Tobacco Smoke Adversely Affects Sustained Benefits of ETI in Cystic Fibrosis
- Admin
- Aug 7
- 3 min read
Among people with cystic fibrosis using ETI, ppFEV1 improvement trajectories began to diverge by tobacco smoke exposure status after 6 months of ETI use.
Tobacco smoke exposure may diminish the level of benefit provided by elexacaftor/tezacaftor/ivacaftor (ETI) in patients with cystic fibrosis (CF) after 6 months, according to study findings published in the Journal of Cystic Fibrosis.
Researchers assessed how tobacco smoke exposure affected the clinical benefits of ETI in people with CF, focusing on changes in lung function and exacerbations. The investigators analyzed retrospective data from the CF Foundation Patient Registry (CFFPR) from January 1, 2019, to December 31, 2021, for patients with CF with a documented prescription of ETI.
Lung function was defined as percent predicted forced expiratory volume in 1 second (ppFEV1), and pulmonary exacerbations (PEx) were regarded as the number of exacerbations treated with intravenous antibiotics within a 12-month period.
ETI increases ppFEV1 and decreases PEx in all PwCF, but this benefit is not sustained past 6 months of ETI therapy among those with [tobacco smoke exposure], thus widening long-term disparities in pulmonary outcomes.
Tobacco smoke exposure (TSE) was based on patient-reported smoking, living in the same household as someone who smokes, or exposure daily or several times per week at any point during the study period.
The ppFEV1 analysis included 15,005 individuals (mean age, 27.7 years; 48.2% female), and the PEx analysis included 14,732 individuals. Among the patients who were prescribed ETI, 2043 (13.6%) had documented TSE. Compared with the unexposed group, participants with TSE were younger, and a reduced proportion were female.
Smoke-exposed patients had a 2.67% decreased ppFEV1 compared with unexposed individuals at baseline. ETI led to an increase in ppFEV1 of 5.29%, with a monthly increase of 0.57% until 6 months of use. The monthly change after month 6 associated with ETI was 0.01% (bmonthly change after ETI [0.57] + b 6-monthly change 6 months after ETI [−0.56] = 0.01).
Among the participants exposed to smoke, the monthly change after month 6 associated with ETI was −0.03% (Ɣmonthly change after ETI [0.57] + Ɣmonthly change 6 months after ETI [−0.56] + Ɣmonthly change 6 months after ETI X TSE [−0.04] = −0.03).
The smoke-exposed and unexposed groups had comparable (8.5%) improvement in ppFEV1 at 6 months after ETI initiation (77.4% vs 80.0%). After 6 months, the model predicted that unexposed patients had a 0.01% monthly increase in ppFEV1 from ETI, and the smoke-exposed group had a 0.03% monthly reduction (0.04% monthly discordance). At 36 months, the difference in ppFEV1 by TSE status was 3.43% (76.3% vs 79.7%, P <.001), compared with a 2.67% difference at baseline (69.1% vs 71.8%, P <.001).
Before ETI use, TSE increased the odds of PEx by 60% (P <.001). On ETI, the smoke-exposed group had more than twice the odds (odds ratio [OR], 2.2; P <.001) of PEx vs those not exposed to smoke. Before using ETI, TSE was associated with an increased probability of having an exacerbation (0.28 vs 0.34; P <.001). ETI was associated with a decreased probability of PEx in both the non-TSE and TSE patient groups (0.16 and 0.23, respectively), although among patients on ETI, the disparity in PEx by TSE status was greater.
In citing study limitations, the researchers noted that the timing of ETI initiation is based on data reported to the CFFPR, and that the study overlapped with the COVID-19 pandemic. Also, other environmental exposures such as proximity to roadways were not available in the CFFPR.
“ETI increases ppFEV1 and decreases PEx in all PwCF, but this benefit is not sustained past 6 months of ETI therapy among those with [tobacco smoke exposure], thus widening long-term disparities in pulmonary outcomes,” the study authors concluded. Accordingly, “efforts must be made to reduce and eliminate smoke exposure in patients with CF,” the study authors added.
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