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1.
Gerontology ; 68(7): 829-839, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34844245

RESUMEN

INTRODUCTION: An early detection of impaired functional performance is critical to enhance symptom management for patients with chronic obstructive pulmonary disease (COPD). However, conventional functional measures based on walking assessments are often impractical for small clinics where the available space to administrate gait-based test is limited. This study examined the feasibility and effectiveness of an upper-extremity frailty meter (FM) in identifying digital measures of functional performance and assessing frailty in COPD patients. METHODS: Forty-eight patients with COPD (age = 68.8 ± 8.5 years, body mass index [BMI] = 28.7 ± 5.8 kg/m2) and 49 controls (age = 70.0 ± 3.0 years, BMI = 28.7 ± 6.1 kg/m2) were recruited. All participants performed a 20-s repetitive elbow flexion-extension test using a wrist-worn FM sensor. Functional performance was quantified by FM metrics, including speed (slowness), range of motion (rigidity), power (weakness), flexion and extension time (slowness), as well as speed and power reduction (exhaustion). Conventional functional measures, including timed-up-and-go test, gait and balance tests, and 5 repetition sit-to-stand test, were also performed. RESULTS: Compared to controls, COPD patients exhibited deteriorated performances in all conventional functional assessments (d = 0.64-1.26, p < 0.010) and all FM metrics (d = 0.45-1.54, p < 0.050). FM metrics had significant agreements with conventional assessment tools (|r| = 0.35-0.55, p ≤ 0.001). FM metrics efficiently identified COPD patients with pre-frailty and frailty (d = 0.82-2.12, p < 0.050). CONCLUSION: This study proposes the feasibility of using a 20-s repetitive elbow flexion-extension test and wrist-worn sensor-derived frailty metrics as an alternative and practical solution to evaluate functional performance in COPD patients. Its simplicity and low risk for test administration may also facilitate its application for remote patient monitoring. Furthermore, in settings where the administration of walking test is impractical, for example, when ventilator support is needed or space is limited, FM may be used as an alternative solution. Future studies are encouraged to use the FM to quantitatively monitor the progressive decline in functional performance and quantify outcomes of rehabilitation interventions.


Asunto(s)
Fragilidad , Enfermedad Pulmonar Obstructiva Crónica , Veteranos , Anciano , Anciano Frágil , Fragilidad/diagnóstico , Evaluación Geriátrica , Humanos , Rendimiento Físico Funcional , Equilibrio Postural , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Estudios de Tiempo y Movimiento
2.
Sleep Breath ; 26(4): 1817-1820, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35034251

RESUMEN

BACKGROUND: Obstructive sleep apnea (OSA) is a frequent comorbid condition in patients with type 2 diabetic (T2DM). Concomitant OSA is associated with a detrimental impact on metabolic control. Both OSA and T2DM independently lead to increased cardiovascular disease and mortality. The impact of OSA on the acceleration of organ dysfunction leading to increased healthcare utilization is unknown. METHODS: This is a retrospective case-control cohort study, a secondary analysis utilizing a nationwide dataset. Patients who underwent elective surgical procedures from 2009 to 2014 were identified. Among these patients, we compared patients with obstructive sleep apnea and those without obstructive sleep apnea. Exact 1:1 matching was performed based on similar characteristics such as age, sex, geographic location, surgical facility environment, performing surgeon, and severity of illness during hospitalization. The subgroup of patients with T2DM with or without OSA was analyzed for post-discharge hospital admissions, intensive care unit (ICU) admissions, emergency room (ER) visits, and outpatient visits. RESULTS: Among 47,719 matched patients of the initial study, this subgroup included 4,567 patients with diabetes and OSA and 3,842 patients with diabetes but no OSA. In the presence of comorbid OSA, patients with T2DM had higher odds of increased healthcare utilization among all the outcomes: inpatient visits increased with an odds ratio of 2.50 (confidence interval (CI) 2.28-2.74) and ICU admissions 1.96 (CI 1.73-2.25) ER 1.93 **(CI 1.75-2.12) and outpatient visits 2.18 (CI 2.00-2.38). Future healthcare utilization per 100 patient-years was also increased significantly among all outcomes (p < 0.0001). CONCLUSIONS: In patients with diabetes undergoing elective surgery, the presence of OSA was associated with higher future healthcare utilization.


