A systematic review and meta-analysis of neuromodulators to treat chronic airway hypersensitivity

Objectives: Chronic laryngitis can present with numerous symptoms, including chronic cough. Patients who do not respond to standard treatment are sometimes diagnosed with chronic airway hypersensitivity (CAH). In many centers, neuromodulators are prescribed off-label despite limited evidence of efficacy. A previous metaanalysis suggested neuromodulator therapy improved cough-related quality-of-life (QoL). This current updated and expanded meta-analysis examined whether neuromodulators reduced cough frequency, reduced cough severity, and/or improved QoL in CAH patients.Data sources: PubMed, Embase, Medline, Cochrane Review, and publication bibliographies were searched from 01/01/2000 to 07/31/2021 using MESH terms.Review methods: PRISMA guidelines were followed. 999 abstracts were identified/screened, 28 studies were fully reviewed, and 3 met inclusion criteria. Only randomized controlled trials (RCT) investigating CAH patients with comparable cough-related outcomes were included. Three authors reviewed potentially eligible papers. Fixedeffect models and calculated pooled estimates using the Inverse-Variance method were used.Results: The estimated difference in change in log coughs per hour (from baseline to intervention end) between treatment and control groups was -0.46, 95%CI [-0.97; 0.05]. Estimated change-from-baseline in VAS scores was -12.24, 95 % CI [-17.84; -6.65] lower for patients who received treatment vs placebo. Estimated changefrom-baseline for LCQ scores was 2.15, 95 % CI [1.49-2.80] higher for patients who receive treatment vs placebo. Only change in LCQ score was clinically significant.Conclusions: This study tentatively suggests that neuromodulators have the potential to reduce cough symptoms associated with CAH. However, high-quality evidence is lacking. This could be due to limited treatment effect or significant limitations in the design and comparability of existing trials. A well-designed and properly powered RCT is needed to authoritatively test the efficacy of neuromodulators for the treatment of CAH. Level of evidence: Level I, evidence from a systematic review or meta-analysis of all relevant RCTs (randomized controlled trial) or evidence-based clinical practice guidelines based on systematic reviews of RCTs or three or more RCTs of good quality that have similar results.