Elsevier

Advances in Pediatrics

Volume 55, Issue 1, September 2008, Pages 99-121
Advances in Pediatrics

Cystic Fibrosis: a Review of Pulmonary and Nutritional Therapies

https://doi.org/10.1016/j.yapd.2008.07.015Get rights and content

Section snippets

Cystic fibrosis genetics

The CF gene was identified in 1989 and to date more than 1500 mutations have been described [1]. The CFTR mutations can be grouped into six classes [2]. Class 1 mutations affect the transcription of CFTR by formation of premature stop codons into the messenger RNA. In most cases the introduction of a premature stop codon results in a truncated protein that will undergo degradation through nonsense-mediated decay, resulting in total absence of CFTR protein. Class 2 mutations involve

Pathophysiology of cystic fibrosis pulmonary disease

The pulmonary manifestations are the main cause of morbidity and mortality in CF patients. CFTR is located on the apical surface of airway epithelial cells and serosal cells of the submucosal glands. A lack of CFTR activity leads to decreased chloride secretion as well as sodium hyperabsorption since one of the physiologic functions of CFTR is to inhibit the epithelial sodium channel [3]. This results in a decreased airway surface liquid volume, which leads to collapse of respiratory cilia,

Treatment of cystic fibrosis lung disease

Treatment of CF lung disease can be broadly divided into two categories based on their primary target within the cascade of CF pathophysiology (see Fig. 1) into symptomatic treatment that addresses downstream effects of the CFTR gene defect and those targeting the underlying abnormality. Symptomatic therapy includes anti-infective and anti-inflammatory therapies as well as agents that improve mucus clearance. Therapies that target the CFTR defect include airway surface fluid hydration, ion

Growth and nutrition

Malnutrition is a key feature of CF. Defective CFTR in the pancreatic epithelium results in ductal obstruction by proteinaceous secretions and acinar destruction. CF patients become pancreatic insufficient when more than 95% of total pancreatic exocrine function is lost [126]. These patients develop fat, protein, and carbohydrate malabsorption and are at risk for fat soluble vitamin deficiencies (ie, vitamins A, D, E, and K) as well as other mineral deficiencies.

Nutrition and lung function are

Cystic fibrosis–related diabetes

Cystic fibrosis–related diabetes (CFRD) can develop in CF patients as a consequence of the pancreatic pathology. The prevalence increases with age; the average age of onset is between 18 and 21 years [142]. It rarely develops in patients younger than age 10 [143]. Therefore, annual screening for CFRD with an oral glucose tolerance test starts at age 10.

The onset of CFRD is often insidious and the diagnosis is usually preceded by a decline in pulmonary function [144], [145]. Therefore, delaying

Summary

In summary, there is a significant interplay between the pulmonary manifestations and nutritional status of CF patients. The advances in CF clinical care in the past 2 decades are mainly attributed to anti-infective therapy as well as aggressive nutritional management. Currently, there are multiple therapeutic agents that are in clinical trial that target either the underlying CFTR defect or the downstream effects of CFTR. The broad spectrum of therapeutic agents being studied as well as the

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