Progress 08/01/02 to 09/30/11
Outputs
OUTPUTS: This is a prospective, observational study designed to evaluate the medical benefits of a routine, statewide neonatal screening program for cystic fibrosis (CF) in Wisconsin. Pediatric patients from five CF Centers in Wisconsin were invited to participate. Enrollment ended 12/31/10 with 171 participants. PARTICIPANTS: Individuals: HuiChuan Lai, Principal Investigator. Directs and oversees the conduct of the study. Suzanne Shoff, Project Manager. Manages enrollment and participation of subjects, conducts activities involving Institutional Review Boards and oversees day-to-day activities. Partner organizations: Wisconsin's State Laboratory of Hygiene, Children's Hospital of Wisconsin (Milwaukee). Medical fellowship was completed by one pulmonologist. Graduate training is ongoing for one Master's student. Advanced training is ongoing for one post-doctoral fellow. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
The impact of infant feeding practices on growth and pulmonary outcomes is nearly complete. Analysis of pulmonary function, pulmonary infections and nutritional status in the recently enrolled newborn screened group compared to the research-based groups of newborn screening and conventional diagnosis, and national CF registry cohorts of newborn screened and conventional diagnosis groups are ongoing.
Publications
- Yan, J., Cheng, Y., Fine, J.P., and Lai, H.J. (2010) Uncovering symptom progression history from disease registry data with application to young cystic fibrosis patients. Biometrics 66:594-602.
- Zhang, Z., Shoff, S.M., and Lai, H.J. (2010) Incorporating genetic potential when evaluating stature in children with cystic fibrosis. J Cystic Fibrosis 9:135-142.
|
Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: This is a prospective, observational study designed to evaluate the medical benefits of a routine, statewide neonatal screening program for cystic fibrosis (CF) in Wisconsin. Approximately 233 subjects, from 6 CF Centers in Wisconsin, will be invited to participate. Currently we are continuing enrollment, and are following consented subjects from 5 CF Centers and patients who moved out of state. To date, 151 patients have enrolled. PARTICIPANTS: Individuals: HuiChuan Lai, Principal Investigator. Directs the conduct of the study. Suzanne Shoff, Project Manager. Manages enrollment of subjects and tracking participation, conducts activities involving Institutional Review Boards, oversees day-to-day activities. Partner organizations: Wisconsin's State Laboratory of Hygiene, Children's Hospital of Wisconsin (Milwaukee). Undergraduate training provided to one undergraduate student. Graduate training completed by one Master's degree student. Graduate training is ongoing for one doctoral student and one post-doctoral fellow. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Extensive medical record review is ongoing to investigate the impact of infant feeding practices on growth. Further work with this data will be instrumental in informing the development of targeted infant feeding guidelines for children with cystic fibrosis. Analysis of pulmonary function and infection in the routine screened group compared to the research-based screened group is underway.
Publications
- Lai, H. J., Shoff, S. M., Farrell, P. M. (2009) Recovery of Birth Weight Z Score Within 2 Years of Diagnosis Is Positively Associated With Pulmonary Status at 6 Years of Age in Children With Cystic Fibrosis. Pediatrics 123: 714-722.
|
Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: This is a prospective, observational study designed to evaluate the medical benefits of a routine, statewide neonatal screening program for cystic fibrosis (CF) in Wisconsin. Approximately 233 subjects, from 6 CF Centers in Wisconsin, will be invited to participate. Currently, we are continuing enrollment, and are following consented subjects from the Madison and Milwaukee CF Centers, and patients who moved out of state. During the reporting period, recruitment plans were modified for the satellite centers in Wisconsin. IRB approval was obtained to conduct enrollment by mail for this sub-group of eligible patients. To date, 50 Madison subjects and 66 Milwaukee subjects have agreed to participate, which represents about 87% of eligible subjects from these 2 centers. Three subjects reside outside of Wisconsin. Approximately 66% of participants have provided dietary information and/or biologic specimens. PARTICIPANTS: Individuals: HuiChuan Lai, Principal Investigator. Directs the conduct of the study. Suzanne Shoff, Project Manager. Manages enrollment of subjects and tracking participation, conducts activities involving Institutional Review Boards, oversees day-to-day activities. Partner organizations: Wisconsin's State Laboratory of Hygiene, Children's Hospital of Wisconsin (Milwaukee). Sarah Jadin, Grace Wu, graduated students. Extensive data collection activities. Assist with data analysis. Training provided for one pediatric pulmonary fellow, two graduate students and two undergraduate students. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Based on feedback from Cystic Fibrosis Center clinicians, we initiated a new protocol to consent satellite center patients by mail. Institutional Review Board approval for the protocol change was recently granted.
