Woodsmoke Particulate + Hypertonic Saline

Airway Inflammation

Deployment of military personnel has been associated with increased respiratory illness likely due, in part, to inhalation of unusual particulate matter (PM), such as from burn pits. Inflammation is a key initial response to inhaled particulates. The investigator has developed a protocol using inhaled wood smoke particles (WSP) as a way to study PM-induced airway inflammation. Exposure to wood smoke particles causes symptoms, even in healthy people, such as eye irritation, cough, shortness of breath, and increased mucous production. The purpose of this research study is to see if a single treatment of inhaled hypertonic saline (HS) can diminish this PM-induced airway inflammation by rapidly clearing the WSP inhaled particles from airway surfaces. The exposure will be 500 ug/m³ of WSP for 2 hours, with intermittent exercise on a bicycle and rest. The wood is burned in a typical wood stove and piped into the chamber.

Military deployment is associated with exposure to novel particulate matter (PM), such as from burn pits, aeroallergens, and increased cigarette consumption. War fighters exposed to these inhalational exposures exhibit immediate and chronic respiratory morbidity. For example, military service personnel surveyed in both the Republic of Korea (ROK) and Kabul, Afghanistan reported a general increase in respiratory morbidity, including asthma and chronic bronchitis, associated with their deployment. Air contaminants in the ROK were characterized by elevated levels of both PM 0.5-2.5 and PM 2.5-10. Similarly, exposures in Kabul were characterized by multiple airborne PM exposures, including those from burn pits. Burn pit PM includes metals, bioaerosols, organic by-products, and biomass combustion particles. These findings indicate that inhaled PM is a likely cause of respiratory morbidity in the field. Inflammation is a key initial response to inhaled particulates. Wood smoke particles (WSP) serve as a model agent to study PM-induced bronchitis. WSP inhalation generates reactive oxidant (and nitrosative) species which cause local injury of airway epithelial cells and release of damage-associated molecular patterns (DAMPs) that activate toll-like receptors (TLR) and interleukin 1 (IL-1)-mediated innate immune responses by resident airway macrophages. Contamination of PM with bioaerosols, which contain lipopolysaccharide (LPS), also activates innate immune responses through toll-like receptor 4 (TLR4) activation of resident airway macrophages. These complementary processes result in recruitment of neutrophils (PMN), which mediate luminal airway inflammation with release of toxic mediators such as neutrophil elastase and myeloperoxidase that promote acute and chronic bronchitis. Therefore, mitigation of PM-induced airway neutrophilic inflammation should be a key focus in order to reduce the respiratory morbidity of military personnel. The investigators have studied a number of pro-inflammatory inhaled agents, such as nebulized LPS, ozone (O3), and WSP, as models of acute neutrophilic bronchitis against which to test a number of therapeutic agents. To this effect, the investigators have reported that inhaled fluticasone inhibits O3-induced and LPS-induced neutrophilic inflammation, and that parenteral anakinra and oral gamma-tocopherol inhibit neutrophilic responses to inhaled LPS. In addition to agents with inherent anti-inflammatory and anti-oxidant properties, rapid clearance of inhaled particles from airway surfaces is a complementary approach to reduce PM-induced airway inflammation. This can be assessed through the measurement of mucociliary clearance (MCC). MCC is dependent on airway secretory cells and submucosal glands that produce a mucin-rich fluid layer on the airway surface and ciliated cells that hydrate and propel mucus out of the lung and into the upper airway. Rates of MCC are dependent on ciliary beat frequency, hydration, and the rheologic properties of mucus. In vitro studies have demonstrated that HS, through an osmotic effect on airway surfaces, improved hydration and mucus rheologic properties, and accelerated mucus transport rates. In addition, the data over the last 30 years has shown that inhaled hypertonic saline (HS) plus cough is the most effective method for acutely clearing the bronchial airways of inhaled, deposited particles. The combined effect is greater than either HS or cough alone. In the studies of asthmatics, the investigators examined the ability of a single HS treatment with a coached cough maneuver to acutely clear radiolabeled Tc99m sulfur colloid particles from airways following LPS exposure. Following HS inhalation and cough clearance maneuvers developed to recover sputum samples for analysis, the investigators observed a rapid clearance of \>50% of the inhaled radiolabelled particles. The investigators hypothesize that if other pro-inflammatory particles (PMs, burn pit particles) were cleared similarly via HS-induced acceleration of MCC shortly after exposure, there would be reductions in acute PM-induced inflammation. Thus, in this study, the investigators will assess the effectiveness of inhaled 5% HS, a dose well tolerated by asthmatics at baseline and after inhaled LPS/allergen challenges for sputum induction, in mitigating WSP-induced airway neutrophilic inflammation in healthy volunteers. Normal saline 0.9% (NS) is not going to be used as a placebo treatment in this study, as inhalation of NS itself impacts the rheologic properties of mucus and MCC and thus would not be a suitable placebo. The investigators will, therefore, compare treatment with 5% HS to no receiving no treatment following WSP exposure.

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