哮喘和慢性阻塞性肺疾病中的小气道疾病七大支柱-为新疗方法提供机遇
2021/05/26
摘要
对早期和轻度阻塞性肺疾病的病理改变的识别揭示了小气道的重要性及其与临床症状的关系。事实上，在常规肺活量测定技术检测到任何明显的气道阻塞之前，已经发现了明显的小气道功能障碍。然而，大多数治疗阻塞性肺病的方法都是针对慢性肺病引起的生理改变和相关临床症状，而不是直接针对气流受限的特定潜在原因或疾病进展的驱动因素。此外，虽然肺活量测定是目前诊断和监测治疗反应的标准，但最广泛使用的测量指标，即第1秒用力呼气量，与早期或轻度疾病的病理变化并不一致，也与个别患者的症状或加重频率不一致。新的功能和成像技术可以更有效地评估小气道功能障碍；然而，我们的理解仍然存在重大差距。提高我们对小气道功能障碍在气道早期疾病中的作用的认识，同时确定新的终端来测量该区域的亚临床变化，即那些未被定义为临床症状或通过标准FEV1确定的变化，可能催生新的直接针对早期气道疾病过程来减缓疾病进展和逆转损害的治疗方法。本专家意见书将讨论哮喘和慢性阻塞性肺疾病背景下的小气道疾病，并强调阻碍早期识别阻塞性肺病的现有认知差距，以及用于临床试验的新的小气道特异性终端的开发和标准化。
Seven Pillars of Small Airways Disease in Asthma and COPD - Supporting Opportunities for Novel Therapies
Omar S Usmani, MeiLan K Han, David A Kaminsky, James Hogg, Josephine Hjoberg, Naimish Patel, Megan Hardin, Christina Keen, Stephen Rennard, François-Xavier Blé, Mary N Brown
Abstract
Identification of pathological changes in early and mild obstructive lung disease has revealed the importance of the small airways and their contribution to symptoms. Indeed, significant small airways dysfunction has been found before any overt airway obstruction is detectable by conventional spirometry techniques. However, most therapies for the treatment of obstructive lung disease target the physiological changes and associated symptoms that result from chronic lung disease, rather than directly targeting the specific underlying causes of airflow disruption or the drivers of disease progression. In addition, while spirometry is the current standard for diagnosis and monitoring of response to therapy, the most widely used measure, forced expiratory volume in 1 second, does not align with the pathological changes in early or mild disease and may not align with symptoms or exacerbation frequency in individual patient. Newer functional and imaging techniques allow more effective assessment of small airways dysfunction; however, significant gaps in our understanding remain. Improving our knowledge of the role of small airways dysfunction in early disease in the airways, along with the identification of novel endpoints to measure sub-clinical changes in this region, i.e. those not captured as symptoms or identified through standard FEV1, may lead to the development of novel therapies that directly combat early airways disease processes with a view to slowing disease progression and reversing damage. This expert opinion paper will discuss small airways disease in the context of asthma and COPD and highlight gaps in current knowledge that impede earlier identification of obstructive lung disease and the development and standardization of novel small airways-specific endpoints for use in clinical trials.
对早期和轻度阻塞性肺疾病的病理改变的识别揭示了小气道的重要性及其与临床症状的关系。事实上，在常规肺活量测定技术检测到任何明显的气道阻塞之前，已经发现了明显的小气道功能障碍。然而，大多数治疗阻塞性肺病的方法都是针对慢性肺病引起的生理改变和相关临床症状，而不是直接针对气流受限的特定潜在原因或疾病进展的驱动因素。此外，虽然肺活量测定是目前诊断和监测治疗反应的标准，但最广泛使用的测量指标，即第1秒用力呼气量，与早期或轻度疾病的病理变化并不一致，也与个别患者的症状或加重频率不一致。新的功能和成像技术可以更有效地评估小气道功能障碍；然而，我们的理解仍然存在重大差距。提高我们对小气道功能障碍在气道早期疾病中的作用的认识，同时确定新的终端来测量该区域的亚临床变化，即那些未被定义为临床症状或通过标准FEV1确定的变化，可能催生新的直接针对早期气道疾病过程来减缓疾病进展和逆转损害的治疗方法。本专家意见书将讨论哮喘和慢性阻塞性肺疾病背景下的小气道疾病，并强调阻碍早期识别阻塞性肺病的现有认知差距，以及用于临床试验的新的小气道特异性终端的开发和标准化。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Chest. 2021 Apr 2;S0012-3692(21)00660-7. doi: 10.1016/j.chest.2021.03.047.)
(Chest. 2021 Apr 2;S0012-3692(21)00660-7. doi: 10.1016/j.chest.2021.03.047.)
Seven Pillars of Small Airways Disease in Asthma and COPD - Supporting Opportunities for Novel Therapies
Omar S Usmani, MeiLan K Han, David A Kaminsky, James Hogg, Josephine Hjoberg, Naimish Patel, Megan Hardin, Christina Keen, Stephen Rennard, François-Xavier Blé, Mary N Brown
Abstract
Identification of pathological changes in early and mild obstructive lung disease has revealed the importance of the small airways and their contribution to symptoms. Indeed, significant small airways dysfunction has been found before any overt airway obstruction is detectable by conventional spirometry techniques. However, most therapies for the treatment of obstructive lung disease target the physiological changes and associated symptoms that result from chronic lung disease, rather than directly targeting the specific underlying causes of airflow disruption or the drivers of disease progression. In addition, while spirometry is the current standard for diagnosis and monitoring of response to therapy, the most widely used measure, forced expiratory volume in 1 second, does not align with the pathological changes in early or mild disease and may not align with symptoms or exacerbation frequency in individual patient. Newer functional and imaging techniques allow more effective assessment of small airways dysfunction; however, significant gaps in our understanding remain. Improving our knowledge of the role of small airways dysfunction in early disease in the airways, along with the identification of novel endpoints to measure sub-clinical changes in this region, i.e. those not captured as symptoms or identified through standard FEV1, may lead to the development of novel therapies that directly combat early airways disease processes with a view to slowing disease progression and reversing damage. This expert opinion paper will discuss small airways disease in the context of asthma and COPD and highlight gaps in current knowledge that impede earlier identification of obstructive lung disease and the development and standardization of novel small airways-specific endpoints for use in clinical trials.
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固有淋巴细胞记忆的分子和表观遗传学机制及其与哮喘的关系
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哮喘患者诱导痰中巨噬细胞的多样性和活化：对疾病严重程度和炎症表型的作用
