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BACKGROUND: MRproANP and COPAVP are prognostic markers for mortality in chronic obstructive pulmonary disease (COPD). Furthermore, these biomarkers predict mortality due to cardiovascular diseases, which are important prognostically determining comorbidities in patients with COPD. However, less is known about these biomarkers in recently diagnosed mild to moderate COPD. Therefore, we analyzed these biomarkers as potential predictors of mortality in recently diagnosed mild to moderate COPD. METHODS: The blood biomarkers considered were copeptin (COPAVP), midregional adrenomedullin (MRproADM), midregional proatrial naturetic peptide (MRproANP), and fibrinogen. Analyses were performed in patients with stable "recently diagnosed mild to moderate COPD" defined by GOLD grades 0-2 and diagnosis of COPD ≤ 5 years prior to inclusion into the COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network), using Cox regression analysis with stepwise adjustment for multiple COPD characteristics, comorbidities, troponin and NT-proBNP. RESULTS: 655 patients with recently diagnosed mild to moderate COPD were included. In the initial regression model, 43 of 655 patients died during the 6-year follow-up, in the final model 27 of 487. Regression analyses with adjustment for confounders identified COPAVP and MRproANP as statistically robust biomarkers (p < 0.05 each) of all-cause mortality, while MRproADM and fibrinogen were not. The fourth quartile of MRproANP (97 pmol/L) was associated with a hazard ratio of 4.5 (95%CI: 1.6; 12.8), and the fourth quartile of COPAVP (9.2 pmol/L) with 3.0 (1.1; 8.0). The results for MRproANP were confirmed in the total cohort of grade 0-4 (n = 1470 finally). CONCLUSION: In patients with recently diagnosed mild to moderate COPD, elevated values of COPVP and in particular MRproANP were robust, independent biomarkers for all-cause mortality risk after adjustment for multiple other factors. This suggests that these markers might be considered in the risk assessment of early COPD.
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Enfermedades Cardiovasculares , Glicopéptidos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Biomarcadores , Fibrinógeno , Enfermedad Pulmonar Obstructiva Crónica/diagnósticoRESUMEN
BACKGROUND: The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities. METHODS: One thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1-4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up. RESULTS: One thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year. CONCLUSION: These findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency. TRIAL REGISTRATION: Trial registration ClinicalTrials.gov, Identifier: NCT01245933. Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010-11, primary completion 2013-12, study completion 2023-09. https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3.
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Enfermedades Cardiovasculares , Comorbilidad , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Femenino , Masculino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Persona de Mediana Edad , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Estudios Transversales , Estudios de Cohortes , Estudios Longitudinales , Progresión de la Enfermedad , Alemania/epidemiología , Estudios de SeguimientoRESUMEN
To determine the most relevant pathogens for CAP in Germany, patients with radiologically confirmed pulmonary infiltrates and at least one clinical sign of lung infection were prospectively recruited within the CAPNETZ cohort from 2004 until 2016. In 990 out of 4.672 patients (21%) receiving complete diagnostics the most prominent change of pathogens was a decrease of S. pneumoniae (58% in 2004 to 37.5% in 2016; p ≤ 0.001, ρ = - 0.148) and an increase of H. influenzae (12.2% to 20.8%; p = 0.001, ρ = 0.104).
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Infecciones Comunitarias Adquiridas , Neumonía Bacteriana , Bacterias , Infecciones Comunitarias Adquiridas/epidemiología , Haemophilus influenzae , Humanos , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/epidemiología , Streptococcus pneumoniaeRESUMEN
Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.
