European Respiratory Review最新文献

The human and economic impact of idiopathic pulmonary fibrosis and other interstitial lung diseases is enormous, and available therapies are of limited utility. A decade after the introduction of the first antifibrotic agents, two new agents are on the horizon. Nerandomilast is an inhibitor of phosphodiesterase 4B, while treprostinil is an analogue of prostacyclin. Both agents increase intracellular cAMP. Although the smooth muscle relaxant properties of agents that increase cAMP have long been leveraged for the treatment of airway and vascular diseases, potential antifibrotic actions of cAMP elevation are much less well appreciated by clinicians and researchers. The purpose of this review is to discuss the mechanistic underpinnings for a beneficial role of cAMP in fibrotic lung diseases. We briefly review the pathogenesis of fibrotic lung disease, the anatomy of the cAMP pathway, and the myriad ways in which this pathway is disrupted in fibrotic diseases. We then focus on the pleiotropic actions by which cAMP opposes the aberrant phenotypes of immune cells, fibroblasts, and epithelial cells that characterise fibrotic diseases. Finally, we highlight some unanswered questions about, and future opportunities for optimising, therapeutic interventions that leverage the cAMP pathway.

The bronchoscopic approach to diagnosing sarcoidosis has evolved significantly with the advent of advanced endoscopic and imaging-guided modalities. Bronchoscopy remains the cornerstone for both histological confirmation and therapeutic intervention, offering minimally invasive access to the mediastinum, lung parenchyma and airways. This review integrates traditional techniques, including bronchoalveolar lavage, endobronchial biopsy and transbronchial biopsy, with advanced modalities such as endobronchial ultrasound-guided transbronchial needle aspiration, transbronchial lung cryobiopsy, endobronchial ultrasound-guided intranodal forceps biopsy and mediastinal cryobiopsy. Emerging tools, including elastography and confocal laser endomicroscopy, are also explored for their potential to enhance diagnostic precision. A stage-based diagnostic algorithm is proposed to guide procedural choices tailored to clinical presentation. The role of bronchoscopy in diagnosing stage 0 and extrapulmonary sarcoidosis is discussed. This comprehensive update synthesises recent evidence to provide a practical framework for clinicians navigating complex diagnostic scenarios in sarcoidosis.

Pulmonary arterial hypertension (PAH) is a severe disease characterised by a progressive thickening and obliteration of pulmonary vessels, resulting in increased vascular resistance, elevated pulmonary artery pressures, and right heart failure. Among the various conditions associated with PAH, systemic sclerosis (SSc) is the most common in Western countries. Compared to other forms of PAH, SSc-PAH presents with a more aggressive clinical course, poorer response to conventional therapies and a worse prognosis. However, despite these differences, the overall management of SSc-PAH remains close to idiopathic PAH; and therefore, there is a crucial need for treatment strategies dedicated to this disease. To help fill this gap, we assessed the level of evidence currently available on SSc-PAH management in a systematic literature review that compiled data regarding conventional therapies, immunosuppressants, nonconventional drugs and surgical/interventional procedures. For each study, we highlighted the results specific to the connective tissue disease or SSc subgroups, the haemodynamic characteristics of the patients, and their comorbidities. By doing so, we identified critical gaps in the field, consisting mostly of the lack of studies focusing on SSc-PAH, a substantial heterogeneity in haemodynamic severity (with notable scarcity of data for mild PAH) and the systematic exclusion of relevant comorbidities (such as interstitial lung disease). Building on these data and our cumulative experience, we provide pragmatic, experience-based suggestions tailored to the management of SSc-PAH, that tries to capture the full scope of clinical situations encountered in these patients and help clinicians manage difficult cases where robust data are lacking.

Background: Pleural malignancies pose a significant clinical challenge due to their poor prognosis and limited treatment options. Hyperthermic intrathoracic chemotherapy (HITHOC) is an emerging modality that has shown promise in treating primary pleural cancers when used with cytoreductive surgery (CRS), but its efficacy in treating pleural malignancies other than mesothelioma remains underexplored. This review aims to evaluate recent advancements in HITHOC use for nonmesothelioma pleural cancers and provide insights into its potential clinical applications.

Methods: A comprehensive Boolean search was conducted using PubMed/Medline and Google Scholar to identify relevant studies on the use of HITHOC for nonmesothelioma pleural cancers. Studies exclusively focused on pleural mesothelioma were excluded. Findings were summarised to address key questions regarding HITHOC's effectiveness, integration with other therapies and obstacles to its broader use.

Results: HITHOC, when combined with CRS, could prolong overall and progression-free survival and reduce complication and mortality rates in patients with advanced pleural cancers. Advances in chemo-immunotherapy, the evolution of minimally invasive techniques and the emergence of precision surgery hold significant promise in the treatment of pleural malignancies.

Conclusion: Given the challenges associated with HITHOC, including protocol variability and technical complexity, future research using larger, multinational datasets is essential to support its broader application and to identify patient-specific characteristics that enhance its efficacy in treating pleural cancers.

Background: COPD is associated with an increased risk of infections, such as herpes zoster, potentially leading to greater morbidity and mortality. This systematic review assessed the evidence on herpes zoster burden in COPD.

Methods: A global systematic literature review and meta-analysis was conducted (MEDLINE/Embase, 2003-2024) on herpes zoster burden (incidence, risk, complications, impact on COPD and healthcare resources) in adults aged ≥18 years with COPD.

