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\begin{document}

\title{Long-term survival: Achilles heel of lung transplantation}



\author[1]{Suresh Manickavel}%
\author[1]{Matthias Loebe}%
\affil[1]{University of Miami School of Medicine}%


\vspace{-1em}



  
  \date{May 22, 2024}


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\begin{abstract}
long-term survival after lung transplantation has increased over recent
years, but still fall short of providing extensive life expectancy for
more than 10 years.%
\end{abstract}%



\sloppy


Long-term survival: Achilles heel of lung transplantation

Suresh Manikavel, Matthias Loebe

Keywords: lung transplant, long-term outcomes, chronic rejection

Lung transplantation is a well-established procedure for patients with
end-stage lung disease. It improves survival and quality of life of
transplant recipients. Still the intervention remains, in some sense,
sort of exchanging one disease with another less morbid disease because
of the potential undesirable consequences that comes with it. Most
importantly the long-term survival following lung transplantation is
considerably low compared to an otherwise healthy age matched
individual. Patients who identified as a potential candidate for this
procedure usually have an expected median survival of less than two
years due to advanced and progressive lung disease and respiratory
failure. Median survival after lung transplantation is about 6 years.
Recipients typically obtain a significant improvement in the quality of
life due to improvement in respiratory function, elimination of oxygen
requirement and alleviation of dyspnea. After a period of recovery
post-procedure, recipients have a high probability of returning to
normal functional capacity. The intensity of post-transplant clinical,
laboratory, and radiographic surveillance and adverse effects of
transplant medications could contribute to some impairment in quality of
life. However, the most striking aspect is the lack of robust long-term
survival benefit with lung transplantation.

In this issue of the journal, Iguidbashian and coworkers quantified this
glaring deficiency by comparing the 10-year survival of lung transplant
recipients with matched controls from general population. There is a
53\% absolute difference in the 10-year-survival between the 2 groups.
Transplant recipients in the study cohort have a 10-year survival rate
of 28\%. Globally, lung transplant survival demonstrates a clear `era
effect' phenomenon characterized by a gradual improvement in the
immediate and long-term survival over the years{[}1{]}. Most striking
progress has been noted in the one-year survival. In 1990, the reported
one-year survival was as low as 45\%, whereas it is around 90\% in
recent cohorts{[}2{]}. Typically, the risk of death is highest in the
first year after surgery due to complications associated with surgery
and infection. However, with progressive improvement in surgical
techniques, pre-operative recipient optimization, and advancements in
the critical care, the immediate survival has improved drastically.

These improvements are also reflected in improved long-term survival in
recent years. Fakhro and coworkers have reported a 30\% 20-year survival
in their cohort {[}3{]}. The study cohort presented here by Iguidbashian
and coworkers includes patients between 1990-2007, which is a major
limitation that needs to be taken into consideration while interpreting
the findings. Hopefully, long-term survival will continue to increase as
progress in lung transplantation is made.

Chronic lung allograft dysfunction is the most common cause of death
among transplant recipients{[}4{]}. Mechanistic underpinnings of CLAD
pathogenesis are still unclear, and it has majorly been a deterministic
process once it begins. Malignancy and infection are two other major
causes of death in transplant recipients. To successfully conduct lung
transplant surgeries and deliver optimal follow up care, it requires an
organization of things including trained specialists, robust protocols,
and personalized care before and after surgery. Diligent preventive care
can avert premature death or complications related to rejection,
infection and malignancy. Analysis of survival data from registry could
muddle the picture and present a less than optimal outcomes. Data from
robust single-center experience could more accurately reflect the
expected survival of lung transplant recipients.

Lung transplantation greatly improves quality of life. It's effect on
longevity continues to be limited. This needs to be addressed when
presenting the option of transplant to patients and their families who
have to deal with advanced lung failure. This therapy can in some cases
provide long-term success, but we have to discuss openly the fact, that
in most patients, life expectancy after transplant will be less than 10
years. This becomes particularly important when one looks at pediatric
lung transplantation: here the benefits that the procedure can offer are
clearly limited, chances of reaching adulthood and finishing school
continue to be rather small. Families need to understand that before
they make the commitment to dedicate emotional and financial resources
to save their sick child. Very difficult and complex discussions cannot
be avoided and will put significant stress on patients, families, and
health care providers.

At the same time, while we acknowledge the present limitations of lung
transplantation, we have to keep working hard to improve outcomes and
understand the mechanisms leading to graft loss in the mid- and long
term. Why do some patients live several decades with the transplanted
lungs? Why do they seem to develop significant degrees of tolerance to
the new organ?

Iguidbashian and coworkers remind us how much progress has been made.
Their paper also reminds us how much more work has to be done to make
lung transplantation a truly long-lasting solution for patients with
advanced lung disease.

{[}1{]} D. C. Chambers \emph{et al.} , ``The International Thoracic
Organ Transplant Registry of the International Society for Heart and
Lung Transplantation: Thirty-fifth adult lung and heart-lung transplant
report---2018; Focus theme: Multiorgan Transplantation,'' \emph{J. Hear.
Lung Transplant.} , 2018, doi: 10.1016/j.healun.2018.07.020.

{[}2{]} R. F. Grossman \emph{et al.} , ``Results of Single-Lung
Transplantation for Bilateral Pulmonary Fibrosis,'' \emph{N. Engl. J.
Med.} , 1990, doi: 10.1056/nejm199003153221104.

{[}3{]} M. Fakhro \emph{et al.} , ``25-year follow-up after lung
transplantation at Lund University Hospital in Sweden: Superior results
obtained for patients with cystic fibrosis,'' \emph{Interact.
Cardiovasc. Thorac. Surg.} , 2016, doi: 10.1093/icvts/ivw078.

{[}4{]} A. R. Glanville \emph{et al.} , ``Chronic lung allograft
dysfunction: Definition and update of restrictive allograft syndrome--A
consensus report from the Pulmonary Council of the ISHLT,''\emph{Journal
of Heart and Lung Transplantation} . 2019, doi:
10.1016/j.healun.2019.03.008.

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