血清吸入皮质类固醇检测用于监测重度哮喘患者的依从性
2021/12/24
摘要
背景:每日吸入糖皮质激素(ICSs)是哮喘管理的基础，但依从性较低。
目的:探讨LC-MS/MS是否可用于检测血清中ICSs，以及血清水平是否与疾病严重程度标志物相关。
方法:我们在8小时的时间内收集了严重哮喘患者的血液样本，这些患者每天至少服用相当于倍氯米松二丙酸的1000毫克。基线采样后，观察患者服用他们通常的早晨剂量。随后分别于吸入后1、2、4、8小时采集血样，采用LC-MS/MS进行分析。研究血清ICS水平与严重程度指标之间的相关性。
结果:共招募了60名患者(41名女性;39例处方维护泼尼松龙的治疗方案;平均年龄:49±12岁;芬特1,63 +/- 20%预测)。吸入8小时后，所有使用布地奈德(n = 10)和二丙酸倍氯米松(15)的患者，以及除1例使用丙酸氟替卡松(28)外的所有患者均检测到血清药物水平。2例患者检出呋喃氟替卡松，无一例患者检出环索奈德。43%的患者通过重复处方记录发现低依从性(<80%)。 血ICS水平与加重率呈负相关，(仅用于丙酸氟替卡松)与FEV1%预测呈正相关。
结论:常用的ICSs在给药后至少8小时可在血液中可靠检测到，因此可作为严重哮喘患者依从性的一种测量方法。较高的病情加重率和较差的肺功能(丙酸氟替卡松)与较低的血液水平相关。
Serum Inhaled Corticosteroid Detection for Monitoring Adherence in Severe Asthma
Alahmadi FH, Keevil B, Elsey L, et al.
Abstract
BACKGROUND: Daily inhaled corticosteroids (ICSs) are fundamental to asthma management, but adherence is low.
OBJECTIVES: To investigate whether LC-MS/MS could be used to detect ICSs in serum and whether serum levels related to markers of disease severity.
METHODS: We collected blood samples over an 8-hour period from patients with severe asthma prescribed at least 1000 mu g daily of beclomethasone dipropionate equivalent. Following baseline sampling, patients were observed taking their usual morning dose. Subsequent blood samples were obtained 1, 2, 4, and 8 hours post inhalation and analyzed by LC-MS/MS. Correlations between serum ICS levels and severity markers were investigated.
RESULTS: A total of 60 patients were recruited (41 females; 39 prescribed maintenance prednisolone; mean age, 49 +/- 12 years; FEV1, 63 +/- 20 %predicted). Eight hours post inhalation, all patients using budesonide (n = 10) and beclomethasone dipropionate (15), and all but 1 using fluticasone propionate (28), had detectable serum drug levels. Fluticasone furorate was detected in 2 patients (of 4), ciclesonide in none (of 7). Low adherence by repeat prescription records (<80%) was identified in 43%. Blood ICS levels correlated negatively with exacerbation rate, and (for fluticasone propionate only) positively with FEV1 %predicted.
CONCLUSIONS: Commonly used ICSs can be reliably detected in the blood at least 8 hours after dosing, and could therefore be used as a measure of adherence in severe asthma. Higher exacerbation rates and poorer lung function (for fluticasone propionate) were associated with lower blood levels.
背景:每日吸入糖皮质激素(ICSs)是哮喘管理的基础，但依从性较低。
目的:探讨LC-MS/MS是否可用于检测血清中ICSs，以及血清水平是否与疾病严重程度标志物相关。
方法:我们在8小时的时间内收集了严重哮喘患者的血液样本，这些患者每天至少服用相当于倍氯米松二丙酸的1000毫克。基线采样后，观察患者服用他们通常的早晨剂量。随后分别于吸入后1、2、4、8小时采集血样，采用LC-MS/MS进行分析。研究血清ICS水平与严重程度指标之间的相关性。
结果:共招募了60名患者(41名女性;39例处方维护泼尼松龙的治疗方案;平均年龄:49±12岁;芬特1,63 +/- 20%预测)。吸入8小时后，所有使用布地奈德(n = 10)和二丙酸倍氯米松(15)的患者，以及除1例使用丙酸氟替卡松(28)外的所有患者均检测到血清药物水平。2例患者检出呋喃氟替卡松，无一例患者检出环索奈德。43%的患者通过重复处方记录发现低依从性(<80%)。 血ICS水平与加重率呈负相关，(仅用于丙酸氟替卡松)与FEV1%预测呈正相关。
结论:常用的ICSs在给药后至少8小时可在血液中可靠检测到，因此可作为严重哮喘患者依从性的一种测量方法。较高的病情加重率和较差的肺功能(丙酸氟替卡松)与较低的血液水平相关。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（J Allergy Clin Immunol Pract, 2021, 9(12): 4279-4287）
（J Allergy Clin Immunol Pract, 2021, 9(12): 4279-4287）
Serum Inhaled Corticosteroid Detection for Monitoring Adherence in Severe Asthma
Alahmadi FH, Keevil B, Elsey L, et al.
Abstract
BACKGROUND: Daily inhaled corticosteroids (ICSs) are fundamental to asthma management, but adherence is low.
OBJECTIVES: To investigate whether LC-MS/MS could be used to detect ICSs in serum and whether serum levels related to markers of disease severity.
METHODS: We collected blood samples over an 8-hour period from patients with severe asthma prescribed at least 1000 mu g daily of beclomethasone dipropionate equivalent. Following baseline sampling, patients were observed taking their usual morning dose. Subsequent blood samples were obtained 1, 2, 4, and 8 hours post inhalation and analyzed by LC-MS/MS. Correlations between serum ICS levels and severity markers were investigated.
RESULTS: A total of 60 patients were recruited (41 females; 39 prescribed maintenance prednisolone; mean age, 49 +/- 12 years; FEV1, 63 +/- 20 %predicted). Eight hours post inhalation, all patients using budesonide (n = 10) and beclomethasone dipropionate (15), and all but 1 using fluticasone propionate (28), had detectable serum drug levels. Fluticasone furorate was detected in 2 patients (of 4), ciclesonide in none (of 7). Low adherence by repeat prescription records (<80%) was identified in 43%. Blood ICS levels correlated negatively with exacerbation rate, and (for fluticasone propionate only) positively with FEV1 %predicted.
CONCLUSIONS: Commonly used ICSs can be reliably detected in the blood at least 8 hours after dosing, and could therefore be used as a measure of adherence in severe asthma. Higher exacerbation rates and poorer lung function (for fluticasone propionate) were associated with lower blood levels.
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严重哮喘患者肥大细胞活化差异与粒细胞炎症的关系
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哮喘通过T细胞核心蛋白聚糖介导的小胶质细胞抑制来减少胶质瘤的形成
