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BACKGROUND: Lung transplantation (LT) requires sustained care for a frequently polypathological condition. Follow-up is focused on three main issues: 1/stability of respiratory function; 2/comorbidity management; 3/preventive medicine. About 3000 LT patients in France are treated in 11 LT centers. Given the increased size of the LT recipient cohort, follow-up might be partially shared with peripheral centers. METHODS: This paper presents the suggestions of a working group of the SPLF (French-speaking respiratory medicine society) on possible modalities of shared follow-up. RESULTS: While the main LT center is tasked with centralizing follow-up, particularly the choice of optimal immunosuppression, an identified peripheral center (PC) may serve as an alternative to deal with acute events, comorbidities and routine assessment. Communication between the different centers should be free-flowing. Shared follow-up may be offered from the 3rd postoperative year to stable and consenting patients, whereas unstable and non-observant patients are poor candidates. CONCLUSION: These guidelines may serve as a reference for any pneumologist wishing to effectively contribute to follow-up, even and especially subsequent to lung transplant.
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Trasplante de Pulmón , Receptores de Trasplantes , Humanos , Estudios de Seguimiento , Francia , Pulmón , Estudios RetrospectivosRESUMEN
INTRODUCTION: Pulmonary siderosis or welder's lung is an occupational lung disease that is usually observed after chronic exposure to iron dust. OBSERVATION: A 55-years-old welder visited hospital with dyspnea linked to occupational exposure. Pulmonary function studies revealed lung function abnormalities with decerase of FEV1 and TPC. Based on the chest Tomography CT results, he was diagnosed with obliterans bronchiolitis. A chest biopsy was performed and the specimen is for a pulmonary siderosis aspect. DISCUSSION: This case of pulmonary siderosis is an unusual one by symptoms, CT images and short latency of exposure. An intense inhalation of iron particles could explain this case and inflammatory process and it highlights need of histological analysis of chest biopsy.
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Exposición Profesional , Siderosis , Soldadura , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Obreros Metalúrgicos , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Siderosis/diagnóstico , Siderosis/etiología , Siderosis/patologíaRESUMEN
OBJECTIVES: Early detection of Pseudomonas aeruginosa lung positivity is a key element in cystic fibrosis (CF) management. PCR has increased the accuracy of detection of many microorganisms. Clinical relevance of P. aeruginosa quantitative PCR (qPCR) in this context is unclear. Our aim was to determine P. aeruginosa qPCR sensitivity and specificity, and to assess the possible time saved by qPCR in comparison with standard practice (culture). METHODS: A multicentre cohort study was conducted over a 3-year period in 96 patients with CF without chronic P. aeruginosa colonization. Sputum samples were collected at each visit. Conventional culture and two-step qPCR (oprL qPCR and gyrB/ecfX qPCR) were performed for 707 samples. The positivity criteria were based on the qPCR results, defined in a previous study as follow: oprL qPCR positivity alone if bacterial density was <730 CFU/mL or oprL qPCR combined with gyrB/ecfX qPCR if bacterial density was ≥730 CFU/mL. RESULTS: During follow up, 36 of the 96 patients with CF were diagnosed on culture as colonized with P. aeruginosa. This two-step qPCR displayed a sensitivity of 94.3% (95% CI 79.7%-98.6%), and a specificity of 86.3% (95% CI 83.4%-88.7%). It enabled P. aeruginosa acquisition to be diagnosed earlier in 20 patients, providing a median detection time gain of 8 months (interquartile range 3.7-17.6) for them. CONCLUSIONS: Implementing oprL and gyrB/ecfX qPCR in the management of patients with CF allowed earlier detection of first P. aeruginosa lung positivity than culture alone.
