Effect of inspiratory pressure support on exercise performance in patients with chronic obstructive pulmonary disease

Title: Effect of inspiratory pressure support on exercise performance in patients with chronic obstructive pulmonary disease. Purpose: This study examined the effects of a non-invasive ventilator on submaximal and maximal exercise performance in patients with chronic obstructive pulmonary disease (COPD). Methods: Fourteen men (66.0 ± 7.4yr) and six women (59.0 ± 7.4yr) with a diagnosis of COPD, a forced expiratory volume! (FEVi) <40%, and the ability to tolerate 12 cmH20 of pressure on a non- invasive ventilator performed two maximal exercise tests on a cycle ergometer, with and without ventilatory assistance prior to exercise. Blood samples, respiratory metabolic measures, heart rate and rating of perceived exertion (RPE) were obtained throughout each exercise test. Results: Peak work rate (W), total exercise time, and respiratory rate were higher (p<0.05) when exercise was preceded by ventilatory support compared to no support. There was no difference in peak oxygen uptake (V02), carbon dioxide (VC02,), heart rate (HR), minute ventilation (VE), tidal volume (VT), blood lactate or RPE between the two experimental conditions. A total of 12 subjects completed at least 5 stages of the exercise protocol, and their physiological response during exercise with NIV and without NIV were compared. RPE was significantly lower during the first 3 min in the NIV condition than the no NIV condition. Circulating levels of blood lactate were lower (p<0.01) during stage 3 in the NIV than the than no NIV condition. There was no difference in RR, VT, HR, %HR, VE, V 0 2and %V02 between the two experimental conditions during sub maximal exercise. Conclusions: Application of non-invasive ventilatory support prior to exercise improves maximal exercise performance, but has no effect on cardio-metabolic response during submaximal exercise in patients with COPD

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Effect of inspiratory pressure support on exercise performance in patients with chronic obstructive pulmonary disease

Title: Effect of inspiratory pressure support on exercise performance in patients with chronic obstructive pulmonary disease. Purpose: This study examined the effects of a non-invasive ventilator on submaximal and maximal exercise performance in patients with chronic obstructive pulmonary disease (COPD). Methods: Fourteen men (66.0 ± 7.4yr) and six women (59.0 ± 7.4yr) with a diagnosis of COPD, a forced expiratory volume! (FEVi) <40%, and the ability to tolerate 12 cmH20 of pressure on a non- invasive ventilator performed two maximal exercise tests on a cycle ergometer, with and without ventilatory assistance prior to exercise. Blood samples, respiratory metabolic measures, heart rate and rating of perceived exertion (RPE) were obtained throughout each exercise test. Results: Peak work rate (W), total exercise time, and respiratory rate were higher (p<0.05) when exercise was preceded by ventilatory support compared to no support. There was no difference in peak oxygen uptake (V02), carbon dioxide (VC02,), heart rate (HR), minute ventilation (VE), tidal volume (VT), blood lactate or RPE between the two experimental conditions. A total of 12 subjects completed at least 5 stages of the exercise protocol, and their physiological response during exercise with NIV and without NIV were compared. RPE was significantly lower during the first 3 min in the NIV condition than the no NIV condition. Circulating levels of blood lactate were lower (p<0.01) during stage 3 in the NIV than the than no NIV condition. There was no difference in RR, VT, HR, %HR, VE, V 0 2and %V02 between the two experimental conditions during sub maximal exercise. Conclusions: Application of non-invasive ventilatory support prior to exercise improves maximal exercise performance, but has no effect on cardio-metabolic response during submaximal exercise in patients with COPD

Natural exposure of horses to mosquito-borne flaviviruses in South-East Queensland, Australia

In 2011 an unprecedented epidemic of equine encephalitis occurred in south-eastern (SE) Australia following heavy rainfall and severe flooding in the preceding 2-4 months. Less than 6% of the documented cases occurred in Queensland, prompting the question of pre-existing immunity in Queensland horses. A small-scale serological survey was conducted on horses residing in one of the severely flood-affected areas of SE-Queensland. Using a flavivirus-specific blocking-ELISA we found that 63% (39/62) of horses older than 3 years were positive for flavivirus antibodies, and of these 18% (7/38) had neutralizing antibodies to Murray Valley encephalitis virus (MVEV), Kunjin virus (WNVKUN) and/or Alfuy virus (ALFV). The remainder had serum-neutralizing antibodies to viruses in the Kokobera virus (KOKV) complex or antibodies to unknown/untested flaviviruses. Amongst eight yearlings one presented with clinical MVEV-encephalomyelitis, while another, clinically normal, had MVEV-neutralizing antibodies. The remaining six yearlings were flavivirus antibody negative. Of 19 foals born between August and November 2011 all were flavivirus antibody negative in January 2012. This suggests that horses in the area acquire over time active immunity to a range of flaviviruses. Nevertheless, the relatively infrequent seropositivity to MVEV, WNVKUN and ALFV (15%) suggests that factors other than pre-existing immunity may have contributed to the low incidence of arboviral disease in SE-Queensland horses during the 2011 epidemic

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society