<p>Serum Amyloid A in Stable COPD Patients is Associated with the Frequent Exacerbator Phenotype</p>

Abstract

Background: We sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotype in stable COPD patients ie, those with two or more exacerbations in the previous year. Methods: Eighty-eight stable, severe, COPD patients (4 females) were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (F E NO); 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-4 were not significantly correlated with FEV 1 % predicted or FVC %predicted. After adjusting for sex, age, BMI, FEV 1 /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 18times greater in the highest SAA quartile (≥124.1 ng/mL) than the lowest SAA quartile (≤44.1 ng/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; an SAA cutoff of 87.0 ng/mL yielded an 80% sensitivity and 61.5% specificity. Conclusion: In stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA may be a useful serum biomarker to inform progression or management in COPD.

Risk of Ischemic Heart Disease in Chronic Obstructive Pulmonary Disease: A Nationwide Cohort Study

“… 30 31 In previous studies, inflammatory mediators such as interferon-γ, interleukin (IL)-1, tumor necrosis factor α, IL-6, and acute phase inflammatory proteins (fibrinogen, C-reactive protein, and amyloid protein) were shown to be involved in the airway as well as in systemic inflammation in COPD. 32 33 34 Because many of these inflammatory mediators are also involved in the activation of immune cells in atheromatous plaques in coronary heart disease, 35 36 COPD-related inflammation may trigger or enhance atherosclerosis in coronary arteries. Third, systemic oxidative stress in COPD may increase the risk of IHD.…”

The Molecular Blueprint for Chronic Obstructive Pulmonary Disease (COPD): A New Paradigm for Diagnosis and Therapeutics

“…Exacerbation episodes lead to a dramatic increase in mortality related to cardiovascular events in COPD. SAA levels can very well anticipate future cardiovascular events; thus, SAA can be scrutinized as a predictor for frequent exacerbation phenotypes and a marker for comorbid cardiovascular disease [ 68 ].…”

High-Density Lipoproteins: A Role in Inflammation in COPD

“…The clinical significance of SAA is related to the fact that high SAA levels are associated with the frequency and severity of COPD exacerbations. SAA levels increase significantly during the acute phase of COPD exacerbations, making SAA a sensitive biomarker of exacerbation severity [ 234 , 235 ]. Moreover, in stable patients with COPD, SAA was independently associated with the phenotype of frequent exacerbations [ 234 ].…”

“…SAA levels increase significantly during the acute phase of COPD exacerbations, making SAA a sensitive biomarker of exacerbation severity [ 234 , 235 ]. Moreover, in stable patients with COPD, SAA was independently associated with the phenotype of frequent exacerbations [ 234 ].…”