罗氟司特用于治疗肥胖患者控制不佳的哮喘时，可能会增加病情加重的风险
2023/02/20
摘要
背景：肥胖症患者常患有严重、难以控制的哮喘。有必要为这一人群开发更好的治疗方法。一种潜在的治疗方法是罗氟司特，一种磷酸二酯酶-4抑制剂，据报道它对治疗哮喘有效，并且可以减重。
目的：探讨罗氟司特治疗肥胖患者哮喘控制不佳的潜在疗效。
方法：一项随机、双盲、安慰剂对照试验，纳入了24周罗氟司特与安慰剂治疗肥胖患者控制不佳的哮喘（体重指数为 30 kg/m 或更高）。主要结局是ACT（哮喘控制测试）评分的变化。
结果：22人被随机分配到罗氟司特组，16人被随机分配到安慰剂组。罗氟司特对 ACT 的变化没有影响（罗氟司特组增加 2.6 [四分位距 (IQR)，0.5-4.4]，安慰剂组增加 2.0 [IQR，0.7-3.3]）。分配给罗氟司特的参与者哮喘控制不佳的风险增加了 3.5 倍（相对风险 [RR] 95% 置信区间 [CI]，1.3-9.4）和 哮喘急诊就诊的风险增加8.1 倍（RR 95% CI，1.01-65.0） )。分配给罗氟司特的10 名参与者 (56%) 需要一个疗程的口服皮质类固醇治疗哮喘发作，而安慰剂组则没有。体重减轻 5% 或更多的患者在哮喘控制方面取得了临床和统计学上的显着改善（ACT 增加了 4.4 [IQR，2.5-6.3]，而体重减轻不到 5% 的患者增加了 1.5 [IQR，0.0-3.0] )。罗氟司特对哮喘控制没有影响。令人担忧的是，罗氟司特与哮喘控制不佳的肥胖个体的恶化风险增加有关。
结论：这些结果突出了研究对不同哮喘患者亚群进行干预的重要性，尤其是肥胖和哮喘患者，他们对药物的反应可能与瘦型哮喘患者不同。体重减轻至少 5% 与改善哮喘控制有关，这表明除罗氟司特以外的促进体重减轻的干预措施可能对治疗肥胖症患者控制不佳的哮喘有效。
Roflumilast May Increase Risk of Exacerbations When Used to Treat Poorly Controlled Asthma in People with Obesity
Dixon AE, Que LG, Kalhan R,
Abstrast
Background: People with obesity often have severe, difficult-to-control asthma. There is a need to develop better treatments for this population. One potential treatment is roflumilast, a phosphodiesterase 4 inhibitor, as it is reported to have efficacy for the treatment of asthma and can promote weight loss.
Objectives: To investigate the potential efficacy of roflumilast for the treatment of poorly controlled asthma in people with obesity.
Methods: A randomized, double-masked, placebo-controlled trial of 24 weeks of roflumilast versus placebo for the treatment of poorly controlled asthma in people with obesity (body mass index of 30 kg/m or higher). The primary outcome was a change in ACT (Asthma Control Test) score.
Results: Twenty-two people were randomized to roflumilast and 16 to placebo. Roflumilast had no effect on change in the ACT (increased by 2.6 [interquartile range (IQR), 0.5-4.4] in those on roflumilast vs. 2.0 [IQR, 0.7-3.3] in those on placebo). Participants assigned to roflumilast had a 3.5-fold (relative risk [RR] 95% confidence interval [CI], 1.3-9.4) increased risk of an episode of poor asthma control and an 8.1-fold (RR 95% CI, 1.01-65.0) increased risk of an urgent care visit for asthma. Ten participants (56%) assigned to roflumilast required a course of oral corticosteroids for asthma exacerbations, and none in the placebo group. Participants losing 5% or more of their body weight experienced a clinically and statistically significant improvement in asthma control (ACT increased by 4.4 [IQR, 2.5-6.3] vs. 1.5 [IQR, 0.0-3.0] in those who lost less than 5%). Roflumilast had no effect on asthma control. Of concern, roflumilast was associated with an increased risk of exacerbation in obese individuals with poorly controlled asthma.
Conclusions: These results highlight the importance of studying interventions in different subpopulations of people with asthma, particularly people with obesity and asthma who may respond differently to medications than lean people with asthma. Weight loss of at least 5% was associated with improved asthma control, indicating that interventions other than roflumilast promoting weight loss may have efficacy for the treatment of poorly controlled asthma in people with obesity.
