Predicting Severity in Cystic Fibrosis With Sweat Chloride

Sweat chloride levels can predict later severity in patients with cystic fibrosis (CF), as confirmed by computed tomography (CT) and lung function tests. The findings of the retrospective study — the first to examine sweat chloride levels at diagnosis to predict later lung disease — were published in Pediatric Pulmonology.

Daan Caudri, MD, PhD, from Erasmus Medical Center-Sophia Children’s Hospital, Rotterdam, The Netherlands and the University of Western Australia, Subiaco, and colleagues sought to predict the severity of CF based on sweat chloride levels in children. Mutations in the CF transmembrane conductance regulator (CFTR) gene affect the absorption of chloride and sodium in airway epithelium.

 

A group of 59 children from a single clinic with confirmed CF (baseline median age 0.5; follow-up median age: 14; 49% male) were included in the study. To qualify for inclusion, patients had to have a sweat chloride test within 1 year of their CF diagnosis; a spirometry-controlled volumetric inspiratory and expiratory chest computed tomography (CT) scan between 2007 and 2012; routine spirometry within a 3-month window from the CT scan; CT in clinically stable patients age between 4 and <26.

CF severity was based on the extent of bronchiectasis, airway wall thickening, mucus plugging, opacities, cysts and bullae on inspiratory CTs, and trapped air on expiratory CTs.

The patients were stratified by age tertiles, with the oldest cohort (15.5-18.2) showing the only significant relationship between sweat chloride levels and CT scans (P =.018), which suggests that sweat chloride testing is not a sensitive predictor for early lung damage. The total CF-CT scores by tertiles from youngest to oldest were −3.7 (P =.327), 1.7 (P =.237), and 5.1 (P =.018).

“Sweat chloride is routinely assessed in the diagnosis cystic fibrosis and is a marker of CFTR function in the skin. It seems logical that a lower sweat chloride level in CF patients is related to more residual CFTR function in the lungs and thereby to a more favorable clinical course,” explained Dr Caudri in an email interview with Pulmonology Advisor.

“Despite this, previous reports failed to show any significant relation[ship] between sweat chloride and improved clinical outcome. Our longitudinal data do show that a higher sweat chloride is significantly associated with more structural lung damage assessed by CT scan,” noted Dr Caudri. “This association was only demonstrable in the older children (>15 years), suggesting that it takes many years for the lung damage to occur. Sweat chloride may be used as a prognostic marker to early identify children at highest risk of morbidity, facilitating personalized treatment strategies.”

Study Limitations

• The retrospective study used a small sample
• Because the study collected samples from one site its generalizability may be limited
• Only children 5 and older were included in the study because researchers used spirometry-controlled expiratory CT scans, a test that requires patient cooperation

Disclosures

Dr Caudri received grant support from a research fellowship from the Rothwell family, a Ter Meulen Grant of the Royal Netherlands Academy of Arts and Sciences, and a Research Fellowship Sophia 2014 from the Sophia Children’s Hospital Fund.

Reference

Caudri D, Zitter D, Bronsveld I, Tiddens H. Is sweat chloride predictive of severity of cystic fibrosis lung disease assessed by chest computed tomography? [published online June 6, 2017]. Pediatr Pulmonol. doi:10.1002/ppul.23739