Anti-JC Virus Antibody Prevalence in Canadian MS Patients.

BACKGROUND: Anti-John Cunningham (JCV) antibodies have been detected in approximately 50% to 60% of multiple sclerosis (MS) patients. Age, sex, and geographic location have been associated with seroprevalence differences. We describe anti-JCV antibody prevalence in the Canadian cohort of patients enrolled in the JCV Epidemiology in MS study. METHODS: This cross-sectional multicenter study evaluated the effects of demographic and disease characteristics on anti-JCV antibody seroprevalence in MS patients irrespective of disease type and treatment. A single blood sample was collected for analysis of anti-JCV antibodies using a two-step enzyme-linked immunosorbent assay (ELISA). Chi-square and logistic regression tests were used to determine significance. RESULTS: A total of 4198 Canadian MS patients participated in the study; the overall anti-JCV antibody prevalence was 56.3% (95% confidence interval: 54.8% to 57.8%). Seroprevalence was significantly associated with age (increasing from 45% in young to 61% in those >60 years), sex, and region (p<0.0001 for age and sex; p=0.005 for region). No significant differences in anti-JCV antibody prevalence were associated with race, MS disease type and duration, or number and duration of treatments. Immunosuppressant use was associated with a higher seroprevalence rate (63.4%) compared with no immunosuppressant use (55.9%; p=0.040). CONCLUSIONS: Canadian MS patients had an overall anti-JCV antibody seroprevalence that was consistent with previous studies using the two-step ELISA. Significant associations of anti-JCV antibody positivity were found with age, sex, region, and immunosuppressant therapy, whereas seroprevalence was not associated with race, MS type, MS duration, or number or duration of MS treatments.

Effects of hydrofluoroalkane and dry powder-formulated corticosteroids on sputum inflammatory markers in asthmatic patients.

BACKGROUND: Inhaled corticosteroids are powerful drugs that can suppress airway inflammation in asthmatic patients. Deposition of most of the inhaled corticosteroid occurs mainly in the central airways. However, a new hydrofluoroalkane formulation of beclomethasone dipropionate (HFA-BDP) is preferentially deposited in the distal airways. Inflammatory characteristics of induced sputum have been shown to differ in samples collected early after sputum induction compared with later. OBJECTIVE: To compare the effects of HFA-BDP and budesonide in a dry powder inhaler (DPI-BUD) on inflammatory cells and inflammatory cytokine expression in early and late induced sputa compared with placebo. METHODS: Seventeen patients with mild, intermittent bronchial asthma were randomly assigned to two treatment groups: eight patients received HFA-BDP and nine patients received DPI-BUD. Each patient was treated with one of the active treatments and placebo (for four weeks), with a two-week washout interval in between. Inflammatory cells and expression of interleukin (IL)-4 and IL-5 were measured in early and late induced sputa before and after active treatment, as well as before and after placebo treatment using immunocytochemistry and in situ hybridization. RESULTS: Compared with placebo, eosinophils were significantly reduced in both early and late induced sputa after HFA-BDP treatment (P<0.05), whereas DPI-BUD had a significant effect only on early induced sputum. Both HFA-BDP and DPI-BUD decreased IL-4 expression in early and late induced sputa, but the effect was more prominent with HFA-BDP. IL-5 expression was reduced in both early and late induced sputa after HFA-BDP treatment. DPI-BUD significantly decreased IL-5 expression in early but not in late induced sputum. The number of lymphocytes was not altered by either treatment. CONCLUSIONS: HFA-BDP reduced eosinophilic inflammation and T helper 2-type cytokine expression in both early and late induced sputa, whereas the effect of DPI-BUD on inflammation was predominantly demonstrated in early induced sputum.

The delivery of chlorofluorocarbon-propelled versus hydrofluoroalkane-propelled beclomethasone dipropionate aerosol to the mechanically ventilated patient: a laboratory study.

UNLABELLED: We describe a laboratory investigation comparing the delivery of chlorofluorocarbon (CFC)- and hydrofluoroalkane (HFA)-formulated beclomethasone dipropionate (BDP) by metered-dose inhaler and holding chamber (AeroChamber HC MV) in a simulation of a mechanically ventilated adult patient. METHODS: We equipped each HC MV (n = 5) with an 8.0 mm diameter endotracheal tube (ETT), locating the HC MV in the inspiratory limb of a breathing circuit linked to a mechanical ventilator set to simulate tidal breathing at tidal volume = 830 mL, respiratory rate = 15 breaths/min, inspiratory-expiratory ratio of 1:2.1, peak inspiratory pressure = 20 cm H(2)O. Temperature and humidity settings were 35+/-1 degrees C and 100% relative humidity (close to body conditions). We compared delivery of 5-actuations of CFC- and HFA-BDP (both 50 microg/actuation), measuring total emitted mass captured by a filter at the distal end of the ETT. In a separate study, we inserted the distal end of the ETT within the entry cone of a cascade impactor so that the aerosol particle size distribution could be determined with the circuit at similar environmental conditions as described previously. We made benchmark measurements with circuit temperature and humidity at room ambient conditions (21+/-1 degrees C and 54+/-5% RH respectively). RESULTS: Total emitted mass (5 measurements/device) was significantly greater for HFA-BDP (14.1+/-1.1 microg/actuation) compared with CFC-BDP (2.4+/-0.8 microg/actuation) (paired t test, p < 0.001). More HFA-BDP (2.7 +/- 0.2 microg/actuation) was lost from the delivery system during exhalation (0.9 +/- 0.4 microg/actuation for CFC-BDP) (p < 0.001). The mass median aerodynamic diameter (MMAD) increased from 1.2 microm (room ambient) to 2.8 microm (higher temperature and humidity conditions) for HFA-BDP. In contrast, MMAD for CFC-BDP remained close to 4.6 microm under either condition, but particles finer than about 4.0 microm increased in size when the circuit was saturated. CONCLUSIONS: Total emitted mass for HFA-BDP was increased by a factor of 5.8 compared with CFC-BDP, due largely to the finer particle size distribution of the HFA-based solution formulation. Additional water vapor required to operate the breathing circuit at close to body conditions resulted in fine particle growth with both formulations.