Asunto(s)
Diabetes Mellitus Tipo 2 , Apnea Obstructiva del Sueño , Humanos , Estudios Retrospectivos , Estudios de Casos y Controles , Cuidados Posteriores , Factores de Riesgo , Alta del Paciente , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/complicaciones , Aceptación de la Atención de Salud , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones
3.
Clin Genet ; 94(6): 502-511, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30152014

RESUMEN

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1 ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV1 which do not follow the expected trends of the normal population. We also show that "normalization" of FVC and FEV1 using general population data to generate percent predicted values underestimates the pulmonary involvement in OI. Within each subtype of OI, we used linear mixed models to find potential correlations between FEV1 and FVC with the clinical variables including mobility, bisphosphonate use, and scoliosis. Our results are an important step in understanding the extent of pulmonary involvement in individuals with OI and for developing pulmonary endpoints for use in the routine patient care as well as in the investigation of new therapies.


Asunto(s)
Pulmón/fisiopatología , Osteogénesis Imperfecta/fisiopatología , Adolescente , Adulto , Anciano , Niño , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Osteogénesis Imperfecta/diagnóstico , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Espirometría , Capacidad Vital , Adulto Joven
4.
Am J Obstet Gynecol ; 212(2): 218.e1-9, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25173187

RESUMEN

OBJECTIVE: The purpose of this study was to test the hypothesis that a standardized multidisciplinary treatment approach in patients with morbidly adherent placenta, which includes accreta, increta, and percreta, is associated with less maternal morbidity than when such an approach is not used (nonmultidisciplinary approach). STUDY DESIGN: A retrospective cohort study was conducted with patients from 3 tertiary care hospitals from July 2000 to September 2013. Patients with histologically confirmed placenta accreta, increta, and percreta were included in this study. A formal program that used a standardized multidisciplinary management approach was introduced in 2011. Before 2011, patients were treated on a case-by-case basis by individual physicians without a specific protocol (nonmultidisciplinary group). Estimated blood loss, transfusion of packed red blood cells, intraoperative complications (eg, vascular, bladder, ureteral, and bowel injury), neonatal outcome, and maternal postoperative length of hospital stay were compared between the 2 groups. RESULTS: Of 90 patients with placenta accreta, 57 women (63%) were in the multidisciplinary group, and 33 women (37%) were in the nonmultidisciplinary group. The multidisciplinary group had more cases with percreta (P = .008) but experienced less estimated blood loss (P = .025), with a trend to fewer blood transfusions (P = .06), and were less likely to be delivered emergently (P = .001) compared with the nonmultidisciplinary group. Despite an approach of indicated preterm delivery at 34-35 weeks of gestation, neonatal outcomes were similar between the 2 groups. CONCLUSION: The institution of a standardized approach for patients with morbidly adherent placentation by a specific multidisciplinary team was associated with improved maternal outcomes, particularly in cases with more aggressive placental invasion (increta or percreta), compared with a historic nonmultidisciplinary approach. Our standardized approach was associated with fewer emergency deliveries.


Asunto(s)
Cesárea/métodos , Protocolos Clínicos , Histerectomía/métodos , Placenta Accreta/cirugía , Retención de la Placenta/cirugía , Adulto , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Estudios de Cohortes , Transfusión de Eritrocitos/estadística & datos numéricos , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Adulto Joven
5.
Nat Med ; 13(5): 567-9, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17450149

RESUMEN

Chronic obstructive pulmonary disease and emphysema are common destructive inflammatory diseases that are leading causes of death worldwide. Here we show that emphysema is an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 (T(H)1) responses, which correlate with emphysema severity. These findings link emphysema to adaptive immunity against a specific lung antigen and suggest the potential for autoimmune pathology of other elastin-rich tissues such as the arteries and skin of smokers.


