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CASE PRESENTATION: A 41-year-old man who currently smokes with previous sporadic use of cocaine and cannabinoids was admitted at the hospital suffering from hemoptysis which had developed 4 days before. The patient was on anticoagulant therapy with rivaroxaban due to paroxysmal atrial fibrillation diagnosed in 2018, for which he had undergone pulmonary vein electrical isolation by radiofrequency and ablation of cavotricuspid isthmus in January 2019. The procedure was completed in July 2019. Treatment with flecainide was introduced due to recurrences of atrial fibrillation. In February 2021, a new attempt at ablation was performed by electrical isolation of the left atrial posterior wall. The latest cardiologic checkup documented an echocardiographic framework of mild left atrial dilatation and normal-sized right ventricle with longitudinal shortening index at the lower limits, and a recurrence of asymptomatic atrial fibrillation at Holter ECG (March 2022).
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Fibrilación Atrial , Hemoptisis , Humanos , Masculino , Adulto , Hemoptisis/etiología , Hemoptisis/diagnóstico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Ecocardiografía , Venas Pulmonares/cirugía , Venas Pulmonares/diagnóstico por imagenRESUMEN
Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as "precision medicine". With respect to bronchiectasis, many comorbidities and underlying causes have been identified. Inflammatory endotypes have also been widely studied and reported. Additionally, several genes have been shown to affect disease progression. However, the lack of a clear classification has also hampered our understanding of the disease's natural course. The aim of this review is, thus, to summarize the current knowledge on biomarkers and actionable targets of this complex pathologic condition and to point out unmet needs, which are required in the design of effective diagnostic and therapeutic trials.
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Little or nothing is known about the correlation between the upper limb deep vein thrombosis (UL-DVT) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the increased risk of UL-DVT in 3 patients with SARS-CoV-2 who require continuous positive airway pressure with a hood and the need for early adequate antithrombotic prophylaxis.
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Betacoronavirus , Presión de las Vías Aéreas Positiva Contínua/efectos adversos , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Extremidad Superior/irrigación sanguínea , Trombosis de la Vena/etiología , Anciano , COVID-19 , Humanos , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Trombosis de la Vena/prevención & controlRESUMEN
BACKGROUND: Extracorporeal photochemotherapy (ECP) for chronic lung allograft dysfunction (CLAD) has been reported as beneficial in a few short-term studies. OBJECTIVES: In this retrospective cohort study on 48 CLAD patients treated by ECP (off-line technique) for a period of >8 years (compared to 58 controls), we explored potential predictors of survival and response. METHODS: Failures were defined as a decrease in forced expiratory volume in 1 s (FEV1) of >10% from ECP initiation. RESULTS: ECP patients were enrolled between February 2003 and December 2013; 14 (29.2%) with restrictive allograft syndrome (RAS) and 34 with bronchiolitis obliterans syndrome. Grade 1 severity was indicated in 58.3%, grade 2 in 20.8%, and grade 3 in 20.8% of patients. The median follow-up was 65 months (cumulative 2,284.4 person-months). Twenty (41.7%) patients died, including 17 (85%) CLAD-related deaths. Among the controls, there were 42 deaths (72.4%), of which 32 (76.2%) were CLAD related, over a median of 51 months (cumulative 3,066.5 person-months; p = 0.09). Among ECP patients, the FEV1 slope flattened out after a decline in the initial months (slope -19 ml/month in months 0-6, +4 in months 36-48 and later; p = 0.001). RAS was associated with poorer survival, whereas a 'rapid decline in the previous 6 months' was not. No ECP side effects or complications were observed. CONCLUSION: Long-term ECP for CLAD is safe and reduces FEV1 decline over time; the RAS phenotype might show a poorer response. ECP deserves to be evaluated in a randomized controlled trial.
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Bronquiolitis Obliterante , Rechazo de Injerto , Trasplante de Pulmón/efectos adversos , Fotoféresis/métodos , Adulto , Aloinjertos/patología , Aloinjertos/fisiopatología , Bronquiolitis Obliterante/diagnóstico , Bronquiolitis Obliterante/mortalidad , Bronquiolitis Obliterante/fisiopatología , Bronquiolitis Obliterante/terapia , Resistencia a Medicamentos , Femenino , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/mortalidad , Rechazo de Injerto/fisiopatología , Rechazo de Injerto/terapia , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Pruebas de Función Respiratoria/métodos , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tiempo , Resultado del TratamientoRESUMEN
Human cosavirus is a novel picornavirus recently identified in feces from children in southern Asia. We report infection with human cosavirus in a patient in the Mediterranean area. The patient was an adult double lung transplant recipient who had chronic diarrhea associated with persistent infection with human cosavirus.
