Cristina Bárbara

Systems Medicine Approaches for the Definition of Complex Phenotypes in Chronic Diseases and Ageing. From Concept to Implementation and Policies

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

AIRWAYS-ICPs (European Innovation Partnership on Active and Healthy Ageing) from concept to implementation

Chronic respiratory diseases (CRDs) are major non-communicable diseases (NCDs) [1, 2] that induce a significant burden. Asthma often occurs along the life cycle from early childhood, affecting 30 million children and adults under 45 years of age in Europe [3]. Chronic obstructive pulmonary disease (COPD) has an estimated annual death rate of over 3 million people globally [1, 2]. The annual direct and indirect costs in the 28 European Union (EU) countries due to COPD or asthma are estimated at 48 billion euros and 34 billion euros respectively [3]. Rhinitis occurs in over 100 million people in Europe, and indirect costs are enormous [4]. Asthma is a common risk factor for COPD [5, 6]. CRDs impact ageing and should be prevented, recognised and managed across the life cycle to promote active and healthy ageing (AHA). There is an urgent need to act globally. AIRWAYS-ICPs is a European Union initiative on multi-sectoral care pathways for chronic respiratory diseases http://ow.ly/Yndtw

Comorbilidades em doentes com doença pulmonar obstrutiva crónica estádio IV

INTRODUCTION Chronic Obstructive Pulmonary Disease (COPD) is associated with several co-morbidities, however their prevalence varies from one study to another. AIM To determine the prevalence of several co-morbidities in patients with COPD severity score GOLD 4 (The Global Initiative for Chronic Obstructive Lung Disease, 2010) followed in ambulatory care, in a University Hospital. METHODS A questionnaire was designed and carried out in order to characterize COPD and its co-morbidities. Clinical files were consulted in order to complete the data. RESULTS 89 patients (87% male) with a mean age of 68 years old, of which 79% were ex-smokers, were included. The average value of FEV1 (forced expiratory volume in one second) was 38% of the expected values and all the patients presented chronic respiratory failure. Thirty-five patients (39%) were frequent exacerbators. Thirty-seven patients (42%) had been hospitalized at least once due to exacerbation of their respiratory disease in the previous year, and 66 patients (74%) hospitalized in the previous five years. Most of the patients (97%) presented at least one comorbidity, with an average of 4 co-morbidities per patient and an average Charlson index of 2. The most frequent co-morbidities were cardiovascular diseases (69%), osteoarticular pathology (51%), erectile dysfunction (48%), sleep apnoea syndrome (43%) dyslipidaemia (35%), cataracts (31%), gastroesophageal reflux (29%) and diabetes (20%). Frequent exacerbators presented an increased risk of having two or more co-morbidities (Odds Ratio of 5), as well as a higher prevalence of gastroesophageal reflux (p=0.0006) and more hospitalizations in the last year and in the previous 5 years (p <0.001). CONCLUSION This study confirmed the high prevalence and the association of co-morbidities in patients with COPD severity score GOLD 4, thus justifying the need for a comprehensive and integrating therapeutic approach.

Pressões máximas respiratórias

RESUMO As autoras fazem uma revisao de literature sobre as metodologias utilizadas pelos diversos autores na medicao das Pressoes Maximas Respirarorias (PMR). Definem a Pressao Inspiratoria Maxima e a Pressao Expiratoria Maxima e descrevem as principais indicacoes para a determinacao das PMR. Nas diferentes metodologias descritas, incluem o tipo de bocal, a presenca de orificio de fuga, o tipo de manometro, o nivel de volume pulmonar em que sao efectuadas as medicoes, o numero de manobras realizadas em cada medicao, a posicao corporal adoptada, o uso de pinca nasal e as equacoes de referencia. Apos a revisao de literatura apresentam uma proposta para o protocolo de medicao das Pressoes Maximas Respiratorias. REV PORT PNEUMOL 2000; VI (4): 297-307

Overview of proteomics studies in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is an underdiagnosed common public health concern causing deleterious effects on metabolic and cardiovascular health. Although much has been learned regarding the pathophysiology and consequences of OSA in the past decades, the molecular mechanisms associated with such processes remain poorly defined. The advanced high-throughput proteomics-based technologies have become a fundamental approach for identifying novel disease mediators as potential diagnostic and therapeutic targets for many diseases, including OSA. Here, we briefly review OSA pathophysiology and the technological advances in proteomics and the first results of its application to address critical issues in the OSA field.

Bronchoalveolar Lavage Proteomics in Patients with Suspected Lung Cancer

Lung cancer configures as one of the deadliest types of cancer. The future implementation of early screening methods such as exhaled breath condensate analysis and low dose computed tomography (CT) as an alternative to current chest imaging based screening will lead to an increased burden on bronchoscopy units. New approaches for improvement of diagnosis in bronchoscopy units, regarding patient management, are likely to have clinical impact in the future. Diagnostic approaches to address mortality of lung cancer include improved early detection and stratification of the cancers according to its prognosis and further response to drug treatment. In this study, we performed a detailed mass spectrometry based proteome analysis of acellular bronchoalveolar lavage (BAL) fluid samples on an observational prospective cohort consisting of 90 suspected lung cancer cases which were followed during two years. The thirteen new lung cancer cases diagnosed during the follow up time period clustered, based on liquid chromatography-mass spectrometry (LC-MS) data, with lung cancer cases at the time of BAL collection. Hundred and thirty-tree potential biomarkers were identified showing significantly differential expression when comparing lung cancer versus non-lung cancer. The regulated biomarkers showed a large overlap with biomarkers detected in tissue samples.

