Improvements in Lung Function Outcomes in Children with Cystic Fibrosis are Associated with Better Nutrition, Fewer Chronic Pseudomonas aeruginosa Infections, and Dornase Alfa Use

doi:10.1016/j.jpeds.2008.07.011

The Journal of Pediatrics

Volume 153, Issue 6, December 2008, Pages 752-757

https://doi.org/10.1016/j.jpeds.2008.07.011 Get rights and content

Objective

To compare lung function and nutritional outcomes in cystic fibrosis (CF) for 2 birth cohorts in our CF center.

Study design

Patients with CF born between 1985 and 2000 treated in our CF center before age 5 years were included. The patients were divided into 2 equal birth cohorts for comparison: birth cohort 1 (born between 1985 and 1992) and birth cohort 2 (born between 1993 and 2000). To compare lung function, we used forced expiratory volume in the first second (FEV₁)% predicted and FEV₁% predicted slope from age 6 to 12 years. We hypothesized that we would find significant improvements in lung function and nutritional outcomes in our patients with CF.

Results

The patients born between 1993 and 2000 (birth cohort 2) had better lung function, a slower rate of decline in lung function, and better nutritional outcomes compared with those born between 1985 and 1992 (birth cohort 1). Factors associated with a slower rate of decline in lung function in both groups were a higher baseline body mass index (BMI)%, a slower BMI% rate of decline, absence of chronic Pseudomonas aeruginosa respiratory infection, and initiation of dornase alfa (Pulmozyme) therapy before age 9 years.

Conclusion

Our results demonstrate dramatically improved lung function and nutritional outcomes in the children with CF in our center. The improvements in lung function outcomes are associated with better nutrition, fewer chronic P aeruginosa infections, and dornase alfa therapy.

Section snippets

Methods

We reviewed our database for lung function and nutritional data for all patients with CF born between 1985 and 2000 treated in our CF center at the Cincinnati Children's Hospital Medical Center before age 5 years. The patients were divided into 2 equal birth cohorts: birth cohort 1 (born between 1985 and 1992) and birth cohort 2 (born between 1993 and 2000).

Lung Function Outcomes

A total of 144 patients with CF born between 1985 and 2000 met the inclusion criteria for comparison of lung function outcomes. There were no significant differences in terms of race, sex, genotype, age of diagnosis, prevalence of pancreatic enzyme supplementation, or prevalence of chronic S aureus infection between birth cohort 1 and birth cohort 2 (Table I). Significant differences were found between the 2 cohorts in the prevalence of chronic P aeruginosa infection (P = .002), the prevalence

Discussion

This longitudinal cohort analysis has demonstrated a statistically significant improvement in the rate of decline in lung function in patients with CF. Studies analyzing the rate of decline in lung function in CF have yielded varied findings. Impaired glucose tolerance and diabetes have been associated with a faster decline in lung function.13, 14 Several studies, including ours, found an association between chronic P aeruginosa respiratory tract infection and a faster decline in lung function.

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Cited by (62)

