Association between COPD exacerbations and lung function decline during maintenance therapy

Abstract

BackgroundLittle is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study.MethodsThe study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline. Effect modification by blood eosinophils was studied through interaction terms.ResultsOf 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS.ConclusionExacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.

CONQUEST Quality Standards: For the Collaboration on Quality Improvement Initiative for Achieving Excellence in Standards of COPD Care

“… 49 Real-life data also showed that elevated BEC was associated with better outcomes for those on triple therapy (vs dual bronchodilator therapy), 50 and in frequent exacerbators is associated with more rapid lung function decline. 12 Higher BEC (ie, >200 cells/µL) may also be a predictor of OCS success in those experiencing exacerbations, 51 and eosinophil guided therapy has been shown to reduce OCS exposure in patients admitted to hospital with acute exacerbation of COPD. 52 Taken together, these results suggest the value of BEC to tailor treatments to specific COPD phenotypes and endotypes.…”

“… 9 This is important since interventions such as smoking cessation and pulmonary rehabilitation 10 , 11 may improve prognosis and drugs such as inhaled corticosteroids (ICS) may improve current symptoms and exacerbations that are associated with rapid lung function loss. 12 Furthermore, patients who experience a greater exacerbation burden after initiation of maintenance therapy have worse lung function at diagnosis and a more rapid lung function decline thereafter, emphasizing the need for better treatment strategies. 13 These findings highlight the importance of earlier intervention among patients with COPD, to more proactively diagnose and manage optimally.…”

Risk Factors of Rapid Lung Function Decline in COPD Patients of Real World

“…In that study, the proportion of patients with a blood eosinophil count ≥ 300/µl was 24.3% and ICS was used by 14.6% (25), while the proportion with a blood eosinophil count ≥ 300/µl was 21.2% and ICS was used by 42.9% in our study. Importantly, in patients with COPD with a high blood eosinophil count, the use of ICS was reported to signi cantly reduce the rate of lung function decline, while FEV 1 decline was more rapid in patients not treated with ICS (18). Additionally, a low blood eosinophil pro le is related with a high bacterial burden (26) and emphysema progression (27).…”

“…Besides demographic risk factors, including a higher age, a lower body mass index (BMI), being a current smoker, and more severe dyspnea (11,14), frequent or acute exacerbation events are important risk factors for the rapid decline in lung function (15)(16)(17). Recent studies indicate that acute exacerbation and a rapid decline in FEV 1 are related with high counts of blood eosinophils (18). However, few researchers report the relative decline of lung function (percentage change from baseline FEV 1 per year [%/year]), rather reporting the absolute decline in lung function (FEV 1 ml per year [ml/year]).…”

The influence of individual characteristics and non‐respiratory diseases on blood eosinophil count

“…In COPD patients, higher B‐Eos levels are associated with an improved response to ICS in preventing exacerbations 13–16 . During exacerbations, higher B‐Eos levels predict greater response to oral corticosteroids, while lower levels are associated with worse outcomes 17,18 . Furthermore, exacerbations are associated with an increased decline in lung function among COPD patients with elevated B‐Eos and without ICS 18 .…”