Comparison of Nutrition and Lung Function Outcomes in Patients with Cystic Fibrosis Living in Canada and the United States

Abstract

Rationale: A 10-year gap in the median age of survival for patients with cystic fibrosis (CF) was reported between patients living in Canada compared with patients living in the United States.

Objectives: Because both malnutrition and poor lung function are associated with an increased risk of mortality in CF, we investigated the temporal and longitudinal trends in lung function and nutrition between Canada and the United States.

Methods: This cohort study used Canadian CF Registry and U.S. CF Foundation Patient Registry data from 1990 to 2013. A unified dataset was created to harmonize the variables collected within the two registries for the purpose of comparing outcomes between the two countries.

Measurements and main results: We conducted three analyses: survival differences by birth cohort; population trends for FEV₁ and body mass index (BMI) over time; and individual patient FEV₁ and BMI trajectories. The study included a total of 37,772 patients in the United States and 5,149 patients in Canada. Patients with CF experienced significant improvements in nutritional status and lung function in both Canada and the United States during the study. In addition, the survival gap between the two countries is narrowing within younger birth cohorts. The improvements for the patients within the United States were most prominent in the BMI trajectories, where patients born after 1990 in the United States have higher BMI that has persisted over time.

Conclusions: The reasons for the observed improvements, and catch-up in the United States, are likely multifactorial and include the introduction of high-fat, high-calorie diets; introduction of newborn screening; and/or improved access to care for CF children in the United States.

Keywords: cystic fibrosis; international comparison; lung function; nutrition; survival.

Figure 1.

Description of the study population. CAN = Canada; Excl. = excluded; pts = patients.

Figure 2.

Probability of survival by birth cohort and country. The probability of surviving to age 20 narrows between Canada and the United States from a difference of 5.5% in the oldest cohort (born before 1980) (A) to 4.3% in the middle cohort (born 1980–1989) (B) and 2.0% in the youngest cohort (born after 1990) (C). CI = confidence interval; OS = overall survival.

Figure 3.

Median (A) FEV₁ and (B) BMI percentile/BMI (kg/m²) from 1990 to 2013 by country, stratified by age group. Canada (solid line) had significantly higher FEV₁ and BMI for all three age groups at the start of the study (1990), whereas the rate of improvement with time was greater in the United States (dashed line) compared with Canada (Table E1). BMI = body mass index.

Figure 4.

Proportion of patients (A) with severe lung disease (FEV₁ < 40% predicted) and (B) who are underweight (BMI percentile <12.5% in children; BMI <18.5 in adults) from 1990 to 2013 by country, stratified by age group. Canada (solid line) had a significantly lower proportion of patients with severe lung disease or who are underweight for all three age groups at the start of the study (1990), whereas the rate of improvement with time was greater in the United States (dashed line) than in Canada. BMI = body mass index.

Figure 5.

Rate of decline of (A) FEV₁% predicted and (B) BMI percentiles by age and country, stratified by birth cohort. Canadian patients consistently started with higher lung function at earlier ages, whereas the U.S. patients experienced improvements in the rate of decline relative to Canada in younger cohorts. The absolute differences in BMI between Canada and the United States were unique to each birth cohort, with Canadian patients having a BMI advantage in the oldest cohort (born before 1980), whereas U.S. patients now have a BMI advantage in the youngest cohort (born after 1990). BMI = body mass index; CAN = Canada.