RESUMO
BACKGROUND: Advance Care Planning (ACP) enables patients and relatives to define and share values, goals and preferences for future medical treatment and care. The IMplementing Pediatric Advance Care Planning Toolkit (IMPACT), developed in the Netherlands, is a method for conducting ACP in pediatric palliative care. Healthcare professionals who were trained to use IMPACT, indicated their need for ongoing support to practice ACP communication skills optimally over time. Therefore, we developed a team-based learning program aimed at teaching participants how to transfer knowledge on ACP, continue practicing ACP communication skills and reflect on ACP conversations within their own team context. The aim of this study was to evaluate the program's transfer of knowledge as well as the professionals' experience and team reflection on ACP. METHODS: A one-day IMPACT train-the-trainer course was developed and a selection of healthcare professionals (facilitators) from pediatric palliative care teams (PPCTs) from all seven Dutch university hospitals and the specialized Center for Pediatric Oncology were invited to participate. Hereafter, facilitators were asked to transfer their course-acquired knowledge to their team members (learners) by organizing two coaching-on-the-job sessions. A mixed-methods design, combining questionnaires and field notes, was used to evaluate the level of knowledge transfer and team reflection achieved. RESULTS: Eighteen healthcare professionals in the role of facilitator participated in the train-the-trainer course. In seven PPCTs one (n = 3) or two (n = 4) coaching-on-the-job session(s) took place, attended by 29 and 17 learners, respectively. In the questionnaires, 11 facilitators indicated that they had to some extent transferred acquired knowledge to their team members as intended. Sixteen out of 21 learners who participated in at least one coaching-on-the-job session, reported (somewhat) increased self-confidence for conducting ACP conversations. The reported main strength of the program was practicing with/learning from colleagues whereas dealing with workload and variation in existing ACP skills within PPCTs need more attention. CONCLUSIONS: The newly developed team-based learning program resulted in intended transfer of knowledge and methodical reflection on ACP in coaching-on-the-job sessions in most participating PPCTs. Planning coaching-on-the-job sessions regarding ACP in pediatric palliative care with multiple healthcare professionals is challenging and needs more emphasis in the training.
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Planejamento Antecipado de Cuidados , Cuidados Paliativos , Pediatria , Humanos , Planejamento Antecipado de Cuidados/normas , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Países Baixos , Pediatria/métodos , Pediatria/educação , Inquéritos e Questionários , Masculino , Feminino , Adulto , Pessoal de Saúde/educação , Equipe de Assistência ao PacienteRESUMO
Phenomenon: Entrustable professional activities (EPAs) delineate major professional activities that an individual in a given specialty must be "entrusted" to perform, ultimately without supervision, to provide quality patient care. Until now, most EPA frameworks have been developed by professionals within the same specialty. As safe, effective, and sustainable health care ultimately depends on interprofessional collaboration, we hypothesized that members of interprofessional teams might have clear and possibly additional insight into which activities are essential to the professional work of a medical specialist. Approach: We recently employed a national modified Delphi study to develop and validate a set of EPAs for Dutch pediatric intensive care fellows. In this proof-of-concept study, we explored what pediatric intensive care physicians' non-physician team members (physician assistants, nurse practitioners, and nurses) constitute as essential professional activities for PICU physicians and how they regarded the newly developed set of nine EPAs. We compared their judgments with the PICU physicians' opinions. Findings: This study shows that non-physician team members share a mental model with physicians about which EPAs are indispensable for pediatric intensive care physicians. Despite this agreement however, descriptions of EPAs are not always clear for non-physician team members who have to work with them on a daily basis. Insights: Ambiguity as to what an EPA entails when qualifying a trainee can have implications for patient safety and trainees themselves. Input from non-physician team members may add to the clarity of EPA descriptions. This finding supports the involvement of non-physician team members in the developmental process of EPAs for (sub)specialty training programs.
