Association of the 1580 (C/T) Polymorphism in the Surfactant Protein B Gene with the Severity of Respiratory Failure after Allogeneic Transplantation.

Respiratory failure is a serious early complication confounding the clinical effect of allogeneic stem cell transplantation and early detection may be crucial for efficient treatment. We introduced a system of intensive oxigenation monitoring in patients transplanted in our center between November 2001 and December 2003. All allogeneic transplanted patients were followed by a twice daily measurement of oxi-index (paO₂/FiO₂) during the transplantation period (untill day + 25). Patients that fulfilled criteria of acute lung injury (oxi-index <300) were treated by O₂ application vs. non-invasive ventilation (NIV). Failure to increase oxi-index above the threshold of 300 led to referral of the patient to ICU were intensified NIV was applied and/or mechanical ventilation (MV) was initiated based on a defined scoring system. 165 patients were followed for the development of ALI. 48 (29.1%) developed oxiindices <300 (ALI). Development of ALI predicted for a significantly higher rate of ICU admissions (37.5% vs. 6.8% in non-ALI patients; p<0.001) and MV (20.8 % vs. 1.7 in non-ALI patients; p<0.001). ALI was most commonly diagnosed during the engraftment period but was at diagnosis not associated with other criteria like respiration rate, CRP and tachycardia. Since members of the pulmonary innate immune system may be associated with the development of ALI and ARDS we screened the 165 patients for the presence of alternative alleles in the Surfactant Protein B (SP-B) gene. A polymorphism at position +1580 (T/C variation) of SP-B has been previously found to be associated with the development of ARDS. Polymorphism of SP-B were not associated with the development of ALI and did not predict for the need of intensified ICU treatment. However, the rate of MV varied considerably. Nine patients with the T/T genotype (9 out of 42, 21.4%) required intubation and mechanical ventilation whereas none of the patients with C/C had to receive MV (0 out of 30; p=0.01).The data indicate that measurement of the oxiindex is an early sensitive parameter of respiratory failure in allogeneic transplantation and that severity of respiratory damage may be predicted by the T allele at the SP-B +1580 site