After careful consideration, the American Thoracic Society canceled its annual meeting that was to take place in Philadelphia, Pennsylvania from May 15-20, because of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although the live events will not proceed as planned, our readers can still find coverage of research that was scheduled to be presented at the meeting. A virtual event is being planned for later this year.
Tobacco smoke exposure inhibited the therapeutic benefit of the cystic fibrosis transmembrane conductance regulator (CFTR) modulators in pediatric patients, according to findings intended to be presented at the American Thoracic Society (ATS) International Conference. (Select research is slated to be presented in a virtual format later this year.)
Tobacco smoke has been shown reduce CFTR functional expression in vitro and contributes to acquired CFTR dysfunction in animal models. Therefore, researchers sought to determine whether tobacco smoke exposure also inhibits the clinical benefit of CFTR modulators, specifically, tezacaftor/ivacaftor. They performed a retrospective analysis of the CF Foundation Patient Registry comparing lung function changes, pulmonary exacerbations, and hospitalizations after tezacaftor/ivacaftor initiation in patients who were exposed to smoke vs patients who were not (ages, 12-18 years). Smoke exposure was determined by annual caregiver self-reports and was estimated using fixed-effects modelling, which accounted for sex, race, and parent education.
A total of 1429 patients (mean age, 14.7 years; 54.6% girls) with CF were prescribed tezacaftor/ivacaftor. The mean baseline forced expiratory volume in 1 second percent predicted (FEV1%) was 83.3%, and 27.6% of patients were exposed to smoke. The FEV1% of children who were not exposed to smoke increased by 0.72% (95% CI, 0.03%-1.41%), whereas the FEV1% of children exposed to smoke decreased by -1.03% (95% CI, -2.5% to 0.5%), according to bivariate analysis. Tezacaftor/ivacaftor contributed to 0.5% FEV1% improvement (95% CI, 0.08%-0.9%; P =.017) in children not exposed to smoke, but provided no benefit to children who were exposed to smoke (-0.44%; 95% CI, -1.01% to 0.13; P =.133).
In addition, smoke exposure increased the odds of children being hospitalized ≥2 times annually and of experiencing ≥2 pulmonary exacerbations annually by 31% (P =.002) and 47% (P =.03), respectively.
“Given the extremely high cost of CFTR modulator therapy, every effort must be taken to eliminate smoke exposure and maximize the therapeutic efficacy of CFTR-directed interventions,” the study authors concluded.
Oates GR, Baker E, Rowe SM, Rutland S, Fowler CM, Harris WT. Tobacco smoke exposure limits therapeutic benefit of a CFTR modulator in pediatric patients with cystic fibrosis. Am J Respir Crit Care Med. 2020;201:A2667.
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This article originally appeared on Pulmonology Advisor