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Over two years, the difference in ppFEV by smoke exposure among tezacaftor/ivacaftor users increased by 1.2% (7.6% to 8.8%, p0.001). In both mixed effects and fixed effects regression models, tezacaftor/ivacaftor use was associated with improved ppFEV among unexposed individuals (1.2% and 1.7%, respectively; p0.001 for both) but provided no benefit among smoke-exposed counterparts (0.3%, p=0.5 and 0.6%, p=0.07, respectively). Tobacco smoke exposure nullifies the therapeutic benefit of tezacaftor/ivacaftor among individuals with
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