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Fibrosis Quística/complicaciones , Diagnóstico Precoz , Técnicas de Diagnóstico Molecular/métodos , Infecciones por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adolescente , Técnicas Bacteriológicas/métodos , Niño , Femenino , Humanos , Masculino , Estudios Prospectivos , Sensibilidad y Especificidad , Esputo/microbiología , Factores de TiempoRESUMEN
OBJECTIVE: To describe the features of pulmonary arterial hypertension (PAH) in elderly patients. METHODS: A single centre, descriptive study of PAH patients consecutively referred to a regional centre, from September 2002 to February, 1st, 2009. The group of patients aged 65 and above at the time of the diagnosis was compared to the younger patients. RESULTS: Sixty-six patients suffering from PAH (group 1) have been investigated by means of right heart catheterisation. There were 24 patients aged 65 and above. Mean pulmonary arterial pressure was lower in the patients aged over 65. The older patient group had more respiratory and/or cardiac co-morbidities, a lower median distance in the 6minute walk test and a higher median Pro-BNP level. Specific PAH treatments were prescribed in both groups. Fifteen patients aged 65 and above were on long-term oxygen therapy (vs four younger patients, p<0.0001). The elderly patients had a median survival of 32 months. CONCLUSION: The diagnosis of PAH in elderly patients is associated with a poor prognosis. The management of these patients needs further studies.
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Hipertensión Pulmonar/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Cateterismo Cardíaco , Estudios de Cohortes , Comorbilidad , Prueba de Esfuerzo , Femenino , Francia , Humanos , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/terapia , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico , Presión Esfenoidal Pulmonar , Adulto JovenRESUMEN
Two strategies are possible for targeting distal airways in asthma. The first one is systemic, with the delivery of medications either orally or intravenously. Montelukast is the only oral drug that has demonstrated its efficacy on distal airways by reducing lung hyperinflation. The second possible strategy is to deliver inhaled medications using ultrafine particles. Studies performed with formoterol-HFA solution (Formoair Modulite), the only available long-acting beta2 agonist with ultrafine particles have shown a non-inferior bronchodilator effect and a good tolerance as compared to inhaled long acting beta2 agonists with non-ultrafine particles. Studies performed with BDP-HFA alone (QVAR) or combined BDP-HFA/formoterol (Fostair) with ultrafine particles have mostly demonstrated their clinical non- inferiority on bronchodilation, quality of life, and symptoms in asthmatic subjects as compared to non-ultrafine inhaled medications. With the exception of a few studies, most publications have been performed in a limited number of patients and for only short durations. The available studies have not yet demonstrated a long-term benefit in terms of additional clinical efficacy of these ultrafine inhaled medications on symptoms, control and exacerbations of asthma.
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Asma/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Agonistas Adrenérgicos beta/uso terapéutico , Etanolaminas/uso terapéutico , Fumarato de Formoterol , Humanos , Nebulizadores y Vaporizadores , Tamaño de la PartículaAsunto(s)
Infecciones por VIH/tratamiento farmacológico , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Adulto , Antirretrovirales/uso terapéutico , Femenino , Infecciones por VIH/complicaciones , Humanos , Factores de Tiempo , Resultado del Tratamiento , Carga ViralRESUMEN
Since 1976, benfluorex has been approved in Europe as a hypolipidemic and hypoglycemic drug, and is commonly used in the treatment of the metabolic syndrome. As a derivative of fenfluramine with an appetite suppressant action, benfluorex is preferentially used in overweight patients. In contrast to fenfluramine and dexfenfluramine, to date, benfluorex has not been reported to be associated with frequent cardiovascular side-effects. The present study reports five cases of severe pulmonary arterial hypertension and one case of valvular heart disease occurring in patients exposed to benfluorex. These individuals were middle age, diabetic females with a body mass index ranging 24.2-49 kg x m(-2). No definite causal effect for cardiovascular disease with benfluorex can be drawn from such case reports. However, as benfluorex, like dexfenfluramine and fenfluramine, is metabolised into active metabolite norfenfluramine, further extensive assessment of drug exposure in newly diagnosed pulmonary arterial hypertension or valvular heart disease patients is warranted.
