Background:Impact of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, such as elexacaftor-tezacaftor-ivacaftor (ETI), on structural changes in the lungs in pwCF is unclear.    

Objective: To determine the impact of ETI on clinical parameters and on structural lung disease as measured by the changes in the chest CT scans in pwCF.

Methods: % predicted FEV1 (ppFEV1), body mass index (BMI) and microbiologic data were collected at initiation and 3-month intervals for 1 year. Chest CT scans were completed before starting ETI therapy (baseline) and at one year on ETI therapy and were analyzed by two pulmonologists independently

Results: Sample size was 67 pwCF, 30 (44.8%) males, median age of 25 (16, 33.5) years.  Significant increases in ppFEV1 (65 ± 21 to 77±21) and BMI (p<0.001 for both) and significant decrease in MRSA and Pseudomonus positicity (-42% for both) were observed by 3 months and all persisted for 1-year.  None of the pwCF had worsening of chest CT parameters during ETI therapy.  At baseline, chest CT scans revealed bronchiectasis in 65 (97%) pwCF and at one-year follow-up, it was absent or decreased in (17%).  Bronchial wall thickening (BWT) noted in 64 (97%) and at one-year follow-up, it was absent or decreased in 58 (86%).  Mucous plugging was noted in 63 (95.5%) and at one-year follow-up, it was absent or decreased in 61(95%).  Hyperinflation/air trapping was noted in 44 (67%) and at one-year, it was decreased or absent in 37(61%) and unchanged in 24 (39%).

Conclusions: ETI significantly improved clinical outcomes and lung disease as documented by improvement in chest CT scans.