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Objectives: The combination of Lumacaftor and Ivacaftor (LUM/IVA) has been approved for treatment of cystic fibrosis (CF) patients homozygous for the Phe508del mutation. Only one report is available detailing the positive effects of LUM/IVA on physical activity (PA) and exercise tolerance. The aim of this study is to assess the long-term impact of this therapy on daily PA and exercise tolerance. Methods: In this 12 month-long multicenter study, lung function and exercise tolerance will be prospectively evaluated through spirometry and cardiopulmonary exercise testing (CPET) in a cohort of CF patients candidate to treatment with LUM/IVA. CPET-related measurements will include: minute ventilation, oxygen uptake (V9O2), indices of ventilatory efficiency, oxygen saturation, registered at peak exercise and throughout the test. Daily PA will be monitored using a multi-sensor armband (SenseWear Pro3 Armband, SWA) that patients will wear at home for seven full consecutive typical days. Health-related quality of life will be assessed by the adult version of the revised Italian CFQ-R questionnaire. All the procedures will be performed at baseline and at 6 and 12 months after initiation of LUM/IVA therapy. Results: Five adults with CF (median age 30 years (range 28 – 43 years); median FEV1 75(68–113)% pred; median BMI 22.1(17.1–24.2)kg/m2) were recruited between June and October 2019. Baseline median V’O2 peak value was 27.0(24.9–38.4)ml/min/kg, corresponding to 67.0(59.7–110.1)% predicted. Conclusions: Preliminary data collected after 6 months on LUM/IVA therapy will be presented at the ERS 2020 event.

Expanding from China around the World, COVID-19 is the disease caused by the Severe Acute Respiratory Syndrome Related Coronavirus 2 (SARS-CoV-2). COVID-19 primarily manifests by hypoxic normo-hypocapnia with preserved lung compliance [1]. In the absence of targeted treatment, sub-intensive clinicians support patients with non-invasive ventilation and anti-inflammatory/anti-viral agents waiting for status improvement. Angiotensin-converting enzyme 2 (ACE2), highly expressed on the external membrane of lungs, heart, kidney and gastrointestinal tract cells, displays the binding site for the spike protein of SARS-CoV-2 [2]. ACE2, identified as counterpart of the Renin-Angiotensin-Aldosterone System (RAAS), converts Angiotensin (Ang) II to Ang-(1-7) and Ang I to Ang-(1-9). ACE2 activity induces vasodilatation and reduces cell growth and inflammatory response. In experimental models that mimic the viral acute respiratory distress syndrome (ARDS), the absence of Ace2 led to inflammation, vascular permeability and lung injury via activation of Ang II pathway [3, 4]. The decrease in ACE2 activity by SARS-CoV-2 can unleash a cascade of injurious effects through a heightened imbalance in the actions of the products of ACE versus ACE2. Moving to a clinical setting, the ACE2 downregulation may be one of the pathways sustaining arterial hypertension [5] and pulmonary arterial hypertension [6]. Therefore, it is conceivable that in COVID-19 a cleavage of membrane ACE2 along with its circulatory levels could impact on the disease progression and clinical worsening [7]. Thus, to support a pathophysiological role of ACE2, the present report shares clinical data from an observational study conducted on 40 patients with a diagnosis of COVID-19, hospitalised in the Cardiorespiratory Sub-Intensive COVID-19 Unit at the Fondazione IRCCS Ca' Granda Policlinico Hospital of Milan., In COVID-19 patients respiratory failure is associated with increase systemic blood pressure conceivably due to the modulation of renin-angiotensin-aldosterone system by SARS-CoV-2 infection.

Introduction: The presence of pulmonary hypertension (PH) before lung transplantation (LuTx) is a well known risk factor for primary graft dysfunction (PGD). However, the role of the comprehensive cardiopulmonary hemodynamic assessed before LuTx is limited. We aimed to explore if other hemodynamic variables may have a role in PGD, besides absolute PH. Methods: a retrospective study was conducted at Policlinico Hospital of Milan (Italy) on adults who underwent LuTx for any indication other than cystic fibrosis from 2011 to 2017. PGD was defined as PaO2/FIO2 Results: among 67 patients (57% male, median age 58 years), 28 (42%) had PGD. PH was prevalent in PGD+ group (57% vs 33%, p=0.045). PAWP showed the strongest difference (PAWP: 13.0 vs 10.0 mmHg, p=0.036), while RAP was slightly higher in PGD+ group (RAP: 7.0 vs 5.5 mmHg, p=0.048). No differences were observed between PVR or IC (PVR: 2.61 vs 2.62 UW, p=0.622; CI: 3.13 vs 3.07 l/min/mq, p=0.760). Conclusion: our data confirm that PH is an important factor in PGD. However normal median values of PVR together with a higher median PAWP may suggest a predominant role of the post capillary component in this disease. From this point of view, RAP may reflect the overload of the right ventricle caused by higher total afterload. Thus, PAWP should be considered in PGD’s development.