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CME

Cystic Fibrosis (CF)

General Information

Description

  • autosomal recessive genetic disease affecting sinuses, lungs, exocrine and endocrine pancreas, small and large intestines, bones, hepatobiliary system, salivary and sweat glands, and vas deferens1,2

Also called

  • mucoviscidosis
  • fibrocystic disease of the pancreas

Definitions

  • Cystic Fibrosis Foundation (CFF) and European Cystic Fibrosis Society (ECFS)
    • suggest avoiding terms such as classic/nonclassic CF, typical/atypical CF, and delayed CF as standardized definitions are lacking
    • definitions of CF and CF-related conditions
      • CF defined as ≥ 2 characteristic clinical features of CF and/or positive newborn screen PLUS laboratory evidence of abnormality in CF transmembrane conductance regulator (CFTR) gene or protein
      • CFTR-related disorder defined as a monosymptomatic clinical entity (such as congenital bilateral absence of vas deferens, pancreatitis, or bronchiectasis) associated with CFTR dysfunction that does not fulfill the diagnostic criteria for CF
      • CFTR-related metabolic syndrome (CRMS) and CF screen positive, inconclusive diagnosis (CFSPID) defined as infant with positive newborn screen for CF and ≥ 1 of the following
        • sweat chloride value < 30 mmol/L and 2 CFTR mutations, of which > 1 has unclear phenotypic consequences
        • intermediate sweat chloride value (30-59 mmol/L) and 0-1 CF-causing mutation
    • References - 4, 21658649J Cyst Fibros 2011 Jun;10 Suppl 2:S86
  • previously used terminology
    • classic CF - clinical presentation consistent with CF (such as signs and symptoms associated with chronic sinopulmonary disease, gastrointestinal or nutritional abnormalities [pancreatitis/pancreatic insufficiency, male infertility, or allergic bronchopulmonary aspergillosis) and sweat chloride concentration > 60 mmol/L
    • nonclassic (or atypical) CF - milder respiratory disease and/or CF phenotype in ≥ 1 organ system with normal (< 30 mEq/L [30 mmol/L]) or borderline (30-60 mEq/L [30-60 mmol/L]) sweat chloride concentration
    • Reference - ECFS recommendations for classification of diseases as CFTR-related disorders (21658649J Cyst Fibros 2011 Jun;10 Suppl 2:S86)

References

General references used

  1. Elborn JS. Cystic fibrosis. Lancet. 2016 Nov 19;388(10059):2519-31
  2. Spoonhower KA, Davis PB. Epidemiology of Cystic Fibrosis. Clin Chest Med. 2016 Mar;37(1):1-8
  3. Brewington J, Clancy JP. Diagnostic Testing in Cystic Fibrosis. Clin Chest Med. 2016 Mar;37(1):31-46
  4. Farrell PM, White TB, Ren CL, et al. Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017 Feb;181S:S4-S15.e1
  5. Mogayzel PJ Jr, Naureckas ET, Robinson KA, et al. Cystic Fibrosis Foundation. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013 Apr 1;187(7):680-9
  6. Floto RA, Olivier KN, Saiman L, 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: executive summary. Thorax. 2016 Jan;71(1):88-90full-text
  7. Ren CL, Morgan RL, Oermann C, 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):271-80, commentary can be found in Ann Am Thorac Soc 2018 Mar;15(3);298

