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1.
Fam Pract ; 41(2): 86-91, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-37672297

RESUMEN

BACKGROUND: The burden of documentation in the electronic medical record has been cited as a major factor in provider burnout. The aim of this study was to evaluate the association between ambient voice technology, coupled with natural language processing and artificial intelligence (DAX™), on primary care provider documentation burden and burnout. METHODS: An observational study of 110 primary care providers within a community teaching health system. The primary objectives were to determine the association between DAX™ usage and provider burnout scores on the Oldenburg Burnout Inventory (OLBI) as well as the effect on documentation time per patient encounter (minutes). RESULTS: The completion rate for the survey was 75% (83/110) and high DAX™ use (>60% of encounters) was seen in 28% of providers (23/83). High DAX™ use was associated with significantly less burnout on the OLBI disengagement sub-score (MD [Mean Difference] -2.1; 95% confidence interval [CI] -3.8 to -0.4) but not the OLBI disengagement sub-score (-1.0; 95% CI -2.9 to 1.0) or total score (MD -3.0; 95% CI -6.4 to 0.3). Nineteen providers with high implementation of DAX™ had pre and postimplementation data on documentation time per encounter. After DAX™ implementation average documentation time in notes per encounter was significantly reduced by 28.8% (1.8 min; 95% CI 1.4-2.2). CONCLUSIONS: The use of ambient voice technology during patient encounters was associated with significantly reduced documentation burden and primary care provider disengagement but not total provider burnout scores.


Asunto(s)
Inteligencia Artificial , Agotamiento Profesional , Humanos , Agotamiento Psicológico , Documentación , Atención Primaria de Salud
2.
J Int Med Res ; 50(11): 3000605221135446, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36324277

RESUMEN

OBJECTIVE: To determine the incidence and significance of ventilator avoidance in patients with critical coronavirus disease 2019 (COVID-19). METHODS: This prospective observational cohort study evaluated hospital mortality and 1-year functional outcome among critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated acute respiratory distress syndrome (ARDS). The explanatory variable was ventilator avoidance, modeled as 'initial refusal' of intubation (yes/no). Modified Rankin Scale (mRS) scores were obtained from surviving patients (or their surrogates) via phone or email questionnaire. RESULTS: Among patients for whom intubation was recommended (n = 102), 40 (39%) initially refused (95% confidence interval [CI] 30%, 49%). The risk of death was 79.3% (49/62) in those who did not initially refuse intubation compared with 77.5% (31/40) in those who initially refused, with an adjusted odds ratio for death of 1.27 (95% CI 0.47, 3.48). The distribution of 1-year mRS scores was not significantly different between groups. CONCLUSION: Among critically ill patients with COVID-19-associated ARDS, ventilator avoidance was common, but was not associated with increased in-hospital mortality or 1-year functional outcome.


Asunto(s)
COVID-19 , Síndrome de Dificultad Respiratoria , Humanos , SARS-CoV-2 , Enfermedad Crítica , Estudios Prospectivos , Síndrome de Dificultad Respiratoria/terapia , Ventiladores Mecánicos
3.
Infect Control Hosp Epidemiol ; 43(4): 490-496, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-33853694

RESUMEN

OBJECTIVE: We hypothesized that healthcare workers (HCWs) with high-risk exposures outside the healthcare system would have less asymptomatic coronavirus 2019 (COVID-19) disease and more symptoms than those without such exposures. DESIGN: A longitudinal point prevalence study was conducted during August 17-September 4, 2020 (period 1) and during December 2-23, 2020 (period 2). SETTING: Community based teaching health system. PARTICIPANTS: All HCWs were invited to participate. Among HCWs who acquired COVID-19, logistic regression models were used to evaluate the adjusted odds of asymptomatic disease using high-risk exposure outside the healthcare system as the explanatory variable. The number of symptoms between exposure groups was evaluated with the Wilcoxon rank-sum test. The risk of seropositivity among all HCS by work exposure was evaluated during both periods. INTERVENTIONS: Survey and serological testing. RESULT: Seroprevalence increased from 1.9% (95% confidence interval [CI], 1.2%-2.6%) to 13.7% (95% CI, 11.9%-15.5%) during the study. Only during period 2 did HCWs with the highest work exposure (versus low exposure) have an increased risk of seropositivity (risk difference [RD], 7%; 95% CI, 1%-13%). Participants who had a high-risk exposure outside of work (compared to those without) had a decreased probability of asymptomatic disease (odds ratio [OR], 0.38; 95% CI, 0.16-0.86) and demonstrated more symptoms (median 3 [IQR, 2-6] vs 1 [IQR, 0-4]; P = .001). CONCLUSIONS: Healthcare-acquired COVID-19 increases the probability of asymptomatic or mild COVID-19 disease compared to community-acquired disease. This finding suggests that infection prevention strategies (including masks and eye protection) may be mitigating inoculum and supports the variolation theory in COVID-19.


