Largest study evaluating survival in systemic sclerosis patients following lung transplantation

Systemic sclerosis (SSc), also known as scleroderma, is a disease affecting the skin and other organs of the body. It is an autoimmune rheumatic disease, meaning that the body's immune system is acting abnormally. Systemic sclerosis typically involves thickening and tightening of the skin, and inflammation and scarring of many body parts leading to problems in the lungs, kidneys, heart, intestinal system and other areas. The disease is relatively rare. Only 75,000 to 100,000 people in the U.S. have it, and more than 75 percent of people with the disease are women.

Hospitals may be reluctant to approve lung transplantation in systemic sclerosis patients due to their concerns about extra-pulmonary involvement that might affect the patients' short- and long-term survival.

Researchers at Columbia University College of Physicians and Surgeons in New York City wanted to find out if adults with systemic sclerosis have a higher one-year mortality rate after lung transplantation compared to patients with interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH) not due to SSc. They performed a retrospective cohort study of 3,763 adults who had undergone double or single lung transplantation in the United States between May 4, 2005 (the date of implementation of the lung allocation score) and September 14, 2012.

"Although many transplant centers are hesitant to offer lung transplantation to patients with SSc due to concern about extra-pulmonary involvement that might affect survival, there are very few data to support the impression that survival is worse in SSc patients compared to non-SSc patients," said Elana J. Bernstein, MD, MSc of Columbia University College of Physicians and Surgeons, and a lead author of the study. "In fact, previous studies -- albeit limited to small case series and small cohort studies -- suggest that adults with SSc have similar mortality rates to adults with ILD and PAH following lung transplantation. We actually hoped to confirm the findings of these prior small studies, thereby perhaps providing an impetus for transplant programs to begin to change their practices and offer lung transplantation to greater numbers of carefully selected patients with SSc who are otherwise suitable candidates for lung transplantation."

The researchers used data provided by the United Network for Organ Sharing. Subjects were included if they were at least 18 years of age at the time of lung transplantation surgery; had a diagnosis of SSc, ILD or PAH; and had transplantation surgery at a center that has performed at least one such procedure for SSc. Subjects were excluded if they had received a heart-lung transplant; if they received a lung from a living donor; or if they had missing data on survival time.

There were 3,763 adults transplanted during the study period who met the study's inclusion criteria: 229 with SSc, 201 with PAH and 3,333 with ILD. In multivariable-adjusted analyses, a diagnosis of SSc was associated with a 48-percent relative increase in the one-year mortality rate compared to a diagnosis of ILD. However, a diagnosis of SSc was not associated with a relative increase in the one-year mortality rate compared to a diagnosis of PAH, a widely accepted indication for lung transplantation.

The study's authors concluded that rather than denying SSc patients lung transplantation as a treatment option because of their diagnosis, other variables need to be identified that will enable risk stratification of these patients prior to surgery, with particular attention to modifiable risk factors.

"We found that adults with SSc undergoing lung transplantation in the United States during the lung allocation score era had a 48 percent relative increase in the risk of death at one year compared to those with ILD. In contrast, the risk of death at one year among those with SSc was comparable to those with PAH, a widely accepted indication for lung transplantation," said Dr. Bernstein. "In additional analyses among one-year survivors, we did not detect an increased risk of three-year mortality among those with SSc compared to those with ILD, and found that adults with SSc actually had a lower risk of death at three years than those with PAH. Future work should aim to prospectively study adults with SSc as they are evaluated for lung transplantation in order to identify potentially modifiable risk factors that can improve transplant outcomes in this population."