Scott A Boitano

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.

As part of the innate immune defense, the polarized conducting lung epithelium acts as a barrier to keep particulates carried in respiration from underlying tissue. Arsenic is a metalloid toxicant that can affect the lung via inhalation or ingestion. We have recently shown that chronic exposure of mice or humans to arsenic (10-50 ppb) in drinking water alters bronchiolar lavage or sputum proteins consistent with reduced epithelial cell migration and wound repair in the airway. In this report, we used an in vitro model to examine effects of acute exposure of arsenic (15-290 ppb) on conducting airway lung epithelium. We found that arsenic at concentrations as low as 30 ppb inhibits reformation of the epithelial monolayer following scrape wounds of monolayer cultures. In an effort to understand functional contributions to epithelial wound repair altered by arsenic, we showed that acute arsenic exposure increases activity and expression of matrix metalloproteinase (MMP)-9, an important protease in lung function. Furthermore, inhibition of MMP-9 in arsenic-treated cells improved wound repair. We propose that arsenic in the airway can alter the airway epithelial barrier by restricting proper wound repair in part through the upregulation of MMP-9 by lung epithelial cells.

The potential for adverse respiratory effects following exposure to electronic (e-) cigarette liquid (e-liquid) flavorings remains largely unexplored. Given the multitude of flavor permutations on the market, identification of those flavor constituents that negatively impact the respiratory tract is a daunting task. In this study we examined the impact of common e-liquid flavoring chemicals on the airway epithelium, the cellular monolayer that provides the first line of defense against inhaled particulates, pathogens, and toxicants.