RESUMEN
Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to prescribed medications for these illnesses. However, there is a technology called CRISPR/Cas9, which uses RNA to guide DNA targeting. This technology has revolutionized our ability to manipulate and visualize the genome, leading to advancements in research and treatment development. It can effectively reverse epigenetic alterations that contribute to drug resistance. Some studies focused on health have shown that targeting genes using CRISPR/Cas9 can be challenging when it comes to reducing drug resistance in patients with respiratory disorders. Nevertheless, it is important to acknowledge the limitations of this technology, such as off-target effects, immune system reactions to Cas9, and challenges associated with delivery methods. Despite these limitations, this review aims to provide knowledge about CRISPR/Cas9 genome editing tools and explore how they can help overcome resistance in patients with respiratory disorders. Additionally, this study discusses concerns related to applications of CRISPR and provides an overview of successful clinical trial studies.
Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Humanos , Edición Génica/métodos , Sistemas CRISPR-Cas/genética , Resistencia a Medicamentos/genética , Animales , Trastornos Respiratorios/genética , Trastornos Respiratorios/terapia , Trastornos Respiratorios/tratamiento farmacológico , Enfermedades Respiratorias/genética , Enfermedades Respiratorias/tratamiento farmacológico , Enfermedades Respiratorias/terapiaRESUMEN
BACKGROUND: Despite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems. OBJECTIVE: Identification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients. MATERIALS AND METHODS: Using a Delphi approach, the leading group reviewed the literature and formulated 14 statements. A multidisciplinary panel of 29 experts were invited to score, for each statement, their agreement on a 1-5 scale. The cut-off level for consensus was 75%, obtained through multiple rounds. RESULTS: The panel agreed that in all RS types, respiratory issues should be faced at an early stage, regardless of epilepsy onset. It is recommended to perform periodically sleep studies in all Congenital Rett Syndrome, and in selected cases with other RS types. Noninvasive ventilation should be considered in all RS subjects with sleep respiratory disorders and in those with hypotonia associated with hypercapnia. Chest physiotherapy should be performed in all RS patients with difficult management of the accumulation of respiratory secretions, using airway clearance techniques and devices (PEP-mask, AMBU bag, or cough machine), more appropriate and tolerated by the patients. The panel recommended individualized programs for the management of scoliosis, and to consider performing gastrostomy in patients at increased risk of ab ingestis pneumonia. CONCLUSIONS: This consensus could support everyday clinical practice on respiratory issues in RS patients, complementary to existing recommendations by regulatory agencies and guidelines.
Asunto(s)
Consenso , Técnica Delphi , Síndrome de Rett , Síndrome de Rett/complicaciones , Síndrome de Rett/terapia , Humanos , Italia , Trastornos Respiratorios/etiología , Trastornos Respiratorios/terapia , Niño , FemeninoRESUMEN
BACKGROUND: Although studies have indicated that extreme temperature is strongly associated with respiratory diseases, there is a dearth of studies focused on children, especially in China. We aimed to explore the association between extreme temperature and children's outpatient visits for respiratory diseases and seasonal modification effects in Harbin, China. METHODS: A distributed lag nonlinear model (DLNM) was used to explore the effect of extreme temperature on daily outpatient visits for respiratory diseases among children, as well as lag effects and seasonal modification effects. RESULTS: Extremely low temperatures were defined as the 1st percentile and 2.5th percentile of temperature. Extremely high temperatures were defined as the 97.5th percentile and 99th percentile of temperature. At extremely high temperatures, both 26 °C (97.5th) and 27 °C (99th) showed adverse effects at lag 0-6 days, with relative risks (RRs) of 1.34 [95% confidence interval (CI): 1.21-1.48] and 1.38 (95% CI: 1.24-1.53), respectively. However, at extremely low temperatures, both - 26 °C (1st) and - 23 °C (2.5th) showed protective effects on children's outpatient visits for respiratory diseases at lag 0-10 days, with RRs of 0.86 (95% CI: 0.76-0.97) and 0.85 (95% CI: 0.75-0.95), respectively. We also found seasonal modification effects, with the association being stronger in the warm season than in the cold season at extremely high temperatures. CONCLUSIONS: Our study indicated that extremely hot temperatures increase the risk of children's outpatient visits for respiratory diseases. Efforts to reduce the exposure of children to extremely high temperatures could potentially alleviate the burden of pediatric respiratory diseases, especially during the warm season.
