Serum Amyloid a in Stable COPD Patients is Associated With the Frequent Exacerbator Phenotype

Abstract

Background: We sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotypein stable COPD patients i.e. those with two or more exacerbations in the previous year.Methods:88 stable, severe, COPD patients (4 females)were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (FENO);inflammatory variables were measured in venous blood. Logistic regression assessed associations between the frequent exacerbator phenotype and systemic inflammation.Results:Compared with infrequent exacerbators, frequent exacerbators (n=10; 11.4%)had greater serum concentration(median (25th-75th quartile)) of serum amyloid A (SAA; 134(84-178) vs. 71(38-116) ng/ml; P=0.024), surfactant protein D (SP-D;15.6(9.0-19.3)vs. 8.5(3.6-14.9) ng/ml; P=0.049) and interleukin-4 (IL-4; 0.12(0.08-1.44)vs. 0.03(0.01-0.10) pg/ml;P=0.001). SAA,SP-D and IL-4were not significantly correlated with FEV1 %predicted or FVC %predicted. After adjusting for sex, age, BMI, FEV1/FVC and smoking pack-years, only SAA remained independently associated with the frequent exacerbator phenotype (OR 1.49[1.09-2.04]; P=0.012).The odds of being a frequent exacerbator was 18-times greater in the highest SAA quartile (³124.1ng/ml) than the lowest SAA quartile (£44.1ng/ml) (OR 18.34[1.30-258.81]; P=0.031), and there was a significant positive trend of increasing OR with increasing SAA quartile (P=0.008). For SAA, the area under the receiver operating characteristic curve was 0.721 for identification of frequent exacerbators with an optimal SAA cut-offof 131.7 ng/ml.Conclusion: In stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA maybe a usefulserum biomarker to inform progression or management in COPD.

Biomarker-based clustering of patients with chronic obstructive pulmonary disease

“…Most COPD studies only focused on one or a limited number of markers of systemic inflammation revealing the heterogeneity within and between the different systemic inflammatory biomarkers (1)(2)(3). Multiple other inflammatory biomarkers exist, and for example, acute phase proteins and the complement system (1,4,5), cytokines and chemokines and their receptors (6)(7)(8)(9)(10), inhibitors of cytokine signaling (11), adhesion molecules (12,13), immunoglobulins (14), growth factors (10,15,16), proteins involved in tissue remodeling (17,18), hormones and adipokines (19,20), coagulation (21,22), and plasma carrier proteins (23,24) have all been shown to be associated with COPD. These data suggest that to better understand the complexity of COPD on a systemic level, a variety of serum markers encompassing a wider scope of inflammatory processes are needed.…”