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Cystic Fibrosis: Past, Present, and Future

Cystic fibrosis (CF) is one of the most common genetic diseases, affecting approximately 40,000 people in the US and over 100,000 worldwide. Despite its relative frequency, many have not heard about the newest treatments for CF that target the genetic basis of the condition. In honor of CF Awareness Month (celebrated each May), we present an overview of CF, its history, and how it serves as an example of the promise of genetic medicine.

What is Cystic Fibrosis?

CF is a progressive condition that most particularly affects the lungs and pancreas. CF presentation can vary greatly among patients, but typical pulmonary issues include persistent cough, chronic lung infections, and wheezing/shortness of breath. Common pancreatic symptoms include insufficiency, malnutrition, and recurrent pancreatitis. A unique feature of CF is a specific form of male infertility caused by the absence of the sperm canals known as congenital bilateral absence of the vas deferens (CBAVD), which affects ~98% of men with CF.1

History of Cystic Fibrosis

CF was first described in 1938; at that time, most patients died before their first birthday. In 2018, The United States CF Registry reported that the estimated median survival for CF patients was 47.4 years, and approximately 55% of CF patients were at least 18 years old. Lifespan of CF patients has increased over the last few decades due to the establishment of specialized CF centers, better control of pulmonary infections, the use of pancreatic enzymes for nutritional support, and lung transplantation.2

A significant milestone occurred in 1989 when the causative gene, known as CFTR, was discovered. CFTR encodes for an ion channel, which regulates the passage of salt and water ions across cell membranes to maintain proper fluid balance within cells. Different CFTR variants cause different problems with ion channel production, processing, or function. Variants are broadly assigned to one of 6 classes based on what type of problem with the channel each one causes—though the effects of some variants overlap multiple classes. The discovery of CFTR, along with subsequent research that has identified over 2000 different variants in the gene, clarified the mechanisms underlying CF disease, allowed for implementation of effective CF carrier screening and newborn screening protocols, explained some of the observed symptom variability between patients, and most recently paved the way for groundbreaking new treatments.

Targeted Treatments

In the past ten years revolutionary drugs (known as CFTR modulators) that are prescribed based on a patient’s genotype (the specific CFTR variants that the patient carries) have become available.2 The first modulator (ivacaftor) was approved for clinical use in 2012 in patients with at least 1 copy of a specific variant. In the decade since ivacaftor’s release, it has been approved for use in patients with additional variants from 2 of the 6 classes. Since 2015, 3 additional modulators (lumacaftor, tezacaftor, elexacaftor) have been approved for use in various combinations with ivacaftor. Combination therapy has allowed for treatment of patients who carry specific variants within a third class. Currently, 90% of CF patients are eligible for a modulator therapy based on their genotype.3

In the relatively short time that modulator therapies have been available, outcome data has been mixed. Some positive effects have been established, including improvement of respiratory symptoms/lung function, weight gain, and generally improved quality of life. However, some significant effects of CF appear unaffected by modulator use, including previously established chronic lung infections and male infertility. Adverse effects have also been experienced (some severe enough to lead to discontinuation of treatment), including hypertension, elevated liver function tests, and possibly increased anxiety and depression. Continued follow-up is needed to establish the impact of these drugs on additional symptoms of CF, and to determine whether the observed benefits of treatment are sustained with long-term use. Additionally, research is needed to assess the long-term safety of these drugs in children, as well as their use in pregnant and breastfeeding women.4

Future of Cystic Fibrosis

In the 85 years since CF was first described, great progress has been made in understanding and treating this condition. But there is more work to be done. Research and clinical trials continue to develop drugs that may benefit the 10% of patients who are ineligible for modulator therapy, alongside efforts to bring improved modulators to all patients. Research is also ongoing into potentially curative gene therapies, exploring technologies that may enable the repair or replacement of malfunctioning CFTR instructions inside of cells. Equally as important as the development of technological breakthroughs, equitable access to current treatment needs to be addressed. Modulator therapies are extremely expensive (with US list prices of approximately $300,000/year), and therefore unavailable to many patients throughout the world.3

Quest Diagnostics offers a comprehensive genetic testing menu to address CF carrier screening and diagnosis. For more information on these options, please refer to our Test Directory or call 866.436.3463 to consult with a Quest Diagnostics genetic counselor.


  1. Cystic Fibrosis Foundation. Accessed March 14, 2023.
  2. Scotet V, L’Hostis C, Ferec C. The changing epidemiology of cystic fibrosis: Incidence, survival and impact of the CFTR gene discovery. Genes. 2020;11:589. doi:10.3390/genes11060589
  3. Haq I, Almulhem M, Soars S, et al. Precision medicine based on CFTR genotype for people with cystic fibrosis. Pharmgenomics Pers Med. 2022;15:91-104. doi:10.2147/PGPM.S245603
  4. Regard L, Martin C, Da Silva J, Burgel P-R. CFTR Modulators: Current status and evolving knowledge. Semin Respir Crit Care Med. 2023;44:186–195. doi:10.1055/s-0042-1758851