Anthony C Oliver1,2, Michael DeSarno1,3, Charles G Irvin4, David Kaminsky4, Jennifer W Tidey5, Stacey C Sigmon1,2,6, Sarah H Heil1,2,6, Diann E Gaalema1,2,6, Dustin Lee7, Janice Y Bunn1,3, Danielle R Davis1,8, Joanna M Streck1,9, Thomas Gallagher1,2, Stephen T Higgins1,2,6. 1. Vermont Center on Behavior and Health, Larner College of Medicine, University of Vermont, Burlington, VT, USA. 2. Department of Psychiatry, Larner College of Medicine, University of Vermont, Burlington, VT, USA. 3. Department of Medical Biostatistics, Larner College of Medicine, University of Vermont, Burlington, VT, USA. 4. Vermont Lung Center, Larner College of Medicine, University of Vermont, Burlington, VT, USA. 5. Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA. 6. Department of Psychological Science, University of Vermont, Burlington, VT, USA. 7. Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 8. Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. 9. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Abstract
INTRODUCTION: This study examined whether exposure to reduced-nicotine-content cigarettes (RNCCs) for 12 weeks alters respiratory health using Fractional Exhaled Nitric Oxide (FeNO), a validated biomarker of respiratory epithelial health, and the Respiratory Health Questionnaire (RHQ), a subject-rated questionnaire on respiratory symptoms. Participants were 747 adult daily smokers enrolled in three double-blind, randomized clinical trials evaluating effects of cigarette nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) in people with affective disorders, opioid use disorder (OUD), or socioeconomic disadvantage. AIMS AND METHODS: FeNO levels and RHQ ratings were collected at baseline and Weeks 6 and 12 following randomization. Multiple regression was used to assess associations of FeNO and RHQ with smoking characteristics. Mixed-model repeated-measures ANOVA was used to evaluate the effects of nicotine content on FeNO and RHQ outcomes over the 12-week study period. RESULTS: FeNO levels but not RHQ ratings varied inversely with smoking characteristics at baseline (Ps < 0.0001) in smokers with affective disorders and socioeconomic disadvantage but less so in those with OUD. Participants with affective disorders and socioeconomic disadvantage, but not those with OUD, who were assigned to RNCCs had higher FeNO levels at Week 12 than those assigned to the 15.8 mg/g dose [F(2,423) = 4.51, p = .01, Cohen's d = 0.21]. No significant dose-related changes in RHQ scores were identified. CONCLUSIONS: Use of RNCCs across a 12-week period attenuates smoking-related reductions in FeNO levels in smokers with affective disorders and socioeconomic disadvantage although not those with OUD. FeNO changes were not accompanied by changes in respiratory-health ratings. TRIAL REGISTRATION: Inclusion and exclusion criteria for the sample and experimental manipulation of the nicotine content of assigned cigarettes are registered: NCT02232737, NCT02250664, NCT02250534. The FeNO measure reported in this manuscript is an exploratory outcome that was not registered. IMPLICATIONS: Should a reduced nicotine content standard be implemented; these results suggest that reduced nicotine content in cigarettes will not exacerbate and instead may attenuate smoking-related decreases in FeNO. This is significant as NO is an important component in maintaining a healthy respiratory system and necessary to defend against infection. Furthermore, the results of the current study demonstrate that the adoption of the reduced nicotine content standard may result in beneficial impacts on respiratory epithelial health among vulnerable populations that are disproportionally affected by the adverse health outcomes precipitated by combustible tobacco use.
INTRODUCTION: This study examined whether exposure to reduced-nicotine-content cigarettes (RNCCs) for 12 weeks alters respiratory health using Fractional Exhaled Nitric Oxide (FeNO), a validated biomarker of respiratory epithelial health, and the Respiratory Health Questionnaire (RHQ), a subject-rated questionnaire on respiratory symptoms. Participants were 747 adult daily smokers enrolled in three double-blind, randomized clinical trials evaluating effects of cigarette nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) in people with affective disorders, opioid use disorder (OUD), or socioeconomic disadvantage. AIMS AND METHODS: FeNO levels and RHQ ratings were collected at baseline and Weeks 6 and 12 following randomization. Multiple regression was used to assess associations of FeNO and RHQ with smoking characteristics. Mixed-model repeated-measures ANOVA was used to evaluate the effects of nicotine content on FeNO and RHQ outcomes over the 12-week study period. RESULTS: FeNO levels but not RHQ ratings varied inversely with smoking characteristics at baseline (Ps < 0.0001) in smokers with affective disorders and socioeconomic disadvantage but less so in those with OUD. Participants with affective disorders and socioeconomic disadvantage, but not those with OUD, who were assigned to RNCCs had higher FeNO levels at Week 12 than those assigned to the 15.8 mg/g dose [F(2,423) = 4.51, p = .01, Cohen's d = 0.21]. No significant dose-related changes in RHQ scores were identified. CONCLUSIONS: Use of RNCCs across a 12-week period attenuates smoking-related reductions in FeNO levels in smokers with affective disorders and socioeconomic disadvantage although not those with OUD. FeNO changes were not accompanied by changes in respiratory-health ratings. TRIAL REGISTRATION: Inclusion and exclusion criteria for the sample and experimental manipulation of the nicotine content of assigned cigarettes are registered: NCT02232737, NCT02250664, NCT02250534. The FeNO measure reported in this manuscript is an exploratory outcome that was not registered. IMPLICATIONS: Should a reduced nicotine content standard be implemented; these results suggest that reduced nicotine content in cigarettes will not exacerbate and instead may attenuate smoking-related decreases in FeNO. This is significant as NO is an important component in maintaining a healthy respiratory system and necessary to defend against infection. Furthermore, the results of the current study demonstrate that the adoption of the reduced nicotine content standard may result in beneficial impacts on respiratory epithelial health among vulnerable populations that are disproportionally affected by the adverse health outcomes precipitated by combustible tobacco use.
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Authors: Stephen T Higgins; Sarah H Heil; Stacey C Sigmon; Jennifer W Tidey; Diann E Gaalema; John R Hughes; Maxine L Stitzer; Hanna Durand; Janice Y Bunn; Jeff S Priest; Christopher A Arger; Mollie E Miller; Cecilia L Bergeria; Danielle R Davis; Joanna M Streck; Derek D Reed; Joan M Skelly; Lauren Tursi Journal: JAMA Psychiatry Date: 2017-10-01 Impact factor: 21.596
Authors: Jennifer W Tidey; Suzanne M Colby; Rachel L Denlinger-Apte; Christine Goodwin; Patricia A Cioe; Rachel N Cassidy; Robert M Swift; Bruce R Lindgren; Nathan Rubin; Sharon E Murphy; Stephen S Hecht; Dorothy K Hatsukami; Eric C Donny Journal: Nicotine Tob Res Date: 2019-12-23 Impact factor: 4.244