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COVID-19 , Enfermedad Crítica , Humanos , SARS-CoV-2RESUMEN
A 62-year-old patient with bronchial asthma and chronic rhinosinusitis underwent inguinal hernia surgery. After the operation, sudden circulatory arrest occurred, requiring cardiopulmonary resuscitation. Coronary angiography revealed a 99â% proximal stenosis of right coronary artery (RCA) with unsuspicious and smooth coronary vessel walls. In the further course, several similar events occurred, but without pathological findings in the coronary angiography. Initially, echocardiography showed slightly reduced left ventricular ejection fraction of 45â%. Chest radiography revealed bilateral pulmonary infiltrates, and white blood cell count showed severe eosinophilia (37â%). Serological antibody testing including ANA, ENA and c-/p-ANCA was negative. Myeloproliferative pathologies were excluded by bone marrow puncture. The patient suffered from emerging dyspnea, weakness, and ongoing weight loss. A methylprednisolone pulse of 250âmg/d for 3 days remained without significant effect, so that the patient was eventually referred to our university hospital due to ongoing clinical deterioration. On admission, the patient suffered from weakness, progressive muscular atrophy, and dyspnea on exertion. Physical examination revealed a right-sided peroneal paralysis. Bronchial lavage detected severe eosinophil alveolitis (37â%), and laboratory findings showed elevated cardiac enzymes and NT-proBNP (Troponin-Tâ>â700âng/l, NT-proBNPâ>â10.000âng/l). Echocardiography revealed a dramatic deterioration of cardiac function (LVEF 16â%). Interdisciplinary discussion between pulmonologists and cardiologists lead to the diagnosis of ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) with pulmonary and cardiac involvement. Initiation of immunosuppressive therapy with methylprednisolone 1000âmg/d for 3 days followed by cyclophosphamide therapy (6 pulses, administered every 4 weeks) led to substantial symptomatic improvement, complete regression of pulmonary infiltrates and marked recovery of cardiac function (LVEF 47â%). CONCLUSION: Serological detection of elevated ANCAs is not necessary for diagnosis of EGPA. Only 30â-â70â% of patients are positive for these, particularly if neurological and/or renal rather than cardiac and/or pulmonary involvement is present. This may be a pitfall in establishing the correct diagnosis. Induction therapy with cyclophosphamide is the preferred treatment for steroid-refractory EGPA with life-threatening organ involvement.
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Síndrome de Churg-Strauss/complicaciones , Eosinofilia/complicaciones , Granulomatosis con Poliangitis/complicaciones , Cardiopatías/complicaciones , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Función Ventricular Izquierda/efectos de los fármacos , Anticuerpos Anticitoplasma de Neutrófilos/uso terapéutico , Síndrome de Churg-Strauss/tratamiento farmacológico , Angiografía Coronaria , Estenosis Coronaria , Ciclofosfamida/uso terapéutico , Disnea/etiología , Ecocardiografía , Eosinofilia/patología , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/inmunología , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Imagen por Resonancia Magnética , Persona de Mediana Edad , Volumen SistólicoRESUMEN
The present guideline provides a new and updated concept of the management of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2016.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment.The recommendations aim at the same time at a structured assessment of risk for adverse outcome as well as an early determination of treatment goals in order to reduce mortality in patients with curative treatment goal and to provide palliation for patients with treatment restrictions.
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Enfermedades Transmisibles , Medicina de Emergencia , Neumonía , Neumología , Adulto , Anciano , Austria , Cuidados Críticos , Alemania , Humanos , Médicos de FamiliaRESUMEN
Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6â% require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic. Acute hypoxemic respiratory insufficiency with dyspnea and high respiratory rate (>â30/min) usually leads to admission to the intensive care unit. Often, bilateral pulmonary infiltrates/consolidations or even pulmonary emboli are already found on imaging. As the disease progresses, some of these patients develop acute respiratory distress syndrome (ARDS). Mortality reduction of available drug therapy in severe COVID-19 disease has only been demonstrated for dexamethasone in randomized controlled trials. The main goal of supportive therapy is to ensure adequate oxygenation. In this regard, invasive ventilation and repeated prone positioning are important elements in the treatment of severely hypoxemic COVID-19 patients. Strict adherence to basic hygiene, including hand hygiene, and the correct wearing of adequate personal protective equipment are essential when handling patients. Medically necessary actions on patients that could result in aerosol formation should be performed with extreme care and preparation.
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COVID-19 , Síndrome de Dificultad Respiratoria , Humanos , Pacientes Internos , Pandemias , Guías de Práctica Clínica como Asunto , SARS-CoV-2RESUMEN
BACKGROUND: Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects. METHODS: We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. RESULTS: 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. CONCLUSION: We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status.
