Newly Published
Critical Care Medicine  |   January 2019
Aquaporin 5 –1364A/C Promoter Polymorphism Is Associated with Pulmonary Inflammation and Survival in Acute Respiratory Distress Syndrome
Author Notes
  • From the Department of Anesthesia, Intensive Care Medicine, and Pain Therapy, University Hospital Knappschaftskrankenhaus Bochum, Bochum, Germany (T.R., K.R., M.A.); and Department of Anesthesia and Intensive Care Medicine, University Duisburg-Essen and University Hospital Essen, Essen, Germany (J.P., M.A.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • J.P. and M.A. contributed equally to this article.
    J.P. and M.A. contributed equally to this article.×
  • Submitted for publication May 13, 2018. Accepted for publication November 13, 2018.
    Submitted for publication May 13, 2018. Accepted for publication November 13, 2018.×
  • Correspondence: Address correspondence to Dr. Rahmel: Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, In der Schornau 23–25, D-44892 Bochum, Germany. Tim.Rahmel@ruhr-uni-bochum.de. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Critical Care Medicine / Critical Care / Infectious Disease / Respiratory System
Critical Care Medicine   |   January 2019
Aquaporin 5 –1364A/C Promoter Polymorphism Is Associated with Pulmonary Inflammation and Survival in Acute Respiratory Distress Syndrome
Anesthesiology Newly Published on January 3, 2019. doi:10.1097/ALN.0000000000002560
Anesthesiology Newly Published on January 3, 2019. doi:10.1097/ALN.0000000000002560
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • Acute respiratory distress syndrome is defined according to clinical criteria, but lack of precise characterization may contribute to negative trials and impede personalized care. Polymorphisms of aquaporin-5, a key mediator of inflammation, may impact outcome.

What This Article Tells Us That Is New:

  • In acute respiratory distress syndrome attributable to bacterial pneumonia, the C-allele of the aquaporin-5 –1364A/C promoter polymorphism is associated with less pulmonary inflammation and greater survival. This may improve characterization of acute respiratory distress syndrome and ultimately facilitate individualized care.

Background: The aquaporin-5 (AQP5) –1364A/C promoter single-nucleotide polymorphism is associated with an altered AQP5 expression and mortality in sepsis. Because AQP5 expression alters neutrophil cell migration, it could affect pulmonary inflammation and survival in bacterially evoked acute respiratory distress syndrome. Accordingly, the authors tested the hypotheses that the AC/CC genotype in patients with bacterially evoked pneumonia resulting in acute respiratory distress syndrome is associated with (1) attenuated pulmonary inflammation and (2) higher 30-day survival.

Methods: In this prospective, observational study, bronchoalveolar lavage and blood sampling were performed within 24 h of intensive care unit admission. In 136 Caucasian patients with bacterially evoked acute respiratory distress syndrome, genotype of the AQP5 –1364A/C promoter polymorphism, bronchoalveolar lavage total protein, albumin, white cell concentrations, and lactate dehydrogenase activity were measured to evaluate the relationship between genotypes and survival.

Results: AC/CC patients as well as survivors showed lower bronchoalveolar lavage protein (0.9 mg/ml vs. 2.3 mg/ml, P < 0.001 and 1.6 mg/ml vs. 2.6 mg/ml, P = 0.035), albumin (0.2 mg/ml vs. 0.6 mg/ml, P = 0.019 and 0.3 mg/ml vs. 0.6 mg/ml, P = 0.028), leukocytes (424 /ml vs. 1,430/ml; P = 0.016 and 768 /ml vs. 1,826/ml; P = 0.025), and lactate dehydrogenase activity (82 U/l vs. 232 U/l; P = 0.006 and 123 U/l vs. 303 U/l; P = 0.020). Thirty-day survival was associated with AQP5 –1364A/C genotypes (P = 0.005), with survival of 62% for AA genotypes (58 of 93) but 86% for C-allele carriers (37 of 43). Furthermore, multiple proportional hazard analysis revealed the AA genotype was at high risk for death within 30 days (hazard ratio, 3.53; 95% CI, 1.38 to 9.07; P = 0.009).

Conclusions: In acute respiratory distress syndrome attributable to bacterial pneumonia, the C-allele of the AQP5 –1364A/C promoter polymorphism is associated with an attenuated pulmonary inflammation and higher 30-day survival. Thus, the AQP5 genotype impacts on inflammation and prognosis in acute respiratory distress syndrome.