RESUMEN
BACKGROUND: Due to the broad range of diagnostic and therapeutic aspects with an increased risk of mortality, lung manifestations of rheumatic diseases are an exciting and important field in the clinical routine of pulmonologists and rheumatologists. OBJECTIVE: Discussion of different presentations in the lung, diagnostics and management of lung manifestation associated with rheumatic diseases. MATERIAL AND METHODS: Analysis and presentation of current literature on the subject. RESULTS: The manuscript presents forms of lung involvement associated with rheumatic diseases, in particular the connective tissue disease-associated interstitial lung disease. Considering the negative impact on survival, rapid and adequate diagnosis is of great importance. In the case of a known underlying rheumatic disease, histological confirmation of interstitial changes is not always necessary. In addition to the patient's history, pulmonary function testing and diagnostic imaging with high-resolution CT-scan (HR-CT) are cornerstones of the diagnostic process. The final diagnosis and therapeutic approach should be determined by a multidisciplinary discussion process. The basis of the treatment is immunosuppressants, however the use antifibrotic drugs is currently under investigation in clinical trials. In the case of advanced lung disease, lung transplantation should be evaluated promptly. CONCLUSION: In the case of pulmonary involvement with rheumatic disease, the teamwork of pulmonologists, rheumatologists and radiologists is of particular importance.
Asunto(s)
Enfermedades del Tejido Conjuntivo , Enfermedades Pulmonares Intersticiales , Enfermedades Reumáticas , Humanos , Inmunosupresores/uso terapéutico , Neumología , ReumatólogosRESUMEN
Posaconazole is an extended-spectrum triazole antifungal used in the treatment and prophylaxis of Aspergillus infections. It is available as oral suspension (POS-Liq) and delayed-release tablets (POS-Tab). The aim of this longitudinal, retrospective study was to compare the clinical effectiveness, toxicity and pharmacokinetics of POS-Liq vs POS-Tab in lung transplant recipients (LTx-recipients), who were treated with both formulations subsequently. Twenty-four consecutive LTx-recipients with 191 documented posaconazole trough levels (PTLs) for POS-Liq or POS-Tab were included. The administered daily doses were 300 mg for POS-Tab and 600 mg (prophylaxis) or 800 mg (therapy) for POS-Liq. Target PTLs were ≥700 ng/mL (prophylaxis) and ≥1250 ng/mL (therapy). The overall prophylactic and therapeutic response rates were 78% and 67%, respectively. No cases of hepatotoxicity or QT-prolongation were observed with either formulation. The achieved target PTLs were tripled under POS-Tab compared to POS-Liq with fewer risk factors for sub-therapeutic PTLs. Concomitant administration of POS-Tab significantly reduced the tacrolimus concentration-to-dose ratio (P = .001). We suggest the use of POS-Tab is appropriate for prophylaxis and therapy of Aspergillus infections in LTx-recipients, since POS-Tab displayed more reliable PTLs with no added adverse events. However, we recommend regular drug monitoring for POS-Liq and for therapy with POS-Tab and that immunosuppressant levels are monitored closely when the posaconazole formulation is switched.
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Antifúngicos/administración & dosificación , Antifúngicos/farmacocinética , Trasplante de Pulmón , Receptores de Trasplantes , Triazoles/administración & dosificación , Triazoles/farmacocinética , Administración Oral , Adulto , Anciano , Antifúngicos/uso terapéutico , Aspergilosis/sangre , Aspergilosis/tratamiento farmacológico , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/uso terapéutico , Monitoreo de Drogas/métodos , Femenino , Humanos , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Suspensiones , Comprimidos , Triazoles/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Pulmonary involvement in patients with underlying autoimmune diseases poses a major diagnostic and therapeutic challenge to the treating physician. Due to the associated increased mortality risk, early diagnosis is crucial. OBJECTIVE: The incidence and mortality rate of connective tissue disease-related interstitial lung diseases (CTD-ILD) and pulmonary hypertension (PH) were evaluated in patients with rheumatic disease including clinical aspects, diagnostic procedure, prognosis and treatment recommendations. MATERIAL AND METHODS: An analysis of remarkable publications was carried out and guidelines are presented. RESULTS: The CTD-ILD and PH are frequent comorbidities with significantly increased mortality risk, especially in patients with systemic sclerosis (SSc). In primary fibrotic and non-inflammatory CTD-ILD, as occurs especially in patients with rheumatoid arthritis, immunosuppressive therapy is only partially effective. Currently, in some eligible patients only lung transplantation remains as a definitive therapy. CONCLUSION: The diagnostics and treatment of CTD-ILD and PH in patients with an underlying autoimmune disease requires an interdisciplinary approach. The effectiveness of antifibrotic treatment needs to be evaluated in the future.
