Gastrointestinal outcomes and confounders in cystic fibrosis

D Borowitz, PR Durie, LL Clarke… - Journal of pediatric …, 2005 - journals.lww.com
D Borowitz, PR Durie, LL Clarke, SL Werlin, CJ Taylor, J Semler, RC De Lisle, P Lewindon…
Journal of pediatric gastroenterology and nutrition, 2005journals.lww.com
Until the mid 20th century, children with cystic fibrosis (CF) died at a young age from a
combination of malnutrition and suppurative lung disease. In the past three to four decades,
coincident with new treatments for pulmonary complications and the use of high-calorie diets
without restrictions on fat intake, there has been marked and progressive improvement in
lung function, nutritional status and survival. However, treatment for pancreatic insufficiency,
which affects most individuals with CF, remains largely unchanged, and there have been …
Until the mid 20th century, children with cystic fibrosis (CF) died at a young age from a combination of malnutrition and suppurative lung disease. In the past three to four decades, coincident with new treatments for pulmonary complications and the use of high-calorie diets without restrictions on fat intake, there has been marked and progressive improvement in lung function, nutritional status and survival. However, treatment for pancreatic insufficiency, which affects most individuals with CF, remains largely unchanged, and there have been few advances in our understanding and management of gastrointestinal problems in this population.
Pancreatic Enzyme Replacement Therapy (PERT), principally using enzyme extracts of porcine origin, has been the mainstay for treating maldigestion resulting from pancreatic insufficiency (PI) for over a century. Powdered PERT was instituted before the 1931 creation of the United States Food and Drug Administration (FDA) and the subsequent Federal Food, Drug and Cosmetic Act of 1938 that required proof of safety and efficacy before approval of drugs for marketing. Enteric-coated microcapsules, the most commonly used PERT, have never been FDA approved. After the epidemic of fibrosing colonopathy in the early 1990s, a condition that was clearly related to high doses of exogenous pancreatic enzymes (1), the FDA initiated a process of re-evaluating the safety and efficacy of PERT. In 2004, the FDA released a draft of a new Guidance Document for public comment (2) that stated that within the next 4 years, all manufacturers of current enzyme products will need to submit a New Drug Application to the FDA with proof of safety in manufacturing, stability and efficacy.
Lippincott Williams & Wilkins