Asunto(s)
COVID-19 , Enfermedades Asintomáticas , COVID-19/epidemiología , Atención a la Salud , Personal de Salud , Humanos , SARS-CoV-2 , Estudios Seroepidemiológicos
5.
Chest ; 160(4): 1534-1551, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34023322

RESUMEN

BACKGROUND: Comprehensive US epidemiologic data for adult pleural disease are not available. RESEARCH QUESTION: What are the epidemiologic measures related to adult pleural disease in the United States? STUDY DESIGN AND METHODS: Retrospective cohort study using Healthcare Utilization Project databases (2007-2016). Adults (≥ 18 years of age) with malignant pleural mesothelioma, malignant pleural effusion, nonmalignant pleural effusion, empyema, primary and secondary spontaneous pneumothorax, iatrogenic pneumothorax, and pleural TB were studied. RESULTS: In 2016, ED treat-and-discharge (T&D) visits totaled 42,215, accounting for charges of $286.7 million. In 2016, a total of 361,270 hospitalizations occurred, resulting in national costs of $10.1 billion. A total of 64,174 readmissions contributed $1.16 billion in additional national costs. Nonmalignant pleural effusion constituted 85.5% of ED T&D visits, 63.5% of hospitalizations, and 66.3% of 30-day readmissions. Contemporary sex distribution (male to female ratio) in primary spontaneous pneumothorax (2.1:1) differs from older estimates (6.2:1). Decadal analyses of annual hospitalization rates/100,000 adult population (2007 vs 2016) showed a significant (P < .001) decrease for malignant pleural mesothelioma (1.3 vs 1.09, respectively), malignant pleural effusion (33.4 vs 31.9, respectively), iatrogenic pneumothorax (17.9 vs 13.9, respectively), and pleural TB (0.20 vs 0.09, respectively) and an increase for empyema (8.1 vs 11.1, respectively) and nonmalignant pleural effusion (78.1 vs 100.1, respectively). Empyema hospitalizations have high costs per case ($38,591) and length of stay (13.8 days). The mean proportion of readmissions attributed to a pleural cause varied widely: malignant pleural mesothelioma, 49%; malignant pleural effusion, 45%; nonmalignant pleural effusion, 31%; empyema, 27%; primary spontaneous pneumothorax, 27%; secondary spontaneous pneumothorax, 27%; and iatrogenic pneumothorax, 20%. Secondary spontaneous pneumothorax had the shortest time to readmission in 2016 (10.3 days, 95% CI, 8.8-11.8 days). INTERPRETATION: Significant epidemiologic trends and changes in various pleural diseases were observed. The analysis identifies multiple opportunities for improvement in management of pleural diseases.


Asunto(s)
Enfermedades Pleurales/epidemiología , Adolescente , Adulto , Anciano , Empiema/economía , Empiema/epidemiología , Femenino , Federación para Atención de Salud , Gastos en Salud , Hospitalización/economía , Humanos , Incidencia , Masculino , Mesotelioma Maligno/economía , Mesotelioma Maligno/epidemiología , Persona de Mediana Edad , Readmisión del Paciente/economía , Enfermedades Pleurales/economía , Derrame Pleural/economía , Derrame Pleural/epidemiología , Derrame Pleural Maligno , Neoplasias Pleurales/economía , Neoplasias Pleurales/epidemiología , Neumotórax/economía , Neumotórax/epidemiología , Tuberculosis Pleural/economía , Tuberculosis Pleural/epidemiología , Estados Unidos/epidemiología , Adulto Joven
6.
Ann Emerg Med ; 76(1): 88-102, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32115203

