Histological Profiles of Lung Allograft Transbronchial Biopsies and Clinical Outcomes After Lung Transplantation

SCIENTIFIC JUSTIFICATION:

With more than three million deaths per year, the chronic obstructive pulmonary disease is currently the third cause of mortality worldwide , and contributes to the growing number of individuals with end-stage lung disease, which is now a major issue for world public health. Overall, for individuals with end-stage lung disease, lung transplantation (LTx) is the only treatment able to increase patient survival and quality of life, with more than 4,500 lung transplantations performed each year.

Despite major progresses made in the last decade regarding organ preservation, procurement and short term outcome little improvements have been made on the histological characterization of rejection, which remains the main determinant of patient death after lung transplantation.

One of the main limitation of histological analysis is the multiplicity of lesions associated with graft outcome and their interpenetration. Historically, the perivascular infiltrate or cellular rejection (A lesions), and the lymphocytic bronchiolitis (B lesions) are the first histological lesions associated with graft dysfunction and stand as key parameters in patient management. In addition to A and B lesions, a wide spectrum of histological lesions of the lung allograft is associated with clinical outcomes.

However, to our best knowledge, only few studies thoroughly investigated the various elementary lesions in the broad scope of histological analysis, and their association with clinical outcomes. Although informative, those studies usually suffer from a small number of patients, convenience clinical samples from registry, and the lack of innovative statistical approach. Overall, the wide spectrum of the allograft lesions has not been investigated using a large number of transbronchial biopsies with standardized protocol and biopsy reading, and a multidimensional approach on deeply phenotyped data.