on behalf of the European Society of Radiology (ESR) and the European Respiratory Society (ERS) @ERSpublicationsThe ESR and ERS agree that Europe's healthcare systems need to allow citizens to benefit from organised pathways to early diagnosis and reduction of mortality of lung cancer. Now is the time to set up and implement large-scale programmes.

In Europe, lung cancer ranks third among the most common cancers, remaining the biggest killer. Since the publication of the first European Society of Radiology and European Respiratory Society joint white paper on lung cancer screening (LCS) in 2015, many new findings have been published and discussions have increased considerably. Thus, this updated expert opinion represents a narrative, non-systematic review of the evidence from LCS trials and description of the current practice of LCS as well as aspects that have not received adequate attention until now. Reaching out to the potential participants (persons at high risk), optimal communication and shared decision-making will be key starting points. Furthermore, standards for infrastructure, pathways and quality assurance are pivotal, including promoting tobacco cessation, benefits and harms, overdiagnosis, quality, minimum radiation exposure, definition of management of positive screen results and incidental findings linked to respective actions as well as cost-effectiveness. This requires a multidisciplinary team with experts from pulmonology and radiology as well as thoracic oncologists, thoracic surgeons, pathologists, family doctors, patient representatives and others. The ESR and ERS agree that Europe's health systems need to adapt to allow citizens to benefit from organised pathways, rather than unsupervised initiatives, to allow early diagnosis of lung cancer and reduce the mortality rate. Now is the time to set up and conduct demonstration programmes focusing, among other points, on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry.

Key PointsAsthma is a heterogeneous syndrome ranging from mild disease with barely noticeable symptoms to very severe disease with constant symptoms that may greatly hinder patients’ quality of life.The aim of asthma treatment is control of asthma and the prevention of risk of exacerbations and fixed airflow limitation.Asthma management must be individualised; tailored not only to the severity of the disease but importantly, to the phenotypic characteristics of the patient and modified according to response to treatment.Educational AimsTo inform readers about the current understanding on the treatment of asthma.To highlight the usefulness of phenotypes in treating asthmatic patients, especially those with severe disease.To introduce the issues of severe asthma management and future planning.Asthma is a common, chronic and heterogeneous syndrome, affecting people of all ages, all races and both sexes. It may range from mild disease with barely noticeable symptoms, to very severe disease with constant symptoms that greatly hinder the life of the patient. Guidelines issued by various medical societies provide guidance on how to diagnose and manage asthmatic patients. It is now increasingly recognised that asthma management must be individualised, tailored not only to the severity of the disease but to the phenotypic characteristics of each patient. The aim of asthma treatment is control of asthma and the prevention of risk of exacerbations and fixed airflow limitation. Asthma control can be easily assessed clinically through simple screening tools such as the use of validated questionnaires and spirometry. The use of inflammatory biomarkers can be an alternative approach that, however, requires more time and resources. Asthma treatment involves the use of controllers, mainly inhaled corticosteroids and long-acting β2-agonists, and relievers, mainly rapid-acting β2-agonists. Controller medications reduce airway inflammation, lead to better symptom control and reduce the risk of future exacerbations. Reliever (rescue) medications alleviate symptoms and prevent exercise-induced bronchoconstriction. Treatment must be based on a “stepwise approach” in order to achieve good control of symptoms and to minimise future risks of exacerbations. That is, less treatment for mild disease, more treatment for severe, uncontrolled disease. Once good asthma control has been achieved and maintained, treatment should be stepped down. In severe asthmatics, phenotypic characterisation becomes more clinically useful and add-on treatment such as anti-immunoglobulin E monoclonal antibodies may be required. Despite our better understanding of asthma, there are still patients who will not respond to treatment and remain symptomatic. Dissemination of guidelines and national plans allowing early diagnosis of asthma as well as access to specialised primary and secondary care for asthmatic patients, personalised treatment and continuity of care may lead to excellence in care and controlled asthma for the majority of patients. Education of the pat...

Background Although tumor-infiltrating T cells represent a favorable prognostic marker for cancer patients, the majority of these cells are rendered with an exhausted phenotype. Hence, there is an unmet need to identify factors which can reverse this dysfunctional profile and restore their anti-tumorigenic potential. Activin-A is a pleiotropic cytokine, exerting a broad range of pro- or anti-inflammatory functions in different disease contexts, including allergic and autoimmune disorders and cancer. Given that activin-A exhibits a profound effect on CD4+ T cells in the airways and is elevated in lung cancer patients, we hypothesized that activin-A can effectively regulate anti-tumor immunity in lung cancer. Methods To evaluate the effects of activin-A in the context of lung cancer, we utilized the OVA-expressing Lewis Lung Carcinoma mouse model as well as the B16F10 melanoma model of pulmonary metastases. The therapeutic potential of activin-A-treated lung tumor-infiltrating CD4+ T cells was evaluated in adoptive transfer experiments, using CD4−/−-tumor bearing mice as recipients. In a reverse approach, we disrupted activin-A signaling on CD4+ T cells using an inducible model of CD4+ T cell-specific knockout of activin-A type I receptor. RNA-Sequencing analysis was performed to assess the transcriptional signature of these cells and the molecular mechanisms which mediate activin-A’s function. In a translational approach, we validated activin-A’s anti-tumorigenic properties using primary human tumor-infiltrating CD4+ T cells from lung cancer patients. Results Administration of activin-A in lung tumor-bearing mice attenuated disease progression, an effect associated with heightened ratio of infiltrating effector to regulatory CD4+ T cells. Therapeutic transfer of lung tumor-infiltrating activin-A-treated CD4+ T cells, delayed tumor progression in CD4−/− recipients and enhanced T cell-mediated immunity. CD4+ T cells genetically unresponsive to activin-A, failed to elicit effective anti-tumor properties and displayed an exhausted molecular signature governed by the transcription factors Tox and Tox2. Of translational importance, treatment of activin-A on tumor-infiltrating CD4+ T cells from lung cancer patients augmented their immunostimulatory capacity towards autologous CD4+ and CD8+ T cells. Conclusions In this study, we introduce activin-A as a novel immunomodulatory factor in the lung tumor microenvironment, which bestows exhausted CD4+ T cells with effector properties.

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Asthma is a heterogeneous disease usually characterised by chronic airway inflammation. It is defined by a history of symptoms such as wheeze, shortness of breath, chest tightness and cough, along with variable airflow limitation [1]. Recently, “cluster” analyses have provided insight into specific subtypes among asthma patients, which share phenotypic characteristics.

Lung cancer is the number one cause of death due to cancer worldwide. According to the World Health Organization, it accounted for 1.69 million new cases in 2015, whereas in Europe, 20.8% of all deaths due to cancer (>266 000 cases) were attributable to lung cancer in 2011 [1, 2].

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