Lung function in children with cystic fibrosis in the USA and UK: a comparative longitudinal analysis of national registry data.

RATIONALE: A previous analysis found significantly higher lung function in the US paediatric cystic fibrosis (CF) population compared with the UK with this difference apparently decreasing in adolescence and adulthood. However, the cross-sectional nature of the study makes it hard to interpret these results. OBJECTIVES: To compare longitudinal trajectories of lung function in children with CF between the USA and UK and to explore reasons for any differences. METHODS: We used mixed effects regression analysis to model lung function trajectories in the study populations. Using descriptive statistics, we compared early growth and nutrition (height, weight, body mass index), infections (Pseudomonas aeruginosa, Staphylococcus aureus) and treatments (rhDnase, hypertonic saline, inhaled antibiotics). RESULTS: We included 9463 children from the USA and 3055 children from the UK with homozygous F508del genotype. Lung function was higher in the USA than in the UK when first measured at age six and remained higher throughout childhood. We did not find important differences in early growth and nutrition, or P.aeruginosa infection. Prescription of rhDNase and hypertonic saline was more common in the USA. Inhaled antibiotics were prescribed at similar levels in both countries, but Tobramycin was prescribed more in the USA and colistin in the UK. S. aureus infection was more common in the USA than the UK. CONCLUSIONS: Children with CF and homozygous F508del genotype in the USA had better lung function than UK children. These differences do not appear to be explained by early growth or nutrition, but differences in the use of early treatments need further investigation.

Effect of Including Important Clinical Variables on Accuracy of the Lung Allocation Score for Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

Rationale: Clinical variables associated with shortened survival in patients with advanced-stage cystic fibrosis (CF) are not included in the lung allocation score (LAS).Objectives: To identify variables associated with wait-list and post-transplant mortality for CF lung transplant candidates using a novel database and to analyze the impact of including new CF-specific variables in the LAS system.Methods: A deterministic matching algorithm identified patients from the Scientific Registry of Transplant Recipients and the Cystic Fibrosis Foundation Patient Registry. LAS wait-list and post-transplant survival models were recalculated using CF-specific variables. This multicenter, retrospective, population-based study of all lung transplant wait-list candidates aged 12 years or older from January 1, 2011, to December 31, 2014, included 9,043 patients on the lung transplant waiting list and 6,110 lung transplant recipients between 2011 and 2014, comprising 1,020 and 677 with CF, respectively.Measurements and Main Results: Measured outcomes were changes in LAS and lung allocation rank. For CF candidates, any Burkholderia sp. (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.2-6.6), 29-42 days hospitalized (HR 2.8; CI 1.3-5.9), massive hemoptysis (HR 2.1; CI 1.1-3.9), and relative drop in FEV1 ≥30% over 12 months (HR 1.7; CI 1.0-2.8) increased wait-list mortality risk; pulmonary exacerbation time 15-28 days (1.8; 1.1-2.9) increased post-transplant mortality risk. A relative drop in FEV1 ≥10% in chronic obstructive pulmonary disease (COPD) candidates was associated with increased wait-list mortality risk (HR 2.6; CI 1.2-5.4). Variability in LAS score and rank increased in patients with CF. Priority for transplant increased for COPD candidates. Access did not change for other diagnosis groups.Conclusions: Adding CF-specific variables improved discrimination among wait-listed CF candidates and benefited COPD candidates.

Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

BACKGROUND & AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess if optimal screening strategies would change. RESULTS: Colonoscopy every 5 years, starting at an age of 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in this population is not clear. CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.

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

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.

Cost-Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

BACKGROUND & AIMS: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared to the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. METHODS: We adjusted the existing Microsimulation Screening Analysis-Colon microsimulation model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess whether optimal screening strategies would change. RESULTS: Colonoscopy every 5 years, starting at age 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in population is not clear. CONCLUSIONS: Using a Microsimulation Screening Analysis-Colon microsimulation model, we found screening of patients with cystic fibrosis for CRC to be cost-effective. Due to the higher risk in these patients for CRC, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT screening) may be limited by restricted evidence available for patients with cystic fibrosis.

Clinical characteristics of cystic fibrosis patients prior to lung transplantation: An international comparison between Canada and the United States.

