重症哮喘中降低奥马珠单抗反应的因素
2018/05/30
摘要
背景：尽管将奥马珠单抗加入常规治疗中，仍然有一些重症哮喘患者表现出较差的疾病控制。我们调查了可能影响大量重症哮喘患者奥马珠单抗反应降低的因素。
方法：回顾性分析340例患者。FEV1％，FVC％，哮喘控制测试（ACT），呼出气一氧化氮（FENO），伴随治疗的降级/升级，急性加重，疾病控制水平，ICS剂量和SABA使用治疗被认为是对奥马珠单抗的反应。
结果:年龄是FEV1％，FVC％，ACT和哮喘控制率降低的独立危险因素。肥胖（与正常体重相比）是急性加重（OR：3.114 [1.509-6.424]，p = 0.002）、疾病部分/未控制（OR：2.665 [1.064-6.680]，p = 0.036）、过度使用SABA（OR：4.448 [1.837-10.768] p = 0.002）和伴随哮喘药物水平不变/增加的决定性条件。此外，肥胖也降低了FEV1（β= -6.981，p = 0.04），FVC（β= -11.689，p = 0.014）和ACT（β= -2.585，p = 0.027）的反应并且与更高的FENO 水平相关（β= 49.045，p = 0.040）。至少有一种合并症是急性加重（OR：1.383 [1.128-1.697]，p = 0.008）和ACT <20（OR：2.410 [1.071-3.690]，p = 0.008）的危险因素。具体而言，慢性心脏疾病与较低的ACT和FVC％相关，而胃食管反流与哮喘部分/未控制相关。鼻息肉是导致恶化和使用较高吸入皮质类固醇剂量的诱发因素。此外，吸烟习惯，花粉或狗/猫皮屑共同敏感也可能会降低奥马珠单抗的反应性。
结论：年龄，肥胖，合并症，吸烟习惯，鼻息肉，过敏性多敏化可能独立于其他的哮喘影响因素降低奥马珠单抗的有效性。
Factors reducing omalizumab response in severe asthma.
Sposato B1, Scalese M2, Milanese M3, Masieri S4, Cavaliere C4, Latorre M5, Scichilone N6, Matucci A7, Vultaggio A7, Ricci A8, Cresti A9, Santus P10, Perrella A11, Paggiaro PL5.
Abstract
BACKGROUND:Despite adding Omalizumab to conventional therapy, several severe asthmatics still show poor disease control. We investigated the factors that may affect a reduced Omalizumab response in a large population of severe asthmatics.
METHODS:340 patients were retrospectively evaluated. FEV1%, FVC%, Asthma Control Test (ACT), fractional exhaled nitric oxide (FENO), possible step-downs/step-ups of concomitant therapies, exacerbations, disease control levels, ICS doses and SABA use, observed at the end of treatment, were considered as a response to Omalizumab.
RESULTS:Age was an independent risk factor for a reduced response concerning FEV1%, FVC%, ACT and for a lower asthma control. Obesity (vs normal weight) was a determinant condition for exacerbations (OR:3.114[1.509-6.424], p = 0.002), for a disease partial/no control (OR:2.665[1.064-6.680], p = 0.036), for excessive SABA use (OR:4.448[1.837-10.768], p = 0.002) and for an unchanged/increased level of concomitant asthma medications. Furthermore, obesity also reduced the response in FEV1 (β = -6.981,p = 0.04), FVC (β = -11.689,p = 0.014) and ACT (β = -2.585, p = 0.027) and was associated with a higher FENO level (β = 49.045,p = 0.040). Having at least one comorbidity was a risk factor for exacerbations (OR:1.383[1.128-1.697], p = 0.008) and for an ACT <20 (OR:2.410[1.071-3.690], p = 0.008). Specifically, chronic heart disease was associated with both a lower ACT and FVC% whereas gastroesophageal reflux with a partial/no asthma control. Nasal polyps were a predisposing factor leading both to exacerbations and to the use of higher inhaled corticosteroids doses. Moreover, smoking habits, pollen or dog/cat dander co-sensitizations may negatively influence Omalizumab response.
CONCLUSIONS:Age, obesity, comorbidities, smoking habits, nasal polyps, allergic poly-sensitization might reduce Omalizumab effectiveness independently to other asthma-influencing factors.
