Guideline sources The following summarized guidelines for the evaluation and management of cystic fibrosis (CF) are prepared by our editorial team based on guidelines from the American Diabetes Association (ADA 2023), the National Society of Genetic Counselors (NSGC 2014), the Clinical Pharmacogenetics Implementation Consortium (CPIC 2014), and the Cystic Fibrosis Foundation (CFF 2013). 1 2 3 4 5 5 5 6 Definition CF is an inherited multiorgan disease characterized by recurrent cough, wheeze, and pneumonia, sinusitis, and male infertility. 5 Epidemiology CF is caused by a mutation in the CF transmembrane conductance regulator gene. 5 Disease course Genetic mutations in CF transmembrane conductance regulator gene result in CF, which causes clinical manifestations of recurrent respiratory symptoms of cough, wheeze, and pneumonias, nasal polyps, sinusitis, finger clubbing, male infertility, exocrine pancreatic insufficiency (steatorrhea, diarrhea, abdominal distension, poor growth in infants, pancreatitis), GERD, meconium ileus, distal intestinal obstruction syndrome, celiac disease, malabsorption, Crohn's disease, constipation, rectal https://web.pathway.md/diseases/recQObj753riIIE2o 1/5 6/23/23, 3:40 AM Cystic fibrosis Pathway prolapse, fatty liver, cirrhosis, diabetes, osteopenia, acute collapse, vaginal candidiasis, and stress incontinence. Disease progression may lead to death. 5 Prognosis and risk of recurrence The in-hospital mortality of CF is 0.71%. 6 Guidelines 1. Screening and diagnosis Carrier testing: Offer carrier testing for CF to: women of reproductive age, regardless of ancestry, and preferably preconceptionally individuals with a family history of CF partners of mutation carriers and people with CF. 2. Diagnostic investigations Genetic testing: review and re-interpret prior carrier screening results in light of current knowledge when individuals present for genetic counseling. The inclusion and exclusion of mutations on available CFTR mutation screening panels remains a dynamic process as new information is learned about the pathogenicity of CFTR mutations. Screening for diabetes: Start annual screening for CF-related diabetes with an oral glucose tolerance by age 10 years in all patients with CF not previously diagnosed with CF-related diabetes. B Do not obtain Hgb A1C as a screening test for CF-related diabetes. D 3. Medical management Ivacaftor: As per CPIC 2014 guidelines, use ivacaftor according to the product label (150 mg every 12 h) for patients 6 years without other diseases; adjust dosing as appropriate in patients with hepatic impairment. A As per CFF 2013 guidelines, administer of ivacaftor to improve lung function and quality of life and reduce exacerbations in patients with CF 6 years of age with at least one G551D CFTR mutation. A Dornase alfa: offer dornase alfa to improve lung function and quality of life, and reduce exacerbations, for individuals with CF, 6 years of age, and with moderate-to-severe lung disease. A https://web.pathway.md/diseases/recQObj753riIIE2o 2/5 6/23/23, 3:40 AM Cystic fibrosis Pathway Inhaled hypertonic saline: implement chronic inhaled hypertonic saline therapy to improve lung function and quality of life and reduce exacerbations in individuals with CF, 6 years of age. B Inhaled tobramycin: offer the chronic use of inhaled tobramycin to improve lung function and quality of life, and reduce exacerbations for patients with CF, 6 years of age, with moderate-to- severe lung disease and P. aeruginosa persistently present in cultures of the airways. A Inhaled aztreonam: initiate chronic inhaled aztreonam therapy to improve lung function and quality of life in patients with CF 6 years of age with moderate-to-severe lung disease and P. aeruginosa persistently present in cultures of the airways. A Other inhaled antibiotics: insufficient evidence to recommend for or against the chronic use of other inhaled antibiotics including carbenicillin, ceftazidime, colistin, or gentamicin to improve lung function and quality of life or reduce exacerbations, in patients with CF 6 years of age, with P. aeruginosa persistently present in cultures of the airways. I Prophylactic azithromycin: implement chronic azithromycin therapy to improve lung function and reduce exacerbations for patients 6 years of age with CF and P. aeruginosa persistently present in cultures of the airways. B Other prophylactic oral antibiotics: insufficient evidence to recommend for or against the routine use of chronic oral antipseudomonal antibiotics to improve lung function and quality of life or reduce exacerbations, in patients with CF 6 years of age with P. aeruginosa persistently present in cultures of the airways. I Inhaled corticosteroids: avoid routine use of ICSs to improve lung function or quality of life and reduce pulmonary exacerbations, for individuals with CF, 6 years of age, without asthma or allergic bronchopulmonary aspergillosis. D Oral corticosteroids: avoid the chronic use of oral corticosteroids to improve lung function, quality