Cystic fibrosis (CF) is a severe multisystem disorder with typical onset in infancy occurring in 1 in every 2000 to 3000 births. CF is most common among people of Northern European descent but can affect people of all ethnicities (Pettit, R., Fellner, C. P T 2014; 29(7): 500-511). Main features of classic CF include chronic, debilitating lung infections, pancreatic insufficiency connected to dietary malabsorption, excess chloride levels in sweat, and absence of the vas deferens. Nearly all male patients are infertile. Severity varies widely, as many genetic and non-genetic modifying factors exist. The average predicted survival for patients with cystic fibrosis is currently just over 40 years (Cystic Fibrosis Foundation Patient Registry 2015 Annual Data Report 2016; www.cff.org). Today, all 50 states within the U.S. offer newborn screening for CF, and the majority of cases are detected within the baby's first year of life (Cystic Fibrosis Foundation 2013; www.cff.org/What-is-CF/Testing/Newborn-Screening-for-CF/ (accessed 11/15/16)). Patients with non-classic CF present with borderline sweat chloride levels and require diagnosis via sequencing of the CFTR gene. These patients present with chronic pancreatitis and isolated obstructive azoospermia.
Since the identification of the cystic fibrosis conductance regulator (CFTR) gene in 1989, therapies for cystic fibrosis have continued to improve the lifespan and quality of life for patients affected by the disorder.
Early diagnosis is crucial because patients with classic cystic fibrosis have special dietary requirements and can often benefit from nutritional therapies. Furthermore, studies have shown that babies that were diagnosed with CF through newborn screening have a significantly better BMI and lung function than those that were diagnosed clinically (Martin et al. Pediatrics 2012; 129(2):e348-e355). Nutritional status can be monitored closely, and interventions including oral pancreatic enzyme replacement therapy (PERT) may be started early to treat pancreatic insufficiency. In 2015, the CF registry found that approximately 87% of patients with CF were prescribed PERT (Cystic Fibrosis Foundation Patient Registry 2015 Annual Data Report 2016; www.cff.org). Specific guidelines have been developed for prescribing PERT for patients of all ages, including infants (Borowitz et al. Journal of Cystic Fibrosis 2013; 12 (6):784-785). When left untreated, infants with malnutrition and pancreatic insufficiency can develop hypoproteinemia, edema, and severe cachexia (Moskowitz et al. GeneReviews 2008; ncbi.hlm.nih.gov/books/NBK1240). Evidence from the CF Foundation's Patient Registry shows that the better the nutritional status, the more likely growth and development will be close to normal and the more slowly lung damage will progress (Bakker et al. Science 1992; 248(5087):1477-1479).
Cystic Fibrosis Modulators
Medications are currently being developed to treat patients with specific CFTR sequence variants. The first of these therapies to be approved by the FDA in 2012 was Ivacaftor, which was developed for the treatment of patients with p.Gly551Asp that occurs in about 4% of CF patients (McPhail and Clancy, Drugs of Today 2013; 49(4):253-260). Since then, Ivacaftor has been approved for the treatment of 9 additional variants including p.Gly178Arg, p.Ser549Asn, p.Ser1251Asn, p.Ser1255Pro, p.Glu1349Asp, and p.Arg117His. It is also being used in conjunction with Lumacaftor for patients that are homozygous for the p.Phe508del variant. Although over 2000 variants within the CFTR gene have been reported, the p.Phe508del mutation is the most common, occurring in about 80% of patients with CF (Cystic Fibrosis Foundation. Patient Registry 2015 Annual Data Report 2016; www.cftr2.org). Together, the combined Ivacaftor plus Lumacaftor therapy is called Orkambi and was approved by the FDA in July 2015 (Vertex 2015; http://investors.vrtx.com/releasedetail.cfm?ReleaseID=920512 (accessed 11/15/16)). On its own, Lumacaftor has been approved for the treatment of 8 variants that cause folding defects within the CFTR protein.
The CF Foundation has made it a goal to identify CF mutations for all affected patients (Cystic Fibrosis Foundation, n.d; www.cff.org). Genetic testing is the first step that will allow healthcare providers to determine the optimal treatment for each patient and eligibility for clinical trials.
For more information on CFTR testing, please see our full Test Description.
This article is a summary of information that has been reported in the biomedical research literature. It is not medical advice for patients. All disease treatments should be under the direction of a qualified healthcare provider.
Last Updated: 4/10/2017