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Educação Baseada em Competências , Internato e Residência , Criança , Humanos , Competência Clínica , Currículo , Cuidados CríticosRESUMO
Entrustable professional activities (EPAs), units of professional practice that require proficient integration of multiple competencies and can be entrusted to a sufficiently competent learner, are increasingly being used to define and inform curricula of health care professionals. The process of developing EPAs can be challenging and requires a deep yet pragmatic understanding of the concepts underlying EPA construction. Based on recent literature and the authors' lessons learned, this article provides the following practical and more or less sequential recommendations for developing EPAs: [1] Assemble a core team; [2] Build up expertise; [3] Establish a shared understanding of the purpose of EPAs; [4] Draft preliminary EPAs; [5] Elaborate EPAs; [6] Adopt a framework of supervision; [7] Perform a structured quality check; [8] Use a Delphi approach for refinement and/or consensus; [9] Pilot test EPAs; [10] Attune EPAs to their feasibility in assessment; [11] Map EPAs to existing curriculum; [12] Build a revision plan.
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Currículo , Internato e Residência , Humanos , Local de Trabalho , Pessoal de Saúde , Educação Baseada em Competências , Competência ClínicaRESUMO
BACKGROUND: The Irish General Practitioner Training (GP) Programme is currently moving to Competency-Based Medical Education (CBME), facilitated by Programmatic Assessment (PA) and Entrustable Professional Activities (EPAs). These new assessment and feedback mechanisms may provide a rich and much sought-after dataset. However, given the possible number of feedback and assessment events, and the variety of modalities used, aggregating and interpreting these can be costly and difficult. Dashboard implementations (DI) have been purposed as a solution to bridge the gap between the large datasets and the training community at all levels. AIMS: To explore the Irish GP training community's perceptions on how an EPAs DI could facilitate the delivery of GP training in Ireland. METHODS: A qualitative approach was taken, using a focus group representative of different groups in the training community. Concurrently, an EPAs DI was developed. Focus group transcripts were analysed in an iterative fashion using Template Analysis to generate themes and subthemes. RESULTS: Numerous advantages were seen in relation to the implementation of an EPAs DI around entrustment decisions, constructive alignment and summative decision-making. These advantages, however, need to be tempered with the realisation that the EPAs DI is not and should not be misinterpreted as being the learning analytic panacea for GP training. CONCLUSION: This paper outlines the perceptions from a postgraduate medical education training community on an EPAs DI, which would be applicable to other training communities considering introducing similar mechanisms.
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Medicina Geral , Internato e Residência , Humanos , Irlanda , Educação Baseada em Competências , Currículo , Grupos Focais , Competência ClínicaRESUMO
INTRODUCTION: Entrustable professional activities (EPAs), discrete profession-specific tasks requiring integration of multiple competencies, are increasingly used to help define and inform curricula of specialty training programmes. Although guidelines exist to help guide the developmental process, deciding what logic to use to draft a preliminary EPA framework poses a crucial but often difficult first step. The logic of an EPA framework can be defined as the perspective used by its developers to break down the practice of a profession into units of professional work. This study aimed to map dominant logics and their rationales across postgraduate medical education and fellowship programmes. METHODS: A scoping review using systematic searches within five electronic databases (Medline, Embase, Google Scholar, Scopus and Web of Science) was performed. Dominant logics of included papers were identified using inductive coding and iterative analysis. RESULTS: In total, 42 studies were included. Most studies were conducted in the United States (n = 22; 52%), Canada (n = 6; 14%) and the Netherlands (n = 4; 10%). Across the reported range of specialties, family medicine (n = 4; 10%), internal medicine (n = 4; 10%), paediatrics (n = 3; 7%) and psychiatry (n = 3; 7%) were the most common. Three dominant logics could be identified, namely, 'service provision', 'procedures' and/or 'disease or patient categories'. The majority of papers (n = 37; 88%) used two or more logics when developing EPA frameworks (median = 3, range = 1-4). Disease or patient groups and service provision were the most common logics used (39% and 37%, respectively). CONCLUSIONS: Most programmes used a combination of logics when trying to capture the essential tasks of a profession in EPAs. For each of the three dominant logics, the authors arrived at a definition and identified benefits, limitations and examples. These findings may potentially inform best practice guidelines for EPA development.
