Clinical Management Group, Woolcock Institute of Medical Research, University of Sydney, NSW, Australia.
University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Lancet. 2017 Jan 14;389(10065):157-166. doi: 10.1016/S0140-6736(16)31399-X. Epub 2016 Nov 30.
Low-dose inhaled corticosteroids (ICS) are highly effective for reducing asthma exacerbations and mortality. Conventionally, ICS treatment is recommended for patients with symptoms on more than 2 days per week, but this criterion has scant evidence. We aimed to assess the validity of the previous symptom-based cutoff for starting ICS by establishing whether there was a differential response to budesonide versus placebo for severe asthma exacerbations, lung function, and asthma symptom control across subgroups identified by baseline asthma symptom frequency.
We did a post-hoc analysis of the 3 year inhaled Steroid Treatment As Regular Therapy (START) study, done in 32 countries, with clinic visits every 3 months. Patients (aged 4-66 years) with mild asthma diagnosed within the previous 2 years and no previous regular corticosteroids were randomised to receive once daily, inhaled budesonide 400 μg (those aged <11 years 200 μg) or placebo. Coprimary outcomes for this analysis were time to first severe asthma-related event (SARE; hospital admission, emergency treatment, or death) and change from baseline in lung function after bronchodilator. Interaction with baseline symptom frequency was investigated, with patients grouped by more than two symptom days per week and two or fewer symptom days per week (divided into no days to 1 day, and more than 1 day to 2 days). Analysis was done by intention to treat.
Of 7138 patients (n=3577 budesonide; n=3561 placebo), baseline symptom frequency was 0-1 days per week for 2184 (31%) participants, more than 1 and less than or equal to 2 symptom days per week for 1914 (27%) participants, and more than 2 symptom days per week for 3040 (43%) participants. For budesonide versus placebo, time to first SARE was longer across symptom frequency subgroups (hazard ratios 0·54 [95% CI 0·34-0·86] for 0-1 symptom days per week, 0·60 [0·39-0·93] for >1 to ≤2 symptom days per week, 0·57 [0·41-0·79] >2 symptom days per week, p=0·94), and the decline in postbronchodilator lung function was less at 3 years' follow-up (p=0·32). For budesonide versus placebo, severe exacerbations requiring oral or systemic corticosteroids were reduced (rate ratio 0·48 [0·38-0·61] 0-1 symptom days per week, 0·56 [0·44-0·71] >1 to ≤2 symptom days per week, and 0·66 [0·55-0·80] >2 symptom days per week, p=0·11), prebronchodilator lung function was higher, and symptom-free days were more frequent (p<0·0001 for all three subgroups), with no interaction by symptom frequency (prebronchodilator p=0·43; symptom-free days p=0·53). Similar results were noted when participants were classified by any guidelines criterion as so-called persistent versus so-called intermittent asthma.
In mild recent-onset asthma, once daily, low-dose budesonide decreases SARE risk, reduces lung function decline, and improves symptom control similarly across all symptom subgroups. The results do not support restriction of inhaled corticosteroids to patients with symptoms on more than 2 days per week and suggest that treatment recommendations for mild asthma should consider both risk reduction and symptoms.
AstraZeneca.
低剂量吸入皮质类固醇（ICS）对于降低哮喘恶化和死亡率非常有效。传统上，建议有症状超过每周 2 天的患者使用 ICS 治疗，但这一标准证据不足。我们旨在通过评估在开始 ICS 时基于症状的先前截止值的有效性来确定在基于基线哮喘症状频率确定的亚组中，布地奈德与安慰剂相比是否存在严重哮喘恶化、肺功能和哮喘症状控制的差异反应。
我们对在 32 个国家进行的为期 3 年的吸入皮质类固醇常规治疗作为起始治疗（START）研究进行了事后分析，每 3 个月进行一次临床访视。患者（年龄为 4-66 岁）在过去 2 年内被诊断为轻度哮喘，且之前未使用过常规皮质类固醇，被随机分配接受每日一次吸入布地奈德 400μg（年龄<11 岁的患者为 200μg）或安慰剂。本次分析的主要终点是首次严重哮喘相关事件（SARE；住院、急诊治疗或死亡）的时间和支气管扩张剂后肺功能的基线变化。我们通过更频繁出现症状（每周>2 天）和更不频繁出现症状（每周 2 天或更少）的患者分组，调查了与基线症状频率的相互作用，进一步将患者分为无症状至 1 天/周、无症状至 2 天/周。分析按意向治疗进行。
在 7138 名患者（n=3577 名布地奈德；n=3561 名安慰剂）中，基线症状频率为每周 0-1 天的参与者有 2184 人（31%），每周 1 天至 2 天的参与者有 1914 人（27%），每周>2 天的参与者有 3040 人（43%）。与安慰剂相比，布地奈德在所有症状亚组中均延长了首次 SARE 的时间（每周无症状至 1 天的患者的危险比为 0.54[95%CI 0.34-0.86]，每周>1 天至≤2 天的患者为 0.60[0.39-0.93]，每周>2 天的患者为 0.57[0.41-0.79]，p=0.94），且在 3 年随访时支气管扩张剂后肺功能下降程度较小（p=0.32）。与安慰剂相比，布地奈德减少了需要口服或全身皮质类固醇治疗的严重恶化（口服或全身皮质类固醇治疗的发生率比为 0.48[0.38-0.61]每周无症状至 1 天，0.56[0.44-0.71]每周>1 天至≤2 天，0.66[0.55-0.80]每周>2 天，p=0.11），基础前肺功能更高，无症状天数更多（所有三个亚组均为 p<0.0001），且与症状频率无相互作用（基础前肺功能 p=0.43；无症状天数 p=0.53）。当根据任何指南标准将参与者分为所谓的持续性哮喘与所谓的间歇性哮喘时，也得到了类似的结果。
在轻度近期发作的哮喘中，每日低剂量布地奈德可降低 SARE 风险，减少肺功能下降，并在所有症状亚组中改善症状控制。结果不支持将吸入皮质类固醇限制用于每周有症状超过 2 天的患者，表明轻度哮喘的治疗建议应同时考虑降低风险和缓解症状。
阿斯利康。