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Enfermedades Cardiovasculares/inducido químicamente , Fenfluramina/análogos & derivados , Fenfluramina/efectos adversos , Depresores del Apetito/efectos adversos , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/patología , Femenino , Enfermedades de las Válvulas Cardíacas/inducido químicamente , Humanos , Persona de Mediana Edad , Válvula Mitral/patología , Sobrepeso/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversosAsunto(s)
Endarterectomía/métodos , Hipertensión Pulmonar/diagnóstico , Anticoagulantes/farmacología , Enfermedad Crónica , Estudios de Cohortes , Humanos , Presión , Estudios Prospectivos , Arteria Pulmonar/patología , Circulación Pulmonar/fisiología , Estudios Retrospectivos , Espirometría , TromboemboliaRESUMEN
The characteristics of patients with rheumatoid arthritis (RA) who develop obliterative bronchiolitis characterised by severe airflow obstruction have been hitherto poorly investigated. A retrospective study of 25 patients with RA and functional evidence of obliterative bronchiolitis (forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) <50% and/or residual volume (RV)/total lung capacity (TLC) >140% predicted) was conducted. Patients (mean+/-SD age 64+/-11 yrs) included 17 never-smokers and eight ex-smokers (10.5+/-5.4 pack-yrs). The diagnosis of RA preceded respiratory symptoms in 88% of cases. Dyspnoea on exertion was present in all patients and bronchorrhea in 44%. High-resolution computed tomography findings included: bronchial wall thickening (96%), bronchiectasis (40%), mosaic pattern (40%), centrilobular emphysema (56%), and reticular and/or ground-glass opacities (32%). Pulmonary function tests showed: FEV(1) 41+/-12% pred, FEV(1)/FVC 49+/-14%, FVC 70+/-20% pred, RV 148+/-68% pred and RV/TLC 142+/-34% pred. Lung biopsy, available in nine patients, demonstrated constrictive, follicular and mixed bronchiolitis. Patients were followed for 48.2+/-49 months. Treatment was poorly effective. Chronic respiratory failure occurred in 40% of patients, and four patients died. Obliterative bronchiolitis associated with rheumatoid arthritis is a severe and under-recognised condition leading to respiratory failure and death in a high proportion of patients.
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Artritis Reumatoide/complicaciones , Bronquiolitis Obliterante/complicaciones , Adulto , Anciano , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Biopsia , Bronquiolitis Obliterante/diagnóstico por imagen , Bronquiolitis Obliterante/tratamiento farmacológico , Bronquiolitis Obliterante/fisiopatología , Lavado Broncoalveolar , Distribución de Chi-Cuadrado , Ecocardiografía , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Radiografía Torácica , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Toracoscopía , Tomografía Computarizada por Rayos X , Capacidad Pulmonar Total , Capacidad VitalRESUMEN
The present review is the summary of an expert workshop that took place in Vence (France) in 2007 on the role of distal airways in asthma. The evidence showing inflammation and remodelling in distal airways, and their possible involvement in asthma control and natural history, was reviewed. The usefulness and limitations of various techniques used for assessing distal airways were also evaluated, including pulmonary function tests and imaging. Finally, the available data studying the benefit of treatment better targeting distal airways in asthma was examined. It was concluded that both proximal and distal airways were involved in asthma and that distal airways were the major determinant of airflow obstruction. Inflammation in distal airways appeared more intense in severe and uncontrolled asthma. Distal airways were poorly attained by conventional aerosol of asthma medications owing to their granulometry, being composed of 3-5 µm particles. Both proximal and distal airways might be targeted either by delivering medications systemically or by aerosol of extra-fine particles. Extra-fine aerosols of long-acting ß-agonists, inhaled corticosteroids or inhaled corticosteroid/long-acting ß-agonist combinations have been shown in short-term studies to be not inferior to non-extra-fine aerosols of comparators. However, available studies have not yet demonstrated that extra-fine inhaled medications offer increased benefit compared with usual aerosols in asthmatic patients.
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Asma/fisiopatología , Pulmón/fisiopatología , Asma/tratamiento farmacológico , Asma/patología , Bronquios/patología , Líquido del Lavado Bronquioalveolar/citología , HumanosRESUMEN
The prognosis of postembolic pulmonary hypertension, a rare and serious disease, has been transformed with the curative intervention of pulmonary endarteriectomy. The screening is based on two key non invasive examinations, the cardiac ultrasound and ventilation-perfusion scintigraphy. The confirmation of the diagnosis and the determination of the best therapeutic options then relies on the expertise of the national reference centre, based on the haemodynamics and the morphological data provided by pulmonary angiography and spiral computerised tomography. Although the technique of endarteriectomy is fully validated, a drug approach is in the assessment process, both in the inoperable forms or when confronted with persistent postsurgical pulmonary hypertension.