Asunto(s)
Trastornos Respiratorios , Enfermedades Respiratorias , Niño , Humanos , Temperatura , Pacientes Ambulatorios , Trastornos Respiratorios/epidemiología , Trastornos Respiratorios/terapia , Enfermedades Respiratorias/epidemiología , Enfermedades Respiratorias/terapia , Frío , Calor , China/epidemiologíaAsunto(s)
COVID-19 , Hipoxia , Terapia por Inhalación de Oxígeno , Trastornos Respiratorios , Caminata , Humanos , COVID-19/complicaciones , COVID-19/terapia , Hipoxia/etiología , Hipoxia/terapia , Oxígeno , Proyectos Piloto , Trastornos Respiratorios/etiología , Trastornos Respiratorios/terapia , Método Doble Ciego , Estudios Cruzados , Automatización , Terapia por Inhalación de Oxígeno/instrumentación , Terapia por Inhalación de Oxígeno/métodosRESUMEN
PURPOSE OF REVIEW: This brief critical review evaluates recent research on the impact of anxiety disorders and post-traumatic stress disorders (PTSD) on patients with chronic obstructive pulmonary disease (COPD) and asthma. In these patients, untreated anxiety and PTSD exacerbate acute symptoms, increase disability and impair quality of life. Therefore, effective interventions are also reviewed. RECENT FINDINGS: Anxiety disorders and PTSD are prevalent in COPD and asthma, worsen symptoms in acute exacerbations, and increase morbidity and healthcare utilization. Pulmonary rehabilitation (PR), cognitive behavioural therapy and pharmacological therapy are each effective in COPD patients with anxiety or PTSD. However, very little work examined therapy for combined anxiety and PTSD in patients with either COPD or asthma. SUMMARY: Despite the high prevalence of anxiety disorder or PTSD in patients with chronic respiratory diseases, a paucity of literature remains demonstrating the efficacy of pharmacological therapies for these conditions. This review highlights the promising benefits of PR on anxiety, but prospective trials are needed to demonstrate the efficacy of interventions with PTSD alone, or with concomitant anxiety.
Asunto(s)
Asma , Enfermedad Pulmonar Obstructiva Crónica , Trastornos Respiratorios , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/terapia , Calidad de Vida , Estudios Prospectivos , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/etiología , Ansiedad/epidemiología , Ansiedad/etiología , Ansiedad/terapia , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Trastornos Respiratorios/etiología , Trastornos Respiratorios/terapiaRESUMEN
Rationale: Respiratory conditions account for a large proportion of health care spending in the United States. A full characterization of spending across multiple conditions and over time has not been performed. Objectives: To estimate health care spending in the United States for 11 respiratory conditions from 1996 to 2016, providing detailed trends and an evaluation of factors associated with spending growth. Methods: We extracted data from the Institute of Health Metrics and Evaluation's Disease Expenditure Project Database, producing annual estimates in spending for 38 age and sex groups, 7 types of care, and 3 payer types. We performed a decomposition analysis to estimate the change in spending associated with changes in each of five factors (population growth, population aging, disease prevalence, service usage, and service price and intensity). Measurements and Main Results: Total spending across all respiratory conditions in 2016 was $170.8 billion (95% confidence interval [CI], $164.2-179.2 billion), increasing by $71.7 billion (95% CI, $63.2-80.8 billion) from 1996. The respiratory conditions with the highest spending in 2016 were asthma and chronic obstructive pulmonary disease, contributing $35.5 billion (95% CI, $32.4-38.2 billion) and $34.3 billion (95% CI, $31.5-37.3 billion), respectively. Increasing service price and intensity were associated with 81.4% (95% CI, 70.3-93.0%) growth from 1996 to 2016. Conclusions: U.S. spending on respiratory conditions is high, particularly for chronic conditions like asthma and chronic obstructive pulmonary disease. Our findings suggest that service price and intensity, particularly for pharmaceuticals, should be a key focus of attention for policymakers seeking to reduce health care spending growth.
