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Inflammatory parameters and imminent exacerbations in COPD patients

During a two-months corticosteroid-free run-in period prior to a long-term intervention study, 8 of 29 patients with stable COPD experienced an exacerbation within 1 to 4 weeks after enrolment. We analysed retrospectively whether clinical and inflammatory parameters in blood and induced sputum at enrolment were associated with the imminent exacerbation. At enrolment, cell differentials were obtained in induced sputum and blood, and markers of neutrophilic (myeloperoxidase: MPO; interleukin-8: IL-8) and eosinophilic (eosinophil cationic protein: ECP) inflammation and of airway permeability (quotient of α-2macroglobulin levels in sputum and serum: Q-A2M) were assessed. The patients had a mean age of 64 y, a mean FEV1 of 1.86 L (equivalent with 63 % of predicted), and showed a mean β2-agonist reversibility of 4.4 % predicted. GOLD stage 2 or 3 was a risk factor as 8 of 20 patients (40%) had an early exacerbation compared to none of 9 with stage 1 (p=0.01). Median blood eosinophil count was significantly higher in those with an exacerbation (p=0.03); a value above the median value for the entire study group was associated with a 13-fold increased risk of experiencing an exacerbation (95% C.I. 1.3 128, p=0.01). The four-fold higher median sputum eosinophil count (67 versus 15 x 103/g) approached significance (p=0.08). No significant differences were found for other inflammatory sputum parameters between patient groups. However, in 3 patients with an early exacerbation Q-A2M values and sputum ECP and MPO levels were at least 10-fold higher than for the other patients with an early exacerbation. Patients with early exacerbations showed either extensive or moderate inflammation, suggestive of two subgroups. In conclusion, we hypothesize that, in addition to disease severity, high blood eosinophil counts and potentially also high sputum eosinophil counts are risk factors for an imminent exacerbation in patients with COPD. C H A P T E R 5