Implementation of standardized cystic fibrosis care algorithm to improve the center data-quality improvement project international collaboration
2023, Journal of Cystic Fibrosis
A collaboration between the University of Michigan (U of M) Cystic Fibrosis Center (CFC) and Marmara University (MU) CFC was initiated to improve the health status of people with cystic fibrosis (pwCF) at MU through implementing Quality Improvement (QI) initiatives. The main aim was to improve lung function in children with FEV1pp <80. The secondary aim was to assess the changes in health related quality of life.
Included in the project were pwCF who received cystic fibrosis (CF) care at the MU CFC and were 6–18 years of age with an FEV1pp <80. Flow charts were created and a standardized CF care algorithm was implemented. Weekly case review were done to develop individualized treatment plans. Appropriate intervention was applied and patient data were assessed at baseline, 3, 6, 9 and 12 months. The Cystic Fibrosis Revised Questionnaire (CFQ-R) was completed.
55 pwCF were included (mean age:11.8 ± 3.3 years). Mean FEV1pp (SD) at baseline, 6 and 12 month was 63.7 (14.6), 66.9 (16.6), 70.4 (19.2), respectively, with a relative increase of 5.0% in 6 months (p:0.002) and 10.5% in 12 months compared to baseline (p<0.001). Physical functioning, eating problems and respiratory symptoms domains of the CFQ-R questionnaire were improved at the end of the one year for 6–13 (p = 0.024, p = 0.009, p = 0.002) and 13–18 year olds (p = 0.013, p = 0.002, p = 0.038).
There was significant improvement in pwCF with FEV1<80%pp after implementing this QI project. The processes and assessments used can be adopted by other low-middle income countries to improve similar measures.
Academy of Nutrition and Dietetics: 2020 Cystic Fibrosis Evidence Analysis Center Evidence-Based Nutrition Practice Guideline
2021, Journal of the Academy of Nutrition and Dietetics
Citation Excerpt :
In the systematic review of the literature, undernutrition demonstrated a clear longitudinal relationship with lung function decline and mortality.30-53 Participants who maintained a weight, length, weight-for-length, and BMI >50th percentile from infancy and early childhood had higher FEV1% (percent forced expiratory volume in 1 second) predicted values 4 to 16 years later, although there was no added improvement for those who maintained growth parameters >85th percentile compared with >50th percentile (Table).31-46 When monitoring clients, RDNs must use clinical judgment to determine whether a child with z scores below this cutoff is actually at nutrition risk or they are stable on a lower growth curve and assessment is not needed.
The Academy of Nutrition and Dietetics Evidence Analysis Center conducted a systematic review of the literature to develop an evidence-based practice guideline for primary nutrition issues in cystic fibrosis (CF). This guideline is designed to complement and build upon existing evidence-based CF nutrition guidelines. The objective of this guideline was to provide recommendations for registered dietitian nutritionists in the United States delivering medical nutrition therapy to individuals with CF and their families that fill gaps in current evidence-based guidelines on topics that are crucial in order to improve health and prevent disease progression. This guideline provides 28 nutrition recommendations to guide medical nutrition therapy, including nutrition screening, nutrition assessment, and dietary intake. For topics outside the scope of this guideline, practitioners are referred to external, evidence-based recommendations. The CF landscape is evolving rapidly with breakthroughs in cystic fibrosis transmembrane regulator modulators changing CF at a cellular level. Medical nutrition therapy for individuals with CF from infancy through advanced age requires novel and individualized approaches. The Academy Evidence Analysis Library CF guidelines provide a framework for expanding upon current knowledge to determine effective nutrition strategies for individuals with CF through long and healthy futures.
Seasonal variation of lung function in cystic fibrosis: Longitudinal modeling to compare a Midwest US cohort to international populations
2021, Science of the Total Environment