Asunto(s)
Asma , Enfermedad Pulmonar Obstructiva Crónica , Trastornos Respiratorios , Enfermedades Respiratorias , Humanos , Estados Unidos/epidemiología , Gastos en Salud , Atención a la Salud , Trastornos Respiratorios/epidemiología , Trastornos Respiratorios/terapia , Enfermedades Respiratorias/epidemiología , Enfermedades Respiratorias/terapia , Asma/epidemiología , Asma/terapiaRESUMEN
Chronic rhinosinusitis with nasal polyps (CRSwNP) associated with type 2 inflammation and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) can be difficult to control with standard medical therapy and sinus surgery. In this group, biologicals are potentially promising treatment options. The phase III clinical trials for omalizumab, dupilumab, mepolizumab and benralizumab in CRSwNP have demonstrated favourable outcomes. Moving forward, direct comparisons among biologicals, refining patient selection criteria for specific biologicals, determining optimal treatment duration and monitoring long-term outcomes are areas of emerging interest. This review summarizes the clinical evidence from the recent 2 years on the role of biologicals in severe CRSwNP and N-ERD, and proposes an approach towards decision-making in their use.
Asunto(s)
Productos Biológicos , Pólipos Nasales , Trastornos Respiratorios , Rinitis , Sinusitis , Humanos , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/complicaciones , Rinitis/tratamiento farmacológico , Rinitis/complicaciones , Sinusitis/tratamiento farmacológico , Sinusitis/complicaciones , Antiinflamatorios no Esteroideos/efectos adversos , Enfermedad Crónica , Terapia Biológica , Trastornos Respiratorios/terapia , Productos Biológicos/uso terapéuticoRESUMEN
Rett syndrome is a neurological disease due to loss-of-function mutations in the transcription factor, Methyl CpG binding protein 2 (MECP2). Because overexpression of endogenous MECP2 also causes disease, we have exploited a targeted RNA-editing approach to repair patient mutations where levels of MECP2 protein will never exceed endogenous levels. Here, we have constructed adeno-associated viruses coexpressing a bioengineered wild-type ADAR2 catalytic domain (Editasewt) and either Mecp2-targeting or nontargeting gfp RNA guides. The viruses are introduced systemically into male mice containing a guanosine to adenosine mutation that eliminates MeCP2 protein and causes classic Rett syndrome in humans. We find that in the mutant mice injected with the Mecp2-targeting virus, the brainstem exhibits the highest RNA-editing frequency compared to other brain regions. The efficiency is sufficient to rescue MeCP2 expression and function in the brainstem of mice expressing the Mecp2-targeting virus. Correspondingly, we find that abnormal Rett-like respiratory patterns are alleviated, and survival is prolonged, compared to mice injected with the control gfp guide virus. The levels of RNA editing among most brain regions corresponds to the distribution of guide RNA rather than Editasewt. Our results provide evidence that a targeted RNA-editing approach can alleviate a hallmark symptom in a mouse model of human disease.
Asunto(s)
Tronco Encefálico , Proteína 2 de Unión a Metil-CpG , Edición de ARN , Trastornos Respiratorios , Síndrome de Rett , Animales , Tronco Encefálico/metabolismo , Modelos Animales de Enfermedad , Humanos , Masculino , Proteína 2 de Unión a Metil-CpG/genética , Ratones , Mutación , Trastornos Respiratorios/genética , Trastornos Respiratorios/terapia , Síndrome de Rett/genética , Síndrome de Rett/terapiaRESUMEN
Allergy and respiratory disorders are common in young athletic individuals. In the context of elite sport, it is essential to secure an accurate diagnosis in order to optimize health and performance. It is also important, however, to consider the potential impact or consequences of these disorders, in recreationally active individuals engaging in structured exercise and/or physical activity to maintain health and well-being across the lifespan. This EAACI Task Force was therefore established, to develop an up-to-date, research-informed position paper, detailing the optimal approach to the diagnosis and management of common exercise-related allergic and respiratory conditions. The recommendations are informed by a multidisciplinary panel of experts including allergists, pulmonologists, physiologists and sports physicians. The report is structured as a concise, practically focussed document, incorporating diagnostic and treatment algorithms, to provide a source of reference to aid clinical decision-making. Throughout, we signpost relevant learning resources to consolidate knowledge and understanding and conclude by highlighting future research priorities and unmet needs.