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Polineuropatías/epidemiología , Polineuropatías/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Índice Tobillo Braquial/tendencias , Estudios de Cohortes , Comorbilidad , Estudios Transversales , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Polineuropatías/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnósticoRESUMEN
Chronic obstructive pulmonary disease (COPD) primarily affects the lungs; however, cardiovascular conditions are among the most common extrapulmonary comorbidities. Besides shared risk factors such as cigarette smoking, pathophysiological connections between the lung and the heart have been identified as mediators of reduced cardiac output. Recent research has focused on hyperinflation of the lung as a pulmonary cause for heart dysfunction. Hyperinflation is a typical lung abnormality seen in COPD; it is characterized by increased residual volume, intrathoracic gas volume, and total lung capacity while vital capacity is decreased. The degree of hyperinflation with airway obstruction is inversely related to left ventricular filling, stroke volume, and cardiac output. The underlying mechanisms are assumed to be compression of the pulmonary veins and thus reduced preload of the left heart as well as decreased pulmonary microvascular blood flow due to compression of the pulmonary vasculature. Treatment with a dual bronchodilator antagonizes this detrimental lung-heart unbalance effectively: Pulmonary blood flow, left ventricular end-diastolic volume, and stroke volume increase in COPD patients without cardiac abnormalities. Similar effects, yet less pronounced, were reported with single bronchodilator therapy. Future work needs to investigate whether these promising findings can be reproduced in COPD patients with cardiovascular diseases.
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Broncodilatadores , Enfermedad Pulmonar Obstructiva Crónica , Volumen Sistólico , Corazón/fisiopatología , Humanos , Pruebas de Función RespiratoriaRESUMEN
Chronic lung allograft dysfunction (CLAD) remains the leading cause of morbidity and mortality after lung transplantation. Diagnosis requires spirometric change, which becomes increasingly difficult with advancing CLAD. Fourier decomposition magnetic resonance imaging (FD-MRI) permits acquisition of ventilated-weighted images during free-breathing. This study evaluates FD-MRI in detecting CLAD in selected patients after bilateral lung transplantation (DLTx). DLTx recipients demonstrating CLAD at various stages participated. Radiologists remained blinded to clinical status until completion of image analysis. Image acquisition used a 1.5-T MR scanner using a spoiled gradient echo sequence. After FD processing and regional fractional ventilation (RFV) quantification, the volume defect percentage at 2 thresholds (VDP1,2 ), median lung RFV and quartile coefficient of dispersion (QCD) were calculated. Sixty-two patients participated. CLAD was present in 29/62 (47%) patients, of whom 17/62 (27%) had forced expiratory volume in 1 second ≤65% at image acquisition. VDP1 was higher among these participants compared to other groups (P < .001). Increased VDP1 was associated with subsequent graft loss, with values >2% showing reduced survival, independent of degree of graft dysfunction (P = .005). VDP2 discriminated between presence or absence of CLAD (area under the curve = 0.71; P = .03). QCD increased significantly with advancing disease (P < .001). In conclusion, FD-MRI-derived parameters demonstrate potential in quantitative CLAD diagnosis and assessment after DLTx.
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Bronquiolitis Obliterante/cirugía , Rechazo de Injerto/diagnóstico , Trasplante de Pulmón/efectos adversos , Imagen por Resonancia Magnética/métodos , Complicaciones Posoperatorias , Disfunción Primaria del Injerto/diagnóstico , Adulto , Aloinjertos , Enfermedad Crónica , Estudios Transversales , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Disfunción Primaria del Injerto/etiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Professional opinions on and assessments of physical performance must be oriented to the individual capacity of the person in question. Moreover, this performance has to be correlated with the expected physical load at work, sports activities or operative stress. This "Load to Capacity Concept" is already a part of an integrative medical assessment, based on clinical experience and common sense, rather than on diagnostic numerical values. An evaluation of work intensity in the context of socio-medical assessment ("lightâ-âmoderateâ-âsevereâ-âvery severe", German Statutory Pension Insurance, based on the German REFAClassification) can now be complemented by well accessible and valid data based on measurements of real-life and professional activities. Also the ratio of continuous power in view of the maximal power output (V'O2 peak) and the power at the aerobic-anaerobic threshold (V'O2 at VT1) is well established. This information is gained by ergospirometry (CPETâ-âCardio Pulmonary Exercise Testing). The focus while interpreting the performance lies on Watt as a physical parameter and on O2-consumption (V'O2 L/min) as the crucial biological correlate. V'O2 is presented as a direct value (L/min) or in complex values like MET (Metabolic Equivalent of Task) and calories (kcal).Recent studies can take advantage of technical progress in this field: rapid sensory measurement, convenient display in graphs and tables. In earlier literature there is ample information on working demands and energy expenditure, supplemented by V'O2-data and MET (see Ainsworth et al.). These studies are helpful for orientation. However, it has to be kept in mind that these studies were done with technical possibilities available then, mostly in a laboratory setting, not under real-life conditions. Portable ergospirometry was not available at that time. Ergospirometry has already proved to be a useful tool in cases where expert opinion is required on compensation claims or questions of early retirement. Positive results of our study on "Occupational Activity of Cleaning Personnel in Clinics" are also reported here.
