RESUMO
This study aimed to investigate the effect of sulfasalazine in preventing and treating intra-abdominal sepsis-induced acute respiratory distress syndrome (ARDS) in a rat model. Forty male Wistar albino rats were used. The rats were randomly divided into four equal groups, and sepsis was induced in 30 rats by intraperitoneal administration of a fecal saline solution prepared from rat feces. Group 1: normal control (n=10) [non-surgical], Group 2: fecal intraperitoneal injection (FIP) (n=10) [untreated septic group], Group 3: FIP+saline (placebo) (n=10) [saline administered intraperitoneally], Group 4 (n=10): FIP+sulfasalazine [250 mg/kg per day administered intraperitoneally]. Computed tomography was performed and blood samples were collected for biochemical and blood gas analysis. The lungs were removed for histopathological studies. Statistically significant reductions in interleukin (IL)-6, IL1-ß, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), and angiopoietin-2 (ANG-2) levels were observed in the sulfasalazine group compared to the FIP+saline group (P<0.001). Nrf2 levels were significantly higher in the sulfasalazine-treated group than in the FIP and FIP+saline groups (P<0.01). Lung tissue scores were significantly reduced in the sulfasalazine group compared to the other sepsis groups. The Hounsfield unit (HU) value was significantly lower in the sulfasalazine group than in the FIP+saline group (P<0.001). PaO2 values were significantly higher in the sulfasalazine-treated group than in the FIP+saline-treated group (P<0.05). Sulfasalazine was shown to be effective in preventing and treating ARDS.
Assuntos
Lesão Pulmonar , Síndrome do Desconforto Respiratório , Sepse , Animais , Masculino , Ratos , Angiopoietina-2/metabolismo , Pulmão , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Wistar , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/prevenção & controle , Sepse/complicações , Sepse/tratamento farmacológico , Sulfassalazina/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Gradually changing respiratory rate (RR) during time to reduce ventilation-induced lung injury has not been investigated. The authors hypothesized that gradual, compared with abrupt, increments in RR would mitigate ventilation-induced lung injury and that recruitment maneuver before abruptly increasing RR may prevent injurious biologic impact. METHODS: Twenty-four hours after intratracheal administration of Escherichia coli lipopolysaccharide, 49 male Wistar rats were anesthetized and mechanically ventilated (tidal volume, 6 ml/kg; positive end-expiratory pressure, 3 cm H2O) with RR increase patterns as follows (n = 7 per group): (1) control 1, RR = 70 breaths/min for 2 h; (2) and (3) abrupt increases of RR for 1 and 2 h, respectively, both for 2 h; (4) shorter RR adaptation, gradually increasing RR (from 70 to 130 breaths/min during 30 min); (5) longer RR adaptation, more gradual increase in RR (from 70 to 130 breaths/min during 60 min), both for 2 h; (6) control 2, abrupt increase of RR maintained for 1 h; and (7) control 3, recruitment maneuver (continuous positive airway pressure, 30 cm H2O for 30 s) followed by control-2 protocol. RESULTS: At the end of 1 h of mechanical ventilation, cumulative diffuse alveolar damage scores were lower in shorter (11.0 [8.0 to 12.0]) and longer (13.0 [11.0 to 14.0]) RR adaptation groups than in animals with abrupt increase of RR for 1 h (25.0 [22.0 to 26.0], P = 0.035 and P = 0.048, respectively) and 2 h (35.0 [32.0 to 39.0], P = 0.003 and P = 0.040, respectively); mechanical power and lung heterogeneity were lower, and alveolar integrity was higher, in the longer RR adaptation group compared with abruptly adjusted groups; markers of lung inflammation (interleukin-6), epithelial (club cell secretory protein [CC-16]) and endothelial cell damage (vascular cell adhesion molecule 1 [VCAM-1]) were higher in both abrupt groups, but not in either RR adaptation group, compared with controls. Recruitment maneuver prevented the increase in VCAM-1 and CC-16 gene expressions in the abruptly increased RR groups. CONCLUSIONS: In mild experimental acute respiratory distress syndrome in rats, gradually increasing RR, compared with abruptly doing so, can mitigate the development of ventilation-induced lung injury. In addition, recruitment maneuver prevented the injurious biologic impact of abrupt increases in RR.
