Upon completion of the chapter, the reader will be able to:
Explain the pathophysiology of cystic fibrosis (CF) and its multiorgan system involvement.
Describe the common clinical presentation and diagnosis of CF.
Consider long-term treatment goals with respect to clinical course and prognosis of CF.
Identify nonpharmacologic therapies for CF management.
Recommend appropriate pharmacologic therapies for chronic CF management.
Design appropriate antibiotic regimens for acute pulmonary exacerbations of CF.
Apply pharmacokinetic principles when calculating drug doses in CF patients.
Formulate monitoring plans for acute and chronic CF pharmacotherapy.
Cystic fibrosis (CF) is an inherited multiorgan system disorder affecting children and, increasingly, adults. It is the most common life-shortening genetic disease among White patients and the major cause of severe chronic lung disease and pancreatic insufficiency in children. Disease generally manifests as mucosal obstruction of exocrine glands caused by defective ion transport within epithelial cells. Due to the array of affected organ systems and complicated medical therapies, appropriate CF treatment necessitates interprofessional team collaboration.
EPIDEMIOLOGY AND ETIOLOGY
In the United States, CF most commonly occurs in White patients, affecting approximately 1 in 3200 individuals. CF is less common in Hispanics (1 in 14,000), African Americans (1 in 15,000), and Asian Americans (1 in 35,000).1 CF is inherited as an autosomal recessive trait, and approximately 1 in 25 White patients are heterozygous carriers. Offspring of a carrier couple (each parent being heterozygous) have a 1 in 4 chance of having the disease (homozygous), a 1 in 2 chance of being a carrier (heterozygous), and a 1 in 4 chance of receiving no trait. The CFTR gene mutation is found on the long arm of chromosome 7 and encodes for the CF transmembrane regulator (CFTR) protein, which functions as a chloride channel to transport water and electrolytes. Over 2000 mutations have been described in the CFTR gene; however, the Phe508del mutation (also known as F508del or ΔF508) is most common and present in about 70% to 90% of CF patients.1–3
CF is a disease of exocrine gland epithelial cells where CFTR expression is prevalent. Normally, these cells transport chloride through CFTR chloride channels with sodium and water accompanying this flux across the cell membrane (Figure 17–1). CFTR is regulated by protein kinases in response to varying levels of the intracellular second messenger cyclic-3′,5′-adenosine monophosphate (cAMP). CFTR also downregulates the epithelial sodium channel and regulates calcium-activated chloride and potassium channels, and it may function in exocytosis and formation of plasma membrane molecular complexes and proteins important in inflammatory responses and mucociliary clearance.3,4 In CF, the CFTR chloride channel is dysfunctional and usually results in decreased chloride secretion and increased sodium absorption, leading to altered viscosity of fluid excreted by the exocrine glands and mucosal obstruction....