Cystic fibrosis (CF) is one of the most common life-shortening genetic disorders with an incidence of 1:4000 live births in the US. CF is characterized by gastrointestinal and pulmonary manifestations. Malnutrition and growth faltering are prevalent, and occur even in infants diagnosed through newborn screening (NBS). Obstructive lung disease with recurrent respiratory infections is inevitable. Although median age of survival has improved steadily and reached 37 years in 2008, 20% of CF deaths still occur before 20 years of age. The overall objective of this research is to quantify the associations among NBS, malnutrition and lung disease in children with CF through epidemiological and clinical studies, with the ultimate goal of developing evidence-based guidelines for improving the quality of diagnosis, medical care and health outcomes of CF.
Specific Aims are: 1) to test the hypothesis that malnutrition and lung disease in CF are determined by """"""""baseline risk"""""""" (e.g., demographics, diagnosis, genotype, phenotype), and """"""""longitudinal risk"""""""" (e.g., changes in the preceding years) by using three ongoing, complimentary databases collected since 1985, namely, the CF Foundation Patient Registry, the Wisconsin Randomized Clinical Trial (RCT) of CF NBS Project and the Wisconsin Routine CF NBS Program, 2) to test the hypothesis that CF NBS implemented in the routine and research settings are similarly effective, by comparing nutritional and pulmonary outcomes of the Wisconsin Routine CF NBS cohort (born 1994-2003) to the Wisconsin RCT CF NBS cohort (born 1985-1994), and 3) to test the hypothesis that exclusive breastfeeding is associated with higher risk of growth faltering but lower risk of respiratory infections in the first two years of life, by conducting a prospective observational study that enrolls CF infants diagnosed through NBS in 2011-2015 soon after birth from four CF Centers in three states (WI, IN and UT) to systematically obtain detailed data on breastfeeding (exclusive/partial, duration) and formula (type, caloric density, amount) at frequent intervals in order to examine the potential benefits and risks of breastfeeding on nutritional and pulmonary outcomes. No other investigation has comparable researchers and tools to conduct the proposed work. The Principal Investigator is a nationally recognized CF epidemiologist known for her expertise in utilizing large complex longitudinal databases for outcome studies. With NIDDK's support since 2002, the Principal Investigator's work related to Specific Aim 1 has generated new, evidence-based knowledge that improved the clinical practices of CF. In view of the nationwide implementation of CF NBS beginning 2010, the clinical and public health impacts as a result of completing Specific Aims 2 and 3 are also foreseeable in the near future. Accomplishing this grant will advance the understanding of critical determinants of malnutrition and lung disease progression in CF, improve clinical practices of CF, enhance health outcomes of children with CF, and resolve the controversy on the potential benefits and risks of breastfeeding associated with CF in order to establish optimal feeding guidelines.
Cystic fibrosis is a genetic disease that affects more than 30,000 Americans. Malnutrition and lung disease reduce survival of cystic fibrosis patients;20% of deaths occur before 20 years of age and half die before mid 30's. This research project includes epidemiological and clinical studies that will generate new knowledge needed to develop evidence-based guidelines for improving the quality of diagnosis, medical care and clinical outcomes of children with cystic fibrosis.
|Ma, Huijuan; Peng, Limin; Zhang, Zhumin et al. (2018) Generalized accelerated recurrence time model for multivariate recurrent event data with missing event type. Biometrics 74:954-965|
|Sanders, Don B; Zhang, Zhumin; Farrell, Philip M et al. (2018) Early life growth patterns persist for 12?years and impact pulmonary outcomes in cystic fibrosis. J Cyst Fibros 17:528-535|
|Zhang, Zhumin; Lindstrom, Mary J; Farrell, Philip M et al. (2016) Pubertal Height Growth and Adult Height in Cystic Fibrosis After Newborn Screening. Pediatrics 137:|
|Wang, Wenjie; Chen, Ming-Hui; Chiou, Sy Han et al. (2016) Onset of persistent pseudomonas aeruginosa infection in children with cystic fibrosis with interval censored data. BMC Med Res Methodol 16:122|
|Sun, Xiaoyan; Peng, Limin; Huang, Yijian et al. (2016) Generalizing Quantile Regression for Counting Processes with Applications to Recurrent Events. J Am Stat Assoc 111:145-156|
|Zhang, Zhumin; Shoff, Suzanne M; Lai, HuiChuan J (2015) Comparing the Use of Centers for Disease Control and Prevention and World Health Organization Growth Charts in Children with Cystic Fibrosis through 2 Years of Age. J Pediatr 167:1089-95|
|Levy, Hara; Farrell, Philip M (2015) New challenges in the diagnosis and management of cystic fibrosis. J Pediatr 166:1337-41|
|Zhang, Zhumin; Lindstrom, Mary J; Lai, HuiChuan J (2013) Pubertal height velocity and associations with prepubertal and adult heights in cystic fibrosis. J Pediatr 163:376-82|
|Lin, Feng-Chang; Cai, Jianwen; Fine, Jason P et al. (2013) Nonparametric estimation of the mean function for recurrent event data with missing event category. Biometrika 100:|
|Shoff, Suzanne M; Tluczek, Audrey; Laxova, Anita et al. (2013) Nutritional status is associated with health-related quality of life in children with cystic fibrosis aged 9-19 years. J Cyst Fibros 12:746-53|
Showing the most recent 10 out of 18 publications