CFTR Dysfunction Likely Associated With Worsened Airway Disease in Smokers

Gene helix
Gene helix
Cystic fibrosis transmembrane conductance regulator dysfunction is associated with worsened airway disease in patients with COPD.

In patients with smoking-related lung disease and chronic obstructive pulmonary disease (COPD), cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is associated with worsened airway disease, according to a study published in the Annals of the American Thoracic Society.

Current and former smokers without a history of CF were recruited from a single center (n=87). Researchers performed spirometry and inspiratory and expiratory volumetric computed tomography (CT) scans, and a radiologist was included in the study to determine the presence or absence of bronchiectasis, defined as the presence of bronchial dilation, or bronchial diameter that was greater than an accompanying pulmonary vessel’s diameter. The researchers hypothesized that dysfunction of the CFTR in smokers was associated with CT bronchiectasis in patients with COPD.

The study cohort included current smokers (49%) and former smokers (52%) with a median of 40 (interquartile range [IQR], 30-57) pack-per-year history. A total of 12 patients presented with visual CT bronchiectasis, of whom 33% had spirometry-defined COPD. Compared with patients without bronchiectasis, those with bronchiectasis had greater sweat chloride values (24 [IQR, 12-40] vs 44 [IQR, 24.5-53] mmol/L; P =.03).

Overall, higher values of sweat chloride were associated with a 4.4-fold increase in visual bronchiectasis (prevalence ratio, 4.4; 95% CI, 1.5-13.5; P =.008). Patients who demonstrated visual mosaic attenuation on CT were more likely to have elevated sweat chloride (43 [IQR, 40-49] vs 22.5 [IQR, 12-40] mmol/L; P =.03].

A total of 25 patients with elevated sweat chloride underwent full-gene CFTR sequencing, which demonstrated that 1 patient carried a common variant causative of CF (p.Phe508del [c.1521_1523delCTT]). Another patient showed likely in cis variants (p.Arg74Trp [c.220C>T] and p.Asp1270Asn [c.3808G>A]) that are possibly associated with CFTR-related disorders.

The study’s observational design, as well as the small number of patients with bronchiectasis included in the final analysis, represented its main limitations.

“The potential for CFTR dysfunction to contribute worsened airway disease in patients with smoking related lung disease and identify a specific sub-phenotype warrants further investigation,” the researchers concluded.


Teerapuncharoen K, Wells JM, Raju SV, et al. Acquired CFTR dysfunction and radiographic bronchiectasis in current and former smokers: a cross-sectional study [published online September 19, 2018]. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.201805-325RL