European Respiratory Review最新文献

Background: The morbidity and mortality associated with influenza viruses are a significant public health challenge. Annual vaccination against circulating influenza strains reduces hospitalisations and increases survival rates but requires a yearly redesign of vaccines against prevalent subtypes. The complex genetics of influenza viruses with high antigenic drift create an ongoing challenge in vaccine development to address dynamic influenza epidemiology. Understanding the evolution of influenza viruses and the vaccine's effectiveness against different types and subtypes is pivotal to designing public health measures against influenza.

Methods: We conducted a systematic review and meta-analysis of 192 705 patients, collecting information on the incidence and severity of the disease. The results of this meta-analysis were further validated using data from 6 594 765 patients from TriNetX. We analysed the prevalence of the most common influenza A virus (IAV) subtypes (H1N1 and H3N2) and influenza B virus (IBV), as well as vaccination effectiveness against them in three age groups, given that age is associated with influenza disease severity.

Results: Our analysis reflects that overall vaccination against H1N1 IAV and IBV is effective in reducing infection and influenza-related complications in children aged <5 years old, individuals between 5 and 65 years old and older adults aged >65 years old. By contrast, while vaccination against H3N2 IAV is effective in protecting against infection in infants <5 years old, it provides reduced protection against infection in older individuals.

Conclusions: Despite higher infection rates, vaccination against H3N2 remains as highly effective as vaccination against H1N1 and IBV in reducing influenza-related morbidity and mortality in all age groups. Detailing vaccine effectiveness in terms of infection protection and disease burden across different age groups is necessary for understanding vaccine impacts in terms of other outcomes, e.g. hospitalisations, mortality and disease severity; for improving vaccine formulations and public awareness; and for enhancing vaccination campaigns to improve coverage and public acceptance.

Asthma is considered severe if it remains uncontrolled despite optimal conventional therapy, characterised by poor symptom control, frequent exacerbations and increased exposure to systemic corticosteroids. This has a significant impact on morbidity, mortality and healthcare resource utilisation. Recent advances in the understanding of asthma heterogeneity and immunopathogenesis have helped delineate precise disease pathways. The discovery of these pivotal pathways has led to the development of highly effective biologic therapies. Currently available asthma biologics target immunoglobulin E, interleukin (IL)-5/IL-5Rα, IL-4Rα and thymic stromal lymphopoietin. Identification of specific asthma phenotypes, utilising easily measurable biomarkers, has paved the way towards personalised and precision asthma management. Biologic therapies play a significant role in reducing exacerbations, hospitalisations and the need for maintenance systemic steroids, while also improving the quality of life in patients with severe asthma. The evidence for their clinical efficacy comes from randomised controlled trials (RCTs), extension studies, metanalyses and real-world data. This review synthesises findings from early, pivotal RCTs and subsequent studies following the approval of biologics for severe asthma. The safety and efficacy data from these studies, completed in a variety of settings, provide practical perspectives on their application and enhance their generalisability.

The systemic use of corticosteroids for patients with severe community-acquired pneumonia (sCAP) remains controversial in clinical practice, particularly in terms of the safety profile of these drugs. This narrative review aims to analyse the available literature data concerning the safety of short-term steroid use in the treatment of sCAP, while also highlighting potential future research directions. Several trials and meta-analyses have evaluated corticosteroid therapy as an adjuvant treatment for sCAP, yielding heterogeneous results regarding its efficacy and safety. Despite the wide variability in results, it is generally accepted that steroids are not associated with a significant risk of healthcare-associated infections, gastrointestinal bleeding or acute kidney injury in patients with sCAP in the short term. Nevertheless, such drugs are linked to hyperglycaemia, necessitating regular monitoring and appropriate management. The influence of steroids on long-term outcomes and their potential risks in viral sCAP still needs to be investigated.