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Enfermedades del Tejido Conjuntivo , Hipertensión Pulmonar , Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , ReumatólogosRESUMEN
Chronic lung allograft dysfunction (CLAD) is a limiting factor for long-term survival in lung transplant recipients. Donor-specific human leukocyte antigen (HLA)-antibodies (DSA) have been suggested as potential risk factors for CLAD. However, their impact on clinical outcome following lung transplantation remains controversial. We performed a single-center study of 120 lung transplant recipients transplanted between 2006 and 2011. Patient sera were investigated before and after transplantation. The sera were screened by means of Luminex(®) technology (Luminex Inc., Austin, TX, USA) for IgG-HLA-class I and class II antibodies (ab). Using single antigen beads, DSA were identified and correlated retrospectively with clinical parameters. After transplantation 39 out of 120 patients (32.5%) were positive for HLA-ab. The incidence of de novo DSA formation was 27 of 120 patients (22.5%). Eleven of 27 (41%) of de novo DSA-positive patients developed BOS compared to 13 of 93 (14%) DSA-negative patients (p = 0.002). Furthermore, the generation of de novo DSA was independently associated with the development of BOS in multivariable analysis [hazard ration (HR) 2.5, 95% confidence interval (CI) 1.0-6.08; p = 0.046). Our results indicate that de novo DSA are associated with the development of BOS after lung transplantation. Monitoring of HLA-ab after transplantation is useful for identifying high-risk patients and offers an opportunity for early therapeutic intervention.
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Anticuerpos/inmunología , Bronquiolitis Obliterante/inmunología , Antígenos HLA/inmunología , Adulto , Femenino , Humanos , Trasplante de Pulmón , Masculino , Persona de Mediana Edad , Donantes de TejidosRESUMEN
Spirometry is a highly standardized method which allows to measure the forced vital capacity (FVC) with high precision and reproducibility. In patients with IPF FVC is directly linked to the disease process which is characterized by scaring of alveoli and shrinkage of the lungs. Consequently, there is ample evidence form clinical studies that the decline of FVC over time is consistently associated with mortality in IPF. As for the first time effective drugs for the treatment of IPF are available it becomes obvious that in studies which could demonstrate that the drug reduces FVC decline, a numerical effect on mortality was also observed, while in one study where a significant effect on FVC decline was missed, there was also no change in mortality. Based on these studies FVC decline is a validated surrogate of mortality in IPF. It is concluded that FVC decline is not only accepted as an endpoint of clinical treatment trials in IPF but is also valid as a patient related outcome parameter which should be considered for the assessment of the efficacy of an IPF drug.
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Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/mortalidad , Guías de Práctica Clínica como Asunto , Espirometría/estadística & datos numéricos , Espirometría/normas , Capacidad Vital , Medicina Basada en la Evidencia , Alemania , Humanos , Incidencia , Pronóstico , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Sensibilidad y Especificidad , Espirometría/métodos , Tasa de SupervivenciaRESUMEN
Idiopathic pulmonary fibrosis is a fatal lung disease with a variable and unpredictable natural history and limited treatment options. Since publication of the ATS-ERS statement on IPF in the year 2000 diagnostic standards have improved and a considerable number of randomized controlled treatment trials have been published necessitating a revision. In the years 2006 - 2010 an international panel of IPF experts produced an evidence-based guideline on diagnosis and treatment of IPF, which was published in 2011. In order to implement this evidence-based guideline into the German Health System a group of German IPF experts translated and commented the international guideline, also including new publications in the field. A consensus conference was held in Bochum on December 3rd 2011 under the protectorate of the "Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGP)" and supervised by the "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF). Most recommendations of the international guideline were found to be appropriate for the german situation. Based on recent clinical studies "weak negative" treatment recommendations for pirfenidone and anticoagulation were changed into "weak positive" for pirfenidone and "strong negative" for anticoagulation. Based on negative results from the PANTHER-trial the recommendation for the combination therapy of prednisone plus azathiorpine plus N-acetlycsteine was also changed into strong negative für patients with definite IPF. This document summarizes essential parts of the international IPF guideline and the comments and recommendations of the German IPF consensus conference.
