RESUMEN
ABSTRACT: Sickle cell disease (SCD) is an autosomal recessive disorder altering the shape of red blood cells, causing harmful obstructions in blood vessels, therefore altering normal blood flow. SCD can escalate quickly into acute chest syndrome (ACS), a life-threatening complication that requires immediate care. This article discusses the pathophysiology, assessment, diagnosis, and treatment of ACS, as well as nursing care and patient education.
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Síndrome Torácico Agudo , Anemia de Células Falciformes , Humanos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , Anemia de Células Falciformes/enfermería , Síndrome Torácico Agudo/etiología , Síndrome Torácico Agudo/terapia , Síndrome Torácico Agudo/diagnóstico , Síndrome Torácico Agudo/fisiopatología , Evaluación en Enfermería , Educación del Paciente como AsuntoRESUMEN
INTRODUCTION: In sickle cell disease (SCD), hemoglobin S (HbS) red blood cells (RBCs) are characteristically deformed and inflexible. Often breaking down in the circulation, they exhibit increased adhesive properties with the endothelium and activated neutrophils and platelets, increasing the risk of occlusion of the microcirculation. SCD is categorized into two sub-phenotypes: hyperhemolytic, associated with priapism, leg ulcers, pulmonary hypertension, and stroke, and high hemoglobin/viscosity, which may promote vaso-occlusion-associated pain, acute chest syndrome, and osteonecrosis. AREAS COVERED: The sub-phenotypes are not completely distinct. Hemolysis may trigger vaso-occlusion, contributing to vascular complications. Targeting P-selectin, a key mediator of cross-talk between hyperhemolysis and vaso-occlusion, may be beneficial for vascular and vaso-occlusion-associated complications. English-language articles from PubMed on the topic of SCD and vaso-occlusive crises (VOCs) were reviewed from 1 January 2000 to 1 January 2019 using the search terms 'sickle cell disease,' 'vaso-occlusive crises,' and 'selectin.' EXPERT OPINION: Besides targeting P-selectin, other strategies to counter VOCs and RBC sickling are being pursued. These include platelet inhibition to counter aggregation, intercellular adhesion, and thrombosis during VOCs; gene therapy to correct the homozygous missense mutation in the ß-globin gene, causing polymerization of HbS; L-glutamine, possibly reducing oxidative stress in sickled RBCs; and fetal hemoglobin inducers.
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Síndrome Torácico Agudo , Enfermedades Vasculares , Síndrome Torácico Agudo/tratamiento farmacológico , Síndrome Torácico Agudo/patología , Síndrome Torácico Agudo/fisiopatología , Femenino , Humanos , Masculino , Osteonecrosis/tratamiento farmacológico , Osteonecrosis/patología , Osteonecrosis/fisiopatología , Dolor/tratamiento farmacológico , Dolor/patología , Dolor/fisiopatología , Enfermedades Vasculares/tratamiento farmacológico , Enfermedades Vasculares/patología , Enfermedades Vasculares/fisiopatologíaAsunto(s)
Síndrome Torácico Agudo/complicaciones , Síndrome Torácico Agudo/diagnóstico , Betacoronavirus , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Síndrome Torácico Agudo/fisiopatología , Adulto , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , COVID-19 , Prueba de COVID-19 , Infecciones por Coronavirus/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Pandemias , Neumonía Viral/fisiopatología , SARS-CoV-2 , Tomografía Computarizada por Rayos XRESUMEN
Rationale: Intraerythrocytic polymerization of Hb S promotes hemolysis and vasoocclusive events in the microvasculature of patients with sickle cell disease (SCD). Although platelet-neutrophil aggregate-dependent vasoocclusion is known to occur in the lung and contribute to acute chest syndrome, the etiological mechanisms that trigger acute chest syndrome are largely unknown.Objectives: To identify the innate immune mechanism that promotes platelet-neutrophil aggregate-dependent lung vasoocclusion and injury in SCD.Methods:In vivo imaging of the lung in transgenic humanized SCD mice and in vitro imaging of SCD patient blood flowing through a microfluidic system was performed. SCD mice were systemically challenged with nanogram quantities of LPS to trigger lung vasoocclusion.Measurements and Main Results: Platelet-inflammasome activation led to generation of IL-1ß and caspase-1-carrying platelet extracellular vesicles (EVs) that bind to neutrophils and promote platelet-neutrophil aggregation in lung arterioles of SCD mice in vivo and SCD human blood in microfluidics in vitro. The inflammasome activation, platelet EV generation, and platelet-neutrophil aggregation were enhanced by the presence of LPS at a nanogram dose in SCD but not control human blood. Inhibition of the inflammasome effector caspase-1 or IL-1ß pathway attenuated platelet EV generation, prevented platelet-neutrophil aggregation, and restored microvascular blood flow in lung arterioles of SCD mice in vivo and SCD human blood in microfluidics in vitro.Conclusions: These results are the first to identify that platelet-inflammasome-dependent shedding of IL-1ß and caspase-1-carrying platelet EVs promote lung vasoocclusion in SCD. The current findings also highlight the therapeutic potential of targeting the platelet-inflammasome-dependent innate immune pathway to prevent acute chest syndrome.
