European Respiratory Review最新文献

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.

COPD is a heterogeneous disease of the lungs characterised by restricted airflow. Chronic inflammation and recurrent bacterial infections are known to be important driving factors in exacerbations of this disease. Despite a marked increase in the number of alveolar macrophages present in the lungs of COPD patients, there is evidence of reduced clearance of pathogenic bacteria, leading to recurrent infection, exacerbation and subsequent lung function decline. This is thought to be attributed to a defect in the phagocytic capability of both alveolar and monocyte-derived macrophages in COPD. In addition to this defect, there is apparent selectivity in bacterial uptake by COPD macrophages because certain pathogenic genera, such as Haemophilus, Moraxella and Streptococcus, are taken up more readily than others. The respiratory microbiome plays a key role in regulating the host immune response both in health and during chronic inflammation. In patients with COPD, there are distinct changes in the composition of the respiratory microbiome, particularly the lower respiratory tract, where dominance of clinically relevant pathogenic species is commonly observed. Whether there are links between these changes in the microbiome and dysfunctional macrophage phagocytosis has not yet been widely studied. This review aims to discuss what is currently known about these phenomena and to explore interactions between macrophages and the respiratory microbiome.

Assessing and treating respiratory muscle dysfunction is crucial for patients with both acute and chronic respiratory failure. Respiratory muscle dysfunction can contribute to the onset of respiratory failure and may also worsen due to interventions aimed at treatment. Evaluating respiratory muscle function is particularly valuable for diagnosing, phenotyping and assessing treatment efficacy in these patients. This review outlines established methods, such as measuring respiratory pressures, and explores novel techniques, including respiratory muscle neurophysiology assessments using electromyography and imaging with ultrasound.Additionally, we review various treatment strategies designed to support and alleviate the burden on overworked respiratory muscles or to enhance their capacity through training interventions. These strategies range from invasive and noninvasive mechanical ventilation approaches to specialised respiratory muscle training programmes. By summarising both established techniques and recent methodological advancements, this review aims to provide a comprehensive overview of the tools available in clinical practice for evaluating and treating respiratory muscle dysfunction. Our goal is to present a clear understanding of the current capabilities and limitations of these diagnostic and therapeutic approaches. Integrating advanced diagnostic methods and innovative treatment strategies should help improve patient management and outcomes. This comprehensive review serves as a resource for clinicians, equipping them with the necessary knowledge to effectively diagnose and treat respiratory muscle dysfunction in both acute and chronic respiratory failure scenarios.

Introduction: Sub-optimal inhaler adherence undermines the efficacy of pharmacotherapy in COPD. Digitalised care pathways are increasingly used to improve inhaler-use behaviour remotely. This review investigated the feasibility and impact of remote electronic inhaler adherence monitoring (EIM) and intervention platforms on clinical outcomes in COPD.

Methods: A literature search was conducted and studies investigating maintenance inhaler use among people with COPD using digital technology were selected. Pairwise and proportional meta-analyses were employed with heterogeneity assessed using I² statistics. When meta-analysis was not feasible, a narrative synthesis of outcomes was conducted.

Results: We included 10 studies including 1432 people with COPD whose maintenance inhaler usage was supported by digital inhalers and apps featuring audiovisual reminders and educational content with or without engagement with healthcare providers (HCPs). Inhaler adherence rate (AR) varied with calculation methods, but an overall suboptimal adherence was observed among people with COPD. HCP-led adherence interventions alongside EIM improved mean AR by 18% (95% CI 9-27) versus passive EIM only. Enhanced AR may reduce COPD-related healthcare utilisation with little impact on health-related quality of life and exacerbation rate. Despite encountering technical issues among 14% (95% CI 5-23%) of participants, 85% (95% CI 76-94%) found digital platforms convenient to use, while 91% (95% CI 79-100%) perceived inhaler reminders as helpful.

Conclusion: Digitalised interventions can enhance maintenance inhaler adherence in COPD but their overall effect on clinical outcomes remains uncertain. Further work is required to tailor interventions to individuals' adherence behaviour and investigate their longer-term impact.

Background: Interstitial lung disease (ILD) encompasses a heterogeneous group of chronic lung conditions with considerable variability in prognosis and response to treatment. People with reduced muscle mass and function, known as sarcopenia, have a higher risk of mortality and adverse clinical outcomes both in the general population and in other chronic disease states. The importance of sarcopenia across the spectrum of patients with ILD is not well established.

Objectives: In this narrative review, we explore the prevalence and clinical implications of sarcopenia in patients with ILD, evaluate the optimal methods to diagnose sarcopenia in this patient population and review treatment interventions.

Findings: Almost one third of patients with chronic forms of ILD have evidence of sarcopenia. Sarcopenia is associated with adverse clinical outcomes and increased risk of mortality in select populations with ILD. Screening tests such as the SARC-F (strength, assistance walking, rise from a chair, climb stairs, falls) questionnaire and clinical assessment tools (including grip strength dynamometry) are well validated. Medical imaging modalities, including computed tomography, are hampered by lack of a gold standard and normative values, but have been used in patients with ILD in acute care and research settings. If sarcopenia is identified, multidimensional interventions such as pulmonary rehabilitation are beneficial.

Conclusion: Sarcopenia is common in patients with ILD and is associated with poorer outcomes. Accordingly, if identified, targeted interventions should be considered. Validated diagnostic criteria exist, but the optimal use of medical imaging techniques in this patient cohort remains an area of uncertainty.