Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; Division of Pulmonary Rehabilitation, Istituti Clinici Scientifici Maugeri, IRCCS, Tradate, Italy.
Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; NIHR Clinical Research Facility, Royal Brompton Hospital, London, UK.
Lancet Respir Med. 2018 Oct;6(10):759-770. doi: 10.1016/S2213-2600(18)30289-3. Epub 2018 Aug 28.
In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia.
AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed.
Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [-0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment.
Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding.
UK National Institute for Health Research.
在纤维化的间质性肺疾病中，运动性呼吸困难与健康相关生活质量（HRQOL）密切相关。呼吸困难通常与氧饱和度降低有关，但关于纤维化间质性肺疾病患者使用便携式氧气的数据很少。我们旨在评估便携式氧气对孤立性运动性低氧患者间质性肺疾病患者 HRQOL 的影响。
AmbOx 是一项前瞻性、开放标签、混合方法、交叉随机对照临床试验，在英国的三个间质性肺疾病中心进行。合格的患者年龄在 18 岁或以上，患有纤维化间质性肺疾病，在静息时不缺氧，但在筛查 6 分钟步行试验（6MWT）中经皮动脉血氧饱和度下降至 88%或更低，并且在过去 2 周内有自我报告的稳定呼吸症状。参与者被随机分配（1:1）接受或不接受氧气治疗 2 周，然后交叉接受另 2 周的治疗。随机分配通过计算机生成的治疗序列进行，该序列按大小恒定的块随机排列（块大小为 10）。主要结局，通过意向治疗评估，是与 2 周无治疗相比，2 周吸氧后 King's Brief Interstitial Lung Disease 问卷（K-BILD）总评分的变化。使用具有治疗顺序作为固定效应的一般线性模型进行分析。通过亚组参与者的半结构化主题引导访谈探索患者观点。这项研究在 ClinicalTrials.gov 上注册，编号为 NCT02286063，目前已对所有参与者完成随访，不再接受新的参与者。
2014 年 9 月 10 日至 2016 年 10 月 5 日期间，随机分配了 84 名患者，41 名患者首先接受便携式氧气治疗，43 名患者不接受氧气治疗。76 名参与者完成了试验。与不吸氧相比，便携式氧气治疗与 K-BILD 总分的显著改善相关（吸氧时平均 55.5[13.8]，不吸氧时平均 51.8[13.6]，治疗顺序调整后的平均差异 3.7[95%CI 1.8 至 5.6]；p<0.0001），以及呼吸困难和活动（平均差异 8.6[95%CI 4.7 至 12.5]；p<0.0001）和胸部症状（7.6[1.9 至 13.2]；p=0.009）亚域的评分。然而，对心理亚域的影响并不显著（2.4[-0.6 至 5.5]；p=0.12）。最常见的不良事件是上呼吸道感染（吸氧组 3 例，不吸氧组 1 例）。发生了 5 例严重不良事件，包括 2 例死亡（每组 1 例），但均认为与治疗无关。
便携式氧气似乎与孤立性运动性低氧患者的 HRQOL 改善相关，并且可能是这群治疗选择有限的患者的有效干预措施。然而，需要进一步的研究来证实这一发现。
英国国家卫生研究院。