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Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/inmunología , Vesículas Extracelulares/inmunología , Inflamasomas/inmunología , Lesión Pulmonar/etiología , Lesión Pulmonar/fisiopatología , Agregación Plaquetaria/inmunología , Síndrome Torácico Agudo/etiología , Síndrome Torácico Agudo/fisiopatología , Anemia de Células Falciformes/fisiopatología , Animales , Humanos , Ratones , Ratones Transgénicos , Modelos Animales , Neutrófilos/inmunologíaRESUMEN
OBJECTIVES: Maternal sickle cell disease (SCD) and multiple gestations are well known separately as causes of high-risk pregnancies, however, there is sparse information available on maternal and perinatal outcome when both conditions occur together. This case series describes the outcomes of women with maternal SCD and twin pregnancy in the largest single-center case series to date. METHODS: Retrospective identification of all twin pregnancies in maternal SCD patients between 2006 and 2016 at Guy's and St. Thomas' Hospital, United Kingdom Results: Eight women were included: seven with HbSS and one with HbSC. Our cohort experienced common SCD-related and pregnancy-related complications such as painful vaso-occlusive crises (VOC), acute chest syndrome (ACS), and pre-eclampsia and less common complications such as peri-partum cardiomyopathy and delayed hemolytic transfusion reaction. Only two out of eight women had relatively uncomplicated pregnancies. Seven out of eight women required transfusion antenatally and there was no maternal or perinatal mortality. A review of the available literature highlighted the lack of available information on this uncommon cohort. It was evident that outcomes have improved over the years, where historical studies demonstrate higher rates of maternal and perinatal mortality. DISCUSSION: The antenatal and postnatal complications described in our study and literature review highlights the significant morbidity and mortality associated with these high-risk pregnancies. CONCLUSION: Our case series highlights the advantage of closer monitoring and comprehensive multidisciplinary care in delivering improved clinical outcomes.
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Síndrome Torácico Agudo/terapia , Transfusión Sanguínea , Preeclampsia/terapia , Complicaciones Hematológicas del Embarazo/terapia , Embarazo Gemelar , Síndrome Torácico Agudo/patología , Síndrome Torácico Agudo/fisiopatología , Adulto , Femenino , Humanos , Preeclampsia/patología , Preeclampsia/fisiopatología , Embarazo , Complicaciones Hematológicas del Embarazo/patología , Complicaciones Hematológicas del Embarazo/fisiopatologíaRESUMEN
BACKGROUND: Posterior reversible encephalopathy syndrome is a neurotoxic condition that occurs as a result of the failure of posterior circulatory autoregulation in response to acute changes in blood pressure. Overperfusion with resultant disruption of the blood-brain barrier results in vasogenic edema, but not infarction. Posterior reversible encephalopathy syndrome can be the presenting feature of postinfectious glomerulonephritis, which has been reported in approximately 5% of hospitalized children, and it has been reported in very few cases of adult patients with sickle cell anemia. We report a very rare case of posterior reversible encephalopathy syndrome that occurred in a child with sickle cell anemia. This presentation should be differentiated from other neurologic manifestations that occur in patients with sickle cell anemia, because management is totally different. CASE PRESENTATION: We report what is to our knowledge the first reported case of a 9-year-old Saudi girl with sickle cell anemia who developed posterior reversible encephalopathy syndrome secondary to asymptomatic poststreptococcal glomerulonephritis. This occurred after full recovery from acute chest syndrome and severe vaso-occlusive crisis. CONCLUSIONS: The purpose of this report is to emphasize that all efforts should be made to explore the causes of different neurologic manifestations that occur in patients with sickle cell anemia, because this will require different pathways of management.
