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In severe cases of idiopathic pulmonary fibrosis (IPF), lung transplantation may be offered. However, lung transplantation is a major surgery in which many complications may develop. The greatest danger is, of course, death. Therefore, it is important that we give due weight to the risk factors associated with higher frequencies of post-transplant complications, as well as mortality. Post-transplant, we need to recognize certain comorbidities that may worsen clinical outcomes. 

Researchers set out to review the current evidence for all aspects of lung transplantation, including important considerations pre- and post-transplant. They published their findings in the European Respiratory Review. We will take a closer look at some of their findings in this article. 

Risk Factors for Lung Transplantation

Current guidelines indicate that a patient should only be considered for lung transplantation if the patient’s 5-year likelihood of survival is high (over 80%). In addition, there are some absolute contraindications for lung transplantation: 

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  • Recent history of cancer 
  • Severe psychosocial issues 
  • Extrapulmonary organ dysfunction that is life-threatening in nature.

For patients who are deemed qualified for lung transplantation by their physician, it is important during presurgical counseling that patients understand that lung transplantation is a high-risk procedure that is attenuated by certain risk factors. 

Advanced age is an important risk factor for developing complications post-surgery. There is still some debate about what the cutoff age should be, given the ethical considerations around treatment equity. However, it can be safely said that patients aged 75 and above are highly unlikely to be considered candidates for lung transplantation. 

This is because studies have shown that elderly patients are at a greater risk of developing malignancies, vascular events, drug toxicities, cognitive decline, and even death. Faced with these potential complications, elderly patients are sometimes better off continuing with antifibrotic therapy, which has improved drastically over the years and can significantly delay the need for lung transplantation. However, there has been an upward trend of offering lung transplantation to older patients; in the United States, more than 40% of lung transplants in 2016 were performed in patients over 65 years of age.

Read more about IPF diagnosis

Another risk factor for lung transplantation is being overweight. A study has shown that patients with a body mass index (BMI) of 25 or more had a 15% to 22% higher rate of post-transplant death. Overweight and obese patients are therefore usually counseled to control their weight through an active, healthy lifestyle, if possible. Besides qualifying for lung transplantation, controlling one’s weight comes with a host of health benefits as well. It should be noted that patients with IPF sometimes gain weight as a side effect of taking corticosteroids. 

Having connective tissue disease (CTD) is also considered a risk factor for lung transplantation. It should be noted that CTD could be the cause of interstitial lung disease (ILD) in the first place, and lung transplantation is often offered to patients with a variety of CTDs, including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, and more. Study findings on the impact of CTD-related ILD on worsening postoperative outcomes are mixed, but the International Society for Heart and Lung Transplantation (ISHLT) considers it to be a risk factor for poorer outcomes. The ISHLT recommends presurgical screening of extrapulmonary diseases in conjunction with rheumatology; this may reveal some contraindications to surgery, such as severe esophageal dysmotility from systemic sclerosis. 

Telomere disorders should also be given due consideration pre-surgery. Telomere shortening has been implicated in the pathogenesis of IPF. It is also associated with a poorer response to immunosuppressants and worse post-transplant outcomes. A study indicated that a telomere shortening of <10th percentile was independently associated with a greater hazard ratio and higher risks of chronic lung allograft dysfunction (CLAD) and primary graft dysfunction. Telomere shortening is also associated with post-transplant medical complications, such as hematological disorders.

Post-Transplantation Comorbidities 

The majority of deaths from lung transplantation are the result of CLAD, though this figure is decreasing with better immunosuppressive treatments. However, there are a number of comorbidities that deserve close attention because they can potentially increase mortality rates in patients who are already immunocompromised from receiving a lung transplant. 

Cardiovascular disease, for example, is observed in around 68% of patients with IPF undergoing cardiac catheterization as part of their presurgical evaluation. Studies have also shown that IPF patients referred for lung transplantation are at an increased risk of developing cardiovascular disease, with all other traditional risk factors taken into consideration. The researchers of this study recommended that “a vigilant approach is required after transplant to monitor symptoms and optimize cardiovascular risk factors.” 

Read more about IPF therapies

Gastrointestinal disease is another comorbidity that deserves close attention post-transplant. One of the most common gastrointestinal problems that can develop postoperatively is gastroesophageal reflux disease (GERD). Current guidelines indicate that post-transplantation GERD can be a cause of pulmonary decline, including CLAD. Therefore, fundoplication is usually offered if GERD symptoms develop and persist post-surgery. Studies have shown that antireflux surgery is associated with better lung function. 

In addition to these more recognized post-transplantation comorbidities, others that are lesser known may also occur, such as chromosomal telomere shortening. This can cause anemia, leukopenia, filgrastim requirement, and thrombocytopenia. Post-transplantation telomere shortening can also cause a host of various complications, including myelodysplastic syndrome, infectious diseases (such as cytomegalovirus), chronic renal disease, and an increased risk of cancer. “Together, the various complications often lead to intolerance of immunosuppression, most frequently leading to reductions or complete cessation of the antiproliferative agent,” the authors of the study wrote. 

Where We Are Heading 

First of all, we must recognize that there is a shortage of organ donors in the United States, and, indeed, globally. This is an important point to highlight because, without lung donors, there simply is no point discussing lung transplantation, at least until an artificial alternative has been developed. Therefore, we must invest in greater awareness of the importance of organ donation. 

Even as we get better at caring for patients with IPF before and after lung transplantation, we need to continue investing in better antifibrotic and immunosuppressive therapies as the mainstay of IPF treatment. 

The more confident we are at improving survival rates and the quality of life of patients postoperatively, the more confident we will be in offering lung transplantation to older and more vulnerable patients. Encouragingly, this is already happening. The study authors stated, “The transplant community is transitioning toward higher-risk, sicker candidates,” and that we are moving towards “personalizing post-transplant care including immunosuppression to reduce infectious and malignant complications while still protecting against CLAD.”


Kapnadak SG, Raghu G. Lung transplantation for interstitial lung disease. Eur Respir Rev. 2021;30(161):210017. doi:10.1183/16000617.0017-2021

Vock DM, Durheim MT, Tsuang WM, et al. Survival benefit of lung transplantation in the modern era of lung allocation. Ann Am Thorac Soc. 2017;14(2):172-181. doi:10.1513/AnnalsATS.201606-507OC