Abstract and Introduction
Abstract
Chronic lung allograft dysfunction (CLAD) is the leading cause of mortality following lung transplantation. We conducted a retrospective cohort study including 397 bilateral lung recipients transplanted in from 1996 to 2009 to determine the association between ambient air pollution, CLAD and mortality. Pollution exposure was assessed using satellite-based estimates of nitrogen dioxide, distance to major roadway and total length of roadways around a patient's home. Cumulative exposures to ozone and particulate matter were estimated from concentrations measured at fixed-site stations near patients' homes using inverse distance weighted interpolation. Cox proportional hazards models were used to estimate the associations of CLAD with air pollution exposure, adjusting for various individual and neighborhood characteristics. During the follow-up, 185 patients developed CLAD (47%) and 101 patients died (25%). Fifty-four deaths (53%) were due to CLAD. We observed an association between CLAD development and road density within 200 m of a patient's home (HR 1.30 [95% CI 1.07–1.58]). Although based on a subgroup of 14 patients, living within 100 m of a highway was associated with a high risk for developing CLAD (HR 4.91 [95% CI 2.22, 10.87]). These data suggest that exposure to traffic-related air pollution is associated with development of CLAD among lung transplant recipients.
Introduction
Chronic lung allograft dysfunction (CLAD) is the leading cause of graft failure and mortality for transplant recipients, accounting for the poor median survival of lung transplant recipients of 5.6 years. CLAD is defined as a sustained loss of forced expiratory volume in 1 s (FEV1) of greater than 20% from baseline in the absence of identifiable etiologies, such as infection, acute rejection or anastomotic complications. Beyond the first year posttransplant, CLAD accounts for over 25% of recipient deaths. The incidence of CLAD approaches 50% within 5 years of lung transplantation, and once diagnosed, median survival is only 3 years.
CLAD is postulated to be the end result of multiple alloimmune and nonalloimmune factors that lead to chronic inflammation and lung injury, including primary graft dysfunction, alloantibodies, acute rejection, infections and gastroesophageal reflux. It is plausible that repeated airway injury from exposure to traffic-associated air pollution could contribute to the development of CLAD.
Several studies have shown associations between chronic exposure to traffic-related air pollution (TRAP) and increased risk of mortality from cardiovascular disease, and the incidence and exacerbations of asthma and chronic obstructive pulmonary disease (COPD) in Canadian cities. Chronic exposure to TRAP has been implicated in impairing lung development in children.
In a cohort study of lung transplant recipients in Belgium, living close to a major roadway, a marker for TRAP exposure, was associated with the development of CLAD and an increased risk of mortality. Identification of a relationship between TRAP and outcomes following transplantation in a geographically distinct cohort of lung transplant recipients would further support the validity of this proposed association, thus allowing for further study into underlying mechanisms toward potential interventions for decreasing allograft dysfunction and mortality. To address this question, we performed a retrospective cohort study of 397 patients who underwent bilateral transplantation in the Toronto Lung Transplant Program.