Kwok Wang Chung, Chan Shung Kay Samuel, Chiang Ka Yan, Ho Chung Man James
Division of Respiratory Medicine, Department of Medicine The University of Hong Kong, Queen Mary Hospital Hong Kong.
Respirol Case Rep. 2024 Aug 6;12(8):e01449. doi: 10.1002/rcr2.1449. eCollection 2024 Aug.
Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with acute exacerbation (AECOPD) being a common sequalae which negatively impact health status, rates of hospitalization and readmission, and disease progression. N-acetylcysteine (NAC) has been studied in COPD in both stable state and acute exacerbations, which has been shown to have small beneficial effects in stable COPD, as well as AECOPD. Yet, there has been lack of study with well-designed protocol to assess the role of NAC in more objective outcomes in AECOPD.
This is a double-blind randomized controlled trial. Patients will be randomized in 1:1 ratio to receive oral NAC at 600 mg twice daily or placebo twice daily with standard of care. Partial pressure of oxygen (PaO), partial pressure of carbon dioxide (PaCO) and the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO/FiO) will be measured on days 1 and 7. The following will be measure at baseline and on day 4 and 7: Forced expiratory volume in one second (FEV), 24-hour sputum volume, oxygen saturation (SaO), end-tidal CO, Leicester Cough Questionnaire (LCQ) score, COPD Assessment Test (CAT) score, grading of wheeze and grade of dyspnoea; blood inflammatory markers (leucocyte count, neutrophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and high sensitivity CRP (hs-CRP)). Patients will be randomized to oral NAC at 600 mg twice daily or placebo for 7 days. The main outcome measures include: The difference in PaO on day 7. Secondary outcome: Change in following parameters on day 4/7 from baseline: FEV, sputum volume, CAT score, LCQ score, SaO, grade of wheeze; mMRC Dyspnoea Scale, end-tidal CO, blood inflammatory marker, change in PaO/FiO ratio from baseline to day 7, PaCO on day 7, 28 and 90 days' mortality, time to wean off supplemental oxygen, length of stay.Primary and secondary outcomes will be compared among the two treatment groups with two-sample -test.
We hypothesize that NAC use in COPD exacerbation can provide benefits in clinical and laboratory parameters.
: ClinicalTrials.gov : NCT05706402. : https://classic.clinicaltrials.gov/ct2/show/NCT05706402 : Registered on 11th January 2023 : The Health and Medical Research Fund (HMRF). : Wang Chung Kwok, Clinical Assistant Professor, Honorary Associate Consultant, Queen Mary Hospital, The University of Hong Kong, Hong Kong. : The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.
慢性阻塞性肺疾病（COPD）是一种常见的呼吸系统疾病，急性加重（AECOPD）是其常见的后遗症，会对健康状况、住院率和再入院率以及疾病进展产生负面影响。N-乙酰半胱氨酸（NAC）已在稳定期和急性加重期的COPD中进行了研究，结果显示其在稳定期COPD以及AECOPD中均有微小的有益作用。然而，缺乏设计良好的方案来评估NAC在AECOPD更客观结局中的作用。
这是一项双盲随机对照试验。患者将按1:1的比例随机分组，分别接受每日两次口服600毫克NAC或每日两次口服安慰剂，并接受标准治疗。在第1天和第7天测量氧分压（PaO）、二氧化碳分压（PaCO）以及动脉血氧分压与吸入氧分数之比（PaO/FiO）。在基线、第4天和第7天测量以下指标：一秒用力呼气容积（FEV）、24小时痰量、血氧饱和度（SaO）、呼气末二氧化碳（EtCO）、莱斯特咳嗽问卷（LCQ）评分、慢性阻塞性肺疾病评估测试（CAT）评分、哮鸣音分级和呼吸困难分级；血液炎症标志物（白细胞计数、中性粒细胞计数、红细胞沉降率（ESR）、C反应蛋白（CRP）和高敏CRP（hs-CRP））。患者将被随机分配至每日两次口服600毫克NAC或安慰剂组，为期7天。主要结局指标包括：第7天PaO的差异。次要结局：第4/7天以下参数相对于基线的变化：FEV、痰量、CAT评分、LCQ评分、SaO、哮鸣音分级；改良英国医学研究委员会（mMRC）呼吸困难量表、呼气末二氧化碳、血液炎症标志物、从基线到第7天PaO/FiO比值的变化、第7天的PaCO、28天和90天死亡率、停用补充氧气的时间、住院时间。两个治疗组之间将通过两样本t检验比较主要和次要结局。
我们假设在COPD加重期使用NAC可在临床和实验室参数方面带来益处。
ClinicalTrials.gov：NCT05706402。网址：https://classic.clinicaltrials.gov/ct2/show/NCT05706402。于2023年1月11日注册。健康与医学研究基金（HMRF）。王仲国，香港大学玛丽医院临床助理教授、名誉副顾问。资助者未参与研究的规划、数据收集、分析和解释，也未参与稿件撰写。
