Abstract：
BACKGROUND: A small amount of evidence suggests that nasal sprays, or physical activity and stress management, could shorten the duration of respiratory infections. This study aimed to assess the effect of nasal sprays or a behavioural intervention promoting physical activity and stress management on respiratory illnesses, compared with usual care.
METHODS: This randomised, controlled, open-label, parallel-group trial was done at 332 general practitioner practices in the UK. Eligible adults (aged ≥18 years) had at least one comorbidity or risk factor increasing their risk of adverse outcomes due to respiratory illness (eg, immune compromise due to serious illness or medication; heart disease; asthma or lung disease; diabetes; mild hepatic impairment; stroke or severe neurological problem; obesity [BMI ≥30 kg/m2]; or age ≥65 years) or at least three self-reported respiratory tract infections in a normal year (ie, any year before the COVID-19 pandemic). Participants were randomly assigned (1:1:1:1) using a computerised system to: usual care (brief advice about managing illness); gel-based spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); saline spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); or a brief behavioural intervention in which participants were given access to a website promoting physical activity and stress management. The study was partially masked: neither investigators nor medical staff were aware of treatment allocation, and investigators who did the statistical analysis were unaware of treatment allocation. The sprays were relabelled to maintain participant masking. Outcomes were assessed using data from participants\' completed monthly surveys and a survey at 6 months. The primary outcome was total number of days of illness due to self-reported respiratory tract illnesses (coughs, colds, sore throat, sinus or ear infections, influenza, or COVID-19) in the previous 6 months, assessed in the modified intention-to-treat population, which included all randomly assigned participants who had primary outcome data available. Key secondary outcomes were possible harms, including headache or facial pain, and antibiotic use, assessed in all randomly assigned participants. This trial was registered with ISRCTN, 17936080, and is closed to recruitment.
RESULTS: Between Dec 12, 2020, and April 7, 2023, of 19 475 individuals screened for eligibility, 13 799 participants were randomly assigned to usual care (n=3451), gel-based nasal spray (n=3448), saline nasal spray (n=3450), or the digital intervention promoting physical activity and stress management (n=3450). 11 612 participants had complete data for the primary outcome and were included in the primary outcome analysis (usual care group, n=2983; gel-based spray group, n=2935; saline spray group, n=2967; behavioural website group, n=2727). Compared with participants in the usual care group, who had a mean of 8·2 (SD 16·1) days of illness, the number of days of illness was significantly lower in the gel-based spray group (mean 6·5 days [SD 12·8]; adjusted incidence rate ratio [IRR] 0·82 [99% CI 0·76-0·90]; p<0·0001) and the saline spray group (6·4 days [12·4]; 0·81 [0·74-0·88]; p<0·0001), but not in the group allocated to the behavioural website (7·4 days [14·7]; 0·97 [0·89-1·06]; p=0·46). The most common adverse event was headache or sinus pain in the gel-based group: 123 (4·8%) of 2556 participants in the usual care group; 199 (7·8%) of 2498 participants in the gel-based group (risk ratio 1·61 [95% CI 1·30-1·99]; p<0·0001); 101 (4·5%) of 2377 participants in the saline group (0·81 [0·63-1·05]; p=0·11); and 101 (4·5%) of 2091 participants in the behavioural intervention group (0·95 [0·74-1·22]; p=0·69). Compared with usual care, antibiotic use was lower for all interventions: IRR 0·65 (95% CI 0·50-0·84; p=0·001) for the gel-based spray group; 0·69 (0·45-0·88; p=0·003) for the saline spray group; and 0·74 (0·57-0·94; p=0·02) for the behavioural website group.
CONCLUSIONS: Advice to use either nasal spray reduced illness duration and both sprays and the behavioural website reduced antibiotic use. Future research should aim to address the impact of the widespread implementation of these simple interventions.
BACKGROUND: National Institute for Health and Care Research.
METHODS: This randomised, controlled, open-label, parallel-group trial was done at 332 general practitioner practices in the UK. Eligible adults (aged ≥18 years) had at least one comorbidity or risk factor increasing their risk of adverse outcomes due to respiratory illness (eg, immune compromise due to serious illness or medication; heart disease; asthma or lung disease; diabetes; mild hepatic impairment; stroke or severe neurological problem; obesity [BMI ≥30 kg/m2]; or age ≥65 years) or at least three self-reported respiratory tract infections in a normal year (ie, any year before the COVID-19 pandemic). Participants were randomly assigned (1:1:1:1) using a computerised system to: usual care (brief advice about managing illness); gel-based spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); saline spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); or a brief behavioural intervention in which participants were given access to a website promoting physical activity and stress management. The study was partially masked: neither investigators nor medical staff were aware of treatment allocation, and investigators who did the statistical analysis were unaware of treatment allocation. The sprays were relabelled to maintain participant masking. Outcomes were assessed using data from participants\' completed monthly surveys and a survey at 6 months. The primary outcome was total number of days of illness due to self-reported respiratory tract illnesses (coughs, colds, sore throat, sinus or ear infections, influenza, or COVID-19) in the previous 6 months, assessed in the modified intention-to-treat population, which included all randomly assigned participants who had primary outcome data available. Key secondary outcomes were possible harms, including headache or facial pain, and antibiotic use, assessed in all randomly assigned participants. This trial was registered with ISRCTN, 17936080, and is closed to recruitment.