RESUMEN

STUDY OBJECTIVE: The best initial strategy for nontension symptomatic spontaneous pneumothorax is unclear. We performed a systematic review and meta-analysis to identify the most efficacious, safe, and efficient initial intervention in adults with nontension spontaneous pneumothorax. METHODS: MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched from January 1950 through December 2019 (print and electronic publications). Randomized controlled trials evaluating needle aspiration, narrow-bore chest tube (<14 F) with or without Heimlich valve insertion, and large-bore chest tube (≥14 F) insertion in spontaneous pneumothorax were included. Network meta-analyses were performed with a Bayesian random-effects model. RESULTS: Twelve studies were included in this review (n=781 patients). Analyses of efficacy (n=12 trials) revealed no significant differences between the interventions studied: narrow- versus large-bore chest tubes, odds ratio (OR) 1.05 (95% credible interval [CrI] 0.38 to 2.87); large-bore chest tube versus needle aspiration, OR 1.25 (95% CrI 0.65 to 2.62); and narrow-bore chest tube versus needle aspiration, OR 1.32 (95% CrI 0.54 to 3.42). Analyses of safety (n=10 trials) revealed a significant difference between needle aspiration and large-bore chest tube interventions: OR 0.10 (95% CrI 0.03 to 0.40). No differences were observed in needle aspiration versus narrow-bore chest tube (OR 0.29 [95% CrI 0.05 to 1.82]), and narrow- versus large-bore chest tube comparisons (OR 0.35 [95% CrI 0.07 to 1.67]). Analyses of efficiency were not pursued because of variation in reporting the length of stay (n=12 trials). Narrow-bore chest tube (<14 F) had the highest likelihood of top ranking in terms of immediate success (surface under the cumulative ranking curve=64%). Needle aspiration had the highest likelihood of top ranking in terms of safety (surface under the cumulative ranking curve=95.8%). CONCLUSION: In the initial management of nontension spontaneous pneumothorax, the optimal strategy between the choices of a narrow-bore chest tube (<14 F, top ranked in efficacy) and needle aspiration (top ranked in safety) is unclear. Complications were more common in large-bore chest tube (≥14 F, including 14-F tube) insertions compared with needle aspiration.


Asunto(s)
Drenaje/métodos , Neumotórax/terapia , Teorema de Bayes , Tubos Torácicos , Investigación sobre la Eficacia Comparativa , Servicios Médicos de Urgencia , Humanos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto
7.
Pulm Med ; 2018: 2035248, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29805807

RESUMEN

BACKGROUND AND OBJECTIVES: Clinical pathways are evidence based multidisciplinary team approaches to optimize patient care. Pleural diseases are common and accounted for 3.4 billion US $ in 2014 US inpatient aggregate charges (HCUPnet data). An institutional clinical pathway ("pleural pathway") was implemented in conjunction with a dedicated pleural service. Design, implementation, and outcomes of the pleural pathway (from August 1, 2014, to July 31, 2015) in comparison to a previous era (from August 1, 2013, to July 31, 2014) are described. METHODS: Tuality Healthcare is a 215-bed community healthcare system in Hillsboro, OR, USA. With the objective of standardizing pleural disease care, locally adapted British Thoracic Society guidelines and a centralized pleural service were implemented in the "pathway" era. System-wide consensus regarding institutional guidelines for care of pleural disease was achieved. Preimplementation activities included training, acquisition of ultrasound equipment, and system-wide education. An audit database was set up with the intent of prospective audits. An administrative database was used for harvesting outcomes data and comparing them with the "prior to pathway" era. RESULTS: 54 unique consults were performed. A total of 55 ultrasound examinations and 60 pleural procedures were performed. All-cause inpatient pleural admissions were lower in the "pathway" era (n = 9) compared to the "prior to pathway" era (n = 17). Gains in average case charges (21,737$ versus 18,818.2$/case) and average length of stay (3.65 versus 2.78 days/case) were seen in the "pathway" era. CONCLUSION: A "pleural pathway" and a centralized pleural service are associated with reduction in case charges, inpatient admissions, and length of stay for pleural conditions.


