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Cystic fibrosis-specific variables improve predicted disease severity in patients on waitlist

New data suggest that the addition of clinical variables specifically associated with reduced survival in cystic fibrosis to the lung allocation score calculation improves prediction of disease severity among patients with advanced-stage cystic fibrosis awaiting lung transplant.

“We conducted this study because we wanted to more accurately determine which patients with cystic fibrosis had a high risk of mortality as they awaited a lung transplant in order to improve their access to a transplant if needed. People with cystic fibrosis are different than the average patient awaiting a lung transplant — they are younger, often have more infections and more commonly have multiple organs that are affected by their disease. Many of these clinical measures of illness progress during these patients’ lifetime but were not adequately captured by the U.S. transplant registry,” Maryam Valapour, MD, MPP, director of Lung Transplant Outcomes at Cleveland Clinic and Senior Lung Transplant Investigator for the U.S. Scientific Registry of Transplant Recipients, wrote in an email to Healio Pulmonology.

“To study this question, the Cystic Fibrosis Foundation and the U.S. Scientific Registry of Transplant Recipients (SRTR) joined forces to merge their patient databases, which was a several-year effort. This database merge was important because it allowed us to analyze clinical factors for patients with cystic fibrosis before they were sick enough to need a lung transplant and then follow their course until they received a transplant. This is the first time we could study the entire clinical picture of an individual with cystic fibrosis because the cystic fibrosis registry did not have complete data on patients once they were listed for a lung transplant and the SRTR did not have data prior to a patient being placed on the transplant waiting list.”

Important findings

The multicenter, retrospective, population-based study used a deterministic matching algorithm to identify patients from the SRTR and the Cystic Fibrosis Foundation Patient Registry (CFFPR).

For their analysis, Valapour and colleagues included 9,043 patients aged 12 years or older on the lung transplant waiting list — of whom 1,020 had cystic fibrosis — and 6,110 lung transplant recipients — of whom 677 had cystic fibrosis — from 2011 to 2014.

Using data from the CFFPR, the researchers selected variables that were reported risk factors for morbidity and mortality in patients with cystic fibrosis.

For patients with cystic fibrosis, the risk for dying while on the transplant waitlist significantly increased with the presence of any Burkholderia species (HR = 2.8; 95% CI, 1.2-6.6), hospitalization for 29 to 42 days (HR = 2.8; 95% CI, 1.3-5.9), massive hemoptysis (HR = 2.1; 95% CI, 1.1-3.9) and a relative drop of 30% or more in FEV₁ during 12 months (HR = 1.7; 95% CI, 1-2.8).

However, there were no significant changes in posttransplant mortality after inclusion of the CFFPR clinical variables, except for an increase among patients with pulmonary exacerbation time of 15 to 28 days in the year before transplant (HR = 1.8; 95% CI, 1.1-2.9).

The addition of CFFPR clinical variables to the lung allocation score also demonstrated an association between a 10% decline in FEV₁ and increased mortality among patients with COPD (HR = 2.6; 95% CI, 1.2-5.4), but did not affect patients with other diagnoses.

“While we expected that addition of new clinical variables would help some patients with cystic fibrosis, we were surprised that the reevaluation of the pulmonary function testing also helped patients with COPD. This unexpected benefit broadened the impact of the findings to a larger number of individuals awaiting lung transplant,” Valapour said.

Looking ahead

Notably, the addition of the CFFPR clinical variables would have changed patients’ transplant rank, the researchers noted, adding that 36.8% of patients with cystic fibrosis in the cohort who died on the waiting list would have had an increase of at least 5 points in the lung allocation score.

“This work has broad application for the cystic fibrosis and COPD populations and may result in important changes to the lung allocation system in the United States. Additionally, this work highlights the importance of population health and the maintenance of large population-based registries. Because the Cystic Fibrosis Foundation had such a comprehensive patient registry that follows its patients from birth onwards and in U.S. transplant system we follow every patient from time of listing for transplant and beyond, we were able to better understand the natural history of disease among patients destined to require a lung transplant. This impeccable data collection and resultant organizational commitment to the database merge allowed us to use this data to better identify those at risk of mortality on the waiting list to improve access to transplant for those most at risk for dying without a transplant,” Valapour said. These data also open the door for further study, she noted.

“It will be important in the future to gather clinical variables that helped us better identify at-risk patients with cystic fibrosis, including antibiotic days, hospitalization days and pulmonary exacerbation days for all patients including those without cystic fibrosis on the U.S. transplant waiting list. This would allow us to study how including these variables may better identify which patients are the most sick, and in the most need of transplant,” Valapour told Healio Pulmonology. – by Melissa Foster

For more information:

Carli Lehr, MD, MS, can be reached on Twitter: @carlilehr_md.

Elliott Dasenbrook, MD, MPH, can be reached on Twitter: elliottdasenbr1.

Maryam Valapour, MD, MPP, can be reached at valapom@ccf.org; Twitter: @MValapour.

Disclosure: This study was supported by the Hennepin Healthcare Research Institute, contractor for the Scientific Registry of Transplant Recipients, as a deliverable under contract for the HHS.