Impacts
Extensive medical record review is ongoing to investigate the impact of infant feeding practices on growth. Further work with this data will be instrumental in informing the development of targeted infant feeding guidelines for children with cystic fibrosis. These preliminary results were presented at the Annual North American Cystic Fibrosis Conference in 2008. Preliminary analysis of growth of the routine screened group (this study's cohort) compared to growth of research-based screening were also presented at the conference and indicate that the growth of children who received routine newborn screening for CF is as good or better than those diagnosed in a research setting. These preliminary findings require longer-term follow-up.
Publications
- No publications reported this period
|
Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: This is a prospective, observational study designed to evaluate the medical benefits of a routine, statewide neonatal screening program for cystic fibrosis (CF) in Wisconsin. Approximately 233 subjects, from 6 CF Centers in Wisconsin, will be invited to participate. Currently, we are continuing enrollment, and are following consented subjects from the Madison and Milwaukee CF Centers. To date, 45 Madison subjects and 60 Milwaukee subjects have agreed to participate, which represents about 85% of eligible subjects from these 2 centers. Approximately 50% of participants have provided dietary information and/or biologic specimens. Patients from the other CF centers will be invited to participate during the next year.
PARTICIPANTS: Individuals: HuiChuan Lai, Principal Investigator. Directs the conduct of the study. Suzanne Shoff, Project Manager. Manages enrollment of subjects and tracking participation, conducts activities involving Institutional Review Boards, oversees day-to-day activities. Partner organizations: Wisconsin's State Laboratory of Hygiene, Children's Hospital of Wisconsin (Milwaukee)
TARGET AUDIENCES: Scientific Community, Health Care Professionals and People with Cystic Fibrosis
Impacts
Because this study is in early stages of data collection, there are no project outcomes to report at this time.
Publications
- No publications reported this period
|
Progress 01/01/06 to 12/31/06
Outputs
Cystic fibrosis (CF) is one of the most common life-threatening genetic disorders with an incidence of 1:3400 in Caucasians. Although CF begins in early infancy, delayed diagnosis is common and often leads to severe malnutrition. Obstructive lung disease is inevitable; the majority of CF patients die from cardiorespiratory failure and one-third die before age 20 years. Advances in the past two decades have proven that CF neonatal screening is feasible and leads to nutritional, pulmonary, and possibly survival benefits. However, controversy exists whether implementing a routine statewide CF neonatal screening program provides similar nutritional and pulmonary benefits proven in the research setting because screening procedures and therapeutic interventions vary widely among screening programs. The objective of this study is to characterize nutritional and pulmonary status of all children with CF (ages 1-11 years at study initiation) identified through the Wisconsin
Routine CF Neonatal Screening Program, which began in 1994. Our aim is to test the hypothesis that implementing the Wisconsin Routine Program provides similar health benefits that have been proven in the research setting. We will compare the health status of this cohort to 2 other cohorts of children with CF that have been monitored extensively in the clinical research setting. We will also compare the Wisconsin Routine Program cohort to a national control cohort derived from the CF Foundation Registry. Data for this longitudinal study will come from ongoing review of subjects' medical records and data in from the CF Registry and through additional surveys. Currently, the project is enrolling subjects and is in the early stages of data collection. Thirty-eight subjects have consented to participation in Madison CF Center and 17 at the Milwaukee CF Center. Initiation of the study at 3 other CF Centers serving Wisconsin residents is ongoing.
Impacts
The scientific information gained from this proposed study will provide new evidence to judge the medical benefits of a routine, statewide neonatal screening program for CF in Wisconsin. The new knowledge will also assist policy makers in planning/implementing future CF newborn screening programs. Current knowledge about the benefits of neonatal screening for CF is derived from studies conducted in the research setting, which incorporated comprehensive evaluation and treatment into study protocol. We intend to evaluate the clinical progression of children, identified as having CF through Wisconsin's routine neonatal screening program, who are seen in a non-research clinical setting, and compare this to the nutritional and pulmonary status of CF children identified through a neonatal screening program in the research setting.
