RESUMEN
BACKGROUND: Non-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions. METHODS: These issues were divided into four main topics (Training, Organization, Responsibilities, and Sustainability) and discussed at a Consensus Conference promoted by the Research Center of the Italian Respiratory Society held in Rome, Italy, 3-4 November 2016. RESULTS AND CONCLUSIONS: Regarding training, important inadequacies emerged regarding specialist training - both the duration of practical training courses and teaching about chronic diseases like COPD. A better integration between university and teaching hospitals would improve the quality of specialization. A better organizational integration between hospital and specialists/general practitioners (GPs) in the local community is essential to improve the diagnostic and therapeutic pathways for chronic respiratory patients. Improving the care pathways is the joint responsibility of respiratory specialists, GPs, patients and their caregivers, and the healthcare system. The sustainability of the entire system depends on a better organization of the diagnostic-therapeutic pathways, in which also other stakeholders such as pharmacists and pharmaceutical companies can play an important role.
RESUMEN
Combined pulmonary fibrosis and emphysema (CPFE) is a computed tomography (CT)-defined syndrome of combined pulmonary fibrosis and emphysema, characterized by subnormal spirometry, impairment of gas exchange, and high prevalence of pulmonary hypertension. Although endothelin-1 (ET-1) plays an important role in the development of lung fibrosis as well as in pulmonary hypertension, no ET-1-targeted therapy is currently recommended. Here we report a case of CPFE successfully treated with ambrisentan, an endothelin-A receptor antagonist, and also discuss the biologic mechanisms underlying the observed therapeutic effects. A 79-year-old man with chronic obstructive pulmonary disease (COPD) was referred to our respiratory unit as an outpatient for dyspnea. Clinical, radiologic, and laboratory findings suggested a diagnosis of chronic hypoxemic, type 1 respiratory failure, due to combined pulmonary fibrosis and emphysema, complicated by severe, precapillary pulmonary hypertension. Pharmacologic treatment with ambrisentan induced an initial improvement in clinical symptoms that proved to be very relevant 9 months later. In order to investigate the biologic mechanisms underlying the clinical effects of ambrisentan, we performed an "in vitro" study on primary cultures of fibrotic human lung fibroblasts, as well as on human umbilical vein endothelial cells, incubated for 24 and 48 h with ET-1, in the absence or presence of an overnight treatment with ambrisentan. ET-1 significantly increased cell proliferation and mitogen-activated protein kinase activation (P < 0.01). These effects were significantly (P < 0.01) inhibited by ambrisentan in both cell cultures. In conclusion, we hypothesize that the clinical benefits induced by ambrisentan in this patient with CPFE can be attributed to its vasodilator and anti-proliferative actions, exerted on pulmonary the vascular bed and lung fibroblasts.