Fast Weight Loss in IPF Patients Linked to Poor Prognosis, Study Suggests

Fast weight loss in people with idiopathic pulmonary fibrosis (IPF), even after lung transplant, is linked with worse prognosis, and may indicate immune system activation, a study suggests.

People who experience greater weight loss over a short period may be at greater risk for poor outcomes.

The research, “Decrements of body mass index are associated with poor outcomes of idiopathic pulmonary fibrosis patients,” was published in the journal PLOS ONE.

Changes in body mass index (BMI) have been tied to the outcomes of people with pulmonary diseases such as chronic obstructive pulmonary disease (COPD). But such changes also are linked to disorders such as rheumatoid arthritis and heart failure.

People with pulmonary fibrosis (PF) tend to lose weight slowly over time as the disease progresses. Although the causes remain unclear, side effects of medications — including nausea and lack of appetite — have been pointed out as one potential driver of weight loss. Another possible driver may be psychological symptoms such as depression, which is fairly common among people with PF.

Now, researchers from the University of Alabama at Birmingham (UAB) and the University of Pittsburgh worked together to shed light on the implications and potential causes of BMI changes in people with IPF.

The team reviewed the clinical records of 131 patients (mean age 68.9 years) followed at the University of Pittsburgh Medical Center (UPMC), and of 148 individuals (mean age 65.3 years) from UAB.

Among these groups, 38 (29%) patients at UPMC and 23 (16%) at UAB underwent lung transplant. The researchers said 47 (36%) patients at UPMC and 89 (60%) at UAB died prior to transplant.

Results at UPMC showed that those who underwent lung transplant or died within the first year of follow-up had experienced a mean BMI reduction of 0.42% per month. Meanwhile, non-transplanted survivors lost 0.09% per month.

The UPMC patients with monthly BMI reductions greater than 0.68% showed a 1.8 lower likelihood of surviving transplant-free, compared with those with more stable BMI. This greater risk in people with rapid weight loss was maintained even when the team excluded potential confounding events from the analysis. One such event was intentional weight loss, which is often necessary before transplant.

Further analysis showed that losing more than 0.68% of BMI per month during the year preceding lung transplant correlated with a 4.6-fold increased risk of death compared with having a more stable body mass index.

Findings in the UAB group were similar, with individuals who had monthly BMI loss greater than 0.68% showing a 2.5-fold increased risk for worse outcomes.

Next, the team analyzed blood samples that were available from UPMC patients. They found that BMI increases over time were associated with higher blood levels of leptin — a hormone associated with body fat metabolism and obesity. Conversely, the BMI increases also were linked to lower amounts of adiponectin, an anti-inflammatory protein. However, neither leptin nor adiponectin predicted outcomes in people with IPF.

The researchers also found that — compared to people with more stable BMI — those with the greatest BMI reductions had a higher proportion of T-cells without the CD28 protein. A low level of CD28 T-cells “is a specific and validated marker of repeated antigen encounters and adaptive immune activation,” the researchers said.

Higher levels of active T-cells (without CD28) are associated with worse transplant-free survival.

Overall, the team concluded that “IPF patients with greatest BMI decrements had worse outcomes, and this effect persisted after lung transplant.”

These findings “could be an impetus for further research to more fully determine causes of the weight loss in IPF patients, and better understand the pathological mechanism(s) that link [BMI changes] to progression and outcome of this lung disease,” the researchers said.

Evaluation of BMI changes, either alone or in combinations with other measures, “could eventually be a useful clinical tool to identify IPF patients with increased risks of near-term mortality,” the investigators added.