Expert review of respiratory medicine最新文献

Introduction: Severe eosinophilic asthma (SEA) is characterized by persistent type 2 airway inflammation and frequent exacerbations despite maximal conventional therapy. The advent of biologics targeting interleukin-5, its receptor, and upstream mediators has markedly changed disease management, offering new therapeutic opportunities for patients with uncontrolled disease.

Areas covered: This review evaluates the safety profiles of currently approved biologics for SEA, including mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab. Evidence was synthesized from randomized controlled trials, open-label extension studies, real-world data, and pharmacovigilance reports. Mepolizumab demonstrates consistent safety with mainly mild adverse events, while reslizumab is effective but rarely associated with myalgia, creatine phosphokinase elevations, and anaphylaxis. Benralizumab shows excellent tolerability, with a low incidence of injection reactions and no excess of serious adverse events. Dupilumab is well tolerated, though blood eosinophilia and conjunctivitis may occur. Tezepelumab approval was supported by favorable safety signals, with mild infections and headache as the most frequent events.

Expert opinion: Current evidence indicates that biologic therapies for SEA are safe and well tolerated, with serious adverse events being rare. Nevertheless, long-term and comparative safety data remain limited, and ongoing pharmacovigilance and post-marketing surveillance are essential to fully define risk profiles.

Introduction: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in young children, causing significant morbidity and mortality worldwide. Early life RSV LRTI adversely impacts the developing lung and immune systems, and has been linked to subsequent long-term respiratory sequelae. Children with Down syndrome (DS), with the combined attributes of structural and functional airway anomalies, immune dysregulation, and congenital heart defects are at heightened risk for increased RSV severity and may benefit from passive immunization of RSV immunoprophylaxis.

Areas covered: This article reviews the evidence for the burden of RSV LRTI, the subsequent health sequelae of RSV LRTI, and the effect of RSV immunoprophylaxis in children with DS. The broader public health value of RSV immunoprophylaxis in improving health-related quality of life beyond RSV-associated short-term morbidity is explored. A systematic search of PubMed, Google Scholar, and MEDLINE on July 2025 was conducted.

Expert opinion: New RSV prophylactic products have been demonstrated to be highly effective in reducing the risk of RSV LRTI in infants and certain high-risk children. Children with DS may benefit from these preventive strategies during early childhood by reducing respiratory and non-respiratory related disease burden and improving quality of life.

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality. It is a complex and heterogeneous condition defined by the presence of an incompletely reversible airflow obstruction.

Area covered: Airway inflammation and remodeling are central to the pathogenesis of this airflow limitation, and eosinophilic or type 2 inflammation has emerged as a measurable and treatable therapeutic target in those patients in whom it is identified. This review addresses the role of type 2 inflammation in COPD pathogenesis as well as current and future therapeutic options.

Expert opinion: The last 15 years has seen the emergence of a precision medicine, type-2 biomarker directed approach to the use of inhaled corticosteroids in COPD, resulting in better targeting of treatment and an increased benefit/risk ratio. We have also seen the approval of first biological therapy against type 2 inflammation in COPD. There is increasing interest in biomarker directed early intervention to prevent progression or even the development of COPD.

Introduction: Pleural infection is a common condition associated with significant morbidity, mortality, and prolonged hospital stay. Whilst antibiotics and chest tube drainage comprise initial management, over one-third of patients experience medical treatment failure, necessitating intrapleural enzyme therapy (IET) or surgery. This review examines advances in diagnosis and management of treatment failure in pleural infection.

Areas covered: A literature search of PubMed, Embase, and Cochrane Library (January 2005- April 2025) was performed using keywords related to pleural infection, diagnostics, biomarkers, and treatment interventions. Treatment failure emerged as a multifactorial process involving delayed presentation, structural and physiological barriers such as increased pleural fluid viscosity, septation formation, pleural thickening, and biofilm development, alongside host factors and microbiological complexity. We review current strategies including antibiotics, chest tube drainage, IET (tPA + DNase), and surgical options, alongside emerging modalities such as next-generation sequencing, pleural biopsy, medical thoracoscopy, saline irrigation, and indwelling catheters.

Expert opinion: Early identification of treatment failure within 48 hours is crucial for guiding escalation. A precision medicine approach integrating microbiological, radiological, and host-response data may redefine standards of care and improve outcomes. Future priorities include early risk stratification, biomarker-guided therapy, microbiome-informed antibiotic strategies, and improving global access to effective treatments.

Introduction: Precision cut lung slices (PCLS) are ex vivo models to study lung diseases. They have numerous advantages related to the presence of different cell types and extracellular matrix. They are an excellent platform to study the biological effects of delivering small molecules with therapeutic potential, such as non-coding RNAs. The aim of this review is to summarize the miRNA and siRNA research on the PCLS model to date and consider therapeutic potential of the proposed solutions.

Areas covered: The review focuses on the methodological aspects of delivery of RNA-based formulations, such as miRNA and siRNA, in the PCLSs model. It covers the area of RNA/miRNA isolation from PCLSs and methods of delivering miRNA and siRNA to PCLSs. Analysis of the reported solutions indicated the need for standardization, regarding the information on transfection efficacy at the RNA and protein levels is incomplete.

Expert opinion: PCLSs are a promising model for studying small RNA-based drug delivery systems. However, existing models require consistent criteria and methods to assess the biological effect. Because of the heterogeneity of PCLS slices within the single studies, future experiments would benefit from including more independent replicates performed using different methods, in order to improve their reproducibility.

Introduction: Both asthma and depression are common diseases that significantly contribute to morbidity and mortality worldwide.