RESULTS: Between Dec 12, 2020, and April 7, 2023, of 19 475 individuals screened for eligibility, 13 799 participants were randomly assigned to usual care (n=3451), gel-based nasal spray (n=3448), saline nasal spray (n=3450), or the digital intervention promoting physical activity and stress management (n=3450). 11 612 participants had complete data for the primary outcome and were included in the primary outcome analysis (usual care group, n=2983; gel-based spray group, n=2935; saline spray group, n=2967; behavioural website group, n=2727). Compared with participants in the usual care group, who had a mean of 8·2 (SD 16·1) days of illness, the number of days of illness was significantly lower in the gel-based spray group (mean 6·5 days [SD 12·8]; adjusted incidence rate ratio [IRR] 0·82 [99% CI 0·76-0·90]; p<0·0001) and the saline spray group (6·4 days [12·4]; 0·81 [0·74-0·88]; p<0·0001), but not in the group allocated to the behavioural website (7·4 days [14·7]; 0·97 [0·89-1·06]; p=0·46). The most common adverse event was headache or sinus pain in the gel-based group: 123 (4·8%) of 2556 participants in the usual care group; 199 (7·8%) of 2498 participants in the gel-based group (risk ratio 1·61 [95% CI 1·30-1·99]; p<0·0001); 101 (4·5%) of 2377 participants in the saline group (0·81 [0·63-1·05]; p=0·11); and 101 (4·5%) of 2091 participants in the behavioural intervention group (0·95 [0·74-1·22]; p=0·69). Compared with usual care, antibiotic use was lower for all interventions: IRR 0·65 (95% CI 0·50-0·84; p=0·001) for the gel-based spray group; 0·69 (0·45-0·88; p=0·003) for the saline spray group; and 0·74 (0·57-0·94; p=0·02) for the behavioural website group.
CONCLUSIONS: Advice to use either nasal spray reduced illness duration and both sprays and the behavioural website reduced antibiotic use. Future research should aim to address the impact of the widespread implementation of these simple interventions.
BACKGROUND: National Institute for Health and Care Research.
摘要：
背景：少量证据表明鼻喷雾剂，或者身体活动和压力管理，可以缩短呼吸道感染的持续时间。这项研究旨在评估鼻腔喷雾剂或促进身体活动和压力管理的行为干预对呼吸系统疾病的影响。与平时的护理相比。
方法：这是随机的，控制,开放标签，在英国的332名全科医生诊所进行了平行组试验.符合条件的成年人（年龄≥18岁）至少有一种合并症或风险因素会增加他们因呼吸道疾病而导致不良结局的风险（例如，严重疾病或药物治疗引起的免疫损害;心脏病;哮喘或肺病;糖尿病;轻度肝功能损害;中风或严重的神经系统问题;肥胖[BMI≥30kg/m2];或年龄≥65岁)或在正常年份至少有三次自我报告的呼吸道感染(即,在COVID-19大流行之前的任何一年）。参与者被随机分配（1：1：1：1）使用计算机系统进行：常规护理（关于管理疾病的简短建议）；基于凝胶的喷雾剂（在感染的第一个迹象或潜在暴露于感染后，每个鼻孔喷雾两次，每天最多6次）；盐水喷雾（在感染的第一个迹象或潜在暴露于感染后，每个鼻孔喷雾两次，每天最多6次）；或简短的行为干预，其中参与者可以访问促进体育锻炼和压力管理的网站。该研究被部分掩盖：研究人员和医务人员都不知道治疗分配，进行统计学分析的研究者并不知晓治疗分配.重新标记喷雾剂以保持参与者掩蔽。使用参与者完成的月度调查和6个月时的调查数据评估结果。主要结果是由于自我报告的呼吸道疾病而患病的总天数（咳嗽，感冒,喉咙痛,鼻窦或耳部感染，流感,或COVID-19)在过去6个月中，在修改后的意向治疗人群中评估，其中包括所有具有主要结局数据的随机分配参与者.关键的次要结果是可能的危害，包括头痛或面部疼痛，和抗生素的使用，在所有随机分配的参与者中进行评估。该试验已在ISRCTN注册，17936080，并已停止招募。
结果：在2020年12月12日至2023年4月7日之间，对19475名个人进行了资格筛选，13799名参与者被随机分配到常规护理(n=3451)，基于凝胶的鼻喷雾剂（n=3448），生理盐水喷鼻剂（n=3450），或促进身体活动和压力管理的数字干预(n=3450)。11612名参与者具有主要结局的完整数据，并被纳入主要结局分析（常规护理组，n=2983；凝胶喷雾组，n=2935；生理盐水喷雾组，n=2967；行为网站组，n=2727）。与常规护理组的参与者相比，平均患病8·2(SD16·1)天，在基于凝胶的喷雾组(平均6·5天[SD12·8];调整后的发病率比率[IRR]0·82[99%CI0·76-0·90];p<0·0001)和盐水喷雾组(6·4天[12·4];0·81[0·74-0·88];p<0·0001)中,但不在分配给行为网站的组中（7·4天[14·7];0·97[0·89-1·06];p=0·46）。最常见的不良事件是基于凝胶的组的头痛或窦性疼痛：常规护理组2556名参与者中的123名（4·8％）；基于凝胶的组的2498名参与者中的199名（7·8％）（风险比1·61[95％CI1·30-1·99]；p<0·0001）；盐水组的2377名参与者中的101（4·5％）（0·91与平时护理相比，所有干预措施的抗生素使用率均较低:凝胶喷雾组的IRR0·65(95%CI0·50-0·84;p=0·001);生理盐水喷雾组的IRR0·69(0·45-0·88;p=0·003);行为网站组的IRR0·74(0·57-0·94;p=0·02).
