Lidocaine Spray Shows Promise for Chronic Cough, Study Says

A new study shows that lidocaine throat spray can be an effective tool against refractory chronic cough (RCC), a debilitating condition for which no licensed treatments exist.

Researchers were primarily interested in investigating lidocaine administered by nebulizer. To their surprise, however, the throat spray showed significant improvement in cough frequency compared with placebo, but the nebulized treatment did not, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice in November.

The study of 26 subjects with RCC who were delivered lidocaine throat spray to the pharynx showed a significant reduction in cough frequency over a 10-hour span as compared with the nebulized treatment and placebo (throat spray, 22.6 coughs/hr; nebulization, 26.9 coughs/hr; and placebo, 27.6 coughs/hr; P = .04,). The greatest effect for the spray was in the first hour after treatment (31.7 coughs/hr vs. 74.2 coughs/hr; P = .004).

Both lidocaine treatments, however, significantly alleviated both the urge to cough (UtC) and cough severity, according to the study.

Investigators brought the throat spray into the study to improve blinding, not as a focus of the study. Nebulized lidocaine produces oropharyngeal anesthesia, while the placebo, of course, does not. Researchers said they wanted participants to have 2 of 3 interventions causing numbness.

Since lidocaine is a nonselective inhibitor of voltage-gated sodium channels, the study points to possible treatment through future sodium channel blockers—ones with fewer irritant effects and longer duration. Sodium channel blockers have been the subject of research interest in recent years.

There have been case reports and studies about the off-license of nebulized lidocaine for RCC and other respiratory disorders, but little in the way of randomized placebo-controlled studies, the authors wrote. The study from researchers in the United Kingdom, Saudi Arabia, Canada, and Japan was the first randomized placebo-controlled study of lidocaine in patients with RCC.

Effective proven treatment for chronic cough—lasting more than 8 weeks—has proven elusive. Finding an RCC treatment would be a benefit for other related health-related impacts besides the cough itself. Many chronic-cough suffers report anxiety, depression, frustration, fatigue, sleep disturbance, vomiting, and stress incontinence, the study said. Prevalence globally of chronic cough is in the 10%-12% range.

Finding explanations for why the throat spray was effective while the nebulized lidocaine was not should have “potential implications for the mode of delivery for future therapies and inform our understanding of the mechanisms underlying RCC,” the authors wrote.

Most patients say their coughing is provoked by sensations such as an irritation, tickle, or itch that also are present in upper respiratory tract infections, the authors wrote. Therefore, treatments have tended to focus on over-the-counter cough syrups and lozenges to relieve these sensations despite a lack of evidence of efficacy. However, the effectiveness of lidocaine throat spray confounds the issue because it works as an anesthetic rather than relieving irritation.

The role of the pharynx in cough has rarely been studied but needs to be, the authors said. The larynx, trachea, and airways are known to be innervated by vagal afferents in the case of the cough reflex. It is possible that effects on the local vagal afferent fibers explain reductions in cough frequency from treatments to the oropharynx. There is also evidence that cough can be mechanically triggered from the pharynx, just as the gag reflex can be.

The study, however, points to a new possibility—applying lidocaine spray to the oropharynx means that activating pharyngeal sensory fibers has a role in the frequency of cough in RCC.

The authors also posited on why nebulized lidocaine was ineffective. Lidocaine is thought to directly active transient receptor potential vanilloid type-1 (TRPV1) and transient receptor potential ankyrin1 (TRPA1) channels on sensory nerves, which would account for the initial painful burning sensation when it’s injected into the skin. In the airway, TRPA1 and TRPV1 are known to evoke coughing, so it’s possible they counteracted the nebulized spray. Also, patients tend to cough when it is initially administered, possibly reducing the deposit of aerosolized particles.

The effectiveness of the spray and the nebulized lidocaine against UtC and cough severity might be due to patients expecting to see improvement from agents that reduce some of sensations that trigger a cough, according to the researchers.

Reference

Abdulqawi R, Satia I, Kanemitsu Y, et al. A randomized controlled trial to assess the effect of lidocaine administered via throat spray and nebulization in patients with refractory chronic cough. J Allergy Clin Immunol Pract. Published online November 28, 2020. doi:10.1016/j.jaip.2020.11.037.