Efficacy of Nasal Sprays in Respiratory Illness Management

Limited evidence suggests that nasal sprays, engagement in physical activity and stress management, may shorten the duration of respiratory infections. A UK study published in The Lancet found that using nasal sprays was linked to reduced illness duration, and both nasal sprays and a behavioral website contributed to decreased antibiotic usage.

Between December 12, 2020, and April 7, 2023, 19,475 individuals were screened, and 13,799 were randomly assigned to four groups: usual care (3451), gel-based nasal spray (3448), saline nasal spray (3450), and a digital intervention promoting physical activity and stress management (3450). Among the 11,612 participants analyzed for the primary outcome, those using gel-based and saline nasal sprays had significantly fewer illness days compared to usual care (mean 6.5 days (SD 12.8) and 6.4 days (12.4), respectively, versus mean 8.2 days (SD 16.1); adjusted incidence rate ratios .82 (99% CI .76–.90) and .81 (.74–.88), both p<.0001).

“This is the largest study to explore the benefit of accessible, easily scalable interventions used preventatively or early in respiratory illness in primary care settings,” according to The Lancet Investigators. “Compared with usual care, both nasal sprays when used at the first sign of a respiratory tract infection had a clinically significant effect on illness duration and reduced number of workdays lost, and all three interventions reduced antibiotic use.”

This UK trial, conducted at 332 general practitioner practices, focused on adults (≥18 years) with comorbidities or frequent respiratory infections. Participants were randomly assigned (1:1:1:1) to receive usual care, gel-based nasal spray, saline nasal spray, or a behavioral intervention via a website promoting physical activity and stress management. The study was partially masked, with outcomes assessed through monthly surveys and a final 6-month survey. The primary outcome measured total days of respiratory illness over 6 months, with key secondary outcomes including potential adverse effects and antibiotic use.

“The study was an open-label trial, and it would be difficult to devise a meaningful placebo since the delivery mechanism (spraying) is an inherent part of the intervention,” explains investigators. “The nasal sprays were relabelled (to retain some form of masking). Furthermore, for some conditions, there are large placebo effects, but for acute respiratory infections even where belief in medication efficacy is high, the estimates from open-label trials suggest no or minimal placebo effect compared with estimates from placebo-controlled trials in the Cochrane reviews, with similar evidence for trials of medicines in COVID-19.”

The digital intervention did not significantly reduce illness duration (7.4 days (14.7); adjusted incidence rate ratio .97 (.89–1.06), p=.46). Participants using the gel-based spray reported more headaches or sinus pain (7.8%) compared to those receiving usual care (4.8%) (risk ratio 1.61 (95% CI 1.30–1.99), p<.0001), while antibiotic use was lower with all interventions compared to usual care (incidence rate ratios .65 (.50–.84), .69 (.45–.88), and .74 (.57–.94), respectively, all p<.05).

This study focused solely on participants with complete primary outcome data, using imputation for secondary outcomes. Outcomes remained consistently significant across intervention groups without adjustments for multiplicity. The study relied on self-reported symptoms without confirming infectious agents and included a sample that differed demographically from the general UK population. Syndromic management without confirming specific pathogens was typical, with challenges observed in participant engagement and adherence, particularly with preventive spray use. Comparison of gel-based and saline sprays showed similar effectiveness, primarily benefiting from nasal cleansing rather than formulation differences. The scalable digital behavioral intervention had modest effects on illness and antibiotic use.

These findings suggest that accessible interventions like nasal sprays and behavioral approaches could play a role in reducing the burden of respiratory infections in primary care settings. They highlight the potential for personalized, non-pharmacological interventions to complement traditional treatments and reduce antibiotic overuse, which is important in healthcare. Further research is needed to optimize intervention strategies, enhance participant engagement, and explore underlying mechanisms to maximize their impact on public health.

Reference

Little P, Vennik J, Rumsby K, et al. Nasal sprays and behavioural interventions compared with usual care for acute respiratory illness in primary care: a randomised, controlled, open-label, parallel-group trial. The Lancet. Published July 11, 2024. Accessed July 22, 2024. DOI: https://doi.org/10.1016/S2213-2600(24)00140-1