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Inflammatory Profile of New Bacterial Strain Exacerbations of Chronic Obstructive Pulmonary Disease

¹ Division of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, University at Buffalo, State University of New York; ² Veterans Affairs Western New York Healthcare System, Buffalo, New York; and ³ Division of Infectious Diseases, Department of Microbiology, and ⁴ Department of Biostatistics, University at Buffalo, State University of New York

Correspondence and requests for reprints should be addressed to Sanjay Sethi, M.D., VA WNY Healthcare System (151), 3495 Bailey Avenue, Buffalo, NY 14215. E-mail: ssethi{at}buffalo.edu

Rationale: Whether the airway and systemic inflammatory profile in bacterial exacerbations of chronic obstructive pulmonary disease (COPD) is distinct from nonbacterial exacerbations is unclear. Previous studies have not used molecular typing of bacterial pathogens, which is required to accurately define bacterial infection in COPD. The relationship between clinical severity and course of exacerbation and inflammation is also not fully understood.

Objectives: To determine if (1) systemic and airway inflammation is distinct in new bacterial strain exacerbations and (2) clinical severity and resolution of exacerbations is related to airway and systemic inflammation.

Methods: In a prospective longitudinal cohort study in COPD, sputum and serum samples obtained before, at, and following exacerbations during a 2-year period were studied.

Measurements and Main Results: Clinical information, molecular typing of bacterial pathogens, sputum IL-8, tumor necrosis factor (TNF)- and neutrophil elastase, and serum C-reactive protein. From 46 patients, 177 exacerbations were grouped as new strain, preexisting strain, other pathogen, and pathogen negative. New strain exacerbations were associated with significantly greater increases from baseline in sputum TNF- and neutrophil elastase, and in serum C-reactive protein compared with the other three groups. Increases in inflammatory markers were similar among the other three groups. Clinical resolution was accompanied by resolution of inflammation to preexacerbation levels, whereas persistent symptoms were paralleled by persistently elevated inflammation. Clinical exacerbation severity was significantly correlated with levels of all four markers.

Conclusions: Neutrophilic airway inflammation and systemic inflammation are more intense with well-defined bacterial exacerbations than with nonbacterial exacerbations. Clinical course of exacerbation and inflammation are closely linked.

Key Words: chronic obstructive pulmonary disease • exacerbation • inflammation

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Changes in airway inflammation with bacterial exacerbations of chronic obstructive pulmonary disease are not consistent among studies. This may be related to lack of molecular characterization of bacterial strains isolated at exacerbation and the timing of stable sampling. What This Study Adds to the Field New bacterial strain exacerbations are associated with more intense airway and systemic inflammation than those with preexisting strains and nonbacterial episodes. Clinical severity and resolution of exacerbation and inflammation are closely linked.

 

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