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Antiinflamatorios/uso terapéutico , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/terapia , Guías de Práctica Clínica como Asunto , Neumología/normas , Tomografía Computarizada por Rayos X/métodos , Alemania , Humanos , Fibrosis Pulmonar Idiopática/sangre , InternacionalidadRESUMEN
The aim of this study was to assess fractional exhaled nitric oxide (FeNO) for the early diagnosis of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX). 611 FeNO measurements in 166 consecutive patients were classified depending on BOS stage at the time of assessment and course during minimum follow-up of 3 months: (1) stable non-BOS, (2) unstable non-BOS, (3) stable BOS and (4) unstable BOS. Unstable course was defined as new onset of BOS≥1 or progression of BOS. FeNO before unstable course was significantly increased in comparison to their stable counterparts (non-BOS: 28.9 ± 1.2 ppb, n = 40 vs. 16.4 ± 0.8 ppb, n = 131 and BOS: 32.5 ± 1.3 ppb, n = 35 vs. 15.3 ± 0.8 ppb, n = 26; p = 0.01 each). Average time from FeNO reading to onset of deterioration was 117 ± 9 days in non-BOS and 136 ± 9 days in BOS patients. The positive and negative predictive value of FeNO >20 ppb for BOS was 69.0% and 96.9%, respectively. Serial measurements demonstrated significantly lower mean individual variation in stable recipients as compared to stable patients switching to unstable course (3.2 ± 0.3 ppb vs. 12.7 ± 1.4 ppb, p = 0.02). In particular, the excellent negative predictive value of persistently low FeNO readings for future BOS make FeNO assessments a useful tool for continuous risk stratification after LTX.
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Bronquiolitis Obliterante/diagnóstico , Trasplante de Pulmón , Óxido Nítrico , Espiración , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , RiesgoRESUMEN
Lung transplantation (LTX) is an established therapeutic option for end-stage lung diseases. The main reasons for limited long-term survival rates are infections and bronchiolitis obliterans syndrome (BOS). An optimal immunosuppressive regimen is of critical importance for the prevention of both complications. Induction therapy is used in approximately 60 % of recipients. However, there are no controlled trials demonstrating a significant long-term survival benefit. The vast majority of patients receive a triple maintenance immunosuppressive therapy consisting of a calcineurin-inhibitor, a cell cycle inhibitor and corticosteroids. So far, no specific immunosuppressive drug combination has proven superiority regarding long-term survival rates. The potential benefits of the proliferation signal inhibitors sirolimus and everolimus remain to be elucidated. Therapeutic options for BOS encompass a switch in maintenance therapy, renewed induction therapy, aerolised cyclosporine, azithromycine, extracorporeal photopheresis and total lymphoid irradiation. Infection prophylaxis after LTX plays a pivotal role to guard against acute complications and for the prevention of BOS. In particular, prophylaxis for pneumocystis and cytomegalovirus disease is very effective. Moreover, colonisation with Pseudomonas aeruginosa and Aspergillus spp. was identified as risk factor for BOS. Consequently, in most transplant centres prophylactic and pre-emptive therapeutic approaches are applied in varying degrees.
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Antiinfecciosos/uso terapéutico , Inmunosupresores/uso terapéutico , Infecciones/tratamiento farmacológico , Infecciones/mortalidad , Complicaciones Posoperatorias/mortalidad , Comorbilidad , Humanos , Trasplante de Pulmón , Complicaciones Posoperatorias/prevención & control , Prevalencia , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Pulmonary hypertension (PH) leads to an increased right ventricular workload, cardiac failure and death. In idiopathic pulmonary arterial hypertension (PAH) the vasodilating vasoactive intestinal peptide (aviptadil) is deficient. The aim of the present study was to test the acute effects on haemodynamics and blood gases, and the safety, of a single dose of inhaled aviptadil in chronic PH. A total of 20 patients with PH (PAH in nine, PH in lung disease in eight and chronic thromboembolic PH in three) inhaled a single 100-microg dose of aviptadil during right-heart catheterisation. Haemodynamics and blood gases were measured. Aviptadil aerosol caused a small and temporary but significant selective pulmonary vasodilation, an improved stroke volume and mixed venous oxygen saturation. Overall, six patients experienced a pulmonary vascular resistance reduction of >20%. In patients with significant lung disease, aviptadil tended to improve oxygenation. The pulmonary vasodilating effect of aviptadil aerosol was modest and short-lived, did not cause any side-effects and led to a reduced workload of the right ventricle without affecting systemic blood pressure. Aviptadil inhalation tended to improve oxygenation in patients with significant lung disease. Further studies are needed to evaluate the full therapeutic potential of aviptadil aerosol, including higher doses and chronic treatment.
