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

Abstract

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. 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. 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. Clinical information, molecular typing of bacterial pathogens, sputum IL-8, tumor necrosis factor (TNF)-alpha 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-alpha 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. 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.