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Síndrome Torácico Agudo/etiología , Anemia de Células Falciformes/complicaciones , Glomerulonefritis/complicaciones , Enfermedades Vasculares/etiología , Síndrome Torácico Agudo/diagnóstico por imagen , Síndrome Torácico Agudo/fisiopatología , Síndrome Torácico Agudo/terapia , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/fisiopatología , Antibacterianos/uso terapéutico , Anticonvulsivantes/uso terapéutico , Antihipertensivos/uso terapéutico , Barrera Hematoencefálica , Circulación Cerebrovascular , Niño , Femenino , Fluidoterapia , Glomerulonefritis/diagnóstico por imagen , Glomerulonefritis/fisiopatología , Glomerulonefritis/terapia , Humanos , Imagen por Resonancia Magnética , Neuroimagen , Síndrome de Leucoencefalopatía Posterior , Resultado del Tratamiento , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/fisiopatología , Enfermedades Vasculares/terapiaRESUMEN
Asthma and sickle cell disease (SCD) are common chronic conditions in children of African ancestry that are characterized by cough, wheeze, and obstructive patterns on pulmonary function. Pulmonary function testing in children with SCD has estimated a prevalence of obstructive lung disease ranging from 13% to 57%, and airway hyper-responsiveness of up to 77%, independent of a diagnosis of asthma. Asthma co-existing with SCD is associated with increased risk of acute chest syndrome (ACS), respiratory symptoms, pain episodes, and death. However, there are inherent differences in the pathophysiology of SCD and asthma. While classic allergic asthma in the general population is associated with a T-helper 2 cell (Th-2 cells) pattern of cell inflammation, increased IgE levels and often positive allergy testing, inflammation in SCD is associated with different inflammatory pathways, involving neutrophilic and monocytic pathways, which have been explored to a limited extent in mouse models and with a dearth of human studies. The current review summarizes the existent literature on sickle cell related airway inflammation and its cross roads with allergic asthma-related inflammation, and discusses the importance of further elucidating and understanding these common and divergent inflammatory pathways in human studies to facilitate development of targeted therapy for children with SCD and pulmonary morbidity.
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Síndrome Torácico Agudo , Anemia de Células Falciformes , Asma , Síndrome Torácico Agudo/epidemiología , Síndrome Torácico Agudo/fisiopatología , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/fisiopatología , Animales , Asma/epidemiología , Asma/fisiopatología , HumanosRESUMEN
The longitudinal pattern of lung function in children with sickle cell anemia (SCA) has shown a decrease in FEV1 % predicted, a risk factor for death in adults with SCA, but predictors for this decline are poorly characterized. In a prospective longitudinal multi-center cohort of children with SCA, we tested the hypotheses that: (1) FEV1 % predicted declines over time; and (2) SCA-specific characteristics and therapy predict this decline. At three clinical centers, children with SCA (HbSS or HbSß0 thalassemia), unselected for respiratory disease, were enrolled in the Sleep and Asthma Cohort (SAC) study. Study-certified pulmonary function technicians performed spirometry and lung volumes. Each assessment was reviewed centrally. Predicted values were determined for TLC, FEV1 , FVC, and FEV1 /FVC ratio. A total of 197 participants, mean age 11.0 years at first testing (range 4-19.3 years), had a minimum of three spirometry measurements, over an average of 4.4 years (range 1.1-6.5 years) from baseline to endpoint. In a multivariable model, FEV1 % predicted declines by 0.3% for every additional year of age (95% CI -0.56 to -0.05, P = .020). Sex, asthma history, hemoglobin, reticulocyte count, white blood cell count, incidence rate of severe acute pain and acute chest syndrome episodes, and hydroxyurea therapy were not associated with a decline in FEV1 % predicted. In a large, rigorously evaluated, prospective cohort of an unselected group of children with SCA, FEV1 % predicted declines minimally over an average of 4 years, and none of the examined disease features predict the decline.
