[en] Lung transplant is the last therapeutic option in some terminal pulmonary diseases. It is known that lung transplant may have several complications, being one of the most frequent the lung rejection. An early diagnosis and treatment of this complication have an important impact in its evolution. Due to the importance of the early diagnosis of lung rejection, new techniques such as the transbronchial cryobiopsy have been developed in the last years. Transbronchial cryobiopsy has demonstrated to be superior in terms of performance than transbronchial forceps biopsy. Therefore, this thesis aims to investigate the possible role of transbronchial cryobiopsy in the diagnostic algorithm of complications after lung transplant. The main interests of this thesis were evaluated, through two prospective studies and a randomized clinical trial, 1) the minimum necessary transbronchial cryobiopsies to accomplish a high diagnostic performance; 2) the radiological characteristics and evolution of new opacities in chest CT after performing transbronchial cryobiopsies; 3) the diagnostic effectiveness and safety of transbronchial cryobiopsies in critically ill patients intubated in the Intensive Care Unit (ICU). In the first study of this thesis three hundred and twenty-one consecutively transbronchial cryobiopsies were performed in 206 patients and at least 6 samples were obtained per procedure. Results showed that obtaining at least 4 samples per procedure improves the histological diagnostic accuracy (p < 0.001) without increasing significantly severe complications. Moreover, our study demonstrated that being unilateral lung transplant recipient (odds ratio, 0.10; CI of 95%, 0.02-0.30; p<0.001) or presenting arterial hypertension during the procedure (odds ratio, 0.31; CI of 95%, 0.12-0.86; p=0.019) seem to be risk factors associated with increased bleeding during the bronchoscopy. In the second study, fifty-one patients were consecutively recruited and only 22 were included. Previously to transbronchial cryobiopsies a chest CT was performed, as well as after 1, 4 and 8 weeks from the procedure. Out of the 22 patients included, 20 (91%) presented 46 opacities larger than 10mm in the post procedure chest CT. These new opacities were defined as either ground glass opacities, solid or cavitated lesions or a combination of both. The ground glass opacities disappeared after four weeks from the procedure and only one cavitated lesion persisted after 6 months from the transbronchial cryobiopsy. Therefore, our study concludes that a pre and post procedure chest CT should be performed when available. Finally, the third study evaluated the diagnostic effectiveness and safety of transbronchial cryobiopsy in critically ill intubated patients from the ICU. Patients were randomly selected in order to carry out either a transbronchial biopsy with biopsy forceps, or cryoprobe of 1.9mm or cryoprobe of 2.4 mm. A total of 89 procedures were performed, showing that using a cryoprobe of 2.4 mm had a superior diagnostic effectiveness when compared to cryoprobe of 1.9 mm (p=0.02) and biopsy forceps (p<0.001). No bleeding events or severe complications were observed.

[es] El trasplante pulmonar es la última opción terapéutica en algunas patologías pulmonares terminales. El rechazo es una de las complicaciones más frecuentes; su diagnóstico y tratamiento precoz marcan la evolución del mismo. La criobiopsia transbronquial es una técnica novedosa que parece mostrar un mayor rendimiento que la biopsia transbronquial con fórceps que es hasta ahora la técnica utilizada de manera rutinaria. Esta tesis aborda aspectos no investigados de la criobiopsia que permitan determinar su papel en el algoritmo diagnóstico de la afectación pulmonar en pacientes con trasplante pulmonar. En concreto la tesis evalúa mediante dos estudios prospectivos y un ensayo clínico randomizado: el número mínimo de criobiopsias transbronquiales que garanticen un rendimiento diagnóstico elevado; determinar y establecer las características radiológicas y evolución de posibles nuevas opacidades en el TC de tórax tras la realización de criobiopsias transbronquiales; y valorar la rentabilidad diagnóstica y seguridad de la criobiopsia transbronquial en pacientes críticos intubados en una Unidad de Cuidados Intensivos. En el primer estudio, tras realizar 321 criobiopsias transbronquiales consecutivas en 206 pacientes y con un máximo de 6 especímenes obtenidos por procedimiento, se pudo establecer que la obtención de al menos 4 muestras aumenta la certeza diagnóstica histológica (p < 0,001) sin aumentar de manera significativa complicaciones graves. Ser receptor de un trasplante pulmonar unilateral (odds ratio, 0,10; intervalo de confianza del 95 %, 0,02-0,30; P < 0,001) o tener hipertensión arterial durante la broncoscopia (odds ratio, 0,31; intervalo de confianza del 95%, 0,12-0,86; P = 0 ,019) parecen ser factores de riesgo asociados al aumento del sangrado. En el segundo estudio, en 22 de 51 pacientes consecutivos se observaron 46 opacidades nuevas > 10 mm, incluidas lesiones en vidrio esmerilado, sólidas, cavitadas o una combinación de estas lesiones en 20 (91%) pacientes en la TC posterior a la criobiopsia. Todas las opacidades en vidrio esmerilado desaparecieron a las 4 semanas. A los 6 meses persistió una única opacidad cavitada. Se recomiendan estudios de TC antes de implementar la criobiopsia transbronquial, siempre que sea posible. En el tercer estudio (prospectivo, aleatorizado y comparativo); en pacientes críticos ventilados mecánicamente en UCI se evaluó el rendimiento diagnóstico, la calidad histológica y la seguridad de la biopsia pulmonar transbronquial utilizando pinzas de biopsia, criosonda de 1,9 mm o de 2,4 mm en 89 procedimientos consecutivos. El rendimiento diagnóstico con criosonda de 2,4 mm (100 %) fueron superior a las de 1,9 mm (p=0,02) y a las de fórceps (p<0,01) y no ocurrieron eventos de sangrado u otras complicaciones graves.