背景：肥胖症患者常患有严重、难以控制的哮喘。有必要为这一人群开发更好的治疗方法。一种潜在的治疗方法是罗氟司特，一种磷酸二酯酶-4抑制剂，据报道它对治疗哮喘有效，并且可以减重。
目的：探讨罗氟司特治疗肥胖患者哮喘控制不佳的潜在疗效。
方法：一项随机、双盲、安慰剂对照试验，纳入了24周罗氟司特与安慰剂治疗肥胖患者控制不佳的哮喘（体重指数为 30 kg/m 或更高）。主要结局是ACT（哮喘控制测试）评分的变化。
结果：22人被随机分配到罗氟司特组，16人被随机分配到安慰剂组。罗氟司特对 ACT 的变化没有影响（罗氟司特组增加 2.6 [四分位距 (IQR)，0.5-4.4]，安慰剂组增加 2.0 [IQR，0.7-3.3]）。分配给罗氟司特的参与者哮喘控制不佳的风险增加了 3.5 倍（相对风险 [RR] 95% 置信区间 [CI]，1.3-9.4）和 哮喘急诊就诊的风险增加8.1 倍（RR 95% CI，1.01-65.0） )。分配给罗氟司特的10 名参与者 (56%) 需要一个疗程的口服皮质类固醇治疗哮喘发作，而安慰剂组则没有。体重减轻 5% 或更多的患者在哮喘控制方面取得了临床和统计学上的显着改善（ACT 增加了 4.4 [IQR，2.5-6.3]，而体重减轻不到 5% 的患者增加了 1.5 [IQR，0.0-3.0] )。罗氟司特对哮喘控制没有影响。令人担忧的是，罗氟司特与哮喘控制不佳的肥胖个体的恶化风险增加有关。
结论：这些结果突出了研究对不同哮喘患者亚群进行干预的重要性，尤其是肥胖和哮喘患者，他们对药物的反应可能与瘦型哮喘患者不同。体重减轻至少 5% 与改善哮喘控制有关，这表明除罗氟司特以外的促进体重减轻的干预措施可能对治疗肥胖症患者控制不佳的哮喘有效。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Ann Am Thorac Soc. 2023 Feb;20(2) doi:10.1513/AnnalsATS.202204-368OC，IF：4.026)
(Ann Am Thorac Soc. 2023 Feb;20(2) doi:10.1513/AnnalsATS.202204-368OC，IF：4.026)
Roflumilast May Increase Risk of Exacerbations When Used to Treat Poorly Controlled Asthma in People with Obesity
Dixon AE, Que LG, Kalhan R,
Abstrast
Background: People with obesity often have severe, difficult-to-control asthma. There is a need to develop better treatments for this population. One potential treatment is roflumilast, a phosphodiesterase 4 inhibitor, as it is reported to have efficacy for the treatment of asthma and can promote weight loss.
Objectives: To investigate the potential efficacy of roflumilast for the treatment of poorly controlled asthma in people with obesity.
Methods: A randomized, double-masked, placebo-controlled trial of 24 weeks of roflumilast versus placebo for the treatment of poorly controlled asthma in people with obesity (body mass index of 30 kg/m or higher). The primary outcome was a change in ACT (Asthma Control Test) score.
Results: Twenty-two people were randomized to roflumilast and 16 to placebo. Roflumilast had no effect on change in the ACT (increased by 2.6 [interquartile range (IQR), 0.5-4.4] in those on roflumilast vs. 2.0 [IQR, 0.7-3.3] in those on placebo). Participants assigned to roflumilast had a 3.5-fold (relative risk [RR] 95% confidence interval [CI], 1.3-9.4) increased risk of an episode of poor asthma control and an 8.1-fold (RR 95% CI, 1.01-65.0) increased risk of an urgent care visit for asthma. Ten participants (56%) assigned to roflumilast required a course of oral corticosteroids for asthma exacerbations, and none in the placebo group. Participants losing 5% or more of their body weight experienced a clinically and statistically significant improvement in asthma control (ACT increased by 4.4 [IQR, 2.5-6.3] vs. 1.5 [IQR, 0.0-3.0] in those who lost less than 5%). Roflumilast had no effect on asthma control. Of concern, roflumilast was associated with an increased risk of exacerbation in obese individuals with poorly controlled asthma.
Conclusions: These results highlight the importance of studying interventions in different subpopulations of people with asthma, particularly people with obesity and asthma who may respond differently to medications than lean people with asthma. Weight loss of at least 5% was associated with improved asthma control, indicating that interventions other than roflumilast promoting weight loss may have efficacy for the treatment of poorly controlled asthma in people with obesity.
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可治疗特征对哮喘控制和生活质量的影响
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孟德尔随机化分析揭示特应性皮炎、哮喘和胃食管反流病之间复杂的遗传相互作用
