重症哮喘的生物学特性与气道重塑
2022/08/19
摘要
哮喘是一种慢性炎症性气道疾病，可导致气流阻塞，这在一定程度上对传统疗法来说是不可逆的，气道重塑的概念的典型表现。重症哮喘患者应用生物制剂已使先前认为不可逆的气流阻塞完全正常化。这强调了区分“固定”气流阻塞和“可逆”气流阻塞的必要性，前者是由于对当前治疗无反应的结构变化造成的，后者通过生物治疗期间的肺功能正常化证明，即使使用大剂量系统性糖皮质激素也无法获得。暴露于环境因素引发气道重塑的炎症反应的机制仍不完全清楚。警报素代表上皮源性细胞因子，可引发导致炎症性气道重塑的免疫事件。生物疗法可以通过解决这些气道炎症变化来改善气流阻塞。此外，生物制剂可能会阻止甚至恢复由于结构变化而导致的“固定”重塑。因此，区分生物制剂的治疗效果（早期和晚期），作为评估这些药物和未来治疗对重症哮喘气道重塑的影响的新范例，看来具有重要的临床意义。
Biologics and Airway Remodeling in Severe Asthma
Gilda Varricchi, Sebastian Ferri, Jack Pepys, Remo Poto, Giuseppe Spadaro, Nappi Emanuele, Giovanni Paoletti, J Christian Virchow, Enrico Heffler, Walter G Canonica
Abstract
Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a "fixed" airflow obstruction due to structural changes unresponsive to current therapies, from a "reversible" one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert "fixed" remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.
哮喘是一种慢性炎症性气道疾病，可导致气流阻塞，这在一定程度上对传统疗法来说是不可逆的，气道重塑的概念的典型表现。重症哮喘患者应用生物制剂已使先前认为不可逆的气流阻塞完全正常化。这强调了区分“固定”气流阻塞和“可逆”气流阻塞的必要性，前者是由于对当前治疗无反应的结构变化造成的，后者通过生物治疗期间的肺功能正常化证明，即使使用大剂量系统性糖皮质激素也无法获得。暴露于环境因素引发气道重塑的炎症反应的机制仍不完全清楚。警报素代表上皮源性细胞因子，可引发导致炎症性气道重塑的免疫事件。生物疗法可以通过解决这些气道炎症变化来改善气流阻塞。此外，生物制剂可能会阻止甚至恢复由于结构变化而导致的“固定”重塑。因此，区分生物制剂的治疗效果（早期和晚期），作为评估这些药物和未来治疗对重症哮喘气道重塑的影响的新范例，看来具有重要的临床意义。
(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)
(Allergy. 2022 Aug 11. doi: 10.1111/all.15473.)
(Allergy. 2022 Aug 11. doi: 10.1111/all.15473.)
Biologics and Airway Remodeling in Severe Asthma
Gilda Varricchi, Sebastian Ferri, Jack Pepys, Remo Poto, Giuseppe Spadaro, Nappi Emanuele, Giovanni Paoletti, J Christian Virchow, Enrico Heffler, Walter G Canonica
Abstract
Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a "fixed" airflow obstruction due to structural changes unresponsive to current therapies, from a "reversible" one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert "fixed" remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.
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哮喘持续气流限制表型的预测因子和相关性：ATLANTIS研究的事后分析
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肥胖对CC16的影响及其在超重/肥胖哮喘中的潜在作用
