title: Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type.
abstract: Long-term outcome prediction in COPD is challenging. We conducted a prospective 5-7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th-75th percentile] 6.1 [5.6-6.5] years, mortality was 55% (95%CI 50%-59%). Discharge ProADM concentration was strongly associated with 5-7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2-17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701-0.789) versus 0.727 (0.681-0.772), (p) = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5-7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment.
authors.affiliation: 1Medical University Clinic, Kantonsspital Aarau , Aarau , Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Grolimund
authors.forename: Alexander
authors.initials: A
authors.lastname: Kutz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Marlowe
authors.forename: Alaadin
authors.initials: A
authors.lastname: Vögeli
authors.forename: Murat
authors.initials: M
authors.lastname: Alan
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
authors.forename: Robert
authors.initials: R
authors.lastname: Thomann
authors.forename: Claudine
authors.initials: C
authors.lastname: Falconnier
authors.forename: Claus
authors.initials: C
authors.lastname: Hoess
authors.forename: Christoph
authors.initials: C
authors.lastname: Henzen
authors.forename: Werner
authors.initials: W
authors.lastname: Zimmerli
authors.forename: Beat
authors.initials: B
authors.lastname: Mueller
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
mesh_terms: D053607:Adrenomedullin / Q000097:blood; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002116:Calcitonin / Q000097:blood; D004417:Dyspnea / Q000145:classification / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000401:mortality*; D018570:Risk Assessment; D012907:Smoking / Q000453:epidemiology; D013557:Switzerland / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin; D002116:Calcitonin; D002097:C-Reactive Protein
keywords: accuracy; blood biomarkers; chronic obstructive pulmonary disease (COPD); long-term all-cause mortality; mortality prediction; multidimensional risk stratification; non-pneumonic exacerbation; pneumonic exacerbation; proadrenomedullin (ProADM)