Where There'S Smoke, There'S Fire

FOR RELATED ARTICLE, SEE PAGE 1490In this issue of CHEST, Moazed et al1Moazed F. Hendrickson C. Conroy A. et al.Cigarette smoking and ARDS after blunt trauma: the influence of changing smoking patterns and resuscitation practices.Chest. 2020; 158: 1490-1498Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar describe the relationship between cigarette smoking and risk of ARDS subsequent to blunt trauma in a large cohort studied between 2005 and 2015. The first results from this cohort (2005-2008) established a correlation between both active and passive cigarette smoke exposure with ARDS caused by blunt trauma.2Calfee C.S. Matthay M.A. Eisner M.D. et al.Active and passive cigarette smoking and acute lung injury after severe blunt trauma.Am J Respir Crit Care Med. 2011; 183: 1660-1665Crossref PubMed Scopus (98) Google Scholar The current report1Moazed F. Hendrickson C. Conroy A. et al.Cigarette smoking and ARDS after blunt trauma: the influence of changing smoking patterns and resuscitation practices.Chest. 2020; 158: 1490-1498Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar demonstrates a threshold effect of smoke exposure and an interaction between active smoke exposure and packed transfusion. This report is timely because of changes in the nature and prevalence of the tobacco habit in the United States, changing resuscitation practices, and overall improvement in supportive critical care, including low tidal volume ventilation strategies. Consistent with other reports, the more recent cohort1Moazed F. Hendrickson C. Conroy A. et al.Cigarette smoking and ARDS after blunt trauma: the influence of changing smoking patterns and resuscitation practices.Chest. 2020; 158: 1490-1498Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar had a lower incidence of ARDS than the cohort studied between 2005 and 2008.2Calfee C.S. Matthay M.A. Eisner M.D. et al.Active and passive cigarette smoking and acute lung injury after severe blunt trauma.Am J Respir Crit Care Med. 2011; 183: 1660-1665Crossref PubMed Scopus (98) Google Scholar FOR RELATED ARTICLE, SEE PAGE 1490 This group’s latest contribution again demonstrates an epidemiologic links between cigarette smoking and lung injury resulting in ARDS. In the past, the association between ARDS and cigarette smoking was controversial, perhaps because of reliance on self-reported tobacco use in medical records, a less reliable source of information on cigarette smoking. The group at University of California at San Francisco has used plasma cotinine as an unbiased biomarker of cigarette smoke exposure and has demonstrated a relation between blunt trauma and ARDS in both passive (plasma cotinine, 0.02-3.08 ng/mL) and active (plasma cotinine >3.08 ng/mL) smoke-exposed individuals.1Moazed F. Hendrickson C. Conroy A. et al.Cigarette smoking and ARDS after blunt trauma: the influence of changing smoking patterns and resuscitation practices.Chest. 2020; 158: 1490-1498Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar,2Calfee C.S. Matthay M.A. Eisner M.D. et al.Active and passive cigarette smoking and acute lung injury after severe blunt trauma.Am J Respir Crit Care Med. 2011; 183: 1660-1665Crossref PubMed Scopus (98) Google Scholar The current observations of an apparent “threshold” effect of smoke exposure suggest that cigarette smoke exposure “primes” the lung for subsequent injury.1Moazed F. Hendrickson C. Conroy A. et al.Cigarette smoking and ARDS after blunt trauma: the influence of changing smoking patterns and resuscitation practices.Chest. 2020; 158: 1490-1498Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Studies in rodents support the concept of a “priming” effect of cigarette smoking.3Gotts J.E. Abbott J. Fang X. et al.Cigarette smoke exposure worsens endotoxin-induced lung injury and pulmonary edema in mice.Nicotine Tobacco Res. 2017; 19: 1033-1039Crossref PubMed Scopus (16) Google Scholar, 4Sakhatskyy P. Wang Z. Borgas D. et al.Double-hit model for cigarette smoke priming for acute lung injury.Am J Physiol Lung Cell Molec Physiol. 2017; 312: L56-L67Crossref PubMed Scopus (13) Google Scholar, 5Lu Q. Sakhatskyy P. Grinnell K. et al.Cigarette smoke causes lung vascular barrier dysfunction via oxidative stress-mediated inhibition of RhoA and focal adhesion kinase.Am J Physiol. 2011; 301: L847-L857Crossref PubMed Scopus (47) Google Scholar Furthermore, studies of cultured lung cells indicate that cigarette smoke extract directly impairs both endothelial5Lu Q. Sakhatskyy P. Grinnell K. et al.Cigarette smoke causes lung vascular barrier dysfunction via oxidative stress-mediated inhibition of RhoA and focal adhesion kinase.Am J Physiol. 