A qualitative exploration of patient flow in a developing Caribbean emergency department

Objectives Emergency departments (EDs) are complex adaptive systems and improving patient flow requires understanding how ED processes work. This is important for developing countries where flow concerns are compounded by resource constraints. The Caribbean is one region with developing emergency care systems and limited research in the area. This study aimed to explore the patient flow process in an emergency department in Trinidad and Tobago, identifying organizational factors influencing patient flow. Methods Multiple qualitative methods, including non-participant observations, observational process mapping and informal conversational interviews were used to explore patient flow. The process maps were generated from the observational process mapping. Thematic analysis was used to analyze the data. Setting The study was conducted at a major tertiary level emergency department in Trinidad and Tobago. Participants Patient and staff journeys in the emergency department were observed. Results Six broad categories were identified- 1) ED organizational work processes, 2) ED design and layout, 3) material resources, 4) nursing staff levels, roles, skill mix and use 5) non-clinical ED staff and 6) external clinical and non-clinical departments. The study findings were combined with existing literature to produce a model of factors influencing ED patient flow. Barriers and facilitators to patient flow were highlighted. Conclusion The knowledge gained may be used to strengthen the emergency care system in the local context. The model of ED patient flow may be used to systematically examine factors influencing patient flow, informing policy and practice. However, the study findings should be validated in other settings

Qualitative exploration of patient flow in a Caribbean emergency department

Objectives Emergency departments (EDs) are complex adaptive systems and improving patient flow requires understanding how ED processes work. This study aimed to explore the patient flow process in an ED in Trinidad and Tobago, identifying organisational factors influencing patient flow. Methods Multiple qualitative methods, including non-participant observations, observational process mapping and informal conversational interviews were used to explore patient flow. The process maps were generated from the observational process mapping. Thematic analysis was used to analyse the data. Setting The study was conducted at a major tertiary level ED in Trinidad and Tobago. Participants Patient and staff journeys in the ED were directly observed. Results Six broad categories were identified: (1) ED organisational work processes, (2) ED design and layout, (3) material resources, (4) nursing staff levels, roles, skill mix and use, (5) non-clinical ED staff and (6) external clinical and non-clinical departments. Within each category there were individual factors that appeared to either facilitate or hinder patient flow. Organisational processes such as streaming, front loading of investigations and the transfer process were pre-existing strategies in the ED while staff actions to compensate for limitations with flow were more intuitive. A conceptual framework of factors influencing ED patient flow is also presented. Conclusion The knowledge gained may be used to strengthen the emergency care system in the local context. However, the study findings should be validated in other settings

Research paradigms and useful inventions in medicine : patents and licensing by teams of clinical and basic scientists in Academic Medical Centers

In recent decades, teams that combine basic scientists with clinical researchers have become an important organizational mechanism to translate knowledge made in basic science (“the bench”) to tangible medical innovations (“the bedside”). Our study explores whether inventing teams that span basic and clinical research are more effective at licensing than teams comprised of inventors from only one domain. We propose that laboratory science and clinical research represent fundamentally different research paradigms that defy a simple arithmetic of combining the skills of individuals on teams. Clinical and basic researchers inhabit distinct cultures of work that yield different, and sometimes conflicting, beliefs and approaches to problem-solving. We claim that the complexity and variability of most human medical problems limits the role of basic science in medical innovation. Instead, we argue that clinical research remains an important engine of innovation, even in a period of rapid advances in molecular and genetics sciences, and advanced analytical techniques, because clinical researchers have unique opportunities for insights that emerge from the joint activities of research and close observations of living patients. Our empirical analysis focuses on patents and licenses from two prominent Academic Medical Centers (AMCs) over a 30 year period. In hazard models of licensing we find, controlling for a range of effects, that inventions by teams composed of clinical researchers (MDs) are more likely to be licensed than inventions by teams of basic scientists (PhDs), and that inventions that include both MDs and PhDs are not more likely to be licensed. This leads us to question the translational model of combining expertise to bridge different domains. We also find that the training of the team leader has an effect on licensing that is independent of team composition, lending support to our interpretation. Our results help inform policy about the relationship between research paradigms, team composition, and successful innovation in bio-medicine

The organizational implications of medical imaging in the context of Malaysian hospitals