Asunto(s)
Autoinmunidad , Elastina/inmunología , Enfisema/etiología , Enfisema/inmunología , Fumar/efectos adversos , Linfocitos B/inmunología , Humanos , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Fumar/inmunología , Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología
6.
Cureus ; 16(5): e59978, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38854342

RESUMEN

Rheumatoid arthritis (RA) is a complex autoimmune disease causing chronic joint inflammation and, in more serious cases, organ involvement. RA typically affects people between the ages of 35 and 60; however, it can also afflict children younger than the age of 16 years and can also demonstrate a pattern of remission later in the disease course. Non-steroidal anti-inflammatory drugs, glucocorticoids, exercise, and patient education are all used in the management of RA, which is divided into symptomatic management and disease-modifying management (disease-modifying antirheumatic drugs) to reduce pain and inflammation, thereby preserving joint function. Janus kinase inhibitors (JAKis) have led to a substantial improvement in the management of RA. By specifically targeting the JAK-signal transducer and activator of transcription pathway, which is essential for immunological modulation, these inhibitors also demonstrate promise in treating various autoimmune illnesses, including inflammatory bowel diseases, giant cell arteritis, ankylosing spondylitis, and psoriatic arthritis. Tofacitinib, baricitinib, upadacitinib, peficitinib, delgocitinib, and filgotinib are examples of FDA-approved JAKis that have distinct properties and indications for treating a range of autoimmune illnesses. JAKis demonstrate a promising treatment approach for managing RA and other autoimmune diseases while enhancing patient outcomes and quality of life. However, due to major safety concerns and the need for long-term success, meticulous patient monitoring is essential.

7.
Am J Physiol Endocrinol Metab ; 304(12): E1359-64, 2013 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-23612995

RESUMEN

In enterocytes, glutamine serves as the major source of energy; another metabolic fate of glutamine is conversion to citrulline. Because sepsis can affect gut function and integrity, alterations in glutamine metabolism may exist and lead to decreased citrulline production. This study aimed to investigate how sepsis affects glutamine metabolism, including its conversion to citrulline, by measuring glutamine and citrulline flux, fractional splanchnic extraction of glutamine and leucine, and the contribution of glutamine nitrogen to citrulline in septic patients and healthy controls. Eight patients with severe sepsis and 10 healthy controls were given primed, constant intravenous infusion of [(2)H2]citrulline and sequential administration of intravenous and enteral [α-(15)N]glutamine and [(13)C]leucine in the postabsorptive state. The results showed that, compared with healthy controls, septic patients had a significantly lower whole body citrulline flux and plasma concentration, higher endogenous leucine flux, and higher glutamine clearance. Fractional splanchnic extraction of leucine was higher in septic patients than in controls, but fractional extraction of glutamine was not different. The majority of the (15)N label transferred from glutamine to citrulline was found at the α-position. These results demonstrate that lower glutamine plasma concentrations in sepsis were a result of increased glutamine clearance. Despite adequate splanchnic uptake of glutamine, there is decreased production of citrulline, suggesting a defect in the metabolic conversion of glutamine to citrulline, decreased uptake of glutamine by the enterocyte but increased uptake by the liver, and/or shunting of glutamine to other metabolic pathways.


Asunto(s)
Citrulina/biosíntesis , Metabolismo Energético/fisiología , Enterocitos/metabolismo , Glutamina/metabolismo , Sepsis/metabolismo , Adulto , Citrulina/sangre , Femenino , Glutamina/sangre , Humanos , Mucosa Intestinal/metabolismo , Leucina/sangre , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Isótopos de Nitrógeno , Circulación Esplácnica/fisiología
8.
Clin Immunol ; 146(2): 77-83, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23280490

RESUMEN

The etiology of status asthmaticus (SA), a complication of severe asthma, is unknown. Fungal exposure, as measured by fungal atopy, is a major risk factor for developing asthma, but the relationship of fungi in SA per se has not previously been reported. In this five patient retrospective case series study, lower respiratory tract cultures were performed on bronchoalveolar lavage or tracheal aspirate fluid, comparing standard clinical laboratory cultures with a specialized technique in which respiratory mucus was removed prior to culture. We show that mucolytic treatment allows an increased detection of fungal growth, especially yeast, from the lower airways of all SA patients. We also demonstrate that inhalation of the yeast Candida albicans readily induces asthma-like disease in mice. Our observations suggest that SA may represent a fungal infectious process, and support additional prospective studies utilizing anti-fungal therapy to supplement conventional therapy, broad-spectrum antibiotics and high-dose glucocorticoids, which can promote fungal overgrowth.


