No abstract

Collection of exhaled breath condensate (EBC) is a non-invasive means of sampling the airway-lining fluid of the lungs. EBC contains numerous measurable mediators, whose analysis could change the management of patients with certain pulmonary diseases. While initially popularized in investigations involving spontaneously breathing patients, an increasing number of studies have been performed using EBC in association with mechanical ventilation. Collection of EBC in mechanically ventilated patients follows basic principles of condensation, but is influenced by multiple factors. Effective collection requires selection of a collection device, adequate minute ventilation, low cooling temperatures, and sampling times of greater than ten minutes. Condensate can be contaminated by saliva, which needs to be filtered. Dilution of samples occurs secondary to distilled water in vapors and humidification in the ventilator circuit. Dilution factors may need to be employed when investigating non-volatile biomarkers. Storage and analysis should occur promptly at −70° C to −80° C to prevent rapid degradation of samples. The purpose of this review is to examine and describe methodologies and problems of EBC collection in mechanically ventilated patients. A straightforward and safe framework has been established to investigate disease processes in this population, yet technical aspects of EBC collection still exist that prevent clinical practicality of this technology. These include a lack of standardization of procedure and analysis of biomarkers, and of normal reference ranges for mediators in healthy individuals. Once these procedural aspects have been addressed, EBC could serve as a non-invasive alternative to invasive evaluation of lungs in mechanically ventilated patients.

Objective This prospective study aims to address mortality in the context of the early pulmonary immune response to burn and inhalation injury. Methods We collected bronchoalveolar lavage (BAL) fluid from 60 burn patients within 14 hours of their injury when smoke inhalation was suspected. Clinical and laboratory parameters and immune mediator profiles were compared to patient outcomes. Results Patients who succumbed to their injuries were older (p=0.005), had a larger % TBSA (total body surface area) burn (p<0.001), and required greater 24-hour resuscitative fluids (p=0.002). Non-survivors had lower BAL fluid concentrations of numerous immunomodulators, including C5a, IL-1β, IL-1RA, IL-8, IL-10, and IL-13 (p<0.05 for all). Comparing only those with the highest Baux scores to account for the effects of age and % TBSA burn on mortality, non-survivors also had reduced levels of IL-2, IL-4, G-CSF, IFN-γ, MIP-1β, and TNF-α (p<0.05 for all). The apparent pulmonary immune hyporesponsiveness in those who died was confirmed by in vitro culture, which revealed that pulmonary leukocytes from non-survivors had a blunted production of numerous immune mediators. Conclusions Our study demonstrates that the early pulmonary immune response to burn and smoke inhalation may be attenuated in patients who succumb to their injuries.

Objective We aimed to determine if the severity of inhalation injury evokes an immune response measurable at the systemic level and to further characterize the balance of systemic pro- and anti-inflammation early after burn and inhalation injury. Summary Background Data Previously we reported that the pulmonary inflammatory response is enhanced with worse grades of inhalation injury, and that those who die from their injuries have a blunted pulmonary immune profile compared to survivors. Methods From August 2007 to June 2011, bronchoscopy was performed on 80 patients admitted to the burn intensive care unit when smoke inhalation was suspected. Of these, inhalation injury was graded into one of five categories (0, 1, 2, 3, and 4), with Grade 0 being the absence of visible injury and Grade 4 corresponding to massive injury. Plasma was collected at the time of bronchoscopy and analyzed for 28 immunomodulating proteins via multiplex bead array or ELISA. Results The concentrations of several plasma immune mediators were increased with worse inhalation injury severity, even after adjusting for age and % TBSA. These included interleukin (IL)-1RA (p=0.002), IL-6 (p=0.002), IL-8 (p=0.026), granulocyte colony stimulating factor (p=0.002), and monocyte chemotactic protein (MCP)-1 (p=0.007). Differences in plasma immune mediator concentrations in surviving and deceased patients were also identified. Briefly, plasma concentrations of IL-1RA, IL-6, IL-8, IL-15, Eotaxin, and MCP-1 were higher in deceased patients compared to survivors (p<0.05 for all), while IL-4 and IL-7 were lower (p<0.05). After adjusting for the effects of age, % TBSA, and inhalation injury grade, plasma IL-1RA remained significantly associated with mortality (OR 3.12, 95% CI 1.03–9.44). Plasma IL-1RA also correlated with % TBSA, inhalation injury grade, fluid resuscitation, Baux score, revised Baux score, Denver score, and the Sequential Organ Failure Assessment score. Conclusion The severity of smoke inhalation injury has systemically reaching effects, which argues in favor of treating inhalation injury in a graded manner. Additionally, several plasma immune mediators measured early after injury were associated with mortality. Of these, IL-1RA appeared to have the strongest correlation with injury severity and outcomes measures, which may explain the blunted pulmonary immune response we previously found in non-survivors.