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Prueba de Esfuerzo/métodos , Corazón/fisiología , HumanosRESUMEN
BACKGROUND: Endobronchial ultrasound (EBUS) bronchoscopy with transbronchial needle aspiration (TBNA) is a well-established tool in mediastinal staging in lung cancer and gains importance in exploration of non-malignant lymphadenopathy. The aim of this study was to evaluate the role of EBUS-TBNA in suspected non-malignant diseases. METHODS: A retrospective, single-center, observation analysis of endobronchial ultrasound bronchoscopy procedures was performed in a university medical center between March 2013 and July 2015. All patients with suspected non-malignant mediastinal lymphadenopathy were included. Cytopathological and microbiological results of EBUS were compared to clinical diagnosis 6 months after procedure and performance of EBUS was contrasted to malignant indications. RESULTS: During study period, 333 EBUS bronchoscopies in 315 patients with mediastinal lymphadenopathy were performed. 111 out of 315 (35â%) patients had neither primary signs nor history of a malignant disease, categorised as patients with suspected non-malignant disease. 245 lymph nodes were sampled (median size 15âmm [IQR10â-â19]). Preferred station for TBNA was lymph node station 7 (38â%). Cytopathological findings revealed non-specific inflammation (nâ=â81; 70â%), carcinoma (nâ=â7; 6â%), epithelioid cell granulomas (nâ=â20; 17â%). 7 samples (6â%) were non-representative. Microbiologic testing of lymph nodes identified 3 infections (Mycobacteria tuberculosis [nâ=â2] and Nocardia nova [nâ=â1]) relevant to antibiotic therapy. Minor adverse events were observed in 9 out of 115 (8â%) patients. Sensitivity of EBUS-TBNA intervention in suspected non-malignant disease was 76â% and specificity 96â%. CONCLUSIONS: EBUS-TBNA revealed a specific cause for suspected non-malignant lymphadenopathy in one-third of cases and was associated with excellent specificity. Predominant specific causes were granuloma, besides from tumor. In 3 patients pathogen could be isolated by TBNA.
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Bronquios/diagnóstico por imagen , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Ganglios Linfáticos/diagnóstico por imagen , Linfadenopatía/diagnóstico , Enfermedades del Mediastino/diagnóstico , Mediastino/diagnóstico por imagen , Bronquios/patología , Broncoscopía , Humanos , Ganglios Linfáticos/patología , Mediastino/patología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , UltrasonografíaRESUMEN
This document is a revision of the guideline for diagnosis and treatment of COPD that replaces the version from 2007. A multitude of recent reports regarding risk factors, diagnosis, assessment, prevention and pharmacological as well as non-pharmacological treatment options made a major revision mandatory. The new guideline is based on the GOLD document taking into account specifics in Germany and Austria.
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Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Neumología/normas , Sociedades Médicas , Austria , Medicina Basada en la Evidencia , Alemania , HumanosRESUMEN
Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized.
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Neumonía Asociada a la Atención Médica/diagnóstico , Neumonía Asociada a la Atención Médica/terapia , Adulto , Estudios Transversales , Alemania , Neumonía Asociada a la Atención Médica/epidemiología , HumanosRESUMEN
Graft failure represents a leading cause of mortality after organ transplantation. Acute late-onset graft failure has not been widely reported. The authors describe the demographics, CT imaging-pathology findings, and treatment of patients presenting with the latter. A retrospective review was performed of lung transplant recipients at two large-volume centers. Acute late-onset graft failure was defined as sudden onset of bilateral infiltrates with an oxygenation index <200 without identifiable cause or concurrent extrapulmonary organ failure. Laboratory, bronchoalveolar lavage (BAL), radiology, and histology results were assessed. Between 2005 and 2016, 21 patients were identified. Median survival was 19 (IQR 13-36) days post onset. Twelve patients (57%) required intensive care support at onset, 12 (57%) required mechanical ventilation, and 6 (29%) were placed on extracorporeal life support. Blood and BAL analysis revealed elevated neutrophilia, with CT demonstrating diffuse ground-glass opacities. Transbronchial biopsy samples revealed acute fibrinoid organizing pneumonia (AFOP), organizing pneumonia, and diffuse alveolar damage (DAD). Assessment of explanted lungs confirmed AFOP and DAD but also identified obliterative bronchiolitis. Patients surviving to discharge without redo transplantation (n = 2) subsequently developed restrictive allograft syndrome. This study describes acute late-onset graft failure in lung allograft recipients, without known cause, which is associated with a dismal prognosis.