This research investigated the implementation and use of medical imaging in the context of Malaysian hospitals. In this report medical imaging refers to PACS, RIS/HIS and imaging modalities which are linked through a computer network. The study examined how the internal context of a hospital and its external context together influenced the implementation of medical imaging, and how this in turn shaped organizational roles and relationships within the hospital itself. It further investigated how the implementation of the technology in one hospital affected its implementation in another hospital. The research used systems theory as the theoretical framework for the study. Methodologically, the study used a case-based approach and multiple methods to obtain data. The case studies included two hospital-based radiology departments in Malaysia. The outcomes of the research suggest that the implementation of medical imaging in community hospitals is shaped by the external context particularly the role played by the Ministry of Health. Furthermore, influences from both the internal and external contexts have a substantial impact on the process of implementing medical imaging and the extent of the benefits that the organization can gain. In the context of roles and social relationships, the findings revealed that the routine use of medical imaging has substantially affected radiographers’ roles, and the social relationships between non clinical personnel and clinicians. This study found no change in the relationship between radiographers and radiologists. Finally, the approaches to implementation taken in the hospitals studied were found to influence those taken by other hospitals. Overall, this study makes three important contributions. Firstly, it extends Barley’s (1986, 1990) research by explicitly demonstrating that the organization’s internal and external contexts together shape the implementation and use of technology, that the processes of implementing and using technology impact upon roles, relationships and networks and that a role-based approach alone is inadequate to examine the outcomes of deploying an advanced technology. Secondly, this study contends that scalability of technology in the context of developing countries is not necessarily linear. Finally, this study offers practical contributions that can benefit healthcare organizations in Malaysia

Big Data Analytic Framework for Organizational Leverage

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Advancing Precision Medicine: Unveiling Disease Trajectories, Decoding Biomarkers, and Tailoring Individual Treatments

Chronic diseases are not only prevalent but also exert a considerable strain on the healthcare system, individuals, and communities. Nearly half of all Americans suffer from at least one chronic disease, which is still growing. The development of machine learning has brought new directions to chronic disease analysis. Many data scientists have devoted themselves to understanding how a disease progresses over time, which can lead to better patient management, identification of disease stages, and targeted interventions. However, due to the slow progression of chronic disease, symptoms are barely noticed until the disease is advanced, challenging early detection. Meanwhile, chronic diseases often have diverse underlying causes and can manifest differently among patients. Besides the external factors, the development of chronic disease is also influenced by internal signals. The DNA sequence-level differences have been proven responsible for constant predisposition to chronic diseases. Given these challenges, data must be analyzed at various scales, ranging from single nucleotide polymorphisms (SNPs) to individuals and populations, to better understand disease mechanisms and provide precision medicine. Therefore, this research aimed to develop an automated pipeline from building predictive models and estimating individual treatment effects based on the structured data of general electronic health records (EHRs) to identifying genetic variations (e.g., SNPs) associated with diseases to unravel the genetic underpinnings of chronic diseases. First, we used structured EHRs to uncover chronic disease progression patterns and assess the dynamic contribution of clinical features. In this step, we employed causal inference methods (constraint-based and functional causal models) for feature selection and utilized Markov chains, attention long short-term memory (LSTM), and Gaussian process (GP). SHapley Additive exPlanations (SHAPs) and local interpretable model-agnostic explanations (LIMEs) further extended the work to identify important clinical features. Next, I developed a novel counterfactual-based method to predict individual treatment effects (ITE) from observational data. To discern a “balanced” representation so that treated and control distributions look similar, we disentangled the doctor’s preference from the covariance and rebuilt the representation of the treated and control groups. We use integral probability metrics to measure distances between distributions. The expected ITE estimation error of a representation was the sum of the standard generalization error of that representation and the distance between the distributions induced. Finally, we performed genome-wide association studies (GWAS) based on the stage information we extracted from our unsupervised disease progression model to identify the biomarkers and explore the genetic correction between the disease and its phenotypes