Asunto(s)
Bronquitis/microbiología , Micosis Fungoide/inmunología , Estado Asmático/microbiología , Traqueítis/microbiología , Adulto , Anciano , Animales , Bronquitis/complicaciones , Bronquitis/inmunología , Candidiasis/complicaciones , Candidiasis/inmunología , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Micosis Fungoide/complicaciones , Estudios Retrospectivos , Estado Asmático/complicaciones , Estado Asmático/inmunología , Traqueítis/complicaciones , Traqueítis/inmunología
9.
Crit Care Med ; 41(3): 706-16, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23425819

RESUMEN

OBJECTIVES: Lactoferrin is a glycoprotein with anti-infective and anti-inflammatory properties found in secretions and immune cells. Talactoferrin alfa, a recombinant form of human lactoferrin, has similar properties and plays an important role in maintaining the gastrointestinal mucosal barrier integrity. In experimental animal models, administration of talactoferrin reduces translocation of bacteria from the gut into the systemic circulation and mortality from sepsis. Our objective was to determine if talactoferrin could reduce 28-day all-cause mortality in patients with severe sepsis and to assess its safety. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter phase 2 trial. SETTING: Adult ICUs and emergency departments in the United States. PATIENTS: One hundred ninety-four adults within 24 hrs of the onset of severe sepsis. INTERVENTIONS: Enterally administered talactoferrin 1.5g or placebo every 8 hrs for up to 28 days or until discharge from the ICU. MEASUREMENTS AND MAIN RESULTS: Modified intention-to-treat analysis was used to assess the primary (28-day all-cause mortality) and secondary endpoints. The all-cause mortality at 28 days was 26.9% in the placebo group and 14.4% in the talactoferrin group (two-sided p = 0.052), representing a 12.5% absolute and a 46.5% relative reduction in mortality, meeting the protocol-specified primary endpoint. Reduction in all cause mortality was sustained at 6 months (p = 0.039). These reductions in mortality were observed across a wide spectrum of subgroups. The drug was well tolerated with a safety profile similar to that of placebo. CONCLUSIONS: Enteral administration of talactoferrin reduced 28-day all-cause mortality in patients with severe sepsis. This reduction in mortality was sustained at 6 months. Talactoferrin was very well tolerated.


Asunto(s)
Lactoferrina/uso terapéutico , Sepsis/tratamiento farmacológico , APACHE , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Mortalidad Hospitalaria/tendencias , Humanos , Infusiones Parenterales , Unidades de Cuidados Intensivos , Lactoferrina/efectos adversos , Masculino , Persona de Mediana Edad , Placebos , Estudios Prospectivos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento
12.
Chest ; 164(2): 441-449, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36801465

RESUMEN

BACKGROUND: Two antifibrotic medications, pirfenidone and nintedanib, are approved for the treatment of idiopathic pulmonary fibrosis (IPF). Little is known about their real-world adoption. RESEARCH QUESTION: What are the real-world antifibrotic utilization rates and factors associated with uptake among a national cohort of veterans with IPF? STUDY DESIGN AND METHODS: This study identified veterans with IPF who received care either provided by the Veterans Affairs (VA) Healthcare System or non-VA care paid for by the VA. Patients who had filled at least one antifibrotic prescription through the VA pharmacy or Medicare Part D between October 15, 2014, and December 31, 2019, were identified. Hierarchical logistic regression models were used to examine factors associated with antifibrotic uptake, accounting for comorbidities, facility clustering, and follow-up time. Fine-Gray models were used to evaluate antifibrotic use by demographic factors, accounting for the competing risk of death. RESULTS: Among 14,792 veterans with IPF, 17% received antifibrotics. There were significant disparities in adoption, with lower uptake associated with female sex (adjusted OR, 0.41; 95% CI, 0.27-0.63; P < .001), Black race (adjusted OR, 0.60; 95% CI, 0.49-0.73; P < .001), and rural residence (adjusted OR, 0.88; 95% CI, 0.80-0.97; P = .012). Veterans who received their index diagnosis of IPF outside the VA were less likely to receive antifibrotic therapy (adjusted OR, 0.15; 95% CI, 0.10-0.22; P < .001). INTERPRETATION: This study is the first to evaluate the real-world adoption of antifibrotic medications among veterans with IPF. Overall uptake was low, and there were significant disparities in use. Interventions to address these issues deserve further investigation.


