European Respiratory Review最新文献

Bronchiectasis is marked by bronchial dilatation, recurrent infections and significant morbidity, underpinned by a complex interplay between microbial dysbiosis and immune dysregulation. The identification of distinct endophenotypes have refined our understanding of its pathogenesis, including its heterogeneous disease mechanisms that influence treatment and prognosis responses. Next-generation sequencing (NGS) has revolutionised the way we view airway microbiology, allowing insights into the "unculturable". Understanding the bronchiectasis microbiome through targeted amplicon sequencing and/or shotgun metagenomics has provided key information on the interplay of the microbiome and host immunity, a central feature of disease progression. The rapid increase in translational and clinical studies in bronchiectasis now provides scope for the application of precision medicine and a better understanding of the efficacy of interventions aimed at restoring microbial balance and/or modulating immune responses. Holistic integration of these insights is driving an evolving paradigm shift in our understanding of bronchiectasis, which includes the critical role of the microbiome and its unique interplay with clinical, inflammatory, immunological and metabolic factors. Here, we review the current state of infection and the microbiome in bronchiectasis and provide views on the future directions in this field.

Bronchiectasis is a complex and heterogeneous inflammatory chronic respiratory disease with an unknown cause in around 30-40% of patients. The presence of airway infection together with chronic inflammation, airway mucociliary dysfunction and lung damage are key components of the vicious vortex model that better describes its pathophysiology. Although bronchiectasis research has significantly increased over the past years and different endotypes have been identified, there are still major gaps in the understanding of the pathophysiology. Genomic approaches may help to identify new endotypes, as has been shown in other chronic airway diseases, such as COPD.Different studies have started to work in this direction, and significant contributions to the understanding of the microbiome and proteome diversity have been made in bronchiectasis in recent years. However, the systematic application of omics approaches to identify new molecular insights into the pathophysiology of bronchiectasis (endotypes) is still limited compared with other respiratory diseases.Given the complexity and diversity of these technologies, this review describes the key components of the pathophysiology of bronchiectasis and how genomics can be applied to increase our knowledge, including the study of new techniques such as proteomics, metabolomics and epigenomics. Furthermore, we propose that the novel concept of trained innate immunity, which is driven by microbiome exposures leading to epigenetic modifications, can complement our current understanding of the vicious vortex. Finally, we discuss the challenges, opportunities and implications of genomics application in clinical practice for better patient stratification into new therapies.

Introduction: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are life-threatening conditions that can progress to death without treatment. Although strong medication adherence (MA) is known to enhance outcomes in chronic illnesses, its association with PAH and CTEPH was sporadically explored. This study aims to examine the MA of patients with PAH or CTEPH, identify factors associated with low adherence and explore the resulting outcomes.

Methods: A systematic review was conducted by searching multiple databases (Medline, Embase, Cochrane Central, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar) from 6 March 1998 to 6 July 2023. We included studies reporting MA as primary or secondary end-points. Study selection, data extraction and methodological quality assessment were performed in duplicate.

Results: 20 studies involving 22 675 patients met the inclusion criteria. Heterogeneity was observed, particularly in the methods employed. MA means ranged from 0.62 to 0.96, with the proportion of patients exhibiting high MA varying from 40% (95% CI 35-45%) to 94% (95% CI 88-97%). Factors associated with low adherence included increased treatment frequency, time since diagnosis and co-payment. High MA seems to be associated with reduced hospitalisation rates, inpatient stays, outpatient visits and healthcare costs.

Conclusions: This systematic review underscores the heterogeneity of MA across studies. Nevertheless, the findings suggest that high MA could improve patients' clinical outcomes and alleviate the economic burden. Identifying factors consistently associated with poor MA could strengthen educational efforts for these patients, ultimately contributing to improved outcomes.