Asunto(s)
Vías Clínicas , Enfermedades Pleurales/terapia , Anciano , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
9.
Respir Care ; 62(12): 1520-1524, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28974644

RESUMEN

BACKGROUND: Usual practice in community health-care settings indicates that arterial catheters are inserted by physicians. In the context of a respiratory therapist (RT)-managed arterial catheter placement protocol being implemented in our community hospital, the current study describes the implementation and outcomes of this RT-managed arterial catheter insertion and maintenance program. METHODS: Tuality Healthcare is a 215-bed community health-care system (10-bed ICU) in Hillsboro, Oregon. With the goal of enhancing the quality of ICU care, an RT-managed multidisciplinary team was implemented to lead the delivery of protocolized ventilator liberation, arterial catheter insertion, and arterial blood gas utilization. Preparation for the program included didactic teaching, simulation-based training, and precepted procedural experience. A database was created for audit and quality improvement purposes. Outcomes and arterial blood gas utilization data were obtained from the audit database and from the hospital electronic health record. RESULTS: During the 4-y period (March 1, 2012, to April 31, 2016), 256 arterial catheter insertion attempts were made by a team of 12 qualified RTs. The success rate for the initial placement attempt by RT was high (94.5% [242 of 256]). Sixty-three percent of arterial lines were placed in patients to help manage severe sepsis/septic shock. No ischemic or infectious complications were reported during the study period. Nearly 40% (96 of 242) of the successful placements by RTs on initial attempts were performed during the night shift, when intensivists were not physically present in the ICU. CONCLUSIONS: This experience establishes the feasibility of an RT-managed arterial catheter placement program in a community ICU. The RT-managed program was characterized by a high degree of success and safety and allowed arterial catheter placement at times when intensivists were not available in the ICU. This experience extends the sparse reported experience of RT-managed arterial catheter placement programs and underscores the value of RTs as members of the ICU team.


Asunto(s)
Cateterismo Periférico/métodos , Cuidados Críticos/métodos , Evaluación de Procesos y Resultados en Atención de Salud , Servicio de Terapia Respiratoria en Hospital/estadística & datos numéricos , Terapia Respiratoria/métodos , Adulto , Arterias , Cateterismo Periférico/normas , Comisión sobre Actividades Profesionales y Hospitalarias , Cuidados Críticos/normas , Bases de Datos Factuales , Estudios de Factibilidad , Femenino , Hospitales Comunitarios/normas , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Oregon , Mejoramiento de la Calidad , Terapia Respiratoria/normas , Servicio de Terapia Respiratoria en Hospital/normas
11.
Chest ; 149(5): 1340-4, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26836891

RESUMEN

Asthma is characterized by chronic airway inflammation. Fractional exhaled nitric oxide (Feno) has emerged as a marker of T-helper cell type 2-mediated allergic airway inflammation. Recent studies suggest a role for Feno testing as a point-of-care tool in the management of patients with asthma. This Topics in Practice Management article reviews current coverage and reimbursement issues related to Feno testing and provides an overview of pertinent recent studies.


Asunto(s)
Asma/diagnóstico , Pruebas Respiratorias/métodos , Óxido Nítrico/análisis , Administración por Inhalación , Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Asma/inmunología , Biomarcadores , Humanos , Inflamación , Cobertura del Seguro , Óxido Nítrico/inmunología , Pruebas en el Punto de Atención/economía , Mecanismo de Reembolso , Células Th2/inmunología
12.
J Crit Care ; 30(1): 178-80, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25457113