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Educação Médica , Internato e Residência , Psiquiatria , Criança , Competência Clínica , Educação Baseada em Competências , Currículo , Humanos , Medicina Interna/educação , Lógica , Psiquiatria/educação , Estados UnidosRESUMO
The COVID-19 pandemic has disrupted many societal institutions, including health care and education. Although the pandemic's impact was initially assumed to be temporary, there is growing conviction that medical education might change more permanently. The International Competency-based Medical Education (ICBME) collaborators, scholars devoted to improving physician training, deliberated how the pandemic raises questions about medical competence. We formulated 12 broad-reaching issues for discussion, grouped into micro-, meso-, and macro-level questions. At the individual micro level, we ask questions about adaptability, coping with uncertainty, and the value and limitations of clinical courage. At the institutional meso level, we question whether curricula could include more than core entrustable professional activities (EPAs) and focus on individualized, dynamic, and adaptable portfolios of EPAs that, at any moment, reflect current competence and preparedness for disasters. At the regulatory and societal macro level, should conditions for licensing be reconsidered? Should rules of liability be adapted to match the need for rapid redeployment? We do not propose a blueprint for the future of medical training but rather aim to provoke discussions needed to build a workforce that is competent to cope with future health care crises.
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COVID-19 , Educação Médica , Internato e Residência , Competência Clínica , Educação Baseada em Competências , Currículo , Objetivos , Humanos , Pandemias , SARS-CoV-2RESUMO
During severe respiratory syncytial virus (RSV) bronchiolitis there is a massive influx of activated neutrophils to the lungs. An exaggerated immune response contributes to lung damage and disease severity during RSV infection. We have previously shown that normal adult neutrophil function can be modulated by agonists of SIRL-1. Here we aimed to measure the potential of two immune checkpoints: SIRL-1 and LAIR-1, to regulate the function of fresh blood and sputum neutrophils from infants with and without severe RSV bronchiolitis. We show a modest inhibition of the oxidative burst through SIRL-1 and LAIR-1, in control and RSV-infected infants. In addition, SIRL-1 and LAIR-1 inhibited neutrophil extracellular traps (NET) formation by sputum neutrophils of RSV patients. Altogether our data show that inhibitory receptors LAIR-1 and SIRL-1 can be used to regulate neutrophil function.
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Neutrófilos/imunologia , Receptores Imunológicos/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Adulto , Armadilhas Extracelulares , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Explosão Respiratória , Escarro/citologia , Escarro/imunologiaRESUMO
BACKGROUND: Neutrophils are the most abundant cell type infiltrating the airways during severe respiratory syncytial virus (RSV) infection. Their exact role in disease pathophysiology remains enigmatic. Therefore, we determined genome-wide RNA expression profiles of local and systemic neutrophils in RSV bronchiolitis to provide further insight into local neutrophil biology. METHODS: We performed a single-center analysis, in 16 infants, admitted to the pediatric intensive care unit with severe RSV bronchiolitis. Neutrophils were isolated from blood and tracheobronchial aspirates (sputum). After low input RNA sequencing, differential expression of genes was determined followed by gene set analysis. RESULTS: Paired transcriptomic analysis of airway versus blood neutrophils showed an inflammatory phenotype, characterized by NF-kB signaling and upregulated expression of IL-6 and interferon pathways. We observed distinct expression of neutrophil activation genes (TNFSF13B, FCER1G). DISCUSSION: Our data indicate that airway neutrophils regulate their function at the transcriptional level in response to viral infection. It also suggests that local interferon drives the neutrophil response of severe RSV bronchiolitis.