Assuntos
Produtos Biológicos , Lesão Pulmonar , Síndrome do Desconforto Respiratório , Ratos , Masculino , Animais , Ratos Wistar , Taxa Respiratória , Molécula 1 de Adesão de Célula Vascular , Síndrome do Desconforto Respiratório/prevenção & controle , Pressão Positiva Contínua nas Vias AéreasRESUMO
COVID-19 is a newly emerged disease that has become a global public health challenge. Due to a lack of knowledge about the virus, a significant number of potential targets for using a particular drug have been proposed. Five cases with a clinical history of biopolymers in the gluteal region that developed iatrogenic allogenosis (IA) are presented here. The 5 cases were put under colchicine treatment for IA crisis and had non-specific symptoms (headache, cough without dyspnea, and arthralgias) with a positive SARS-CoV-2 test. Their close contacts had mild to severe symptoms and three of them died. In the SARS-CoV-2 infection different inflammatory pathways are altered where colchicine reduces cytokine levels as well as the activation of macrophages, neutrophils, and the inflammasome. The possible mechanisms that colchicine may use to prevent acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection are also reviewed in this article.
Assuntos
Anti-Inflamatórios/uso terapêutico , Tratamento Farmacológico da COVID-19 , Colchicina/uso terapêutico , Síndrome do Desconforto Respiratório/prevenção & controle , Moduladores de Tubulina/uso terapêutico , Adulto , COVID-19/complicações , COVID-19/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/virologia , Índice de Gravidade de DoençaRESUMO
Pediatric acute respiratory distress syndrome (PARDS) is a frequent diagnosis in critical care. This inflammatory process has different stages characterized by mild-to-severe hypoxia, and the management will vary according to the severity. New definitions for pediatric patients were published in 2015; new epidemiological evidence revising those definitions has helped understand the mortality associated with PARDS and the impact on ventilation. The strategies to protect the lungs during mechanical ventilation have been successful in reducing mortality and complications. In clinical situations where high levels of critical support are limited, other therapies with a lower level of evidence can be attempted to gain time without worsening the ongoing pulmonary injury. We offer a complete narrative revision of this syndrome, with the critical management of these patients as a priority.
El síndrome de dificultad respiratoria aguda pediátrica (SDRAP) es un diagnóstico frecuente en cuidados intensivos. Este proceso inflamatorio se caracteriza por diferentes grados de hipoxia, de leve a grave, y el manejo varía de acuerdo con la gravedad. En 2015 se publicaron nuevas definiciones para pacientes pediátricos, así como nueva evidencia epidemiológica, que toma como punto de partida dichas definiciones, lo cual ha ayudado a entender la mortalidad asociada y el impacto del manejo ventilatorio con respecto a la morbilidad en este síndrome. Las estrategias que protegen los pulmones durante la ventilación mecánica han sido exitosas en reducir la mortalidad y las complicaciones subsecuentes. En situaciones en las que existen limitaciones que impiden suministrar altos niveles de soporte crítico se pueden implementar otras medidas de menor evidencia para ganar tiempo e impedir que se extiendan las lesiones pulmonares. A continuación, se ofrece una revisión narrativa completa de este síndrome, con un enfoque que prioriza el manejo crítico de estos pacientes.
Assuntos
Respiração Artificial , Síndrome do Desconforto Respiratório , Criança , Humanos , Pulmão , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório/prevenção & controleRESUMO
OBJECTIVE: To evaluate the association that protective mechanical ventilation (MV), based on VT and maximum distending pressure (MDP), has with mortality in patients at risk for ARDS. METHODS: This was a prospective cohort study conducted in an ICU and including 116 patients on MV who had at least one risk factor for the development of ARDS. Ventilatory parameters were collected twice a day for seven days, and patients were divided into two groups (protective MV and nonprotective MV) based on the MDP (difference between maximum airway pressure and PEEP) or VT. The outcome measures were 28-day mortality, ICU mortality, and in-hospital mortality. The risk factors associated with the adoption of nonprotective MV were also assessed. RESULTS: Nonprotective MV based on VT and MDP was applied in 49 (42.2%) and 38 (32.8%) of the patients, respectively. Multivariate Cox regression showed that protective MV based on MDP was associated with lower in-hospital mortality (hazard ratio = 0.37; 95% CI: 0.19-0.73) and lower ICU mortality (hazard ratio = 0.40; 95% CI: 0.19-0.85), after adjustment for age, Simplified Acute Physiology Score 3, and vasopressor use, as well as the baseline values for PaO2/FiO2 ratio, PEEP, pH, and PaCO2. These associations were not observed when nonprotective MV was based on the VT. CONCLUSIONS: The MDP seems to be a useful tool, better than VT, for adjusting MV in patients at risk for ARDS.
