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Prevalence and Impact of Active and Passive Cigarette Smoking in Acute Respiratory Distress Syndrome

Hsieh, S. Jean MD; Zhuo, Hanjing MD, MPH; Benowitz, Neal L. MD; Thompson, B. Taylor MD; Liu, Kathleen D. MD, PhD, MAS; Matthay, Michael A. MD; Calfee, Carolyn S. MD, MAS; and the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network

doi: 10.1097/CCM.0000000000000418
Clinical Investigations

Objectives: Cigarette smoke exposure has recently been found to be associated with increased susceptibility to trauma- and transfusion-associated acute respiratory distress syndrome. We sought to determine 1) the incidence of cigarette smoke exposure in a diverse multicenter sample of acute respiratory distress syndrome patients and 2) whether cigarette smoke exposure is associated with severity of lung injury and mortality in acute respiratory distress syndrome.

Design: Analysis of the Albuterol for the Treatment of Acute Lung Injury and Omega Acute Respiratory Distress Syndrome Network studies.

Setting: Acute Respiratory Distress Syndrome Network hospitals.

Patients: Three hundred eighty-one patients with acute respiratory distress syndrome.

Interventions: None.

Measurements and Main Results: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol, a validated tobacco-specific marker, was measured in urine samples from subjects enrolled in two National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network randomized controlled trials. Urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels were consistent with active smoking in 36% of acute respiratory distress syndrome patients and with passive smoking in 41% of nonsmokers (vs 20% and 40% in general population, respectively). Patients with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels in the active smoking range were younger and had a higher incidence of alcohol misuse, fewer comorbidities, lower severity of illness, and less septic shock at enrollment compared with patients with undetectable 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels. Despite this lower severity of illness, the severity of lung injury did not significantly differ based on biomarker-determined smoking status. Cigarette smoke exposure was not significantly associated with death after adjusting for differences in age, alcohol use, comorbidities, and severity of illness.

Conclusions: In this first multicenter study of biomarker-determined cigarette smoke exposure in acute respiratory distress syndrome patients, we found that active cigarette smoke exposure was significantly more prevalent among acute respiratory distress syndrome patients compared to population averages. Despite their younger age, better overall health, and lower severity of illness, smokers by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol had similar severity of lung injury as patients with undetectable 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. These findings suggest that active cigarette smoking may increase susceptibility to acute respiratory distress syndrome in younger, healthier patients.

1Division of Critical Care Medicine, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.

2Cardiovascular Research Institute, University of California, San Francisco, CA.

3Division of Clinical Pharmacology and Experimental Therapeutics, University of California, San Francisco, CA.

4Center for Tobacco Control Research and Education, University of California, San Francisco, CA.

5Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

6Division of Nephrology, Department of Medicine, University of California, San Francisco, CA.

7Department of Anesthesia, University of California, San Francisco, CA.

8Division of Pulmonary and Critical Care, Department of Medicine, University of California, San Francisco, CA.

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The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome participants can be viewed in Appendix 1.

Dr. Hsieh’s institution received grant support from the Albert Einstein College of Medicine Institute of Clinical and Translational Research (8KL2TR0000088-05), (Mentored career development award) and from the National Institute on Aging (NIA) National Institutes of Health (NIH) (8KL2TR0000088-05) (Grants for Early Medical/Surgical Specialists Transition into Aging Research Award (1R03AG040673GEMSSTAR). Her institution received grant support from 1 UL1 TR001073-01, 1 TL1 TR001072-01, and 1 KL2 TR001071-01 (Einstein-Montefiore Clinical and Translational Science Awards). Dr. Benowitz provided expert testimony against tobacco companies, consulted for Pfizer and GlaxoSmithKline, received grant support from the NIH (DA12393) and University of California, San Francisco Comprehensive Cancer Center, and received royalties from McGraw Hill. His institution received grant support from the NIH and the Flight Attendants Medical Research Institute. Dr. Thompson’s institution received grant support from the NIH. Dr. Liu served as board member for Astute Biomedical (Clinical Events Adjudication Committee), Complexa (Scientific Advisory Board), and Cytopheryx (Data Safety Monitoring Board); consulted for Abbvie and Chemocentryx; received support from Abbott (gift of reagents for biomarker assays) and CMIC Group (gift of reagents for biomarker assays); has stock options with Amgen; and received support for travel from the American Thoracic Society and the American Society of Nephrology. Dr. Liu and her institution received grant support from the NIH. Dr. Matthay served as board member for Roche–Genentech (chair of Data Safety Monitoring Board); consulted for GlaxoSmithKline and Cerus; received grant support from GlaxoSmithKline, National Heart, Lung, and Blood Institute (NHLBI) (Acute Respiratory Distress Syndrome Network N01-HR-56165–56713, HL51856), and National Institute of Allergy and Infectious Diseases; and received support for article research from the NIH. His institution received grant support from the NHLBI. Dr. Calfee received grant support from the NIH and GlaxoSmithKline, received support for travel from American Thoracic Society, and received support for article research from the NIH (HL090833, HL110969, and UL1 RR024131). The NHLBI ARDS Network received grant support from the U.S. Department of Health and Human Services (HHSN268200536165C through HHSN268200536176C, HHSN268200536179C; 1 UL1 TR001073-01, 1 TL1 TR001072-01, and 1 KL2 TR001071-01 [Einstein-Montefiore CTSA]). Her institution received grant support from the Flight Attendant Medical Research Institute and the NIH and consulted for Cerus. Dr. Zhuo has disclosed that she does not have any potential conflicts of interest.

For information regarding this article, E-mail: shsieh@montefiore.org

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