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Bronquiolite/genética , Bronquiolite/imunologia , Neutrófilos/imunologia , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/imunologia , Transcriptoma , Fator Ativador de Células B/genética , Bronquiolite/sangue , Feminino , Humanos , Lactente , Interferons/imunologia , Pulmão/citologia , Pulmão/imunologia , Masculino , NF-kappa B/imunologia , RNA , Receptores Fc/genética , Infecções por Vírus Respiratório Sincicial/sangueRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is a global cause of severe respiratory morbidity and mortality in infants. While preventive and therapeutic interventions are being developed, including antivirals, vaccines and monoclonal antibodies, little is known about the global molecular epidemiology of RSV. INFORM is a prospective, multicenter, global clinical study performed by ReSViNET to investigate the worldwide molecular diversity of RSV isolates collected from children less than 5 years of age. METHODS: The INFORM study is performed in 17 countries spanning all inhabited continents and will provide insight into the molecular epidemiology of circulating RSV strains worldwide. Sequencing of > 4000 RSV-positive respiratory samples is planned to detect temporal and geographical molecular patterns on a molecular level over five consecutive years. Additionally, RSV will be cultured from a subset of samples to study the functional implications of specific mutations in the viral genome including viral fitness and susceptibility to different monoclonal antibodies. DISCUSSION: The sequencing and functional results will be used to investigate susceptibility and resistance to novel RSV preventive or therapeutic interventions. Finally, a repository of globally collected RSV strains and a database of RSV sequences will be created.
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Genoma Viral , Epidemiologia Molecular/métodos , Polimorfismo Genético , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano/genética , Anticorpos Monoclonais/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Pré-Escolar , Farmacorresistência Bacteriana/genética , Feminino , Genótipo , Humanos , Imunização Passiva , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Vírus Sincicial Respiratório Humano/imunologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
IL-17 and T-helper (Th)17 cells contribute to viral airway pathology in human newborns. Because umbilical cord blood T cells fail to differentiate toward the Th17 lineage in the presence of autologous antigen-presenting cells, we asked whether Th17 cells are present in young infants that experience respiratory viral infection. To this end, we analyzed tracheal aspirate samples from infant patients suffering from acute respiratory syncytial virus (RSV) infection and healthy infant controls. Acute RSV infection associates with elevated IL-17 and accumulation of CD161(+) T cells in acute RSV infected lungs. Correspondingly, local Th17 polarizing cytokines were increased. In peripheral blood, we show that Th17 cells are absent in healthy 1-month-old infants, but are present in acute RSV patients. The triggering of pathogen-associated pattern receptors TLR4 and TLR7 promotes the generation of a Th17-polarizing cytokine environment by 1-month-old infant dendritic cell (DC). We thus conclude that although Th17 cells are absent in healthy newborns, Th17 cells are present in peripheral blood and the airways of infants that experience viral infection, thereby contributing to airway immunopathology.
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Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/imunologia , Células Th17/imunologia , Adulto , Polaridade Celular , Citocinas/biossíntese , Células Dendríticas/imunologia , Humanos , Lactente , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Infecções por Vírus Respiratório Sincicial/patologia , Receptores Toll-Like/metabolismoRESUMO
OBJECTIVE: Respiratory syncytial virus lower respiratory tract infection is the most frequent cause of respiratory insufficiency necessitating mechanical ventilation in infants during the winter season. Recently, we presented a new animal model to show that mechanical ventilation aggravates respiratory syncytial virus-induced pulmonary inflammation by distinct mechanisms. We now use this model to study whether low tidal volume mechanical ventilation causes less ventilator-induced lung injury in the presence of respiratory syncytial virus lower respiratory tract infection. DESIGN: Randomized controlled experimental study. SETTING: University Medical Center animal laboratory. SUBJECTS: Male BALB/c mice, 6-8 weeks old and weighing 20-28 g. INTERVENTIONS: Mice were inoculated with respiratory syncytial virus or mock virus on day 0 and ventilated on day 1 or 5 with high (12 mL/kg) or low (6 mL/kg) tidal volume for 5 hours. MEASUREMENTS AND MAIN RESULTS: Total and differential cell counts as well as cytokine concentrations were determined in bronchoalveolar lavage fluid. Compared with nonventilated respiratory syncytial virus-infected mice, high tidal volume ventilation of respiratory syncytial virus-infected mice on day 5 enhanced bronchoalveolar lavage fluid total cell count (0.35 vs 0.99 × 10e6/mL; p < 0.01), neutrophils (0.02 vs 0.17 × 10e6/mL; p < 0.01), interleukin-6 (58 vs 250 pg/mL; p < 0.01), and keratinocyte-derived chemokine (95 vs 335 pg/mL; p < 0.01) levels. In low tidal volume ventilation of respiratory syncytial virus-infected mice, no significant difference in cell counts or cytokine concentrations was observed compared with spontaneous breathing respiratory syncytial virus-infected controls on both days. CONCLUSIONS: Low tidal volume mechanical ventilation causes less ventilation-induced cellular and cytokine influx into the bronchoalveolar space during respiratory syncytial virus lower respiratory tract infection.
