SCIENTIFIC
Cystic Fibrosis in West Virginia: A Review and Update
AUTHORS:
ABSTRACT
Mark A. Colantonio MD 1 Casandra Arevalo Marcano MD 2 Kyle Chapman MD 3
AFFILIATIONS:
1
Department of Medicine, West Virginia University, Morgantown, West Virginia, USA
2
Department of Pediatrics, Division of Pediatric Pulmonology, Morgantown, West Virginia, USA
3
Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, West Virginia University, Morgantown, West Virginia, USA
CORRESPONDING AUTHOR:
Mark A. Colantonio MD macolantonio @ hsc. wvu. edu
DISCLOSURES: None
ETHICS STATEMENT: Not applicable
FUNDING: None
EPIDEMIOLOGY
Cystic fibrosis( CF) is an autosomal recessive genetic disorder with over 2,000 genetic variants. 1 It is estimated that 30,000 Americans and 70,000 individuals worldwide are affected by CF, with 1 / 2,500 births affected each year. 1, 2 Though typically in the realm of pediatrics, the United States( US) CF Patient Registry revealed 7 % of cases are diagnosed in adulthood. 3 Specific to West Virginia( WV), prevalence of CF among the Medicaid population has been reported to be 0.09 %; however, sparse data exists regarding the exact prevalence among the adult and pediatric populations. 4 As of 2022, roughly 250 adult patients carried a diagnosis of CF throughout WV. 5
A review of cystic fibrosis( CF), including epidemiology, pathogenesis, screening, diagnosis, and treatment is provided, along with a brief introduction to the Mountain State Cystic Fibrosis Center. Treatment challenges
PATHOGENESIS
It was not until 1989 that Dr. Francis Collins discovered the gene responsible for CF. 6 CF is secondary to mutations of the cystic fibrosis transmembrane conductance regulator( CFTR) gene, a chloride dependent channel regulated by adenosine triphosphate phosphorylation. 2, 7 This transmembrane protein is essential for normal lung parenchymal function. 1 Dysfunctional chloride channels can lead to disruption of fluid homeostasis, leading to thickened secretions. 1, 8 Dr. Paul di Sant’ Agnese first identified elevated sweat chloride levels in 1948 among infants diagnosed with CF. This observation was later adopted as a screening test for the disease. 1 More than 1,000 CFTR variations have been identified, and mutations have been classified into subgroups by protein expression( Table 1). 9 Transmembrane dysfunction can present with chronic respiratory infections, leading to bronchiectasis, structural lung disease, and airflow obstructions, in addition to extrapulmonary manifestations, including pancreatic insufficiency, infertility, and malnutrition. 7, 10
Class Mutation Outcome
TABLE 1
in the management of pediatric and adult patients with CF in rural areas, such as West Virginia, and the future directions of CF care are also described.
SCREENING AND DIAGNOSIS
Due to complications associated with CF, early diagnosis is essential. Added to the US Recommended Uniform Newborn Screening Panel in 2006, CF is included in newborn screening country-wide. 11 CF is often suspected in newborns presenting with failure to thrive; however, those without pancreatic involvement may go undiagnosed. 8 Standardized screening includes measurement of serum immunoreactive trypsinogen levels, followed by genetic testing for CFTR variants in those with elevated trypsinogen levels. 8 Follow-up genetic testing is useful in those with intermediate results on sweat chloride testing. 1 Despite widespread screening, some individuals are not diagnosed until adulthood, leading to malnourishment, cognitive delay, or irreversible chronic lung disease in adulthood. 12 Although CF was once a disease diagnosed post-mortem in infants, modern advances in therapy have led to a dramatic improvement in life expectancy, and CF is no longer exclusively a pediatric disease. 13, 14 Hence, clinicians who care for adults must remain vigilant for proper diagnosis and management of this patient population.
I Premature stop codon( G542X, W1282X and R553X) II Dysfunctional protein processing( Phe508del) III Dysfunctional protein regulation( G551D) IV Disruption of ion conductance( R117H) V
Inadequate amount of surface protein VI Membrane protein instability( Phe508del)
Description of CFTR class mutations and common phenotypic expressions. 7, 9
12 • www. wvsma. org