The Translational Status of Cancer Liquid Biopsies

Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. This can be achieved by leveraging omics information for accurate molecular characterization of tumors. Tumor tissue biopsies are currently the main source of information for molecular profiling. However, biopsies are invasive and limited in resolving spatiotemporal heterogeneity in tumor tissues. Alternative non-invasive liquid biopsies can exploit patient’s body fluids to access multiple layers of tumor-specific biological information (genomes, epigenomes, transcriptomes, proteomes, metabolomes, circulating tumor cells, and exosomes). Analysis and integration of these large and diverse datasets using statistical and machine learning approaches can yield important insights into tumor biology and lead to discovery of new diagnostic, predictive, and prognostic biomarkers. Translation of these new diagnostic tools into standard clinical practice could transform oncology, as demonstrated by a number of liquid biopsy assays already entering clinical use. In this review, we highlight successes and challenges facing the rapidly evolving field of cancer biomarker research. Lay Summary: Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. The discovery of biomarkers for precision oncology has been accelerated by high-throughput experimental and computational methods, which can inform fine-grained characterization of tumors for clinical decision-making. Moreover, advances in the liquid biopsy field allow non-invasive sampling of patient’s body fluids with the aim of analyzing circulating biomarkers, obviating the need for invasive tumor tissue biopsies. In this review, we highlight successes and challenges facing the rapidly evolving field of liquid biopsy cancer biomarker research

Incidence of myocardial injury in patients submitted to carotid endarterectomy: a systematic review

INTRODUÇÃO Lesão miocárdica após cirurgia não cardíaca (MINS) está associada a maiores taxas de mortalidade e de eventos adversos cardiovasculares major a curto e longo prazo em doentes submetidos a endarterectomia carotídea (CEA). No entanto, a sua incidência ainda não é clara neste subgrupo de doentes. Neste sentido, esta revisão sistemática com meta-análise visa determinar a incidência de MINS em doentes submetidos a CEA. MATERIAIS E MÉTODOS Três bases de dados eletrónicas MEDLINE, Scopus e Web of Science foram utilizadas para procurar estudos que avaliassem a ocorrência de MINS no período pós-operatório de doentes submetidos a CEA. A incidência de MINS foi agrupada por meta-análise de efeitos aleatórios, com exploração de fontes de heterogeneidade por meta-regressão. Adicionalmente, a incidência de MINS relativa a subgrupos de doentes (anestesia geral vs. regional) foi analisada. A avaliação da qualidade dos estudos foi realizada utilizando National Heart, Lung, and Blood Institute (NHLBI) Study Quality Assessment Tool for Observational Cohorts and Cross-Sectional Studies e Risk of Bias 2 tools. RESULTADOS Vinte estudos foram incluídos, com um total de 117.933 participantes. Quatro desses eram ensaios clínicos randomizados controlados (RCT), sendo os restantes estudos de coorte. Todos os estudos observacionais apresentavam um risco de viés global alto, excetuando Pereira Macedo et al. Três desses tinham população repetida, pelo que só os dados do estudo mais recente foram considerados. Por outro lado, todos os RCT tinham um risco de viés global baixo. Em doentes submetidos a anestesia regional, a incidência de MINS em estudos primários variava entre 2% e 15,3%, comparando com 0-42,5% para anestesia geral. A incidência meta-analítica de MINS após CEA foi de 6,3% [95% CI 2,0%-10,6%], mas foi observada heterogeneidade severa (I2 = 99,1%). CONCLUSÃO MINS aparenta ser relativamente comum em doentes submetidos a CEA. A heterogeneidade severa observada aponta para a necessidade de estudos adicionais maiores adotando definições de MINS consistentes e valores de corte equivalentes.BACKGROUND Myocardial injury following noncardiac surgery (MINS) is associated with higher mortality and major adverse cardiovascular event rates in the short- and long-term in patients undergoing carotid endarterectomy (CEA). However, its incidence is still unclear in this subset of patients. Therefore, this systematic review with meta-analysis aims to determine the incidence of MINS in patients undergoing CEA. MATERIALS AND METHODS Three electronic databases MEDLINE, Scopus, and Web of Science were used to search for studies assessing the occurrence of MINS in the postoperative setting of patients undergoing CEA. The incidence of MINS was pooled by random-effects meta-analysis, with sources of heterogeneity being explored by meta-regression. Additionally, the incidence of MINS regarding subgroups of patients (general anesthesia vs. regional anesthesia) was also analysed. Assessment of studies' quality was performed using National Heart, Lung, and Blood Institute (NHLBI) Study Quality Assessment Tool for Observational Cohorts and Cross-Sectional Studies, and Risk of Bias 2 tools. RESULTS Twenty studies were included, with a total of 117,933 participants. Four of them were randomized controlled trials (RCT), while the remaining were cohort studies. All observational cohorts had an overall high risk of bias, except for Pereira Macedo et al. Three of them had repeated population, thus only data from the most recent one was considered. On the other hand, all RCT had an overall low risk of bias. In patients under regional anesthesia, the incidence of MINS in primary studies ranged between 2% and 15.3%, compared to 0-42.5% for general anesthesia. The meta-analytical incidence of MINS after CEA was of 6.3% [95% CI 2.0%-10.6%], but severe heterogeneity was observed (I2 = 99.1%). CONCLUSION MINS appears to be relatively common among patients undergoing CEA. The observed severe heterogeneity points to the need for further larger studies adopting consistent definitions of MINS and equivalent cut-off values

