Infection and Airway Inflammation Human Model of

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Tracheal Aspirates in Long-term Mechanically Ventilated Patients : A Human Model of Gram-Negative Infection and Airway Inflammation Lucy B. Palmer, Gerald C. Smaldone, Sanford Simon, Thomas O'Riordan and Lorraine Morra Chest 1995;108;1326-1332 DOI 10.1378/chest.108.5.1326 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/108/5/1326

Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1995by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692

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Tracheal

in Long-term Aspirates Mechanically Ventilated Patients*

A Human Model of Gram-Negative Infection and Airway Inflammation Lucy B. Palmer, MD; Gerald C. Smaldone, MD, PhD; Sanford Simon, PhD; Thomas O'Riordan, MD; and Lorraine Morra

It is well known that patients requiring long-term me¬ chanical ventilation and tracheostomy have nearly universal airway colonization with Gram-negative or¬ ganisms. However, useful parameters to objectively describe the airway inflammation associated with air¬ way instrumentation and colonization have not been well defined. In our respiratory care unit, patients who are medically stable except for ventilator dependence are readily available for longitudinal assessment of airway secretions and therefore provide a unique for studying airway inflammation and in¬ population fection. To quantitate production of respiratory secre¬ tions, we instituted a uniform protocol of suctioning over a 6-h period. Further, we devised a method of dilution and homogenization of tracheal aspirates that permits reproducible intrasample total cell counts (coefficient of variation, 4.6%). With these techniques, patients were then studied serially over a 4- to 7-week period. Total cellofcount, inflammatory cell differential, and two indices airway inflammation, human neu¬ trophil elastase (HLE) and soluble-intercellular adhe¬ sion molecule-1 (sICAM-1) studied in the sol phase of secretions were monitored. The mean total cell count was 42.2xlO6 cells per gram of secretions when pa¬ tients were clinically stable and not receiving antibi¬ otics. The average differential was neutrophils 69.9%,

dysfunction or injury associated with cystic fibrosis, mechanical ventilation, and bron¬ chiectasis apparently result in a common state of chronic Gram-negative colonization and airway inflam¬ mation. The ability to study and monitor serially the effect of a variety of therapeutic agents on this airway inflammation and infection may enhance our ability to both understand and treat Gram-negative infections. Studies of this problem in humans are difficult. Serial TPhe mucosal ¦*¦

*From the Departments of Medicine, Pulmonary/Critical Care Division (Drs. Palmer, Smaldone, O'Riordan and Ms. Morra) and (Dr. Simon), State University of New York at Stony Biochemistry Brook. Supported by operational grant 371318 of University Medical Center, Stony Brook, NY. Manuscript received November 16, 1994; revision accepted April 7, 1995. Reprint requests: Dr. Palmer, Pulmonary Critical Care Division, State University of New York at Stony Brook, HSC TI 7-040, Stony Brook, NY 11794-8172 1326

macrophages 26.9%, and lymphocytes 2.8%. Mean active HLE was 35.6 pg/mL and mean sICAM-1 was 83 ng/mL. Six patients during the period of observation received intravenous oral or aerosolized antibiotics for tracheobronchitis. A threefold drop in volume of secretions was measured (p