BACKGROUND: Cystic fibrosis (CF) patients from Canada have better-reported post-lung transplant survival compared to patients from the United States. We hypothesized the clinical characteristics of CF patients prior to lung transplant differ between the two countries. METHODS: Population-based cohort study utilizing combined Canadian CF Registry and US CF Foundation Patient Registry data from 1986 to 2013. Demographic and clinical variables were analyzed prior to lung transplant. RESULTS: Between 1986 and 2013, 607 (10.2%) CF patients underwent lung transplantation in Canada and 3428 (7.5%) in the United States. A lower proportion of recipients had growth of B. cepacia complex prior to transplant in the United States compared to Canada (0.8% vs 4.3%). Lung function was similar between recipients from the two countries. The proportion of patients classified as underweight was significantly higher in the United States compared to Canada (39.8% vs 28.0%; SD 26.1) despite higher rates of feeding tube use (42.5% vs 28.6%; SD 29.0). CONCLUSIONS: CF lung transplant recipients from the United States have similar lung function, lower rates of B. cepacia complex, and worse nutritional parameters prior to transplant compared to counterparts in Canada. Future studies are necessary to evaluate the impact of these differences on post-transplant survival.

Survival Comparison of Patients With Cystic Fibrosis in Canada and the United States: A Population-Based Cohort Study.

BACKGROUND: In 2011, the median age of survival of patients with cystic fibrosis reported in the United States was 36.8 years, compared with 48.5 years in Canada. Direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias. OBJECTIVE: To use a standardized approach to calculate cystic fibrosis survival estimates and to explore differences between Canada and the United States. DESIGN: Population-based study. SETTING: 42 Canadian cystic fibrosis clinics and 110 U.S. cystic fibrosis care centers. PATIENTS: Patients followed in the Canadian Cystic Fibrosis Registry (CCFR) and U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) between 1990 and 2013. MEASUREMENTS: Cox proportional hazards models were used to compare survival between patients followed in the CCFR (n = 5941) and those in the CFFPR (n = 45 448). Multivariable models were used to adjust for factors known to be associated with survival. RESULTS: Median age of survival in patients with cystic fibrosis increased in both countries between 1990 and 2013; however, in 1995 and 2005, survival in Canada increased at a faster rate than in the United States (P < 0.001). On the basis of contemporary data from 2009 to 2013, the median age of survival in Canada was 10 years greater than in the United States (50.9 vs. 40.6 years, respectively). The adjusted risk for death was 34% lower in Canada than the United States (hazard ratio, 0.66 [95% CI, 0.54 to 0.81]). A greater proportion of patients in Canada received transplants (10.3% vs. 6.5%, respectively [standardized difference, 13.7]). Differences in survival between U.S. and Canadian patients varied according to U.S. patients' insurance status. LIMITATION: Ascertainment bias due to missing data or nonrandom loss to follow-up might affect the results. CONCLUSION: Differences in cystic fibrosis survival between Canada and the United States persisted after adjustment for risk factors associated with survival, except for private-insurance status among U.S. patients. Differential access to transplantation, increased posttransplant survival, and differences in health care systems may, in part, explain the Canadian survival advantage. PRIMARY FUNDING SOURCE: U.S. Cystic Fibrosis Foundation.

Early Life Growth Trajectories in Cystic Fibrosis are Associated with Pulmonary Function at Age 6 Years.

OBJECTIVE: To determine whether severity of lung disease at age 6 years is associated with changes in nutritional status before age 6 within individual children with cystic fibrosis (CF). STUDY DESIGN: Children with CF born between 1994 and 2005 and followed in the CF Foundation Patient Registry from age ≤2 through 7 years were assessed according to changes in annualized weight-for-length (WFL) percentiles between ages 0 and 2 years and body mass index (BMI) percentiles between ages 2 and 6 years. The association between growth trajectories before age 6 and forced expiratory volume in 1 second (FEV1)% predicted at age 6-7 years was evaluated using multivariable linear regression. RESULTS: A total of 6805 subjects met inclusion criteria. Children with annualized WFL-BMI always >50th percentile (N = 1323 [19%]) had the highest adjusted mean (95% CI) FEV1 at 6-7 years (101.8 [100.1, 103.5]). FEV1 at 6-7 years for children whose WFL-BMI increased >10 percentile points by age 6 years was 98.3 (96.6, 100.0). This was statistically significantly higher than FEV1 for children whose WFL-BMI was stable (94.4 [92.6, 96.2]) or decreased >10 percentile points (92.9 [91.1, 94.8]). Among children whose WFL-BMI increased >10 percentile points, achieving and maintaining WFL-BMI >50th percentile at younger ages was associated with significantly higher FEV1 at 6-7 years. CONCLUSIONS: Within-patient changes in nutritional status in the first 6 years of life are significantly associated with FEV1 at age 6-7 years. The establishment of a clear relationship between early childhood growth measurements and later lung function suggests that early nutritional interventions may impact on eventual lung health.

