Publications (2)13.11 Total impact
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Article: Dose-response effects of TPI ASM8 in asthmatics after allergen.
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ABSTRACT: TPI ASM8 contains two modified antisense oligonucleotides (AON) targeting the beta subunit (β(c) ) of the IL-3, IL-5, GM-CSF receptors and the chemokine receptor CCR3. A previous study suggested that TPI ASM8 had broader effects than just inhibition of eosinophils in asthmatics. We assessed whether TPI ASM8 caused a dose-dependent attenuation in the inflammatory and physiological changes after inhaled allergen challenge (AIC). This single-center, open-label, stepwise-ascending dose study was conducted in fourteen stable, mild allergic asthmatics. Following placebo AIC, subjects underwent AIC after 4 days treatment with 1, 2, and 4 mg BID and finally 8 mg once daily (OD) of TPI ASM8, inhaled via the I-Neb™ nebuliser. Treatments were separated by 2-3-week washout periods. TPI ASM8 was safe and well tolerated at all doses. TPI ASM8 8 mg OD reduced eosinophils in sputum after AIC (by 60.9% at 7 h and 68.4% at 24 h post-AIC, P=0.016 and P=0.007, respectively). Additionally, TPI ASM8 8 mg OD significantly attenuated the early and late airway responses as shown by the reduction in the area under the curve by 45% (P=0.016) and 59%, (P=0.0015), respectively, the increase in eosinophil cationic protein (ECP) by up to 57% (P=0.021), and airway responsiveness to methacholine by more than 1 doubling dose (P=0.012). A dose-response relationship was noted, and efficacy was maintained with once per day administration. TPI ASM8 attenuated a broad range of inflammatory and physiological changes after AIC, suggesting that CCR3, IL-3, and GM-CSF also are important targets for the management of asthma.Allergy 05/2011; 66(9):1242-8. · 6.27 Impact Factor -
Article: Randomised controlled trial of weightlifting exercise in patients with chronic airflow limitation.
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ABSTRACT: BACKGROUND PATIENTS: with chronic airflow obstruction are often limited by muscle fatigue and weakness. As exercise rehabilitation programmes have produced modest improvements at best a study was designed to determine whether specific muscle training techniques are helpful. Thirty four patients with chronic airflow limitation (forced expiratory volume in one second (FEV1) 38% of predicted values) were stratified for FEV1 to vital capacity (VC) ratio less than 40% and arterial oxygen desaturation during exercise and randomised to a control or weightlifting training group. In the experimental group training was prescribed for upper and lower limb muscles as a percentage of the maximum weight that could be lifted once only. It was carried out three times a week for eight weeks. Three subjects dropped out of each group; results in the remaining 14 patients in each group were analysed. Adherence in the training group was 90%. In the trained subjects muscle strength and endurance time during cycling at 80% of maximum power output increased by 73% from 518 (SE69) to 898 (95) s, with control subjects showing no change (506 (86) s before training and 479 (89) s after training). No significant changes in maximum cycle ergometer exercise capacity or distance walked in six minutes were found in either group. Responses to a chronic respiratory questionnaire showed significant improvements in dyspnoea and mastery of daily living activities in the trained group. Weightlifting training may be successfully used in patients with chronic airflow limitation, with benefits in muscle strength, exercise endurance, and subjective responses to some of the demands of daily living.Thorax 03/1992; 47(2):70-5. · 6.84 Impact Factor
