SCAP due to DTR pathogens. We propose an integrative algorithm based on the different scores, taking into account local epidemiological data, where ideally each center should have an antimicrobial stewardship program.
Bassetti M, Giacobbe DR, Magnasco L
… +3 more, Fantin A, Vena A, Castaldo N
Semin Respir Crit Care Med
· 2024 Apr · PMID 38301712
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Despite advancements in health systems and intensive care unit (ICU) care, along with the introduction of novel antibiotics and microbiologic techniques, mortality rates in severe community-acquired pneumonia (sCAP) pati...Despite advancements in health systems and intensive care unit (ICU) care, along with the introduction of novel antibiotics and microbiologic techniques, mortality rates in severe community-acquired pneumonia (sCAP) patients have not shown significant improvement. Delayed admission to the ICU is a major risk factor for higher mortality. Apart from choosing the appropriate site of care, prompt and appropriate antibiotic therapy significantly affects the prognosis of sCAP. Treatment regimens involving ceftaroline or ceftobiprole are currently considered the best options for managing patients with sCAP. Additionally, several other molecules, such as delafloxacin, lefamulin, and omadacycline, hold promise as therapeutic strategies for sCAP. This review aims to provide a comprehensive summary of the key challenges in managing adults with severe CAP, focusing on essential aspects related to antibiotic treatment and investigating potential strategies to enhance clinical outcomes in sCAP patients.
Semin Respir Crit Care Med
· 2024 Feb · PMID 38286138
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In the last decade, fungal respiratory diseases have been increasingly investigated for their impact on the clinical course of people with cystic fibrosis (CF), with a particular focus on infections caused by spp. The m...In the last decade, fungal respiratory diseases have been increasingly investigated for their impact on the clinical course of people with cystic fibrosis (CF), with a particular focus on infections caused by spp. The most common organisms from this genus detected from respiratory cultures are and , followed by , , and . These species have been identified to be both chronic colonizers and sources of active infection and may negatively impact lung function in people with CF. This review article discusses definitions of aspergillosis, challenges in clinical practice, and current literature available for laboratory findings, clinical diagnosis, and treatment options for pulmonary diseases caused by spp. in people with CF.
Semin Respir Crit Care Med
· 2024 Feb · PMID 38286137
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Imaging plays an important role in the various forms of -related pulmonary disease. Depending on the immune status of the patient, three forms are described with distinct imaging characteristics: invasive aspergillosis a...Imaging plays an important role in the various forms of -related pulmonary disease. Depending on the immune status of the patient, three forms are described with distinct imaging characteristics: invasive aspergillosis affecting severely immunocompromised patients, chronic pulmonary aspergillosis affecting less severely immunocompromised patients but suffering from a pre-existing structural lung disease, and allergic bronchopulmonary aspergillosis related to respiratory exposure to species in patients with asthma and cystic fibrosis. Computed tomography (CT) has been demonstrated more sensitive and specific than chest radiographs and its use has largely contributed to the diagnosis, follow-up, and evaluation of treatment in each condition. In the last few decades, CT has also been described in the specific context of cystic fibrosis. In this particular clinical setting, magnetic resonance imaging and the recent developments in artificial intelligence have shown promising results.
Semin Respir Crit Care Med
· 2024 Feb · PMID 38286136
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Full text
The filamentous fungus causes a wide spectrum of diseases in the human lung, with being the most pathogenic and allergenic subspecies. The broad range of clinical syndromes that can develop from the presence of in the...The filamentous fungus causes a wide spectrum of diseases in the human lung, with being the most pathogenic and allergenic subspecies. The broad range of clinical syndromes that can develop from the presence of in the respiratory tract is determined by the interaction between host and pathogen. In this review, an oversight of the different clinical entities of pulmonary aspergillosis is given, categorized by their main pathophysiological mechanisms. The underlying immune processes are discussed, and the main clinical, radiological, biochemical, microbiological, and histopathological findings are summarized.
Semin Respir Crit Care Med
· 2024 Feb · PMID 38266999
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Pulmonary aspergillosis constitutes an increasingly prevalent and potentially fatal complex of mycotic diseases, caused by different species of The broad spectrum of pathological manifestations associated with pulmonary...Pulmonary aspergillosis constitutes an increasingly prevalent and potentially fatal complex of mycotic diseases, caused by different species of The broad spectrum of pathological manifestations associated with pulmonary aspergillosis necessitates a differentiation of commensalism from saprophytic colonization, hypersensitivity reactions, and true invasive infections, which highlights the importance of histopathology as a gold standard in a diagnostic setting. For the past decades, changes in terminology and contradicting contributions from different diagnostic disciplines have made the classification of pulmonary aspergillosis rather confusing. This review offers a categorization of aspergillosis lesions based on what can be histopathologically identified and distinguished, differentiating between acute invasive infection and forms of subacute, chronic, and allergic diseases and coinfections, and summarizes important manifestations of lesions associated with the different forms of pulmonary aspergillosis.