Assuntos
Respiração Artificial , Síndrome do Desconforto Respiratório , Humanos , Respiração com Pressão Positiva , Estudos Prospectivos , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/prevenção & controle , Fatores de RiscoRESUMO
BACKGROUND: The ARDS (Acute Respiratory Distress Syndrome) is a severe respiratory syndrome that was recently associated as the main death cause in the COVID-19 pandemic outbreak. Hence, in order to prevent ARDS, the pulmonary function maintenance has been the target of several pharmacological approaches. However, there is a lack of reports regarding the use of effective pharmaceutical active natural products (PANPs) for early treatment and prevention of COVID-19-related ARDS. Therefore, the aim of this work was to conduct a systematic review regarding the PANPs that could be further studied as alternatives to prevent ARDS. Consequently, this work can pave the way to spread the use of PANPs on the prevention of ARDS in COVID-19-confirmed or -suspected patients. METHODS: The search strategy included scientific studies published in English from 2015 to 2020 that promoted the elucidation of anti-inflammatory pathways targeting ARDS by in vitro and/or in vivo experiments using PANPs. Then, 74 studies regarding PANPs, able to maintain or improve the pulmonary function, were reported. CONCLUSIONS: The PANPs may present different pulmonary anti-inflammatory pathways, wherein (i) reduction/attenuation of pro-inflammatory cytokines, (ii) increase of the anti-inflammatory mediators' levels, (iii) pulmonary edema inhibition and (iv) attenuation of lung injury were the most observed biological effects of such products in in vitro experiments or in clinical studies. Finally, this work highlighted the PANPs with promising potential to be used on respiratory syndromes, allowing their possible use as alternative treatment at the prevention of ARDS in COVID-19-infected or -suspected patients.
Assuntos
Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Tratamento Farmacológico da COVID-19 , Mediadores da Inflamação/antagonistas & inibidores , Síndrome do Desconforto Respiratório/prevenção & controle , Animais , Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , COVID-19/diagnóstico , COVID-19/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/metabolismoRESUMO
The COVID-19 pandemic has reached most of the countries worldwide causing death, which often results from an inflammatory storm associated with severe acute respiratory syndrome (SARS). This has prompted researchers to seek specific novel and definitive treatments urgently. In this context, it is interesting to evaluate the preventive and therapeutic effects of existing pharmacological agents that could be useful. In this regard, vitamin D supplementation, particularly in individuals likely to be deficient, may be a promising option. Vitamin D is a hormone that modulates many of the same inflammatory and oxidative signaling pathways triggered during COVID-19. For example, vitamin D suppresses the actions of the renin-angiotensin system, which has a determining role in the pathophysiology of the inflammatory response related to COVID-19. This paper analyzes the evidence that vitamin D supplementation might be a valuable preventive/therapeutic measure in groups at risk for or infected with COVID-19. It also discusses how clinical studies could be best designed to evaluate the possible advantages of vitamin D supplementation for the benefit of public health during the pandemic.
Assuntos
COVID-19/prevenção & controle , Suplementos Nutricionais , Pandemias/prevenção & controle , Síndrome do Desconforto Respiratório/prevenção & controle , SARS-CoV-2/metabolismo , Vitamina D/uso terapêutico , Animais , COVID-19/epidemiologia , COVID-19/metabolismo , COVID-19/patologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologiaRESUMO
It has been 50 years since the first description of the respiratory distress syndrome or acute respiratory distress syndrome (ARDS), advances from the physiopathological view are immense, unfortunately, the case fatality rate has had little variation, it is important to disseminate the knowledge to achieve the proper diagnosis and treatment.
Han pasado 50 años desde la descripción original del síndrome de distrés respiratorio o síndrome de dificultad respiratoria aguda (SDRA), los avances desde el punto de vista fisiopatológico son inmensos, desgraciadamente la letalidad ha tenido poca variación, por ello sigue siendo importante difundir el conocimiento requerido para lograr el diagnóstico y tratamiento adecuados.