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Factores de Edad , Anemia de Células Falciformes/fisiopatología , Volumen Espiratorio Forzado , Pulmón/fisiopatología , Síndrome Torácico Agudo/etiología , Síndrome Torácico Agudo/fisiopatología , Adolescente , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Asma/complicaciones , Asma/fisiopatología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Hidroxiurea/uso terapéutico , Mediciones del Volumen Pulmonar , Masculino , Pronóstico , Rasgo Drepanocítico/complicaciones , Rasgo Drepanocítico/fisiopatología , Espirometría , Adulto Joven , Talasemia beta/complicaciones , Talasemia beta/fisiopatologíaRESUMEN
Sound transmission and resulting airway wall vibration in a complex multiscale viscoelastic model of the subglottal bronchial tree was calculated using a modified one-dimensional (1D) branching acoustic waveguide approach. This is an extension of previous work to enable use of complex airway trees that are partially derived from subject-specific medical images, without the need for self-similarity in the geometric structure. The approach was validated numerically for simplified airway geometries, as well as experimentally by comparison to previous studies. A comprehensive conducting airway tree with about 60 000 branches was then modified to create fibrotic, bronchoconstrictive, and pulmonary infiltrate conditions. The fibrotic case-systemic increase in soft tissue stiffness-increased the Helmholtz resonance frequency due to the increased acoustic impedance. Bronchoconstriction, with geometric changes in small conducting airways, decreased acoustic energy transmission to the peripheral airways due in part to the increased impedance mismatch between airway orders. Pulmonary infiltrate significantly altered the local acoustic field in the affected lobe. Calculation of acoustic differences between healthy versus pathologic cases can be used to enhance the understanding of vibro-acoustic changes correlated to pathology, and potentially provide improved tools for the diagnosis of pulmonary diseases that uniquely alter the acoustics of the airways.
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Acústica , Síndrome Torácico Agudo/fisiopatología , Bronquios/fisiopatología , Broncoconstricción , Enfermedades Pulmonares Obstructivas/fisiopatología , Modelos Anatómicos , Modelos Teóricos , Fibrosis Pulmonar/fisiopatología , Sonido , Síndrome Torácico Agudo/diagnóstico por imagen , Síndrome Torácico Agudo/patología , Bronquios/diagnóstico por imagen , Bronquios/patología , Estudios de Casos y Controles , Simulación por Computador , Elasticidad , Humanos , Enfermedades Pulmonares Obstructivas/diagnóstico por imagen , Enfermedades Pulmonares Obstructivas/patología , Movimiento (Física) , Análisis Numérico Asistido por Computador , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/patología , Reproducibilidad de los Resultados , Factores de Tiempo , Vibración , ViscosidadRESUMEN
Platelet activation and platelet-derived cytokines contribute to the vascular inflammation and increased thrombotic activity known to occur in patients with sickle cell anemia (SCA). CD40 ligand (CD40L), a platelet-associated pro-inflammatory molecule that promotes endothelial cell activation, is elevated in the circulation of SCA patients. We sought to evaluate the association of CD40L and inflammation with sickle-related clinical complications and laboratory variables in SCA patients. Soluble CD40L, thrombospondin (TSP)-1 and tumor necrosis factor (TNF)-α were determined in the platelet-poor plasma of healthy individuals and steady-state SCA patients by ELISA. Lifetime clinical complications were verified by detailed review of patients' medical records. We found that plasma CD40L was associated with acute chest syndrome (ACS), and that SCA patients with a lifetime history of ACS (ACS+) presented significantly higher plasma CD40L and TSP-1 than patients who had never experienced ACS (ACS-). In the ACS+ group, both platelet-derived proteins (CD40L and TSP-1) correlated with mean corpuscular volume, mean corpuscular hemoglobin and reticulocyte hemoglobin, while in the ACS- group, CD40L correlated with low red blood cell counts, hemoglobin, hematocrit and lactate dehydrogenase, and TSP-1 correlated with reticulocyte percentage and white blood cell count. As expected, CD40L and TSP-1 correlated with platelet counts in both groups. These data highlight the possible role of platelet activation in ACS and suggest that plasma sCD40L, together with TSP-1, may represent a potential marker of susceptibility to ACS in SCA.