Publications
- Grosse SD, Rosenfeld M, Devine OJ, Lai HJ, Farrell PM. 2006. Potential impact of newborn screening for cystic fibrosis on child survival: a systematic review and analysis. Journal of Pediatrics.149:362-366.
- Lai HJ. 2006 Classification of nutritional status in patients with cystic fibrosis. Current Opinions in Pulmonary Medicine. 12;422-427.
|
Progress 01/01/05 to 12/31/05
Outputs
The overall goal of this study is to determine whether malnutrition predisposes patients with cystic fibrosis (CF) to increased risks of pulmonary deterioration. We are utilizing two ongoing, complementary longitudinal databases (CF Foundation Patient Registry, abbreviated as CFF Registry, and the Wisconsin CF Neonatal Screening Project) collected since 1985 to quantify the relationships between malnutrition, lung disease and survival. Baseline and short-term risk models were employed to evaluate specific aspects of this temporal association. Baseline models were developed under the assumption that CF is associated with variable degree of severity, and patients having milder CF, in comparison with those having more severe CF, have better prognosis that is independent from subsequent treatment. Baseline results indicated that patients diagnosed early through prenatal/neonatal screening for CF (SCREEN) have a lower risk of shortened survival compared to those diagnosed
at variables ages because of signs and symptoms (SYMPTOM). Further, in the SYMPTOM group, the risk of shortened survival was highest in patients presenting with respiratory symptoms and malnutrition, followed by those presenting with respiratory symptoms alone or malnutrition alone, and lowest in patients presenting with other less severe symptoms. A greater risk of poor lung function was observed in patients with meconium ileus and in the SYMPTOM group, compared to the SCREEN group. For short-term risk models, we hypothesized that pulmonary decline is caused, in part, by short-term nutritional decline that is manifested as persistent malnutrition or worsening malnutrition during the preceding 3-4 years. The risk of having poor lung function at age 6 was significantly lowered as various indices of nutritional status at age 3, increased. Overall, our findings indicate that, while persistent and worsening height Z-score exhibited similar associations to lung function tests, patients
with persistently low body mass index Z-scores (BMIZ) had worse lung function than those with worsening BMIZ. We also evaluated the relationship of sustained, normal plasma linoleic acid levels (PLA) and sustained, high energy intake (HEN) to physical growth during the period of 0-2 years after diagnosis. Adequate growth was defined as attaining a weight Z-score (WtZ) comparable to WtZ at birth. Sixty-eight percent of screened patients and 54 percent of conventionally diagnosed patients achieved adequate growth within 2 years of diagnosis. Compared to having neither HEN or PLA, the likelihood of being a responder was greatest with combined HEN and PLA (p<0.01), followed by HEN only (p=0.04). In conclusion, HEN and PLA are critical in promoting adequate weight gain in newly diagnosed children with CF. We are in the process of extending the diet/growth analyses to the age period of 2-10 years of age and have also initiated developing short-term risk models pertinent to the adolescent
period.
Impacts
This project has generated new and important information with regard to how mode of diagnosis and initial disease presentation may influence survival and lung disease outcome in CF patients. Knowledge gained from these baseline risk models will allow us to develop a system to classify intrinsic disease severity in newly diagnosed CF patients. Knowledge gained from short-term risk models, which are currently being developed, will lead to better understanding of the timing and rate of nutritional deterioration and their relationships to pulmonary deterioration. The clinical impact as a result of completing this project are highly significant. In fact, the PI's work has already changed the clinical practices of CF. For example, Dr. Lai proved that the percentage of ideal body weight (percentIBW) index, which has been used to define nutrition failure in CF children for more than a decade, erroneously classifies nutritional status and recommended this index to be
abandoned. This recommendation prompted the CF Foundation to form an Ad Hoc Committee in January 2005 to revise their current Clinical Nutrition Practice Guidelines. Dr. Lai is a key member in this committee. In addition, other findings from this project will be used by the CF Foundation Ad Hoc Nutrition Classification Committee to develop new standards to evaluate treatment responsiveness.