Area covered: This review was conducted through PubMed as a search engine and discusses the similarities with respect to epidemiology, contributing factors and disease pathogenesis for both depression and asthma. The goal of this review was to assess the available evidence on the links between asthma and depression. These diseases share common epidemiologic characteristics including an increased prevalence in higher income countries, and each is an independent risk factor for development of the other. They share common risk factors including genetic, maternal, and socioeconomic factors. Common pathophysiologic mechanisms in asthma and depression include similar cytokine signaling pathways. Despite the striking similarities in terms of epidemiology, risk factors, and pathophysiologic pathways, few studies have investigated the effects of treating depression on asthma outcomes. The intersection between asthma and depression is remarkable and the available literature suggests treatment of co-morbid depression may improve asthma outcomes. Further investigation into the treatment of depression in asthma is warranted.

Expert opinion: Understanding the connection between depressive symptoms and asthma is important for improving asthma outcomes. High-quality studies assessing anti-depressant therapy in those with asthma and depressive symptoms are needed.

Introduction: Asthma is a common chronic disease which disproportionately affects women. While sex hormones are hypothesized to be involved in changes to asthma during puberty, menstruation, pregnancy and menopause, more research is needed to understand the precise mechanisms involved.

Areas covered: This review summarizes the challenges in the treatment of asthma during puberty, pregnancy and menopause. PubMed was searched in the past 10 years for 'puberty/pregnancy/menopause' AND 'asthma.' Non-adherence to asthma treatment is a particular challenge in adolescence and pregnancy. Studies have shown a reduction in the use of inhaled corticosteroids, short acting beta agonists and oral corticosteroids in the first trimester compared to pre-pregnancy. Women perceive a risk of these medications which may contribute to non-adherence during pregnancy. Greater understanding of specific risks of asthma on pregnancy outcomes will assist healthcare professionals in making considered decisions for optimized treatment, including provision of an action plan and correction of inhaler technique. During menopause, new onset asthma can occur, and women with respiratory symptoms should be investigated for an asthma diagnosis so as to receive the required treatment.

Expert opinion: A personalized medicine approach which assesses treatable traits and provides holistic care may improve outcomes for women with asthma during puberty, pregnancy and menopause.

Introduction:  Lung transplant candidates (LTC) and recipients (LTR) frequently suffer from impaired exercise capacity and reduced quality of life. Telerehabilitation (TR) offers a viable alternative for patients with limited access to center-based rehabilitation.

Methods: This systematic review assessed TR's clinical efficacy in LTC and LTR populations. Methods: Eligible trials were identified by searching the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus databases. Continuous data were extracted for relevant outcomes and analyzed using the RevMan software as the pooled mean difference (PMD) and 95%CI in a fixed-effect meta-analysis model.

Results: Seven studies (n = 230; mean age = 54.2 years) were included. TR significantly improved 6-minute walk distance in LTR (PMD:65.78 m [5.15-126.42], p = 0.03, I² = 0%).The Duke Activity Status Index scores showed significant improvement in LTC and LTR (PMD:-11.98 [-17.99-5.97], p < 0.0001, I² = 83%).

Conclusion:  Several telerehabilitation trials have suggested potential benefits in improving exercise capacity, physical fitness, and quality of life in LTC and LTR, both before and after transplantation. However, the overall quality of the evidence remains low. Further research is needed to evaluate the impact of telerehabilitation on clinical outcomes, and feasibility, and cost-effectiveness of these rehabilitation delivery model in this population.

Registration: The review protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42022378573).

Introduction: Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by the accumulation of surfactant-derived material in the alveolar spaces due to impaired macrophage function. Autoimmune PAP (aPAP) is caused by neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) and accounts for over 90% of cases. PAP causes respiratory symptoms and, in severe cases, respiratory failure necessitating lung transplantation. Early diagnosis and intervention are crucial. This narrative review is based on a PubMed literature search last performed 30 March 2025.

Areas covered: This review examines the pathophysiology, diagnosis, and treatment of PAP. We focus on GM-CSF autoantibody testing and bronchoalveolar lavage (BAL) for diagnosis and treatment modalities including whole lung lavage (WLL) and inhaled GM-CSF therapy. The use of rituximab, plasmapheresis, and lung transplantation for refractory cases is also discussed.

Expert opinion: The advent of WLL and GM-CSF has advanced the care of patients with aPAP. However, challenges still remain in managing treatment-resistant cases, and for patients with non-autoimmune forms of PAP where treatment options are more limited. Further research is needed to optimize therapeutic strategies, especially for patients who do not respond to first-line treatments. Timely diagnosis and early intervention remain essential for improving patient outcomes.

Introduction: Severe asthma in children is a chronic, heterogeneous condition that significantly impacts quality of life and poses management challenges. The introduction of biological therapies has transformed treatment paradigms, offering targeted interventions for patients with specific phenotypes.

Areas covered: This review provides an overview of the current evidence on biologic therapies approved for pediatric severe asthma, including omalizumab, mepolizumab, benralizumab, and dupilumab. We discuss their mechanisms of action, pivotal clinical trials, real-world data, and practical considerations for use. A comprehensive literature search was performed using PubMed, Embase, and major conference proceedings up to May 2025. We also examine emerging biologic agents targeting upstream pathways, such as tezepelumab and anti-IL-33 therapies, and explore the concept of asthma remission and its implications for long-term disease trajectories.

Expert opinion: Biologics represent a significant advancement in pediatric asthma management, enabling for tailored treatments based on underlying pathophysiology. However, challenges persist in optimizing patient selection, enhancing access, and comprehending long-term outcomes. Future research should focus on early intervention strategies, cost-effectiveness analyses, and the potential for disease-modifying effects in children.