Estimates of young breast cancer survivors at risk for infertility in the U.S.

BACKGROUND: Standard treatments for breast cancer can impair fertility. It is unknown how many U.S. survivors are at risk for infertility. We estimated the population at risk for infertility secondary to treatment among reproductive-aged breast cancer survivors. METHODS: We combined data from three sources: the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results cancer registry data on incident breast cancers diagnosed in women aged 15-44 years between 2004 and 2006; treatment data from NPCR's 2004 Breast and Prostate Cancer Data Quality and Patterns of Care (PoC) study; and data on women's intentions to have children from the 2006-2010 National Survey of Family Growth (NSFG). RESULTS: In the cancer registry data, an average of 20,308 women with breast cancer aged <45 years were diagnosed annually. Based on estimates from PoC data, almost all of these survivors (97%, 19,416 women) were hormone receptor positive or received chemotherapy and would be at risk for infertility. These women need information about the impact of treatments on fertility. Estimates based on NSFG data suggest approximately half of these survivors (9,569 women) might want children and could benefit from fertility counseling and fertility preservation. CONCLUSION: Nearly all young breast cancer survivors in the U.S. are at risk for infertility. Physicians should discuss the potential impact of treatment on fertility. A smaller but sizeable number of at-risk survivors may be interested in having children. Given the magnitude of potential infertility and its quality-of-life implications, these survivors should have access to and potential coverage for fertility services.

Treatment of small as well as large declines in lung function enhances recovery to baseline in people with CF.

BACKGROUND: The benefit of antibiotic treatment of acute drops in FEV1 percent predicted (FEV1pp) has been clearly established, but data from the early 2000s showed inconsistent treatment. Further, there is no empirical evidence for what magnitude of drop is clinically significant. METHODS: We used data from the CF Foundation Patient Registry (CFFPR) from 2016 to 2019 to determine the association between treatment (any IV antibiotics, only oral or newly prescribed inhaled antibiotics, or no antibiotic therapy) following a decline of ≥5% from baseline FEV1pp and return to 100% baseline FEV1pp days using multivariable logistic regression including an interaction between the magnitude of decline and treatment category. RESULTS: Overall, 16,495 PWCF had a decline: 16.5% were treated with IV antibiotics, 25.0% non-IV antibiotics, and 58.5% received no antibiotics. Antibiotic treatment was more likely for those with lower lung function, history of a positive PA culture, older age and larger FEV1 decline (p < 0.001). Treatment with IV antibiotics or oral/inhaled antibiotics was associated with a higher odds of recovery to baseline compared to no treatment across all levels of decline, including declines of 5%-10%. CONCLUSIONS: A large proportion of acute drops in FEV1pp continue to be untreated, especially in younger patients and those with higher baseline lung function. Acute drops as small as 5% predicted are less likely to be recovered if antibiotic treatment is not prescribed. These findings suggest the need for more aggressive antimicrobial treatment of acute drops in FEV1, including those of a magnitude previously believed to be associated with self-recovery.

Clinical outcomes at 9-10 years of age in children born with cystic fibrosis transmembrane conductance regulator related metabolic syndrome.

BACKGROUND AND OBJECTIVES: There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR). METHODS: We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010 and 2020. We classified all patients based on the clinical diagnosis reported by the CF care center and the diagnosis using CFF guideline definitions for CF and CRMS, classifying children into groups based on agreement between clinical report and guideline criteria. Descriptive statistics for the cohort were calculated for demographics, nutritional outcomes, and microbiology for the first year of life and lung function and growth outcomes were summarized for ages 6-10 years. RESULTS: From 2010 to 2020, there were 8765 children with diagnosis of CF or CRMS entered into the CFFPR with sufficient diagnostic data for classification, of which 7591 children had a clinical diagnosis of CF and 1174 had a clinical diagnosis of CRMS. CRMS patients exhibited normal nutritional indices and pulmonary function up to age 9-10 years. The presence of respiratory bacteria associated with CF, such as Pseudomonas aeruginosa from CRMS patients ranged from 2.1% to 9.1% after the first year of life. CONCLUSIONS: Children with CRMS demonstrate normal pulmonary and nutritional outcomes into school age. However, a small percentage of children continue to culture CF-associated respiratory pathogens after infancy.