Publications
- Lai HC, Cheng Y, Farrell PM. 2005. The survival advantage of cystic fibrosis patients diagnosed through neonatal screening: Evidence from the US Cystic Fibrosis Patient Registry data. J Pediatr 147:S57-S63.
- Shoff SM, Ahn H, Davis LA, Lai HC. 2006. Temporal associations between energy intake, plasma linoleic acid and growth improvement in response to treatment initiation after diagnosis of cystic fibrosis. Pediatrics 117:391-399.
- Abstracts presented at the 19th Annual North American Cystic Fibrosis Conference, October 2005, Baltimore, MD
- Cheng Y, Ahn H, Lai HJ. 2005 Comparison of persistent versus worsening malnutrition to lung disease outcones in young children with cystic fibrosis.
- Zhang Z, Cheng Y, Lai HJ. 2005 Characterization of the timing and magnitude of linear growth velocity in adolescents with cystic fibrosis.
|
Progress 01/01/04 to 12/31/04
Outputs
The overall goal of this project is to address the following primary hypothesis: malnutrition predisposes patients with cystic fibrosis (CF) to increased risks of pulmonary deterioration. Two ongoing, complementary longitudinal databases collected since 1985 were utilized to quantify the relationships between malnutrition, lung disease outcome and survival. During the last project period, we have completed the development of baseline risk models, which predict survival and lung disease outcomes based on demographic and disease characteristics present at the time of CF diagnosis. Findings from baseline risk models generated two publications. In addition, we have initiated the development of short-term risk models. These models are designed to gain insights on how and at what rate nutritional deterioration contributes to subsequent pulmonary failure or death, after taking into account for baseline risks. The first study was conducted to identify appropriate indicators
of malnutrition. Our results lead to the conclusion that body mass index percentile rather than percentage of ideal body weight should be used as the indicator for underweight, which has also been published. Several studies are being conducted to combine body mass index percentile with other indicators of growth to the development of short-term risk models.
Impacts
This project has generated new and important information regarding CF disease progression, which can be utilized to improve survival and the quality of life of CF patients. Knowledge gained from the baseline risk models, which are designed to examine whether demographic and disease characteristics present at the time of CF diagnosis predict prognosis, will allow us to develop a system to classify intrinsic disease severity in newly diagnosed CF patients to facilitate clinical care of patients with CF.
Publications
- Lai HC, Cheng Y, Cho H, Kosorok MR, Farrell PM. Association between initial disease presentation, lung disease outcomes and survival in patients with cystic fibrosis. Am J Epidemiol 2004;159:537-546.
- Li Z, Lai HC, Kosorok MR, Laxova A, Rock MJ, Splaingard ML, Farrell PM. Longitudinal pulmonary status in cystic fibrosis children presenting with melonium ileus. Pediatr Pulmonol 2004;38:277-84.
- Zhang Z, Lai HC. Comparison of body mass index percentile and percentage of body weight for screening malnutrition in children with cystic fibrosis. Am J Clin Nutr 2004;80:982-91.
- Lai HC, Cheng Y, Farrell PM. The survival advantage of cystic fibrosis patients diagnosed through neonatal screening: Evidence from the US Cystic Fibrosis Patient Registry data. J Pediatr 2005 (In press)
- Cheng Y, Ahn H, Lai HC. Associations between malnutrition and lung disease outcomes in young children with cystic fibrosis. Pediatr Pulmonol 2004 suppl: abstract no. 381. (Presented in the 18th Annual North American Cystic Fibrosis Conference, October 2004, St Louis, MO)
|
Progress 01/01/03 to 12/31/03
Outputs
The overall goal of this project is to address the following primary hypothesis: malnutrition predisposes patients with cystic fibrosis (CF) to increased risks of pulmonary deterioration. Two ongoing, complementary longitudinal databases collected since 1985 were utilized to quantify the relationships between malnutrition, lung disease outcome and survival. During the last project period, we have focused our studies to answer the question whether the demographic and disease characteristics present at the time of CF diagnosis predict prognosis that is independent from subsequent treatment. Our first study was conducted to determine if the mode of diagnosis and initial disease presentation influence lung disease and survival in CF patients. The study population included 27,703 patients who were reported to the 1986-2000 CF Foundation Registry. Patients were segregated into 4 diagnostic categories: meconium ileus (MI), prenatal/neonatal screening (SCREEN), positive
family history (FH), and symptoms other than MI (SYMPTOM). Patients in the MI or the SYMPTOM groups were associated with significantly greater risks of shortened survival, Pseudomonas aeruginosa (Pa) acquisition, and forced expiratory volume in one second (FEV-1) below 70% of predicted, when compared to those in the SCREEN group. Within the SYMPTOM group, the greatest risks of shortened survival, Pa acquisition and FEV-1 < 70% occurred in patients presenting with combined respiratory and gastrointestinal symptoms, followed by respiratory or gastrointestinal symptoms alone; the best outcomes were in patients with other presenting features. Additionally, patients with presumably severe genotypes (delta F508 plus other class I, II, III mutations in both alleles) had greater risks of shortened survival and Pa acquisition compared to patients with presumably mild genotype (class IV or V mutations in one or both alleles). Results from this study will be published in the American Journal of
Epidemiology in March of 2004.