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Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Fentolamina/administración & dosificación , Péptido Intestinal Vasoactivo/administración & dosificación , Péptido Intestinal Vasoactivo/metabolismo , Adulto , Aerosoles , Anciano , Presión Sanguínea , Combinación de Medicamentos , Femenino , Insuficiencia Cardíaca/patología , Ventrículos Cardíacos/patología , Humanos , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Oxígeno/metabolismoRESUMEN
The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted and supportive treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to general and supportive therapy of PAH. This article summarizes the results and recommendations of this working group.
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Cardiología/normas , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Guías de Práctica Clínica como Asunto , Neumología/normas , Antihipertensivos/uso terapéutico , Determinación de la Presión Sanguínea/normas , Terapia Combinada/normas , Endarterectomía/normas , Alemania , HumanosRESUMEN
OBJECTIVES: The aim of the study was to determine whether automated quantification of pulmonary perfused blood volume (PBV) in dual-energy computed tomography pulmonary angiography (DE-CTPA) can be used to assess the severity of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Automated quantification of PBV was performed in 25 consecutive CTEPH patients undergoing DE-CTPA. PBV values were correlated with cardiac index and pulmonary vascular resistance quantified by right heart catheterization and walking distance in the 6-minute walk test using Pearson's correlation coefficient and multivariate linear regression analysis to control for age and gender. RESULTS: DE-CTPA derived PBV values inversely correlated with systolic (râ=â-0.64, pâ=â0.001) and mean (râ=â-0.57, pâ=â0.004) pulmonary arterial pressure. There was a trend for PBV values to inversely correlate with pulmonary vascular resistance (râ=â-0.20, pâ=â0.35). No significant correlation was found between PBV values and cardiac index or 6-minute walking distance. These correlations were confirmed to be independent of age and gender on multivariate linear regression analysis. CONCLUSION: DE-CTPA can be used for an automated quantification of pulmonary PBV in chronic thromboembolic pulmonary hypertension. PBV values correlate inversely with systolic and mean pulmonary arterial pressure and can thus be used to estimate the severity of pulmonary hypertension in these patients. Citation Format: â¢âMeinel FG, Graef A, Thierfelder KM etâal. Automated Quantification of Pulmonary Perfused Blood Volume by Dual-Energy CTPA in Chronic Thromboembolic Pulmonary Hypertension. Fortschr Röntgenstr 2014; 186: 151â-â156.
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Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/fisiopatología , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Angiografía , Volumen Sanguíneo , Determinación del Volumen Sanguíneo/métodos , Enfermedad Crónica , Femenino , Humanos , Hipertensión Pulmonar/etiología , Masculino , Persona de Mediana Edad , Embolia Pulmonar/complicaciones , Intensificación de Imagen Radiográfica/métodos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Interstitial lung diseases (ILD) are a heterogeneous group of parenchymal lung disorders eventually resulting in respiratory failure that can be classified into those with known and unknown causes. ILD are characterized by deposition of cellular and non-cellular components into the lung parenchyma but vary widely in etiology, clinico-radiologic presentation, histiopathologic features, and clinical course. A combination of clinical context, medical and environmental history, physiologic testing, lung imaging, serologic testing and histiologic findings obtained through bronchoscopic or surgical lung biopsy provides the basis for a precise diagnosis. In particular, high-resolution computed tomography of the chest and recognition of the prognostic importance of separating usual interstitial pneumonia (UIP) from other idiopathic interstitial pneumonias (IIP) have profoundly changed the management of patients with ILD. Besides, smoking cessation, avoidance of antigen or inorganic dust exposure, corticosteroids alone or in combination with azathioprine and cyclophosphamide are still the mainstay of therapy for most entities. However, the poor response rates to immunosuppressive therapy for UIP patients and frequent adverse effects highlight the need for new therapeutic strategies confirmed by randomized clinical trials to guide treatment. So far, lung transplantation remains the treatment of last resort for eligible patients with progressive lung fibrosis and timely referral for transplant evaluation is mandatory owing to limited donor availability.