结论：建议使用任何一种鼻喷雾剂可缩短病程，同时使用喷雾剂和行为网站可减少抗生素的使用。未来的研究应旨在解决广泛实施这些简单干预措施的影响。
背景：国家卫生和护理研究所。
方法：这是随机的，控制,开放标签，在英国的332名全科医生诊所进行了平行组试验.符合条件的成年人（年龄≥18岁）至少有一种合并症或风险因素会增加他们因呼吸道疾病而导致不良结局的风险（例如，严重疾病或药物治疗引起的免疫损害;心脏病;哮喘或肺病;糖尿病;轻度肝功能损害;中风或严重的神经系统问题;肥胖[BMI≥30kg/m2];或年龄≥65岁)或在正常年份至少有三次自我报告的呼吸道感染(即,在COVID-19大流行之前的任何一年）。参与者被随机分配（1：1：1：1）使用计算机系统进行：常规护理（关于管理疾病的简短建议）；基于凝胶的喷雾剂（在感染的第一个迹象或潜在暴露于感染后，每个鼻孔喷雾两次，每天最多6次）；盐水喷雾（在感染的第一个迹象或潜在暴露于感染后，每个鼻孔喷雾两次，每天最多6次）；或简短的行为干预，其中参与者可以访问促进体育锻炼和压力管理的网站。该研究被部分掩盖：研究人员和医务人员都不知道治疗分配，进行统计学分析的研究者并不知晓治疗分配.重新标记喷雾剂以保持参与者掩蔽。使用参与者完成的月度调查和6个月时的调查数据评估结果。主要结果是由于自我报告的呼吸道疾病而患病的总天数（咳嗽，感冒,喉咙痛,鼻窦或耳部感染，流感,或COVID-19)在过去6个月中，在修改后的意向治疗人群中评估，其中包括所有具有主要结局数据的随机分配参与者.关键的次要结果是可能的危害，包括头痛或面部疼痛，和抗生素的使用，在所有随机分配的参与者中进行评估。该试验已在ISRCTN注册，17936080，并已停止招募。
结果：在2020年12月12日至2023年4月7日之间，对19475名个人进行了资格筛选，13799名参与者被随机分配到常规护理(n=3451)，基于凝胶的鼻喷雾剂（n=3448），生理盐水喷鼻剂（n=3450），或促进身体活动和压力管理的数字干预(n=3450)。11612名参与者具有主要结局的完整数据，并被纳入主要结局分析（常规护理组，n=2983；凝胶喷雾组，n=2935；生理盐水喷雾组，n=2967；行为网站组，n=2727）。与常规护理组的参与者相比，平均患病8·2(SD16·1)天，在基于凝胶的喷雾组(平均6·5天[SD12·8];调整后的发病率比率[IRR]0·82[99%CI0·76-0·90];p<0·0001)和盐水喷雾组(6·4天[12·4];0·81[0·74-0·88];p<0·0001)中,但不在分配给行为网站的组中（7·4天[14·7];0·97[0·89-1·06];p=0·46）。最常见的不良事件是基于凝胶的组的头痛或窦性疼痛：常规护理组2556名参与者中的123名（4·8％）；基于凝胶的组的2498名参与者中的199名（7·8％）（风险比1·61[95％CI1·30-1·99]；p<0·0001）；盐水组的2377名参与者中的101（4·5％）（0·91与平时护理相比，所有干预措施的抗生素使用率均较低:凝胶喷雾组的IRR0·65(95%CI0·50-0·84;p=0·001);生理盐水喷雾组的IRR0·69(0·45-0·88;p=0·003);行为网站组的IRR0·74(0·57-0·94;p=0·02).
结论：建议使用任何一种鼻喷雾剂可缩短病程，同时使用喷雾剂和行为网站可减少抗生素的使用。未来的研究应旨在解决广泛实施这些简单干预措施的影响。
背景：国家卫生和护理研究所。
