TOPIC: Transplantation
      TYPE: Original Investigations
      PURPOSE: Cystic fibrosis (CF) often leads to progressive lung disease necessitating lung transplant (LTx). CF is associated with malnutrition and, for many, low body mass index (BMI). Most LTx programs in the United States (US) have BMI thresholds as an absolute contraindication to transplant. However, the CF Foundation recommends LTx referral for patients with a low BMI and advanced CF lung disease, because malnutrition is modifiable. We aimed to determine whether patients with advanced CF lung disease and BMI <17 kg/m2 are referred for lung transplant less often than those with higher BMI, and whether they face an increased risk of death without referral.
      METHODS: We used a dataset that merged the CF Foundation Patient Registry with the UNOS transplant registry. Adults (≥18 yrs) were included if they had initial onset of advanced lung disease (FEV1 ≤ 40% predicted; not marked as an exacerbation or hospitalization, "stable") between May 1, 2005 and December 31, 2016. Survival was analyzed using proportional hazards regression models with cause-specific risks of: 1) referral for LTx; and 2) death without referral. BMI ≤ 17 kg/m2 was the predictor of interest. Analyses were adjusted for possible confounders, including age, education, insurance, race, sex, FEV1 % predicted, oxygen therapy, pulmonary exacerbations, Burkholderia cepacia, and diabetes.
      RESULTS: There were 5,130 adult CF patients who met our inclusion criteria. Of these, 1,208 (24%) patients were referred for LTx, 1,193 (23%) died without being referred, and the remaining 2,729 (43%) were alive without being referred as of December 31, 2016. Patients with BMI ≤ 17 kg/m2 accounted for 14% of referrals but 23% of deaths without referral. Proportional hazards regression with cause-specific risks found that patients with BMI ≤ 17 kg/m2 were less likely to be referred for LTx (HR 0.82, 95% CI 0.69 - 0.97, p=0.02) and more likely to die without referral (HR 1.67, 95% CI 1.45 - 1.93, p<0.001). A sensitivity analysis suggested that the association of BMI ≤ 17 kg/m2 with LTx referral or death without referral varied between UNOS geographic regions, with a range in HR from 0.16 (95% CI 0.02 - 1.20) to 1.13 (95% CI 0.73 - 1.75) for referral and 1.02 (95% CI 0.55 - 1.90) to 2.85 (95% CI 1.62 - 4.99) for death without referral. UNOS Regions with lower HR for referral generally had higher HR for death without referral.
      CONCLUSIONS: Patients with advanced CF lung disease and BMI <17 kg/m2 have a lower likelihood to be referred for LTx and an increased risk of dying without referral than those with higher BMI. This relationship varies geographically within the US, likely reflecting differences in CF Center and LTx program practices.
      CLINICAL IMPLICATIONS: Low BMI is a barrier to LTx referral for patients with CF. Early referral for LTx in this group, with concurrent interventions to encourage weight gain, is recommended to decrease the risk of death without LTx.
      DISCLOSURES: No relevant relationships by Moira Aitken, source=Admin input
      no disclosure on file for Christopher Goss;
      No relevant relationships by Travis Hee Wai, source=Web Response
      No relevant relationships by Ann Jennerich, source=Web Response
      No relevant relationships by Siddhartha Kapnadak, source=Web Response
      No relevant relationships by Joseph Pryor, source=Web Response
      No relevant relationships by Kathleen Ramos, source=Web Response