Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease

There is increasing evidence that chronic obstructive pulmonary disease (CO PD) is associated with chronic inflammation in the airways and lung parench yma; however, little is known about the inflammatory response during acute COPD exacerbation. The objectives of this study were (I) to determine if in flammatory markers associated with neutrophilic inflammation and activation increase at times of acute COPD exacerbation relative to the clinically st able state, and (2) to determine whether the presence of acute bacterial or viral infection at the time of COPD exacerbation could be correlated with increases in sputum markers of inflammation. Induced sputum was collected f rom patients with COPD when they were clinically stable, during the time of an acute exacerbation, and 1 mo later. Sputum was analyzed at each time po int for soluble markers associated with neutrophilic inflammation; myeloper oxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 ( IL-8). Serologic assays on acute and convalescent sera were performed for r espiratory viruses, and induced sputum was also subject to quantitative bac terial cultures, viral cultures, and polymerase chain reaction (PCR) for de tection of respiratory viruses. Fourteen of the 50 patients enrolled in the study met predetermined criteria for an acute COPD exacerbation over the 1 5-mo study period. TNF-alpha and IL-8 were significantly elevated in the sp utum of patients during acute COPD exacerbation compared with when they wer e clinically stable (p = 0.01 and p = 0.05, respectively). Concentrations o f these cytokines declined significantly 1 mo after the exacerbation. Three of 14 patients (21%) had confirmed bacterial or viral respiratory tract in fections. Patients with documented infection did not demonstrate greater in creases in sputum levels of inflammatory cytokines during exacerbations com pared with patients without demonstrable infection. We conclude that marker s of airway neutrophilic inflamation increase at the time of acute COPD exa cerbation and then decline 1 mo later, and that this acute inflammatory res ponse appears to occur independently of a demonstrable viral or bacterial a irway infection.