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Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Embolia Pulmonar/cirugía , Angiografía , Endarterectomía , Humanos , Hipertensión Pulmonar/etiología , Selección de Paciente , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada EspiralRESUMEN
OBJECTIVE: to assess the effects of an educational program in asthmatic patients, following treatment readjustment. METHODS: moderate to severe asthmatic adults underwent a run-in period (up to 45 days) in order to optimize their treatment. Patients were then randomized to an educational or control group over a one-year period. Education consisted of five individual sessions covering: pathophysiology of asthma, role of medication and side-effects, asthma triggers and their avoidance, detection of an asthma flare-up, and self-management plan based on symptoms and peak-flow monitoring. MAIN OUTCOME CRITERION: symptom-free days over the study period (SFD). RESULTS: a total of 72 patients were enrolled (36 in the "education group" and 36 in the "control group"), 54 of whom completed the study. Mean SFD was comparable in the two groups (88% in the education group and 89% in the control group, respectively). When the analysis was restricted to the education group, those patients who complied perfectly with the action plan (n = 5) exhibited a higher SFD, compared to the others (97% vs. 87%, p = 0.009). CONCLUSION: both education and control groups showed high and comparable percentages of SFD. Compliance with self-management plans appears to be an important determining factor in educational programs.
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Asma/terapia , Educación del Paciente como Asunto , Autocuidado , Adolescente , Adulto , Anciano , Asma/epidemiología , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado/fisiología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Cooperación del Paciente , Estudios Prospectivos , Calidad de VidaRESUMEN
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with different related disorders such as congenital bilateral absence of the vas deferens, chronic idiopathic pancreatitis, or disseminated bronchiectasis (DB). Many different disease-causing mutations are associated with DB, particularly the 5T allele (IVS 8 polyT tract), a variant of the splice acceptor site at the end of intron 8 that affects the efficiency with which the site is used. It therefore affects the accuracy of exon 9 splicing and hence expression of the functional CFTR protein. In this study we quantified transcripts from nasal biopsies of patients with DB compared to normal controls. We developed a real-time quantitative reverse transcription polymerase chain reaction assay (using the TaqMan system) to evaluate the relative amounts of accurately spliced transcript, and transcript lacking exon 9. Patients with the 5T allele had increased amounts of aberrant transcript: in genotypes 5T/7T, 7T/7T and 9T/7T, mean fractions of 38.4%, 3.5% and 0.6%, respectively, of transcripts had been spliced incorrectly. There was also some evidence that nasal biopsies can provide similar information on transcripts to bronchial biopsies. This functional test is of interest for monitoring the amount of CFTR transcript in different clinical situations or to monitor the effect of drugs on CFTR transcription.
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Bronquiectasia/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Procesamiento Postranscripcional del ARN/genética , Colorantes Fluorescentes , Variación Genética , Humanos , Empalme del ARNRESUMEN
This article aims to examine educational strategies in the context of the overall management of the asthmatic patient. The objectives are analysed from the viewpoints of the both the patient and the health care professionnal. The complexity of the manifestations of asthma and the variability of perception of symptoms require a personalised approach to education. The asthmatic patients, co-operation with their therapeutic management, in particular in matters of compliance, reveals problems common to other chronic conditions. If an agreement can be reached during an exchange of beliefs and points of view, this will lead to the most appropriate choice of therapy. The evaluation of educational strategies has been the subject of many publications and sequential studies must be distinguished from randomised controlled trials. Sequential studies of educational strategies generally include severe asthmatics, previously under-treated. The improvement in measured parameters of morbidity is often striking but it is difficult to separate the true effect of education from that of improved total management, particularly the introduction of preventative treatment. Randomised trials with an "uneducated" control group give more conflicting results. A particular emphasis may be placed on action plans based on monitoring of peak flow and/or symptoms. Finally the inclusion of educational strategies in the training programmes of health care professionnals is now well established and its impact should be evaluated.