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Síndrome Torácico Agudo/sangre , Síndrome Torácico Agudo/complicaciones , Anemia de Células Falciformes/sangre , Ligando de CD40/sangre , Síndrome Torácico Agudo/fisiopatología , Adolescente , Adulto , Anemia de Células Falciformes/complicaciones , Biomarcadores/sangre , Femenino , Humanos , Inflamación , Masculino , Registros Médicos , Persona de Mediana Edad , Activación Plaquetaria , Recuento de Plaquetas , Trombospondina 1/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
In patients with sickle cell disease (SCD), the polymerization of intraerythrocytic hemoglobin S promotes downstream vaso-occlusive events in the microvasculature. While vaso-occlusion is known to occur in the lung, often in the context of systemic vaso-occlusive crisis and the acute chest syndrome, the pathophysiological mechanisms that incite lung injury are unknown. We used intravital microscopy of the lung in transgenic humanized SCD mice to monitor acute vaso-occlusive events following an acute dose of systemic lipopolysaccharide sufficient to trigger events in SCD but not control mice. We observed cellular microembolism of precapillary pulmonary arteriolar bottlenecks by neutrophil-platelet aggregates. Blood from SCD patients was next studied under flow in an in vitro microfluidic system. Similar to the pulmonary circulation, circulating platelets nucleated around arrested neutrophils, translating to a greater number and duration of neutrophil-platelet interactions compared with normal human blood. Inhibition of platelet P-selectin with function-blocking antibody attenuated the neutrophil-platelet interactions in SCD patient blood in vitro and resolved pulmonary arteriole microembolism in SCD mice in vivo. These results establish the relevance of neutrophil-platelet aggregate formation in lung arterioles in promoting lung vaso-occlusion in SCD and highlight the therapeutic potential of targeting platelet adhesion molecules to prevent acute chest syndrome.
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Anemia de Células Falciformes/complicaciones , Arteriolas/patología , Pulmón/patología , Selectina-P/efectos de los fármacos , Adhesividad Plaquetaria/efectos de los fármacos , Síndrome Torácico Agudo/fisiopatología , Síndrome Torácico Agudo/prevención & control , Anemia de Células Falciformes/fisiopatología , Animales , Arteriolas/citología , Plaquetas/metabolismo , Plaquetas/patología , Embolia/patología , Embolia/fisiopatología , Femenino , Humanos , Pulmón/irrigación sanguínea , Pulmón/metabolismo , Pulmón/ultraestructura , Masculino , Ratones , Ratones Transgénicos , Neutrófilos/metabolismo , Neutrófilos/patología , Selectina-P/metabolismo , Adhesividad Plaquetaria/fisiología , Receptor Toll-Like 4/metabolismoRESUMEN
ABSTRACT Objective: To evaluate pulmonary function and functional capacity in children and adolescents with sickle cell disease. Methods: This was a cross-sectional study involving 70 children and adolescents (8-15 years of age) with sickle cell disease who underwent pulmonary function tests (spirometry) and functional capacity testing (six-minute walk test). The results of the pulmonary function tests were compared with variables related to the severity of sickle cell disease and history of asthma and of acute chest syndrome. Results: Of the 64 patients who underwent spirometry, 15 (23.4%) showed abnormal results: restrictive lung disease, in 8 (12.5%); and obstructive lung disease, in 7 (10.9%). Of the 69 patients who underwent the six-minute walk test, 18 (26.1%) showed abnormal results regarding the six-minute walk distance as a percentage of the predicted value for age, and there was a ≥ 3% decrease in SpO2 in 36 patients (52.2%). Abnormal pulmonary function was not significantly associated with any of the other variables studied, except for hypoxemia and restrictive lung disease. Conclusions: In this sample of children and adolescents with sickle cell disease, there was a significant prevalence of abnormal pulmonary function. The high prevalence of respiratory disorders suggests the need for a closer look at the lung function of this population, in childhood and thereafter.
