Impact on patients' health status following early identification of a COPD exacerbation.

The current study aimed to assess the impact on patient health status during an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 421 COPD patients were enrolled in a multicentre, single-arm study with a 6-month observational follow-up period. Patients received two inhalations of Symbicort 200 Turbuhaler(R) twice a day. Patients were assessed before the run-in period, at baseline and at 1, 3 and 6 months. Patients were instructed to report a change in respiratory symptoms lasting >24 h. This defined an AECOPD. In addition to the initial call, the St George's Respiratory Questionnaire (SGRQ), COPD Control Questionnaire (CCQ), Medical Research Council (MRC) dyspnoea scale and activities of daily living (ADL) were completed at 5-7 and 12-14 days. A group of 176 patients reported at least one AECOPD. Exacerbations were associated with statistically significant mean changes (worsening) in the SGRQ activity and impact domains at onset (mean +/- sd 12.1 +/- 18.1 and 14.0 +/- 15.2), during the first (9.8 +/- 19.0 and 9.4 +/- 16.6) and second weeks (3.1 +/- 15.5 and 3.3 +/- 14.7). Clinically significant deterioration in SGRQ impact scores was shown in 71% of patients following early identification, with 55 and 37% during the first and second weeks of an AECOPD, respectively. Acute exacerbation severely impacts on health status. The current study provides valuable information on the change in health status during an acute exacerbation of chronic obstructive pulmonary disease that can be utilised for future trials that evaluate therapeutic intervention.

Inter-operator variation in ELISPOT analysis of measles virus-specific IFN-gamma-secreting T cells.

The ELISPOT assay is a highly sensitive technique used for the detection of individual cytokine releasing cells. We have developed an IFN-gamma ELISPOT assay utilizing unfractionated frozen peripheral blood mononuclear cells (PBMC) to quantify the frequency of measles virus (MV)-specific IFN-gamma-secreting T cells in 117 healthy children who had been previously immunized with two doses of the measles-mumps-rubella vaccine. We have also estimated the variability associated with the quantification of ELISPOT plates and compared the number of MV-specific IFN-gamma-secreting T cells for each subject as determined by two different operators of an ELISPOT reader. The median frequency of MV-specific IFN-gamma-producing memory T cells detected by this assay was 0.005 % and 0.01 % as determined by an in-house and commercial operator, respectively. Although we found a significant correlation (r = 0.83, p<0.0001) between the number of spots counted by the commercial and in-house operators of an ELISPOT reader, the median number of spots counted by the commercial operator was twice the number of spots counted by an in-house operator (p<0.001). This demonstrates the importance of using a common ELISPOT reader and operator, among other parameters, to quantify the number of spots when a large volume of plates are being scanned and analyzed.

Lack of association between transporter associated with antigen processing (TAP) and HLA-DM gene polymorphisms and antibody levels following measles vaccination.

The transporter associated with antigen processing (TAP) and human leukocyte antigen-DM (HLA-DM) genes are involved in the antigen-processing pathway of both HLA class I and class II-restricted antigen presentation. We hypothesized that polymorphisms within the TAP and DM genes may influence antibody levels following measles vaccination. We examined TAP and DM polymorphisms in 242 school children from Olmsted County, Minnesota, USA who received one dose of measles-mumps-rubella-II (MMR-II) vaccine at the age of 15 months. Based on the level of serum measles-specific immunoglobulin G (IgG) antibodies, subjects were classified as seronegatives (n = 72) or seropositives (n = 170). We determined TAP1 and TAP2 allele types by polymerase chain reaction (PCR) amplification of specific alleles (PASA) and determined DM allele type by PCR amplification followed by direct sequencing of the polymorphic sites. We analysed the data for any TAP or DM allelic association with antibody levels post measles vaccination using the chi-square test and univariate linear regression analysis. We found no trend in the overall distribution of TAP and DM genotype frequencies between seronegative and seropositive subjects, suggesting that TAP and DM polymorphism and antibody levels following measles vaccination are not directly associated. In addition, we did not find an association between TAP (TAP1, P = 0.71; TAP2, P = 0.87) or DM (DMA, P = 0.42; DMB, P = 0.71) homozygosity and seronegativity to measles vaccine in this study group. Our study suggests that TAP and DM gene polymorphisms do not influence antibody levels post measles vaccination.