RESUMEN

INTRODUCTION: Obstructive sleep apnea (OSA) is a common disorder affecting between 5% and 24% of men and women. The prevalence of OSA in the intensive care unit (ICU) population is unknown. This study was undertaken to determine the prevalence of OSA in patients admitted to the ICU and to determine if OSA is an independent predictor of mortality. METHODS: This is a retrospective study using an Acute Physiology and Chronic Health Evaluation III database cross-referenced to a comprehensive clinical database to identify patients with and without OSA admitted to medical, surgical, and mixed ICUs at a large academic medical center. RESULTS: Between January 2003 and December 2005, 15077 patients were admitted to the ICUs; and of these, 1183 (7.8%) had a physician-documented diagnosis of OSA. Eight hundred thirty-five (71%) patients had polysomnographic testing at our institution with a documented apnea-hypopnea index more than 5 per hour. Patients with OSA were younger (59.1 ± 14.0 vs 62.3 ± 18.0), male (58.9% vs 53.7%), and had lower Acute Physiology and Chronic Health Evaluation III scores (45.3 ± 24.1 vs 54.9 ± 27.7). Predicted mortality (10.3% ± 16.4% vs 16.3 ± 21.7), median ICU length of stay (1.13 vs 1.50 days), ICU mortality (2.4% vs 6.2%), and hospital mortality (3.9% vs 11.4%) were all reduced in patients with OSA, P values < .001. When adjusted for the severity of illness, OSA was independently associated with decreased hospital mortality, (0.408; 95% confidence interval, 0.298-0.557). CONCLUSIONS: Obstructive sleep apnea is common in patients admitted to the ICU. Obstructive sleep apnea was associated with a reduction in both ICU and hospital mortality.


Asunto(s)
Cuidados Críticos/estadística & datos numéricos , Mortalidad Hospitalaria , Apnea Obstructiva del Sueño/mortalidad , APACHE , Adulto , Factores de Edad , Anciano , Apnea/diagnóstico , Intervalos de Confianza , Femenino , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores Sexuales
13.
F1000Res ; 3: 254, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25878773

RESUMEN

BACKGROUND: Malignant Pleural Effusion (MPE) is common with advanced malignancy. Palliative care with minimal adverse events is the cornerstone of management. Although talc pleurodesis plays an important role in treatment, the best modality of talc application remains controversial.   OBJECTIVE: To compare rates of successful pleurodesis, rates of respiratory and non-respiratory complications between thoracoscopic talc insufflation/poudrage (TTI) and talc slurry (TS).  DATA SOURCES AND STUDY SELECTION: MEDLINE (PubMed, OVID),  EBM Reviews (Cochrane database of Systematic Reviews, ACP Journal Club, DARE, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment and NHS Economic Evaluation Database), EMBASE and Scopus. Randomized controlled trials published between 01/01/1980 - 10/1/2014 and comparing the two strategies were selected.  RESULTS: Twenty-eight potential studies were identified of which 24 studies were further excluded, leaving four studies. No statistically significant difference in the probability of successful pleurodesis was observed between TS and TTI groups (RR 1.06; 95 % CI 0.99-1.14; Q statistic, 4.84). There was a higher risk of post procedural respiratory complications in the TTI group compared to the TS group (RR 1.91, 95% CI= 1.24-2.93, Q statistic 3.15). No statistically significant difference in the incidence of non-respiratory complications between the TTI group and the TS group was observed (RR 0.88, 95% CI= 0.72-1.07, Q statistic 4.61). CONCLUSIONS: There is no difference in success rates of pleurodesis based on patient centered outcomes between talc poudrage and talc slurry treatments.  Respiratory complications are more common with talc poudrage via thoracoscopy.

14.
Chest ; 143(4): 1060-1065, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23238692

RESUMEN

BACKGROUND: The long-term safety of patient-administered nebulized lidocaine for control of chronic cough has not been established. METHODS: We performed a retrospective study of adults who received a prescription and nurse education for nebulized lidocaine for chronic cough between 2002 and 2007. A survey questionnaire inquiring about adverse reactions and the effectiveness of nebulized lidocaine was developed and administered to these individuals after the nebulized lidocaine trial. We conducted two mailings and a postmailing phone follow-up to nonresponders. When adverse events were reported in the questionnaire response, a structured phone interview was conducted to obtain additional details. RESULTS: Of 165 eligible patients, 99 (60%) responded to the survey. Responders were a median age of 62 years (range, 29-87 years); 77 (79%) were women, and 80 (82%) were white. The median duration of cough was 5 years before treatment with nebulized lidocaine. Of the patients who used nebulized lidocaine (93% of survey responders), 43% reported an adverse event. However, none of these events required an emergency visit, hospitalization, or antibiotic therapy for aspiration pneumonia. The mean (SD) of the pretreatment cough severity score was 8.4 (1.6) and posttreatment was 5.9 (3.4) (P < .001). Of the patients reporting improvement in cough symptoms (49%), 80% reported improvement within the first 2 weeks. CONCLUSIONS: Adults tolerated self-administration of nebulized lidocaine for difficult-to-control chronic cough. No serious adverse effects occurred while providing symptomatic control in 49% of patients.


