Activity ID
11652Expires
June 6, 2024Format Type
Journal-basedCME Credit
1Fee
$30CME Provider: JAMA
Description of CME Course
Importance Cystic fibrosis, a genetic disorder defined by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, affects more than 30 000 individuals in the US and approximately 89 000 worldwide. Absent or decreased function of the CFTR protein is associated with multiorgan dysfunction and shortened life expectancy.
Observations CFTR is an anion channel in the apical membrane of epithelial cells. Loss of function leads to obstructed exocrine glands. Of people with cystic fibrosis in the US, approximately 85.5% have the gene variant F508del. Manifestations of cystic fibrosis in patients with the F508del gene variant begin in infancy with steatorrhea, poor weight gain, and respiratory symptoms (coughing, wheezing). As people with cystic fibrosis age, chronic respiratory bacterial infections cause loss of lung function and bronchiectasis. With the availability of universal newborn screening in multiple countries including the US, many people with cystic fibrosis are asymptomatic at diagnosis. With multidisciplinary care teams that included dietitians, respiratory therapists, and social workers, treatment of cystic fibrosis can slow disease progression. Median survival has improved from 36.3 years (95% CI, 35.1-37.9) in 2006 to 53.1 years (95% CI, 51.6-54.7) in 2021. Pulmonary therapies for patients with cystic fibrosis consist of mucolytics (eg, dornase alfa), anti-inflammatories (eg, azithromycin), and antibiotics (such as tobramycin delivered by a nebulizer). Four small molecular therapies, termed CFTR modulators, that facilitate CFTR production and/or function have received regulatory approval. Examples are ivacaftor and elexacaftor-tezacaftor-ivacaftor. For example, in patients with 1 F508del variant, the combination of ivacaftor, tezacaftor, and elexacaftor improved lung function from −0.2% in the placebo group to 13.6% (difference, 13.8%; 95% CI, 12.1%-15.4%) and decreased the annualized estimated rate of pulmonary exacerbations from 0.98 to 0.37 (rate ratio, 0.37; 95% CI, 0.25-0.55). Improved respiratory function and symptoms have lasted up to 144 weeks in postapproval observational studies. An additional 177 variants are eligible for treatment with the elexacaftor-tezacaftor-ivacaftor combination.
Conclusion Cystic fibrosis affects approximately 89 000 people worldwide and is associated with a spectrum of disease related to exocrine dysfunction, including chronic respiratory bacterial infections and reduced life expectancy. First-line pulmonary therapies consist of mucolytics, anti-inflammatories, and antibiotics, and approximately 90% of people with cystic fibrosis who are 2 years or older may benefit from a combination of ivacaftor, tezacaftor, and elexacaftor.
Disclaimers
1. This activity is accredited by the American Medical Association.
2. This activity is free to AMA members.
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ABMS Lifelong Learning CME Activity
Allergy and Immunology
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Ophthalmology
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Pathology
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NoNOTE: If a Member Board has not deemed this activity for MOC approval as an accredited CME activity, this activity may count toward an ABMS Member Board’s general CME requirement. Please refer directly to your Member Board’s MOC Part II Lifelong Learning and Self-Assessment Program Requirements.
Educational Objectives
To identify the key insights or developments described in this article
Keywords
Medical Education, Hypertension
Competencies
Medical Knowledge
CME Credit Type
AMA PRA Category 1 Credit
DOI
10.1001/jama.2023.8120