Bronchiectasis and nontuberculous mycobacteria (NTM) are intricately intertwined, with NTM capable of being both a cause and consequence of bronchiectatic disease. This narrative review focuses on the common ground of bronchiectasis and NTM pulmonary disease (NTM-PD) in terms of diagnostic approach, underlying risk factors and treatment strategies. NTM-PD diagnosis relies on a combination of clinical, radiological and microbiological criteria. Although their epidemiology is complicated by detection and reporting biases, the prevalence and pathogenicity of NTM species vary geographically, with Mycobacterium avium complex and Mycobacterium abscessus subspecies most frequently isolated in bronchiectasis-associated NTM-PD. Diagnosis of nodular bronchiectatic NTM-PD should prompt investigation of host factors, including disorders of mucociliary clearance, connective tissue diseases and immunodeficiencies, either genetic or acquired. Treatment of NTM-PD in bronchiectasis involves a multidisciplinary approach and considers the (sub)species involved, disease severity and comorbidities. Current guideline-based antimicrobial treatment of NTM-PD is considered long, cumbersome and unsatisfying in terms of outcomes. Novel treatment regimens and strategies are being explored, including rifampicin-free regimens and inclusion of clofazimine and inhaled antibiotics. Host-directed therapies, such as immunomodulators and cytokine-based therapies, might enhance antimycobacterial immune responses. Optimising supportive care, as well as pathogen- and host-directed strategies, is crucial, highlighting the need for personalised approaches tailored to individual patient needs. Further research is warranted to elucidate the complex interplay between host and mycobacterial factors, informing more effective management strategies.

Acute respiratory distress syndrome (ARDS) poses a significant and widespread public health challenge. Extensive research conducted in recent decades has considerably improved our understanding of the disease pathophysiology. Nevertheless, ARDS continues to rank among the leading causes of mortality in intensive care units and its management remains a formidable task, primarily due to its remarkable heterogeneity. As a consequence, the syndrome is underdiagnosed, prognostication has important gaps and selection of the appropriate therapeutic approach is laborious. In recent years, the noncoding transcriptome has emerged as a new area of attention for researchers interested in biomarker development. Numerous studies have confirmed the potential of long noncoding RNAs (lncRNAs), transcripts with little or no coding information, as noninvasive tools for diagnosis, prognosis and prediction of the therapeutic response across a broad spectrum of ailments, including respiratory conditions. This article aims to provide a comprehensive overview of lncRNAs with specific emphasis on their role as biomarkers. We review current knowledge on the circulating lncRNAs as potential markers that can be used to enhance decision making in ARDS management. Additionally, we address the primary limitations and outline the steps that will be essential for integration of the use of lncRNAs in clinical laboratories. Our ultimate objective is to provide a framework for the implementation of lncRNAs in the management of ARDS.

Introduction: This review quantifies the mean treatment effect of exercise-based interventions on balance and falls risk in people with COPD.

Methods: A structured search strategy (2000-2023) was applied to eight databases to identify studies evaluating the impact of exercise-based interventions (≥14 days in duration) on balance or falls in people with COPD. Pooled mean treatment effects (95% confidence intervals (CIs), 95% prediction intervals (PIs)) were calculated for outcomes reported in five or more studies. Inter-individual response variance and the promise of behaviour change techniques (BCTs) were explored.

Results: 34 studies (n=1712) were included. There were greater improvements in balance post intervention compared to controls for the Berg Balance Scale (BBS) (mean 2.51, 95% CI 0.22-4.80, 95% PI -4.60-9.63), Timed Up and Go (TUG) test (mean -1.12 s, 95% CI -1.69- -0.55 s, 95% PI -2.78-0.54 s), Single-Leg Stance (SLS) test (mean 3.25 s, 95% CI 2.72-3.77 s, 95% PI 2.64-3.86 s) and Activities-specific Balance Confidence (ABC) scale (mean 8.50%, 95% CI 2.41-14.58%, 95% PI -8.92-25.92%). Effect on falls remains unknown. Treatment effects were larger in male versus mixed-sex groups for the ABC scale and SLS test, and in balance training versus other exercise-based interventions for the BBS and TUG test. Falls history was not associated with changes in balance. Meta-analysis of individual response variance was not possible and study-level results were inconclusive. Eleven promising BCTs were identified (promise ratio ≥2).

Conclusion: Evidence for the effect of exercise-based interventions eliciting clinically important improvements in balance for people with COPD is weak, but targeted balance training produces the greatest benefits. Future exercise interventions may benefit from inclusion of the identified promising BCTs.