Assuntos
Neutrófilos , Respiração com Pressão Positiva/efeitos adversos , Respiração com Pressão Positiva/métodos , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Quimiocinas/análise , Modelos Animais de Doenças , Interleucina-6/análise , Contagem de Leucócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Infecções por Vírus Respiratório Sincicial/complicações , Volume de Ventilação Pulmonar , Lesão Pulmonar Induzida por Ventilação Mecânica/etiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/patologiaAssuntos
Bronquiolite Viral/imunologia , Armadilhas Extracelulares/imunologia , Neutrófilos/imunologia , Receptores Imunológicos/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/imunologia , Bronquiolite Viral/patologia , Feminino , Humanos , Masculino , Neutrófilos/patologia , Infecções por Vírus Respiratório Sincicial/patologiaRESUMO
INTRODUCTION: Given the complexity of teaching clinical reasoning to (future) healthcare professionals, the utilization of serious games has become popular for supporting clinical reasoning education. This scoping review outlines games designed to support teaching clinical reasoning in health professions education, with a specific emphasis on their alignment with the 8-step clinical reasoning cycle and the reflective practice framework, fundamental for effective learning. METHODS: A scoping review using systematic searches across seven databases (PubMed, CINAHL, ERIC, PsycINFO, Scopus, Web of Science, and Embase) was conducted. Game characteristics, technical requirements, and incorporation of clinical reasoning cycle steps were analyzed. Additional game information was obtained from the authors. RESULTS: Nineteen unique games emerged, primarily simulation and escape room genres. Most games incorporated the following clinical reasoning steps: patient consideration (step 1), cue collection (step 2), intervention (step 6), and outcome evaluation (step 7). Processing information (step 3) and understanding the patient's problem (step 4) were less prevalent, while goal setting (step 5) and reflection (step 8) were least integrated. CONCLUSION: All serious games reviewed show potential for improving clinical reasoning skills, but thoughtful alignment with learning objectives and contextual factors is vital. While this study aids health professions educators in understanding how games may support teaching of clinical reasoning, further research is needed to optimize their effective use in education. Notably, most games lack explicit incorporation of all clinical reasoning cycle steps, especially reflection, limiting its role in reflective practice. Hence, we recommend prioritizing a systematic clinical reasoning model with explicit reflective steps when using serious games for teaching clinical reasoning.
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Raciocínio Clínico , Humanos , Ocupações em Saúde/educação , Competência Clínica , Jogos de Vídeo , EnsinoRESUMO
Background: Developing theoretical courses for post-graduate medical training that are aligned to current workplace-based learning practices and adaptive to change in the field is challenging, especially in (sub) specialties where time for re-design is limited and needs to be performed while education continues. Approach: An instructional design method was applied based on flexible co-design to improve post-graduate theoretical courses in child and adolescent psychiatry (CAP) in the Netherlands. In four phases over a period of three years, courses were re-designed at a national level. Evaluation: Once common vision and learning goals were agreed upon and the prototype was developed (phases 1 and 2), the first courses could be tested in daily practice (phase 3). Phase 4 refined these courses in brief iterative cycles and allowed for designing additional courses building on and adding to previous experiences in brief iterative cycles. The resulting national theoretical courses re-allocated resources previously spent on a local level using easily accessible online tools. This allowed trainees to align content with their clinical rotations, personal preferences and training schedules. Reflection: The development of theoretical courses for post-graduate medical training in smaller medical (sub-)specialties with limited resources may profit from a flexible instructional design method. We consider the potential merit of such a method to other medical specialties and other (inter-)national efforts to develop theoretical teaching courses. A longer-term implementation evaluation is needed to show to what extent the investment made in the re-design proves to be future-proof and enables rapid adaptation to changes in the field.