The multimorbidity of asthma and rhinitis: from epidemiologic data to molecular traits

RESUMO: Introdução e Objetivos: A asma afeta a vida de várias centenas de milhões de pessoas de todas as idades, em todo o mundo. Apesar dos avanços nas últimas décadas, a asma e a sua inerente multimorbilidade permanecem um ónus significativo para as pessoas com a doença, para as suas famílias e para a sociedade e economia da saúde. Um número elevado de questões permanece por responder, abrangendo vários aspetos da doença, relacionados com lacunas no conhecimento científico atual, desde a epidemiologia à fisiopatologia e aos cuidados prestados à pessoa com asma. O objetivo principal desta dissertação foi contribuir para a abordagem de algumas destas questões relativas à asma e a sua associação com a rinite. Em particular, os trabalhos originais visavam: (1) estimar a prevalência de asma em Portugal e analisar a sua associação com a rinite em grupos populacionais particularmente vulneráveis e sobre os quais há carência de dados a nível internacional - crianças e idosos; (2) identificar características para um reconhecimento precoce de asma, através de fenótipos clínicos multidimensionais de sibilância recorrente em idade pré-escolar, estabelecidos “sem hipóteses pré-definidas" e relacionados com a persistência de asma na adolescência; (3) analisar a associação entre parâmetros funcionais respiratórios das vias aéreas superiores e inferiores, em conjunto com a avaliação subjetiva do controlo da rinite alérgica e da asma, em crianças em idade escolar; (4) explorar estratégias inovadoras para identificar características metabólicas associadas ao fenótipo de asma e rinite alérgica em crianças, em amostras colhidas de forma não invasiva. Métodos: Esta dissertação baseou-se em três tipos de estudos: 1. Estudos transversais, baseados na população nacional, de cidadãos que viviam em Portugal, tendo sido aplicados questionários por entrevista, usando procedimentos padronizados, para a obtenção de dados epidemiológicos relativos à asma e à rinite. Para o estudo pediátrico, foram analisados os dados de todos os indivíduos com idade inferior a 18 anos que participaram no estudo INAsma (estudo por entrevista telefónica, de base populacional, nacional, para estimar a prevalência de asma em Portugal). O estudo dirigido aos idosos foi desenhado para estimar a prevalência de rinite em adultos com 65 anos ou mais, residentes em Portugal continental, tendo sido os dados colhidos por entrevista direta; 2. Estudo prospetivo de coorte de crianças com idade inferior a 7 anos com sibilância recorrente, avaliadas sistematicamente em pontos de tempo específicos, até 13 anos de seguimento. Foram desenvolvidos modelos de regressão logística multivariável para persistência de asma na adolescência, com base em respostas a questionários e resultados de testes cutâneos por picada. Os fenótipos clínicos foram identificados por análise de agrupamento das variáveis (cluster), selecionadas com base na análise de regressão logística, e comparados a respeito da persistência de asma, uso de tratamentos de controlo e avaliação funcional respiratória em idade escolar e na adolescência; 3. Estudo transversal, caso-controlo, de crianças em idade escolar, com rinite alérgica e asma, e crianças saudáveis (amostra emparelhada para a idade e género), avaliadas no que diz respeito a: - Análise laboratorial funcional respiratória, i.e., avaliações sequenciais do débito inspiratório máximo nasal (PNIF) antes e após a aplicação de vasoconstritor tópico nasal, e espirometria com prova de broncodilatação. O teste de controlo da rinite alérgica e da asma para crianças (CARATkids) foi utilizado para a avaliação subjetiva do controlo destas doenças. As associações entre os parâmetros de avaliação funcional respiratória e de controlo subjetivo foram analisadas usando modelos de regressão linear múltipla. - Análise laboratorial analítica por espectroscopia de ressonância magnética nuclear (NMR) para análise metabolómica não dirigida das amostras de urina e saliva de cada criança. Os dados espectroscópicos e clínicos foram analisados estatisticamente, incluindo abordagens multivariável e univariável. Adicionalmente foram colhidas amostras de condensado de ar exalado (EBC) de voluntários, em conjunto com amostras de ar ambiente da sala de colheitas. As amostras colhidas foram analisadas por NMR, com comparação dos espectros resultantes.Resultados: A prevalência estimada de