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Asma/terapia , Educación del Paciente como Asunto/métodos , Humanos , Cooperación del PacienteAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Linfoma no Hodgkin/tratamiento farmacológico , Fibrosis Pulmonar/etiología , Adulto , Anciano , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Quimioterapia Combinada , Resultado Fatal , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Humanos , Masculino , Metotrexato/administración & dosificación , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Vindesina/administración & dosificaciónRESUMEN
Recurrence after surgery for bronchial carcinoid tumors is very uncommon in cases of typical tumors and occasionally seen in cases of atypical tumors. We observed two cases of recurrence in an unusual location, the pleura. Somatostatin analog and MIBG scinigrams were useful for diagnosis. Treatment required surgical excision of the relapsing tumor, cytoreductive hepatic surgery or hepatic arterial chemoembolization for liver metastases, chemotherapy, interferon, radionuclide therapy, and somatostatin analogs for carcinoid syndrome.
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Neoplasias de los Bronquios , Tumor Carcinoide , Recurrencia Local de Neoplasia , Neoplasias Pleurales , Neoplasias de los Bronquios/diagnóstico , Neoplasias de los Bronquios/terapia , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/terapia , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/terapia , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/terapiaRESUMEN
Human immunodeficiency virus (HIV) infection has been associated with a wide spectrum of pulmonary disease. We report three HIV-seropositive patients with rapidly worsening airway obstruction associated with bronchiectasis. All subjects (age range 33-39 yrs) were cigarette smokers. Two had previously used intravenous drugs. The CD4 lymphocyte count ranged 40-250 cells x mm(-3). All individuals had complained of increasing dyspnoea for 3-6 months. Within 1 yr, they all developed severe airway obstruction with a decrease in both forced expiratory volume in one second (FEV1) and ratio of FEV1 to forced vital capacity (FEV1/FVC) to less than 60% of predicted value, and a decrease in mean forced expiratory flow at 25-75% of the forced vital capacity (FEF25-75) to less than 35% of predicted value. Computed tomography of the chest disclosed bilateral dilated and thickened bronchi. No classical causes of genetic or acquired bronchiectasis were identified in our patients. Recurrent bacterial bronchitis occurred in the follow-up period of the three patients. In conclusion, unusually rapid airway obstruction associated with bronchiectasis should be added to the wide spectrum of respiratory complications of human immunodeficiency virus infection.
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Bronquiectasia/complicaciones , Infecciones por VIH/complicaciones , Enfermedades Pulmonares Obstructivas/complicaciones , Adulto , Bronquiectasia/diagnóstico , Progresión de la Enfermedad , Femenino , Seropositividad para VIH , Humanos , Enfermedades Pulmonares Obstructivas/diagnóstico , Masculino , Pruebas de Función Respiratoria , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Despite promising results, the efficacy of polymerase chain reaction (PCR) for clinical management of cytomegalovirus (CMV) infection in transplanted patients is still controversial. METHODS: A prospective study of CMV detection, with concurrent shell vial cultures and PCR in blood and bronchoalveolar lavage (BAL), was conducted in 13 lung transplant recipients, monitored for 15 months (range: 1-42 months). CMV DNA was detected by PCR amplification of a 406-bp fragment in the Us region and a 290-bp fragment in the immediate early region of the viral genome. RESULTS: When comparing PCR to viral culture, the sensitivity and specificity of CMV DNA detection were 100% and 65.7% in blood (n=122) and 100% and 75% in BAL (n=104). The positive and negative predictive values of PCR for a forthcoming diagnosis of CMV infection were 50% and 97% in blood, and 67% and 85% in BAL. Seventeen CMV infections were evaluated at the end of treatment: when PCR was still positive either in blood or BAL, CMV infection relapsed within 35+/-5 days; when PCR was negative, CMV infection relapsed after 142+/-57 days (P=0.01). CONCLUSIONS: Negative CMV detection by PCR strongly advocates against a forthcoming CMV infection. PCR assay seems to be a good predictor for early recurrence of CMV infection, and would be useful for monitoring the response to antiviral therapy.
