Serum Activin A and B levels predict outcome in patients with acute respiratory failure — ASN Events

Serum Activin A and B levels predict outcome in patients with acute respiratory failure (#66)

David M De Kretser 1 , Jon G Bensley 1 , Ville Petilla 2 , Rita Linko 2 , Mark P Hedger 1 , Susan Hayward 1 , Robert I McLachlan 3 , Carolyn Allan 3 , Helen Ludlow 4 5 , David J Phillips 1
  1. Monash University, Clayton, Vic, Australia
  2. Helsinki University Hospital, Helsinki, Finland
  3. Prince Henrys Institute, Clayton, Victoria, Australia
  4. Oxford Brookes University, Oxford, UK
  5. Oxford Brookes University, Oxford, UK

Mortality is high in patients with Acute Respiratory Failure [ARF] and novel biomarkers are needed to predict patient outcomes and to guide potential future therapies. The activins A and B, and their binding protein, follistatin, proteins that regulate FSH secretion, have recently been shown to be important regulators of inflammation and fibrosis but no substantial data are available concerning their roles in ARF. We measured serum levels of activin A, B and follistatin, in 518 patients with ARF from the FINNALI study1 and compared their concentrations to those obtained in 138 normal subjects to form a reference range.

Serum activin A, B and follistatin were measured by specific assays and the results analyzed according to diagnostic groups as well as according to standard measures in intensive care. Multivariable logistic regression was used to create a model to predict death at 90 days and 12 months.

Serum activin A and B were significantly elevated in most patients and in most of the diagnostic groups. Patients who had activin A and/or B concentrations above the reference maximum were significantly more likely to die in the 12 months following admission [either activin A or B above reference maximum: Positive Likelihood Ratio [LR+] 1.65 [95%CI 1.28-2.12, P=0.00013]; both activin A and B above reference maximum: LR+ 2.78 [95%CI 1.96-3.95, P<0.00001]. The predictive model at 12 months had an overall accuracy of 80.2% [95%CI 76.6-83.3%].

The measurement of activin A and B levels in patients with ARF assists in predicting those at greatest risk of death. Given the existing data from animal studies linking high activin A levels to significant inflammatory challenges, the results from this study suggest that approaches to modulate activin A and B bioactivity should be explored as potential therapeutic agents.1 

  1. 1. Linko R et al Intensive Care Med 2009; 35:1352-61.