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Diarrea/diagnóstico , Trasplante de Pulmón , Infecciones por Picornaviridae/diagnóstico , Picornaviridae/genética , Adulto , Diarrea/virología , Heces/virología , Femenino , Humanos , Italia , Tipificación Molecular , Infecciones por Picornaviridae/virología , Análisis de Secuencia de ADN , Trasplante , Proteínas Estructurales Virales/genéticaRESUMEN
BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are serious complications in lung transplant recipients. No consensus on EBV DNAemia levels predictive of PTLD has been reached. In addition, in many instances EBV DNAemia is determined in patients with suggestive symptoms only. METHODS: The characteristics of five patients with PTLD as well as the prevalence of EBV DNAmia in a cohort of 137 consecutive patients receiving lung transplantation are described. RESULTS: Twenty-six out of 137 patients (18.9%) were excluded from the analysis because lost at follow-up or dead from PTLD-independent reasons within three months of transplantation. EBV DNA in peripheral blood mononuclear cells (PBMC) was determined in 83/111 patients (74.8%) because of potential PTLD-related symptoms, while 28 patients (25.2%) showed no symptoms and were not examined. EBV DNAemia was positive in 53/83 patients (63.8%), and negative in 30/83 patients (36.2%). PTLD was diagnosed in five (4.5%) patients at a median time of 270 (range 120-870) days following transplantation. All five PTLD (three large B-cell lymphomas, one Hodgkin lymphoma and one possible pre-neoplastic lesion) were potentially associated with EBV infection. However, only 3/5 patients with PTLD had detectable EBV DNAemia: < 1,000 copies EBV DNA/1 × 105 PBMC in one patient and > 1,000 copies EBV DNA/1 × 105 PBMC in two patients. CONCLUSION: A systematic multidisciplinary (clinical, radiologic, virologic and histologic) approach is mandatory for the diagnosis and management of PTLD in lung transplant recipients, while monitoring of symptomatic patients only may provide an incomplete or late picture of the clinical problem. In addition, staining for EBV antigens and quantification of EBV DNA in biopsy specimens should always be performed to understand the role of EBV infection in the pathogenesis of PTLD.
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ADN Viral/análisis , Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Trasplante de Pulmón/efectos adversos , Trastornos Linfoproliferativos/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Adulto , Anciano de 80 o más Años , Estudios de Cohortes , Dermatoglifia del ADN , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/virología , Femenino , Estudios de Seguimiento , Herpesvirus Humano 4/inmunología , Humanos , Italia , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Trasplante de Pulmón/inmunología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/virología , Masculino , Persona de Mediana Edad , Carga Viral/inmunologíaRESUMEN
Cladophialophora boppii is a dematiaceous fungus, which has been reported only rarely to be the cause of cutaneous infection. Herein we describe a C boppii parenchymal and bronchial infection in a lung transplant recipient. We also illustrate the clinicoradiologic patterns and review possible treatment options for these difficult infections.
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Ascomicetos/patogenicidad , Enfermedades Pulmonares Fúngicas/diagnóstico , Trasplante de Pulmón , Pulmón/microbiología , Micosis/diagnóstico , Enfisema/cirugía , Humanos , Pulmón/patología , Enfermedades Pulmonares Fúngicas/patología , Masculino , Persona de Mediana Edad , Micosis/patología , Fibrosis Pulmonar/cirugíaRESUMEN
Radiofrequency thermal ablation (RFTA) is a local tumor-destructing technique that can potentially modulate the host immune response through mechanisms that are not clearly defined. We assessed whether RFTA could affect multiple systemic inflammatory and immunological parameters, including CD25+Foxp+ cells, in patients with primary or metastatic lung tumors. Three days after RFTA, a moderate and temporary systemic inflammatory response developed, as demonstrated by the increase in peripheral neutrophils and monocytes and in plasma levels of proinflammatory chemokines (MIP-1alpha, MIP-1beta, eotaxin, and interleukin[IL]-8) and acute phase reactants (complement C3 and C4, serum amyloid, alpha1 antichymotrypsin, and C-reactive protein). Moreover, we found a concomitant release of the anti-inflammatory factor IL-10. Thirty days after RFTA, a significant reduction in CD25+Foxp3+ counts with an increase in CD4+ T-cell proliferation and number of interferon-gamma-secreting cells was observed. The reduction in CD25+Foxp3+ cells lasted up to 90 days after treatment. The use of RFTA in lung cancer patients has an immunomodulatory activity: it induces a self-limiting systemic inflammation early and later a reduction of circulating CD25+Foxp3+ Tregs. In addition to tumor ablation, downmodulation of this regulatory subset might be an important mechanism involved in the long-term clinical efficacy of RFTA.