Assuntos
Síndrome do Desconforto Respiratório , História do Século XX , Humanos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/história , Síndrome do Desconforto Respiratório/prevenção & controle , Fatores de TempoRESUMO
Malaria is a serious disease and was responsible for 429,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications of severe malaria; it is characterized by a high mortality rate and can even occur after antimalarial treatment when parasitemia is not detected. Rodent models of ALI/ARDS show similar clinical signs as in humans when the rodents are infected with murine Plasmodium. In these models, it was shown that the induction of the enzyme heme oxygenase 1 (HO-1) is protective against severe malaria complications, including cerebral malaria and ALI/ARDS. Increased lung endothelial permeability and upregulation of VEGF and other pro-inflammatory cytokines were found to be associated with malaria-associated ALI/ARDS (MA-ALI/ARDS), and both were reduced after HO-1 induction. Additionally, mice were protected against MA-ALI/ARDS after treatment with carbon monoxide- releasing molecules or with carbon monoxide, which is also released by the HO-1 activity. However, high HO-1 levels in inflammatory cells were associated with the respiratory burst of neutrophils and with an intensification of inflammation during episodes of severe malaria in humans. Here, we review the main aspects of HO-1 in malaria and ALI/ARDS, presenting the dual role of HO-1 and possibilities for therapeutic intervention by modulating this important enzyme.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Heme Oxigenase-1/farmacologia , Heme Oxigenase-1/uso terapêutico , Malária/tratamento farmacológico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Permeabilidade Capilar , Monóxido de Carbono/farmacologia , Monóxido de Carbono/uso terapêutico , Citocinas/metabolismo , Modelos Animais de Doenças , Endotélio , Humanos , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Malária/complicações , Proteínas de Membrana , Camundongos , Neutrófilos , Plasmodium/patogenicidade , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/prevenção & controle , RoedoresRESUMO
Students presenting with varying degrees of respiratory symptoms and distress occur commonly in the school setting. It is important to develop a differential diagnosis for respiratory distress, to initiate stabilization of the student with life-threatening symptoms, and to triage these students to an appropriate level of care (back to the classroom, home with their guardian with follow up at their primary health care provider's office, or directly to the closest emergency department via Emergency Medical Services). This article describes the initial assessment and management of a student presenting with respiratory distress.
Assuntos
Crianças com Deficiência , Diagnóstico de Enfermagem , Síndrome do Desconforto Respiratório/enfermagem , Estudantes , Criança , Humanos , Guias de Prática Clínica como Assunto , Síndrome do Desconforto Respiratório/prevenção & controle , Serviços de Saúde Escolar , Serviços de Enfermagem EscolarRESUMO
BACKGROUND: Ventilation with low tidal volume (VT) is well recognized as a protective approach to patients with acute respiratory distress syndrome (ARDS), but the optimal level of positive end-expiratory pressure (PEEP) remains uncertain. This study aims to evaluate two protective ventilatory strategies sequentially applied in patients with early ARDS. METHODS: In this prospective cohort study, fifteen patients were ventilated during 24 h with positive end-expiratory pressure (PEEP) adjusted according to the ARDSnet low-PEEP table (ARDSnet-24 h). During the next 24 h, nine patients with PaO2/FIO2 ratio below 350 mmHg were ventilated with PEEP titrated according to the Open Lung Concept protocol (ARDSnet + OLC). In the other six patients, regardless of their PaO2/FIO2 ratio, the ARDSnet remained for a further 24 h (ARDSnet-48 h). Ventilatory variables, arterial blood-gas and cytokine were obtained at baseline, 24 and 48 h. Additionally, whole-lung-computed tomography was acquired at 24 and 48 h. RESULTS: A sustained improvement in PaO2/FIO2 ratio (P = 0.008) with a decrease in collapsed regions (P = 0.008) was observed in the ARDSnet + OLC group compared with the ARDSnet-24 h group. A reduction in IL-6 in plasma (P < 0.02) was observed throughout the protocol in the ARDSnet + OLC group. Compared with the ARDSnet-48 h group, the ARDSnet + OLC presented smaller amounts of collapsed areas (P = 0.018) without significant differences in hyperinflated regions and in driving and plateau pressures. CONCLUSIONS: In this set of patients with early ARDS, mechanical ventilation with an individually tailored PEEP sustained improved pulmonary function with better aeration, without significant increase in hyperinflated areas". TRIAL REGISTRATION: Brazilian Clinical Trials Registry (ReBec). RBR-5zm9pr. 04th November 2015.