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Corticoesteroides/uso terapéutico , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/terapia , Trasplante de Pulmón , Fumar/efectos adversos , Broncoscopía/métodos , Diagnóstico Diferencial , Quimioterapia Combinada , Polvo , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/patología , Pronóstico , Fibrosis Pulmonar/diagnóstico , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/terapia , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: The aim of this study was to determine the actual cost per intensive care unit (ICU) day in Germany based on routine data from an electronic patient data management system as well as analysis of cost-driving factors. A differentiation between days with and without mechanical ventilation was performed. METHODS: On the ICU of a German focused-care hospital (896 beds, 12 anesthesiology ICU beds), cost per treatment day was calculated with or without mechanical ventilation from the perspective of the hospital. Costs were derived retrospectively with respect to the period between January and October 2006 by cost-unit accounting based on routine data collected from the ICU patients. Patients with a length of stay of at least 2 days on the ICU were included. Demographic, clinical and economical data were analyzed for patient characterization. RESULTS: Data of 407 patients (217 male and 190 female) were included in the analysis, of which 159 patients (100 male, 59 female) were completely or partially mechanically ventilated. The mean simplified acute physiology (SAPS) II score at the onset of ICU stay was 28.2. Average cost per ICU day was 1,265 EUR and costs for ICU days with and without mechanical ventilation amounted to 1,426 EUR and 1,145 EUR, respectively. Personnel costs (50%) showed the largest cost share followed by drugs plus medicinal products (18%) and infrastructure (16%). CONCLUSIONS: For the first time, a cost analysis of intensive care in Germany was performed with routine data based on the matrix of the institute for reimbursement in hospitals (InEK). The results revealed a higher resource use on the ICU than previously expected. The large share of personnel costs on the ICU was evident but is comparable to other medical departments in the hospital. The need for mechanical ventilation increases the daily costs of resources by approximately 25%.
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Cuidados Críticos/economía , Unidades de Cuidados Intensivos/economía , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Costos y Análisis de Costo , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Modelos Económicos , Respiración Artificial/economía , Estudios Retrospectivos , Factores Sexuales , Factores SocioeconómicosRESUMEN
Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term survival after lung transplantation. Previous studies suggested respiratory viral tract infections are associated with the development of BOS. To identify the impact of virus detection in bronchoalveolar lavage (BAL) fluid, we analyzed BAL samples from 87 consecutive lung transplant recipients for human herpesvirus (HHV)-6, Epstein-Barr virus, Herpes simplex virus 1/2, Cytomegalovirus, respiratory syncytical virus and adenovirus by PCR. Acute rejection, BOS and death were recorded for a mean follow-up time of 3.27 +/- 0.47 years. Results of PCR analysis and other potential risk factors were entered into a Cox regression analysis of BOS predictors and death. Only acute rejection was a distinct risk factor for BOS of all stages, death and death from BOS. HHV-6 was detected in 20 patients. Univariate and multivariate analysis revealed that HHV-6 was associated with an increased risk to develop BOS > orb = stage 1 and death, separate from the risk attributable to acute rejection. Identification of HHV-6 DNA in BAL fluid is a potential risk factor for BOS. Our results warrant further studies to elucidate a possible causal link between HHV-6 and BOS.
