Efficacy of nasal sprays in managing respiratory illness

Nasal sprays and behavioral interventions that reduce reliance on antibiotics to treat respiratory infections can help mitigate the development of antimicrobial resistance.

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Limited evidence suggests that nasal sprays, physical activity, and stress management may shorten the duration of respiratory infections. The Lancet magazine Use of nasal sprays was associated with a shorter duration of illness, and both nasal sprays and behavioral therapy contributed to a reduction in antibiotic use.

Between December 12, 2020 and April 7, 2023, 19,475 people were screened and 13,799 were randomized to one of four groups: usual care (n=3,451), gel-based nasal spray (n=3,448), saline nasal spray (n=3,450), and a digital intervention promoting physical activity and stress management (n=3,450). Of the 11,612 participants analyzed for the primary outcome, those who used gel-based nasal spray and saline nasal spray had significantly fewer sick days compared with usual care (mean 6.5 days (SD 12.8) and 6.4 days (12.4) vs mean 8.2 days (SD 16.1), respectively; adjusted incidence rate ratios .82 (99% CI .76 to .90) and .81 (.74 to .8 …

“This is the largest study to investigate the benefits of an accessible, scalable intervention used to prevent or treat early respiratory disease in a primary care setting.” Lancet The researchers wrote: “Compared with usual care, use of both nasal sprays at the first sign of respiratory infection had clinically significant effects in reducing illness duration and missed work days, and all three interventions reduced antibiotic use.”

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

“This study was open-label and the administration mechanism (nebulization) is an intrinsic part of the intervention, making it difficult to devise a meaningful placebo,” the researchers explained. “The nasal spray was relabeled (to maintain some form of masking). Furthermore, although placebo effects are large for some conditions, for acute respiratory infections, even when confidence in the drug's effectiveness is high, estimates from open-label trials suggest no or minimal placebo effects compared with estimates from placebo-controlled trials in the Cochrane review, and there is similar evidence in trials of drugs for COVID-19.”

The digital interventions did not significantly reduce illness duration (7.4 (14.7) days; adjusted incidence rate ratio 0.97 (0.89–1.06); p=0.46). Participants who used the gel-based spray were more likely to report headache or sinus pain (7.8%) compared with those who received usual care (4.8%) (risk ratio 1.61 (95% CI 1.30–1.99); p<.0001). However, antibiotic use was lower across all interventions compared with usual care (incidence rate ratios 0.65 (0.50–0.84), 0.69 (0.45–0.88), and 0.74 (0.57–0.94), respectively; all p<.05).

The study only included participants with complete primary outcome data and used imputation methods for secondary outcomes. Results were consistently significant across intervention groups without adjustment for multiplicity. The study relied on self-reported symptoms without identifying infectious agents and included a demographically distinct sample from the general UK population. Syndromic management without identifying specific pathogens was common and challenges were seen in participant engagement and adherence, particularly with regard to the use of prophylactic sprays. A comparison of gel-based sprays and saline sprays showed similar efficacy, mainly benefiting from nasal irrigation rather than differences in formulation. The scalable digital behavioral intervention had a modest effect on illness and antibiotic use.

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

reference

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