Asunto(s)
Fibrosis Pulmonar Idiopática , Veteranos , Humanos , Femenino , Anciano , Estados Unidos/epidemiología , Medicare , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/diagnóstico , Piridonas/uso terapéutico
13.
Sleep Med ; 89: 60-64, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34906781

RESUMEN

BACKGROUND: Hospital readmissions and outpatient visits contribute to the significant burden on healthcare systems. Obstructive sleep apnea (OSA) is a chronic medical condition that is associated with cardiovascular comorbidities and other chronic conditions. Inpatient and outpatient healthcare utilization rates in patients with OSA following hospitalization are unclear. METHODS: This. retrospective case-control cohort study utilized a nationwide database to assess if OSA is associated with higher healthcare utilization post-hospitalization. We compared healthcare utilization among patients with OSA versus without OSA between 2009 and 2014 after matching for demographic variables, geographic location, hospital environment, reason for admission, and severity of illness during hospitalization. We measured future healthcare utilization by the number of ICU admissions, hospital admissions, emergency room visits, and outpatient visits after being discharged from the index hospitalization. RESULTS: Two equal-sized cohorts comprised of 85,912 matched pairs were obtained. The OSA cohort demonstrated significantly higher rates of future ICU admissions, hospital admissions, emergency room visits, and outpatient visits. Matching for comorbid cardiovascular conditions continued to demonstrate higher healthcare utilization in the OSA group. Short-term outcomes during the index hospitalization were relatively similar between groups. CONCLUSIONS: This retrospective database study demonstrated that OSA may be an independent marker of higher future healthcare utilization. On the other hand, the length of stay during the index hospitalization was not elevated. Prospective studies are needed to confirm these findings and investigate the impact of directing additional resources to inpatients with OSA.


Asunto(s)
Readmisión del Paciente , Apnea Obstructiva del Sueño , Estudios de Casos y Controles , Humanos , Pacientes Ambulatorios , Estudios Retrospectivos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapia
14.
J Racial Ethn Health Disparities ; 9(2): 519-526, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33694124

RESUMEN

IMPORTANCE: Recent reports indicate differences in COVID-19-related care and outcomes between Black and White Americans. OBJECTIVE: We examine the COVID-19-related healthcare utilization and mortality by race and ethnicity of patients tested for SARS-CoV-2 in the Veterans Health Administration (VHA). DESIGN: A retrospective cohort study. SETTING: We used the VHA COVID-19 shared data resources between February 1 and June 30, 2020. PARTICIPANTS: Veterans tested for SARS-CoV-2 virus by VHA. EXPOSURE(S): Three racial-ethnicity groups of Black, Hispanic, and White (as reference) veterans. MAIN OUTCOME(S) AND MEASURE(S): Main outcomes are testing rate, positivity rate, hospitalization rate, ICU admission rate, and in-hospital mortality. Controlling for sex, age, and Elixhauser comorbidity index, we report adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) from logistic regression models. RESULTS: Of the 8,667,996 active veteran enrollees, 252,702 were tested by VHA from February to June, 2020, with 20,500 positive results and 4,790 hospitalizations. The testing rate was 4.4% among Black and 4.7% among Hispanic veterans compared to White veterans, 2.8%. The testing positivity rate was similarly elevated among Black (12.2%) and Hispanic (11.6%) veterans compared to White veterans (6.0%). The aORs of hospitalization in Black veterans (1.88; 95% CI 1.74, 2.03) and Hispanic veterans (1.41; 95% CI 1.25, 1.60) were higher compared to White veterans. No significant differences by race and ethnicity were observed in OR or aOR of ICU admission and in-hospital death among hospitalized patients. CONCLUSIONS AND RELEVANCE: On a national level, the VHA was more likely to test and hospitalize Black and Hispanic veterans compared to White veterans, but there were no significant differences in ICU admission or in-hospital mortality among those hospitalized. This pattern of differences may relate to social determinants of health, factors affecting access to non-VHA care, or preferences for VHA care affecting initial care seeking, but not in-hospital outcomes.