Silicotuberculosis, the combination of silicosis and pulmonary tuberculosis (TB), remains a substantial clinical and public health problem in high TB burden countries with silica-exposed workforces. The objectives of this narrative review are to propose a definition of silicotuberculosis which includes post-tuberculous lung disease, to emphasise the importance of understanding how the two diseases modify each other, and to identify as yet unanswered questions relevant to clinical practice and disease control and mitigation. The unique aetiological relationship between silica exposure and TB is now firmly established, as is the accelerated impairment and mortality imposed by TB on individuals with silicosis. However, the rich clinical, pathology and laboratory literature on combined disease from the pre-TB treatment era appears to have been largely forgotten. The close clinical and pathological appearance of the two diseases continues to pose a challenge to imaging, diagnosis and pathological description, while inconsistent evidence regarding TB treatment and TB preventive treatment prevails. Many other topics raise questions to be answered, inter alia: the range of phenotypes of combined disease; the rates and determinants of disease progression; the role of computed tomography in identifying and characterising combined disease; appropriate screening practice; acceptable policies of management of workers that combine risk reduction with social security; and the workplace respirable silica concentration that protects against the excess TB attributable to inhaled silica.

The Epithelial Science Expert Group convened on 18-19 October 2023, in Naples, Italy, to discuss the current understanding of the fundamental role of the airway epithelium in asthma and other respiratory diseases and to explore the future direction of patient care. This review summarises the key concepts and research questions that were raised. As an introduction to the epithelial era of research, the evolution of asthma management throughout the ages was discussed and the role of the epithelium as an immune-functioning organ was elucidated. The role of the bronchial epithelial cells in lower airway diseases beyond severe asthma was considered, as well as the role of the epithelium in upper airway diseases such as chronic rhinosinusitis. The biology and application of biomarkers in patient care was also discussed. The Epithelial Science Expert Group also explored future research needs by identifying the current knowledge and research gaps in asthma management and ranking them by priority. It was identified that there is a need to define and support early assessment of asthma to characterise patients at high risk of severe asthma. Furthermore, a better understanding of asthma progression is required. The development of new treatments and diagnostic tests as well as the identification of new biomarkers will also be required to address the current unmet needs. Finally, an increased understanding of epithelial dysfunction will determine if we can alter disease progression and achieve clinical remission.

Digital twins have recently emerged in healthcare. They combine advances in cyber-physical systems, modelling and computation techniques, and enable a bidirectional flow of information between the physical and virtual entities. In respiratory medicine, progress in connected devices and artificial intelligence make it technically possible to obtain digital twins that allow real-time visualisation of a patient's respiratory health. Advances in respiratory system modelling also enable the development of digital twins that could be used to predict the effectiveness of different therapeutic approaches for a patient. For researchers, digital twins could lead to a better understanding of the gene-environment-time interactions involved in the development of chronic respiratory diseases. For clinicians and patients, they could facilitate personalised and timely medicine, by enabling therapeutic adaptations specific to each patient and early detection of disease progression. The objective of this review is to allow the reader to explore the concept of digital twins, their feasibility in respiratory medicine, their potential benefits and the challenges to their implementation.

Objectives: Accurate measurement of exercise capacity is an important prognostic indicator for people with cystic fibrosis (pwCF); however, gold-standard, cardiopulmonary exercise tests are commonly unavailable. This review systematically describes the clinimetric properties of field exercise tests for pwCF.

Methods: A systematic review was undertaken for studies reporting field exercise tests in pwCF. Four electronic databases were searched for studies published from 1990 to January 2024. Where available, clinimetric properties reported included reliability, validity, responsiveness and interpretability.

Results: 4041 studies were identified with 153 eligible for inclusion. 10 different field exercise tests were described, including six walk/run tests (incremental shuttle walk test (ISWT), modified shuttle test-15 levels (MST-15), MST-25 levels (MST-25), 20-m shuttle test, 6-min walk test (6MWT) and 12-min walk test (12MWT)), three step tests (3-min step test (3MST), incremental step test and Alfred step test (A-STEP)) and the 1-min sit-to-stand test (1STS). Reliability was found for the ISWT, MST-15, 6MWT, 1STS and 3MST (intraclass correlation coefficients >0.80). The ISWT, MST-15 and 6MWT were found to be valid (concurrent and discriminate). Responsiveness was supported for the 6MWT only. Four tests (MST-15, 6MWT, 3MST and 1STS) demonstrated ceiling effects.

