Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management.
Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management.
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DOI：
10.1016/s0140-6736(15)60693-6
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发表时间：
2015-05-02
期刊：
影响因子：
--
通讯作者：
Martinez FJ
中科院分区：
文献类型：
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作者：
Woodruff PG;Agusti A;Roche N;Singh D;Martinez FJ
慢性阻塞性肺疾病（COPD）是一种常见、复杂和异质性的疾病，在全球范围内造成了相当大且不断增长的发病率、死亡率和医疗费用。为了解释COPD的复杂性，我们必须鉴定具有相似临床特征、预后和/或治疗需求的患者组，即所谓的临床表型。这种策略对于研究来说是合乎逻辑的，但它可能具有有限的临床价值，因为临床表型可能在同一患者中重叠，并且相同的临床表型可能由不同的生物学机制引起。为了使评估与治疗选择相匹配，GOLD的最新迭代将治疗目标重新组织为两类（改善症状，即，呼吸困难和健康状况，并降低未来的风险，如FEV 1水平和急性加重史所预测的），从而更接近使用目前可用的支气管扩张剂和抗炎药物的个体化药物。然而，未来的治疗选择可能包括靶向内型，其反映了由不同病理生理机制定义的患者亚型。这些内型的特异性生物标志物对于临床实践将是特别有用的，特别是当单独的临床表型不足以鉴定潜在的内型时。目前，已经提出了一系列有限的潜在COPD内源性和生物标志物。我们将从针对特定炎症通路的新兴药物在COPD中的概念验证试验中获得经验性知识。在每种情况下，这些试验的成功可能需要特定的内分型和生物标志物的努力，因为这些途径可能只在一部分患者中有效。人类疾病的网络分析提供了更好地了解疾病病理生物学复杂性的可能性，同时促进了新的治疗方案的开发，重要的是，对复杂疾病进行了重新分类。所有这些发展都为COPD的临床个性化治疗铺平了道路。
Chronic obstructive pulmonary disease (COPD) is a common, complex and heterogeneous condition which is responsible for considerable and growing morbidity, mortality and healthcare expense worldwide. In order to decipher the complexity of COPD, it is imperative that we identify groups of patients with similar clinical characteristics, prognosis and/or therapeutic needs, so called clinical phenotypes. This strategy is logical for research but it may be of limited clinical value because clinical phenotypes may overlap in the same patient and the same clinical phenotype could result from different biological mechanisms. With the goal of matching assessment to treatment choices, the most recent iteration of GOLD reorganized treatment objectives into two categories (improving symptoms, i.e., dyspnoea and health status, and decreasing future risk, as predicted by FEV1 level and exacerbations history), thus moving closer to individualized medicine using currently available bronchodilators and anti-inflammatory medications. Yet, future therapeutic options are likely to include targeting endotypes which reflect subtypes of patients defined by a distinct pathophysiological mechanism. Specific biomarkers of these endotypes would be particularly useful for clinical practice, especially when clinical phenotype alone is insufficient to identify the underlying endotype. Currently, a limited series of potential COPD endotypes and biomarkers have been suggested. We will gain empiric knowledge from proof of concept trials in COPD with emerging drugs that target specific inflammatory pathways. In each instance, specific endotyping and biomarker efforts will likely be required for success of these trials, since the pathways are likely to be operative in only a subset of patients. Network analysis of human diseases offers the possibility of a better understanding of disease patho-biologic complexity while facilitating the development of new therapeutic alternatives and, importantly, a reclassification of complex diseases. All these development should pave the way towards personalized treatment of COPD in the clinic.