Heterogeneity in Survival in Adult Patients With Cystic Fibrosis With FEV(1) < 30% of Predicted in the United States.

Lung transplantation (LTx) is frequently considered for patients with cystic fibrosis (CF) when the FEV1 reaches < 30%. This study estimated transplant-free survival for patients with CF and an FEV1 < 30% and identified predictors of death without LTx. We conducted a retrospective cohort study using the CF Foundation Patient Registry from January 1, 2003 to December 31, 2013. Adult patients (≥ 18 years) with FEV1 < 30% prior to LTx were included. We performed Kaplan-Meier survival estimates censored at LTx. Multivariable Cox proportional hazard regression identified predictors of mortality. There were 3,340 patients with an FEV1 < 30%. Death without LTx occurred in 1,250 patients (37.4%); 951 patients (28.5%) underwent LTx; 918 patients (27.5%) remained alive without LTx at the end of follow-up; and 221 patients (6.6%) were lost to follow-up. Median transplant-free survival after FEV1 < 30% was 6.6 years (95% CI, 5.9-7.0). Adjusted predictors of death without LTx included supplemental oxygen use (hazard ratio [HR], 2.1; 95% CI, 1.7-2.6), Burkholderia cepacia infection (HR, 1.8; 95% CI, 1.3-2.6), BMI ≤ 18 (HR, 1.6; 95% CI, 1.3-1.9), female sex (HR, 1.6; 95% CI, 1.2-2.0), CF-related diabetes in patients receiving insulin (HR, 1.4; 95% CI, 1.2-1.8), and ≥ one exacerbation per year (HR, 1.7; 95% CI, 1.3-2.2 vs. 0 exacerbations). Median survival was > 6.5 years for patients with CF and an FEV1 < 30%, exceeding prior survival estimates. There was substantial heterogeneity in survival, with some patients with CF dying soon after reaching this lung function threshold and others living for many years. For this reason, we conclude that FEV1 < 30% remains an important marker of disease severity for patients with CF. Patients with a supplemental oxygen requirement or frequent exacerbations should have prompt referral because of their increased risk of death.

Ramos KJ ，Quon BS ，Heltshe SL ，Mayer-Hamblett N ，Lease ED ，Aitken ML ，Weiss NS ，Goss CH ... -  《-》

Mortality Risk and Pulmonary Function in Adults With Cystic Fibrosis at Time of Wait Listing for Lung Transplantation.

Lung transplantation (LTx) benefit for survival in cystic fibrosis (CF) patients placed on the wait list is not well studied. To predict the relationship between initial forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) and the hazard ratio (HR) associated with LTx in CF patients, the United Network for Organ Sharing database was queried from 2005 to 2006 for adult patients with CF. Survival was assessed from wait list entry time until death on wait list, death after LTx, or censoring. Multivariate Cox proportional hazards models were used to assess the effect of LTx. The first model estimated the HR of LTx with adjustment for FEV1 or FVC and other covariates, and the second model estimated the HR of LTx conditional on FEV1 or FVC at listing. Two hundred seventy-eight patients with CF were included in the cohort, and 277 were used for survival analysis. Lung transplantation reduced the risk for death controlling for FEV1 (HR, 0.601; 95% confidence interval, 0.375 to 0.964; p = 0.035) or controlling for FVC (HR, 0.547; 95% confidence interval, 0.336 to 0.889; p = 0.015). Interaction models found that the HR of LTx varied significantly across initial FEV1 and FVC, with the predicted LTx HR and 95% confidence interval being protective (HR < 1) at FEV1 of 25% or less and FVC of 40% or less, respectively. The benefit of LTx in adults with CF was significant at a lower baseline FEV1 than expected. A threshold for baseline FVC was established below which LTx was protective.

Hayes D Jr ，Kirkby S ，Whitson BA ，Black SM ，Sheikh SI ，Tobias JD ，Mansour HM ，Kopp BT ... -  《-》

Survival and Lung Transplant Outcomes for Individuals With Advanced Cystic Fibrosis Lung Disease Living in the United States and Canada: An Analysis of National Registries.

