Smoke inhalation enhances early alveolar leukocyte responsiveness to endotoxin
ABSTRACT Pulmonary dysfunction after smoke inhalation and thermal injury is associated with excessive morbidity and mortality. The purpose of this study was to evaluate alveolar leukocyte function after thermal injury and smoke inhalation.
Twenty-one patients with thermal injury only (n = 8); thermal injury and smoke inhalation injury (n = 8); and nonburned controls (n = 5) were assessed by means of bronchoscopically directed lavage (bronchoalveolar lavage [BAL]) on the first and fourth days postinjury. BAL-isolated pulmonary leukocytes were assessed for number, composition, viability, and production of tumor necrosis factor (TNF)alpha, interleukin (IL)-8, and IL-6 in response to 100 ng/mL of lipopolysaccharide (LPS) (mean +/- SEM; significance at p < 0.05).
Six of eight Smoke patients had gross evidence of lung injury. On day 1, Smoke and Burn BAL isolates yielded greater cell counts than Control (10.6 vs. 4.5 vs. 2.4 x 10(6)/mL). Smoke macrophages on day 1 produced more TNFalpha (1.2 vs. 0.2 ng/mL), IL-6 (8.0 vs. 1.9 ng/mL), and IL-8 (85 vs. 32 ng/mL) after LPS stimulation compared with respective unstimulated (0 ng/mL of LPS) day-1 Smoke cells. LPS-stimulated Burn cells on day 1 produced more IL-8 (150 vs. 62 ng/mL) but not TNFalpha (0.4 vs. 0.25 ng/mL) or IL-6 (1.8 vs. 0.69 ng/mL), when compared with respective unstimulated Burn cells. By day 4, LPS-stimulated Smoke and Burn cells produced significantly more TNFalpha (Smoke, 0.41 vs. 0.16 ng/mL; Burn, 0.87 vs. 0.51 ng/mL) and IL-6 (Smoke, 2.5 vs. 0.47 ng/mL; Burn, 4.1 vs. 1.47 ng/mL), but not IL-8 (Smoke, 51.1 vs. 51.1 ng/mL; Burn, 54.4 vs. 55.6 ng/mL), compared with respective unstimulated day-4 cells.
Smoke inhalation induces a massive influx of alveolar leukocytes that are primed for an early, enhanced LPS-activated cytokine response compared with alveolar leukocytes isolated after burn injury alone or normal controls.
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ABSTRACT: This prospective study aims to address mortality in the context of the early pulmonary immune response to burn and inhalation injury. The authors collected bronchoalveolar lavage 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 with patient outcomes. Patients who succumbed to their injuries were older (P = .005), had a larger % TBSA burn (P < .001), and required greater 24-hour resuscitative fluids (P = .002). Nonsurvivors had lower bronchoalveolar lavage fluid concentrations of numerous immunomodulators, including C5a, interleukin (IL)-1β, IL-1RA, IL-8, IL-10, and IL-13 (P < .05 for all). Comparing only those with the highest Baux scores to account for the effects of age and % TBSA burn on mortality, nonsurvivors also had reduced levels of IL-2, IL-4, granulocyte colony-stimulating factor, interferon-γ, macrophage inflammatory protein-1β, and tumor necrosis factor-α (P < .05 for all). The apparent pulmonary immune hyporesponsiveness in those who died was confirmed by in vitro culture, which revealed that pulmonary leukocytes from nonsurvivors had a blunted production of numerous immune mediators. This study demonstrates that the early pulmonary immune response to burn and smoke inhalation may be attenuated in patients who succumb to their injuries.Journal of burn care & research: official publication of the American Burn Association 01/2012; 33(1):26-35. DOI:10.1097/BCR.0b013e318234d903 · 1.55 Impact Factor
- Réanimation 12/2009; 18(8). DOI:10.1016/j.reaurg.2009.09.005
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ABSTRACT: Inhalation injury (INHI) associated with thermal injury has been shown to increase the rate of mortality. Several investigators have shown that patients with inhalation and burn injuries will require increased fluid volumes during acute resuscitation when compared with patients with burn injury alone. Other groups have examined the use of lung compliance and airway resistance as predictors of outcome in patients with INHI. We hypothesized that increased fluid requirements would more closely correlate with perturbations in pulmonary performance than with mere presence or absence of INHI or the degree of injury by bronchoscopic criteria. We performed a retrospective chart review during a period of 3 years. We identified 80 patients with suspected INHI that required intubation, mechanical ventilation, and fiber optic bronchoscopy in the first 24 hours of their admission. Variables collected included age, sex, weight and %TBSA burned, as well as blood alcohol level, the presence of head and neck burns and escharotomies, and admission carbon monoxide levels. Patients were classified into five groups according to a grading system of INHI (0, 1, 2, 3, and 4), derived from findings at initial bronchoscopy and based on AIS criteria. The following pulmonary parameters were noted at regular intervals: mode of ventilation, tidal volume, peak inspiratory pressures, mean airway pressures, and compliance. The P:F ratio also was recorded at regular intervals. Total fluid volume infused was noted at 0-, 24-, and 48-hour intervals, and was calculated as ml/kg/%TBSA. Outcomes were measured by in-hospital survival, ventilator days, intensive care unit days, and total length of stay. Patients were well matched for %TBSA among the different bronchoscopic grades of INHI, and those with grades 2, 3, and 4 injuries had a significantly worse survival than those with grades 0 or 1 (P = .03). However, grades 2, 3, and 4 did not have increased acute fluid requirements when compared with grades 1 and 2 injuries. Initial pulmonary compliance likewise did not correlate with acute fluid requirements. However, those patients with a P:F ratio less than 350 at presentation had a statistically significant increase in ml/kg/%TBSA compared with those with P:F >350 (P = .03). They did not have more ventilator days or a statistically worse survival. Fiber optic bronchoscopy is useful in the diagnosis of INHI, and overall survival is worse in those patients with worse grades of injury by bronchoscopic criteria. However, the P:F ratio may be a more accurate predictor of increased fluid requirements during the acute resuscitation.Journal of burn care & research: official publication of the American Burn Association 01/2007; 28(1):80-3. DOI:10.1097/BCR.0B013E31802C889F · 1.55 Impact Factor