Inspiratory muscle training in COPD patients

AIM The aim of this study was to evaluate the impact a specific inspiratory muscle training (IMT) protocol had on dyspnoea, lung function, respiratory muscle pressure, tolerance to exercise and quality of life in a group of patients with chronic obstructive pulmonary disease (COPD) POPULATION: We studied 13 patients with moderate to very severe COPD divided into a control group (n=5) with an average FEV1 43.9 +/- 10.1% of predicted value and an IMT group (n=8) with FEV1 57.8 +/- 12.1 % of predicted value. While this study group underwent IMT for five consecutive weeks, the control group did not undergo any kind of training. RESULTS Using a specific IMT protocol significantly improved maximal inspiratory pressure (MIP) in the study group (initial MIP - 83.3+/- 21.4 versus final MIP- 98.4+/-17.8 cmH2O;p<0.01). The same result was seen with the St. George Respiratory Questionnaire (SGRQ) score in the study group (initial score 58+/-2.2 versus final score 50+/-2.1; p<0.05). No changes were recorded in the variables studied in the control group. CONCLUSIONS The use of IMT in patients with moderate to very severe COPD induced an improvement in inspiratory muscle force with a consequent improvement in the quality of life in relation to symptoms.

Obstructive sleep apnea : epidemiology and portuguese patients profile

INTRODUCTION Obstructive Sleep Apnea (OSA) is characterized by recurrent episodes of apnea and hypopnea, secondary to collapse of the upper airways during sleep. OSA is frequently associated to cardiovascular complications. In Portugal, its magnitude is unknown. METHODS In 2014 a cross-sectional study was performed using the Portuguese General Practitioner (GP) Sentinel Network (Rede Médicos Sentinela). Participants GP reported all OSA cases diagnosed and registered in their lists of users on the 31 December 2013. Frequency of OSA has been estimated by sex and age. OSA patients were also characterized by method of diagnosis, treatment, and underlying conditions. Association between risk factors and severe OSA (odds ratio) was calculated using a logistic regression model adjusting confounding. RESULTS Prevalence of OSA on the population aged 25 years or more was 0.89% (95 CI: 0.80-1.00%); it was higher in males 1.47% (95 CI: 1.30-1.67%) and in those aged between 65 and 74 (2.35%). Most had severe OSA (48.4%). Hypertension (75.9%), obesity (74.2%) and diabetes mellitus (34.1%) were the most frequent comorbidities. Being a male (OR: 2.6; 95 CI: 1.2-5.8) and having obesity (OR: 4.0; 95 CI: 1.8-8.6) were associated with an increased risk of severe OSA. CONCLUSION Found frequency of OSA was lower than other countries estimates, which may be explained by differences on case definition but can also suggest underdiagnosis of this condition as reported by other authors.

Pulmonary function in portuguese firefighters

INTRODUCTION Portugal has had a high rate of forest fires in recent years. Inhaled wood smoke can have short- and long-term effects on the lung function of people exposed to it. STUDY OBJECTIVES To assess the lung function of active wildland (forest) firefighters. METHODS Cross-sectional study. A self-questionnaire on personal and work habits was used and spirometry values were obtained using Piko-6 for a 209 people sample. RESULTS We found a high rate of smoking (42.9%) and an 11.8% prevalence of obstruction. 41.7% of the obstructed individuals were non-smokers, did not state a knowledge of any respiratory disease, engaged in no other activity that could be related to lung function decrease and did not wear airway protection apparatus. 85.7% did not use any airway protection apparatus when firefighting due to lack of such equipment in their brigades. CONCLUSIONS Data showed that there is a high pre- valence of smoking habits in this sample of Portuguese firefighters; there is an unsatisfactory usage of airway protection apparatus and the prevalence of airway obstruction is higher than the COPD prevalence in the Portuguese population. We recommend stopping smoking and use of equipment for respiratory protection.

Pulmonary Rehabilitation in COPD: Effect of 2 Aerobic Exercise Intensities on Subject-Centered Outcomes—A Randomized Controlled Trial

BACKGROUND: Exercise training is an important component of pulmonary rehabilitation, but it remains questionable how training intensity affects patient-centered outcomes. The aim of this study was to compare the effects of 2 aerobic training intensities on health-related quality of life (HRQOL), symptom control, and exercise tolerance in subjects with COPD. METHODS: Thirty-four subjects with mild to very severe COPD participated in an equivalence/non-inferiority randomized controlled trial with a parallel group blinded to 60 or 80% maximum work rate (Wmax) aerobic training intensity. The intervention was an out-patient pulmonary rehabilitation program conducted 3 times/week for 8 weeks. Outcomes were assessed with the St George Respiratory Questionnaire (primary outcome), Mahlers dyspnea index, London Chest Activity of Daily Living scale, 6-min walk test, and constant-load and incremental exercise tests. RESULTS: Subjects were randomly allocated to aerobic training intensity of 60% Wmax (group 1, n = 17) or 80% Wmax (group 2, n = 17). Although there were significant improvements in all outcomes for both groups, there were no between-group differences in mean change in the St George Respiratory Questionnaire (P = .31, 95% CI −12.0 to 3.9), Mahlers dyspnea index (P = .38), London Chest Activity of Daily Living scale (P = .92), 6-min walk test (P = .50, 95% CI 6.2–71.1), constant-load exercise test (P = .50), and incremental exercise test (P = .12). There was only one exercise-related adverse event of cardiac symptoms. CONCLUSIONS: Aerobic training intensity of at least 60% Wmax has a positive impact on COPD patient-centered outcomes, with no additional benefit of increasing intensity to 80% Wmax in HRQOL, symptom control, and exercise tolerance, challenging the present clinical attitude of rehabilitation professionals. (ClinicalTrials.gov registration NCT01944072.)