Asunto(s)
Hipersensibilidad , Trastornos Respiratorios , Enfermedades Respiratorias , Deportes , Comités Consultivos , Ejercicio Físico , Humanos , Hipersensibilidad/diagnóstico , Hipersensibilidad/etiología , Hipersensibilidad/terapia , Trastornos Respiratorios/diagnóstico , Trastornos Respiratorios/etiología , Trastornos Respiratorios/terapia , Enfermedades Respiratorias/diagnóstico , Enfermedades Respiratorias/etiología , Enfermedades Respiratorias/terapiaRESUMEN
OBJECTIVES: to identify nursing interventions in rehabilitation, within the scope of functional respiratory reeducation, which allow a respiratory function improvement in people with respiratory disease. METHODS: systematic literature review using the MEDLINE database search, adopting the PICO mnemonic and the Joanna Briggs Institute's assessment of the level of evidence and methodological quality. The search for randomized controlled trials was carried out in June 2021 considering the period from 2015 to 2020, in English or Portuguese. RESULTS: a sample of nine randomized controlled trials with methodological quality was obtained which highlighted the use of positive expiratory pressure devices as an important component and intervention for respiratory functional reeducation. CONCLUSIONS: nursing interventions in rehabilitation with an emphasis on functional respiratory reeducation are essential, showing improvements in people's general health.
Asunto(s)
Trastornos Respiratorios , Enfermedades Respiratorias , Humanos , Trastornos Respiratorios/terapia , Enfermedades Respiratorias/terapiaRESUMEN
Chinese medicine for intestinal regulation is an emerging method for pediatric respiratory disorders, which has better clinical value when combined with NIV (Non-invasive ventilation). This study aims to observe the clinical efficacy of NIV plus Chinese medicine for intestinal regulation in Chinese children with respiratory disorders. Thirty-nine patients admitted to Huaihua First People's Hospital, between March 2016 and July 2018 were enrolled, including 14 children with chronic hypercapnic respiratory failure, 19 with non-surgical OSAS, 5 with OB and 1 with central hypoventilation syndrome. After NIV, the blood gas carbon dioxide retention and labored breathing were improved, respiratory rate and heart rate were decreased and the feeding condition of some children improved. After NIV treatment, clinical symptoms of children with OSAS were significantly ameliorated. In polysomnography monitoring, the AHI, OAI and SpO2 were significantly enhanced following NIV. In addition, patients with OB and central hypoventilation had different degrees of improvement of their symptoms. NIV plus Chinese medicine for intestinal regulation alleviate the clinical symptoms and enhances the quality of life of children with chronic hypercapnic respiratory failure. Some children could be transferred out of the intensive care unit and into home mechanical ventilation.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Intestinos/efectos de los fármacos , Pulmón/fisiopatología , Ventilación no Invasiva , Trastornos Respiratorios/terapia , Respiración , Factores de Edad , Niño , Preescolar , China , Terapia Combinada , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Humanos , Lactante , Intestinos/fisiopatología , Masculino , Ventilación no Invasiva/efectos adversos , Calidad de Vida , Recuperación de la Función , Trastornos Respiratorios/diagnóstico , Trastornos Respiratorios/fisiopatología , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Las enfermedades neuromusculares (ENM) afectan los distintos componentes de la unidad motora. Desde el diagnóstico deben ser seguidos por un equipo interdisciplinario, donde el neumólogo pediátrico desempeña un papel importante en la valoración de la pérdida de fuerza muscular cuando afecta a la musculatura respiratoria o de la vía aérea superior. Objetivos: conocer las diferentes enfermedades neuromusculares atendidas en el Centro Hospitalario Pereira Rossell, analizar las características de la población y describir los resultados de los principales estudios solicitados por la policlínica de neumológica pediátrica. Metodología: estudio descriptivo, analítico y retrospectivo de los pacientes con enfermedad neuromuscular atendidos en el Centro Hospitalario Pereira Rossell entre el 1/6/2006 y el 31/12/2019. Resultados: las patologías neuromusculares más frecuentemente encontradas fueron distrofias musculares, miopatías, distrofia miotónica de Steinert y atrofia muscular espinal. No tienen diagnóstico definitivo 21/73 pacientes. La espirometría mostró una alteración restrictiva en la mayoría de los pacientes. Para descartar trastornos respiratorios del sueño se realizó oximetría nocturna con gasometría al despertar. La hipoventilación nocturna y las apneas obstructivas fueron las alteraciones encontradas. En 12/73 se inició ventilación no invasiva. Conclusiones: los pacientes con ENM experimentan un deterioro progresivo de la función respiratoria que contribuye a una elevada tasa de morbimortalidad. La evaluación y seguimiento regular de la función respiratoria junto con estudios de sueño, son fundamentales para el inicio oportuno de ventilación no invasiva.
