Balter M S, Adams S G, Chapman K R
Asthma Education Clinic, Mt. Sinai Hospital, University of Toronto, Toronto, Canada.
Chest. 2001 Dec;120(6):1829-34. doi: 10.1378/chest.120.6.1829.
Inhaled corticosteroids have the potential to produce upper-airway side effects such as hoarseness. As new compounds and delivery devices are developed and compared, it is difficult to quantify their adverse upper-airway effects.
We undertook the following study to test the ability of an acoustic analysis technique to quantify changes in vocal function in steroid-naive patients with asthma who receive inhaled beclomethasone dipropionate (BDP), 1,000 microg/d for 4 months.
Patients self-administered one of four regimens of inhaled BDP. Group 1 patients received one 250-microg puff qid via metered-dose inhaler (MDI); group 2 patients received one 250-microg puff qid via MDI with a holding chamber; group 3 patients received two 250-microg puffs bid via MDI; and group 4 patients received two 250-microg puffs bid via MDI with a holding chamber. A smaller cohort of nonsmoking asthmatic patients was managed without steroid intervention for 4 months. At baseline and again at 8 weeks and 16 weeks after the initiation of BDP treatment, patients underwent spirometry and methacholine challenge. At baseline and again at 2, 4, 8, 12, and 16 weeks, patients underwent voice recording for analysis of voice parameters. The recorded vowels were low-pass filtered (10 KHz), digitized (22 KHz), and analyzed by software to obtain two acoustic measures: (1) jitter, the cycle-to-cycle variation in the time period of the voice signal; and (2) shimmer, the cycle-to-cycle variation in voice signal amplitude.
We recruited 77 patients for randomization to inhaled steroid therapy and 10 patients who continued to receive only occasional inhaled bronchodilator therapy. In all active treatment groups, FEV(1), FVC, and provocative concentration of methacholine causing a 20% fall in FEV(1) improved significantly after BDP treatment. Mean jitter scores, a measurement of variation in voice pitch, were not significantly influenced by BDP treatment. However, mean shimmer scores, a reflection of perturbation in vocal amplitude, fell significantly (p < 0.05) in the active treatment groups. These reductions in shimmer scores were not significantly different in the active treatment groups. Shimmer scores in the bronchodilator-treated group were unchanged during the 16 weeks of follow-up.
Our data show that a simple and noninvasive acoustic analysis of voice is sensitive to subclinical changes associated with inhaled corticosteroid therapy. We have shown that 1,000 microg/d of inhaled BDP actually improves specific acoustic measures of voice in patients with inadequately controlled asthma. These improvements were uninfluenced by dosing schedule and whether a spacing chamber was used.
吸入性糖皮质激素有可能产生如声音嘶哑等上呼吸道副作用。随着新化合物和给药装置的研发及比较,很难对其不良上呼吸道效应进行量化。
我们开展了以下研究,以测试一种声学分析技术量化未使用过类固醇的哮喘患者吸入二丙酸倍氯米松(BDP)1000μg/天,持续4个月后嗓音功能变化的能力。
患者自行使用四种吸入BDP方案中的一种。第1组患者通过定量吸入器(MDI)每天4次,每次吸入1剂250μg;第2组患者通过带储雾罐的MDI每天4次,每次吸入1剂250μg;第3组患者通过MDI每天2次,每次吸入2剂250μg;第4组患者通过带储雾罐的MDI每天2次,每次吸入2剂250μg。一小群不吸烟的哮喘患者在未使用类固醇干预的情况下进行了4个月的治疗。在基线以及BDP治疗开始后的8周和16周再次进行时,患者接受了肺功能测定和乙酰甲胆碱激发试验。在基线以及2、4、8、12和16周再次进行时,患者进行嗓音录音以分析嗓音参数。记录的元音经过低通滤波(10kHz)、数字化(22kHz),并通过软件进行分析以获得两项声学指标:(1)抖动,即嗓音信号时间段内的逐周期变化;(2)闪烁,即嗓音信号幅度的逐周期变化。
我们招募了77例患者随机接受吸入性类固醇治疗,以及10例继续仅偶尔接受吸入性支气管扩张剂治疗的患者。在所有积极治疗组中,BDP治疗后第1秒用力呼气容积(FEV₁)、用力肺活量(FVC)以及使FEV₁下降20%的乙酰甲胆碱激发浓度均有显著改善。平均抖动评分,一种嗓音音高变化的测量指标,未受到BDP治疗的显著影响。然而,平均闪烁评分,一种嗓音幅度扰动的反映,在积极治疗组中显著下降(p<0.05)。这些闪烁评分的降低在积极治疗组中无显著差异。支气管扩张剂治疗组的闪烁评分在16周的随访期间未发生变化。
我们的数据表明,一种简单且无创的嗓音声学分析对与吸入性糖皮质激素治疗相关的亚临床变化敏感。我们已经表明,每天吸入1000μg的BDP实际上改善了控制不佳的哮喘患者嗓音的特定声学指标。这些改善不受给药方案以及是否使用储雾罐的影响。