Characterizing seasonal trend in lung function in individuals with chronic lung disease may lead to timelier treatment of acute respiratory symptoms and more precise distinction between seasonal exposures and variability. Limited research has been conducted to assess localized seasonal fluctuation in lung function decline in individuals with cystic fibrosis (CF) in context with routinely collected demographic and clinical data. We conducted a longitudinal cohort study of 253 individuals aged 6–22 years with CF receiving care at a pediatric Midwestern US CF center with median (range) of follow-up time of 4.7 (0–9.95) years, implementing two distinct models to estimate seasonality effects. The outcome, lung function, was measured as percent-predicted of forced expiratory volume in 1 s (FEV₁). Both models showed that older age, being male, using Medicaid insurance and having Pseudomonas aeruginosa infection corresponded to accelerated FEV₁ decline. A sine wave model for seasonality had better fit to the data, compared to a linear model with categories for seasonality. Compared to international cohorts, seasonal fluctuations occurred earlier and with greater volatility, even after adjustment for ambient temperature. Average lung function peaked in February and dipped in August, and FEV₁ fluctuation was 0.81% predicted (95% CI: 0.52 to 1.1). Adjusting for temperature shifted the peak and dip to March and September, respectively, and decreased FEV₁ fluctuation to 0.45% predicted (95% CI: 0.08 to 0.82). Understanding localized seasonal variation and its impact on lung function may allow researchers to perform precision public health for lung diseases and disorders at the point-of-care level.
Evaluating the impact of 2006 Australasian Clinical Practice Guidelines for nutrition in children with cystic fibrosis in Australia
2018, Respiratory Medicine
Citation Excerpt :
Age, sex, pancreatic status, dornase alfa (Pulmozyme) therapy, number of ever-colonised positive sample of Pseudomonas aeruginosa and presence of a G551D mutation were considered as potential confounders in this study. Dornase alfa (Pulmozyme) was included to the analysis as a possible confounder because of its mucolytic therapy use, which might be an indication of a more severe lung disease and could potentially result in poorer nutritional outcomes in children undertaking this therapy [26]. Dornase alfa (Pulmozyme) was listed on the Australian Pharmaceutical Benefits Scheme in 1996 and recommended for children age of six years or older [27].
To determine the association between the implementation of the 2006 Australasian Clinical Practice Guidelines for Nutrition in Cystic Fibrosis (CF) and the nutritional status of children participating in the Australian Cystic Fibrosis Data Registry (ACFDR).
This research consisted of a quantitative study using ACFDR data and a survey of clinicians and dietitians treating children with CF. Two independent cohorts of children (2–5 years and 6–11 years) were selected from ACFDR between 1998 and 2014 (N = 2304). Generalised estimating equation model was used to assess weight, height and body mass index (BMI) z-scores for each patient before and after the implementation of the nutrition guidelines. A nationwide online survey was sent to 48 clinicians to explore the enablers and barriers to implementation of the guidelines.
Data analysis showed significant increase (p < 0.05) in mean weight, height and BMI z-scores ranging from 0.06 to 0.18 after implementation of the guidelines in both cohorts of children. Nineteen (39%) clinicians participated in the survey. The majority of the respondents adopted the recommendations into their practice and used the guidelines as part of their professional development. Structural barriers included a lack of adequate staff resources and clinic space for consultations, inappropriate staff classification, high staff turnover and lack of mentoring support.
In children participating in the ACFDR, nutritional status improved after the implementation of the 2006 guidelines. Survey results revealed enablers and barriers to guideline implementation and will inform implementation strategies for the revised Australasian nutrition guidelines for CF, released in 2017.
Use of FEV<inf>1</inf> in cystic fibrosis epidemiologic studies and clinical trials: A statistical perspective for the clinical researcher
2017, Journal of Cystic Fibrosis
Forced expiratory volume in 1 s (FEV₁) is an established marker of cystic fibrosis (CF) disease progression that is used to capture clinical course and evaluate therapeutic efficacy. The research community has established FEV₁ surveillance data through a variety of observational data sources such as patient registries, and there is a growing pipeline of new CF therapies demonstrated to be efficacious in clinical trials by establishing improvements in FEV₁.
In this review, we summarize from a statistical perspective the clinical relevance of FEV₁ based on its association with morbidity and mortality in CF, its role in epidemiologic studies of disease progression and comparative effectiveness, and its utility in clinical trials. In addition, we identify opportunities to advance epidemiologic research and the clinical development pipeline through further statistical considerations.