Asunto(s)
Anestésicos Locales/efectos adversos , Anestésicos Locales/uso terapéutico , Tos/tratamiento farmacológico , Lidocaína/efectos adversos , Lidocaína/uso terapéutico , Nebulizadores y Vaporizadores , Adulto , Anciano , Anciano de 80 o más Años , Anestésicos Locales/administración & dosificación , Enfermedad Crónica , Femenino , Humanos , Entrevistas como Asunto , Lidocaína/administración & dosificación , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento
15.
Mayo Clin Proc ; 82(11): 1350-5, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17976354

RESUMEN

OBJECTIVE: To evaluate our experience with patients who presented with chronic cough and how exhaled nitric oxide predicted response to inhaled corticosteroid (ICS) therapy. PATIENTS AND METHODS: This retrospective observational study of 114 patients evaluated for chronic cough with measured exhaled nitric oxide and methacholine challenge testing was conducted from December 1, 2004, through November 30, 2005. Clinical records were extracted. Patients with no documented follow-up were contacted by telephone and administered a questionnaire. RESULTS: In 64 patients, ICS therapy was started or the current ICS dose increased. Forty-one patients had elevated exhaled nitric oxide levels (defined as >or=35 ppb), 36 (88%) of whom had significant improvement in their chronic cough (likelihood ratio of a positive response, 4.9; 95% confidence interval, 2.2-10.9). Twenty-three patients with exhaled nitric oxide levels in the reference range were also prescribed ICS, and only 2 had cough improvement (likelihood ratio of a negative response, 0.07; 95% confidence interval, 0.02-0.25). Patients had documented follow-up that ranged from 4 weeks to 16 months. A cutoff of 38 ppb was found to best differentiate ICS responders and nonresponders. CONCLUSIONS: Measurement of exhaled nitric oxide accurately predicted response to ICS therapy for chronic cough. Patients with a positive exhaled nitric oxide test result had a strong likelihood of response to ICS, whereas a negative exhaled nitric oxide test result indicated an unlikely response to ICS. This finding may potentially have an impact on how patients with chronic cough are evaluated and treated.


Asunto(s)
Corticoesteroides/uso terapéutico , Tos/tratamiento farmacológico , Tos/metabolismo , Óxido Nítrico/metabolismo , Administración por Inhalación , Pruebas Respiratorias , Broncoconstrictores , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Funciones de Verosimilitud , Masculino , Cloruro de Metacolina , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad
16.
Am J Respir Cell Mol Biol ; 32(6): 490-7, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15746433

RESUMEN

Exuberant inflammatory responses are associated with respiratory failure during Pneumocystis pneumonia. Alveolar epithelial cells (AECs) promote Pneumocystis attachment and proliferation, but also contribute prominently to host cytokine-mediated inflammation during pneumonia. Recent investigations indicate that AECs produce macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-alpha (TNF-alpha) following challenge with Pneumocystis carinii. Nuclear factor-kappaB (NF-kappaB) is a ubiquitous transcription factor critical for regulation of proinflammatory cytokine expression. Herein, we assess rat AEC NF-kappaB responses to challenge with a P. carinii beta-glucan cell wall component (PCBG). Prominent nuclear translocation of p65 NF-kappaB was demonstrated following PCBG challenge. NF-kappaB activation was in part mediated through Protein Kinase C (PKC) signaling pathways. PCBG challenge of AECs was also shown to induce MIP-2 and TNF-alpha mRNA production, a response that was ameliorated by NF-kappaB inhibition. MIP-2 protein expression was also dramatically increased by PCBG challenge, in a manner that was significantly attenuated by both PKC and NF-kappaB inhibition. The data further demonstrate that AEC chemokine responses were not mediated by the recently described dectin-1 receptor, but instead involved participation of cell surface lactosylceramide. These data support a significant role for AECs in host responses during Pneumocystis pneumonia, and further indicate that beta-glucan induces inflammatory cytokine production through NF-kappaB-dependent mechanisms.