asma ativa em crianças foi de 8,4% (intervalo de confiança a 95% (95%CI) 6,6%-10,7%). As prevalências estimadas de rinite e de asma diagnosticada por médico em idosos foram 29,8% (95CI% 28,4%-31,3%) e 10,9% (95%CI 9,9%-11,9%), respetivamente. Foi encontrada uma associação forte entre asma e rinite a nível populacional, tanto nas crianças (odds-ratio (OR) 5,2, 95%CI 3,1-8,9), como nos idosos (OR variando de 8,3 95%CI 6,1-11,4 na rinite intermitente ligeira, a 39,9 95%CI 27,5-58,0 na rinite persistente moderada-grave). No estudo de coorte, a presença de atopia e de rinite em idade pré-escolar foram fatores de risco independentes para a persistência de asma na adolescência (OR 11,8 95%CI 4,0-34,6 e OR 10,4 95%CI 3,7-29,1, respetivamente). Foram identificados três fenótipos de sibilância em idade pré-escolar, que foram preditivos para a persistência de asma, uso de medicamentos de controlo e parâmetros funcionais respiratórios em idade escolar e na adolescência. A multimorbilidade, em particular a presença de rinite, com ou sem atopia, associou-se a um pior prognóstico. Na avaliação funcional nasal e pulmonar, observaram-se correlações entre os valores de PNIF pré e pós-vasoconstritor e do débito expiratório máximo instantâneo (PEF) e volume expiratório forçado no primeiro segundo (FEV1), pré e pós-broncodilatação, observado independentemente da presença de rinite e asma. O melhor modelo de regressão linear múltipla para o PNIF incluiu as variáveis PEF, idade e género. Em crianças com rinite alérgica e asma, não foi encontrada associação entre o PNIF e a pontuação no questionário CARATkids, exceto no que diz respeito à obstrução nasal auto-reportada. A análise metabolómica não dirigida em amostras de saliva e urina mostrou um subconjunto de áreas do espetro de NMR significativamente diferente nas crianças com rinite alérgica e asma, em comparação com crianças saudáveis. Alguns metabolitos que contribuíram para estas áreas do espetro foram identificados: arginina, taurina, citrato e aspartato (na saliva), e quinolinato, butirato, pantotenato, gluconato, pseudouridina e lisina (na urina). Observou-se uma correlação entre parâmetros espirométricos e a concentração urinária dos metabolitos quinolinato, butirato e pantotenato, enquanto a dos metabolitos quinolinato, gluconato e pseudouridina estava correlacionada com os níveis de óxido nítrico no ar exalado (FeNO). Observou-se uma associação entre a presença de sensibilização alergénica múltipla e as concentrações urinárias de quinolinato e salivares de citrato e aspartato. O perfil metabólico do EBC foi semelhante à composição espectral do ar ambiente. Discussão e Conclusões: Estes estudos epidemiológicos foram os primeiros de base populacional nacional que reportaram a prevalência de sintomas de asma em todas as idades pediátricas, bem como de sintomas de rinite, sua classificação e associação com asma em idosos. Os resultados reforçaram a asma como uma doença comum em crianças e em idosos, frequentemente associada a rinite. Em crianças com sibilância recorrente em idade pré-escolar, a presença de multimorbilidade, particularmente rinite com ou sem atopia associada, tende a prever um pior prognóstico no que respeita à persistência de asma e compromisso da função respiratória em idade escolar e na adolescência. Estes resultados apoiam a necessidade de uma abordagem integrada da rinite e da asma, desde idades precoces. Para a avaliação funcional respiratória global, o PNIF pode constituir uma medida objetiva complementar à avaliação subjetiva do controlo da rinite alérgica e da asma, em crianças em idade escolar. Os resultados sugerem que na interpretação dos valores do PNIF nesta faixa etária, os valores do PEF devem idealmente ser considerados, para além da idade e do género. A análise metabolómica exploratória de amostras de urina e saliva revelou subconjuntos de áreas do espectro de NMR associadas à rinite alérgica e asma em crianças, gerando novas hipóteses que necessitam de análises suplementares. Os resultados obtidos na análise do perfil metabólico do EBC reforçaram a importância do controlo do ar ambiente durante a colheita de amostras e a necessidade de procedimentos analíticos que permitam distinguir a presença de compostos exógenos nas amostras de EBC. Em resumo, os resultados apresentados nesta dissertação adicionam evidência para uma avaliação global integrada da asma em conjunto com a rinite, tanto na prática clínica, como na investigação. Prevemos