The prognosis for patients with cystic fibrosis (CF) continues to improve because of a combination of advances in the understanding of disease pathophysiology, implementation of early screening and diagnosis, and greater emphasis on proactive management to prevent deterioration and disease progression.
Cystic fibrosis is the most common life-shortening genetic disease among Caucasians, who represent 94% of the CF population in the United States.1 The probability of a Caucasian child being born with CF is approximately 1 in 2500.2 By comparison, the likelihood of CF in the Hispanic American and African American populations are 1 in 13,500 and 1 in 15,100 live births, respectively. It is estimated that there are currently 70,000 individuals living with CF worldwide, 30,000 of whom reside in the United States.1 Children account for more than half of the CF population. The number of affected Americans continues to increase as new cases are diagnosed (approximately 1000 per year) and improvements in treatment and diagnosis enhance longevity. Indeed, within the past 20 years, the predicted median survival age for patients with CF has increased by more than 10 years (Table 1).1
Cystic fibrosis is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR protein was first classified as a chloride channel, but has subsequently been shown to facilitate or regulate the transport of other ions, such as sodium (through the epithelial sodium channel), thiocyanate, and bicarbonate.3,4 The CFTR protein is present in the epithelia of various tissues, including that of the lungs, sweat glands, gastrointestinal tract, vas deferens, and pancreas, where it helps regulate salt and water absorption and excretion.5
Disease-causing mutations in the CFTR gene impede protein production, stability, or activity, resulting in less available functional protein.4 In the lung, the ensuing perturbations in ion transport cause airway surface liquid depletion resulting in defective mucociliary clearance. Added to this is an abnormal inflammatory response, whose relation to the ion transport abnormality is unclear. Together, these physiologic changes lead to an iterative cascade of obstruction, inflammation, infection, and, ultimately, progressive, irreversible lung damage.3
Other manifestations of dysfunctional CFTR include pancreatic insufficiency resulting from ductal obstruction, meconium ileus because of increased viscosity of intestinal mucus, and congenital bilateral absence of the vas deferens (CBAVD) caused by obstruction of the Wolffian ducts during fetal development.5,6 The influence of CFTR mutations on nonrespiratory organ systems affects growth, nutritional status, and fertility, but it is the lung disease that is predominantly responsible for CF-related morbidity and mortality.7
One of the keys to improvements in CF outcomes has been the increasing adoption of a proactive approach to care, which includes the broad implementation of newborn screening (NBS). According to data from the Cystic Fibrosis Foundation Patient Registry, more than 61% of CF diagnoses in the United States in 2012 were made through NBS.1 The rationale for instituting NBS programs is to mitigate the negative impact of untreated CF on lung structure and function and to prevent nutritional deterioration by providing appropriate monitoring and treatment.
It has long been known that infants with pancreatic insufficiency due to CF demonstrate poor growth and inadequate weight gain. Researchers are now beginning to appreciate that structural changes of the lungs have already begun to manifest within the first year of life in affected individuals.8,9 Lung disease is generally not clinically apparent at these early stages because these nascent structural and physiologic abnormalities (eg, bronchial dilatation, bronchial wall thickening, gas trapping) and bacterial infections are usually asymptomatic during infancy.8
Identification of patients through NBS has been associated with improved nutritional status, better cognitive function, improved pulmonary status/lung function, and fewer hospitalizations.10-14 Newborn screening also has the potential to decrease the risk of life-threatening complications and death in infancy, and to reduce treatment costs.7,15 Indeed, comparisons with historical data indicate an increased probability of survival into early adulthood for those diagnosed as the result of NBS.12 For parents, the expedited time to diagnosis reduces distress and provides opportunities for genetic counseling, which could influence future childbearing decisions.7