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INTRODUCTION

Key Clinical Questions

  • image How do mutations in the cystic fibrosis (CF) gene relate to the clinical manifestations of the disease?

  • image What criteria help determine when a CF patient should be admitted to the hospital for respiratory complications of the disease?

  • image What treatment modalities are most effective in restoring lung function to baseline for CF respiratory exacerbations?

  • image Why is CF-related diabetes (CFRD) important to control during acute pulmonary exacerbations as well as at baseline?

  • image What are the most effective treatment modalities for the two most common pulmonary complications of CF: massive hemoptysis and pneumothorax?

DEFINITION AND OVERVIEW

Cystic fibrosis (CF) is an autosomal recessive disease due to mutations in the CF transmembrane conductance regulator (CFTR) gene. The CFTR gene is expressed in epithelial cells in a variety of organs including the lung, sinuses, pancreas, sweat gland, intestine, liver, and vas deferens, and thus CF is a multiorgan disease. CF is the most common inherited life-shortening disease of Caucasians in the United States. More than 90% of the morbidity and the mortality are due to lung disease. CF lung disease is characterized by the triad of altered mucociliary clearance, chronic polymicrobial infection of the airways, and an exaggerated inflammatory response. The ultimate outcome of CF lung disease is destruction of the normal airway architecture and death due to respiratory failure.

With therapy, primarily aimed at slowing the progression of lung disease and improving nutrition, median survival is approaching 40 years of age. Unfortunately, there is no cure for CF. However, for CF patients with select CFTR mutations, there have been recent advancements and FDA approval of CFTR potentiator/corrector medications. The first FDA approved CFTR potentiator, ivacaftor, exerts its effects by improving the function of the defective CFTR protein. Unfortunately, ivacaftor benefits a small segment (about 5%) of the CF population with specific CFTR mutations (eg, G551D). More recently, a combination pill comprised of the potentiator ivacaftor and a CFTR corrector, lumacaftor, has been approved for CF patients homozygous for the ΔF508 mutation. This accounts for approximately 50% of the CF patients in North America. These medications are metabolized by the CYP3A system, and particular care must be taken by the hospitalist whenever additional medications that alter CYP3A function (such as many anti-fungal medications) are added into the therapeutic regimen for CF patients currently on one of these CFTR potentiator/corrector medications. Despite these therapeutic advancements, clinical improvements for patients with CF on these newer medications remain modest. As such, there remains ongoing aggressive research and development for other CFTR potentiators and correctors. The average CF adult can expect to spend 2 to 3 hours a day taking a variety of inhaled medications, ingest 30 to 50 pills per day, and be hospitalized about once per year for a period of a few days to weeks. Even with insurance, most CF patients have out-of-pocket health care costs approximately $10,000 per year.

In contrast, some ...

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