Neuromuscular diseases (NMD) affect the different components of the motor system. As of diagnosis, they should be followed by an interdisciplinary team, in which pediatric pulmonologists play an important role in assessing the loss of muscle strength when NMD affects the respiratory or upper airway muscles. Objectives: to learn about the different neuromuscular diseases treated at the Pereira Rossell Hospital Center, to analyze the characteristics of this population and to describe the results of the main studies requested by the pediatric pulmonology clinic. Methodology: descriptive, analytical and retrospective study of patients with neuromuscular disease treated at the Pereira Rossell Hospital Center between 6/1/2006 and 12/31/2019. Results: the most frequent neuromuscular pathologies were muscular dystrophies, myopathies, Steinert's myotonic dystrophy and spinal muscular atrophy. 21/73 patients did not have a definitive diagnosis. Spirometry showed a restrictive alteration in most of the patients. To rule out respiratory sleep disorders, nocturnal oximetry with blood gas was performed upon awakening, with nocturnal hypoventilation and obstructive apneas being the alterations found. In 12/73 non-invasive ventilation was applied. Conclusions: patients with NMD experience a progressive deterioration of respiratory function that contributes to a high rate of morbidity and mortality. Regular evaluation and monitoring of respiratory function, along with sleep studies, are essential for the timely initiation of non-invasive ventilation.
As doenças neuromusculares (DNM) afetam os diferentes componentes da unidade motora. Desde o diagnóstico, os pacientes devem ser acompanhados por uma equipe interdisciplinar, onde o pneumologista pediátrico desempenha um papel importante na avaliação da perda de força muscular quando atinge a musculatura respiratória ou das vias aéreas superiores. Objetivos: conhecer as diferentes doenças neuromusculares tratadas no Centro Hospitalar Pereira Rossell, analisar as características desta população e descrever os resultados dos principais estudos solicitados à policlínica de pneumologia pediátrica. Metodologia: estudo descritivo, analítico e retrospectivo de pacientes com doenças neuromusculares atendidos no Centro Hospitalar Pereira Rossell entre 01/06/2006 e 31/12/2019. Resultados: as patologias neuromusculares mais encontradas foram distrofias musculares, miopatias, distrofia miotônica de Steinert e atrofia muscular espinhal. 21/73 pacientes não tiveram um diagnóstico definitivo. A espirometria mostrou alteração restritiva na maioria dos pacientes. Para afastar distúrbios respiratórios do sono, foi realizada oximetria noturna com gasometria ao despertar, sendo a hipoventilação noturna e as apneias obstrutivas as alterações encontradas. Em 12/73 foi iniciada ventilação não invasiva. Conclusões: os pacientes com DNM experimentam uma deterioração progressiva da função respiratória que contribui para uma alta taxa de morbidade e mortalidade. A avaliação regular e o monitoramento da função respiratória, juntamente com os estudos do sono, são essenciais para o início oportuno da ventilação não invasiva.