RESUMO Objetivo: Avaliar a função pulmonar e a capacidade funcional em crianças e adolescentes com doença falciforme. Métodos: Estudo transversal com 70 crianças e adolescentes com doença falciforme (8-15 anos), submetidos a testes de função respiratória (espirometria) e de capacidade funcional (teste de caminhada de seis minutos). Os resultados da avaliação da função pulmonar foram comparados com variáveis relacionadas à gravidade da doença falciforme e à presença de história de asma e de síndrome torácica aguda. Resultados: Dos 64 pacientes submetidos à espirometria, 15 (23,4%) apresentaram resultados alterados: distúrbio ventilatório restritivo, em 8; (12,5%) e distúrbio respiratório obstrutivo, em 7 (10,9%). Dos 69 pacientes submetidos ao teste de caminhada de seis minutos, 18 (26,1%) apresentaram resultados alterados na distância em % do previsto para a idade, e houve uma queda ≥ 3% na SpO2 em 36 (52,2%) dos pacientes. Não houve associações significativas entre função pulmonar alterada e as outras variáveis analisadas, exceto para hipoxemia e distúrbio ventilatório restritivo. Conclusões: Observou-se uma significativa prevalência de alterações na função pulmonar nesta amostra de crianças e adolescentes com doença falciforme. A elevada prevalência de distúrbios ventilatórios sugere a necessidade de um olhar mais atento à função pulmonar desde a infância nessa população.
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Humanos , Masculino , Femenino , Niño , Adolescente , Anemia de Células Falciformes/fisiopatología , Pulmón/fisiopatología , Prueba de Paso , Síndrome Torácico Agudo/epidemiología , Síndrome Torácico Agudo/fisiopatología , Asma/epidemiología , Asma/fisiopatología , Brasil/epidemiología , Estudios Transversales , Análisis Multivariante , Pruebas de Función Respiratoria , Enfermedades Respiratorias/epidemiología , EspirometríaRESUMEN
RATIONALE: Patient factors associated with development of abnormal lung function in children with sickle cell anemia (SCA) have not been fully characterized. OBJECTIVES: To characterize lung function abnormalities among children with SCA and to determine whether these steady-state lung function results were associated with morbidity before or after testing among children with SCA. METHODS: This study was part of the prospective National Institutes of Health-funded Sleep and Asthma Cohort Study. Children with HbSS or Hb Sß(o) (SCA) were enrolled without regard for sickle cell-related comorbidities or diagnosis of asthma. Lung function was measured by spirometry and plethysmography on the same day, when free of acute disease. Standardized asthma symptom questionnaires and review of the medical records were also performed. MEASUREMENTS AND MAIN RESULTS: A total of 149 children aged 6 to 19 years completed lung function testing, of whom 139 participants had retrospective morbidity data from birth to the test date, and 136 participants were followed prospectively for a median of 4.3 years from the test date. At baseline, percentages with normal, obstructive, restrictive, nonspecific, and mixed lung function patterns were 70, 16, 7, 6, and 1, respectively. Neither retrospective rates of pain nor acute chest syndrome was associated with lung function patterns. Furthermore, baseline lung function pattern was not predictive of future pain or acute chest syndrome episodes. CONCLUSIONS: The majority of children with SCA have lung function that is within the normal range. Abnormal lung function patterns were not associated with prior vasoocclusive pain or acute chest syndrome episodes, and baseline lung function patterns did not predict future vasoocclusive pain or chest syndrome episodes.
