Air Pollution Risky After Lung Transplant

For lung transplant recipients, exposure to higher air pollution levels was linked to an increased risk of death or graft failure, a retrospective cohort study found.

Living in a zip code exposed to elevated ambient fine particulate matter levels was associated with an increased hazard of death or graft failure, with an adjusted hazard ratio of 1.08 at the old Environmental Protection Agency standard of 12 μg/m³ and 1.07 at the new threshold of 9 μg/m³ (P=0.02 and P=0.003, respectively).

Each additional 1 μg/m³ of exposure at the zip code level raised the hazard by 1% (P=0.004), as researchers led by Olawale Amubieya, MD, PhD, of the University of California Los Angeles, reported in JAMA Network Open.

The findings are in line with others linking larger particle size air pollutants to the same risks, the researchers noted. The mechanism of the link is likely multifactorial, they speculated, “including direct injury to the lung via particle deposition and absorption, systemic inflammatory response, and immune dysregulation.”

Compared to recipients of other solid organ transplants, lung transplant recipients have shorter survival after transplant. This is partially attributed to the lung’s exposure to outside environmental factors, like infectious organisms, pollutants, smoke, and dust. Particles less than 2.5 microns in diameter (PM_2.5) can penetrate into small airways, which makes them a greater risk to health compared with larger particles.

“For most patients, relocation to regions of the world with lower ambient levels of air pollution is not feasible,” Natalia Belousova, MD, of Foch Hospital in Suresnes, France, and Chung-Wai Chow, MD, PhD, of the University Health Network in Toronto, wrote in an invited commentary.

However, they suggested that patients “may benefit at the individual level from simple interventions, such as use and regular exchange of high-efficiency particulate air filters in the home and staying indoors or wearing N95 or FFP2 [filtering facepiece respirator] masks on high air pollution days.”

Researchers used data from the United Network for Organ Sharing together with patients’ 5-digit zip code of residence at the time of transplant for all U.S. lung transplant recipients from 2005 through 2016. Patients were assigned zip code-level annual PM_2.5 exposure estimates beginning the year of transplant using previously published annual estimates based on chemical transport modeling, satellite-based measures, and ground-based measures.

The composite outcome of time to death or graft failure was adjusted for age, sex, race and ethnicity, body mass index, underlying lung disease category, single versus bilateral transplant, need for life support prior to transplant, Lung Allocation Score, type of health insurance, and medical center of transplant.

Of the 18,265 patients included in the analysis, 40.2% were female and 83.5% were white, with a mean age of around 55. Over 90% lived in the low exposure zip codes, with PM_2.5 levels below 12 μg/m³. A significantly higher proportion of Black and Hispanic or Latino transplant recipients and a lower proportion of white recipients lived in the high exposure zip codes. Per capita income in the high exposure group was higher than in the low exposure group. The most common diagnosis for transplant recipients was restrictive lung disease, followed by obstructive pulmonary disease.

Median graft survival was 4.87 years for patients in the high PM_2.5 group, and 5.84 years for those in the low PM_2.5 group.

The editorialists noted that the study examined only the baseline exposure at the time of transplant, making it “even more remarkable that an association was found between early exposure and poor outcomes when granular data, such as seasonal variation and cumulative exposure during the calendar year, were not considered.”

Limitations included the potential for misclassification error and the use of zip code to indicate residence, which can be less specific than other measures and didn’t account for those who might have had a prolonged hospitalization outside their home zip code. Estimation of longitudinal exposure was not possible, because the registry used does not capture patient relocation during follow-up.

Unmeasured confounders, like other zip code-based social determinants of health, could have also contributed to poor health outcomes, the researchers noted. Details on treatment, like chronic immunosuppression or macrolide therapy, were unavailable. The registry also didn’t capture short- or immediate-term outcomes after lung transplant like primary graft dysfunction, acute rejection, or chronic lung allograft dysfunction, which may be connected to air pollution exposure.

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