Complement system in lung transplantation.

The complement system is a cascade of multiple proteins that have been known to mediate inflammatory response. This tightly regulated system has been recognized to play a role in adaptive immunity via humoral and cell-mediated processes. There is evidence from animal and human studies that the complement system is involved in various outcomes of solid organ transplantation. Most of the studies have been done in the field of kidney transplantation. In this paper, we review the studies looking at lung transplantation. The complement cascade appears to have a prominent role in mediating lung allograft damage in the setting of ischemia-reperfusion injury, humoral rejection, as well as chronic allograft dysfunction. In this review, we look at the available data regarding the role of complement in these outcomes and propose some ideas about future direction of research in this field.

Inadequate (Ax) Transbronchial Lung Transplant Biopsies-Scope and the Potential Contributing Factors.

BACKGROUND: Transbronchial biopsy is the cornerstone for the evaluation of graft function after lung transplant and a standard of care to diagnose acute cellular rejection. However, the yield from these biopsies is variable, with about 15% to 50% of samples being judged as nondiagnostic, leading to additional procedures. The factors contributing to the nondiagnostic sampling have not been delineated, and the discordance in sample assessment between the bronchoscopist and pathologist has not been quantified. METHODS: A retrospective cohort of patients who had bronchoscopies with biopsies for surveillance and graft assessment at a large-volume transplant center was studied. The occurrence of nondiagnostic alveolar sampling was assessed, and the patient demographics and procedural characteristics were compared with the diagnostic group. RESULTS: We included 128 patients in our study and found the inadequacy rate for alveolar tissue sampling to be 15.5%. The median number of passes made by the bronchoscopist was 9, and the number of samples assessed by the bronchoscopist was 8, with a median of 6 adequate samples identified by the pathologist. The frequency of previous biopsies, history of prior inadequate samples, need for a higher number of pass attempts, presence of airway abnormalities, and the use of general anesthesia increased the odds of inadequate sampling. CONCLUSIONS: Patients with the identified factors may be at risk of inadequate sampling on transbronchial biopsies. The bronchoscopist could consider getting additional samples to avoid a nondiagnostic alveolar sample. Further multicenter studies would help to elucidate other contributing factors.

Impact of Tacrolimus Trough Variability on Acute Rejection Following Lung Transplantation.

BACKGROUND: Acute rejection is a risk factor for the development of chronic lung allograft dysfunction, the leading cause of morbidity and mortality in lung transplant recipients. Calcineurin inhibitors are the cornerstone of immunosuppression regimens after lung transplantation. METHODS: We retrospectively evaluated the association of tacrolimus level variability with total acute rejection score at 12 months post-transplant. Secondary outcomes included the development of chronic lung allograft dysfunction and antibody-mediated rejection at 24months post-transplant. There were 229 lung transplant recipients included. RESULTS: The mean (standard deviation) total rejection score of the cohort was 1.6 (1.7). Patients with high tacrolimus variability at 0 to 3, 3 to 6, and 6 to 12 months on average scored 0.18 (mean 1.6 vs 1.5; 95% CI): -0.3 to 0.66, P =.46), 0.14 (mean 1.7 vs 1.5; 95% CI: -0.32 to 0.6, P = .55), and 0.12 (mean 1.6 vs 1.5; 95% CI: -0.34 to 0.58, P = .62) point higher in 12-month total acute rejection scores, respectively; however, these differences were not statistically significant. The incidences of chronic lung allograft dysfunction and antibody-mediated rejection were numerically greater in the high variability group throughout certain periods; however, this was not consistent throughout all study timeframes and statistical significance was not evaluated. CONCLUSIONS: High tacrolimus variability was not associated with increased 12-month total acute rejection score. Further studies are needed to assess long-term outcomes with tacrolimus level variability.