Recommendation grading systems used

  • American Diabetes Association (ADA) evidence grading system for clinical practice recommendations
    • Grade A
      • clear evidence from well-conducted, generalizable, randomized controlled trials (RCTs) that are adequately powered, including evidence from well-conducted multicenter trial or meta-analysis that incorporated quality ratings in analysis
      • compelling nonexperimental evidence, specifically, "all or none" rule developed by Center for Evidence Based Medicine at Oxford
      • supportive evidence from well-conducted RCTs that are adequately powered, including evidence from well-conducted trial at ≥ 1 institution or meta-analysis that incorporated quality ratings in analysis
    • Grade B
      • supportive evidence from well-conducted cohort studies, including evidence from well-conducted prospective cohort study or registry or meta-analysis of cohort studies
      • supportive evidence from a well-conducted case-control study
    • Grade C
      • supportive evidence from poorly controlled or uncontrolled studies
        • evidence from randomized clinical trials with ≥ 1 major or ≥ 3 minor methodologic flaws that could invalidate results
        • evidence from observational studies with high potential for bias (such as case series with comparison to historical controls)
        • evidence from case series or case reports
      • conflicting evidence with weight of evidence supporting recommendation
    • Grade E - expert consensus or clinical experience
    • Reference - ADA 2019 standards of medical care in diabetes: introduction (Diabetes Care 2019 Jan;42(Suppl 1):S1)
  • International Society for Pediatric and Adolescent Diabetes (ISPAD) uses American Diabetes Association (ADA) grading system
    • Grade A
      • clear evidence from well-conducted, generalizable, randomized controlled trials (RCTs) that are adequately powered, including multicenter trials or meta-analyses incorporating quality ratings
      • compelling nonexperimental evidence, specifically, "all or none" rule developed by Center for Evidence Based Medicine at Oxford
      • supportive evidence from well-conducted RCTs that are adequately powered, including evidence from well-conducted trials at ≥ 1 institutions
    • Grade B
      • supportive evidence from well-conducted cohort studies, including prospective cohort studies or registry or meta-analyses of cohort studies
      • supportive evidence from well-conducted case-control study
    • Grade C
      • supportive evidence from poorly controlled or uncontrolled studies , including
        • RCTs with ≥ 1 major or ≥ 3 minor methodological flaws that could invalidate results
        • observational studies with high potential for bias
        • case series or case reports
      • conflicting evidence with weight of evidence supporting recommendation
    • Grade E - expert consensus or clinical experience
    • Reference - ISPAD 2018 clinical practice consensus guideline on management of cystic fibrosis-related diabetes in children and adolescents (Pediatr Diabetes 2018 Oct;19 Suppl 27:64PDF
  • Cystic Fibrosis Foundation (CFF) uses United States Preventive Services Task Force (USPSTF) grades of recommendation
    • Grade A - CFF strongly recommends that clinicians provide the service to eligible patients, based on good evidence that the service improves important health outcomes and that benefits substantially outweigh harms
    • Grade B - CFF recommends that clinicians provide the service to eligible patients, based on at least fair evidence that the service improves important health outcomes and that benefits outweigh harms
    • Grade C - CFF makes no recommendation for or against routinely providing the service, based on at least fair evidence that the service can improve health outcomes but the balance of benefits and harms is too close to justify a general recommendation
    • Grade D - CFF recommends against routinely providing the service to asymptomatic patients, based on at least fair evidence that the service is ineffective or that harms outweigh benefits
    • Grade I - CFF concludes that the evidence is insufficient to recommend for or against routinely providing the service; evidence that the service is effective is lacking, of poor quality, or conflicting, and balance of benefits and harms cannot be determined
    • see USPSTF Grade Definitions for details
    • Reference - CFF guideline on nutrition-related management of children and adults with cystic fibrosis (18442507J Am Diet Assoc 2008 May;108(5):832)
  • Cystic Fibrosis Foundation (CFF) uses United States Preventive Services Task Force (USPSTF) grades of recommendation
    • Grade A - CFF recommends the service based on high certainty that net benefit is substantial
    • Grade B - CFF recommends the service based on high certainty that net benefit is moderate or moderate certainty that net benefit is moderate to substantial
    • Grade C - CFF recommends against routinely providing the service based on moderate or high certainty that net benefit is small; there may be considerations that support providing the service to an individual patient
    • Grade D - CFF recommends against the service based on moderate or high certainty that the service has no net benefit or that the harm outweighs the benefits
    • Grade I - CFF concludes that current evidence is insufficient to assess balance of benefits and harms of the service; evidence is lacking, of poor quality, or conflicting, and balance of benefits and harms cannot be determined
    • see USPSTF Grade Definitions for details
    • References
  • Cystic Fibrosis Foundation (CFF) uses United States Preventive Services Task Force (USPSTF) grades of recommendation
    • Grade A - CFF strongly recommends that clinicians routinely provide this therapy based on high certainty that net benefit is substantial
    • Grade B - CFF recommends that clinicians routinely provide this therapy based on high certainty that net benefit is moderate or moderate certainty that net benefit is moderate to substantial
    • Grade C - CFF recommends that clinicians consider providing this therapy to selected patients depending on individual circumstances; however, for most individuals without signs or symptoms, there is likely to be only small benefit from this therapy
    • Grade D - CFF recommends against this therapy based on moderate or high certainty that the service has no net benefit or that harms outweigh benefits
    • Grade I - CFF concludes that current evidence is insufficient to assess balance of benefits and harms of the service; evidence is lacking, of poor quality, or conflicting, and balance of benefits and harms cannot be determined
    • see USPSTF Grade Definitions for details
    • References
  • Cystic Fibrosis Foundation (CFF) uses United States Preventive Services Task Force (USPSTF) grades of recommendation
    • Grade A - CFF strongly recommends that clinicians routinely provide this therapy based on high certainty that net benefit is substantial
    • Grade B - CFF recommends that clinicians routinely provide this therapy based on high certainty that net benefit is moderate or moderate certainty that net benefit is moderate to substantial
    • Grade C - CFF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences based on at least moderate certainty that net benefit is small
    • Grade D - CFF recommends against this therapy based on moderate or high certainty that the service has no net benefit or that harms outweigh benefits
    • Grade I - CFF concludes that current evidence is insufficient to assess balance of benefits and harms of the service; evidence is lacking, of poor quality, or conflicting, and balance of benefits and harms cannot be determined
    • Consensus recommendation - recommendation made in cases of limited or absent evidence based on clinical experience and use of existing evidence from other patient populations
    • Reference - CFF clinical practice guideline on preschoolers with cystic fibrosis (Pediatrics 2016 Apr;137(4).doi: 10.1542/peds.2015-1784.full-text)
  • Cystic Fibrosis Foundation (CFF) uses Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) grades of recommendation
    • Strong recommendation - most individuals should receive this intervention; adherence to this recommendation according to guideline could be used as quality criterion or performance indicator
    • Conditional recommendation - different choices will be appropriate for individual patients and clinicians must help each patient arrive at management decision consistent with her or her values and preferences; decision aids may be useful
    • Reference - CFF pulmonary guideline on use of cystic fibrosis transmembrane conductance regulator modulator therapy (Ann Am Thorac Soc 2018 Mar;15(3):271), commentary can be found in Ann Am Thorac Soc 2018 Mar;15(3);298

Synthesized Recommendation Grading System for DynaMed Content

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    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
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  • Editorial Team role definitions
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How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T116913, Cystic Fibrosis (CF); [updated 2018 Nov 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T116913. Registration and login required.

Published by EBSCO Information Services. Copyright © 2020, EBSCO Information Services. All rights reserved. No part of this may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission.

EBSCO Information Services accepts no liability for advice or information given herein or errors/omissions in the text. It is merely intended as a general informational overview of the subject for the healthcare professional.

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