Asunto(s)
COVID-19 , Veteranos , COVID-19/terapia , Etnicidad , Mortalidad Hospitalaria , Humanos , Aceptación de la Atención de Salud , Estudios Retrospectivos , SARS-CoV-2 , Estados Unidos/epidemiología , Salud de los Veteranos
15.
Fed Pract ; 39(8): e0310, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36425807

RESUMEN

Background: During a surge of COVID-19 cases, the volume of acute care patients with hypoxemic respiratory failure placed a high burden of responsibility on internal medicine, pulmonary and critical care medicine, and clinical pharmacy services. Observations: We describe the COVID-19 Tele-Huddle Program, a novel approach to communication between key stakeholders in COVID-19 patient care through a daily video conferencing huddle. The program was implemented during a 4-week surge in COVID-19 cases at a large, academic medical center in Houston, Texas. Data collected during the COVID-19 Tele-Huddle Program included the type and number of interventions implemented, number of patients discussed, and COVID-19 therapies provided. In addition, hospital medicine team members completed a user-experience survey. Conclusions: A multidisciplinary consultation service using video conferencing can support the care of patients with high disease severity without overwhelming existing inpatient medical, intensive care, and pharmacy services.

16.
J Allergy Clin Immunol ; 125(6): 1369-1378.e2, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20430426

RESUMEN

BACKGROUND: Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide. Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease. OBJECTIVE: We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors. METHODS: Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103). We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions. We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice. RESULTS: HRVs are isolated from nasal and lung fluid from subjects with AE-COPD. Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a T(H)1 and T(H)2 cell cytokine phenotype during acute infection. HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong T(H)1 and T(H)2 immune responses from CD4 T cells. Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-gamma production from CD4 T cells. CONCLUSION: Our findings suggest that patients with severe COPD show T(H)1- and T(H)2-biased responses during AE-COPD. HRV-encoded proteinase 2A, like other microbial proteinases, could provide a T(H)1- and T(H)2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD. Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Cisteína Endopeptidasas/administración & dosificación , Infecciones por Picornaviridae/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Rhinovirus/inmunología , Proteínas Virales/administración & dosificación , Adulto , Anciano , Animales , Hiperreactividad Bronquial , Líquido del Lavado Bronquioalveolar , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Células Cultivadas , Cisteína Endopeptidasas/farmacología , Células Dendríticas/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Infecciones por Picornaviridae/complicaciones , Infecciones por Picornaviridae/virología , Neumonía , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/virología , Rhinovirus/enzimología , Rhinovirus/patogenicidad , Células TH1/inmunología , Células Th2/inmunología , Proteínas Virales/farmacología
17.
Sleep Med ; 81: 294-299, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33744518

RESUMEN

BACKGROUND: Obstructive sleep apnea is prevalent among those undergoing elective surgery and likely introduces a risk of adverse outcomes. To understand its impact, we aimed to compare healthcare utilization in postsurgical patients with obstructive sleep apnea compared to controls matched on the surgical care environment. METHODS: This is a retrospective case-control cohort study using a nationwide database. Among patients undergoing elective surgical procedures during 2009-2014, we compared patients with obstructive sleep apnea with those without obstructive sleep apnea. The two cohorts were matched based on age, sex, type of surgery, performing surgeon, the hospital where the procedure was performed, and various All-Patient-Refined Diagnosis-Related-Groups severity indices. The primary effect of interest was short-term healthcare utilization. We also compared long-term hospital admissions, intensive care unit admissions, emergency room visits and outpatient visits. RESULTS: 47,719 subjects and controls were matched on a 1:1 basis. As the subjects were matched, the two groups did not differ on age, percent female, and various Diagnosis-Related-Groups severity indices. The obstructive sleep apnea group had more comorbid conditions and a higher Elixhauser index. Short-term healthcare utilization measured by the length of stay and mortality related to index procedure did not increase in the sleep apnea group. In hierarchical logistical regression analysis, the presence of sleep apnea predicted higher long-term health care utilization. CONCLUSIONS: Our data suggests that the presence of sleep apnea was not associated with increased post elective surgical length of stay and mortality; however, the presence of obstructive sleep apnea was associated with long-term health care utilization.