Conclusion: This review supports the reliability, validity and responsiveness of the 6MWT in pwCF. The ISWT and MST-15 were found to be valid. The 1STS is reliable and feasible, but its utility is limited by ceiling effects. The 3MST, MST-25, 20-m shuttle test, incremental step test, A-STEP and 12MWT require further investigations of their clinimetric properties.

Worldwide, there has been a dramatic increase in the use of paediatric home mechanical ventilation (HMV). In this review, we examine this rapid evolution in clinical practice through the prism of two distinct groups of children: those with neurodisability/medical complexity and patients with neuromuscular disease. We illustrate the changes in service provision for these two groups that are driven by a recognition that early intervention with HMV can enhance quality of life for these children and may complement the beneficial effects of novel disease-modifying medications to improve survival. Alongside this, we highlight the importance of balancing patient expectations with clinical need and discuss the ethical challenges that may be encountered when delivering HMV to this increasing population of children.

Obstructive sleep apnoea (OSA) contributes to cerebrovascular diseases and cognitive decline. Preclinical studies support the deleterious impact on the brain of intermittent hypoxia (IH), one of the main components of OSA, but heterogeneity in rodent species and brain regions studied, or induced by IH paradigms, can challenge interpretation of the studies. Hence, we conducted a systematic review and meta-analysis to evaluate the impact of IH on rodent brain oxidative stress, inflammation, apoptosis and the expression of brain-derived neurotrophic factor (BDNF) and hypoxia-inducible factor 1 (HIF-1). PubMed and Web of Science searches identified 663 articles related to IH exposure, of which 60 were included. The examined outcomes were oxidative stress, inflammation, apoptosis, HIF-1 or BDNF in brains. Standardised mean difference was used to compare studies. Metaregressions were performed to clarify the impact of IH exposure parameters, rodent characteristics or cerebral localisation on these outcomes. IH-induced oxidative stress (increased malondialdehyde (MDA) and NADPH oxidase (NOX) and decreased superoxide dismutase), increased inflammation (tumour necrosis factor-α, NF-κB and inducible nitric oxide synthase), HIF-1 and apoptosis evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labelling and cleaved caspase-3. In contrast, B-cell lymphoma 2 (BCL2) and BDNF expression were not significantly modified. Metaregressions showed that MDA, NOX and BDNF were associated with determinants of IH cycles (inspired oxygen fraction and duration of hypoxia) and some parameters depended on localisation. Rodent characteristics had little impact on the outcomes. Our meta-analysis robustly establishes that IH, independently of other confounders, has a strong effect on the brain by inducing oxidative stress, inflammation and apoptosis in rodent models. Our findings support the interest of considering and treating cerebral consequences of OSA in clinical practice.

The advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy, especially the triple therapy combining the drugs elexacaftor, tezacaftor, ivacaftor (ETI), has significantly changed the course of the disease in people with cystic fibrosis (pwCF). ETI, which is approved for the majority (80-90%) of pwCF, partially restores CFTR channel function, resulting in improved mucociliary clearance and, consequently, improved lung function, respiratory symptoms and pulmonary exacerbations. The bacterial burden of classical CF pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus is reduced without reaching eradication in the majority of infected patients. Limited data is available on less common or emerging bacterial pathogens. ETI has a positive effect on the lung microbiome but does not fully restore it to a healthy state. Due to the significant reduction in sputum production under ETI, respiratory samples such as deep-throat swabs are commonly taken, despite their inadequate representation of lower respiratory tract pathogens. Currently, there are still unanswered questions related to this new therapy, such as the clinical impact of infection with cystic fibrosis (CF) pathogens, the value of molecular diagnostic tests, the durability of the effects on respiratory infection and the role of fungal and viral infections. This article reviews the changes in bacterial lung infections and the microbiome in CF to provide evidence for the use of antibiotics in the era of ETI.