Clinical Outcomes and Inflammatory Responses of the Frequent Exacerbator in Pulmonary Rehabilitation: A Prospective Cohort Study

Abstract

Frequent exacerbators of Chronic Obstructive Pulmonary Disease (COPD) is a distinct clinical phenotype characterised by systemic inflammation. Study objectives were to determine clinical outcomes of pulmonary rehabilitation in frequent exacerbators and the impact this has on the key surrogate markers of this phenotype. Eighty-five mild-very severe COPD patients (FEV1 pred, 52 ± 18%) were categorised as frequent (≥2 exacerbations per year, n = 50) or infrequent exacerbators (≤1 exacerbation per year, n = 35). The primary outcomes were completion rates of pulmonary rehabilitation (clinical) and plasma fibrinogen (biological). Secondary outcomes were: incremental shuttle (ISWT) & endurance shuttle walk tests (ESWT), chronic respiratory disease questionnaire (CRQ), hospital anxiety and depression scale (HADS), plasma C-reactive protein (CRP), blood leukocyte counts, blood neutrophil activation (CD11b, CD62L, CD66b) and subsets (mature, immature, suppressive, progenitor). Fibrinogen and CRP concentrations were determined via ELISA’s with neutrophil activation markers assessed using flow cytometry. Frequent exacerbators were less likely to complete pulmonary rehabilitation (44% vs 69%; p = 0.025). Both groups experienced improvements in ISWT (p < 0.001), ESWT (p < 0.001), all domains of the CRQ (p < 0.001) and Depression (p = 0.017). Pulmonary rehabilitation reduced resting concentrations of fibrinogen (frequent exacerbators = 12%, infrequent exacerbators = 4%, p = 0.033) and % of progenitor blood neutrophils (p = 0.015) in both groups, with reductions in total blood leukocyte (p = 0.018) and neutrophil counts (p = 0.018) also observed in frequent exacerbators. No significant reductions in CRP concentration (p = 0.937), neutrophil activation (CD11b, p = 0.553; CD62L, p = 0.070; CD66b, p = 0.317), or other neutrophil subsets (mature, p = 0.313; immature, p = 0.756; suppressive, p = 0.259) were observed. Frequent exacerbators of COPD were less likely to complete pulmonary rehabilitation, but those who complete experience similar benefits to infrequent exacerbators. Pulmonary rehabilitation may serve to have immune-modulatory properties for frequent exacerbators.