European Respiratory Review最新文献

Pulmonary veno-occlusive disease (PVOD), also known as "pulmonary arterial hypertension (PAH) with overt features of venous/capillary involvement", is a rare cause of PAH characterised by substantial small pulmonary vein and capillary involvement, leading to increased pulmonary vascular resistance and right ventricular failure. Environmental risk factors have been associated with the development of PVOD, such as occupational exposure to organic solvents and chemotherapy, notably mitomycin. PVOD may also be associated with a mutation in the EIF2AK4 gene in heritable forms of disease. Distinguishing PVOD from PAH is critical for guiding appropriate management. Chest computed tomography typically displays interlobular septal thickening, ground-glass opacities and mediastinal lymphadenopathy. Life-threatening pulmonary oedema is a complication of pulmonary vasodilator therapy that can occur with any class of PAH drugs in PVOD. Early referral to a lung transplant centre is essential due to the poor response to therapy when compared with other forms of PAH. Histopathological analysis of lung explants reveals microvascular remodelling with typical fibrous veno-occlusive lesions. This review covers the main features distinguishing PVOD from PAH and two clinical cases that illustrate the challenges of PVOD management.

Lung fibrosis is a complex process, with unknown underlying mechanisms, involving various triggers, diseases and stimuli. Different cell types (epithelial cells, endothelial cells, fibroblasts and macrophages) interact dynamically through multiple signalling pathways, including biochemical/molecular and mechanical signals, such as stiffness, affecting cell function and differentiation. Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing interstitial lung disease (fILD), characterised by a notably high mortality. Unfortunately, effective treatments for advanced fILD, and especially IPF and non-IPF progressive fibrosing phenotype ILD, are still lacking. The development of pharmacological therapies faces challenges due to limited knowledge of fibrosis pathogenesis and the absence of pre-clinical models accurately representing the complex features of the disease. To address these challenges, new model systems have been developed to enhance the translatability of preclinical drug testing and bridge the gap to human clinical trials. The use of two- and three-dimensional in vitro cultures derived from healthy or diseased individuals allows for a better understanding of the underlying mechanisms responsible for lung fibrosis. Additionally, microfluidics systems, which replicate the respiratory system's physiology ex vivo, offer promising opportunities for the development of effective therapies, especially for IPF.

The treatable traits approach represents a strategy for patient management. It is based on the identification of characteristics susceptible to treatments or predictive of treatment response in each individual patient. With the objective of accelerating progress in research and clinical practice relating to such a treatable traits approach, the Portraits event was convened in Barcelona, Spain, in November 2022. Here, while reporting the key concepts that emerged from the discussions during the meeting, we review the current state of the art related to treatable traits and chronic respiratory diseases management, and we describe the possible actions that clinicians can take in clinical practice to implement the treatable traits framework. Furthermore, we explore the new concept of GETomics and the new models of research in the field of COPD.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and potentially life-threatening complication of acute pulmonary embolism. It is characterised by persistent fibro-thrombotic pulmonary vascular obstructions and elevated pulmonary artery pressure leading to right heart failure. The diagnosis is based on two steps, as follows: 1) suspicion based on symptoms, echocardiography and ventilation/perfusion scan and 2) confirmation with right heart catheterisation, computed tomography pulmonary angiography and, in most cases, digital subtraction angiography. The management of CTEPH requires a multimodal approach, involving medical therapy, interventional procedures and surgical intervention. This clinical–radiological–pathological correlation paper illustrates the diagnostic and therapeutic management of two patients. The first had chronic thromboembolic pulmonary disease without pulmonary hypertension at rest but with significant physical limitation and was successfully treated with pulmonary endarterectomy. The second patient had CTEPH associated with splenectomy and was considered unsuitable for surgery because of exclusive subsegmental lesions combined with severe pulmonary hypertension. The patient benefited from multimodal treatment involving medical therapy followed by multiple sessions of balloon pulmonary angioplasty. Both patients had normalised functional capacity and pulmonary haemodynamics 3–6 months after the interventional treatment. These two examples show that chronic thromboembolic pulmonary diseases are curable if diagnosed promptly and referred to CTEPH centres for specialist treatment.

Asthma is the most common chronic medical condition in pregnancy. Asthma exacerbations in pregnancy are unpredictable, and are associated with adverse maternal and fetal perinatal outcomes such as preterm birth and low birthweight. Goals of asthma management in pregnancy are to establish effective asthma control and prevent exacerbations. Optimising the management of asthma in pregnancy is an important goal of practice and future research.

Treatable traits is a precision medicine paradigm proposed for the management of airways diseases, which holistically addresses the complexity and heterogeneity of airways disease. It is an individualised treatment approach that aims to improve outcomes. This makes treatable traits well suited for pregnant women with asthma, who have a high prevalence of obesity, mental health conditions, poor symptom perception and suboptimal asthma management skills including low treatment adherence. These traits are measurable and treatable. In this review, we explore current knowledge on the burden of asthma, maternal and perinatal consequences of asthma during pregnancy, the treatable traits paradigm, the prevalence of treatable traits in pregnant women with asthma, and consider how the treatable traits paradigm can be integrated into the management of asthma in pregnancy.

COPD is a highly prevalent, chronic and irreversible obstructive airway disease without curative treatment. Standard therapeutic strategies, both non-pharmacological and pharmacological, have only limited effects on lung function parameters of patients with severe disease. Despite optimal pharmacological treatment, many patients with severe COPD still have a high burden of dyspnoea and a poor quality of life. If these patients have severe lung emphysema, with hyperinflation as the driver of symptoms and exercise intolerance, lung volume reduction may be an effective treatment with a significant impact on lung function, exercise capacity and quality of life. Currently, different lung volume reduction approaches, both surgical and bronchoscopic, have shown encouraging results and have been implemented in COPD treatment recommendations. Nevertheless, choosing the optimal lung volume reduction strategy for an individual patient remains challenging. Moreover, there is still room for improving durability of effect and safety in all available procedures. Ongoing and innovative research is essential to push this field forwards. This review provides an overview of results and limitations of the current lung volume reduction options for patients with severe lung emphysema and hyperinflation.

Ever since the second world symposium on pulmonary hypertension (PH) held in Evian, France, in 1998, PH has been classified into five major clinical groups. Group 5 PH includes a variety of distinct conditions with unclear and/or multifactorial underlying pathologies. Management of these patients is challenging as the number of patients within these groups is often small, not all individuals with certain underlying conditions are affected by PH and patients exhibit distinct symptoms due to different underlying diseases. Studies and clinical trials in these groups are largely lacking and mostly restricted to case series and registry reports. Nonetheless, the worldwide burden of group 5 PH is estimated to be significant in terms of the prevalence of some associated diseases. Group 5 PH encompasses six subgroups, including haematological disorders (inherited and acquired chronic haemolytic anaemia and chronic myeloproliferative disorders), systemic disorders (sarcoidosis, pulmonary Langerhans's cell histiocytosis and neurofibromatosis type 1), metabolic disorders (glycogen storage diseases and Gaucher disease), chronic renal failure with or without haemodialysis, pulmonary tumour thrombotic microangiopathy and fibrosing mediastinitis.