Elexacaftor/tezacaftor/ivacaftor, a game-changer in cystic fibrosis: The Portuguese experience.

BACKGROUND: Phase 3 trials of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) combination treatment in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele showed profound short-term effects on lung function, weight, and pulmonary exacerbations (PEx). The authors conducted a 12-month study to add evidence on the real-world long-term effectiveness and safety of CFTR modulator therapy with ELX/TEZ/IVA in Portuguese CF adult population. METHODS: Ambispective, multicentre, observational, real-life study involving all the Portuguese CF Reference Centres. Adult patients on treatment with ELX/TEZ/IVA combination outside clinical trials were included. Demographics, efficacy, and safety variables on the first 12 months of treatment were compared with the pre-treatment year. RESULTS: 132 adult people with CF were included, of which 119 completed 12 months treatment (mean duration of treatment 21.5 months). Mean age was 31.7 ± 11.0 years, 53 % patients were homozygous for the F508del variant, baseline sweat chloride was 86.7 ± 25.9 mmol/L and pre-treatment percent-predicted FEV1 was 77.9 ± 19.7 %. At 1 year, mean absolute change from baseline in FEV1 was +0.46L (95 % CI: 0.37, 0.55; p < 0.001) and +13.9 percentage points (95 % CI: 11.5, 16.2; p < 0.001). PEx episodes decreased by 78 % (p < 0.001) and hospitalizations for PEx decreased by 91.4 % (p < 0.001). Body mass index (BMI) increased 1.2 kg/m2 (95 % CI: 0.9, 1.5; p < 0.001). Mean sweat chloride variation was -44.5 mmol/L (95 % CI: -49.8, -39.2; p < 0.001). No correlation was found between sweat chloride and lung function (r = -0.116, p = 0.335). There were no major safety concerns. Of note, headache was reported in 7.6 % and neuropsychiatric manifestations occurred in 12.6 % treated patients, being anxiety and depressive disorders the most common. CONCLUSIONS: ELX/TEZ/IVA treatment in Portuguese adults with CF was associated with significant improvement in lung function, a drop in PEx and PEx-related hospitalizations and increase in BMI at 12 months and was well tolerated. These results add knowledge to our understanding of clinical benefits and tolerability of ELX/TEZ/IVA. Careful evaluation of adverse effects of ELX/TEZ/IVA therapy and its determinants, mainly concerning mental health, are a research priority.

COPD and Cardiovascular Disease.

COPD is one of the major public health problems in people aged 40 years or above. It is currently the 4th leading cause of death in the world and projected to be the 3rd leading cause of death by 2020. COPD and cardiac comorbidities are frequently associated. They share common risk factors, pathophysiological processes, signs and symptoms, and act synergistically as negative prognostic factors. Cardiac disease includes a broad spectrum of entities with distinct pathophysiology, treatment and prognosis. From an epidemiological point of view, patients with COPD are particularly vulnerable to cardiac disease. Indeed, mortality due to cardiac disease in patients with moderate COPD is higher than mortality related to respiratory failure. Guidelines reinforce that the control of comorbidities in COPD has a clear benefit over the potential risk associated with the majority of the drugs utilized. On the other hand, the true survival benefits of aggressive treatment of cardiac disease and COPD in patients with both conditions have still not been clarified. Given their relevance in terms of prevalence and prognosis, we will focus in this paper on the management of COPD patients with ischemic coronary disease, heart failure and dysrhythmia.

Understanding COPD: A vision on phenotypes, comorbidities and treatment approach.

Chronic Obstructive Pulmonary Disease (COPD) phenotypes have become increasingly recognized as important for grouping patients with similar presentation and/or behavior, within the heterogeneity of the disease. The primary aim of identifying phenotypes is to provide patients with the best health care possible, tailoring the therapeutic approach to each patient. However, the identification of specific phenotypes has been hindered by several factors such as which specific attributes are relevant, which discriminant features should be used for assigning patients to specific phenotypes, and how relevant are they to the therapeutic approach, prognostic and clinical outcome. Moreover, the definition of phenotype is still not consensual. Comorbidities, risk factors, modifiable risk factors and disease severity, although not phenotypes, have impact across all COPD phenotypes. Although there are some identified phenotypes that are fairly consensual, many others have been proposed, but currently lack validation. The on-going debate about which instruments and tests should be used in the identification and definition of phenotypes has contributed to this uncertainty. In this paper, the authors review present knowledge regarding COPD phenotyping, discuss the role of phenotypes and comorbidities on the severity of COPD, propose new phenotypes and suggest a phenotype-based pharmacological therapeutic approach. The authors conclude that a patient-tailored treatment approach, which takes into account each patient's specific attributes and specificities, should be pursued.

[Minimally invasive thoracic surgery: a fifteen-years experience]. / Cirurgia torácica minimamente invasiva. Experiêcia de 15 anos.

The evolution of surgical techniques has rendering possible for thoracic surgery to be performed efficiently and safely, with less aggressive approaches. Being less traumatic, minimally invasive surgery allows a faster post-operative recovery, less complications and reduces in patient days and morbidity. The authors consider as minimally invasive approaches the video-assisted thoracic surgery, as well as the minithoractomy and the ministernotomy. The present paper reviews thoracic surgeries performed for the last 15 years in a cardiothoracic surgical unit using a minimally invasive surgical approach.

[Relapsing pleural effusion and gastric polyposis: a case report]. / Derrame pleural recidivante e polipose gástrica - Caso clínico.

The authors present the case of a lymphoproliferative disorder (LPD) with pleuro-pulmonary involvement. It was a very aggressive primary gastric lymphoma of the MALT subtype, diagnosed in an 86-year-old woman admitted in Pulmonology ward at our Hospital with pleural effusion. Helicobacter pylori search was negative, what is infrequent. The disease was already disseminated at the time of the diagnosis and did not respond to various treatment modalities, what is also an uncommon finding. Clinical presentation, diagnosis and management of this disease are reviewed, pointing out its unique features and comparing the particular aspects of this case with the published literature. The authors stress that LPD is an important diagnosis to be held in mind in the case of a pleural effusion of unknown aetiology.

Asthma hospital admission and mortality in mainland Portugal 2000-2007.

We conducted a review of asthma hospital admissions in mainland Portugal 2000-2007 to evaluate if one of the aims of the National Asthma Control Programme, a 20% reduction in hospital admissions in children and adolescents in 2007, had been achieved. Using the Health Services Central Administration data base we reviewed 24271 admissions and saw that 48.7% of patients admitted were aged under 19 years old and that 61.8% were aged 40 years old or under. Mean global annual asthma hospital admission rate was 30.79 per 100,000 inhabitants. Mean global hospital stay was 5.94 days, range 2.93 - 9.73 days, depending on the age group. We saw a drop in admission in both the northern and the Lisbon and Tagus Valley regions over the 8 year period. 189 patients died, 25 of who were aged 40 years old or under. The mortality rate ranged from 0.162 in 2002 to 0.324 per 100,000 inhabitants in 2005, with a mean patient death of 0.77 patients per 100 admissions. Mean annual costs were in excess of euro3.3 million, meaning an estimated annual financial asthma burden of around euro117.5 million in Portugal. We concluded that many asthma sufferers in Portugal do have sufficient disease controlled. Improved management would equal better quality of life and reduced disease costs.