2011; 301: L847-L857Crossref PubMed Scopus (47) Google Scholar,6Schweitzer K.S. Hatoum H. Brown M.B. et al.Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides.Am J Physiol Lung Cell Mol Physiol. 2011; 301: L836-L846Crossref PubMed Scopus (94) Google Scholar and epithelial barrier function.6Schweitzer K.S. Hatoum H. Brown M.B. et al.Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides.Am J Physiol Lung Cell Mol Physiol. 2011; 301: L836-L846Crossref PubMed Scopus (94) Google Scholar Potential mechanisms include endothelial apoptosis,7Sakhatskyy P. Miranda G.A.G. Newton J. et al.Cigarette smoke-induced lung endothelial apoptosis and emphysema are associated with impairment of FAK and eIF2α..Microvasc Res. 2014; 94: 80-89Crossref PubMed Scopus (24) Google Scholar,8Damico R. Simms T. Kim B.S. et al.p53 mediates cigarette smoke-induced apoptosis of pulmonary endothelial cells: inhibitory effects of macrophage migration inhibitor factor.Am J Respir Cell Mol Biol. 2011; 44: 323-332Crossref PubMed Scopus (53) Google Scholar altered RhoA GTPase signaling,5Lu Q. Sakhatskyy P. Grinnell K. et al.Cigarette smoke causes lung vascular barrier dysfunction via oxidative stress-mediated inhibition of RhoA and focal adhesion kinase.Am J Physiol. 2011; 301: L847-L857Crossref PubMed Scopus (47) Google Scholar effects on cytoskeletal filaments,5Lu Q. Sakhatskyy P. Grinnell K. et al.Cigarette smoke causes lung vascular barrier dysfunction via oxidative stress-mediated inhibition of RhoA and focal adhesion kinase.Am J Physiol. 2011; 301: L847-L857Crossref PubMed Scopus (47) Google Scholar,9Borgas D. Chambers E. Newton J. et al.Cigarette smoke disrupted lung endothelial barrier integrity and increased susceptibility to acute lung injury via histone deacetylase 6.Am J Resp Cell Mol Biol. 2016; 54: 683-696Crossref PubMed Scopus (33) Google Scholar changes in ceramides,6Schweitzer K.S. Hatoum H. Brown M.B. et al.Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides.Am J Physiol Lung Cell Mol Physiol. 2011; 301: L836-L846Crossref PubMed Scopus (94) Google Scholar and mitochondrial dysfunction.10Wang Z, White A, Wang X, et al. Mitochondrial fission mediated cigarette smoke-induced pulmonary endothelial injury [published online ahead of print July 16, 2020]. Am J Resp Cell Mol Biol. https://doi.org/10.1165/rcmb.2020-0008OC.Google Scholar,11Ballweg K. Mutze K. Konigshoff M. et al.Cigarette smoke extract affects mitochondrial function in alveolar epithelial cells.Am J Physiol Lung Cell Mol Physiol. 2014; 307: L895-L907Crossref PubMed Scopus (73) Google Scholar Finally, cigarette smoke exposure enhances lung inflammatory responses to “second hits.”4Sakhatskyy P. Wang Z. Borgas D. et al.Double-hit model for cigarette smoke priming for acute lung injury.Am J Physiol Lung Cell Molec Physiol. 2017; 312: L56-L67Crossref PubMed Scopus (13) Google Scholar Thus, there is considerable biological evidence supporting the epidemiologic studies. As the authors of this report note, it is also possible that the growing use of electronic devices for nicotine self-administration may also “prime” the lungs for subsequent injury. In support of that concept, in vitro studies show that aerosolized nicotine delivery systems stimulate inflammation and cause epithelial injury.12Serpa G.L. Renton N.D. Lee N. et al.ENDS aerosol-induced cell death and dysfunction in macrophages and lung epithelial cells.Am J Resp Cell Mol Biol. 2020; 63: 306-316Crossref PubMed Scopus (9) Google Scholar In summary, growing evidence from epidemiologic and biological studies supports a role for cigarette smoke exposure as a predisposing factor in the development of ARDS. It will be important for clinical trials in ARDS to assess exposure to cigarette smoke and electronic nicotine delivery devices when assessing comorbidities and outcomes of clinical interventions. Many other questions are yet to be answered, such as whether there might be an effective therapeutic that could prevent the “priming” effect of cigarette smoke exposure on lung injury. Cigarette Smoking and ARDS After Blunt Trauma: The Influence of Changing Smoking Patterns and Resuscitation PracticesCHESTVol. 158Issue 4PreviewDespite changes in resuscitation and smoking patterns, cigarette smoking remains associated with an increased risk of developing ARDS. However, this relationship changed over time, with passive smokers at particularly increased risk of developing ARDS in later years, which may be related to changes in smoking patterns or transfusion practices over time. These findings highlight the need for additional mechanistic and epidemiologic studies of the effects of low levels of cigarette smoke exposure on lung health. Full-Text PDF