Altering cough reflex sensitivity with aerosolized capsaicin paired with behavioral cough suppression: a proof-of-concept study

Background: The purpose of this prospective, quasi-experimental, single cohort proof-of-concept study was to determine feasibility and proof-of-concept of programmatically decreasing cough sensitivity through use of cough suppression strategies following inhalation of aerosolized capsaicin, in gradually increasing doses, across repeated treatment sessions. Methods: Five healthy adults, ages 20-32 years of age, enrolled and completed the study. The study commenced in three phases. Phase I consisted of baseline cough sensitivity testing using pharmaceutical-grade aerosolized capsaicin, delivered via a Koko DigiDoser with nebulizer. The single-inhale, dose-response method was used. Doses that elicited two coughs (C2) and five coughs (C5) were recorded. Testing ceased when participants met the C5 threshold or when they had been given the maximum close of 1,000 mu mol/L. Phase II consisted of 5-6 treatment sessions, during which participants were exposed to increasing doses of aerosolized capsaicin while implementing behavioral cough suppression strategies. In phase III, cough sensitivity was re-tested at 1 and 3 weeks post-treatment. Participants were given explicit instructions to not try to suppress their cough. Participants who did not reach the C2 or C5 threshold at 1,000 mu mol/L were assigned a score of 1,250 mu mol/L. Results: Each participant demonstrated a gradual increase in maximum capsaicin dose suppressed during each treatment session, with each successfully suppressing at 1,000 mu mol/L by the final treatment session. C2 was greater than baseline in 4 of the 5 participants at 1 week post-treatment, and in 3 of the 5, at 3 weeks post-treatment. C5 was greater in all 5 participants at both post-treatment time points. In fact, 4 of the 5 participants did not reach the C5 threshold during either post-treatment testing sessions. Wilcoxon's Signed Rank Test, using the logC2 and logC5 values, revealed a significant difference relative to baseline in logC5 at 1 week (z=-2.02, P=0.04) and 3 weeks (z=-2.03, P=0.04) post-treatment. The difference in logC2 neared significance at 1 week post-treatment z=-1.77, P=0.077), but was insignificant at 3 weeks post-treatment (z=-1.46, P=0.144). Conclusions: This study demonstrates the potential of treating patients with refractory chronic cough (RCC), due to cough hypersensitivity, with a progressive desensitization approach paired with behavioral cough suppression. Additional research is needed using a randomized, placebo-controlled trial with patients with RCC.