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Ablación por Catéter/métodos , Mediadores de Inflamación/sangre , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/cirugía , Linfocitos T Reguladores/citología , Proteínas de Fase Aguda/análisis , Anciano de 80 o más Años , Animales , Proteínas Sanguíneas/análisis , Proliferación Celular , Citocinas/sangre , Regulación hacia Abajo , Electroforesis en Gel Bidimensional , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/sangre , Humanos , Subunidad alfa del Receptor de Interleucina-2/sangre , Neoplasias Pulmonares/patología , Recuento de Linfocitos , Subgrupos Linfocitarios/citología , Subgrupos Linfocitarios/metabolismo , Masculino , Persona de Mediana Edad , Linfocitos T Reguladores/metabolismo , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the rate of return to work after transplantation and its determinants in a clinically-stable population of patients transplanted and followed-up at a single institution in Italy. METHODS: 151 thoracic organ transplant recipients (72 lung, 79 heart) were examined. Patients were asked about daily activities, level of education, employment and clinical condition. A six-minute walking test was performed with measurement of dyspnoea using the Borg scale. Quality of Life was evaluated with the SF-36 and GHQ questionnaires. RESULTS: Before transplantation 131 patients (87%), (70 heart and 61 lung) worked. After transplantation, 51 patients (39%) went back to work and 3 more started working. We found that younger age, a better quality of life (mainly in the mental domain), having had an occupation previously (particularly as an entrepreneur/freelancer), and having been off work for less than 24 months, were independent predictors of return to work. CONCLUSIONS: Considering their good, objective and subjective, functional status, some patients who could have returned to work, chose not to. Identifying factors which affect return to work might help health professionals to adopt the best course of treatment and psychological support in order to fulfil this goal; however, return to work should not be considered as the only expression of a patient's real psychophysical condition.
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Empleo/estadística & datos numéricos , Trasplante de Corazón , Trasplante de Pulmón , Prueba de Esfuerzo , Femenino , Trasplante de Corazón/psicología , Humanos , Modelos Logísticos , Trasplante de Pulmón/psicología , Masculino , Persona de Mediana Edad , Calidad de Vida , Recuperación de la Función , Perfil de Impacto de Enfermedad , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: We conducted a prospective study to compare sonography, color Doppler sonography, and contrast-enhanced sonography for the detection and characterization of portal and hepatic vein thrombosis complicating hepatic malignancies. SUBJECTS AND METHODS: Three hundred sixteen patients with biopsy-proved hepatic tumors were studied at baseline and 3 months later with sonography, color Doppler sonography, and contrast-enhanced sonography. Thrombosis was defined as the presence of intraluminal echogenic material at sonography, absence of intraluminal color signals at color Doppler sonography, and presence of nonenhancing intraluminal area at contrast-enhanced sonography. Thrombi were considered malignant if they displayed continuity with tumor tissue at sonography, intrathrombus color signals at color Doppler sonography, and enhancing signals at contrast-enhanced sonography, both having arterial waveforms at Doppler spectral examination. Definitive diagnoses were obtained by sonographically guided biopsy except for thrombi displaying at conventional sonography unequivocal continuity with tumor tissue. RESULTS: Thrombosis was detected in 79 (25.0%) of 316 patients at baseline and in 83 (26.3%) of 316 patients after 3 months. Eighty-one (97.6%) of the 83 thrombi were malignant. Definitive diagnosis was performed by imaging in 60 (72.3%) of the 83 cases and by biopsy in 23 cases (27.7%). For thrombus detection, contrast-enhanced sonography displayed significantly higher sensitivity than color Doppler sonography (p = 0.004) and borderline superiority over sonography (p = 0.058). For thrombus characterization, contrast-enhanced sonography was significantly more sensitive than color Doppler sonography (p < 0.0005) and conventional sonography (p = 0.02). CONCLUSION: Contrast-enhanced sonography is superior to sonography and color Doppler sonography for the detection and characterization of portal and hepatic vein thrombosis complicating hepatic malignancies.