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Bronquiolitis Obliterante/mortalidad , Líquido del Lavado Bronquioalveolar/virología , Herpesvirus Humano 6 , Trasplante de Pulmón/mortalidad , Infecciones por Roseolovirus/mortalidad , Infecciones por Adenoviridae/mortalidad , Adulto , Bronquiolitis Obliterante/virología , Estudios de Cohortes , Infecciones por Citomegalovirus/mortalidad , ADN Viral/análisis , Infecciones por Virus de Epstein-Barr/mortalidad , Femenino , Herpes Simple/mortalidad , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Herpesvirus Humano 6/genética , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/virología , Factores de RiesgoRESUMEN
The antioxidant glutathione (GSH) is increased in the epithelial lining fluid (ELF) of chronic smokers. The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), also known as gamma-glutamylcysteine synthetase, consisting of a heavy, catalytic (GCLC) and a light, modulatory (GCLM) subunit. To determine the contribution of bronchoalveolar lavage (BAL) cells to GSH levels in ELF, BAL was performed in eight smokers and eight never-smokers. Intra- and extracellular total glutathione (GSHt) levels and GCL subunit expression were assessed. GSHt was increased in ELF from smokers (1,090.1 +/- 163.0 microM versus 559.2 +/- 48.2 microM). GSHt content of BAL cells (nmol x mg protein(-1)) was decreased in smokers without differences reaching statistical significance (8.0 +/- 1.4 versus 12.4 +/- 2.6). GCLM expression was also reduced in smokers (0.6 +/- 0.1 versus 2.8 +/- 0.4) and correlated with intracellular GSHt content. There was no significant difference in GCLC expression and in differential cell counts in BAL fluid. The authors conclude that smoking does increase glutathione levels in the epithelial lining fluid but not intracellular levels in bronchoalveolar lavage cells. The data suggest that the intracellular glutathione concentration of bronchoalveolar lavage cells (predominately alveolar macrophages) is regulated by the modulatory glutamate-cysteine ligase subunit rather than the catalytic subunit.
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Líquido del Lavado Bronquioalveolar/química , Glutamato-Cisteína Ligasa/metabolismo , Macrófagos Alveolares/metabolismo , Fumar/metabolismo , Adulto , Líquido del Lavado Bronquioalveolar/citología , Dominio Catalítico , Recuento de Células , Femenino , Glutatión/metabolismo , Humanos , Masculino , Pruebas de Función Respiratoria , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no ParamétricasRESUMEN
Epithelial cells actively participate in inflammatory airway disease by liberating mediators such as arachidonate metabolites and cytokines. Inhibition of phosphodiesterases (PDEs) may be a useful anti-inflammatory approach. The PDE isoenzyme pattern and the effects of PDE inhibition on mediator generation were analyzed in primary cultures of human and porcine airway epithelial cells (AEC) and in the bronchial epithelial cell line BEAS-2B. PDE4 and PDE5 were detected in lysates of all cell types studied. In primary cultures of human AEC, the PDE4 variants PDE4A5, PDE4C1, PDE4D2, and PDE4D3 were identified by polymerase chain reaction analysis. Evidence of the recently described PDE7 was obtained by rolipram- insensitive cyclic adenosine monophosphate (cAMP) degradation, and its presence was verified by the demonstration of PDE7 messenger RNA. Primary cultures of human airway epithelium also expressed PDE1. Enhanced epithelial cAMP levels, induced by forskolin and PDE4 inhibition, increased formation of prostaglandin E2 (PGE2), but not of interleukin (IL)-8 or 15-hydroxyeicosatetraenoic acid (15-HETE) in airway epithelial cells. Increased cyclic guanosine monophosphate levels in these cells provoked by sodium nitroprusside and the PDE5 inhibitor zaprinast reduced the PGE2 synthesis, whereas 15-HETE and IL-8 formation were unchanged. The data suggest that PDE isoenzymes are important in airway inflammation and that PDE inhibitors exert anti-inflammatory effects by acting on AEC.
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Bronquios/enzimología , Glicoproteínas/metabolismo , Isoenzimas/metabolismo , Tráquea/enzimología , Animales , Secuencia de Bases , Bronquios/citología , Células Cultivadas , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Cartilla de ADN , Dinoprostona/metabolismo , Células Epiteliales/enzimología , Humanos , Ácidos Hidroxieicosatetraenoicos/metabolismo , Interleucina-8/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Porcinos , Tráquea/citologíaRESUMEN
Conventional manual compression and subsequent application of pressure bandages is associated with prolonged immobility and significant patient discomfort. Routine anticoagulation as well as the use of new interventional devices and platelet inhibiting strategies lead to a higher incidence of local bleeding complications after diagnostic cardiac catheterization or coronary angioplasty. Immediate sheath removal increases patient comfort. The Angio-Seal system uses a biodegradable anchor and collagen plug for sealing of arterial puncture sites. Several studies showed the safety and efficacy of this device. Technical deployment success ranges between 88 and 100%. Significant reduction in time to hemostasis allows for earlier patient ambulation and shorter in-hospital stay compared to manual compression with peripheral complications not being increased.