Modulation of protective reflex cough by acute immune driven inflammation of lower airways in anesthetized rabbits

PLoS One. 2019 Dec 30;14(12):e0226442. doi: 10.1371/journal.pone.0226442. eCollection 2019.

Abstract

Chronic irritating cough in patients with allergic disorders may reflect behavioral or reflex response that is inappropriately matched to the stimulus present in the respiratory tract. Such dysregulated response is likely caused by sensory nerve damage driven by allergic mediators leading to cough hypersensitivity. Some indirect findings suggest that even acid-sensitive, capsaicin-insensitive A-δ fibers called "cough receptors" that are likely responsible for protective reflex cough may be modulated through immune driven inflammation. The aim of this study was to find out whether protective reflex cough is altered during acute allergic airway inflammation in rabbits sensitized to ovalbumin. In order to evaluate the effect of such inflammation exclusively on protective reflex cough, C-fiber mediated cough was silenced using general anesthesia. Cough provocation using citric acid inhalation and mechanical stimulation of trachea was realized in 16 ovalbumin (OVA) sensitized, anesthetized and tracheotomised rabbits 24h after OVA (OVA group, n = 9) or saline challenge (control group, n = 7). Number of coughs provoked by citric acid inhalation did not differ between OVA and control group (12,2 ±6,1 vs. 17,9 ± 6,9; p = 0.5). Allergic airway inflammation induced significant modulation of cough threshold (CT) to mechanical stimulus. Mechanically induced cough reflex in OVA group was either up-regulated (subgroup named "responders" CT: 50 msec (50-50); n = 5 p = 0.003) or down-regulated (subgroup named "non responders", CT: 1200 msec (1200-1200); n = 4 p = 0.001) when compared to control group (CT: 150 msec (75-525)). These results advocate that allergen may induce longer lasting changes of reflex cough pathway, leading to its up- or down-regulation. These findings may be of interest as they suggest that effective therapies for chronic cough in allergic patients should target sensitized component of both, reflex and behavioral cough.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Anesthesia
  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Citric Acid / adverse effects*
  • Cough / blood
  • Cough / chemically induced
  • Cough / immunology*
  • Disease Models, Animal
  • Eosinophils / metabolism
  • Female
  • Leukocyte Count
  • Male
  • Ovalbumin / adverse effects*
  • Rabbits
  • Reflex / immunology*
  • Respiratory Hypersensitivity / blood
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / therapy

Substances

  • Citric Acid
  • Ovalbumin

Grants and funding

This work was supported by Ministry of High Education and Research of France (Ministère de l’Enseignement supérieur et de la Recherche) under contrat EA3450 DevAH. http://www.enseignementsup-recherche.gouv.fr/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.