Chean D, Windsor C, Lafarge A
… +6 more, Dupont T, Nakaa S, Whiting L, Joseph A, Lemiale V, Azoulay E
Semin Respir Crit Care Med
· 2024 Apr · PMID 38266998
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Due to higher survival rates with good quality of life, related to new treatments in the fields of oncology, hematology, and transplantation, the number of immunocompromised patients is increasing. But these patients are...Due to higher survival rates with good quality of life, related to new treatments in the fields of oncology, hematology, and transplantation, the number of immunocompromised patients is increasing. But these patients are at high risk of intensive care unit admission because of numerous complications. Acute respiratory failure due to severe community-acquired pneumonia is one of the leading causes of admission. In this setting, the need for invasive mechanical ventilation is up to 60%, associated with a high hospital mortality rate of around 40 to 50%. A wide range of pathogens according to the reason of immunosuppression is associated with severe pneumonia in those patients: documented bacterial pneumonia represents a third of cases, viral and fungal pneumonia both account for up to 15% of cases. For patients with an undetermined etiology despite comprehensive diagnostic workup, the hospital mortality rate is very high. Thus, a standardized diagnosis strategy should be defined to increase the diagnosis rate and prescribe the appropriate treatment. This review focuses on the benefit-to-risk ratio of invasive or noninvasive strategies, in the era of omics, for the management of critically ill immunocompromised patients with severe pneumonia in terms of diagnosis and oxygenation.
Semin Respir Crit Care Med
· 2024 Apr · PMID 38228165
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Respiratory viruses are increasingly recognized as a cause of community-acquired pneumonia (CAP). The implementation of new diagnostic technologies has facilitated their identification, especially in vulnerable populatio...Respiratory viruses are increasingly recognized as a cause of community-acquired pneumonia (CAP). The implementation of new diagnostic technologies has facilitated their identification, especially in vulnerable population such as immunocompromised and elderly patients and those with severe cases of pneumonia. In terms of severity and outcomes, viral pneumonia caused by influenza viruses appears similar to that caused by non-influenza viruses. Although several respiratory viruses may cause CAP, antiviral therapy is available only in cases of CAP caused by influenza virus or respiratory syncytial virus. Currently, evidence-based supportive care is key to managing severe viral pneumonia. We discuss the evidence surrounding epidemiology, diagnosis, management, treatment, and prevention of viral pneumonia.
Semin Respir Crit Care Med
· 2024 Feb · PMID 38228164
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As microbiological tests play an important role in our diagnostic algorithms and clinical approach towards patients at-risk for pulmonary aspergillosis, a good knowledge of the diagnostic possibilities and especially the...As microbiological tests play an important role in our diagnostic algorithms and clinical approach towards patients at-risk for pulmonary aspergillosis, a good knowledge of the diagnostic possibilities and especially their limitations is extremely important. In this review, we aim to reflect critically on the available microbiological diagnostic modalities for diagnosis of pulmonary aspergillosis and formulate some future prospects. Timely start of adequate antifungal treatment leads to a better patient outcome, but overuse of antifungals should be avoided. Current diagnostic possibilities are expanding, and are mainly driven by enzyme immunoassays and lateral flow device tests for the detection of antigens. Most of these tests are directed towards similar antigens, but new antibodies towards different targets are under development. For chronic forms of pulmonary aspergillosis, anti- IgG antibodies and precipitins remain the cornerstone. More studies on the possibilities and limitations of molecular testing including targeting resistance markers are ongoing. Also, metagenomic next-generation sequencing is expanding our future possibilities. It remains important to combine different test results and interpret them in the appropriate clinical context to improve performance. Test performances may differ according to the patient population and test results may be influenced by timing, the tested matrix, and prophylactic and empiric antifungal therapy. Despite the increasing armamentarium, a simple blood or urine test for the diagnosis of aspergillosis in all patient populations at-risk is still lacking. Research on diagnostic tools is broadening from a pathogen focus on biomarkers related to the patient and its immune system.
Méndez R, González-Jiménez P, Mengot N
… +1 more, Menéndez R
Semin Respir Crit Care Med
· 2024 Apr · PMID 38224700
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Treatment failure and clinical stability are important outcomes in community-acquired pneumonia (CAP). It is essential to know the causes and risk factors for treatment failure and delay in reaching clinical stability in...Treatment failure and clinical stability are important outcomes in community-acquired pneumonia (CAP). It is essential to know the causes and risk factors for treatment failure and delay in reaching clinical stability in CAP. The study of both as well as the associated underlying mechanisms and host response are key to improving outcomes in pneumonia.