不同吸入药物对慢性阻塞性肺疾病频繁咳嗽患者治疗效果的影响

The effect of different inhaled drugs on the treatment of patients with frequent cough in chronic obstructive pulmonary disease

目的比较慢性阻塞性肺疾病(慢阻肺)频繁咳嗽患者使用不同吸入药物的治疗效果,包括症状变化和急性加重。方法本研究来源于RealDTC研究,研究对象为2016年12月至2023年3月中南大学湘雅二医院呼吸与危重症医学科门诊数据库中的稳定期慢阻肺患者,收集患者的人口学特征、吸烟状况、生物燃料暴露史、过去1年急性加重病史、肺功能、慢阻肺评估测试(CAT)评分、改良版英国医学研究委员会呼吸困难问卷(mMRC)评分及吸入药物方案。定义CAT评分中第1项咳嗽分数≥2分为频繁咳嗽患者,根据吸入药物类型将频繁咳嗽患者分为长效抗胆碱药物(LAMA)、长效β2受体激动剂(LABA)+LAMA、吸入性糖皮质激素(ICS)+LABA和ICS+LABA+LAMA组。第6个月随访时,收集CAT评分,评估症状控制情况,包括最小临床改善(MCID)(定义为第6个月的CAT评分相对于基线降低≥2分)和咳嗽症状改善(定义为咳嗽分数相对于基线降低≥1分)。在1年的随访中,评估急性加重的次数。多因素logistic回归分析评估慢阻肺频繁咳嗽患者不同吸入药物与预后之间的关系。结果共纳入653例慢阻肺频繁咳嗽患者,CAT评分为(16.4±6.1)分,咳嗽分数为3(2,3)分。随访6个月,403例(61.7%)患者达到了MCID,394例(60.3%)患者咳嗽症状改善;随访1年,227例(34.8%)的患者发生了急性加重。接受吸入药物治疗后,LAMA、LABA+LAMA、ICS+LABA、ICS+LABA+LAMA四组频繁咳嗽患者的CAT评分、咳嗽分数均较治疗前下降(均P<0.05)。LAMA、LABA+LAMA、ICS+LABA、ICS+LABA+LAMA四组间ΔCAT、MCID和急性加重的比例差异具有统计学意义(均P<0.05),Δ咳嗽分数、咳嗽分数降低≥1分比例差异无统计学意义(均P>0.05)。多因素logistic回归分析结果显示,与使用LAMA或ICS+LABA药物治疗的患者相比,使用LABA+LAMA或ICS+LABA+LAMA药物治疗的慢阻肺频繁咳嗽患者更容易达到MCID,更少发生急性加重(均P<0.05)。结论与LAMA或ICS+LABA相比,接受LABA+LAMA或ICS+LABA+LAMA药物治疗的慢阻肺频繁咳嗽患者症状更容易改善,并且发生急性加重的风险更低。

Objective To compare the therapeutic effects of different inhaled medications on patients with frequent cough in chronic obstructive pulmonary disease(COPD),including changes in symptoms and acute exacerbation.Methods This study was based on the RealDTC study,and the study subjects were stable COPD patients from the Department of Pulmonary and Critical Care Medicine,the Second Xiangya Hospital,Central South University from December 2016 to March 2023.The demographic characteristics,smoking status,history of biofuel exposure,history of acute exacerbation in the past year,lung function,COPD Assessment Test(CAT)score,modified British Medical Research Council Respiratory Difficulty Questionnaire(mMRC)score,and inhalation medication regimen of the patients were collected.Patients with frequent cough are defined as having a cough score of≥2 in the first item of the CAT score.According to the type of inhaled medication,patients with frequent cough are divided into l long-acting muscarine anticholinergic(LAMA),long-actingβ2 agonists(LABA)+LAMA,inhaled corticosteroids(ICS)+LABA,and ICS+LABA+LAMA groups.At the 6th month follow-up,CAT scores were collected and symptom control was evaluated,including minimum clinical improvement(MCID)(defined as a decrease of≥2 points from baseline in CAT scores at the 6th month)and improvement in cough symptoms(defined as a decrease of≥1 point from baseline in cough scores).During a one-year follow-up,the number of acute exacerbations was evaluated.The relationship between different inhaled medications and prognosis in patients with frequent cough in COPD was evaluated using multivariate logistic regression analysis.Results A total of 653 patients with frequent cough in COPD were included,with a CAT score of(16.4±6.1)and a cough score of 3(2,3).After 6 months of follow-up,403 patients(61.7%)achieved MCID,and 394 patients(60.3%)had improved cough symptoms;During a one-year follow-up,227 patients(34.8%)experienced acute exacerbation.After receiving inhalation medication treatment,the CAT scores and cough scores of four groups of patients with frequent cough,namely LAMA,LABA+LAMA,ICS+LABA,and ICS+LABA+LAMA,decreased compared to before treatment(all P<0.05).There was a statistically significant difference in the proportion of△CAT score,MCID,and acute exacerbation among the four groups of LAMA,LABA+LAMA,ICS+LABA,and ICS+LABA+LAMA(all P<0.05),while there was no statistically significant difference in the proportion of△cough score and cough score reduction≥1 point(all P>0.05).The results of multivariate logistic regression analysis showed that compared with patients treated with LAMA or ICS+LABA drugs,patients with frequent cough in COPD treated with LABA+LAMA or ICS+LABA+LAMA drugs were more likely to achieve MCID and less likely to experience acute exacerbation(all P<0.05).Conclusions Compared with LAMA or ICS+LABA,patients with frequent cough in COPD who receive LABA+LAMA or ICS+LABA+LAMA drug treatment are more likely to improve symptoms and have a lower risk of acute exacerbation.