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Educação de Pós-Graduação em Medicina , Humanos , Educação de Pós-Graduação em Medicina/métodos , Países Baixos , Currículo/tendências , Psiquiatria do Adolescente/educação , Psiquiatria do Adolescente/métodos , Psiquiatria Infantil/educação , Psiquiatria Infantil/métodosRESUMO
Background: Most faculty development programs in health professions education, pivotal in cultivating competent and effective teachers, focus on systematic, planned and formal learning opportunities. A large part of clinical teaching however, encompasses ad-hoc, informal and interprofessional workplace-based learning whereby individuals learn as part of everyday work activities. To fully harness the educational potential embedded in daily healthcare practices, prioritizing interprofessional faculty development for workplace-based learning is crucial. Approach: Utilizing the 'ADDIE' instructional design framework we developed, implemented and evaluated an interprofessional faculty development program for workplace-based learning. This program, encompassing seven formal training sessions each with a different theme and five individual workplace-based assignments, aimed to support clinical teachers in recognizing and optimizing informal learning. Outcomes: The pilot program (n = 10) and first two regular courses (n = 13 each) were evaluated using questionnaires containing Likert scale items and open textboxes for narrative comments. The quality and relevance of the program to the clinical work-place were highly appreciated. Additional valued elements included practical knowledge provided and tools for informal workplace-based teaching, the interprofessional aspect of the program and the workplace-based assignments. Since its development, the program has undergone minor revisions twice and has now become a successful interprofessional workplace-based alternative to existing faculty development programs. Reflection: This faculty development program addresses the specific needs of healthcare professionals teaching in clinical settings. It stands out by prioritizing informal learning, fostering collaboration, and supporting integration of formal training into daily practice, ensuring practical application of learned knowledge and skills. Furthermore, it emphasizes interprofessional teaching and learning, enhancing workplace environments.
Assuntos
Relações Interprofissionais , Desenvolvimento de Pessoal , Local de Trabalho , Humanos , Local de Trabalho/normas , Local de Trabalho/psicologia , Desenvolvimento de Pessoal/métodos , Inquéritos e Questionários , Educação Interprofissional/métodos , Desenvolvimento de Programas/métodos , Docentes de Medicina/educação , Projetos Piloto , Docentes/educaçãoRESUMO
OBJECTIVE: Opioids are frequently used during mechanical ventilation for severe viral infection in infancy. Opioid receptors have immunomodulatory properties, but nothing is known about their antiviral effects. We therefore aimed to investigate the role of opioid receptors in virus-induced airway inflammation. PATIENTS AND INTERVENTIONS: Two single nucleotide polymorphisms in OPRM1 and OPRD1 were genotyped in 465 infants with severe respiratory syncytial virus infection and 930 control subjects. Subsequently, the mechanism by which opioid receptors affect clinical outcome in respiratory syncytial virus bronchiolitis was studied in BALB/c mice. Animals were injected daily with nalmefene, a nonselective opioid receptor antagonist, and infected by intranasal inoculation of respiratory syncytial virus 24 hrs after the first dose of nalmefene. The potential therapeutic effect of pharmaceutical opioids was studied using µ (DAMGO), κ (U50488), and Δ (DPDPE) opioid receptor agonists 48 hrs after infection. MEASUREMENTS AND MAIN RESULTS: In our human study, the A118G single nucleotide polymorphism rs1799971 was associated with respiratory syncytial virus disease severity (p = 0.015). In mice, nalmefene treatment increased viral titers and was associated with more pronounced weight loss. Increased viral replication was associated with increased levels of cytokines and chemokines in the bronchoalveolar lavage fluid, enhanced bronchoalveolar cellular influx, and exaggerated lung pathology. Pharmaceutical opioids, in particular DPDPE, did not affect viral replication. They did induce a decreased influx of neutrophils, but an increased influx of lymphocytes and monocytes into the bronchoalveolar lumen during respiratory syncytial virus infection. CONCLUSIONS: Using a human study and an experimental model, we show that opioid receptor signaling has a potential beneficial role in the outcome of respiratory viral disease. We show that opioid receptor signaling is required to control respiratory syncytial virus replication and thereby to control disease severity. However, we also show that caution is required before using pharmaceutical opioids as anti-inflammatory or antiviral treatment of patients with viral respiratory infection.