Assuntos
Respiração com Pressão Positiva/métodos , Atelectasia Pulmonar/prevenção & controle , Síndrome do Desconforto Respiratório/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Gasometria , Feminino , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Atelectasia Pulmonar/complicações , Atelectasia Pulmonar/diagnóstico por imagem , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/complicações , Tomografia Computadorizada Espiral , Adulto JovemRESUMO
FUNDAMENTO: el Centro Nacional Coordinador de Ensayos Clínicos, el Centro Nacional de Sanidad Agropecuaria y unidades de cuidados intensivos cubanas, ejecutaron ensayos clínicos con SURFACEN® para tratar el síndrome de dificultad respiratoria. OBJETIVO:describir la actuación ética en el diseño, conducción y monitoreo de estos ensayos clínicos, así como determinar su validez interna y externa. MÉTODOS: se realizó un estudio prospectivo y descriptivo entre 2004 y 2014. Se diseñaron protocolos, cuadernos de recogida de datos, consentimiento informado; se planificaron sitios clínicos, recursos humanos y materiales; se capacitaron investigadores clínicos y se monitoreó la ejecución de ensayos clínicos fase II, III y IV, que evaluaron el efecto, la eficacia, efectividad y seguridad del SURFACEN® para tratar el síndrome de dificultad respiratoria en tres grupos poblacionales: neonatos, niños (entre 28 días y 18 años de edad) y adultos. RESULTADOS: participaron 41 unidades de cuidados intensivos (17 de neonatología, 7 de pediatría y 17 de adultos). Se evaluaron 1 413 pacientes y se incluyeron 306. Se capacitaron en Buenas Prácticas Clínicas 709 profesionales de la salud. Del monitoreo, revisión de la documentación y los procederes realizados, se evidenció el cumplimiento de las normas éticas para la investigación en humanos. La validez interna de los resultados se demostró con la objetividad de la observación, comparación recurrente y asignación aleatoria de tratamientos, planificación y ejecución conforme a las Guías de Buenas Prácticas Clínicas. La validez externa se evidenció en la modificación del registro sanitario del producto con la aprobación de tres nuevas indicaciones: en el síndrome de dificultad respiratoria aguda en pediatría y adultos, así como el uso temprano (primeras 2 horas de vida) en recién nacidos pre-términos. CONCLUSIONES: el diseño, la conducción y el monitoreo de ensayos clínicos con SURFACEN® cumplimentó los principios éticos básicos para la investigación clínica y garantizó la validez interna y externa de los resultados.
BACKGROUND: the Coordinating National Center of Clinical Trial, the National Center of Agricultural Health and the Cuban intensive care units carried out clinical trials with SURFACEN® to treat respiratory distress syndrome. Objective: to describe the ethical in the design, conduction and monitoring of these clinical trials, as well as determine its internal and external validity. METHODS: a descriptive, prospective study was conducted between 2004 and 2014. Protocols, data collecting notebooks and informed consent were designed; clinical sites, human and material resources were planned; clinical investigators were trained; also, the implementation of clinical trials stages II, III, and IV that evaluated the effect, effectiveness and security of SURFACEN® to treat respiratory distress syndrome in three population groups: newborn babies, infants, children (up to 18 years old) and adults, was monitored. RESULTS: forty-one intensive care units participated (17 of neonatology, 7 for pediatric patients and 17 for adults), 1 413 patients were evaluated and 306 were included and 709 health professionals were trained in Good Clinical Practice. The performance of the ethical norms for the investigation in human beings could be shown in the monitoring, the revision of the documentation and the carried-out procedures. The internal validity of the results could be shown through the objectivity of the observation, the recurrent comparison and the random assignment of treatments, and through the planning and performance according to the Guides of Good Clinical Practice. The external validity could be shown in the change of the legislation of the product with the approval of three new indications: for the acute respiratory distress syndrome in pediatric patients and adults and for preterm babies with an early use (two hours old). CONCLUSIONS: the design, conduction and monitoring of clinical trials with SURFACEN® performed the basic ethical principles for the clinical investigation and guaranteed the internal and external validity of the results.
