Could It Be Cystic Fibrosis (CF)?

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Signs & Symptoms Delayed Diagnosis Diversity of CF Patients Establishing CF Diagnosis

CF Signs & Symptoms to Look Out For

Sinus and lower respiratory symptoms¹

Chronic sinusitis
Nasal polyps
Bronchiectasis, chronic or recurrent lower airway infection (especially Pseudomonas infection)
Allergic bronchopulmonary aspergillosis
Nontuberculous mycobacterial (NTM) infection

GI, reproductive, other symptoms¹

Recurrent pancreatitis
Male infertility
Abnormal GI motility, rectal prolapse
Elevated liver enzymes, cirrhosis
Fat-soluble vitamin deficiencies^a

NOTE: Common symptoms at first presentation of CF are in bold type; uncommon are in regular type.

Have you considered CF?
These are some of the clinical signs and symptoms that are consistent with CF

What is CF?

Cystic fibrosis (CF) is a systemic, multi-organ disease that is caused by mutations in both cystic fibrosis transmembrane conductance regulator (CFTR) alleles.² Mutations in the CFTR gene may cause impaired cellular processing and trafficking, including an absence of or reduction in channel numbers, channel function, or both.² Some presenting manifestations of CF can include chronic sinusitis, bronchiectasis, NTM infection, recurrent pancreatitis, respiratory symptoms and/or male infertility.¹

Reduced CFTR quantity

Reduced CFTR function

images cftr protein reduced functionality

Impact on the lungs

The insufficient flow of chloride and water create mucus buildup that can result in abnormal mucociliary clearance and airway inflammation. This leads to progressive lung damage, including mucus plugging, air trapping, air wall thickening, and bronchiectasis.^2-4

Bronchiectasis is a common symptom of CF⁵

Bronchiectasis is a common
symptom of CF⁵

Rates of CF testing in bronchiectasis populations have been estimated to be between 5.5% and 12%.^6,7b

Other symptoms consistent with CFTR dysfunction^8,9

Upper respiratory symptoms

Rhinosinusitis

Lower respiratory symptoms

NMT infection or isolation of Pseudomonas aeruginosa or Staphylococcus aureus

Other

Extrapulmonary features

Malabsorption/GI symptoms
Pancreatitis
Intestinal obstruction

Male infertility

CF is one possible cause of bronchiectasis

^aMay present as ecchymosis, anemia, edema, night blindness, or skin rash.¹

^bStudies of US rates are not published; these percentages are based on testing rates in Italy and the United Kingdom, respectively.^6,7

Reasons for Late Diagnosis^10-13

Born before implementation of or in a country without NBS^a

Racial and ethnic disparities in CFTR mutations contained in standard NBS panels

Harbor rare CFTR mutations not included in standard genetic panels

Misdiagnosed for another pulmonary disease (e.g., bronchiectasis, NTM infection)

Lack of access to healthcare services

Delayed CF diagnosis may ultimately lead to disparities in treatment, care, and outcomes over time¹⁴

^aWhile all states now perform NBS for CF, there are variations in the approach and some approaches may miss some CF diagnoses.¹³

CF Can Affect a Diverse Population

CF has traditionally been thought of as a disease affecting exclusively people of European descent.¹⁵ However, increasing numbers of people with CF of non-White backgrounds have been diagnosed and reported in the US CFFPR.¹⁶

Diversity in age distribution of CF diagnosis

Diversity in age distribution
of CF diagnosis

Although universal CF NBS was implemented in the United States in 2009 and enabled early identification of CF, there are people with CF who are not diagnosed until adulthood.^13a,16

CF is caused by numerous mutations in the CFTR gene that vary across racial and ethnic groups^14,18,19

The most common CFTR mutation is F508del. 85.4% of those in the US CFFPR who have been genotyped have at least 1 copy of this variant¹⁶
Prevalence of F508del mutation varies by ancestry¹⁸

Hispanic, Black, Asian, and Native American people are more likely to have rare CFTR mutations¹⁸

^aData from the 2022 US CFFPR.
^bThis study was in patients diagnosed with CF from the US CFFPR.¹⁸
^cPercentages are rounded and may not add up to exactly 100%.

Considerations to Investigate Whether It's CF

Common diagnostic tests for CF

Sweat chloride test: Sweat chloride concentration is the standard for diagnosing CF and an important marker of CFTR function^20a
CFTR genotyping: Genotyping is potentially helpful in the diagnostic workup for CF²⁰

Consider whether it is CF by…

IDENTIFYING

Older, non-White patients with bronchiectasis or other symptoms suggestive of CFTR dysfunction^1,5,16

REFERRING

Appropriate individuals for sweat chloride testing, regardless of race/ethnicity or age^{1,14,16,17,20}

SENDING

Appropriate individuals to a CF care center for additional diagnostic workups and/or care

Click here to find a CF care center

Benefits of diagnosis and treatment

Earlier and accurate diagnosis of CF in all patients is important due to clinical and psychological consequences²¹
Treatment is available for people with CF in the U.S. through specialized CF care centers^22,23
- Once diagnosed, treatments are available for patients with CF that can contribute to improve quality of life and life expectancy^14,16
The median age of survival in people with CF has increased in the last 10-20 years due to earlier diagnosis and treatment^10,16
- The median predicted survival age of an individual born with CF in 2022 was 68.2 years (95% CI: 63.0, 76.2 years)^16b

The treatment landscape continues to expand for those with rarer CF mutations and for the plurality of undiagnosed populations

^aWhen accompanied by clinical suspicion, such as positive newborn screen, clinical features, and/or family history of CF.

