Background: Reactive oxygen species (ROS) may contribute to airway injury a
nd the development of the bronchiolitis obliterans syndrome (BOS) following
lung transplantation (LT). Chemically active iron released from ferritin s
tores and nitric oxide (NO)-derived radicals may add to the oxidative burde
n.
Methods: We determined the concentrations of ferritin and the aqueous NO de
rivative nitrite (NO2-) within bronchoalveolar lavage fluid (BALF) of 14 st
able LT recipients (ST) and 7 subjects with BOS and 21 normal controls. We
also assessed the relationship between BALF ferritin and hemosiderin-laden
macrophages (HLMs) using a hemosiderin score (HS) and determined BALF album
in concentration as a marker of microvascular leakage.
Results: BALF ferritin concentrations and HSs were significantly elevated i
n LT recipients overall compared with normal controls (p < 0.05). BALF NO2-
levels were elevated in BOS subjects and STs compared with normal controls
(p = 0.002 and p 0.09, respectively), but there was no difference between
transplant groups. BALF albumin concentrations were elevated in BOS patient
s compared with normal controls (p = 0.02) and ST (p = 0.05), but there was
no difference between STs and controls. There was a significant relationsh
ip between BALF ferritin concentration and HS in LT recipients overall (r((
s)) = 0.7, p < 0.001). In BOS subjects, but not ST, BALF ferritin was signi
ficantly related to BALF albumin (r((s)) = 0.8, p = 0.05) and there was a w
eak relationship with NO2- concentration (r((s)) = 0.6, p = 0.1). BALF NO2-
was strongly related to BAL %neutrophils in BOS subjects (r((s)) = 0.9, p
< 0.01), but there was no such relationship in STs.
Conclusions: Our findings suggest that the allograft could be subject to si
gnificant iron-generated oxidative stress, which may be exacerbated by NO a
nd neutrophil-derived ROS, particularly in BOS. Microvascular leakage may b
e a feature of established chronic rejection, which potentiates the iron ov
erload and contributes to further airway damage and remodeling.