Impacts
This project has generated new and important information regarding CF disease progression, which can be utilized to improve survival and the quality of life of CF patients. Knowledge gained will allow us to develop a system to classify intrinsic disease severity in newly diagnosed CF patients to facilitate clinical care of patients with CF.
Publications
- Lai HC, Cheng Y, Cho H, Kosorok MR, Farrell PM. Association between initial disease presentation, lung disease outcomes and survival in patients with cystic fibrosis. Am J Epidemiol 2004; vol 159; issue 6. (In press.)
|
Progress 01/01/02 to 12/31/02
Outputs
The overall goal of this project is to address the following primary hypothesis: malnutrition predisposes patients with cystic fibrosis (CF) to increased risks of pulmonary deterioration. Two ongoing, complementary longitudinal databases collected since 1985 were utilized to quantify the relationships between malnutrition, lung disease outcome and survival. During the last project period, we have focused our studies to answer the question whether the demographic and disease characteristics present at the time of CF diagnosis predict prognosis that is independent from subsequent treatment. Our first study examined extensively the relationships between gender, age and mode of presentation at the time of CF diagnosis. The study population consisted of 11,275 patients who were diagnosed during 1986-1998 and reported to the CF Foundation Registry. Parallel analyses were performed on data obtained from Wisconsin patients identified prospectively during 1985-1994 (from a
randomized clinical trial). Analyses on the registry data showed that females identified because of symptoms other than meconium ileus (MI) were diagnosed at significantly older ages (median = 12.7 months) than males (median = 8.7 months), p < 0.001. The delay in diagnosis for females was most evident among non-MI patients presenting with respiratory symptoms only (median = 40.7 versus 22.3 months, p < 0.001). Analyses on Wisconsin patients demonstrated no significant gender differences in respiratory symptoms between males and females during their first 10 years of life. A delay in the diagnosis of females with CF was discovered, suggesting either differential recognition of respiratory symptoms or a gender bias. Our next study was designed to examine whether patients presenting with "mild CF" compared to those presenting with "severe CF" at the time of diagnosis are associated with better clinical outcomes. The MILD group included patients who were identified via prenatal/neonatal
screening or a positive family history before 3 months of age, and who were asymptomatic at the time of diagnosis. The SEVERE group included patients who were diagnosed at variable ages because of signs or symptoms of CF. Initial analyses demonstrated that patients in the MILD group were associated with lower risk of death compared to patients in the SEVERE group. Currently, we are performing additional analyses to examine whether the observed survival differences between the MILD and the SEVERE groups also extend to nutritional and pulmonary outcomes. Preliminary results showed that acquisition of P. aeruginosa was significantly earlier in the SEVERE than the MILD group. We expect to publish results from these studies during 2003.
Impacts
This project has generated new and important information regarding CF disease progression, which can be utilized to improve survival and the quality of life of CF patients. Knowledge gained from the baseline risk models, which are designed to examine whether demographic and disease characteristics present at the time of CF diagnosis predict prognosis, will allow us to develop a system to classify intrinsic disease severity in newly diagnosed CF patients to facilitate clinical care of patients with CF.
Publications
- Lai HC, Kosorok MR, Laxova A, Farrell PM. Delayed diagnosis in females with cystic fibrosis in the United States. Am J Epidemiology 2002;156:165-173.
|
|