^bThis prediction does not consider the potential impact of CFTR modulators on younger individuals with CF or additional future improvements in clinical care.¹⁶

CFFPR, Cystic Fibrosis Foundation Patient Registry; CI: confidence interval; GI, gastrointestinal; NBS, newborn screening; NTM, nontuberculous mycobacterial

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These organizations are separate from and not associated with Vertex Pharmaceuticals Incorporated.

References: 1. Sosnay PR, White TB, Farrell PM, et al. Diagnosis of cystic fibrosis in nonscreened populations. J Pediatr. 2017;181(suppl):S52-S57.e2. doi:10.1016/j.jpeds.2016.09.068. 2. Ratjen F, Bell SC, Rowe SM, Goss CH, Quittner AL, Bush A. Cystic fibrosis. Nat Rev Dis Primers. 2015;1:15010. doi:10.1038/nrdp.2015.10. 3. Morrison CB, Markovetz MR, Ehre C. Mucus, mucins, and cystic fibrosis. Pediatr Pulmonol. 2019;54(suppl 3):S84-S96. doi:10.1002/ppul.24530. 4. Wielpütz MO, Puderbach M, Kopp-Schneider A, et al. Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med. 2014;189(8):956-965. doi:10.1164/rccm.201309-1659OC. 5. Sly PD, Gangell CL, Chen L, et al; AREST CF Investigators. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med. 2013;368(21):1963-1970. doi:10.1056/NEJMoa1301725. 6. Hill AT, Routh C, Welham S. National BTS bronchiectasis audit 2012: Is the quality standard being adhered to in adult secondary care? Thorax. 2014;69(3):292-294. doi:10.1136/thoraxjnl-2013-203739. 7. Aliberti S, Hill AT, Mantero M, et al; SIP Bronchiectasis Audit Working Group. Quality standards for the management of bronchiectasis in Italy: a national audit. Eur Respir J. 2016;48(1):244-248. doi:10.1183/13993003.00232-2016. 8. Redondo M, Keyt H, Dhar R, Chalmers JD. Global impact of bronchiectasis and cystic fibrosis. Breathe (Sheff). 2016;12(3):222-235. doi:10.1183/20734735.007516. 9. Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet. 2018;392(10150):880-890. doi:10.1016/S0140-6736(18)31767-7. 10. McBennett KA, Davis PB, Konstan MW. Increasing life expectancy in cystic fibrosis: advances and challenges. Pediatr Pulmonol. 2022;57(suppl 1):S5-S12. doi:10.1002/ppul.25733 11. Cystic Fibrosis Trust. Cystic fibrosis: late diagnosis. Factsheet. August 2020. Accessed September 9, 2024. https://www.cysticfibrosis.org.uk/sites/default/files/2020-12/Late%20diagnosis%20factsheet%20Sep%202020.pdf. 12. McColley SA, Martiniano SL, Ren CL, et al. Disparities in first evaluation of infants with cystic fibrosis since implementation of newborn screening. J Cyst Fibros. 2023;22(1):89-97. 13. Sontag MK, Miller JI, McKasson S, et al. Newborn screening for cystic fibrosis: a qualitative study of successes and challenges from universal screening in the United States. Int J Neonatal Screen. 2022;8(3):38. doi:10.3390/ijns8030038. 14. Cystic Fibrosis Foundation. Dispelling misconceptions about CF. Accessed September 9, 2024. 15. Guo J, Garratt A, Hill A. Worldwide rates of diagnosis and effective treatment for cystic fibrosis. J Cyst Fibros. 2022;21(3):456-462. doi:10.1016/j.jcf.2022.01.009. 16. Cystic Fibrosis Foundation Patient Registry. 2022 Annual Data Report to the Center Directors. Bethesda, Maryland. ©2022 Cystic Fibrosis Foundation. Accessed September 9, 2024. https://www.cff.org/media/31216/download. 17. 2022 Cystic Fibrosis Foundation Patient Registry Highlights. Bethesda, Maryland. ©2023 Cystic Fibrosis Foundation. Accessed September 9, 2024. https://www.cff.org/media/29691/download. 18. Schrijver I, Pique L, Graham S, Pearl M, Cherry A, Kharrazi M. The spectrum of CFTR variants in nonwhite cystic fibrosis patients: implications for molecular diagnostic testing. J Mol Diagn. 2016;18(1):39-50. doi:10.1016/j.jmoldx.2015.07.005. 19. CFTR2. Clinical and functional translation of CFTR2 Variant List. Last updated on April 7, 2023. Accessed September 9, 2024. https://cftr2.org/mutations_history. 20. Farrell PM, White TB, Ren CL, et al. Diagnosis of cystic fibrosis: consensus guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017;181(suppl):S4-S15.e1. doi:10.1016/j.jpeds.2016.09.064. 21. Southern KW, Addy C, Bell SC, et al. Standards for the care of people with cystic fibrosis; establishing and maintaining health. J Cyst Fibros. 2024;23(1):12-28. doi:10.1016/j.jcf.2023.12.002 22. Cystic Fibrosis Foundation. Care centers. Accessed September 9, 2024. https://www.cff.org/managing-cf/care-centers 23. Cystic Fibrosis Foundation. Your CF care team. Accessed September 9, 2024. https://www.cff.org/managing-cf/your-cf-care-team

Could It Be CF?

CF Signs & Symptoms to Look Out For

Reasons for Late Diagnosis10-13

CF Can Affect a Diverse Population

Considerations to Investigate Whether It's CF

You May Also Be Interested In

Reasons for Late Diagnosis^10-13