Neuroimmune recognition and regulation in the respiratory system is a complex and highly coordinated process involving interactions between the nervous and immune systems to detect and respond to pathogens, pollutants and other potential hazards in the respiratory tract. This interaction helps maintain the health and integrity of the respiratory system. Therefore, understanding the complex interactions between the respiratory nervous system and immune system is critical to maintaining lung health and developing treatments for respiratory diseases. In this review, we summarise the projection distribution of different types of neurons (trigeminal nerve, glossopharyngeal nerve, vagus nerve, spinal dorsal root nerve, sympathetic nerve) in the respiratory tract. We also introduce several types of cells in the respiratory epithelium that closely interact with nerves (pulmonary neuroendocrine cells, brush cells, solitary chemosensory cells and tastebuds). These cells are primarily located at key positions in the respiratory tract, where nerves project to them, forming neuroepithelial recognition units, thus enhancing the ability of neural recognition. Furthermore, we summarise the roles played by these different neurons in sensing or responding to specific pathogens (influenza, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, human metapneumovirus, herpes viruses, Sendai parainfluenza virus, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, amoebae), allergens, atmospheric pollutants (smoking, exhaust pollution), and their potential roles in regulating interactions among different pathogens. We also summarise the prospects of bioelectronic medicine as a third therapeutic approach following drugs and surgery, as well as the potential mechanisms of meditation breathing as an adjunct therapy.

Paediatric sleep diagnostics is performed using complex multichannel tests in specialised centres, limiting access and availability and resulting in delayed diagnosis and management. Such investigations are often challenging due to patient size (prematurity), tolerability, and compliance with "gold standard" equipment. Children with sensory/behavioural issues, at increased risk of sleep disordered breathing (SDB), often find standard diagnostic equipment difficult.SDB can have implications for a child both in terms of physical health and neurocognitive development. Potential sequelae of untreated SDB includes failure to thrive, cardiopulmonary disease, impaired learning and behavioural issues. Prompt and accurate diagnosis of SDB is important to facilitate early intervention and improve outcomes.The current gold-standard diagnostic test for SDB is polysomnography (PSG), which is expensive, requiring the interpretation of a highly specialised physiologist. PSG is not feasible in low-income countries or outwith specialist sleep centres. During the coronavirus disease 2019 pandemic, efforts were made to improve remote monitoring and diagnostics in paediatric sleep medicine, resulting in a paradigm shift in SDB technology with a focus on automated diagnosis harnessing artificial intelligence (AI). AI enables interrogation of large datasets, setting the scene for an era of "sleep-omics", characterising the endotypic and phenotypic bedrock of SDB by drawing on genetic, lifestyle and demographic information. The National Institute for Health and Care Excellence recently announced a programme for the development of automated home-testing devices for SDB. Scorer-independent scalable diagnostic approaches for paediatric SDB have potential to improve diagnostic accuracy, accessibility and patient tolerability; reduce health inequalities; and yield downstream economic and environmental benefits.

Lower respiratory tract infections (LRTIs) present a significant global health burden, exacerbated by the rise in antimicrobial resistance (AMR). The persistence and evolution of multidrug-resistant bacteria intensifies the urgency for alternative treatments. This review explores bacteriophage (phage) therapy as an innovative solution to combat bacterial LRTIs. Phages, abundant in nature, demonstrate specificity towards bacteria, minimal eukaryotic toxicity, and the ability to penetrate and disrupt bacterial biofilms, offering a targeted approach to infection control. The article synthesises evidence from systematic literature reviews spanning 2000-2023, in vitro and in vivo studies, case reports and ongoing clinical trials. It highlights the synergistic potential of phage therapy with antibiotics, the immunophage synergy in animal models, and the pharmacodynamics and pharmacokinetics critical for clinical application. Despite promising results, the article acknowledges that phage therapy is at a nascent stage in clinical settings, the challenges of phage-resistant bacteria, and the lack of comprehensive cost-effectiveness studies. It stresses the need for further research to optimise phage therapy protocols and navigate the complexities of phage-host interactions, particularly in vulnerable populations such as the elderly and immunocompromised. We call for regulatory adjustments to facilitate the exploration of the long-term effects of phage therapy, aiming to incorporate this old-yet-new therapy into mainstream clinical practice to tackle the looming AMR crisis.