title: Tracheobronchial protease inhibitors, body surface area burns, and mortality in smoke inhalation.
abstract: The objective of this study was to assess tracheobronchial protease inhibitor concentrations longitudinally and determine whether initial concentrations predict subsequent lung injury and mortality in intubated burn victims. Tracheobronchial suction fluid was collected every 2 hours for 36 hours. Alpha-1-antitrypsin (AAT), secretory leukocyte peptidase inhibitor (SLPI), alpha-2-macroglobulin (A2M), and cell and differential counts were assayed. Partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FIO2) and peak airway pressure (PAP) were recorded for 72 hours. Standard statistics were used to evaluate cross-sectional relationships; random coefficient (mixed) models were used to evaluate temporal trends in marker concentrations and relation to clinical outcomes. Among 29 patients, 24 (83%) developed hypoxemia (PaO2/FIO2 <200); six died within 2 weeks. When adjusted for gender, age, %TBSA burn, and positive end-expiratory pressure setting, A2M (P = .007) and neutrophils (P = .032) increased linearly during 36 hours, and SLPI decreased (P = .038). Initial SLPI concentration was a negative predictor of maximum PAP (P = .009). None of the markers predicted longitudinal change in PaO2/FIO2. Mean levels of AAT and A2M in initial samples were significantly lower in patients with >35% TBSA burn (P = .010 and .033, respectively), when compared with patients with less severe burns. However, patients with increased A2M in combination with >35% TBSA burn had a 6-fold (95% CI: 1.8-20) increased relative risk of death. Tracheobronchial AAT and A2M levels were significantly lower in patients with more severe burns and increased over time. Initial SLPI levels predicted subsequent PAP. Increased early A2M in combination with extensive burn predicted early mortality.
authors.affiliation: University of Arizona Mel and Enid Zuckerman College of Public Health, Community, Environment and Policy Division, Tucson, Arizona 85724, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Kurzius-Spencer
authors.forename: Kevin
authors.initials: K
authors.lastname: Foster
authors.forename: Sally
authors.initials: S
authors.lastname: Littau
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Richey
authors.forename: Beth M
authors.initials: BM
authors.lastname: Clark
authors.forename: Duane
authors.initials: D
authors.lastname: Sherrill
authors.forename: Scott
authors.initials: S
authors.lastname: Boitano
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Caruso
authors.forename: Jefferey L
authors.initials: JL
authors.lastname: Burgess
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism*; D001772:Blood Cell Count; D002056:Burns / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D006801:Humans; D007442:Intubation, Intratracheal; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000378:metabolism; D015208:Smoke Inhalation Injury / Q000378:metabolism* / Q000401:mortality*; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053481:Secretory Leukocyte Peptidase Inhibitor; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins
references.citation: Eur Surg Res. 2000;32(6):337-46
references.pmid: 11182617
references.citation: J Trauma. 1982 Oct;22(10):869-71
references.pmid: 7131606
references.citation: J Appl Physiol (1985). 1997 May;82(5):1433-7
references.pmid: 9134889
references.citation: Burns. 1992 Oct;18(5):362-7
references.pmid: 1445624
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Jan;278(1):L51-8
references.pmid: 10645890
references.citation: Crit Care Med. 1995 Jan;23(1):171-8
references.pmid: 8001368
references.citation: J Clin Invest. 1986 Jun;77(6):1952-61
references.pmid: 3486887
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1233-41
references.pmid: 11350803
references.citation: Genes Dev. 1987 Apr;1(2):161-71
references.pmid: 3500093
references.citation: Biochem Soc Trans. 2007 Apr;35(Pt 2):273-6
references.pmid: 17371258
references.citation: Cell. 1997 Feb 7;88(3):417-26
references.pmid: 9039268
references.citation: J Aerosol Med. 2004 Winter;17(4):289-98
references.pmid: 15684729
references.citation: Thorax. 1998 Feb;53(2):114-6
references.pmid: 9624296
references.citation: J Appl Physiol (1985). 1990 Aug;69(2):694-9
references.pmid: 1699920
references.citation: Inhal Toxicol. 2002 Feb;14(2):133-40
references.pmid: 12122576
references.citation: Thorax. 2004 Feb;59(2):164-9
references.pmid: 14760160
references.citation: FEBS Lett. 1994 Jun 13;346(2-3):171-4
references.pmid: 8013628
references.citation: J Burn Care Res. 2006 Nov-Dec;27(6):848-53
references.pmid: 17091081
references.citation: J Burn Care Res. 2008 Mar-Apr;29(2):311-8
references.pmid: 18354287
references.citation: J Trauma. 2004 Oct;57(4):696-700; dicussion 700-1
references.pmid: 15514521
references.citation: Am J Respir Cell Mol Biol. 2003 Sep;29(3 Pt 1):295-302
references.pmid: 12936906
references.citation: Respiration. 2000;67(5):533-8
references.pmid: 11070458
references.citation: J Clin Invest. 1991 Feb;87(2):482-8
references.pmid: 1671391
references.citation: J Appl Physiol (1985). 2008 Aug;105(2):678-84
references.pmid: 18436699
references.citation: Am J Surg. 1985 Dec;150(6):716-20
references.pmid: 4073365
references.citation: J Burn Care Rehabil. 1985 Nov-Dec;6(6):490-4
references.pmid: 3855227
references.citation: J Trauma. 1991 Nov;31(11):1477-86
references.pmid: 1942167
references.citation: J Clin Invest. 1988 Jul;82(1):26-36
references.pmid: 3260605
references.citation: J Trauma. 1992 Dec;33(6):807-12
references.pmid: 1474619
references.citation: J Appl Physiol (1985). 1988 Mar;64(3):1107-13
references.pmid: 3366733