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Venas Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/complicaciones , Vena Porta/diagnóstico por imagen , Ultrasonografía Doppler en Color , Trombosis de la Vena/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosfolípidos , Estudios Prospectivos , Hexafluoruro de Azufre , Trombosis de la Vena/etiologíaRESUMEN
BACKGROUND: Bronchiolitis obliterans syndrome is the main long-term complication of lung transplantation that limits survival of lung transplant patients. Its pathophysiologic mechanisms are still poorly understood but it seems to result from a chronic immunologic/inflammatory insult leading to excessive fibroproliferation. The aim of this longitudinal study of 44 lung recipients was to determine whether a number of bronchoalveolar lavage and clinical variables are associated with a higher risk of developing bronchiolitis obliterans syndrome. METHODS: Bronchoalveolar lavage studies involved assessment of several cytokines including: interleukin-8, monocyte chemoattractant protein-1, regulated-upon-activation normal T cell expressed and secreted (RANTES), gamma-interferon, interleukin-12, interleukin-10 and transforming growth factor-beta. RESULTS: The predictivity of bronchoalveolar lavage (BAL) features with respect to onset of bronchiolitis obliterans syndrome was assessed by the Cox regression model. Among clinical variables, bacterial and viral infections were found to significantly predict occurrence of bronchiolitis obliterans syndrome (hazard ratio [HR] for bacterial infection: 13.044, 95% confidence interval [CI] 1.34 to 126.69, p = 0.027; HR for viral infections: 4.88, 95% CI 1.004 to 22.87, p = 0.05). Among BAL variables, only IL-12 was significantly predictive of bronchiolitis obliterans syndrome (HR 0.956, 95% CI 0.901 to 1.01, p = 0.03). In addition, in a sub-group cross-sectional analysis, bronchiolitis obliterans syndrome patients were compared with clinically stable patients, and significant increases in median levels of interleukin-8 and monocyte chemoattractant protein-1 BAL fluid were detected. CONCLUSIONS: These findings support the contention that interleukin-12 plays a role in the modulation of the local pro-/anti-fibrotic balance of allograft airways.
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Bronquiolitis Obliterante/inmunología , Líquido del Lavado Bronquioalveolar/inmunología , Interleucina-12/inmunología , Trasplante de Pulmón/inmunología , Adulto , Infecciones Bacterianas/diagnóstico , Estudios de Cohortes , Femenino , Rechazo de Injerto , Humanos , Interleucina-12/fisiología , Estudios Longitudinales , Masculino , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Virosis/diagnósticoRESUMEN
BACKGROUND: The subset of CD4+CD25+ regulatory T cells, recently identified in humans, may play a central role in the regulation of immune tolerance to graft survival. METHODS: This study assesses the frequency and functional profile of CD4+CD25+CD69- cells in the peripheral blood of lung transplant recipients (>3 years from transplantation), 10 of whom were in a stable clinical condition and 11 of whom demonstrated chronic rejection (bronchiolitis obliterans syndrome). We also studied a group of seven healthy subjects. RESULTS: The frequency of CD4+ T cells expressing CD25 (CD4+CD25+) and the highest levels (CD25) were lower in patients with bronchiolitis obliterans syndrome compared with healthy subjects and subjects in a stable clinical condition (P < or = 0.01). Purified CD4+CD25+ cells exhibited a regulatory functional profile in vitro: they were hyporesponsive, suppressed the proliferation of CD4+CD25- cells, and produced interleukin-10. CONCLUSION: These results provide in vivo evidence that peripheral CD4+CD25+ T cells may represent an important regulatory subset in lung transplantation.
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Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Trasplante de Pulmón/inmunología , Adulto , Anciano , Bronquiolitis Obliterante/inmunología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/química , Femenino , Rechazo de Injerto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Receptores de Interleucina-2/análisis , Resultado del TratamientoRESUMEN
BACKGROUND: QuantiFeron-TB (QIFN) is a whole-blood interferon-;gamma assay for the recognition of cell-mediated immune response to Mycobacterium tuberculosis infection. OBJECTIVES: To compare the QIFN assay with the tuberculin skin test (TST) in patients with newly diagnosed culture-proven tuberculosis (TB) and healthy volunteers with high or low risk of latent M tuberculosis infection and to identify factors associated with discordance between tests. METHOD: Two-hundred fifty-eight subjects underwent both assays. All participants completed a detailed questionnaire, and data from TB patients' medical records were collected. RESULTS: In the entire study population, agreement between tests was moderate and the correlation between the magnitude of QIFN response and the TST induration diameter was significant. In volunteers with no known risk of exposure to M tuberculosis, the specificity of the assays was comparable. However, in subjects with active TB or those vaccinated with bacille Calmette-Guérin, the QIFN assay detected more reactors than did the TST. In these individuals, agreement between assays was poor and no correlation or only a weak correlation was found between the diameter of TST induration and the magnitude of the interferon-gamma responses. CONCLUSIONS: The sensitivity of the QIFN assay is greater than that of the TST in patients with active TB before the initiation of anti-TB chemotherapy, but its specificity is influenced more by bacille Calmette-Guérin vaccination. The QIFN assay may provide an improvement over the current practice of the use of the TST to support diagnosis of active M tuberculosis infection in the clinic; however, QIFN cannot be considered an adequate replacement for the TST in the screening for latent infection.
