Price David, Chisholm Alison, Ryan Dermot, Crockett Alan, Jones Rupert
Research in Real Life Ltd, Old Winery Business Park, Cawston, Norwich, UK.
Prim Care Respir J. 2010 Dec;19(4):342-51. doi: 10.4104/pcrj.2010.00066.
Therapeutic interventions in chronic obstructive pulmonary disease (COPD) shown to reduce exacerbations include smoking cessation, vaccination and appropriate pharmacological therapy. Long-acting bronchodilators are the cornerstone of COPD pharmacotherapy, whereas inhaled corticosteroids and mucolytics have shown benefit in subgroups of patients. Despite management with existing therapies, clinical trials confirm the persistent nature of exacerbations throughout the course of the disease. Roflumilast - a phosphodiesterase-4 (PDE4) inhibitor - received European Marketing Approval in 2010 and represents a new class of drug in the management of COPD. Through selective inhibition of the PDE4 enzyme, roflumilast prevents the breakdown of cyclic AMP, which plays an important role in regulating inflammatory cell activity. Early trials in patients with a forced expiratory volume in one second (FEV1) less than 50% predicted suggest that roflumilast offers sustained and significant improvement in lung function and a reduction in exacerbations compared with placebo, irrespective of concomitant bronchodilator therapy. Common adverse events include headache, diarrhoea and weight loss, with the majority occurring at the beginning of treatment, being transient and not leading to sequelae. Serious adverse events tended to be low across all studies. Roflumilast is currently licensed in Europe, and is indicated as maintenance treatment in severe COPD (i.e. in patients with post-bronchodilator FEV1 <50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as an add-on to bronchodilator treatment. Clear identification of patients eligible for roflumilast will require improved characterisation and phenotyping of patients in primary care, including lung function measurement, accurate health status classification, and recording of chronic cough and regular sputum production.
已证实可减少慢性阻塞性肺疾病(COPD)急性加重的治疗干预措施包括戒烟、接种疫苗和适当的药物治疗。长效支气管扩张剂是COPD药物治疗的基石,而吸入性糖皮质激素和黏液溶解剂已在部分患者亚组中显示出益处。尽管采用现有疗法进行管理,但临床试验证实了疾病全过程中急性加重的持续性。罗氟司特——一种磷酸二酯酶-4(PDE4)抑制剂——于2010年获得欧洲上市许可,代表了COPD管理中的一类新型药物。通过选择性抑制PDE4酶,罗氟司特可防止环磷腺苷(cAMP)分解,而环磷腺苷在调节炎症细胞活性中起重要作用。对一秒用力呼气容积(FEV1)低于预计值50%的患者进行的早期试验表明,与安慰剂相比,罗氟司特可使肺功能得到持续且显著的改善,并减少急性加重,无论是否同时使用支气管扩张剂治疗。常见不良事件包括头痛、腹泻和体重减轻,大多数发生在治疗开始时,为一过性,不会导致后遗症。在所有研究中,严重不良事件的发生率往往较低。罗氟司特目前在欧洲获得许可,适用于有频繁急性加重病史的成年患者中与慢性支气管炎相关的重度COPD(即支气管扩张剂治疗后FEV1<预计值50%的患者),作为支气管扩张剂治疗的附加维持治疗。明确识别适合使用罗氟司特的患者需要在初级保健中对患者进行更好的特征描述和表型分析,包括肺功能测量、准确的健康状况分类以及慢性咳嗽和咳痰情况的记录。