Lung donor smoking linked to primary graft dysfunction risk, not mortality
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Key takeaways:
- In contrast to past studies, mortality did not rise among recipients with a lung from a donor with smoke exposure.
- An elevated primary graft dysfunction risk was seen across three definitions of smoke exposure.
Following transplantation, recipients with a lung from a donor who had tobacco smoke exposure did not have higher mortality, according to results published in American Journal of Respiratory and Critical Care Medicine.
However, these recipients did face a heightened risk for primary graft dysfunction (PGD), according to researchers.
“Although the impact of increased PGD risk on perioperative resource use should not be minimized, the ability to increase the donor pool without impacting survival has the potential to markedly improve options for the population of patients with advanced lung disease currently waiting for lung transplantation,” Joshua M. Diamond, MD, MSCE, associate medical director of the Penn Lung Transplant Program and associate professor of medicine at the Hospital of the University of Pennsylvania, and colleagues wrote.
Using data from the 2012 to 2018 Lung Transplant Outcomes Group cohort study, Diamond and colleagues analyzed lung transplant recipients in a multicenter prospective cohort study to determine how donor smoke exposure impacts the risk for PGD and mortality.
Researchers used three different definitions/measurements to identify active donor smoking: urinary nicotine cotinine (n = 527), urinary tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; n = 510) and clinical history/documentation (n = 470; mean age, 56.1 years; 40.4% women).
Of these populations, the highest prevalence of current donor smoking was found in measures of urinary cotinine of 9 ng/mL or more (43%), followed by clinical data (37%), urinary cotinine of 30 ng/mL or more (34%) and urinary NNAL (28%).
This study included 155 transplant recipients with a lung from a donor who met all the above smoking definitions and 152 recipients with a lung from a donor who met none of the definitions.
Based on the definition of donor smoking used, the risk for PGD varied during logistic regression analysis; however, all definitions raised the risk for this injury.
The highest risk for PGD was observed when active donor smoking was defined by urinary cotinine of at least 9 ng/mL (absolute risk difference, 11.5%; 95% CI, 3.8%-19.2%), followed by urinary cotinine of at least 30 ng/mL (absolute risk difference, 11.2%; 95% CI, 3.1%-19.2%), clinical data (absolute risk difference, 6.5%; 95% CI, –2.8% to 15.8%) and urinary NNAL (absolute risk difference, 5.7%; 95% CI, –3.4% to 14.9%).
Researchers noted a nonsignificant link between PGD risk and urinary NNAL, as well as between PGD risk and clinical data.
Across the urinary smoking definitions/measurements, passive donor smoking also elevated the absolute risk for PGD. The greatest risk was found when passive donor smoking was defined by urinary cotinine of at least 9 ng/mL (absolute risk difference, 15.3%; 95% CI, 0.9%-29.7%), followed by urinary cotinine of at least 30 ng/mL (absolute risk difference, 14.1%; 95% CI, 3.2%-24.9%) and urinary NNAL (absolute risk difference, 5%; 95% CI, –3.5% to 13.7%). The relationship between PGD risk and urinary NNAL was again not significant, according to researchers.
During survival analysis, researchers found that none of the donor smoking definitions heightened 1-year or 3-year mortality among transplant recipients with any donor smoke exposure vs. no donor smoke exposure.
This finding remained true in a sensitivity analysis including only the recipients with a lung from a donor who met all three smoking definitions.
“The transplant community has the potential to mitigate waitlist death with augmented access to organs currently considered extended-criteria or poor quality solely because of donor smoking history,” Diamond and colleagues wrote.
“Furthermore, globally improving measurements of donor risk are needed to further safely increase the potential lung donor pool, assist with potential donor-recipient matching and improve the current methods for considering organ acceptance at the time of allograft offer,” Diamond and colleagues continued.
Perspective
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Lung transplantation prolongs survival and quality of life for patients with severe end-stage lung diseases such as cystic fibrosis, COPD, idiopathic pulmonary fibrosis and pulmonary hypertension. Similar to other organ transplantation programs, there is a relative shortage of donor lungs available to meet the needs of patients who are eligible for transplantation. Extensive research and innovation are addressing this organ shortage by developing strategies to better preserve donor organs for transplantation and, thus, to potentially increase the donor pool by adding donor lungs that previously might not have been considered suitable for transplantation.
Prior research had indicated that donor lungs from smokers were associated with an increased risk of severe acute lung injury (also known as PGD) in recipients after lung transplantation. Other research had shown that this form of acute lung injury was associated with an increased risk of mortality in lung transplant recipients. Thus, there has been considerable debate as to whether donor smoking status should be used to remove lungs from smokers from the donor pool.
In this study, Diamond and colleagues performed a detailed analysis of risks associated with donor lung smoking status using clinical data acquired from a registry of 470 lung transplant patients. Similar to previously reported studies, there was an increased risk of PGD in patients who received a donor lung from a smoker, albeit the association was weaker than in prior reports. Most importantly, the study showed no risk of increased mortality in lung transplant patients who received a lung from a smoker compared with a nonsmoker. This finding was robust as it was consistent regardless of the method used to ascertain smoking status.
These results are helpful and are not surprising. They suggest that lung transplant care has evolved, such that even if patients develop PGD as a result of receiving a donor lung from a smoker, their overall mortality risk is unchanged. They are impactful because they support the practice of considering donor lungs regardless of donor smoking status. This should help to maintain the pool of available donor lungs. Hopefully, recently developed approaches to improve donor lung viability will further increase the donor pool so that the outcomes for patients with severe end-stage lung disease will improve going forward.
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