Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease.

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2 years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1 second (FEV1) ⩽ 40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modeled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1, 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43-0.90; P = 0.008) and 0.60 (0.48-0.82; P < 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ⩽ 49.2% predicted versus 10.9% for those with a Wpeak > 49.2% predicted (P < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection.

Association between elevated peripheral blood eosinophil count and respiratory outcomes in adults with cystic fibrosis.

BACKGROUND: Elevated blood eosinophil counts are linked to worse outcomes in asthma and COPD, but have yet to be well characterized in CF. We hypothesized that higher stable visit blood eosinophil counts are associated with increased rates of lung function decline and pulmonary exacerbations (PEx). METHODS: We performed a retrospective analysis of adult CF patients (≥19 years) enrolled from 2012 to 2018 in a prospective cohort study focused on blood biomarkers. We included individuals with at least one year of follow-up post-stable visit blood draw and compared clinical characteristics by blood eosinophil count (<300 cells/µL vs. ≥300 cells/µL). We used multivariate mixed-effects linear regression to estimate annual change in ppFEV1. Multivariable poisson and linear regression models were used to estimate rate of PEx requiring IV antibiotics and to compare CF Respiratory Symptom Diary-Chronic Respiratory Infection Symptom Scores (CFRSD-CRISS), respectively. RESULTS: Of 109 patients, 17 (15.6%) had eosinophil counts ≥300 cells/µL. After adjustment for age, sex, BMI, and baseline ppFEV1, there was no association between high vs. low eosinophil group and rates of lung function decline (difference in slope -0.04%/y; 95% CI -1.5 to +1.4) or rates of PEx requiring IV antibiotics (IRR 1.46; 95% CI 0.75 to 2.65). The high eosinophil group had a higher mean CFRSD-CRISS score at stable visit (adjusted mean difference 9.3; 95% CI 2.9 to 16.0). CONCLUSIONS: The high eosinophil group experienced increased respiratory symptoms, but the rates of lung function decline and PEx were comparable between groups.

Factors influencing clinical trial participation for adult and pediatric patients with cystic fibrosis.

There remains a limited understanding of the factors influencing clinical trial participation for individuals with Cystic Fibrosis (CF). A comprehensive survey was developed to examine the interests, preferences, and barriers/facilitators to research and clinical trial participation for CF patients. A consecutive sample of 198 CF adults attending the St. Paul's Hospital CF Clinic and parents of children with CF attending the BC Children's Hospital CF Clinic from Vancouver, Canada were surveyed. Parents of pediatric patients were less comfortable with blood collection, required more safety data prior to participating, and were more concerned about potential side effects. Very few respondents (<10%) appeared able/willing to fulfill the typical requirements to participate in a phase 1 clinical trial. Overall, there were more similarities than differences between the responses of adult and parents of pediatric CF patients. The patient-centered information can be used to inform the design of future clinical trials to enhance feasibility.

The impact of cystic fibrosis-related diabetes on health-related quality of life.

Cystic fibrosis-related diabetes (CFRD) is a well-known comorbidity among the CF population. To investigate whether CFRD impacts health-related quality of life (HRQoL), domain scores from the Cystic Fibrosis Questionnaire-Revised for adolescents and adults over 14 years old (CFQ-R 14+) were compared between CF individuals with CFRD on insulin, CFRD not on insulin, impaired glucose tolerance, and normal blood glucose tolerance. The median score for the Treatment Burden domain was significantly worse for individuals with CFRD on insulin (p < 0.001) compared to the other diagnostic groups, and this association remained significant following adjustment for confounding variables. In conclusion, the additional requirement for insulin significantly contributes to treatment burden in adults with CFRD and therefore novel strategies to reduce treatment burden for this group are urgently needed.