Cystic Fibrosis (CF)


Cystic fibrosis (CF) is a life-threatening, inherited disease in which thick, sticky mucus accumulates in multiple organ systems, causing dysfunction, particularly in the respiratory, digestive, and reproductive systems. Although it is a rare disease, it is the most common chronic lung disease affecting children and adolescents.1

Prognosis

Most children with CF obtain a diagnosis by 2 years of age, particularly with newborn screening implementation across medical facilities in the United States. Rarely, milder forms of the disease remain undetected until the individual reaches adolescence or young adulthood.1

Due to early diagnosis, most children with CF remain in good health until adulthood, participating in school with many finishing college and finding jobs. Eventually, chronic lung disease progresses to the point of disability and is usually the reason for morbidity and mortality in individuals with CF.1

Thanks to advancements in medical and surgical treatment, individuals with CF survive into their third or fourth decade on average.1,2 In the United States, individuals with CF are expected to live past 40 years of age. Due to currently available treatments, it is estimated that at least 80% of patients with CF will reach adulthood.2

Many factors influence patient prognosis, including age at diagnosis, symptom severity, clinical presentation, and rate of disease progression within involved organ systems.2 

Factors Improving Prognosis

In previous studies, newborns screened for CF had less severe malnutrition than unscreened infants.3,4 Newborn screening combined with aggressive nutritional therapy enabled infants to achieve weight and height measurements above the 10th percentile during childhood despite inherently worse pancreatic disease compared to children with delayed diagnoses.4

Children with improved weight-for-age percentile rankings by the age of 4 years due to improved nutritional status also demonstrated higher height-for-age percentiles, improved pulmonary function, decreased CF complications, and increased survival advantage into late adolescence (18 years).5 

According to a review of 2 randomized control trials, 88% of screened newborns maintained normal pulmonary function by 7 years of age, compared with 75% of unscreened newborns; however, over time, varying factors changed long-term pulmonary outcomes regardless of screening. Cost estimation suggests that screening is cheaper than traditional diagnostic measures.3  

Factors reducing the rate of CF disease progression and the severity of symptoms include more frequent monitoring of clinical status, pulmonary function tests, and cultures for respiratory pathogens, as well as increased use of effective treatments to manage acute pulmonary episodes, such as intravenous antibiotics.6

Patients with CF who have higher levels of aerobic fitness demonstrate improved survival rates compared to those with diminished aerobic fitness, indicating that measurements of the maximum rate of oxygen consumption (VO2) may predict prognosis.7   

Factors Worsening Prognosis

Multiple factors have been associated with worse survival outcomes, including female sex, ethnicity, poor nutritional status, decreased lower lung function, and microbiology.8   

Patients with severe CF transmembrane conductance regulator (CFTR) genotypes demonstrated increased mortality at every age over 32 years as well as an increased predisposition to CF-related diabetes (CFRD) compared to those with milder genotypes (P =.002). Female patients with severe CFTR genotypes exhibited increased CFRD and mortality rates at every age compared to male patients. Prognosis is worse in individuals with CFRD, especially over 30 years of age, compared to patients who have CF without diabetes.9

Female sex correlates with an earlier onset and a higher frequency of pulmonary exacerbations. Physical inactivity in female patients results in more variable pulmonary function with steeper declines than those in female patients who are more physically active.10-13

Low socioeconomic status negatively affects prognosis in CF, with reported increases in mortality, Pseudomonas aeruginosa pulmonary infections, severe pulmonary dysfunction, and pulmonary exacerbations. Patients with low socioeconomic status are less likely to receive lung transplantations and have worse nutritional statuses.10

Cystic fibrosis is most common in white patients; however, an increasing number of patients with CF are minorities.10 Cystic fibrosis patients with Hispanic ancestry have higher mortality rates than white patients.14 Individuals of African and Hispanic descent demonstrate more severe pulmonary disease progression than white patients.15,16

Nonadherence of CF patients to using prescribed inhaled therapies poses a treatment problem with negative influences on pulmonary function and health outcomes due to disease progression. Factors contributing to nonadherence include demographic and psychosocial factors, treatment beliefs, and time and convenience of inhaled therapy.17