Asunto(s)
Procedimientos Quirúrgicos Electivos , Apnea Obstructiva del Sueño , Estudios de Casos y Controles , Femenino , Humanos , Aceptación de la Atención de Salud , Estudios Retrospectivos , Apnea Obstructiva del Sueño/epidemiología
18.
Clin Sci (Lond) ; 117(1): 23-30, 2009 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-19105791

RESUMEN

Arginine has vasodilatory effects, via its conversion by NO synthase into NO, and immunomodulatory actions which play important roles in sepsis. Protein breakdown affects arginine availability and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore affect NO synthesis in patients with sepsis. The objective of the present study was to investigate whole-body in vivo arginine and citrulline metabolism and NO synthesis rates, and their relationship to protein breakdown in patients with sepsis or septic shock and in healthy volunteers. Endogenous leucine flux, an index of whole-body protein breakdown rate, was measured in 13 critically ill patients with sepsis or septic shock and seven healthy controls using an intravenous infusion of [1-13C]leucine. Arginine flux, citrulline flux and the rate of conversion of arginine into citrulline (an index of NO synthesis) were measured with intravenous infusions of [15N2]guanidino-arginine and [5,5-2H2]citrulline. Plasma concentrations of nitrite plus nitrate, arginine, citrulline and asymmetric dimethylarginine were measured. Compared with controls, patients had a higher leucine flux and higher NO metabolites, but arginine flux, plasma asymmetric dimethylarginine concentration and the rate of NO synthesis were not different. Citrulline flux and plasma arginine and citrulline were lower in patients than in controls. Arginine production was positively correlated with the protein breakdown rate. Whole-body arginine production and NO synthesis were similar in patients with sepsis and septic shock and healthy controls. Despite increased proteolysis in sepsis, there is a decreased arginine plasma concentration, suggesting inadequate de novo synthesis secondary to decreased citrulline production.


Asunto(s)
Arginina/metabolismo , Citrulina/metabolismo , Óxido Nítrico/biosíntesis , Choque Séptico/metabolismo , Arginina/análogos & derivados , Estudios de Casos y Controles , Femenino , Homeostasis , Humanos , Leucina/metabolismo , Masculino , Persona de Mediana Edad
19.
J Thorac Dis ; 11(Suppl 14): S1800-S1809, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31632757

RESUMEN

Chronic obstructive pulmonary disease (COPD) is a major chronic debilitating condition with significant impact on quality of life, symptoms, comorbidity, health care utilization and longevity. The main pathophysiological hallmark of COPD is expiratory flow limitation which impairs the ability of respiratory system to adequately and properly ventilate. To be able to prognosticate and manage patients with COPD, various societies have developed classifications of disease severity. Current classification schemes combine three elements that include lung function, patient reported symptoms (shortness of breath) and frequency of exacerbations. Global Initiative for Obstructive Lung Disease (GOLD), an international guideline for diagnosis and management of COPD, started using this approach since the 2011 revision. Management according to this scheme has been developed and is in use. Comprehensive COPD management is multifaceted. It includes pharmacologic management, patient education, smoking cessation, influenza and pneumococcal vaccinations, depression and anxiety management, pulmonary rehabilitation, and if indicated, home oxygen therapy. The following chapter will review management recommendations currently in use for stable COPD. We intend to make the chapter to the point and practical and avoid an exhaustive review of the literature.

20.
Fed Pract ; 36(9): 430-435, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31571812

RESUMEN

For patients with chronic obstructive pulmonary disease, a home-based, interactive telehealth program can improve accessibility to pulmonary rehabilitation and reduce travel costs.

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