Results: 22 studies on herpes zoster burden in COPD were included. The pooled herpes zoster incidence rate per 1000 person-years in adults with COPD aged ≥18 years was 10.98 (95% CI 8.28-14.56), increasing to 13.95 (10.80-18.02) in adults aged ≥50 years. The pooled risk ratio of developing herpes zoster was 1.49 (1.17-1.89) in adults aged ≥18 years with COPD and 1.86 (1.28-2.69) in COPD treated with corticosteroids. The pooled rate ratio of developing post-herpetic neuralgia (persistent pain lasting ≥90 days) was 1.50 (1.10-2.04) in adults with herpes zoster and COPD versus with herpes zoster alone. Herpes zoster was linked to higher healthcare costs and resource use, and may be associated with COPD exacerbations. Study designs, settings, case definitions, sample sizes and study periods differed, resulting in heterogeneity.

Conclusions: Adults with COPD have an increased risk of herpes zoster and complications and an associated burden on healthcare systems, with higher risks in those on corticosteroids. Herpes zoster vaccines offer effective protection, including for adults with COPD, and could help reduce the disease and its economic burden.

The lungs are innervated by both afferent and efferent nerve fibres that regulate key respiratory functions, including the cough reflex, airway tone, mucus secretion, and the detection of mechanical and chemical stimuli. In asthma, airway hyperresponsiveness and inflammation are, in part, modulated by the nervous system. Recent findings have identified neuroplasticity as a pathological feature of severe asthma, suggesting that altered neural remodelling contributes to disease symptoms. Additionally, growing evidence highlights bidirectional interactions between the airway nervous system and local immune cells, which play a crucial role in modulating each other's activity. In this review, we explore the emerging roles of airway neuroplasticity and neuroimmune interactions in the development of type 2 inflammation in asthma. We focus on the involvement of neuropeptides and cytokines in mediating this bidirectional crosstalk, aiming to elucidate the mechanistic link between neural remodelling and immune activation and to identify novel targets for pharmacological intervention.

The adult lung is continuously exposed to environmental insults such as pathogens, pollutants and toxins, necessitating robust regenerative mechanisms to maintain tissue integrity and function. Epithelial regeneration relies on the activity and plasticity of resident stem and progenitor cell populations that are spatially distributed across airway and alveolar compartments. Basal cells in the conducting airways and alveolar type (AT) 2 cells in the alveoli act as regional stem cells, capable of self-renewal and multilineage differentiation. Additionally, variant club cells, bronchioalveolar stem cells (BASCs) and newly identified secretory and transitional cell types such as respiratory airway secretory and AT0 cells have emerged as critical players in lung repair. Cellular plasticity, the ability of differentiated cells to dedifferentiate or transdifferentiate, enables rapid adaptation to injury but may also contribute to chronic lung disease when dysregulated. Ageing and chronic injury reduce regenerative capacities, leading to failed repair, fibrotic remodelling or epithelial simplification, as seen in diseases such as idiopathic pulmonary fibrosis and COPD. Recent advances in single-cell and spatial transcriptomics have revealed cellular heterogeneity, novel progenitor states and transitional intermediates that underpin both normal repair and disease pathogenesis. In this review, we integrate findings from animal models and human lung studies to highlight conserved and divergent mechanisms governing cell fate decisions. We discuss how niche signals, transcriptional programmes and extrinsic cues shape epithelial regeneration and explore the therapeutic implications of targeting epithelial plasticity in chronic lung disease.

The lung may be the organ whose mechanical environment needs to be most finely tuned to achieve optimal function. These needs have to be fulfilled at multiple scales, from proper force transmission between the chest wall and the parenchyma to reduction of surface tension by surfactants inside the alveoli. In addition, a plethora of mechanical loads and forces takes place within the lung, from the passive stretch withstood by epithelial cells lining the alveoli, to active forces generated by smooth muscle cells to control airway calibre or cilia beating by ciliary cells in the bronchi to clear debris. Furthermore, the acellular structures in the lung are finely tuned in composition and mechanical properties, from the viscoelastic properties of the mucus to trap pathogens, to the collagen- and elastin-rich extracellular matrix that enables the lung to display elastic recoil at resting volumes but stiffen as it approaches total lung capacity. In this review, we describe the mechanical interplay between the cell types found in the lung, as well as cellular responses to their mechanical niche. We further describe how these responses are altered in diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. In addition, key proteins in mechanotransduction events are detailed, stressing their potential role as therapeutical targets for lung diseases. Finally, we also include a sex perspective to lung pathologies and highlight engineered model systems that may be used to advance our understanding of mechanical forces in experimental investigations or towards lung regeneration.

Background: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterised by progressive accumulation of surfactant-derived lipoproteinaceous material within alveoli, impairing gas exchange and causing respiratory insufficiency. Despite therapeutic advances such as whole lung lavage, substantial heterogeneity persists in outcome selection and reporting across studies, limiting comparability and evidence synthesis.

Objective: To systematically map and categorise outcomes and outcome measures reported in studies of PAP treatments and establish a foundation for developing a standardised core outcome set (COS).

Methods: A scoping review was conducted across four databases and two clinical trial registries (May 2024, updated May 2025). Eligible studies included those reporting treatment outcomes in patients of any age with PAP. Outcomes and measures were extracted and categorised using the Core Outcome Measures in Effectiveness Trials taxonomy.

Results: From 8475 screened records, 62 studies met the inclusion criteria, encompassing 31 distinct outcomes and 92 corresponding outcome measures. Physiological parameters dominated reporting, including arterial oxygenation (n=55, 89%; such as arterial oxygen tension and alveolar-arterial oxygen gradient) and lung function indices (n=53, 85%; such as diffusing capacity of the lung for carbon monoxide and forced vital capacity) were most frequently assessed. In contrast, patient-centred outcomes such as quality of life were reported in only 10 (16%) studies, while adverse events were relatively well-reported (n=41, 66%).

Conclusions: The reporting of outcomes and outcome measures in PAP studies is highly variable. There is an urgent need for a COS tailored to PAP that focuses on physiological outcomes, adverse events and patient-reported outcomes.