Impact of loss to follow-up on survival estimation for cystic fibrosis.

PURPOSE: Deaths among those lost to follow-up (LTFU) in the Cystic Fibrosis Foundation Patient Registry (CFFPR) are critically important to the epidemiology of cystic fibrosis (CF). Unreported deaths could impact estimates of survival if LTFU is associated with disease trajectory. METHODS: We characterized the LTFU population (1986-2017) from the CFFPR and identified deaths via linkage with the National Death Index (NDI). Median predicted survival age and conditional survival were estimated with and without additional deaths and person-time from the NDI. RESULTS: Of the 10,582 individuals LTFU in the CFFPR, 2,460 (23.2%) matched to an NDI death record. Individuals who died after LTFU with a CF diagnosis were 43% female, 91% White/non-Hispanic, 59% had advanced CF lung disease based on last CFFPR recorded forced expiratory volume in one second (FEV1) %predicted <40 and 18% were post-lung transplant. Median predicted survival age during the most recent period available, 2013-2017, increased from 44.3 years (95% CI: 43.2, 45.7) to 45.8 years (95% CI 44.5, 47.1) with the inclusion of NDI data. CONCLUSIONS: Inclusion of deaths and additional person-time among those LTFU changed the point estimate of median predicted survival for most time periods and increased the point estimate from 2009 onwards.

Lung Function Decline in Cystic Fibrosis: Impact of Data Availability and Modeling Strategies on Clinical Interpretations.

Rationale: Studies estimating the rate of lung function decline in cystic fibrosis have been inconsistent regarding the methods used. How the methodology used impacts the validity of the results and comparability between studies is unknown. Objectives: The Cystic Fibrosis Foundation established a work group whose tasks were to examine the impact of differing approaches to estimating the rate of decline in lung function and to provide analysis guidelines. Methods: We used a natural history cohort of 35,252 individuals with cystic fibrosis aged ⩾6 years in the Cystic Fibrosis Foundation Patient Registry (CFFPR), 2003-2016. Modeling strategies using linear and nonlinear forms of marginal and mixed-effects models, which have previously quantified the rate of forced expiratory volume in 1 second (FEV1) decline (percent predicted per year), were evaluated under clinically relevant scenarios of available lung function data. Scenarios varied by sample size (overall CFFPR, medium-sized cohort of 3,000 subjects, and small-sized cohort of 150), data collection/reporting frequency (encounter, quarterly, and annual), inclusion of FEV1 during pulmonary exacerbation, and follow-up length (<2 yr, 2-5 yr, entire duration). Results: Rate of FEV1 decline estimates (percent predicted per year) differed between linear marginal and mixed-effects models; overall cohort estimates (95% confidence interval) were 1.26 (1.24-1.29) and 1.40 (1.38-1.42), respectively. Marginal models consistently estimated less rapid lung function decline than mixed-effects models across scenarios, except for short-term follow-up (both were ∼1.4). Rate of decline estimates from nonlinear models diverged by age 30. Among mixed-effects models, nonlinear and stochastic terms fit best, except for short-term follow-up (<2 yr). Overall CFFPR analysis from a joint longitudinal-survival model implied that an increase in rate of decline of 1% predicted per year in FEV1 was associated with a 1.52-fold (52%) increase in the hazard of death/lung transplant, but the results exhibited immortal cohort bias. Conclusions: Differences were as high as 0.5% predicted per year between rate of decline estimates, but we found estimates were robust to lung function data availability scenarios, except short-term follow-up and older age ranges. Inconsistencies among previous study results may be attributable to inherent differences in study design, inclusion criteria, or covariate adjustment. Results-based decision points reported herein will support researchers in selecting a strategy to model lung function decline most reflective of nuanced, study-specific goals.

Variability in cancer death certificate accuracy by characteristics of death certifiers.