que a avaliação funcional nasal possa ser generalizada na prática clínica, numa abordagem global funcional das vias aéreas. O conjunto de metabolitos identificados na análise exploratória metabolómica estimula a continuação dos estudos nesta área para validação dos resultados, seguida da identificação das moléculas/vias metabólicas responsáveis pelas diferenças encontradas, o seu papel na fisiopatologia da rinite alérgica e asma e, por fim, como potenciais (novos) alvos terapêuticos.ABSTRACT: Introduction and Aims: Worldwide and across all age groups, asthma affects the lives of several hundred million people. In spite of the advances over the last decades, asthma and its multimorbidity continue to impart a significant onus on individuals with the disease, their families and society and also on health economies. A high number of unmet needs remain to be resolved, related to gaps in current scientific knowledge covering many aspects of asthma, from epidemiology and pathophysiology to patient care. The main objective of this dissertation was to contribute to address some of these existing unmet needs in asthma and its link with rhinitis. In particular, the original work aimed to (1) estimate nationwide asthma prevalence and analyze its association with rhinitis in particularly vulnerable and internationally data-lacking population groups – the children and the elderly; (2) unveil features for an early recognition of asthma, identifying multidimensional “hypothesis-free” early childhood wheezing clinical phenotypes related to asthma persistence in adolescence; (3) analyze the association between nasal and lower airway function, together with the subjective evaluation of allergic rhinitis and asthma concurrent control in children; (4) explore innovative strategies to uncover “unbiased” differentiating metabolic features of childhood allergic rhinitis and asthma multimorbidity in non-invasively collected samples. Methods: This dissertation was based on three types of studies: 1. Cross-sectional, population-based, nationwide surveys of citizens living in Portugal, applied by interview using standardized procedures, to collect epidemiological data related to asthma and rhinitis and to analyze the association between these two conditions. For the pediatric study, data from all individuals aged below 18 years who participated in the INAsma study (population-based, all-age, nationwide telephone interview study to estimate asthma prevalence in Portugal) was analyzed. The elderly-targeted study was originally designed to estimate rhinitis prevalence in individuals aged 65 years or above living in mainland Portugal and the data was collected by direct face-to-face interview; 2. Prospective cohort study of children aged below 7 years with recurrent wheezing, systematically evaluated at specific time-points, up to 13 years of follow-up. Multivariable logistic regression models for persistent asthma in adolescence were developed based on questionnaires and skin prick tests data. Clinical phenotypes were identified by cluster analysis of variables selected with the logistic regression analysis, and compared for predicting asthma prevalence, use of control treatments and lung function in childhood and adolescence; 3. Cross-sectional, case-control study of school-aged children with allergic rhinitis and asthma multimorbidity and healthy children (matched for age and gender), evaluated with respect to: a. Respiratory functional laboratorial assessments, i.e., sequential assessments of peak nasal inspiratory flow (PNIF) before and after nasal decongestion and spirometry with bronchodilation test. The Control of Allergic Rhinitis and Asthma Test for children (CARATkids) was used for these diseases concurrent subjective control evaluation. Associations between objective and subjective scores were investigated by multiple linear regression models. b. Analytical laboratorial study using untargeted metabolomics analysis by nuclear magnetic resonance (NMR) spectroscopy of urine and saliva samples collected from each child. Spectroscopic and clinical data were subjected to statistical analysis including multivariable and univariable approaches. Additionally, exhaled breath condensate (EBC) samples were collected from volunteers, together with room air samples, which were analyzed by NMR spectroscopy. The resulting spectra were compared.Results: The estimated prevalence of current asthma in children was 8.4% (95% confidence interval (CI) 6.6%-10.7%). The prevalence of rhinitis and of physician-diagnosed asthma in the elderly were estimated to be 29.8% (95%CI 28.4%-31.3%) and 10.9% (95%CI 9.9%-11.9%), respectively. A strong association between asthma and rhinitis at the population-level was found both in children (odds-ratio (OR) 5.2, 95%CI 3.1-8.9) and in the elderly (OR varying from 8.3, 95%CI 6.1-11.4 in mild intermittent rhinitis to 39.9, 95%CI 27.5-58.0 in moderate-severe persistent rhinitis). In the cohort study, atopy and rhinitis at preschool-age were independent risk factors for asthma persistence in adolescence (OR 11.8, 95%CI 4.0-34.6, and OR 10.4, 95%CI 3.7-29.1, respectively). Three distinct early childhood wheezing phenotypes were identified, which were predictive of asthma persistence, use of control treatments and lung function in school-age and adolescence. Multimorbidity, particularly rhinitis, with or without associated atopy, tended to predict a worse prognosis. In the nasal and lung function study, baseline and decongested PNIF correlated with baseline and post-bronchodilation peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) in school-aged children, observed independently of rhinitis and asthma diagnosis. The best linear regression model for PNIF included the variables PEF, age and gender. In children with allergic rhinitis and asthma, no association was found between PNIF and CARATkids scores, except for nasal obstruction self-report. Untargeted metabolomics analysis of saliva and urine samples revealed a subset of the spectral areas significantly different in the children with allergic rhinitis and asthma, compared to healthy controls. Some metabolites contributing to these variables were identified: arginine, taurine, citrate and aspartate (in saliva), and quinolinate, butyrate, pantothenate, gluconate, pseudouridine and lysine (in urine). Urinary quinolinate, butyrate and pantothenate concentrations correlated with spirometric parameters, while quinolinate, gluconate and pseudouridine concentrations correlated with exhaled nitric oxide (FeNO) levels. Urinary quinolinate and salivary citrate and aspartate were associated with multiple allergenic sensitization. The EBC metabolic profile was found to be highly comparable to the ambient air spectral composition. Discussion and Conclusions: These were the first population-based nationwide epidemiologic studies reporting asthma symptoms prevalence among all pediatric ages, and rhinitis prevalence, its classification and association with asthma in the elderly. Our results further support that asthma is a common disease in children and the elderly, frequently associated with rhinitis. In early childhood, the presence of multimorbidity, particularly rhinitis with or without associated atopy, tended to predict a worse prognosis of recurrent wheezing regarding asthma persistence and impaired lung function in later childhood and adolescence. These results reinforce the need for a global, integrated care pathway in asthma and rhinitis, since early ages. In this integrated assessment, PNIF may provide complementary objective information to subjective concurrent control assessment of allergic rhinitis and asthma in school-aged children. The results suggested that PEF values should ideally be considered, besides age and gender, when interpreting PNIF values in this age group. Exploratory metabolomics revealed differentiating subsets of NMR spectral features in saliva and urine associated with allergic rhinitis and asthma multimorbidity in children, generating hypotheses to be further analyzed. The results obtained in the EBC metabolic profile analysis reinforced the importance of ambient air controls during samples collection and the need for analytical procedures to distinguish exogenously originated metabolites in EBC. In summary, the results presented in this dissertation added compelling information for an integrated, global assessment of asthma together with rhinitis, in clinical practice and in research. We foresee the clinical general application of nasal and lung function evaluation in a global airways assessment strategy. The differentiating subsets of metabolites found in exploratory metabolomics analysis stimulate further studies in order to validate our findings, followed by the identification of molecules/metabolic pathways involved, its role in allergic rhinitis and asthma pathophysiology and ultimately the potential as (novel) therapeutic targets