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Portador Sano , Interferón gamma/sangre , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Pulmonar/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infecciones por Mycobacterium/sangre , Infecciones por Mycobacterium/diagnóstico , Probabilidad , Valores de Referencia , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Prueba de Tuberculina , Tuberculosis Pulmonar/sangreRESUMEN
BACKGROUND: The aim of our study was to compare clinical and BAL features of patients with bronchiolitis obliterans organizing pneumonia (BOOP) with those of patients with usual interstitial pneumonia (UIP) and control subjects. PATIENTS AND METHODS: This study reports on 14 patients with idiopathic BOOP. Diagnosis was made upon histology. Lung function tests were mostly normal. Chest X-ray and CT showed always a patchy consolidation, often associated with ground glass pattern. BAL was performed for cytology and for ELISA assessment of several cytokines (IL8, ILI0, IL12, gamma-interferon, IL 18, monocyte chemoattractant protein- 1). RESULTS: Cytology of BAL in BOOP showed a pattern of lymphocytic alveolitis (Lymphocytes: 0.36 x 10(6)/ml) associated with an increase in neutrophil and eosinophil counts (0.13 and 0.04 x 10(6)/ml respectively). Mean BALf levels in pg/ml of MCP-1, IL12 and IL18 were significantly increased in BOOP with respect to controls and UIP patients, while in UIP patients only a significant increase of IL8, MCP-1 and IL18 with respect to controls was detected. In addition, BALf levels of IL10, an anti-inflammatory cytokine, were significantly higher in BOOP patients with respect to controls and UIP patients. CONCLUSION: These findings are consistent with a marked degree of macrophage and lymphocyte activation in BOOP with an expansion of T helper-1 response. The concomitant increase of IL10 could be related to a limitation of the inflammatory process and the fibrotic evolution typical of this clinical picture.
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Líquido del Lavado Bronquioalveolar/química , Neumonía en Organización Criptogénica/inmunología , Citocinas/análisis , Enfermedades Pulmonares Intersticiales/inmunología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Estudios de Casos y Controles , Quimiocina CCL2/análisis , Neumonía en Organización Criptogénica/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interferón gamma/análisis , Interleucinas/análisis , Enfermedades Pulmonares Intersticiales/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Encouraging results in transplantation of other solid organs led to investigation of the use of tacrolimus in lung transplantation as a salvage immunosuppressant in persistent acute rejection. METHODS: The incidence and severity of acute rejection and the number of steroid pulses were analyzed in 20 lung recipients who were converted from a cyclosporine- to a tacrolimus-based immunosuppressive regimen because of refractory biopsy-proven acute rejection. RESULTS: Tacrolimus was started 12.0 +/- 13.0 months after transplantation, and the mean follow-up was 25.0 +/- 13.7 months. After shifting to tacrolimus, a significant decline was observed in both the number of acute rejections per patient (3.0 +/- 1.56 to 0.85 +/- 1.14, p < 0.0001), and the incidence of acute rejection per 100 patient-days (1.52 +/- 0.99 to 0.14 +/- 0.21, p < 0.0001). Furthermore, the average histologic grade of rejection decreased from 1.9 +/- 0.8 to 0.4 +/- 0.5 (p < 0.0001). Methylprednisolone pulses similarly decreased from 1.9 +/- 1.3/patient to 0.3 +/- 0.7/patient (p < 0.0001). During cyclosporine immunosuppression, the mean forced expiratory volume in 1 second decreased to 84.4% +/- 13.3% of individual best value. The average lung function parameters were stable 3 months after the change of medication, and then began to improve. After an average follow-up of 36.5 +/- 19.2 months, 2 patients have developed bronchiolitis obliterans syndrome (one has Stage 1 and one has Stage 3). CONCLUSION: Conversion to a tacrolimus-based immunosuppressive regimen for refractory acute lung rejection is associated with reduced incidence and severity of acute rejection episodes, steroid sparing, and stabilization or improvement of pulmonary function.