Cohort Definition Name: “Cystic Fibrosis”
Contributor name: Jill Hardin
Contributor OrcId: 0000-0003-2682-2187
Logic Description: 1 code of cystic fibrosis and a second code within 1 to 365 days post index
Recommended study application: outcome
Assertion statement: This cohort definition was executed on at least one real person-level observational health data source and resulted in a cohort with at least 1 person.
Submitted cohort definition:
CysticFibrosis.txt (2.0 KB)
Target Clinical Description
Overview:
Cystic fibrosis (CF) is a hereditary autosomal recessive disorder primarily affecting the respiratory and digestive systems. It is characterized by abnormal production of thick and sticky mucus that leads to obstructed airways, respiratory infections, and impaired digestion. CF is caused by mutations in the CFTR gene, which encodes a protein involved in ion transport across cell membranes. The accumulation of thick mucus in the airways and other organs results in chronic inflammation and progressive lung damage, as well as complications in the gastrointestinal and other systems.
Synonyms:
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Mucoviscidosis
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CF
Presentation:
Clinical presentation of cystic fibrosis includes: respiratory symptoms, chronic cough, wheezing, recurrent lung infections (e.g., pneumonia, bronchitis), and shortness of breath. Pancreatic insufficiency leading to malabsorption, steatorrhea, and malnutrition; meconium ileus in newborns. Other manifestations include poor weight gain and delayed growth. Impaired ion transport leads to elevated sweat chloride levels. Lung infections are the leading cause of death in CF patients.
Diagnostics Evaluation:
Every state in the US now routinely screens newborns for cystic fibrosis. A blood sample is checked for elevated immunoreactive trypsinogen (IRT), which is released by the pancreas. To confirm the diagnosis, skin sweat chloride levels are measured; in CF, sweat chloride levels are elevated > 60 mmol/L. Genetic testing is also done, to identify mutations in the CFTR gene, which supports or confirms the diagnosis. Pulmonary function tests and chest radiographs are done to measure lung function. Measurement of fecal fat content allows for assessment of steatorrhea, caused by impaired pancreatic function in CF.
Differential Diagnoses:
Conditions that could be mistaken for cystic fibrosis include primary ciliary dyskinesia, bronchiectasis due to other causes, immunodeficiencies.
Treatment Plan:
There is no cure for cystic fibrosis, but treatment can reduce symptoms and complications and improve quality of life. The treatment plan for cystic fibrosis includes airway clearance techniques, such as chest physiotherapy, postural drainage, and exercise to help clear mucus from the airways. Bronchodilators are used to open airways and improve breathing. Antibiotics, both systemic and inhaled, are used for treatment of respiratory infections, which are common in CF. Pancreatic enzyme supplements are used to prevent steatorrhea and resultant malnutrition. The are increased caloric needs in CF, and steatorrhea leads to fat soluble vitamin loss in the stool, so nutritional support is provided to supplement calories and ensure adequate vitamin intake. For patients with advanced lung disease, lung transplantation may be an option. For patients with advanced lung disease, lung transplantation may be an option. CFTR modulators are options for patients with certain gene mutations. These medications improve the function of the faulty CFTR protein, and may improve lung function and weight. The newest combination medication containing elexacaftor, ivacaftor and tezacftor (Trikafta®) is approved by the FDA for people ages 12 years and older. The combination medication containing tezacaftor and ivacaftor (Symdeko®) is approved for people ages 6 years and older. The combination medication containing lumacaftor and ivacaftor (Orkambi®) is approved for people ages 2 years and older. Ivacaftor (Kalydeco®) has been approved for people who are 6 years and older.
Prognosis:
In the short term, patients with cystic fibrosis may experience acute exacerbations of respiratory symptoms, requiring prompt treatment to prevent irreversible lung damage. Advances in medical management have improved long-term outcomes, but cystic fibrosis remains a chronic and progressive condition. Lifelong multidisciplinary care is essential for optimizing quality of life and extending survival.
Subtypes:
There are no specific subtypes of cystic fibrosis for this report.
References:
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Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005;352(19):1992-2001.
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Welsh MJ, Ramsey BW, Accurso F, et al. Cystic fibrosis. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. McGraw Hill MedicalError. Accessed August 9, 2023.
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Cystic Fibrosis Foundation. Patient Registry 2020 Annual Data Report. Bethesda, Maryland: Cystic Fibrosis Foundation; 2020. https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2020-Patient-Registry-Annual-Data-Report.pdf. Accessed August 9, 2023.
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Elborn JS. Cystic fibrosis. Lancet. 2016;388(10059):2519-2531.
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Cutting GR. Cystic fibrosis genetics: from molecular understanding to clinical application. Nat Rev Genet. 2015;16(1):45-56.
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Flume PA, Mogayzel PJ Jr, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: airway clearance therapies. Respir Care. 2009;54(4):522-537.
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Mayer-Hamblett N, Rosenfeld M, Emerson J, et al. Overweight, underweight, and mortality in a large cohort of young patients with cystic fibrosis. J Pediatr. 2017;181:
The Phevaluator results show that the sensitivity is highest for the definition using 1 code for CF and ranges from 0.93 (DOD) to 0.997 (Pharmetrics Plus). The sensitivities for the definition requiring 2 CF codes are lower ranging from 0.648 (MDCD) to 0.99 (Pharmetrics Plus). The PPVs are highest for definition requiring 2 CF codes ranging from 0.71 (EHR) to 0.889 (Pharmetrics Plus). The definition requiring a CF code followed by treatment in 180 days after index yielded low sensitivity and similar PPV as the two code definition. For this use case of background rates we recommend the 2x code algorithm which has good sensitivity and reasonable PPV. There seems to be some evidence that CF is over diagnosed which could lead to lower PPV. This might be a good case to use the 2x phenotype as it raises the PPV with only a moderate drop in sensitivity.