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Enfermedades Neuromusculares/clasificación , Enfermedades Neuromusculares/epidemiología , Trastornos Respiratorios/etiología , Trastornos Respiratorios/terapia , Uruguay/epidemiología , Estudios Transversales , Estudios Retrospectivos , Ventilación no Invasiva , Enfermedades Neuromusculares/complicaciones , Enfermedades Neuromusculares/diagnósticoRESUMEN
Preclinical studies suggest mesenchymal stromal cell extracellular vesicles (MSC-EVs) reduce inflammation and improve organ function in lung diseases; however, an objective analysis of all available data is needed prior to translation. Using rigorous meta-research methods, we determined the effectiveness of MSC-EVs for preclinical respiratory diseases and identified experimental conditions that may further refine this therapy. A systematic search of MEDLINE/Embase identified 1167 records. After screening, 52 articles were included for data extraction and evaluated for risk of bias and quality of reporting in study design. A random effects meta-analysis was conducted for acute lung injury (ALI; N = 23), bronchopulmonary dysplasia (BPD; N = 8) and pulmonary arterial hypertension (PAH; N = 7). Subgroup analyses identified EV methods/characteristics that may be associated with improved efficacy. Data is presented as standardized mean differences (SMD) or risk ratios (RR) with 95% confidence intervals (CI). For ALI, MSC-EVs markedly reduced lung injury (SMD -4.33, CI -5.73 to -2.92), vascular permeability (SMD -2.43, CI -3.05 to -1.82), and mortality (RR 0.39, CI 0.22 to 0.68). Small EVs were more consistently effective than large EVs whereas no differences were observed between tissue sources, immunocompatibility or isolation techniques. For BPD, alveolarization was improved by MSC-EVs (SMD -1.45, CI -2.08 to -0.82) with small EVs more consistently beneficial then small/large EVs. In PAH, right ventricular systolic pressure (SMD -4.16, CI -5.68 to -2.64) and hypertrophy (SMD -2.80, CI -3.68 to -1.91) were significantly attenuated by EVs. In BPD and PAH, EVs isolated by ultracentrifugation demonstrated therapeutic benefit whereas tangential flow filtration (N = 2) displayed minimal efficacy. Lastly, risk of bias and quality of reporting for experimental design were consistently unclear across all studies. Our findings demonstrate clear potential of MSC-EVs to be developed as therapy for acute and chronic lung diseases. However, greater transparency in research design and direct comparisons of isolation technique and EV subtypes are needed to generate robust evidence to guide clinical translation. Protocol Registration: PROSPERO CRD42020145334.
Asunto(s)
Vesículas Extracelulares/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Trastornos Respiratorios/terapia , Enfermedad Aguda , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , HumanosRESUMEN
Endogenous glucocorticoids (GCs) are steroid hormones that signal in virtually all cell types to modulate tissue homeostasis throughout life. Also, synthetic GC derivatives (pharmacological GCs) constitute the first-line treatment in many chronic inflammatory conditions with unquestionable therapeutic benefits despite the associated adverse effects. GC actions are principally mediated through the GC receptor (GR), a ligand-dependent transcription factor. Despite the ubiquitous expression of GR, imbalances in GC signalling affect tissues differently, and with variable degrees of severity through mechanisms that are not completely deciphered. Congenital or acquired GC hypersensitivity or resistance syndromes can impact responsiveness to endogenous or pharmacological GCs, causing disease or inadequate therapeutic outcomes, respectively. Acquired GC resistance is defined as loss of efficacy or desensitization over time, and arises as a consequence of chronic inflammation, affecting around 30% of GC-treated patients. It represents an important limitation in the management of chronic inflammatory diseases and cancer, and can be due to impairment of multiple mechanisms along the GC signalling pathway. Among them, activation of the mitogen-activated protein kinases (MAPKs) and/or alterations in expression of their regulators, the dual-specific phosphatases (DUSPs), have been identified as common mechanisms of GC resistance. While many of the anti-inflammatory actions of GCs rely on GR-mediated inhibition of MAPKs and/or induction of DUSPs, the GC anti-inflammatory capacity is decreased or lost in conditions of excessive MAPK activation, contributing to disease susceptibility in tissue- and disease- specific manners. Here, we discuss potential strategies to modulate GC responsiveness, with the dual goal of overcoming GC resistance and minimizing the onset and severity of unwanted adverse effects while maintaining therapeutic potential.
