Diagnosing Cystic Fibrosis in Adults

Abstract

Diagnosing cystic fibrosis (CF) in adulthood is not a rare occurrence for CF centers despite the popular belief that the diagnosis is achieved almost universally in childhood by means of newborn screening or early clinical presentation. The purpose of this review article is to highlight specific considerations of adult diagnosis of CF. Obtaining a diagnosis of CF at any age is exceptionally important to ensure optimal treatment, monitoring, and support. In the new era of more personalized treatment with the advent of transformative therapies targeting the underlying protein defect, accurate diagnosis is of increasing importance. This review highlights the diagnostic algorithm leading to a new diagnosis of CF in adults. The diagnosis is usually confirmed in the presence of a compatible clinical presentation, evidence of cystic fibrosis transmembrane conductance regulator (CFTR) protein dysfunction, and/or identification of variants in the CFTR gene believed to alter protein function. Achieving the diagnosis, however, is not always straightforward as CFTR protein function exists on a continuum with different organs displaying varying sensitivity to diminution in function. We highlight the current knowledge regarding the epidemiology of CF diagnosed in adults and outline the various clinical presentations, including pulmonary and extrapulmonary, which are more common in this population. We expand on the stepwise testing procedures that lead to diagnosis, paying particular attention to additional levels of testing which may be required to achieve an accurate diagnosis. There continues to be an important need for both pulmonary and other specialists to be aware of the potential for later presentation of CF, as the improvements in treatment over decades have had large positive impacts on prognosis for people with this condition.

Delayed identification of compound heterozygous (Phe508del/Arg117His) cystic fibrosis variants in a patient awaiting liver transplantation

“…The top modes of presentation were persistent/acute respiratory infection (53.9%), bronchiectasis (10%), family history (14%) and nasal polyps (7.1%) 5. While many of these adult-diagnosed cases were those born before newborn screening (NBS), it is also crucial to note that false negatives on NBS are possible due to residual CFTR function and pancreatic sufficiency at the time of testing 6 7…”

“…The impact of CFTR variants depends on their individual effect on CFTR function,6 the second CFTR variant, potential modifier genes8 and environmental factors 9. There are over 2100 CFTR variants listed in the Cystic Fibrosis Mutation Database10 grouped into six classes based on their effect on the CFTR; for example, class I variants result in no functional protein being produced, whereas class IV variants lead to the production of protein but affect channel functioning and may be associated with milder diseases 11–13.…”

Evaluating the contribution of the Glittre‐ADL test in adults with cystic fibrosis

“…Between April 2022 and March 2023, a cross-sectional observational study was carried out with 34 consecutive CF patients (out of 37 eligible patients) who were regularly seen at the Piquet Carneiro Polyclinic of the State University of Rio de Janeiro, Rio de Janeiro, Brazil. The inclusion criteria were age ≥18 years, a diagnosis based on clinical history compatible with CF, and two sweat tests with chloride ions ≥60 mEq/L and/or two mutations identified in the CF transmembrane conductance regulator gene (Barry & Simmonds, 2023). The exclusion criteria were patients with physical disability making it difficult to perform the exercise tests, an acute exacerbation in the last 3 weeks, and cardiopulmonary, orthopedic, or neurological diseases unrelated to CF.…”

“…Cystic fibrosis (CF) is an important autosomal recessive genetic disease clinically identified by chronic lung disease, exocrine pancreatic insufficiency, and a high concentration of electrolytes in sweat (Barry & Simmonds, 2023). Advances in the diagnosis and treatment of CF in recent decades have considerably increased its survival, so the number of adults who need to be treated is growing (Barry & Simmonds, 2023).…”

“…Cystic fibrosis (CF) is an important autosomal recessive genetic disease clinically identified by chronic lung disease, exocrine pancreatic insufficiency, and a high concentration of electrolytes in sweat (Barry & Simmonds, 2023). Advances in the diagnosis and treatment of CF in recent decades have considerably increased its survival, so the number of adults who need to be treated is growing (Barry & Simmonds, 2023). With longer survival, the worsening of the disease becomes more evident, such as the development of polymicrobial infections and progressive deterioration of lung function, impairing health‐related quality of life (HRQoL) (Arikan et al., 2015).…”