Tracheal Diverticula in People with Cystic Fibrosis on Elexacaftor/Tezacaftor/Ivacaftor: An Italian Multicenter Retrospective Study

Abstract

Background/Objectives: Cystic Fibrosis (CF) is an autosomal recessive genetic disorder caused by variants in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Recently, a targeted therapy for CF has been developed, represented by the CFTR modulators that enhance or restore the function of the CFTR protein. The most recent is the combination of three modulators, Elexacaftor, Tezacaftor, and Ivacaftor (ETI). This study describes the presentation, management, and follow-up of tracheal diverticulum (TD) in pwCF receiving ETI therapy. Methods: This retrospective study included people with CF (pwCF) on ETI treatment and followed up in two CF Italian centers who developed an asymptomatic TD, diagnosed incidentally at chest CT scan. Results: Among 268 pwCF receiving ETI, three (1.19%) were diagnosed with TD identified after chest CT and were included in this study. Endoscopic confirmation was obtained in one patient. All patients were on inhaled colistimethate, two of them for chronic Pseudomonas aeruginosa colonization, and one undergoing eradication therapy. Conclusions: TD may be identified in chest CT obtained in pwCF in treatment with ETI. Further studies and a longer follow up are needed to confirm these findings.

Keywords: bronchoscopy; cystic fibrosis; elexacaftor/tezacaftor/ivacaftor; tracheal diverticulum.

Figure 1

(A) Axial and (B) coronal lung windows at chest CT showing the tracheal diverticulum at the right posterolateral wall of the trachea in a cystic fibrosis patient (Patient 1). White arrows show the tracheal diverticulum.

Figure 2

Bronchoscopy images of the tracheal diverticula identified in Patient 1, located at the right posterolateral wall (A) and the right paracarinal area (B). Black arrows show the orifice of the tracheal diverticulum into the tracheal lumen.

Figure 3

(A) Axial and (B) coronal lung windows at chest CT showing the tracheal diverticulum at the right posterolateral wall of the trachea in a cystic fibrosis patient (Patient 2). Black arrows show the tracheal diverticulum.

Figure 4

Axial lung window at chest CT showing the tracheal diverticulum at the right posterolateral wall of the trachea in a cystic fibrosis patient (Patient 3). White arrow shows the tracheal diverticulum.

Figure 5

Bronchoscopy images obtained in Patient 3, showing mucosal granuloma in the tracheal wall (A) and bronchial walls (B).

Figure 6

Proposal of management of incidental TD at chest CT in pwCF.