title: Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Comorbidities contribute to disease severity and mortality in patients with chronic obstructive pulmonary disease (COPD). Comorbidities have been studied individually and were mostly based on self-reports. The coexistence of objectively identified comorbidities and the role of low-grade systemic inflammation in the pathophysiology of COPD remain to be elucidated.
  
  
  OBJECTIVE
  To cluster 13 clinically important objectively identified comorbidities, and to characterize the comorbidity clusters in terms of clinical outcomes and systemic inflammation.
  
  
  METHODS
  A total of 213 patients with COPD (FEV1, 51 ± 17% predicted; men, 59%; age, 64 ± 7 yr) were included prospectively. Comorbidities were based on well-known cut-offs identified in the peer-reviewed English literature. Systemic inflammatory biomarkers were determined in all patients. Self-organizing maps were used to generate comorbidity clusters.
  
  
  RESULTS
  A total of 97.7% of all patients had one or more comorbidities and 53.5% had four or more comorbidities. Five comorbidity clusters were identified: (1) less comorbidity, (2) cardiovascular, (3) cachectic, (4) metabolic, and (5) psychological. Comorbidity clusters differed in health status but were comparable with respect to disease severity. An increased inflammatory state was observed only for tumor necrosis factor (TNF) receptors in the metabolic cluster (geometric mean [lower and upper limit]; TNF-R1, 2,377 [1,850, 3,055] pg/ml, confidence, 98.5%; TNF-R2, 4,080 [3,115, 5,344] pg/ml, confidence, 98.8%) and only for IL-6 in the cardiovascular cluster (IL-6, 3.4 [1.8, 6.6] pg/ml; confidence, 99.8%).
  
  
  CONCLUSIONS
  Multimorbidity is common in patients with COPD, and different comorbidity clusters can be identified. Low-grade systemic inflammation is mostly comparable among comorbidity clusters. Increasing knowledge on the interactions between comorbidities increases the understanding of their development and contributes to strategies for prevention or improved treatment.
authors: Program Development Centre, CIRO+, Centre of Expertise for Chronic Organ Failure, Horn, The Netherlands. lowievanfleteren@ciro-horn.nl
authors: Lowie E G W
authors: LE
authors: Vanfleteren
authors: Martijn A
authors: MA
authors: Spruit
authors: Miriam
authors: M
authors: Groenen
authors: Swetlana
authors: S
authors: Gaffron
authors: Vanessa P M
authors: VP
authors: van Empel
authors: Piet L B
authors: PL
authors: Bruijnzeel
authors: Erica P A
authors: EP
authors: Rutten
authors: Jos
authors: J
authors: Op 't Roodt
authors: Emiel F M
authors: EF
authors: Wouters
authors: Frits M E
authors: FM
authors: Franssen
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002100:Cachexia / Q000453:epidemiology*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D016000:Cluster Analysis; D015897:Comorbidity; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology*; D008659:Metabolic Diseases / Q000453:epidemiology*; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology* / Q000503:physiopathology; D012044:Regression Analysis; D048069:Tumor Necrosis Factors / Q000097:blood
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D048069:Tumor Necrosis Factors