Assuntos
Humanos , Recém-Nascido , Adulto Jovem , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Síndrome do Desconforto Respiratório , Síndrome do Desconforto Respiratório/prevenção & controle , Síndrome do Desconforto Respiratório/reabilitação , Síndrome do Desconforto Respiratório/terapia , Surfactantes Pulmonares/uso terapêutico , Ensaios Clínicos como Assunto , Epidemiologia Descritiva , Estudos ProspectivosRESUMO
Although it is in the Tropics where nearly half of the world population lives and infectious disease burden is highest, little is known about the impact of influenza pandemics in this area. We investigated the mortality impact of the 2009 influenza pandemic relative to mortality rates from various outcomes in pre-pandemic years throughout a wide range of latitudes encompassing the entire tropical, and part of the subtropical, zone of the Southern Hemisphere (+5(°)N to -35(°)S) by focusing on a country with relatively uniform health care, disease surveillance, immunization and mitigation policies: Brazil. To this end, we analyzed laboratory-confirmed deaths and vital statistics mortality beyond pre-pandemic levels for each Brazilian state. Pneumonia, influenza and respiratory mortality were significantly higher during the pandemic, affecting predominantly adults aged 25 to 65 years. Overall, there were 2,273 and 2,787 additional P&I- and respiratory deaths during the pandemic, corresponding to a 5.2% and 2.7% increase, respectively, over average pre-pandemic annual mortality. However, there was a marked spatial structure in mortality that was independent of socio-demographic indicators and inversely related with income: mortality was progressively lower towards equatorial regions, where low or no difference from pre-pandemic mortality levels was identified. Additionally, the onset of pandemic-associated mortality was progressively delayed in equatorial states. Unexpectedly, there was no additional mortality from circulatory causes. Comparing disease burden reliably across regions is critical in those areas marked by competing health priorities and limited resources. Our results suggest, however, that tropical regions of the Southern Hemisphere may have been disproportionally less affected by the pandemic, and that climate may have played a key role in this regard. These findings have a direct bearing on global estimates of pandemic burden and the assessment of the role of immunological, socioeconomic and environmental drivers of the transmissibility and severity of this pandemic.
Assuntos
Influenza Humana/mortalidade , Modelos Biológicos , Pandemias , Clima Tropical , Adulto , Idoso , Brasil/epidemiologia , Feminino , História do Século XXI , Humanos , Imunização , Influenza Humana/história , Influenza Humana/prevenção & controle , Influenza Humana/terapia , Pessoa de Meia-Idade , Pneumonia/história , Pneumonia/mortalidade , Pneumonia/prevenção & controle , Pneumonia/terapia , Síndrome do Desconforto Respiratório/história , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/prevenção & controle , Síndrome do Desconforto Respiratório/terapiaRESUMO
Pneumonectomy is associated with high rates of morbimortality, with postpneumonectomy pulmonary edema being one of the leading causes. An intrinsic inflammatory process following the operation has been considered in its physiopathology. The use of corticosteroids is related to prevention of this edema, but no experimental data are available to support this hypothesis. We evaluated the effect of methylprednisolone on the remaining lungs of rats submitted to left pneumonectomy concerning edema and inflammatory markers. Forty male Wistar rats weighing 300 g underwent left pneumonectomy and were randomized to receive corticosteroids or not. Methylprednisolone at a dose of 10 mg/kg was given before the surgery. After recovery, the animals were sacrificed at 48 and 72 h, when the pO2/FiO2 ratio was determined. Right lung perivascular edema was measured by the index between perivascular and vascular area and neutrophil density by manual count. Tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) were evaluated by immunohistochemistry light microscopy. There was perivascular edema formation after 72 h in both groups (P = 0.0031). No difference was observed between operated animals that received corticosteroids and those that did not concerning the pO2/FiO2 ratio, neutrophil density or TGF-β expression. The tissue expression of VEGF was elevated in the animals that received methylprednisolone both 48 and 72 h after surgery (P = 0.0243). Methylprednisolone was unable to enhance gas exchange and avoid an inflammatory infiltrate and TGF-β expression also showed that the inflammatory process was not correlated with pulmonary edema formation. However, the overexpression of VEGF in this group showed that methylprednisolone is related to this elevation.
