Non-CF Human airway epithelial cells were obtained from macroscopically normal, tumor-free, anonymous bronchial tissue obtained from lung cancer patients undergoing resection surgery for lung cancer at Erasmus MC Rotterdam, approved by the Medical ethical committee of the Erasmus MC (METC 2012-512; P5, P10, P11, P24, all-male, ex-smokers 58–76 years old). All CF primary epithelial cells, five donors aged 12–32 years no history of smoking (Table 1) and one non-CF sample or (BP954) were obtained from the CF Translational Center, McGill University, Montreal, Canada according to a protocol approved by the Institutional Ethics Protocol Review Board of McGill University (#A08-M70-14B).

Short circuit current responses to forskolin (ΔIscForsk) for well-differentiated primary bronchial epithelial cells used in this study, after treatment with correctors.

Non-CF data were collected from 11 donors HBEC-ALI (P1), and their mean short circuit current response to the cAMP agonist forskolin (ΔI scForsk, 48.4 ± 4.5 μA/cm2, Mean ± S.E.M) was used to calculate the average CFTR function after the rescue of CF cells expressed as % of non-CF (WT). CF HBEC ALI cells (P1, N = 3) were treated with lumacaftor (VX-809), 1 μM for 24 h, or elexacaftor (VX-445) plus tezacaftor (VX-661), 3 μM each for 24 h, followed by treatment with forskolin and ivacaftor (VX770) 300 nM. SEM is 10% or less of the average shown in all experiments. n/a: assay not performed for this donor.

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