Association of Systemic Inflammation with Depressive Symptoms in Individuals with COPD

Hilary C Strollo,1 Seyed M Nouraie,1 Karin F Hoth,2 Craig M Riley,3 Chad Karoleski,1 Yingze Zhang,1 Nicola A Hanania,4 Russell P Bowler,5,6 Jessica Bon,1 Frank C Sciurba1 1University of Pittsburgh Medical Center, Department of Medicine, Department of Pulmonary Allergy and Critical Care Medicine, Pittsburgh, PA, USA; 2University of Iowa Carver College of Medicine, Department of Psychiatry, Iowa City, IA, USA; 3Chester County Hospital, University of Pennsylvania Health System, West Chester, PA, USA; 4Baylor College of Medicine, Department of Pulmonary, Critical Care and Sleep Medicine, Houston, TX, USA; 5National Jewish Health, Department of Medicine, Denver, CO, USA; 6University of Colorado School of Medicine, Denver, CO, USACorrespondence: Hilary C StrolloUniversity of Pittsburgh Medical Center, Department of Medicine, Department of Pulmonary Allergy and Critical Care Medicine, NW 628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USATel +1 412-692-2210Fax +1 412-692-4842Email strolloh2@upmc.eduRationale: Depression is a prevalent comorbidity of chronic obstructive pulmonary disease (COPD) that, along with COPD, has been associated with inflammation. An association between inflammation and depression in COPD has not been validated in a large COPD cohort.Methods: Individuals from the University of Pittsburgh SCCOR cohort and the COPDGene cohort with tobacco use history and airway obstruction (FEV1/FVC < 0.7) were evaluated using the Beck Depression Inventory II (BDI-II) and the Hospital Anxiety and Depression Scale (HADS), respectively. Participants completed symptom-related questionnaires and plasma IL-6 measurements. T-test, Fisher’s Exact tests and logistic regression were used for statistical analysis.Results: The SCCOR cohort included 220 obstructed participants: 44% female and 21.4% with elevated depressive symptoms. GOLD staging distribution was predominantly stage I and II. The COPDGene cohort included 745 obstructed participants: 44% female and 13.0% with elevated depressive symptoms. GOLD distribution was predominantly stage II and III. In the SCCOR cohort, correlation between IL-6 and depressive symptoms trended toward significance (p= 0.08). Multivariable modeling adjusted for FEV1, age, gender and medical comorbidities showed a significant association (OR = 1.70, 95% CI = 1.08– 2.69). IL-6 was significantly associated with elevated depressive symptoms in COPDGene in both univariate (p=0.001) and multivariable modeling (OR = 1.52, 95% CI =1.13– 2.04).Conclusion: Elevated plasma IL-6 levels are associated with depressive symptoms in individuals with COPD independent of airflow limitation and comorbid risk factors for depression. Our results suggest that systemic inflammation may play a significant and possibly bidirectional role in depression associated with COPD.Keywords: IL-6, depression, beck depression inventory, BDI, HADS, TNF-a, CRP, SCCOR, COPDGen