Diagnosis and Monitoring of Cystic Fibrosis

VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.

At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.

Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.

Çiğdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpaşa in Istanbul, Turkey, told Medscape Medical News that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.

Genetic Testing Picks Up Missed Cases

In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).

Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.

The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.

They found that cystic fibrosis was confirmed in only 30% newborns, while genetic testing could identify nine cases otherwise missed by SCT. “The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”

Biomarkers for Monitoring Cystic Fibrosis Exacerbations

C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.

Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.

Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).

All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:

• CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.

In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.

Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, told Medscape Medical News that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.

Korkmaz and Aslan reported no relevant financial relationships.

Manuela Callari is a freelance science journalist specializing in human and planetary health. Her words have been published in The Medical Republic, Rare Disease Advisor, The Guardian, MIT Technology Review, and others.