Assuntos
Analgésicos Opioides/farmacologia , Bronquiolite/virologia , Polimorfismo Genético , Receptores Opioides delta/genética , Receptores Opioides mu/genética , Receptores Opioides/genética , Infecções por Vírus Respiratório Sincicial/virologia , Replicação Viral/efeitos dos fármacos , Analgésicos Opioides/uso terapêutico , Animais , Bronquiolite/tratamento farmacológico , Bronquiolite/genética , Bronquiolite/imunologia , Estudos de Casos e Controles , Quimiocinas/metabolismo , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lactente , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Receptores Opioides/metabolismo , Respiração Artificial , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/genética , Infecções por Vírus Respiratório Sincicial/imunologia , Sistema Respiratório/virologia , Transdução de Sinais/efeitos dos fármacos , Carga ViralRESUMO
BACKGROUND: Hemorrhagic shock (HS) is known to induce an inflammatory response by activating the immune system. This response is mainly caused by primed polymorphonuclear granulocytes (PMNs). Trauma patients often require mechanical ventilation (MV), which can cause additional pulmonary and systemic inflammation. The aim of this study was to evaluate the role of MV in the development of systemic and pulmonary inflammation in a HS model in rats. MATERIALS AND METHODS: In male Sprague-Dawley rats, the effect of MV and HS on the systemic and pulmonary inflammatory responses was measured and compared. In five groups (control, sham, MV, HS, and MV + HS), the inflammation was measured at time point 300 min after the start of the experiment. RESULTS: The systemic inflammatory response, expressed in absolute numbers of PMNs in blood and blood growth related oncogene (GRO-KC) levels, was significantly higher in MV rats compared with that in other groups. The pulmonary inflammatory response, expressed by PMNs in bronchoalveolar lavage fluid (BALF), BALF interleukin 6, BALF GRO-KC, and myeloperoxidase activity, was significantly higher in all ventilated rats compared with that in the controls or HS rats. There was, however, no additional effect of HS in MV as the inflammatory indices were similar in both groups. CONCLUSIONS: Our data show that HS alone has minimal effect on the development of inflammation. MV (alone or in combination with HS) is the determining factor in inducing an inflammatory response. These results emphasize the importance of local (pulmonary) ventilation-induced damage in the development of systemic inflammation.
Assuntos
Inflamação/etiologia , Respiração Artificial/efeitos adversos , Choque Hemorrágico/complicações , Animais , Masculino , Neutrófilos/fisiologia , Pneumonia/etiologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Posttraumatic lung contusion is common after blunt chest trauma, and patients often need ventilatory support. Lung contusion induces an inflammatory response signified by primed polymorph neutrophil granulocytes (PMNs) in blood and tissue. Mechanical ventilation (MV) can also cause an inflammatory response. The aim of this study was to develop an animal model to investigate the effect of high-volume ventilation on the inflammatory response in blunt chest trauma. MATERIALS AND METHODS: We assigned 23 male Sprague-Dawley rats to either MV or bilateral lung contusion followed by MV. We used three extra rats as controls. Lung contusion was induced by a blast generator, a device releasing a single pressure blast wave centered on the chest. We determined tissue and systemic inflammation by absolute PMN numbers in blood and bronchoalveolar lavage fluid (BALF), myeloperoxidase, interleukin (IL)-6, IL 1ß, growth-related oncogene-KC, and IL-10 in both plasma and BALF. RESULTS: Survival after blunt chest trauma was correlated to the distance to the blast generator. Compared with controls, both MV and blast plus MV rats showed increased systemic and pulmonary inflammation, expressed by higher PMNs, myeloperoxidase levels, and cytokine levels in both blood and BALF. Blast plus MV rats showed a higher systemic and pulmonary inflammatory response than MV rats. CONCLUSIONS: The blast generator generated reproducible blunt chest trauma in rats. Mechanical ventilation after lung contusion induced a larger overall inflammatory response than MV alone, which indicates that local damage contributes not only to local inflammation, but also to systemic inflammation. This emphasizes the importance of lung protective ventilation strategies after pulmonary contusion.