Understanding how health outcomes differ for patients with advanced cystic fibrosis (CF) lung disease living in the United States compared with Canada has health policy implications. What are rates of lung transplant (LTx) and rates of death without LTx in the United States and Canada among individuals with FEV1 < 40% predicted? This was a retrospective population-based cohort study, 2005 to 2016, using the US CF Foundation, United Network for Organ Sharing, and Canadian CF registries. Individuals with CF and at least two FEV1 measurements < 40% predicted within a 5-year period, age ≥ 6 years, without prior LTx were included. Multivariable competing risk regression for time to death without LTx (LTx as a competing risk) and time to LTx (death as a competing risk) was performed. There were 5,899 patients (53% male) and 905 patients (54% male) with CF with FEV1 < 40% predicted living in the United States and Canada, respectively. Multivariable competing risk regression models identified an increased risk of death without LTx (hazard ratio [HR], 1.79; 95% CI, 1.52-2.1) and decreased LTx (HR, 0.66; 95% CI, 0.58-0.74) among individuals in the United States compared with Canada. More pronounced differences were seen in the patients in the United States with Medicaid/Medicare insurance compared with Canadians (multivariable HR for death without LTx, 2.24 [95% CI, 1.89-2.64]; multivariable HR for LTx, 0.54 [95% CI, 0.47-0.61]). Patients of nonwhite race were also disadvantaged (multivariable HR for death without LTx, 1.56 [95% CI, 1.32-1.84]; multivariable HR for LTx, 0.47 [95% CI, 0.36-0.62]). There are lower rates of LTx and an increased risk of death without LTx for US patients with CF with FEV1 < 40% predicted compared with Canadian patients. Findings are more striking among US patients with CF with Medicaid/Medicare health insurance, and nonwhite patients in both countries, raising concerns about underuse of LTx among vulnerable populations.

Ramos KJ ，Sykes J ，Stanojevic S ，Ma X ，Ostrenga JS ，Fink A ，Quon BS ，Marshall BC ，Faro A ，Petren K ，Elbert A ，Goss CH ，Stephenson AL ... -  《-》

Reduced survival in adult cystic fibrosis despite attenuated lung function decline.

There is limited data on disease progression and survival in adult diagnosis cystic fibrosis (CF). This study evaluates change of lung function over time and rates of death/lung transplant in adult diagnosis CF. The CF Foundation Patient Registry was reviewed for patients diagnosed 1993-2003. Rate of FEV1 decline was calculated up to 2010 for age groups 6-11, 12-17, and 18 and above. Kaplan Meier method was used for 10 and 15year survival rate calculations for patients diagnosed as adults. Cox Proportional hazards models using predictors affecting disease progression and survival without transplant were run. Between 1993 and 2003, 11,884 patients were diagnosed with CF, of which 2848 were ages 6 and older. Annual rate of change of FEV1% predicted over 5years differed by diagnosis age group: -1.42% per year for ages 6-11, -2.04% for ages 12-17 and -1.13% for ages 18-65 (p<0.0001). Pseudomonas aeruginosa infection was associated with faster rates of lung function decline in all age groups. Survival without transplant for CF patients diagnosed at ≥18years were 76% and 65% by 10 and 15years, respectively. Of adults with FEV1 of >70% predicted at diagnosis, 95% were alive without transplant at 10years, whereas of those with FEV1<40% predicted at diagnosis, 31% were alive without transplant at 10years. Lung function declines at a slower rate in adult diagnosis CF. However, particularly in those with low lung function at diagnosis, rates of death or transplant in adult diagnosis CF after 10 and 15years is not negligible.

Keating C ，Poor AD ，Liu X ，Chiuzan C ，Backenroth D ，Zhang Y ，DiMango E ... -  《-》

Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation.

Hayes D Jr ，Kopp BT ，Tobias JD ，Woodley FW ，Mansour HM ，Tumin D ，Kirkby SE ... -  《-》