title: Obesity paradox in patients with community-acquired pneumonia: Is inflammation the missing link?
abstract: OBJECTIVE
  Positive associations between body mass index (BMI) and clinical outcomes have been found and are called "the obesity survival paradox." However, whether obesity has protective effects or if this paradox is because of confounding remains unclear. Herein, we analyzed the effects of weight on long-term mortality in a large cohort of patients with community-acquired pneumonia (CAP) and investigated whether the differential effects of obesity on inflammation pathways accounted for mortality differences.
  
  
  METHODS
  For this secondary analysis, we followed prospectively for 6 y 763 CAP patients who were previously included in a multicenter trial (the ProHOSP Trial). To assess associations of BMI with mortality and with several inflammatory biomarker levels, we calculated three regression models adjusted for severity: the pneumonia severity index (PSI); fully adjusted for PSI, age, sex, metabolic factors, cardiovascular diseases, and other comorbidities; and fully adjusted including biomarker levels.
  
  
  RESULTS
  Within the 763 patients studied, all-cause 6-y mortality was significantly lower in obese patients (BMI >30 kg/m2) compared with normal-weight patients (BMI 18.5-25 kg/m2), with a severity-adjusted hazard ratio of 0.641 (95% confidence interval 0.462-0.889) and robust results in fully adjusted and fully adjusted plus biomarker models. No associations of increased BMI and C-reactive protein, procalcitonin, or white blood cell count were found, but BMI > 30 kg/m2was associated with higher proadrenomedullin levels.
  
  
  CONCLUSIONS
  Over a 6-y long-term follow-up, we found obesity to be associated with lower all-cause mortality in CAP patients, confirming the obesity paradox in this population. However, differences in inflammatory pathways did not explain these findings.
authors.affiliation: Internal Medicine, Kantonsspital Münsterlingen, Switzerland; University Department of Medicine, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Nina
authors.initials: N
authors.lastname: Braun
authors.affiliation: Internal Medicine, Kantonsspital Münsterlingen, Switzerland.
authors.forename: Claus
authors.initials: C
authors.lastname: Hoess
authors.affiliation: University Department of Medicine, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kutz
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, Universitätsspital Basel, Basel, Switzerland.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
authors.affiliation: Department of Internal Medicine, Bürgerspital Solothurn, Solothurn, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Thomann
authors.affiliation: Department of Internal Medicine, Luzerner Kantonsspital, Lucerne, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Henzen
authors.affiliation: Basel University Medical Clinic, Liestal, Switzerland.
authors.forename: Werner
authors.initials: W
authors.lastname: Zimmerli
authors.affiliation: University Department of Medicine, Kantonsspital Aarau, Aarau, Switzerland; Medical Faculty of the University of Basel, Basel, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Mueller
authors.affiliation: University Department of Medicine, Kantonsspital Aarau, Aarau, Switzerland; Medical Faculty of the University of Basel, Basel, Switzerland. Electronic address: Schuetzph@gmail.com.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
mesh_terms: D053607:Adrenomedullin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002116:Calcitonin / Q000097:blood; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D015897:Comorbidity; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007958:Leukocyte Count; D018448:Models, Immunological; D009026:Mortality; D009765:Obesity / Q000097:blood / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D011014:Pneumonia / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D012306:Risk; D012720:Severity of Illness Index; D016019:Survival Analysis; D013557:Switzerland / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin; D002116:Calcitonin; D002097:C-Reactive Protein
keywords: Inflammation; Obesity paradox; Pneumonia