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

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 (F_ENO);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 (25^th-75^th 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.