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Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/virología , Citomegalovirus/genética , ADN Viral/sangre , Trasplante de Pulmón/fisiología , Adolescente , Adulto , Antivirales/uso terapéutico , Evaluación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
In spite of improvements in single or double lung transplantation (LT) technique, complications after LT are not uncommon; the most frequent ale anastomotic complications, infections and rejection (acute or chronic). Early detection of complications of LT allows the optimal therapeutic option to be taken, yielding decreased morbidity and mortality. In some cases, CT plays a key role in early detection of several complications of LT that may not be depicted with other diagnostic modalities, so that knowledge of their CT features is important. In this pictorial review, the authors describe the spectrum of CT features of the complications of LT (including reimplantation response, mechanical problems, acute and chronic rejection, infection, lymphoproliferative disorders, recurrence of the initial disease and complications involving the pleura and the anastomotic sites). In addition, the authors analyze the value of CT compared to that of the other available modalities for the detection of complications of LT.
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Trasplante de Pulmón/efectos adversos , Tomografía Computarizada por Rayos X , Adulto , Anastomosis Quirúrgica , Biopsia con Aguja/efectos adversos , Bronquios/cirugía , Femenino , Rechazo de Injerto/diagnóstico por imagen , Humanos , Pulmón/diagnóstico por imagen , Trastornos Linfoproliferativos/diagnóstico por imagen , Trastornos Linfoproliferativos/etiología , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/diagnóstico por imagen , Neumotórax/diagnóstico por imagen , Neumotórax/etiología , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/etiologíaRESUMEN
BACKGROUND: With regard to limiting the systemic effects of cyclosporine A and obtaining better control of acute pulmonary allograft rejection, local immunosuppressive therapy with aerosolized cyclosporine A seems of interest. Given the in situ immunologic mechanisms of acute rejection, as well as the anatomic structure of the lung, this therapy is feasible as previously described by others. The aim of our study is to determine the pharmacokinetic parameters of nebulized cyclosporine A and the best modalities of administration. METHODS: In a pharmacokinetic study, the cyclosporine A was given either by intramuscular injection (10 mg/kg) or by aerosol at 10 and 25 mg/kg doses; 70 rats were killed at 25 and 50 minutes and 2, 4, 6, 8, 12, 24, or 48 hours after cyclosporine A administration. Cyclosporine A levels were measured in whole blood and in the lung. The areas under the concentration time curves were determined. Twenty-four lung transplantations were then performed. The rats were killed on postoperative day 9. Acute rejection was scored on a scale of 0 to 4, and cyclosporine A trough levels were measured in the lung and in the blood. RESULTS: With a jet nebulizer, the mass median aerodynamic diameter was 2.5 microns, with a standard geometric deviation of 2.3. In blood, the area under the concentration curve was greater for intramuscular (80.6 ng.hr/ml) than for aerosol administrations at 10 (15.1 ng.hr/ml) and 25 mg/kg (41.0 ng.hr/ml) doses. In the lungs, the area under the concentration curve was greater for the aerosol route at 25 mg/kg doses (588 ng.hr/mg) than for the low-dose (200 ng.hr/mg) or intramuscular administration (200 ng.hr/mg). The lung targeting index of cyclosporine A (ratio area under the concentration curve-lungs/area under the concentration curve-blood) was greater for both aerosol administrations than for the intramuscular route. In the study of the prevention of acute rejection, rats without immunosuppression (n = 6), rats receiving daily doses of cyclosporine A intramuscularly (10 mg/kg), and rats with aerosolized cyclosporine A daily (10 and 25 mg/kg/day) showed mean grades of acute rejection of, respectively, 4, 2.03 +/- 0.27, 2.33 +/- 0.52, and 2.17 +/- 0.46. The deposition of nebulized cyclosporine A was lower in transplanted than in native lung. CONCLUSIONS: Nebulized cyclosporine A allows better pulmonary concentration than intramuscular administration, and results in lower systemic levels. Prevention of acute rejection is as good with aerosolized cyclosporine A as with intramuscular cyclosporine A. This first pharmacokinetic study of nebulized cyclosporine A could lead to clinical applications.