Death certificates are the source for mortality statistics and are used to set public health goals. Accurate death certificates are vital in tracking outcomes of cancer. Deaths may be certified by physicians or other medical professionals, coroners, or medical examiners. Idaho is one of 3 states that participated in a Centers for Disease Control and Prevention-funded study to assess the concordance between cancer-specific causes of death and primary cancer site among linked cancer registry/death certificate data. We investigated variability in the accuracy of cancer death certificates by characteristics of death certifiers, including certifier type (physician vs coroner), physician specialty, years of experience as death certifier, and number of deaths certified. This study showed significant differences by certifier type/physician specialty in the accuracy of cancer mortality measured by death certificates. Nonphysician coroners had lower accuracy rates compared with physicians. Although nonphysician coroners certified less than 5% of cancer deaths in Idaho, they were significantly less likely to match the primary site from the cancer registry. Results from this study may be useful in the future training of death certifiers to improve the accuracy of death certificates and cancer mortality statistics.

Obesity in Cystic fibrosis: prevalence, trends and associated factors data from the US cystic fibrosis foundation patient registry.

Strong emphasis has been placed historically on increasing weight and improving nutritional status in cystic fibrosis patients. Due to correlation between nutritional indices (e.g. BMI) and lung function, CF Nutrition Guidelines have recommended BMI percentile goals at the 50th percentile or higher. Trends in increasing BMI across CF programs suggest significantly increasing proportions of overweight and obese status in recent years. We identify that between 2000 and 2019 there has been a relative decrease in underweight status by ∼40%, simultaneously with a > 300% increase in overweight status, and >400% increase in obesity. Patient specific factors associated with higher prevalence of obesity included age ≥46, living in a zip code where the median income was < $20,000, having at least one allele with a class IV or V mutation, a ppFEV1 >90 prescribed ivacaftor, and not prescribed pancreatic enzymes. Program specific factors were not identified.

Bone mineral density screening by DXA for people with cystic fibrosis: A registry analysis of patient and program factors influencing rates of screening.

BACKGROUND: Current guidelines recommend screening for Cystic Fibrosis (CF) related bone disease (CFBD) using dual-energy x-ray absorptiometry (DXA) for all people ≥ 18 years of age and select people ≥ 8 years of age. However, adherence to these guidelines is variable. This study aims to evaluate screening practices among adult programs in the US and identify patient and program-based characteristics which may influence screening. METHODS: The CF Foundation Patient Registry (CFFPR) was used to identify all people over the age of 18 who were seen at adult CF programs and received screening for CFBD using DXA at least once between 2014 and 2018. Associations with patient and program level characteristics were assessed using the Chi Square test. Patient level variables were also examined using standardized difference to assess for meaningful clinical differences in rates of screening. RESULTS: From 2014 to 2018, a total of 15,134 people over the age of 18 were identified in the CFFPR. Of these people, 9,023 (60%) received a DXA during the time period. The median rate of screening by program was 66% and programs in the highest quartile of screening obtained DXAs on >76% of their population. At the program level, larger size and increased adherence to other guideline practices such as OGTT screening and 4 visits, 4 cultures in a year correlated with higher rates of screening for CFBD. At the patient-level, people with lower lung function (FEV1 <90%) and those with CF related diabetes were more likely to be screened. People without health insurance were less likely to receive recommended screening. CONCLUSION: Screening practices for CFBD vary widely across adult programs in the US despite recommendations to screen all people over the age of 18. Factors identified in this analysis may be used to identify those people at highest risk of missing appropriate screening. CFBD has significant implications for our patients and therefore routine screening should be emphasized as part of standard care moving forward.

Real-world Associations of US Cystic Fibrosis Newborn Screening Programs With Nutritional and Pulmonary Outcomes.

Importance: Newborn screening (NBS) for cystic fibrosis (CF) has been universal in the US since 2010, but its association with clinical outcomes is unclear. Objective: To describe the real-world effectiveness of NBS programs for CF in the US on outcomes up to age 10 years. Design, Setting, and Participants: This was a retrospective cohort study using CF Foundation Patient Registry data from January 1, 2000, to December 31, 2018. The staggered implementation of NBS programs by state was used to compare longitudinal outcomes among children in the same birth cohort born before vs after the implementation of NBS for CF in their state of birth. Participants included children with an established diagnosis of CF born between January 1, 2000, to December 31, 2018, in any of the 44 states that implemented NBS for CF between 2003 and 2010. Data were analyzed from October 5, 2020, to April 22, 2022. Exposures: Birth before vs after the implementation of NBS for CF in the state of birth. Main Outcomes and Measures: Longitudinal trajectory of height and weight percentiles from diagnosis, lung function (forced expiratory volume in 1 second, [FEV1] percent predicted) from age 6 years, and age at initial and chronic infection with Pseudomonas aeruginosa using linear mixed-effects and time-to-event models adjusting for birth cohort and potential confounders. Results: A total of 9571 participants (4713 female participants [49.2%]) were eligible for inclusion, with 4510 (47.1%) in the pre-NBS cohort. NBS was associated with higher weight and height percentiles in the first year of life (weight, 6.0; 95% CI, 3.1-8.4; height, 6.6; 95% CI, 3.8-9.3), but these differences decreased with age. There was no association between NBS and FEV1 at age 6 years, but the percent-predicted FEV1 did increase more rapidly with age in the post-NBS cohort. NBS was associated with older age at chronic P aeruginosa infection (hazard ratio, 0.69; 95% CI, 0.54-0.89) but not initial P aeruginosa infection (hazard ratio, 0.88; 95% CI, 0.77-1.01). Conclusions and Relevance: NBS for CF in the US was associated with improved nutritional status up to age 10 years, a more rapid increase in lung function, and delayed chronic P aeruginosa infection. In the future, as highly effective modulator therapies become available for infants with CF, NBS will allow for presymptomatic initiation of these disease-modifying therapies before irreversible organ damage.

