BACKGROUND
The diagnosis and treatment of bacterial pneumonia in patients who are receiving mechanical ventilation remain a difficult challenge. The triggering receptor expressed on myeloid cells (TREM-1) is a member of the immunoglobulin superfamily, and its expression on phagocytes is specifically up-regulated by microbial products. The presence of soluble TREM-1 (sTREM-1) in bronchoalveolar lavage fluid from patients receiving mechanical ventilation may be an indicator of pneumonia.
METHODS
We conducted a prospective study of 148 patients receiving mechanical ventilation in whom infectious pneumonia was suspected. A rapid immunoblot technique was used to measure sTREM-1 in bronchoalveolar-lavage fluid. Two independent intensivists who were unaware of the results of the sTREM-1 assay determined whether community- acquired pneumonia and ventilator-associated pneumonia were present or absent.
RESULTS
The final diagnosis was community-acquired pneumonia in 38 patients, ventilator- associated pneumonia in 46 patients, and no pneumonia in 64 patients. The presence of sTREM-1 by itself was more accurate than any clinical findings or laboratory values in identifying the presence of bacterial or fungal pneumonia (likelihood ratio, 10.38; sen- sitivity, 98 percent; specificity, 90 percent). In multiple logistic-regression analysis, the presence of sTREM-1 was the strongest independent predictor of pneumonia (odds ratio, 41.5).
CONCLUSIONS
In patients receiving mechanical ventilation, rapid detection of sTREM-1 in bronchoal- veolar-lavage fluid may be useful in establishing or excluding the diagnosis of bacterial or fungal pneumonia
The DIAGNOSIS AND TREATMENT OF infectious pneumonia in patients who are receiving mechanical ventilation remain a
major challenge for clinicians.1,2 A presumptive clinical diagnosis of pneumonia is often made when a new radiographic infiltrate develops in a patient with fever, leukocytosis, and purulent tracheal se- cretions and when microorganisms are isolated from the airways. Unfortunately, many noninfec- tious processes may be responsible for fever and new pulmonary infiltrates in patients who are receiv- ing mechanical ventilation, and clinical approaches lead to an overestimation of the incidence of pneu- monia.3-5 Moreover, whatever the microbiologic diagnostic procedure chosen,5-9 further laborato- ry processing and delays of 24 to 48 hours are re- quired for definitive quantitative microbial culture results. Meanwhile, clinicians often feel uncomfort- able about the diagnosis and may administer un- needed antibiotics while awaiting laboratory results. Therefore, many biologic markers have been stud- ied in an effort to improve the diagnostic procedure but with disappointing results.10-16
The triggering receptor expressed on myeloid cells (TREM-1) is a member of the immunoglobu- lin superfamily17 whose expression on phagocytes is up-regulated by exposure to bacteria and fungi. TREM-1 mediates the acute inflammatory response to microbial products.18 Human tissues infected with bacteria are infiltrated with neutrophils and monocytes that express high levels of TREM-1.18 Conversely, TREM-1 is only weakly expressed in samples from patients with noninfectious inflam- matory disorders.18 TREM-1 is also shed by the membrane of activated phagocytes and can be found in a soluble form in body fluids. We evaluated wheth- er the presence of soluble TREM-1 (sTREM-1) in bronchoalveolar-lavage fluid from patients who are receiving mechanical ventilation is a good indicator of infectious pneumonia.
METHODS
STUDY POPULATION
The institutional review board approved the study, and patients or their relatives provided written in- formed consent before enrollment. All patients 18 years of age or older who were hospitalized in our medical intensive care unit (ICU) were prospective- ly enrolled in the study if they required mechanical ventilation and there was a clinical suspicion of in- fectious pneumonia, defined by a new and persis- tent infiltrate on chest radiography associated with
at least one of the following: purulent tracheal se- cretions, a body temperature of at least 38.3°C, and leukocytosis (more than 10,000 leukocytes per cu- bic millimeter) or leukopenia (fewer than 4000 leu- kocytes per cubic millimeter). Ventilator-associated pneumonia was defined by acquisition of the dis- ease after 48 hours of mechanical ventilation.
The following items were recorded for each pa- tient on admission into the ICU: age, sex, severity of underlying medical condition stratified according to the criteria of McCabe and Jackson,20 the Sim- plified Acute Physiology Score II (SAPS II) (scores can range from 0 to 163, with higher scores indi- cating a higher risk of death),21 the Sepsis-related Organ Failure Assessment score (the total score can range from 0 to 24; with scores for each organ sys- tem [respiration, coagulation, liver, cardiovascular, central nervous system, and kidney] ranging from 0 [normal] to 4 [most abnormal]),22 and the reason for admission to the ICU.
The following base-line variables were also re- corded at enrollment: SAPS II score; the Sepsis- related Organ Failure score; body temperature; leukocyte count; ratio of the partial pressure of ar- terial oxygen to the fraction of inspired oxygen (PaO2:FiO2); serum levels of C-reactive protein and procalcitonin; presence of shock, defined by a systolic arterial pressure below 90 mm Hg with signs of peripheral hypoperfusion or the need for a continuous infusion of vasopressor or inotropic agents23; duration of mechanical ventilation; and previous use of antimicrobial therapy. A clinical pulmonary infection score was calculated as pre- viously described.19 The duration of mechanical ventilation and the length and the outcome (death or discharge) of stay in the ICU were also recorded.
CONFIRMATION OF THE DIAGNOSIS Mini–bronchoalveolar lavage and processing of microbiologic specimens were performed as de- scribed in detail elsewhere.8,10 Briefly, mini–bron- choalveolar lavage was performed with the use of the Combicath, a single-sheathed, 50-cm, sterile, plugged, telescopic catheter (Plastimed). The recov- ered fluid (about two thirds of the 20 ml of saline [0.9 percent sodium chloride] that had been in- stilled) was divided into two samples: one was used for direct microscopical examination and quanti- tative culture; the other was centrifuged at 10,000 revolutions per minute for 30 minutes, and the supernatant was frozen at ¡80°C until used for sTREM-1 and cytokine measurements. The concen- tration of microorganisms considered clinically
significant for the potential diagnosis of pneumo- nia was more than 103 colony-forming units per milliliter of bronchoalveolar-lavage fluid.8
A post hoc diagnosis of pneumonia was made on the basis of a combination of already mentioned clinical criteria with microbiologic evidence of mi- crobial infection. These criteria were similar to those used for ventilator-associated pneumonia by Pugin and coworkers.19 Pneumonia was considered to be absent when an alternative cause for pulmonary infiltrate was established and there was nonsig- nificant bacterial growth in culture of bronchoal- veolar-lavage fluid in association with full recovery from fever, infiltrate, and leukocytosis without anti- microbial therapy. Two intensivists reviewed all medical records pertaining to the patient and in- dependently classified the diagnosis as community- acquired pneumonia, ventilator-associated pneu- monia, or no pneumonia. A consensus concerning the diagnosis was achieved in all cases. Both inten- sivists were unaware of the results of sTREM-1 and cytokine measurements.
CS 340 Milestone One Guidelines and Rubric Overview: For this assignment, you will implement the fundamental operations of create, read, update,
Retail Transaction Programming Project Project Requirements: Develop a program to emulate a purchase transaction at a retail store. This
7COM1028 Secure Systems Programming Referral Coursework: Secure
Create a GUI program that:Accepts the following from a user:Item NameItem QuantityItem PriceAllows the user to create a file to store the sales receip
CS 340 Final Project Guidelines and Rubric Overview The final project will encompass developing a web service using a software stack and impleme
