Innate immunity mediating inflammation secondary to endotracheal intubation.
ABSTRACT OBJECTIVE To investigate the inflammatory markers associated with short-term endotracheal intubation in healthy surgical patients. DESIGN An observational and prospective study of subjects scheduled for same-day surgery procedures. SETTING Level I trauma center. PATIENTS Fourteen healthy patients intubated for same-day surgery procedures. The median duration of surgery was 3 hours. INTERVENTIONS Serial lavages above the tracheal cuff were obtained at the beginning of surgery, at 1 hour, and at the end of surgery; samples were assayed for cellular counts and levels of cytokines and complement 5a (C5a). RESULTS The total number of polymorphonuclear cells (PMNs) increased almost 10-fold from intubation to extubation (P < .01). The levels of 3 of the cytokines measured in tracheal lavage supernatants were significantly elevated over the time of intubation: tumor necrosis factor (TNF) (P < .01), interleukin 6 (IL-6) (P < .01), and IL-1β (P < .025). Levels of IL-8 showed an upward trend over time but were not significantly increased; C5a levels were significantly elevated over time (P < .05). CONCLUSIONS Short-term intubation in healthy patients resulted in significant tracheal inflammation. Involvement of the innate immune system as documented in the present study provides information that may help to better understand the pathophysiologic characteristics of subglottic stenosis and other endotracheal injuries secondary to endotracheal intubation.
SourceAvailable from: Maria Jaensson[Show abstract] [Hide abstract]
ABSTRACT: Background Postoperative sore throat and hoarseness are common minor complications following airway manipulation. This study was primarily done to determine gender differences in the incidence of these symptoms and the location of POST after laryngeal mask airway (LMA) and endotracheal tube (ETT). Methods A total of 112 men and 185 women were included during a four month period. All patients were evaluated postoperatively and after 24 hours about the occurrence of sore throat, its location and hoarseness. If the patients had any symptom, they were followed-up at 48, 72 and 96 hours until the symptoms resolved. Results There was no significant gender difference in postoperative sore throat (POST) and postoperative hoarseness (PH) when analyzing both airway devices together. The incidence of sore throat and hoarseness were higher postoperatively after an ETT than an LMA (32% vs. 19%, p = 0.012) and 57% vs. 33% (p < 0.001) respectively. Significantly more women than men had POST after an LMA (26% vs. 6%, p = 0.004). No significant gender difference was found in either POST or PH after an ETT or in the incidence of PH after an LMA. More patients located their pain below the larynx after an ETT vs. an LMA (24% vs. 4%). Pain above the larynx was more common after an LMA than an ETT (52% vs. 37%). Conclusions In a clinical setting where women are intubated with a smaller size ETT than men, there were no significant differences in POST or PH between genders. Additionally, more women than men have POST when an LMA is used. Awareness of POST and PH may help streamline patients in whom the best airway device could be used during anesthesia and surgery.BMC Anesthesiology 07/2014; 14(56). DOI:10.1186/1471-2253-14-56 · 1.33 Impact Factor
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ABSTRACT: We undertook to describe the genetic and protein composition of subglottic stenosis (SGS) by measuring an array of protein expression and messenger RNA levels within human SGS tissue. We also sought to compare this human array to cytokine expression from a murine model of SGS in order to confirm the effective translational nature of our animal model. Human granulation tissue from 10 patients with early symptomatic SGS was compared to control bronchus. The expression levels of 24 different cytokines were measured by a Luminex protein assay and real-time polymerase chain reaction. The protein expression in human SGS mirrors that seen in murine SGS. Transforming growth factor β1, interleukin 1β, and matrix metalloproteinase 9 were markedly elevated in both human and mouse SGS tissues. The protein array showed a statistically significant elevation in the proinflammatory cytokines tumor necrosis factor α, interleukin 1, granulocyte macrophage colony-stimulating factor, and interferon γ. This is the first study, to our knowledge, to measure an array of protein expression within human SGS tissue. The expression profile suggests that symptomatic tracheal granulation tissue is mostly within the early inflammatory phase of wound healing and has only begun fibrotic and angiogenic remodeling. This study validates our murine model of SGS, and also helps to define the exact pathways of tissue injury, in the hope of leading to new treatments for this difficult condition.The Annals of otology, rhinology, and laryngology 01/2014; 123(1):65-70. DOI:10.1177/0003489414521146 · 1.05 Impact Factor
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ABSTRACT: Activations of the complement C5a (C5a) and the urokinase-type plasminogen activator (uPA) are commonly seen together during sepsis. However, the mechanism linking these two important pathways remains elusive. We used the C57BL/6 J mice model of sepsis induced by cecal ligation puncture (CLP) procedure, injected anti-C5aR or rottlerin through the tail vein to neutralize C5aR or PKC-δ, and then isolated peritoneal macrophages. Total RNA was isolated from the cells and analyzed by quantitative PCR. Our study revealed that neutralizing C5aR markedly inhibited sepsis-induced uPA receptor (uPAR) expression and its downstream signaling in macrophage. Similarly, neutralizing uPAR suppressed sepsis activation of C5a signaling. Importantly, inhibition of PKC-δ largely blocked sepsis-induced expression of C5aR and uPAR. Our study demonstrates a crosstalk between the complement C5a signaling and the fibrinolytic uPA pathways, which may depend on each other to maintain their expression and signaling, and reveals a central role of PKC-δ in mediating sepsis-induced activation of these pathways.Agents and Actions 03/2014; 63(7). DOI:10.1007/s00011-014-0729-1 · 2.14 Impact Factor