Asunto(s)
Quimiocinas/metabolismo , FN-kappa B/metabolismo , Pneumocystis carinii/metabolismo , Neumonía por Pneumocystis/inmunología , Mucosa Respiratoria/microbiología , beta-Glucanos/metabolismo , Animales , Antígenos CD/metabolismo , Quimiocina CXCL2 , Expresión Génica/inmunología , Técnicas In Vitro , Lactosilceramidos/metabolismo , Lectinas Tipo C , Proteínas de la Membrana/metabolismo , Monocinas/genética , Monocinas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neumonía por Pneumocystis/metabolismo , Proteína Quinasa C/metabolismo , Alveolos Pulmonares/citología , Alveolos Pulmonares/inmunología , Alveolos Pulmonares/microbiología , Ratas , Mucosa Respiratoria/citología , Mucosa Respiratoria/inmunología , Factor de Necrosis Tumoral alfa/genética
17.
Semin Respir Infect ; 18(1): 40-7, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12652453

RESUMEN

Pneumocystis carinii remains an important cause of pneumonia in immunosuppressed hosts. Severe Pneumocystis pneumonia is characterized by an intense neutrophilic inflammatory response resulting in gas exchange abnormalities, diffuse alveolar damage, and respiratory failure. The inflammatory response directed against P. carinii involves a complex series of interactions between alveolar macrophages, CD4+ T lymphocytes, polymorphonuclear cells, and their various products. CD4+ T lymphocytes are crucial to host defense against P. carinii. Alveolar macrophages also provide essential functions that significantly enhance clearance of P. carinii infection. In addition, host proteins play an important role in augmenting the host inflammatory responses to this organism. Although essential for effective clearance of infection, excessive inflammatory responses also predispose the host to the development of lung injury and respiratory compromise. Understanding the complex processes involved in the host inflammatory response and its potential for causing lung injury may enable development of novel therapeutic approaches for this and other important fungal lung infections.


Asunto(s)
Neumonía por Pneumocystis/etiología , Neumonía por Pneumocystis/inmunología , Neumonía/complicaciones , Neumonía/inmunología , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/inmunología , Humanos , Neumonía/terapia , Neumonía por Pneumocystis/terapia , Insuficiencia Respiratoria/terapia
18.
J Biol Chem ; 278(3): 2043-50, 2003 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-12419803

RESUMEN

Infiltration of the lungs with neutrophils promotes respiratory failure during severe Pneumocystis carinii (PC) pneumonia. Recent studies have shown that alveolar epithelial cells (AECs), in addition to promoting PC attachment, also participate in lung inflammation by the release of cytokines and chemokines. Herein, we demonstrate that a PC beta-glucan rich cell wall isolate (PCBG) stimulates the release of macrophage inflammatory protein-2 (MIP-2) from isolated AECs through a lactosylceramide-dependent mechanism. The results demonstrate that MIP-2 mRNA and protein production is significantly increased at both early and late time points after PCBG challenge. Although CD11b/CD18 (Mac-1, CR3) is the most widely studied beta-glucan receptor, we demonstrate that CD11b/CD18 is not present on AECs. This study instead demonstrates that preincubation of AECs with an antibody directed against the membrane glycosphingolipid lactosylceramide (CDw17) results in a significant decrease in MIP-2 secretion. Preincubation of the anti-CDw17 antibody with solubilized lactosylceramide reverses this effect. Furthermore, incubation of AECs with inhibitors of glycosphingolipid biosynthesis, including N-butyldeoxyno jirimycin and d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl, also results in a significant decrease in AEC MIP-2 production following challenge with PCBG. These data demonstrate that PC beta-glucan induces significant production of MIP-2 from AECs and that CDw17 participates in the glucan-induced inflammatory signaling in lung epithelial cells during PC infection.


Asunto(s)
Antígenos CD/metabolismo , Pared Celular/metabolismo , Glucanos/metabolismo , Lactosilceramidos/metabolismo , Monocinas/metabolismo , Pneumocystis/metabolismo , Alveolos Pulmonares/metabolismo , Animales , Quimiocina CXCL2 , Quimiocinas CXC , Células Epiteliales/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Monocinas/genética , Alveolos Pulmonares/citología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley
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