title: Predictors of chronic obstructive pulmonary disease exacerbations.
abstract: OBJECTIVE
  A frequent-exacerbation phenotype of chronic obstructive pulmonary disease (COPD) exists that is independent of disease severity. Establishment of methods to predict 'frequent exacerbators' is critical. The purpose of this review is to critically assess the recent literature regarding predicting COPD exacerbations, and to provide recommendations for future research.
  
  
  RESULTS
  Although there are many studies in which inflammatory biomarkers have been used in an attempt to predict future exacerbations, it is likely that these biomarkers represent a consequence rather than the cause. Genetic predictors are involved in causal pathways. Thus, genetics should be investigated in order to understand the exacerbation mechanism and to develop new therapeutic approaches. Some single nucleotide-type genetic polymorphisms are associated with exacerbations, and the individuals with genotypes protective against infection are less susceptible to exacerbations. In contrast, we reported that loss of Siglec-14, a lectin likely involved in host defense, was associated with a reduced COPD exacerbation risk.
  
  
  CONCLUSIONS
  We should take into consideration that a protein involved in host defense such as Siglec-14, that could also trigger exaggerated response, might also generate unwanted local and systemic inflammation, which could be detrimental to a host and could generate COPD with a frequent-exacerbation phenotype, its progression, and its comorbidities.
authors.affiliation: aRespiratory Care Clinic, Nippon Medical School bDepartment of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishii
authors.forename: Kozui
authors.initials: K
authors.lastname: Kida
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D018570:Risk Assessment; D012720:Severity of Illness Index
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D037102:Lectins; D011956:Receptors, Cell Surface; C514213:SIGLEC14 protein, human; D002097:C-Reactive Protein