PMID- 31251375
OWN - NLM
STAT- MEDLINE
DCOM- 20200218
LR  - 20200502
IS  - 2574-3805 (Electronic)
IS  - 2574-3805 (Linking)
VI  - 2
IP  - 6
DP  - 2019 Jun 5
TI  - Experimental Acute Exposure to Thirdhand Smoke and Changes in the Human Nasal 
      Epithelial Transcriptome: A Randomized Clinical Trial.
PG  - e196362
LID - 10.1001/jamanetworkopen.2019.6362 [doi]
LID - e196362
AB  - 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 x 10-3) and mitochondrial inner membrane 
      (q = 7.21 x 10-6). Reactome pathway analysis identified terms associated with 
      upregulation of DNA repair mechanisms, such as nucleotide excision repair 
      (q = 1.05 x 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.
FAU - Pozuelos, Giovanna L
AU  - Pozuelos GL
AD  - Department of Molecular, Cell and Systems Biology, University of California, 
      Riverside.
FAU - Kagda, Meenakshi S
AU  - Kagda MS
AD  - Department of Molecular, Cell and Systems Biology, University of California, 
      Riverside.
FAU - Schick, Suzaynn
AU  - Schick S
AD  - Department of Medicine, University of California, San Francisco.
FAU - Girke, Thomas
AU  - Girke T
AD  - Department of Botany and Plant Sciences, University of California, Riverside.
FAU - Volz, David C
AU  - Volz DC
AD  - Department of Environmental Sciences, University of California, Riverside.
FAU - Talbot, Prue
AU  - Talbot P
AD  - Department of Molecular, Cell and Systems Biology, University of California, 
      Riverside.
LA  - eng
GR  - S10 OD016290/OD/NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190605
PL  - United States
TA  - JAMA Netw Open
JT  - JAMA network open
JID - 101729235
RN  - 0 (Air Pollutants)
RN  - 0 (Smoke)
RN  - 0 (Tobacco Smoke Pollution)
SB  - IM
MH  - Adult
MH  - Air Pollutants/*adverse effects
MH  - Cell Death/physiology
MH  - Cell Survival/physiology
MH  - Cross-Over Studies
MH  - DNA Repair/physiology
MH  - Environmental Exposure/adverse effects
MH  - Female
MH  - Gene Expression/physiology
MH  - Healthy Volunteers
MH  - Humans
MH  - Middle Aged
MH  - Nasal Mucosa/*physiology
MH  - Smoke/*adverse effects
MH  - Stress, Physiological/physiology
MH  - Tobacco Smoke Pollution/adverse effects
MH  - Transcriptome/*physiology
PMC - PMC6604097
COIS- Conflict of Interest Disclosures: Ms Pozuelos reported grants from the National 
      Institutes of Health during the conduct of the study. Dr Kagda reported grants 
      from the National Institutes of Health during the conduct of the study. Dr Schick 
      reported grants from the University of California during the conduct of the 
      study. No other disclosures were reported.
EDAT- 2019/06/30 06:00
MHDA- 2020/02/19 06:00
PMCR- 2019/06/28
CRDT- 2019/06/29 06:00
PHST- 2019/06/29 06:00 [entrez]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2020/02/19 06:00 [medline]
PHST- 2019/06/28 00:00 [pmc-release]
AID - 2736932 [pii]
AID - zoi190250 [pii]
AID - 10.1001/jamanetworkopen.2019.6362 [doi]
PST - epublish
SO  - JAMA Netw Open. 2019 Jun 5;2(6):e196362. doi: 10.1001/jamanetworkopen.2019.6362.