Asunto(s)
Regulación de la Expresión Génica , Glucocorticoides/metabolismo , Sistema de Señalización de MAP Quinasas , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Animales , Enfermedades Autoinmunes/terapia , Enfermedad Crónica , Activación Enzimática , Heterocigoto , Humanos , Inflamación/metabolismo , Leucemia/terapia , Errores Innatos del Metabolismo/metabolismo , Ratones , Mutación , Polimorfismo Genético , Isoformas de Proteínas , Receptores de Glucocorticoides/deficiencia , Trastornos Respiratorios/terapia , Transducción de Señal , Enfermedades de la Piel/terapia , Resultado del TratamientoRESUMEN
The current national coverage determinations (NCDs) for noninvasive ventilation for patients with thoracic restrictive disorders, COPD, and hypoventilation syndromes were formulated in 1998. New original research, updated formal practice guidelines, and current consensus expert opinion have accrued that are in conflict with the existing NCDs. Some inconsistencies in the NCDs have been noted, and the diagnostic and therapeutic technology has also advanced in the last quarter century. Thus, these and related NCDs relevant to bilevel positive airway pressure for the treatment of OSA and central sleep apnea need to be updated to ensure the optimal health of patients with these disorders. To that end, the American College of Chest Physicians organized a multisociety (American Thoracic Society, American Academy of Sleep Medicine, and American Association for Respiratory Care) effort to engage experts in the field to: (1) identify current barriers to optimal care; (2) highlight compelling scientific evidence that would justify changes from current policies incorporating best evidence and practice; and (3) propose suggestions that would form the basis for a revised NCD in each of these 5 areas (thoracic restrictive disorders, COPD, hypoventilation syndromes, OSA, and central sleep apnea). The expert panel met during a 2-day virtual summit in October 2020 and subsequently crafted written documents designed to achieve provision of "the right device to the right patient at the right time." These documents have been endorsed by the participating societies following peer review and publication in CHEST and will be used to inform efforts to revise the current NCDs.
Asunto(s)
Ventilación no Invasiva , Trastornos Respiratorios , Benchmarking , Consenso , Humanos , Medicare , Ventilación no Invasiva/instrumentación , Ventilación no Invasiva/métodos , Ventilación no Invasiva/normas , Selección de Paciente , Trastornos Respiratorios/clasificación , Trastornos Respiratorios/etiología , Trastornos Respiratorios/terapia , Estados UnidosRESUMEN
BACKGROUND: Chronic respiratory diseases (CRD), are common public health problems with high prevalence, disability and mortality rates worldwide. Further uneven distribution of the health workforce is a major barrier to the effective diagnosis and treatment of CRDs. Teleconsultation between a specialist and non-specialist could possibly bridge the gap in access to health care and decrease CRD burden in remote areas. This review investigates the evidence for the effective use of specialist to non-specialist teleconsultation in the management of CRDs in remote areas and identifies instances of good practice and knowledge gaps. METHODS: We searched for articles till November 2020, which focused on specialist to non-specialist teleconsultations for CRD diagnosis or management. Two independent reviewers conducted the title and abstract screening and extracted data from the selected papers and the quality was assessed by Joanna Briggs Institute's (JBI) tool. A descriptive and narrative approach was used due to the heterogeneous nature of the selected studies. RESULTS: We found 1715, articles that met the initial search criteria, but after excluding duplicates and non-eligible articles, we included 10 research articles of moderate quality. These articles were from nine different studies, all of which, except one, were conducted in high-income countries. The studies reported results in terms of impact on the patients, and the health care providers including primary care physicians (PCP) and specialists. The teleconsulting systems used in all the selected papers primarily used audio modes in addition to other modes like the audio-video medium. The included studies reported primarily non-clinical outcomes including effectiveness, feasibility, acceptability and usability of the teleconsultation systems and only three described the clinical outcomes. The teleconsultation was predominantly conducted in the PCP's office with the specialist located remotely. CONCLUSIONS: We found relatively few, papers which explored specialist to non-specialist teleconsultation in management of CRDs, and no controlled trials. Two of the included papers described systems, which were used for other diseases in addition to the CRD. The available literature although not generalisable, encourages the use of specialist to non-specialist teleconsultation for diagnosis and management of CRDs.