Assuntos
Animais , Masculino , Ratos , Anti-Inflamatórios/farmacologia , Glucocorticoides/farmacologia , Metilprednisolona/farmacologia , Edema Pulmonar/prevenção & controle , Fator de Crescimento Transformador beta/biossíntese , Fatores de Crescimento do Endotélio Vascular/biossíntese , Análise de Variância , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Imuno-Histoquímica , Pulmão/metabolismo , Pneumonectomia/efeitos adversos , Edema Pulmonar/etiologia , Distribuição Aleatória , Ratos Wistar , Síndrome do Desconforto Respiratório/prevenção & controleRESUMO
Pneumonectomy is associated with high rates of morbimortality, with postpneumonectomy pulmonary edema being one of the leading causes. An intrinsic inflammatory process following the operation has been considered in its physiopathology. The use of corticosteroids is related to prevention of this edema, but no experimental data are available to support this hypothesis. We evaluated the effect of methylprednisolone on the remaining lungs of rats submitted to left pneumonectomy concerning edema and inflammatory markers. Forty male Wistar rats weighing 300 g underwent left pneumonectomy and were randomized to receive corticosteroids or not. Methylprednisolone at a dose of 10 mg/kg was given before the surgery. After recovery, the animals were sacrificed at 48 and 72 h, when the pO(2)/FiO(2) ratio was determined. Right lung perivascular edema was measured by the index between perivascular and vascular area and neutrophil density by manual count. Tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-ß) were evaluated by immunohistochemistry light microscopy. There was perivascular edema formation after 72 h in both groups (P = 0.0031). No difference was observed between operated animals that received corticosteroids and those that did not concerning the pO(2)/FiO(2) ratio, neutrophil density or TGF-ß expression. The tissue expression of VEGF was elevated in the animals that received methylprednisolone both 48 and 72 h after surgery (P = 0.0243). Methylprednisolone was unable to enhance gas exchange and avoid an inflammatory infiltrate and TGF-ß expression also showed that the inflammatory process was not correlated with pulmonary edema formation. However, the overexpression of VEGF in this group showed that methylprednisolone is related to this elevation.
Assuntos
Anti-Inflamatórios/farmacologia , Glucocorticoides/farmacologia , Metilprednisolona/farmacologia , Edema Pulmonar/prevenção & controle , Fator de Crescimento Transformador beta/biossíntese , Fatores de Crescimento do Endotélio Vascular/biossíntese , Análise de Variância , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Imuno-Histoquímica , Pulmão/metabolismo , Masculino , Pneumonectomia/efeitos adversos , Edema Pulmonar/etiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Síndrome do Desconforto Respiratório/prevenção & controleRESUMO
A definição da síndrome do desconforto respiratório agudo (SDRA), simplificada pela Conferência Americana e Europeia de Consenso em SDRA de 1998, inclui a presença de infiltrado pulmonar bilateral, relação pressão parcial arterial de oxigênio/fração inspirada de oxigênio < 200 mmHg e pressão capilar pulmonar < 18 mmHg ou ausência de sinais de insuficiência cardíaca esquerda. Atualmente, o entendimento mais complexo da SDRA inclui sua análise mais detalhada pela tomografia de tórax e por outros métodos de imagem. A utilização de marcadores genéticos e biomarcadores plasmáticos e no lavado broncoalveolar antecipará o diagnóstico e o prognóstico de SDRA. A introdução de sistemas automáticos de diagnóstico e a análise de fatores de risco e de fatores prognósticos associados à SDRA ajudarão no entendimento mais aprofundado da doença para seu melhor tratamento e diminuição de suas taxas de mortalidade.
The definition of acute respiratory distress syndrome (ARDS) was simplified at the 1998 American-European Consensus Conference of 1998 and now includes the following: bilateral pulmonary infiltrates; arterial oxygen tension/fraction of inspired oxygen < 200 mmHg; and pulmonary capillary wedge pressure < 18 mmHg or no signs of left heart failure. Recently, tomography and other imaging methods have allowed the chest to be analyzed in greater detail, thereby leading to a more complex understanding of ARDS. The use of genetic markers and biomarkers in plasma and bronchoalveolar lavage could lead to earlier ARDS diagnosis, thereby improving prognosis. The introduction of automatic diagnostic screening, together with the analysis of risk factors and prognostic factors associated with the syndrome, will deepen the understanding of ARDS, improving treatment and potentially reducing the associated mortality rates.
