电子鼻用于评估慢性阻塞性肺病患者吸入倍氯米松/*治疗和戒断效果呼吸气体分析

breathomics for assessing the effects of treatment and withdrawal with inhaled beclomethasone/formoterol in patients with copd
电子鼻用于评估慢性阻塞性肺病患者吸入倍氯米松/*治疗和戒断效果呼吸气体分析
paolo montuschi 1*†, giuseppe santini 1†, nadia mores 1†, alessia vignoli 2†, francesco macagno3, rugia shoreh4, leonardo tenori 2, gina zini 5, leonello fuso3,
chiara mondino6, corrado di natale7, arnaldo d’amico7, claudio luchinat 2, peter j. barnes 8 and tim higenbottam9
1 department of pharmacology, faculty of medicine, catholic university of the sacred heart, university hospital agostino gemelli foundation, rome, italy,
2magnetic resonance center (cerm), university of florence, florence, italy,
3 department of internal medicine and geriatrics, catholic university of the sacred heart, university hospital agostino gemelli foundation, rome, italy,
4 department of drug sciences, faculty of pharmacy, university “g. d’annunzio”, chieti, italy,
5 department of hematology, faculty of medicine, catholic university of the sacred heart, university hospital agostino gemelli foundation, rome, italy,
6 department of allergology, ‘bellinzona e valli’ hospital, bellinzona, switzerland,
7 department of electronic engineering, university of tor vergata, rome, italy,
8 airway disease section, faculty of medicine, national heart and lung institute, imperial college, london, united kingdom,
9 faculty of pharmaceutical medicine, royal college of physicians, london, united kingdom
background:prospective pharmacological studies on breathomics profiles in copd patients have not been previously reported. we assessed the effects of treatment and withdrawal of an extrafine inhaled corticosteroid (ics)-long-acting b2-agonist (laba) fixed dose combination (fdc) using a multidimensional classification model including breathomics.
关于慢性阻塞性肺病患者的呼吸组学资料的前瞻性药理学研究尚未报道。我们采用包括呼吸计量学在内的多维分类模型评估了超精细吸入皮质类固醇(ics)长效b2激动剂(laba)固定剂量组合(fdc)的治疗和停药的效果。
methods:a pilot, proof-of-concept, pharmacological study was undertaken in 14 copd patients on maintenance treatment with inhaled fluticasone propionate/salmeterol (500/50 μg b.i.d.) for at least 8 weeks (visit 1). patients received 2-week treatment with inhaled beclomethasone dipropionate/formoterol (100/6 μg b.i.d.) (visit 2), 4-week treatment with formoterol alone (6 μg b.i.d.) (visit 3), and 4-week treatment with beclomethasone/formoterol (100/6 μg b.i.d.) (visit 4). exhaled breath analysis with two e-noses, based on different technologies, and exhaled breath condensate (ebc) nmr-based metabolomics were performed. sputum cell counts, sputum supernatant and ebc prostaglandin e2 (pge2) and 15-f2t-isoprostane, fraction of exhaled nitric oxide, and spirometry were measured.
在14名慢性阻塞性肺病患者中进行了一项试点、概念验证和药理研究,采用吸入倍氯米松/*(500/50μg b.i.d.)维持治疗至少8周(visit1)。患者接受了2周的吸入倍氯米松/*治疗(100/6μg b.i.d.)(visit2),4周的单独使用*治疗(6μg b.i.d.)(visit3),4周的使用倍氯米松/*治疗(100/6μg b.i.d.)(visit4)。利用两个电子鼻,基于不同的技术进行呼气分析,并利用基于呼气冷凝液(ebc)的核磁共振代谢组学进行呼气分析。测量痰细胞计数、痰上清液和ebc前列腺素e2(pge2)和15-f2t-异前列素、呼气中一氧化氮的分数和肺活量。
results:compared with formoterol alone, ebc acetate and sputum pge2, reflecting airway inflammation, were reduced after 4-week beclomethasone/formoterol. three independent breathomics techniques showed that extrafine beclomethasone/formoterol short-term treatment was associated with different breathprints compared with regular fluticasone propionate/salmeterol. either ics/laba fdc vs. formoterol alone was associated with increased pre-bronchodilator fef25−75% and fev1/fvc (p = 0.008–0.029). the multidimensional model distinguished fluticasone propionate/salmeterol vs. beclomethasone/formoterol, fluticasone propionate/salmeterol vs. formoterol, and formoterol vs. beclomethasone/formoterol (accuracy > 70%, p < 0.01).
与单用*相比,4周倍氯米松/*后,反映气道炎症的ebc醋酸盐和痰pge2降低。三种独立的呼吸测量技术表明,与常规的*/沙美特罗相比,特细倍氯米松/*短期治疗与不同的呼吸图相关。与单用*相比,ics/laba fdc与支气管扩张剂前fef25-75%和fev1/fvc增加相关(p=0.008-0.029)。多维模型区分了*/沙美特罗与倍氯米松/*、*/沙美特罗与*、*与倍氯米松/*(精确度>70%,p<0.01)
conclusions:breathomics could be used for assessing ics treatment and withdrawal in copd patients. large, controlled, prospective pharmacological trials are required to clarify the biological implications of breathomics changes. eudract number: 2012-001749-42
呼吸计量学可用于评估慢性阻塞性肺病患者的ics治疗和戒断。需要进行大规模的、对照的、前瞻性的药理学试验来阐明呼吸系统变化的生物学意义。eudract号:2012-001749-42
keywords: breathomics, inhaled corticosteroids, long-acting b2-agonists, copd, pharmacotherapy
关键词:呼吸组学,吸入皮质类固醇,长效b2激动剂,慢性阻塞性肺病,药物治疗

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