BACKGROUND: Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia. METHODS: The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination. RESULTS: A total of 111 patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype. CONCLUSIONS: The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia.
BACKGROUND: Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia. METHODS: The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination. RESULTS: A total of 111 patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype. CONCLUSIONS: The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia.
Authors: S Idell; K K James; E G Levin; B S Schwartz; N Manchanda; R J Maunder; T R Martin; J McLarty; D S Fair Journal: J Clin Invest Date: 1989-08 Impact factor: 14.808
Authors: A Sapru; J G Zaroff; L Pawlikowska; K D Liu; K K Khush; L A Baxter-Lowe; V Hayden; R L Menza; M Convery; V Lo; A Poon; H Kim; W L Young; J Kukreja; M A Matthay Journal: Am J Transplant Date: 2012-03-05 Impact factor: 8.086
Authors: Krisztina Madách; István Aladzsity; Agnes Szilágyi; George Fust; János Gál; István Pénzes; Zoltán Prohászka Journal: Crit Care Date: 2010-04-29 Impact factor: 9.097
Authors: Nuala J Meyer; Zhongyin John Daye; Melanie Rushefski; Richard Aplenc; Paul N Lanken; Michael G S Shashaty; Jason D Christie; Rui Feng Journal: BMC Med Genet Date: 2012-06-28 Impact factor: 2.103
Authors: Esther K Wolthuis; Alexander P J Vlaar; Jorrit-Jan H Hofstra; Joris J T H Roelofs; Vivian de Waard; Nicole P Juffermans; Marcus J Schultz Journal: Crit Care Res Pract Date: 2011-07-14
Authors: Jason D Christie; Mark M Wurfel; Rui Feng; Grant E O'Keefe; Jonathan Bradfield; Lorraine B Ware; David C Christiani; Carolyn S Calfee; Mitchell J Cohen; Michael Matthay; Nuala J Meyer; Cecilia Kim; Mingyao Li; Joshua Akey; Kathleen C Barnes; Jonathan Sevransky; Paul N Lanken; Addison K May; Richard Aplenc; James P Maloney; Hakon Hakonarson Journal: PLoS One Date: 2012-01-25 Impact factor: 3.240