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Bronquiolitis Obliterante/etiología , Rechazo de Injerto/etiología , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/etiología , Bronquiolitis Obliterante/diagnóstico por imagen , Bronquiolitis Obliterante/patología , Líquido del Lavado Bronquioalveolar/química , Oxigenación por Membrana Extracorpórea , Femenino , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico por imagen , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/patología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X/métodos , Trasplante HomólogoRESUMEN
Regulatory T cells (Treg) can regulate alloantigens and may counteract chronic lung allograft dysfunction (CLAD) in lung transplantation. We analyzed Treg in peripheral blood prospectively and correlated percentages of subpopulations with the incidence of CLAD at 2 years. Among lung-transplanted patients between January 2009 and July 2011, only patients with sufficient Treg measurements were included into the study. Tregs were measured immediately before lung transplantation, at 3 weeks and 3, 6, 12, and 24 months after transplantation and were defined as CD4+ CD25high T cells and further analyzed for CTLA4, CD127, FoxP3, and IL-2 expressions. Between January 2009 and July 2011, 264 patients were transplanted at our institution. Among the 138 (52%) patients included into the study, 31 (22%) developed CLAD within 2 years after transplantation. As soon as 3 weeks after lung transplantation, a statistically significant positive association was detected between Treg frequencies and later absence of CLAD. At the multivariate analysis, increasing frequencies of CD4+ CD25high CD127low , CD4+ CD25high FoxP3+ and CD4+ CD25high IL-2+ T cells at 3 weeks after lung transplantation emerged as protective factors against development of CLAD at 2 years. In conclusion, higher frequencies of specific Treg subpopulations early after lung transplantation are protective against CLAD development.
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Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/inmunología , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/métodos , Disfunción Primaria del Injerto/prevención & control , Aloinjertos , Antígenos CD4/metabolismo , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Factores de Transcripción Forkhead/metabolismo , Humanos , Inmunofenotipificación , Interleucina-2/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Subunidad alfa del Receptor de Interleucina-7/metabolismo , Masculino , Persona de Mediana Edad , Disfunción Primaria del Injerto/inmunología , Disfunción Primaria del Injerto/metabolismo , Pronóstico , Estudios Prospectivos , Factores de TiempoRESUMEN
Background Determining the underlying diagnosis is essential for the targeted and specific treatment of bronchiectasis. Primary ciliary dyskinesia (PCD) is a rare genetic disease, which is characterized by abnormalities in ciliary structure and/or function and which may result in bronchiectasis. The disease is probably underestimated among adults with bronchiectasis due to the fact that extensive diagnostic testing is required and that the recognition of PCD is low. Objective To evaluate a feasible screening algorithm for PCD among adults with bronchiectasis. Methods Data from all patients who presented to our bronchiectasis outpatient clinic from June 2010 until July 2016 were retrospectively analysed from our database. Nasal NO (nNO) and a modified PICADAR score (PrImary CiliAry DyskinesiA Rule) were measured and compared in the two groups of PCD-bronchiectasis and non-PCD-bronchiectasis. Results 185 of 365 patients (75 males, 110 females) had a sufficient measurement of nNO concentration and complete clinical data and were eligible for analysis. The mean (SD) nNO concentration in nL/ml was significant lower in the PCD group compared to the non-PCD group (25 [31] and 227 [112] nL/min, respectively; pâ<â0.001). A nNO level of 77ânL/min had the best discriminative value to differentiate between the two groups. Patients with PCD had a significant higher modified PIDACAR score than patients without PCD (5 2 and 1 1, respectively [pâ<â0.001]). Using ROC curve analysis, the modified PICADAR score of 2 had the best discriminative value with a sensitivity of 1.00 and a specificity of 0.89. Conclusions Low nNO concentration and the modified PICADAR score are suitable and cheap screening tests for PCD in adults with bronchiectasis.