Our understanding of CF disease course, therapeutics, and clinical care has evolved immensely in the past decades, in large part due to the thoughtful application of rigorous research methods and meaningful clinical endpoints such as FEV₁. A continued commitment to conduct research that minimizes the potential for bias, maximizes the limited patient population, and harmonizes approaches to FEV₁ analysis while maintaining clinical relevance, will facilitate further opportunities to advance CF care.
Association of growth and nutritional parameters with pulmonary function in cystic fibrosis: a literature review
2016, Revista Paulista de Pediatria
Revisar a literatura que aborda a relação entre os parâmetros de crescimento e nutricionais com a função pulmonar em pacientes pediátricos com fibrose cística.
Dados foram coletados de artigos publicados nos últimos 15 anos em Inglês,Português e Espanhol através de pesquisa nas bases de dados eletrônicas – PubMed, Cochrane, Medline, Lilacs e Scielo – usando as palavras‐chave: fibrose cística, crescimento, nutrição, função pulmonar utilizando combinações variadas. Os artigos que analisaram a associação de longo prazo entre parâmetros de crescimento e nutricionais, com ênfase em crescimento, com doença pulmonar em fibrose cística, foram incluídos, sendo excluídos aqueles que analisaram apenas a relação entre os parâmetros nutricionais e fibrose cística e aqueles em que o objetivo era descrever a doença.
Sete estudos foram incluídos, com um total de 12.455 pacientes. Seis relataram relação entre parâmetros de crescimento e função pulmonar, incluindo um estudo que analisou apenas a associação de parâmetros de crescimento com a função pulmonar, e todos os sete relataram associação entre parâmetros nutricionais e função pulmonar.
A revisão sugere que a gravidade da doença pulmonar, determinada por espirometria, está associada com crescimento corporal e o estado nutricional em fibrose cística. Assim, a intervenção nesses parâmetros pode contribuir para um melhor prognóstico e expectativa de vida em pacientes com fibrose cística.
To review the literature addressing the relationship of growth and nutritional parameters with pulmonary function in pediatric patients with cystic fibrosis.
A collection of articles published in the last 15 years in English, Portuguese and Spanish was made by research in electronic databases – PubMed, Cochrane, Medline, Lilacs and Scielo – using the keywords cystic fibrosis, growth, nutrition, pulmonary function in varied combinations. Articles that addressed the long term association of growth and nutritional parameters, with an emphasis on growth, with pulmonary disease in cystic fibrosis, were included, and we excluded those that addressing only the relationship between nutritional parameters and cystic fibrosis and those in which the aim was to describe the disease.
Seven studies were included, with a total of 12,455 patients. Six studies reported relationship between growth parameters and lung function, including one study addressing the association of growth parameters, solely, with lung function, and all the seven studies reported relationship between nutritional parameters and lung function.
The review suggests that the severity of the lung disease, determined by spirometry, is associated with body growth and nutritional status in cystic fibrosis. Thus, the intervention in these parameters can lead to the better prognosis and life expectancy for cystic fibrosis patients.

View all citing articles on Scopus

: The authors have no conflicts of interest to disclose. There was no sponsor involvement in the design of this study or in the preparation of this manuscript for publication.

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Original articleImprovements in Lung Function Outcomes in Children with Cystic Fibrosis are Associated with Better Nutrition, Fewer Chronic Pseudomonas aeruginosa Infections, and Dornase Alfa Use

Objective

Study design

Results

Conclusion

Section snippets

Methods

Lung Function Outcomes

Discussion

J Pediatr

Chest

Am J Clin Nutr

J Pediatr

J Pediatr

J Pediatr

Prediction of mortality in patients with cystic fibrosis

N Engl J Med

Predictive 5-year survivorship model of cystic fibrosis

Am J Epidemiol

Patient registry 2006: annual data report

Improving rate of decline of FEV1 in young adults with cystic fibrosis

Thorax

Identifying treatments that halt progression of pulmonary disease in cystic fibrosis

Pediatr Res

Original article
Improvements in Lung Function Outcomes in Children with Cystic Fibrosis are Associated with Better Nutrition, Fewer Chronic Pseudomonas aeruginosa Infections, and Dornase Alfa Use

Improving rate of decline of FEV₁ in young adults with cystic fibrosis