of life, or reduce exacerbations for individuals with CF 6 years of age without asthma or allergic bronchopulmonary aspergillosis. D Leukotriene modifiers: insufficient evidence to recommend for or against the routine chronic use of leukotriene modifiers to improve lung function and quality of life or reduce exacerbations, in patients with CF 6 years of age. I Inhaled anticholinergics: insufficient evidence to recommend for or against the chronic use of inhaled anticholinergic bronchodilators to improve lung function and quality of life or reduce exacerbations in patients with CF 6 years of age. I Inhaled beta-2 adrenergic receptor agonists: insufficient evidence to recommend for or against chronic use of inhaled -2 adrenergic receptor agonists to improve lung function and quality of life or reduce exacerbations in patients with CF 6 years of age. I Oral antistaphylococcal antibiotics: insufficient evidence to recommend for or against the chronic use of oral antistaphylococcal antibiotics to improve lung function and quality of life or reduce exacerbations in individuals with CF, 6 years of age and older, with S. aureus persistently present in cultures of the airways. I https://web.pathway.md/diseases/recQObj753riIIE2o 3/5 6/23/23, 3:40 AM Cystic fibrosis Pathway N-acetylcysteine and glutathione: insufficient evidence to recommend for or against the chronic use of inhaled or oral N-acetylcysteine or inhaled glutathione to improve lung function and quality of life or reduce exacerbations in patients with CF 6 years of age. I Ibuprofen: initiate chronic oral ibuprofen, at a peak plasma concentration of 50-100 mg/mL, to slow the loss of lung function, for patients with CF 6-17 years of age with an FEV in 1 second 60% of predicted. B 4. Specific circumstances Patients with cystic fibrosis-related diabetes: Initiate insulin to attain individualized glycemic goals in patients with CF-related diabetes. A Obtain annual monitoring for complications beginning 5 years after the diagnosis of CF-related diabetes. B 5. Patient education Post-carrier screening counseling: genetic counselors offering CF carrier screening should ensure that they are providing the most current information to patients regarding the range of symptoms, potential treatment options, and quality of life issues associated with CF and the CFTR-related disease spectrum. References 1. Mogayzel PJ Jr, Naureckas ET, Robinson KA et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013 Apr 1;187 7 680 9. Open 2. Steven E. Kahn, Cheryl A.M. Anderson, John B. Buse et al. Standards of Care in Diabetes 2023. Diabetes Care. 2023 Jan;46 Supplement_1 S1 S291. Open 3. Langfelder-Schwind E, Karczeski B, Strecker MN et al. Molecular testing for cystic fibrosis carrier status practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2014 Feb;23 1 5 15. Open 4. Clancy JP, Johnson SG, Yee SW et al. Clinical Pharmacogenetics Implementation Consortium CPIC guidelines for ivacaftor therapy in the context of CFTR genotype. Clin Pharmacol Ther. 2014 Jun;95 6 592 7. Open 5. Jane C Davies, Eric W F W Alton, Andrew Bush. Cystic fibrosis. 2007 Dec 15;335 7632 1255 9.2007 Dec 15;335 7632 1255 9. Open 6. Abhinav Agrawal, Abhishek Agarwal, Dhruv Mehta et al. Nationwide trends of hospitalizations for cystic fibrosis in the United States from 2003 to 2013. 2017 Aug;6 3 191 198.2017 Aug;6 3 191 198. Open 7. Mogayzel PJ Jr, Naureckas ET, Robinson KA et al. Cystic Fibrosis Foundation pulmonary guideline. pharmacologic approaches to prevention and eradication of initial Pseudomonas aeruginosa infection. Ann Am Thorac Soc. 2014 Dec;11 10 1640 50. Open https://web.pathway.md/diseases/recQObj753riIIE2o 4/5 6/23/23, 3:40 AM Cystic fibrosis Pathway 8. Saiman L, Siegel JD, LiPuma JJ et al. Infection prevention and control guideline for cystic fibrosis: 2013 update. Infect Control Hosp Epidemiol. 2014 Aug;35 Suppl 1 S1 S67. Open 9. Lahiri T, Hempstead SE, Brady C et al. Clinical Practice Guidelines From the Cystic Fibrosis Foundation for Preschoolers With Cystic Fibrosis. Pediatrics. 2016 Apr;137 4 . pii: e20151784. Open 10. Abhinav Agrawal, Abhishek Agarwal, Dhruv Mehta et al. Nationwide trends of hospitalizations for cystic fibrosis in the United States from 2003 to 2013. Intractable Rare Dis Res. 2017 Aug; 6 3 191 198. Open 11. Jane C Davies, Eric W F W Alton, and Andrew Bush. Cystic fibrosis. BMJ. 2007 Dec 15; 335 7632 1255 1259. Open 12. Philip M Farrell, Terry B White, Clement L Ren et al. Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017 Feb;181S S4 S15.e1. Open 13. Clement L Ren, Rebecca L Morgan, Christopher Oermann et al. Cystic Fibrosis Foundation Pulmonary Guidelines. Use of Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy in Patients with Cystic Fibrosis. Ann Am Thorac Soc. 2018 Mar;15 3 271 280. Open 14. R Andres Floto, Kenneth N Olivier, Lisa Saiman et al. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax. 2016 Jan;71 Suppl 1 Suppl 1):i1 22. Open https://web.pathway.md/diseases/recQObj753riIIE2o 5/5