Asunto(s)
Pruebas Respiratorias , Bronquiectasia/diagnóstico , Trastornos de la Motilidad Ciliar/diagnóstico , Tamizaje Masivo , Óxido Nítrico/análisis , Adulto , Anciano , Bronquiectasia/etiología , Trastornos de la Motilidad Ciliar/etiología , Estudios de Cohortes , Femenino , Alemania , Humanos , Síndrome de Kartagener/diagnóstico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Valores de Referencia , Proyectos de Investigación , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Antibiotic resistance is a part of bacterial evolution and therefore unavoidable. In the context of missing novel treatment options, the restrictive use of available antibiotics in order to decelerate the spread of resistance is of high importance. This is the aim of Antibiotic Stewardship (ABS). ABS consists of two sides: a structural one and an individual one. The former deals with the formation of ABS teams, the analysis of antibiotic usage and resistance development, and the implementation of certain measures to improve antibiotic use; the latter is reflected by concrete bedside decisions: How can (broad) spectrum antibiotics be spared without harming the patient? This can be achieved, for example, by de-escalation, limiting duration of treatment, and avoiding nonindicated use. Typical nonindicated uses in both in- and outpatients are viral respiratory tract infections, asymptomatic bacteriuria and nonbacterial exacerbations of chronic obstructive pulmonary disease. Furthermore, respiratory colonization in ventilated patients, ventilator-associated tracheobronchitis, "prolonged" perioperative prophylaxis, and contaminated blood cultures reflect situations where antibiotics should be avoided. In the future, ABS will benefit from accelerated pathogen and resistance detection because early adequate treatment not only lowers the usage of antibiotics but can also improve patient outcome.
Asunto(s)
Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Farmacorresistencia Bacteriana , Medicina de Precisión , Programas de Optimización del Uso de los Antimicrobianos/organización & administración , HumanosRESUMEN
Chronic Pseudomonas aeruginosa colonization in the airways of patients with chronic obstructive pulmonary disease (COPD) is probably associated with increased mortality and morbidity and a faster progress of COPD, although this has not been conclusively proven by studies. Studies demonstrating an improvement in prognosis in COPD patients by early eradication of Pseudomonas or at least a reduction of the bacterial burden by either inhaled or oral antibiotic maintenance therapy, are missing. An impact on the exacerbation rate has only been shown for macrolide maintenance treatment; however, this effect could be explained by the inclusion of patients with bronchiectasis in the studies. This is a group of patients for whom the effect of this kind of antibiotic treatment is well known. Further studies on the prevention and treatment of chronic Pseudomonas colonization in COPD patients are urgently needed. The stability of the respiratory microbiome probably plays an essential role in the course of the disease and should be established as a study endpoint.
Asunto(s)
Antibacterianos/uso terapéutico , Macrólidos/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/patogenicidad , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Administración por Inhalación , Administración Oral , Bronquiectasia/tratamiento farmacológico , Bronquiectasia/microbiología , Bronquiectasia/mortalidad , Progresión de la Enfermedad , Humanos , Cuidados a Largo Plazo , Infecciones por Pseudomonas/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Tasa de Supervivencia , VirulenciaRESUMEN
The role of mammalian target of rapamycin (mTOR) inhibitors in de novo immunosuppression after lung transplantation is not well defined. We compared Everolimus versus mycophenolate mofetil in an investigator-initiated single-center trial in Hannover, Germany. A total of 190 patients were randomly assigned 1:1 on day 28 posttransplantation to mycophenolate mofetil (MMF) or Everolimus combined with cyclosporine A (CsA) and steroids. Patients were followed up for 2 years. The primary endpoint was freedom from bronchiolitis obliterans syndrome (BOS). The secondary endpoints were incidence of acute rejections, infections, treatment failure and kidney function. BOS-free survival in intention-to-treat (ITT) analysis was similar in both groups (p = 0.174). The study protocol was completed by 51% of enrolled patients. The per-protocol analysis shows incidence of bronchiolitis obliterans syndrome (BOS): 1/43 in the Everolimus group and 8/54 in the MMF group (p = 0.041). Less biopsy-proven acute rejection (AR) (p = 0.005), cytomegalovirus (CMV) antigenemia (p = 0.005) and lower respiratory tract infection (p = 0.003) and no leucopenia were seen in the Everolimus group. The glomerular filtration rate (GFR) decreased in both groups about 50% within 6 months. Due to a high withdrawal rate, the study was underpowered to prove a difference in BOS-free survival. The dropout rate was more pronounced in the Everolimus group. Secondary endpoints indicate potential advantages of Everolimus-based protocols but also a potentially higher rate of drug-related serious adverse events.