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Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , Asma/epidemiología , Asma/fisiopatología , Pulmón/fisiopatología , Síndrome Torácico Agudo/fisiopatología , Adolescente , Niño , Comorbilidad , Femenino , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Dolor/fisiopatología , Estudios Prospectivos , Pruebas de Función Respiratoria , Fenómenos Fisiológicos Respiratorios , Factores de Riesgo , Espirometría , Encuestas y Cuestionarios , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Acute chest syndrome (ACS) is the most common cause of death among sickle cell disease (SCD) adult patients. Pulmonary vascular dysfunction (PVD) and acute cor pulmonale (ACP) are common during acute respiratory distress syndrome (ARDS) and their prevalence may be even more important during ARDS related to ACS (ACS-ARDS). The objective of this study was to evaluate the prevalence and prognosis of PVD and ACP during ACS-ARDS. PATIENTS AND METHODS: This was a retrospective analysis over a 10-year period of patients with moderate-to-severe ARDS. PVD and ACP were assessed by echocardiography. ARDS episodes were assigned to ACS-ARDS or nonACS-ARDS group according to whether the clinical insult was ACS or not, respectively. To evaluate independent factors associated with ACP, significant univariable risk factors were examined using logistic regression and propensity score analyses. RESULTS: A total of 362 patients were analyzed, including 24 ACS-ARDS. PVD and ACP were identified, respectively, in 24 (100%) and 20 (83%) ACS-ARDS patients, as compared with 204 (60%) and 68 (20%) nonACS-ARDS patients (Pâ<â0.0001). The mortality did not differ between ACS-ARDS and nonACS-ARDS patients. Both the crude (odds ratio [OR], 19.9; 95% confidence interval [CI], 6.6-60; Pâ<â0.0001), multivariable adjustment (OR, 27.4; 95% CI, 8.2-91.5; Pâ<â0.001), and propensity-matched (OR, 11.7; 95% CI, 1.2-110.8; Pâ=â0.03) analyses found a significant association between ACS-ARDS and ACP. CONCLUSIONS: All SCD patients presenting with moderate-to-severe ARDS as a consequence of ACS experienced PVD and more than 80% of them exhibited ACP. These results suggest a predominant role for PVD in the pathogenesis of severe forms of ACS.
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Anemia de Células Falciformes/fisiopatología , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome Torácico Agudo/fisiopatología , Adulto , Ecocardiografía , Femenino , Hemodinámica/fisiología , Humanos , Modelos Logísticos , Masculino , Enfermedad Cardiopulmonar/fisiopatología , Estudios Retrospectivos , Adulto JovenRESUMEN
In spite of significant strides in the treatment of sickle cell disease (SCD), SCD crises are still responsible for high morbidity and early mortality. While most patients initially seek care in the acute setting for a seemingly uncomplicated pain episode (pain crisis or vaso-occlusive crisis), this initial event is the primary risk factor for potentially life-threatening complications. The pathophysiological basis of these illnesses is end-organ ischemia and infarction combined with the downstream effects of hemolysis that results from red blood cell sickling. These pathological changes can occur acutely and lead to a dramatic clinical presentation, but are frequently superimposed over a milieu of chronic vasculopathy, immune dysregulation, and decreased functional reserve. In the lungs, acute chest syndrome is a particularly ominous lung injury syndrome with a complex pathogenesis and potentially devastating sequelae, but all organ systems can be affected. It is, therefore, critical to understand the SCD patients' susceptibility to acute complications and their risk factors so that they can be recognized promptly and managed effectively. Blood transfusions remain the mainstay of therapy for all severe acute crises. Recommendations and indications for the safest and most efficient implementation of transfusion strategies in the critical care setting are therefore presented and discussed, together with their pitfalls and potential future therapeutic alternatives. In particular, the importance of extended phenotypic red blood cell matching cannot be overemphasized, due to the high prevalence of severe complications from red cell alloimmunization in SCD.