Assuntos
Humanos , Masculino , Feminino , Adulto , Síndrome do Desconforto Respiratório/classificação , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/prevenção & controleRESUMO
BACKGROUND: Aerobic exercise decreases pulmonary inflammation and remodeling in experimental models of allergic asthma. However, the effects of aerobic exercise on pulmonary inflammation of nonallergic origin, such as in experimental models of acute lung injury induced by lipopolysaccharide (LPS), have not been evaluated. OBJECTIVE: The present study evaluated the effects of aerobic exercise in a model of LPS-induced acute lung injury. METHODS: BALB/c mice were divided into four groups: Control, Aerobic Exercise, LPS, and Aerobic Exercise + LPS. Swimming tests were conducted at baseline and at 3 and 6 wk. Low-intensity swimming training was performed for 6 wk, four times per week, 60 min per session. Intranasal LPS (1 mg x kg(-1) (60 microg per mouse)) was instilled 24 h after the last swimming physical test in the LPS and Aerobic Exercise + LPS mice, and the animals were studied 24 h after LPS instillation. Exhaled nitric oxide, respiratory mechanics, total and differential cell counts in bronchoalveolar lavage, and lung parenchymal inflammation and remodeling were evaluated. RESULTS: LPS instillation resulted in increased levels of exhaled nitric oxide (P < 0.001), higher numbers of neutrophils in the bronchoalveolar lavage (P < 0.001) and in the lung parenchyma (P < 0.001), and decreased lung tissue resistance (P < 0.05) and volume proportion of elastic fibers (P < 0.01) compared with the Control group. Swim training in LPS-instilled animals resulted in significantly lower exhaled nitric oxide levels (P < 0.001) and fewer neutrophils in the bronchoalveolar lavage (P < 0.001) and the lung parenchyma (P < 0.01) compared with the LPS group. CONCLUSIONS: These results suggest that low-intensity swimming training inhibits lung neutrophilic inflammation, but not remodeling and impaired lung mechanics, in a model of LPS-induced acute lung injury.
Assuntos
Lipopolissacarídeos/farmacologia , Condicionamento Físico Animal , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/prevenção & controle , Natação/fisiologia , Análise de Variância , Animais , Líquido da Lavagem Broncoalveolar , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Mecânica RespiratóriaRESUMO
O papel da resposta imunológica durante a infecção pelo vírus Influenza H1N1 não está totalmente estabelecido, mas acredita-se que atue de forma decisiva no agravamento do quadro e no aparecimento da síndrome de desconforto respiratório agudo. O papel de terapias imunomoduladoras no controle de infecções virais também não é consensual e faltam dados de literatura para se definir as indicações de seu uso. Neste relato de caso, apresentamos, segundo nosso conhecimento, pela primeira vez, o relato de um paciente transplantado cardíaco que apresentou infecção pelo vírus H1N1 e evoluiu de forma favorável, trazendo um questionamento sobre o real papel da terapia imunossupressora como fator de risco para a forma grave da doença.
The role of the immune response during Influenza H1N1 virus infection is not yet fully established, but it is believed that it decisively participates in the severity of the disease as well as in the development of acute respiratory distress syndrome. The role of immunomodulating therapies in the control of viral infections is not a consensus either, and data from the literature defining the indications for their use are lacking. The present report is, to our knowledge, the first on a heart transplant patient who developed H1N1 virus infection and had a favorable outcome, thus generating discussion on the real role of immunosuppressive therapy as a risk factor for the severe form of the disease.
El rol de la respuesta inmunológica durante la infección por el virus Influenza H1N1 no está totalmente establecido, sino que se cree que él actúe de forma decisiva en el agravamiento del cuadro y en el surgimiento del síndrome de distrés respiratorio agudo. El papel de terapias inmunomoduladoras en el control de infecciones virales también no es consensual y nos faltan datos de la literatura para definirse las indicaciones de su utilización. En este caso clínico presentamos, según nuestro conocimiento, por primera vez, el relato de un paciente transplantado cardiaco que presentó infección por el virus H1N1 y evolucionó de forma favorable, y aprovechamos para poner en cuestión el real papel de la terapia inmunosupresora como factor de riesgo para la forma severa de la enfermedad.