RESUMEN
Bronchiolitis obliterans syndrome (BOS) limits long-term survival of lung transplant recipients, and airflow obstruction in these patients likely originates in the small airways. 61 double lung transplant recipients performed multiple breath nitrogen washouts to obtain indices of acinar and conductive ventilation heterogeneity (Sacin, Scond). There was a significant association of BOS status with Sacin (Kruskal-Wallis; p<0.001) but not with Scond (p=0.1). These results demonstrate that it is the structural alteration of the terminal bronchioles, generating ventilation heterogeneity at the level of the diffusion front, and not the bronchioles located more proximally, that is driving the airflow obstruction that determines BOS status.
Asunto(s)
Células Acinares/patología , Bronquiolitis Obliterante/etiología , Volumen Espiratorio Forzado/fisiología , Rechazo de Injerto/complicaciones , Trasplante de Pulmón/efectos adversos , Pulmón/fisiopatología , Bronquiolitis Obliterante/patología , Bronquiolitis Obliterante/fisiopatología , Progresión de la Enfermedad , Femenino , Rechazo de Injerto/patología , Rechazo de Injerto/fisiopatología , Humanos , Masculino , Pruebas de Función Respiratoria , Índice de Severidad de la EnfermedadRESUMEN
Because bronchial hyperresponsiveness has been linked to the bronchiolitis obliterans syndrome (BOS), we determined PD(20) methacholine (PD(20(M))), PD(15) hypertonic saline (PD(15(HS))) and their dose-response slopes (DRS(M) and DRS(HS)) in 8 single and 18 double lung transplant recipients within 1 year of lung transplantation and examined the relationship to bronchoalveolar lavage cell profiles and subsequent development of BOS. Twenty-two patients (81%) had a positive methacholine and 6 (25%) a positive hypertonic saline challenge. A positive PD(15(HS)) was associated with an increased risk for BOS at 2 years (odds ratio 12.6, 95% confidence interval 1.3-123.5, p < 0.05), and time to BOS was significantly and negatively related to DRS(HS) (r = -0.5, p < 0.05) - that is, the greater the response, the shorter the time to BOS. Interestingly, DRS(HS) correlated positively with recipient:donor total lung capacity ratio (r = 0.5, p < 0.05), but there was no relationship between either challenge result and airway inflammation. Methacholine hyperresponsiveness is common after lung transplantation but is not prognostic, whereas response to hypertonic saline may reflect recipient:donor size matching and provide useful information regarding the potential for BOS development.