Pilar Azevedo

SELDI-TOF biomarker signatures for cystic fibrosis, asthma and chronic obstructive pulmonary disease

OBJECTIVES The aim of this work was to establish protein profiles in serum and nasal epithelial cells of cystic fibrosis individuals in comparison with controls, asthma and chronic obstructive pulmonary disease patients for specific biomarker signatures identification. DESIGN AND METHODS Protein extracts were analyzed by Surface Enhanced Laser Desorption/Ionization Time-Of-Flight Mass-Spectrometry (SELDI-TOF-MS). RESULTS The mass spectra revealed a set of peaks with differential expression in serum and nasal cells among the different groups studied, resulting into peak signatures representative/specific of each pathology. Logistic regressions were applied to those peaks; sensitivity, specificity, Youdens indexes and area under the curve (AUC) of the respective receiver operating characteristic (ROC) curves were compared. DISCUSSION Multivariate analysis demonstrated that combination of peaks has a better predictive value than the individual ones. These protein signatures may serve as diagnostic/prognostic markers for the studied diseases with common clinical features, or as follow-up assessment markers of therapeutic interventions.

Profiling the erythrocyte membrane proteome isolated from patients diagnosed with chronic obstructive pulmonary disease

Structural and metabolic alterations in erythrocytes play an important role in the pathophysiology of Chronic Obstructive Pulmonary Disease (COPD). Whether these dysfunctions are related to the modulation of erythrocyte membrane proteins in patients diagnosed with COPD remains to be determined. Herein, a comparative proteomic profiling of the erythrocyte membrane fraction isolated from peripheral blood of smokers diagnosed with COPD and smokers with no COPD was performed using differential (16)O/(18)O stable isotope labeling. A total of 219 proteins were quantified as being significantly differentially expressed within the erythrocyte membrane proteomes of smokers with COPD and healthy smokers. Functional pathway analysis showed that the most enriched biofunctions were related to cell-to-cell signaling and interaction, hematological system development, immune response, oxidative stress and cytoskeleton. Chorein (VPS13A), a cytoskeleton related protein whose defects had been associated with the presence of cell membrane deformation of circulating erythrocytes was found to be down-regulated in the membrane fraction of erythrocytes obtained from COPD patients. Methemoglobin reductase (CYB5R3) was also found to be underexpressed in these cells, suggesting that COPD patients may be at higher risk for developing methemoglobinemia. This article is part of a Special Issue entitled: Integrated omics.

New advances in the therapy of non-cystic fibrosis bronchiectasis

Non-cystic fibrosis bronchiectasis remains a common and important respiratory disease to date. It is a chronic pathology and consequently the patients usually require continuous treatment. In recent decades therapies that do not have scientific evidence of their benefits have been commonly used in non-cystic fibrosis bronchiectasis. Cystic fibrosis has provided the experience to extrapolate therapeutic approaches to other bronchiectasis patients. Finally, in the last few years some trials have been carried out specifically in non-cystic fibrosis bronchiectasis which aim to assess the efficacy of some of the treatments which are commonly used but sometimes without clear indication. This review will discuss the recent results from these trials, namely mucoactive, anti-inflammatory and antibiotic therapy. Several trials are ongoing and we hope they will be able to add clarification to the management of these patients.

Cystic fibrosis - characterization of the adult population in Portugal.

INTRODUCTION The incidence of cystic fibrosis (CF) in Portugal is estimated at 1:8000 live births, although there is a lack of accurate statistics. The average life expectancy has been steadily increasing and CF is no longer an exclusively pediatric disease. OBJECTIVES Characterize the Portuguese adult population with the diagnosis of CF. METHODS Retrospective study based on clinical data of adult CF follow-up patients in the three specialized centers in Portugal where all of CF patients are seen, during 2012. RESULTS In 2012, there were 89 follow-up patients, 48 (54%) female and 15 (17%) lung transplanted. The average age was 31.3±9 years. The median age at diagnosis was 13 years and 34 (38%) were diagnosed in adulthood. The most frequent mutation was F508del (54.9%). Of the 89 patients, 49 patients (56%) had pancreatic insufficiency, 7 (9%) were diabetic and 42 patients (47.7%) had a body mass index (BMI) <20kg/m(2). As to ventilatory function, the average value of the forced expiratory volume in 1s (FEV1) was 58.45±28.59%. Only one of 77 patients did not have chronic airway infection. The most commonly isolated germ was methicillin-sensitive Staphylococcus aureus in 49 patients (55%). During 2012, two patients (2.2%) died at the ages of 21 and 36 years. DISCUSSION This study is the first description of the Portuguese adult CF population, which is particularly important since it can give us a better understanding of the real situation. A significant percentage of these patients were diagnosed in adulthood, which highlights the need for diagnostic suspicion in a patient with chronic lung disease and atypical manifestations.

Cystic fibrosis – Comparison between patients in paediatric and adult age

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Although most cases are diagnosed in childhood, diagnosis in adults is apparently increasing. OBJECTIVE Evaluate the adult population with CF, comparing patients who were diagnosed before and after 18 years of age. METHODS Retrospective analysis of patients followed in three main medical centres in Portugal in 2012. Comparison of two groups: G1 - patients diagnosed at <18 years and G2 - patients diagnosed at ≥18 years. RESULTS 89 adults were identified: 61.8% in G1, 38.2% in G2. Gender distribution was similar in both groups. Average age in G2 was higher (38.3±8.4 vs. 26.8±6.1 years, p<0.001). Respiratory symptoms most frequently led to CF diagnosis in all patients, mainly in adulthood. There was a greater percentage of patients homozygous for the mutation delF508 in G1 (43.6 vs. 8.8%, p=0.02). Respiratory and pancreatic function, and body mass index (BMI) showed a higher severity in G1 (G1 vs. G2: FEV1: 54.6±27.3 vs. 29.9±64.6%, p=0.177; pancreatic insufficiency 72.7 vs. 26.5%, p<0.001; BMI 20.2±3.4 vs. 22.2±4.8, p=0.018). Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus were the most frequently isolated microorganisms. Lung transplantation rate was higher in G2 (20.6 vs. 10.9%, p=0.231) while mortality rate was higher in G1 (0 vs. 3.6%, p=0.261). Hospital admission rate was higher in G1 as well as mortality rate. CONCLUSION The results suggest that patients with CF diagnosed in childhood have characteristics that distinguish them from those diagnosed in adulthood, and these differences may have implications for diagnosis, prognosis and life expectancy.