Cystic Fibrosis

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General Information

Cystic Fibrosis Week

Cystic fibrosis (CF), the most common life-limiting inherited illness of Caucasians, occurs due to an impaired chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This channel, located in the surface of the respiratory epithelium, leads to defective salt and water transport into the airway lumen causing thickened mucus and impaired clearance of secretions. There are over 1,500 identified mutations of the CFTR gene, which are divided into 6 classes based on the type and degree of CFTR dysfunction.

CF is characterized by chronic pulmonary (lung) disease, and the majority of patients also have chronic gastrointestinal symptoms with malabsorption of fats and proteins leading to poor growth. CF pulmonary disease is characterized by progressive decline in lung function and recurrent bronchopulmonary exacerbations, accounting for the majority of morbidity and mortality of the disease.

In the past, CF was diagnosed when children or adults became symptomatic, typically with either poor growth and/or recurrent sinopulmonary symptoms. However, diagnosing CF now occurs through newborn screening in all states in the U.S., which allows the majority of children to be diagnosed in infancy, and before they are symptomatic. Diagnosis is made through a combination of newborn screening, sweat chloride testing, genetic studies, symptoms, and family history.

The development of CF-specific therapies available to target the sequelae of CFTR dysfunction have dramatically extended the median life expectancy of patients with CF to 40 years of age in the U.S. These treatments include pancreatic enzyme replacement therapy, chest physiotherapy (use of various techniques to transmit vibratory forces through the airways and promote mucus clearance), inhaled antibiotics, and inhaled agents to improve mucus clearance (such as hypertonic saline and dornase-alpha). Newborn screening now allows families and physicians to initiate treatment in the first months of life, hopefully prior to significant lung damage occurring, with a focus on preservation of lung health as well as growth and nutrition.

Revolutionary new therapies for CF are being developed that target the dysfunctional CFTR itself, as opposed to the downstream consequences of the dysfunctional chloride channel. These small molecules, often referred to as potentiators and correctors, increase the availability of functional CFTR channels in the cell membrane, which in turn improves mucus clearance in the lung. These molecules are mutation - or class -specific. Ivacaftor, the first of these molecules to be FDA approved, is currently labeled for use in approximately 5% of CF patients and has been shown to significantly improve lung function and weight/growth while decreasing the frequency of pulmonary exacerbations in these patients. . A combination of ivacaftor and lumicaftor has been shown to have more modest effects in patients with the most common CFTR mutation, and is currently being reviewed for FDA approval. Similar therapies, including combinations of small molecules, are being developed to target other CFTR mutations and classes.

Four Facts About Cystic Fibrosis

    1. Cystic fibrosis (CF) is an inherited chronic disease that leads to life-threatening lung infections and digestive problems. It is a rare disease, affecting 30,000 children and adults in the United States (70,000 worldwide). Currently, there is no cure for the disease and the median predicted age of survival is in the late 30s and rising.

    2. More than 10 million Americans are symptomless carriers of the defective CF gene.

    3. All babies born in the United States are screened for CF at birth as part of newborn screening (NBS).

    4. Ivacaftor (Kalydeco™), the first therapy targeting the basic defect in CF, was approved by the U.S. Food and Drug Administration in 2012.