Asthma and COPD are two chronic inflammatory disorders of the airway characterized by airflow limitation. While many similarities exist between these two diseases, they are pathologically distinct due to the involvement of different inflammatory cells; predominantly neutrophils, CD8 lymphocytes in COPD and eosinophils and CD4 lymphocytes in asthma. Cigarette smoking is associated with accelerated decline of lung function, increased mortality, and worsening of symptoms in both asthma and COPD. Furthermore, exposure to cigarette smoke can alter the inflammatory mechanisms in asthma to become similar to that seen in COPD with increasing CD8 cells and neutrophils and may therefore alter the response to therapy. Cigarette smoke exposure has been associated with a poor response to inhaled corticosteroids which are recommended as first line anti-inflammatory medications in asthma and as an add-on therapy in patients with severe COPD with history of exacerbations. While the main proposed mechanism for this altered response is the reduction of the histone deacetylase 2 (HDAC2) enzyme system, other possible mechanisms include the overexpression of GR-β, activation of p38 MAPK pathway and increased production of inflammatory cytokines such as IL-2, 4, 8, TNF-α and NF-Kß. Few clinical trials suggest that leukotriene modifiers may be an alternative to corticosteroids in smokers with asthma but there are currently no drugs which effectively reduce the progression of inflammation in smokers with COPD. However, several HDAC2 enhancers including low dose theophylline and other potential anti-inflammatory therapies including PDE4 inhibitors and p38 MAPK inhibitors are being evaluated.
Aim : To compare the effects of propiverine and oxybutynin on ambulatory urodynamic monitoring (AUM) parameters, safety, and tolerability in patients with overactive bladder. Methods : This was a randomized, double-blind, placebo-controlled, multicentre, crossover study. Patients ( n = 77) received two of the following treatments during two 2-week periods: propiverine 20 mg once daily, propiverine 15 mg three times daily, oxybutynin 5 mg three times daily, and placebo. AUM parameters, salivary flow, visual near point, and heart rate were assessed. Results : A consistent order in the efficacy between active treatment groups was observed for the reduction in mean involuntary detrusor contractions (IDCs; oxybutynin 15 mg ≤ propiverine 45 mg ≤ propiverine 20 mg). Differences between the oxybutynin and propiverine 20 mg groups were statistically significant for several AUM endpoints. Statistically significant differences between the oxybutynin and both propiverine groups were also noted in salivary flow rate and heart rate (oxybutynin 15 mg < both propiverine regimens) and in heart rate variability (both propiverine regimens < oxybutynin 15 mg). All active treatments lengthened visual near point. The incidence of dry mouth was significantly more pronounced in the oxybutynin group than in either propiverine group. Treatment with propiverine 45 mg resulted in the highest rates of constipation, lengthening of the visual near point, and effects on heart rate. Conclusions : Oxybutynin 15 mg was more effective than propiverine 20 mg in reducing symptomatic and asymptomatic IDCs in ambulatory patients. The primary differences between the two drugs were the incidence and type of adverse events, which varied with the antimuscarinic receptor specificity of each agent.
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