Prevalence, variability, and predictors of sinus surgery in pediatric patients with cystic fibrosis.

INTRODUCTION: Chronic rhinosinusitis is common among individuals with cystic fibrosis (CF) and has an impact on quality of life. Sinus surgery is a treatment option, but minimal literature exists regarding prevalence and indications. METHODS: Using the linked CF Foundation Patient Registry (CFFPR) - Pediatric Health Information Systems (PHIS) database, we investigated variability in receipt of surgery, predictors of surgery, and time to first surgery. We included individuals less than 18 receiving care between 2006 and 2015 at a CF Foundation care program that is also a PHIS-participating-hospital. We used logistic regression to examine predictors of receipt of surgery and a Kaplan-Meier curve to examine time to first surgery among those born 2005-2007. RESULTS: There were 11,545 children and adolescents and 2156 (18.7%) received at least one surgery. Variation in number of surgeries was observed across hospitals (median: 63 [IQR, 33-110]). There was an inconsistent pattern between receipt of surgery and markers of disease severity; those receiving surgery having increased odds of treatment use and pulmonary exacerbations and decreased odds of lower lung function and body mass index. Among the cohort of young children, 159 (14%) had at least one surgery with a median age at first surgery of 5.6 (IQR, 3.9-7.0). CONCLUSIONS: The use of sinus surgery is frequent, but variable, among children and adolescents. Clinical factors are associated with receipt of surgery, but further understanding is needed on other factors that impact variability in use. Our study indicates the need for additional evaluation of the management of CF-related CRS and indications for surgery.

Decreased survival in cystic fibrosis patients with a positive screen for depression.

BACKGROUND: The International Depression Epidemiological Study (TIDES) found elevated rates of screen positivity for depression and anxiety among individuals with cystic fibrosis (CF). Depression is associated with worse adherence and health-related quality of life in CF. We investigated the relationship with mortality. METHODS: Subjects were untransplanted participants in TIDES 12+ years of age receiving care at one of 45 collaborating US CF care centers who completed the Hospital Anxiety and Depression Scale and/or Center for Epidemiologic Studies Depression Scale during a stable visit between 2006 and 2010. Clinical characteristics and mortality data were obtained from the CF Foundation Patient Registry. The association of a positive screen with 5-year survival was evaluated using Cox Proportional Hazards modeling. RESULTS: Of 1005 eligible patients, 25% screened positive for depression and 34% screened positive for anxiety. Patients who screened positive for depression were more likely to be older, have a residual function mutation, public insurance, and more pulmonary exacerbations in the screening year. There were 96 deaths. The unadjusted 5-year Hazard Ratio (HR) for death among those with depression was 2.0; 95% CI (1.3, 3.0)]. When adjusted for predetermined potential confounders the HR for the entire population was 1.4; 95% CI (0.9, 2.2). The adjusted HR was higher in adults [1.6; 95% CI (1.0, 2.4)] and those screening in the severe range [2.0; 95% CI (1.2, 3.4)]. Anxiety was not associated with mortality. CONCLUSIONS: A positive depression screen is associated with increased mortality among adults with CF. Research into the etiology of this relationship is needed.

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.

BACKGROUND: 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. RESEARCH QUESTION: 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? STUDY DESIGN AND METHODS: 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. RESULTS: 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]). INTERPRETATION: 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.