Asunto(s)
Síndrome Torácico Agudo/terapia , Anemia Aplásica/terapia , Anemia de Células Falciformes/terapia , Antibacterianos/uso terapéutico , Insuficiencia Multiorgánica/terapia , Terapia por Inhalación de Oxígeno , Púrpura Trombocitopénica Trombótica/terapia , Accidente Cerebrovascular/terapia , Síndrome Torácico Agudo/etiología , Síndrome Torácico Agudo/fisiopatología , Anemia Aplásica/etiología , Anemia Aplásica/fisiopatología , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , Tipificación y Pruebas Cruzadas Sanguíneas/métodos , Progresión de la Enfermedad , Transfusión de Eritrocitos/métodos , Recambio Total de Sangre/métodos , Humanos , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/fisiopatología , Dolor/etiología , Manejo del Dolor , Síndrome de Leucoencefalopatía Posterior , Púrpura Trombocitopénica Trombótica/etiología , Púrpura Trombocitopénica Trombótica/fisiopatología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatologíaRESUMEN
OBJECTIVE:: To evaluate pulmonary function and functional capacity in children and adolescents with sickle cell disease. METHODS:: This was a cross-sectional study involving 70 children and adolescents (8-15 years of age) with sickle cell disease who underwent pulmonary function tests (spirometry) and functional capacity testing (six-minute walk test). The results of the pulmonary function tests were compared with variables related to the severity of sickle cell disease and history of asthma and of acute chest syndrome. RESULTS:: Of the 64 patients who underwent spirometry, 15 (23.4%) showed abnormal results: restrictive lung disease, in 8 (12.5%); and obstructive lung disease, in 7 (10.9%). Of the 69 patients who underwent the six-minute walk test, 18 (26.1%) showed abnormal results regarding the six-minute walk distance as a percentage of the predicted value for age, and there was a ≥ 3% decrease in SpO2 in 36 patients (52.2%). Abnormal pulmonary function was not significantly associated with any of the other variables studied, except for hypoxemia and restrictive lung disease. CONCLUSIONS:: In this sample of children and adolescents with sickle cell disease, there was a significant prevalence of abnormal pulmonary function. The high prevalence of respiratory disorders suggests the need for a closer look at the lung function of this population, in childhood and thereafter. OBJETIVO:: Avaliar a função pulmonar e a capacidade funcional em crianças e adolescentes com doença falciforme. MÉTODOS:: Estudo transversal com 70 crianças e adolescentes com doença falciforme (8-15 anos), submetidos a testes de função respiratória (espirometria) e de capacidade funcional (teste de caminhada de seis minutos). Os resultados da avaliação da função pulmonar foram comparados com variáveis relacionadas à gravidade da doença falciforme e à presença de história de asma e de síndrome torácica aguda. RESULTADOS:: Dos 64 pacientes submetidos à espirometria, 15 (23,4%) apresentaram resultados alterados: distúrbio ventilatório restritivo, em 8; (12,5%) e distúrbio respiratório obstrutivo, em 7 (10,9%). Dos 69 pacientes submetidos ao teste de caminhada de seis minutos, 18 (26,1%) apresentaram resultados alterados na distância em % do previsto para a idade, e houve uma queda ≥ 3% na SpO2 em 36 (52,2%) dos pacientes. Não houve associações significativas entre função pulmonar alterada e as outras variáveis analisadas, exceto para hipoxemia e distúrbio ventilatório restritivo. CONCLUSÕES:: Observou-se uma significativa prevalência de alterações na função pulmonar nesta amostra de crianças e adolescentes com doença falciforme. A elevada prevalência de distúrbios ventilatórios sugere a necessidade de um olhar mais atento à função pulmonar desde a infância nessa população.