New knowledge about the neural aspects of cough has revealed a complex network of pathways that initiate cough. The effect of inflammation on cough neural processing occurs at multiple peripheral and central sites within the nervous system. Evidence exists that direct or indirect neuroimmune interaction induces a complex response, which can be altered by mediators released by the sensory or parasympathetic neurons and vice versa. The aim of this study was to clarify changes of cough reflex sensitivity - the activity of airway afferent nerve endings - in asthmatic children.25 children with asthma and 15 controls were submitted to cough reflex sensitivity measurement - capsaicin aerosol in doubling concentrations (from 0.61 to 1250 µmol/l) was inhaled by a single breath method. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Asthmatic children' (11 boys and 14 girls, mean age 9 ± 1 yrs) cough reflex sensitivity (geometric mean, with the 95 % CI) for C2 was 4.25 (2.25-8.03) µmol/l vs. control C2 (6 boys and 9 girls, mean age 8 ± 1 yrs) was 10.61 (5.28-21.32) µmol/l (p=0.024). Asthmatic children' C5 was 100.27 (49.30-203.93) µmol/l vs. control C5 56.53 (19.69-162.35) µmol/l (p=0.348). There was a statistically significant decrease of C2 (cough threshold) in the asthmatic patients relative to controls (p-value for the two-sample t-test of log(C2) for the one-sided alternative, p-value = 0.024). The 95 % confidence interval for the difference of the mean C2 in asthma vs. control, [1.004, 6.207]. For C5, the difference was not statistically significant (p-value = 0.348). There was a statistically significant decrease of cough reflex sensitivity (the activity of airway afferent nerve endings) - C2 value in the asthmatic children relative to controls.

Department of Pathological Physiology Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovak

Zobrazit více v PubMed

CHANG AB, PHELAN PD, ROBERTSON CF. Cough receptor sensitivity in children with acute and non-acute asthma. Thorax. 1997;52:770–774. doi: 10.1136/thx.52.9.770. PubMed DOI PMC

CHUNG KF, MCGARVEY L, MAZZONE SB. Chronic cough as a neuropathic disorder. Lancet Respir Med. 2013;1:414–422. doi: 10.1016/S2213-2600(13)70043-2. PubMed DOI

DRIESSEN AK, McGOVERN AE, NARULA M, YANG SK, KELLER JA, FARRELL MJ, MAZZONE SB. Central mechanisms of airway sensation and cough hypersensitivity. Pulm Pharmacol Ther. 2017;47:9–15. doi: 10.1016/j.pupt.2017.01.010. PubMed DOI

HELLEBRANDOVÁ L, CHLUMSKÝ J, VOSTATEK P, NOVÁK D, RÝZNAROVÁ Z, BUNC V. Airflow limitation is accompanied by diaphragm dysfunction. Physiol Res. 2016;65:469–479. doi: 10.33549/physiolres.933064. PubMed DOI

KÁDKOVÁ A, SYNYTSYA V, KRUSEK J, ZÍMOVÁ L, VLACHOVÁ V. Molecular basis of TRPA1 regulation in nociceptive neurons. A review. Physiol Res. 2017;66:425–439. doi: 10.33549/physiolres.933553. PubMed DOI

KANTAR A, SEMINARA M. Why chronic cough in children is different. Pulm Pharmacol Ther. 2019;56:51–55. doi: 10.1016/j.pupt.2019.03.001. PubMed DOI

McCORMACK DG, MAK JC, COUPE MO, BARNES PJ. Calcitonin gene-related peptide vasodilation of human pulmonary vessels. J Appl Physiol. 1989;67:1265–1270. doi: 10.1152/jappl.1989.67.3.1265. PubMed DOI

MIKAMI N, MATSUSHITA H, KATO T, KAWASAKI R, SAWAZAKI T, KISHIMOTO T, OGITANI Y, WATANABE K, MIYAGI Y, SUEDA K, FUKADA S, YAMAMOTO H, TSUJIKAWA K. Calcitonin gene-related peptide is an important regulator of cutaneous immunity: effect on dendritic cell and T cell functions. J Immunol. 2011;86:6886–6893. doi: 10.4049/jimmunol.1100028. PubMed DOI

MORICE AH, FONTANA GA, BELVISI MG, BIRRING SS, CHUNG KF, DICPINIGAITIS PV, KASTELIK JA, MCGARVEY LP, SMITH JA, TATAR M, WIDDICOMBE J. ERS guidelines on the assessment of cough. Eur Respir J. 2007;29:1256–1276. doi: 10.1183/09031936.00101006. PubMed DOI

MORICE AH, McGARVEY LP, DICPINIGAITIS PV. Cough hypersensitivity syndrome is an important clinical concept: a pro/con debate. Lung. 2012;190:3–9. doi: 10.1007/s00408-011-9351-y. PubMed DOI

NIIMI A, CHUNG KF. Evidence for neuropathic processes in chronic cough. Pulm Pharmacol Ther. 2015;35:100–104. doi: 10.1016/j.pupt.2015.10.004. PubMed DOI

NIIMI A, FUKUMITSU K, TAKEDA N, KANEMITSU Y. Interfering with airway nerves in cough associated with asthma. Pulm Pharmacol Ther. 2019;59:101854. doi: 10.1016/j.pupt.2019.101854. PubMed DOI

NUMAO T, AGRAWAL DK. Neuropeptides modulate human eosinophil chemotaxis. J Immunol. 1992;149:3309–3315. PubMed

SONG WJ, CHANG YS. Cough hypersensitivity as a neuro-immune interaction. Clin Transl Allergy. 2015;5:24. doi: 10.1186/s13601-015-0069-4. PubMed DOI PMC

SONG WJ, MORICE AH. Cough hypersensitivity syndrome: a few more steps forward. Allergy Asthma Immunol Res. 2017;9:394–402. doi: 10.4168/aair.2017.9.5.394. PubMed DOI PMC

UNDEM BJ, TAYLOR-CLARK T. Mechanisms underlying the neuronal-based symptoms of allergy. J Allergy Clin Immunol. 2014;133:1521–1534. doi: 10.1016/j.jaci.2013.11.027. PubMed DOI PMC

VARECHOVA S, PLEVKOVA J, HANACEK J, TATAR M. Role of gender and pubertal stage on cough sensitivity in childhood and adolescence. J Physiol Pharmacol. 2008;59:719–726. PubMed

ZACCONE EJ, LIEU T, MUROI Y, POTENZIERI C, UNDEM BE, GAO P, HAN L, CANNING BJ, UNDEM BJ. Parainfluenza 3-induced cough hypersensitivity in the guinea pig airways. PLoS One. 2016;11:e0155526. doi: 10.1371/journal.pone.0155526. PubMed DOI PMC

Association of selected inflammatory biomarkers with cough reflex sensitivity in asthmatic children

Legacy of Prof. Juraj Korpáš: International Impact of Slovak School of Experimental Respirology