References

  1. Cystic fibrosis. MedlinePlus. Updated January 3, 2022. Accessed January 11, 2022.
  2. Sharma GD. Cystic fibrosis: prognosis. Medscape. Updated September 28, 2020. Accessed January 11, 2022.
  3. Southern KW, Mérelle MME, Dankert-Roelse JE, Nagelkerke AD. Newborn screening for cystic fibrosis. Cochrane Database Syst Rev. 2009;2009(1):CD001402. doi:10.1002/14651858.CD001402.pub2
  4. Farrell PM, Kosorok MR, Rock MJ, et al.; Wisconsin Cystic Fibrosis Neonatal Screening Study Group. Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Pediatrics. 2001;107(1):1-13. doi:10.1542/peds.107.1.1
  5. Yen EH, Quinton H, Borowitz D. Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis. J Pediatr. 2013;162(3):530-535.e1. doi:10.1016/j.jpeds.2012.08.040
  6. Johnson C, Butler SM, Konstan MW, Morgan W, Wohl MEB. Factors influencing outcomes in cystic fibrosis: a center-based analysis. Chest. 2003;123(1):20-27. doi:10.1378/chest.123.1.20
  7. Nixon PA, Orenstein DM, Kelsey SF, Doershuk CF. The prognostic value of exercise testing in patients with cystic fibrosis. N Engl J Med. 1992;327(25):1785-1788. doi:10.1056/NEJM199212173272504
  8. Corriveau S, Sykes J, Stephenson AL. Cystic fibrosis survival: the changing epidemiology. Curr Opin Pulm Med. 2018;24(6):574-578. doi:10.1097/MCP.0000000000000520
  9. Lewis C, Blackman SM, Nelson A, et al. Diabetes-related mortality in adults with cystic fibrosis. Role of genotype and sex. Am J Respir Crit Care Med. 2015;191(2):194-200. doi:10.1164/rccm.201403-0576OC 
  10. McGarry ME, Williams WA II, McColley SA. The demographics of adverse outcomes in cystic fibrosis. Pediatr Pulmonol. 2019;54(Suppl 3):S74-S83. doi:10.1002/ppul.24434
  11. Block JK, Vandemheen KL, Tullis E, et al. Predictors of pulmonary exacerbations in patients with cystic fibrosis infected with multi-resistant bacteria. Thorax. 2006;61(11):969-974. doi:10.1136/thx.2006.061366
  12. Patterson JM, Wall M, Berge J, Milla C. Associations of psychosocial factors with health outcomes among youth with cystic fibrosis. Pediatr Pulmonol. 2009;44(1):46-53. doi:10.1002/ppul.20925
  13. Schneiderman-Walker J, Wilkes DL, Strug L, et al. Sex differences in habitual physical activity and lung function decline in children with cystic fibrosis. J Pediatr. 2005;147(3):321-326. doi:10.1016/j.jpeds.2005.03.043
  14. Rho J, Ahn C, Gao A, Sawicki GS, Keller A, Jain R. Disparities in mortality of Hispanic patients with cystic fibrosis in the United States. A national and regional cohort study. Am J Respir Crit Care Med. 2018;198(8):1055-1063. doi:10.1164/rccm.201711-2357OC
  15. McGarry ME, Neuhaus JM, Nielson DW, Burchard E, Ly NP. Pulmonary function disparities exist and persist in Hispanic patients with cystic fibrosis: a longitudinal analysis. Pediatr Pulmonol. 2017;52(12):1550-1557. doi:10.1002/ppul.23884
  16. Hamosh A, FitzSimmons SC, Macek M Jr, Knowles MR, Rosenstein BJ, Cutting GR. Comparison of the clinical manifestations of cystic fibrosis in black and white patients. J Pediatr. 1998;132(2):255-259. doi:10.1016/s0022-3476(98)70441-x
  17. Lomas P. Enhancing adherence to inhaled therapies in cystic fibrosis. Ther Adv Respir Dis. 2014;8(2):39-47. doi:10.1177/1753465814524471

Reviewed by Harshi Dhingra, MD, on 1/11/2022.

READ MORE ON CF