背景：尽管将奥马珠单抗加入常规治疗中，仍然有一些重症哮喘患者表现出较差的疾病控制。我们调查了可能影响大量重症哮喘患者奥马珠单抗反应降低的因素。
方法：回顾性分析340例患者。FEV1％，FVC％，哮喘控制测试（ACT），呼出气一氧化氮（FENO），伴随治疗的降级/升级，急性加重，疾病控制水平，ICS剂量和SABA使用治疗被认为是对奥马珠单抗的反应。
结果:年龄是FEV1％，FVC％，ACT和哮喘控制率降低的独立危险因素。肥胖（与正常体重相比）是急性加重（OR：3.114 [1.509-6.424]，p = 0.002）、疾病部分/未控制（OR：2.665 [1.064-6.680]，p = 0.036）、过度使用SABA（OR：4.448 [1.837-10.768] p = 0.002）和伴随哮喘药物水平不变/增加的决定性条件。此外，肥胖也降低了FEV1（β= -6.981，p = 0.04），FVC（β= -11.689，p = 0.014）和ACT（β= -2.585，p = 0.027）的反应并且与更高的FENO 水平相关（β= 49.045，p = 0.040）。至少有一种合并症是急性加重（OR：1.383 [1.128-1.697]，p = 0.008）和ACT <20（OR：2.410 [1.071-3.690]，p = 0.008）的危险因素。具体而言，慢性心脏疾病与较低的ACT和FVC％相关，而胃食管反流与哮喘部分/未控制相关。鼻息肉是导致恶化和使用较高吸入皮质类固醇剂量的诱发因素。此外，吸烟习惯，花粉或狗/猫皮屑共同敏感也可能会降低奥马珠单抗的反应性。
结论：年龄，肥胖，合并症，吸烟习惯，鼻息肉，过敏性多敏化可能独立于其他的哮喘影响因素降低奥马珠单抗的有效性。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(Eur J Intern Med. 2018 Jan 29. pii: S0953-6205(18)30026-8. doi: 10.1016/j.ejim.2018.01.026. [Epub ahead of print])
(Eur J Intern Med. 2018 Jan 29. pii: S0953-6205(18)30026-8. doi: 10.1016/j.ejim.2018.01.026. [Epub ahead of print])
Factors reducing omalizumab response in severe asthma.
Sposato B1, Scalese M2, Milanese M3, Masieri S4, Cavaliere C4, Latorre M5, Scichilone N6, Matucci A7, Vultaggio A7, Ricci A8, Cresti A9, Santus P10, Perrella A11, Paggiaro PL5.
Abstract
BACKGROUND:Despite adding Omalizumab to conventional therapy, several severe asthmatics still show poor disease control. We investigated the factors that may affect a reduced Omalizumab response in a large population of severe asthmatics.
METHODS:340 patients were retrospectively evaluated. FEV1%, FVC%, Asthma Control Test (ACT), fractional exhaled nitric oxide (FENO), possible step-downs/step-ups of concomitant therapies, exacerbations, disease control levels, ICS doses and SABA use, observed at the end of treatment, were considered as a response to Omalizumab.
RESULTS:Age was an independent risk factor for a reduced response concerning FEV1%, FVC%, ACT and for a lower asthma control. Obesity (vs normal weight) was a determinant condition for exacerbations (OR:3.114[1.509-6.424], p = 0.002), for a disease partial/no control (OR:2.665[1.064-6.680], p = 0.036), for excessive SABA use (OR:4.448[1.837-10.768], p = 0.002) and for an unchanged/increased level of concomitant asthma medications. Furthermore, obesity also reduced the response in FEV1 (β = -6.981,p = 0.04), FVC (β = -11.689,p = 0.014) and ACT (β = -2.585, p = 0.027) and was associated with a higher FENO level (β = 49.045,p = 0.040). Having at least one comorbidity was a risk factor for exacerbations (OR:1.383[1.128-1.697], p = 0.008) and for an ACT <20 (OR:2.410[1.071-3.690], p = 0.008). Specifically, chronic heart disease was associated with both a lower ACT and FVC% whereas gastroesophageal reflux with a partial/no asthma control. Nasal polyps were a predisposing factor leading both to exacerbations and to the use of higher inhaled corticosteroids doses. Moreover, smoking habits, pollen or dog/cat dander co-sensitizations may negatively influence Omalizumab response.
CONCLUSIONS:Age, obesity, comorbidities, smoking habits, nasal polyps, allergic poly-sensitization might reduce Omalizumab effectiveness independently to other asthma-influencing factors.
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