Dataset Information

Experimental Acute Exposure to Thirdhand Smoke and Changes in the Human Nasal Epithelial Transcriptome: A Randomized Clinical Trial.

ABSTRACT: Importance:No previous studies have shown that acute inhalation of thirdhand smoke (THS) activates stress and survival pathways in the human nasal epithelium. Objective:To evaluate gene expression in the nasal epithelium of nonsmoking women following acute inhalation of clean air and THS. Design, Setting, and Participants:Nasal epithelium samples were obtained from participants in a randomized clinical trial (2011-2015) on the health effects of inhaled THS. In a crossover design, participants were exposed, head only, to THS and to conditioned, filtered air in a laboratory setting. The order of exposures was randomized and exposures were separated by at least 21 days. Ribonucleic acid was obtained from a subset of 4 healthy, nonsmoking women. Exposures:By chance, women in the subset were randomized to receive clean air exposure first and THS exposure second. Exposures lasted 3 hours. Main Outcomes and Measures:Differentially expressed genes were identified using RNA sequencing with a false-discovery rate less than 0.1. Results:Participants were 4 healthy, nonsmoking women aged 27 to 49 years (mean [SD] age, 42 [10.2] years) with no chronic diseases. A total of 389 differentially expressed genes were identified in nasal epithelium exposed to THS, while only 2 genes, which were not studied further, were affected by clean air. Enriched gene ontology terms associated with stress-induced mitochondrial hyperfusion were identified, such as respiratory electron transport chain (q?=?2.84?×?10-3) and mitochondrial inner membrane (q?=?7.21?×?10-6). Reactome pathway analysis identified terms associated with upregulation of DNA repair mechanisms, such as nucleotide excision repair (q?=?1.05?×?10-2). Enrichment analyses using ingenuity pathway analysis identified canonical pathways related to stress-induced mitochondrial hyperfusion (eg, increased oxidative phosphorylation) (P?=?.001), oxidative stress (eg, glutathione depletion phase II reactions) (P?=?.04), and cell survival (z score?=?5.026). Conclusions and Relevance:This study found that acute inhalation of THS caused cell stress that led to the activation of survival pathways. Some responses were consistent with stress-induced mitochondrial hyperfusion and similar to those demonstrated previously in vitro. These data may be valuable to physicians treating patients exposed to THS and may aid in formulating regulations for the remediation of THS-contaminated environments.

SUBMITTER: Pozuelos GL

PROVIDER: S-EPMC6604097 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Experimental Acute Exposure to Thirdhand Smoke and Changes in the Human Nasal Epithelial Transcriptome: A Randomized Clinical Trial.

Pozuelos Giovanna L GL Kagda Meenakshi S MS Schick Suzaynn S Girke Thomas T Volz David C DC Talbot Prue P

JAMA network open 20190605 6

<h4>Importance</h4>No previous studies have shown that acute inhalation of thirdhand smoke (THS) activates stress and survival pathways in the human nasal epithelium.<h4>Objective</h4>To evaluate gene expression in the nasal epithelium of nonsmoking women following acute inhalation of clean air and THS.<h4>Design, setting, and participants</h4>Nasal epithelium samples were obtained from participants in a randomized clinical trial (2011-2015) on the health effects of inhaled THS. In a crossover d ...[more]

PMID: 31251375

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Project description:BackgroundThirdhand smoke (THS) is the persistent residue resulting from secondhand smoke (SHS) that accumulates in dust, objects, and on surfaces in homes where tobacco has been used, and is reemitted into air. Very little is known about the extent to which THS contributes to children's overall tobacco smoke exposure (OTS) levels, defined as their combined THS and SHS exposure. Even less is known about the effect of OTS and THS on children's health. This project will examine how different home smoking behaviors contribute to THS and OTS and if levels of THS are associated with respiratory illnesses in nonsmoking children.MethodsThis project leverages the experimental design from an ongoing pediatric emergency department-based tobacco cessation trial of caregivers who smoke and their children (NIHR01HD083354). At baseline and follow-up, we will collect urine and handwipe samples from children and samples of dust and air from the homes of smokers who smoke indoors, have smoking bans or who have quit smoking. These samples will be analyzed to examine to what extent THS pollution at home contributes to OTS exposure over and above SHS and to what extent THS continues to persist and contribute to OTS in homes of smokers who have quit or have smoking bans. Targeted and nontargeted chemical analyses of home dust samples will explore which types of THS pollutants are present in homes. Electronic medical record review will examine if THS and OTS levels are associated with child respiratory illness. Additionally, a repository of child and environmental samples will be created.DiscussionThe results of this study will be crucial to help close gaps in our understanding of the types, quantity, and clinical effects of OTS, THS exposure, and THS pollutants in a unique sample of tobacco smoke-exposed ill children and their homes. The potential impact of these findings is substantial, as currently the level of risk in OTS attributable to THS is unknown. This research has the potential to change how we protect children from OTS, by recognizing that SHS and THS exposure needs to be addressed separately and jointly as sources of pollution and exposure.Trial registrationClinicalTrials.gov Identifier: NCT02531594 . Date of registration: August 24, 2015.

Dataset Information

Experimental Acute Exposure to Thirdhand Smoke and Changes in the Human Nasal Epithelial Transcriptome: A Randomized Clinical Trial.

Publications

Experimental Acute Exposure to Thirdhand Smoke and Changes in the Human Nasal Epithelial Transcriptome: A Randomized Clinical Trial.

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