Asunto(s)
Consulta Remota , Trastornos Respiratorios , Especialización , Enfermedad Crónica , Humanos , Consulta Remota/estadística & datos numéricos , Trastornos Respiratorios/terapia , Especialización/estadística & datos numéricosRESUMEN
Epilepsy is a debilitating disorder of uncontrollable recurrent seizures that occurs as a result of imbalances in the brain excitatory and inhibitory neuronal signals, that could stem from a range of functional and structural neuronal impairments. Globally, nearly 70 million people are negatively impacted by epilepsy and its comorbidities. One such comorbidity is the effect epilepsy has on the autonomic nervous system (ANS), which plays a role in the control of blood circulation, respiration and gastrointestinal function. These epilepsy-induced impairments in the circulatory and respiratory systems may contribute toward sudden unexpected death in epilepsy (SUDEP). Although, various hypotheses have been proposed regarding the role of epilepsy on ANS, the linking pathological mechanism still remains unclear. Channelopathies and seizure-induced damages in ANS-control brain structures were some of the causal/pathological candidates of cardiorespiratory comorbidities in epilepsy patients, especially in those who were drug resistant. However, emerging preclinical research suggest that neurotransmitter/receptor dysfunction and synaptic changes in the ANS may also contribute to the epilepsy-related autonomic disorders. Thus, pathological mechanisms of cardiorespiratory dysfunction should be elucidated by considering the modifications in anatomy and physiology of the autonomic system caused by seizures. In this regard, we present a comprehensive review of the current literature, both clinical and preclinical animal studies, on the cardiorespiratory findings in epilepsy and elucidate the possible pathological mechanisms of these findings, in hopes to prevent SUDEP especially in patients who are drug resistant.
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Encéfalo/fisiopatología , Epilepsia/fisiopatología , Frecuencia Cardíaca/fisiología , Mecánica Respiratoria/fisiología , Muerte Súbita e Inesperada en la Epilepsia , Animales , Sistema Nervioso Autónomo/fisiología , Capacidad Cardiovascular/fisiología , Epilepsia/diagnóstico , Epilepsia/terapia , Cardiopatías/diagnóstico , Cardiopatías/fisiopatología , Cardiopatías/terapia , Humanos , Trastornos Respiratorios/diagnóstico , Trastornos Respiratorios/fisiopatología , Trastornos Respiratorios/terapia , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Convulsiones/terapia , Muerte Súbita e Inesperada en la Epilepsia/prevención & control , Resultado del TratamientoRESUMEN
INTRODUCTION: The end-of-life symptom prevalence of non-cancer patients have been described mostly in hospital and institutional settings. This study aims to describe the average symptom trajectories among non-cancer patients who are community-dwelling and used home care services at the end of life. MATERIALS AND METHODS: This is a retrospective, population-based cohort study of non-cancer patients who used home care services in the last 6 months of life in Ontario, Canada, between 2007 and 2014. We linked the Resident Assessment Instrument for Home Care (RAI-HC) (standardized home care assessment tool) and the Discharge Abstract Databases (for hospital deaths). Patients were grouped into four non-cancer disease groups: cardiovascular, neurological, respiratory, and renal (not mutually exclusive). Our outcomes were the average prevalence of these outcomes, each week, across the last 6 months of life: uncontrolled moderate-severe pain as per the Pain Scale, presence of shortness of breath, mild-severe cognitive impairment as per the Cognitive Performance Scale, and presence of caregiver distress. We conducted a multivariate logistic regression to identify factors associated with having each outcome respectively, in the last 6 months. RESULTS: A total of 20,773 non-cancer patient were included in our study, which were analyzed by disease groups: cardiovascular (n = 12,923); neurological (n = 6,935); respiratory (n = 6,357); and renal (n = 3,062). Roughly 80% of patients were > 75 years and half were female. In the last 6 months of life, moderate to severe pain was frequent in the cardiovascular (57.2%), neurological (42.7%), renal (61.0%) and respiratory (58.3%) patients. Patients with renal disease had significantly higher odds for reporting uncontrolled moderate to severe pain (odds ratio [OR] = 1.21; 95% CI: 1.08 to 1.34) than those who did not. Patients with respiratory disease reported significantly higher odds for shortness of breath (5.37; 95% CI, 5.00 to 5.80) versus those who did not. Patients with neurological disease compared to those without were 9.65 times more likely to experience impaired cognitive performance and had 56% higher odds of caregiver distress (OR = 1.56; 95% CI: 1.43 to 1.71). DISCUSSION: In our cohort of non-cancer patients dying in the community, pain, shortness of breath, impaired cognitive function and caregiver distress are important symptoms to manage near the end of life even in non-institutional settings.