Increased Tachykinin Levels in Induced Sputum from Asthmatic and Cough Patients with Acid Reflux

Overview

Journal Thorax

Date 2007 Jan 26

PMID 17251314

Citations 30

Authors

Robert N Patterson

Brian T Johnston

Joy E S Ardill

Liam G Heaney

Lorcan P A McGarvey

Affiliations

Soon will be listed here.

Abstract

Background: Acid reflux may aggravate airway disease including asthma and chronic cough. One postulated mechanism concerns a vagally-mediated oesophageal-tracheobronchial reflex with airway sensory nerve activation and tachykinin release.

Aim: To test the hypothesis that patients with airways disease and reflux have higher airway tachykinin levels than those without reflux.

Methods: Thirty-two patients with airways disease (16 with mild asthma and 16 non-asthmatic subjects with chronic cough) underwent 24 h oesophageal pH monitoring. Acid reflux was defined as increased total oesophageal acid exposure (% total time pH<4 of >4.9% at the distal probe). All subjects underwent sputum induction. Differential cell counts and concentrations of substance P (SP), neurokinin A (NKA), albumin and alpha2-macroglobulin were determined.

Results: SP and NKA levels were significantly higher in patients with reflux than in those without (SP: 1434 (680) pg/ml vs 906 (593) pg/ml, p=0.026; NKA: 81 (33) pg/ml vs 52 (36) pg/ml, p=0.03). Significantly higher tachykinin levels were also found in asthmatic patients with reflux than in asthmatic patients without reflux (SP: 1508 (781) pg/ml vs 737 (512) pg/ml, p=0.035; NKA: median (interquartile range 108 (85-120) pg/ml vs 75 (2-98) pg/ml, p=0.02). In patients with asthma there was a significant positive correlation between distal oesophageal acid exposure and SP levels (r=0.59, p=0.01) and NKA levels (r=0.56, p=0.02). Non-significant increases in SP and NKA were measured in patients with cough with reflux (SP: 1534.71 (711) pg/ml vs 1089 (606) pg/ml, p=0.20; NKA: 56 (43) pg/ml vs 49 (17) pg/ml, p=0.71). No significant difference in differential cell counts or any other biochemical parameter was noted between study groups.

Conclusion: This study demonstrates increased airway tachykinin levels in patients with asthma and cough patients with coexistent acid reflux. This suggests airway sensory nerve activation in this population.

Citing Articles

An underlying mechanism behind interventional pulmonology techniques for refractory asthma treatment: Neuro-immunity crosstalk.

Liao X, Gao S, Xie F, Wang K, Wu X, Wu Y Heliyon. 2023; 9(10):e20797.

PMID: 37867902 PMC: 10585236. DOI: 10.1016/j.heliyon.2023.e20797.

Advancing Lung Immunology Research: An Official American Thoracic Society Workshop Report.

Rahimi R, Cho J, Jakubzick C, Khader S, Lambrecht B, Lloyd C Am J Respir Cell Mol Biol. 2022; 67(1):e1-18.

PMID: 35776495 PMC: 9273224. DOI: 10.1165/rcmb.2022-0167ST.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - .

Rouadi P, Idriss S, Bousquet J, Laidlaw T, Azar C, Al-Ahmad M World Allergy Organ J. 2021; 14(12):100618.

PMID: 34963794 PMC: 8666560. DOI: 10.1016/j.waojou.2021.100618.

Neuroimmune Pathophysiology in Asthma.

Pavon-Romero G, Serrano-Perez N, Garcia-Sanchez L, Ramirez-Jimenez F, Teran L Front Cell Dev Biol. 2021; 9:663535.

PMID: 34055794 PMC: 8155297. DOI: 10.3389/fcell.2021.663535.

Current therapies for gastro-oesophageal reflux in the setting of chronic lung disease: state of the art review.

McDonnell M, Hunt E, Ward C, Pearson J, OToole D, Laffey J ERJ Open Res. 2021; 6(4).

PMID: 33693049 PMC: 7927787. DOI: 10.1183/23120541.00190-2019.

References

Reynolds P, Scicchitano R, Holmes M . Pre-protachykinin-A mRNA is increased in the airway epithelium of smokers with chronic bronchitis. Respirology. 2001; 6(3):187-97. DOI: 10.1046/j.1440-1843.2001.00333.x. View

van Rensen E, Hiemstra P, Rabe K, Sterk P . Assessment of microvascular leakage via sputum induction: the role of substance P and neurokinin A in patients with asthma. Am J Respir Crit Care Med. 2002; 165(9):1275-9. DOI: 10.1164/rccm.2110092. View

Yamauchi K, Kobayashi H, Tanifuji Y, Kato C, Suzuki K, Inoue H . Effects of esophageal acid perfusion on cough responsiveness in patients with bronchial asthma. Chest. 2002; 122(2):505-9. DOI: 10.1378/chest.122.2.505. View

Daoui S, DAgostino B, Gallelli L, Alt X, Rossi F, Advenier C . Tachykinins and airway microvascular leakage induced by HCl intra-oesophageal instillation. Eur Respir J. 2002; 20(2):268-73. DOI: 10.1183/09031936.02.00250902. View

Lee S, Kim M, Shin C, Shim J, Kim H, Kang K . Substance P-immunoreactive nerves in endobronchial biopsies in cough-variant asthma and classic asthma. Respiration. 2003; 70(1):49-53. DOI: 10.1159/000068413. View

Ghaed N, Stein M . Assessment of a technique for scintigraphic monitoring of pulmonary aspiration of gastric contents in asthmatics with gastroesophageal reflux. Ann Allergy. 1979; 42(5):306-8. View

Mansfield L, Hameister H, Spaulding H, Smith N, Glab N . The role of the vague nerve in airway narrowing caused by intraesophageal hydrochloric acid provocation and esophageal distention. Ann Allergy. 1981; 47(6):431-4. View

Joos G, Pauwels R, VAN DER STRAETEN M . Effect of inhaled substance P and neurokinin A on the airways of normal and asthmatic subjects. Thorax. 1987; 42(10):779-83. PMC: 460951. DOI: 10.1136/thx.42.10.779. View

Martling C, Lundberg J . Capsaicin sensitive afferents contribute to acute airway edema following tracheal instillation of hydrochloric acid or gastric juice in the rat. Anesthesiology. 1988; 68(3):350-6. DOI: 10.1097/00000542-198803000-00005. View

10.

Masclee A, de Best A, de Graaf R, Cluysenaer O, Jansen J . Ambulatory 24-hour pH-metry in the diagnosis of gastroesophageal reflux disease. Determination of criteria and relation to endoscopy. Scand J Gastroenterol. 1990; 25(3):225-30. View

11.

Sontag S, OConnell S, Khandelwal S, Miller T, Nemchausky B, Schnell T . Most asthmatics have gastroesophageal reflux with or without bronchodilator therapy. Gastroenterology. 1990; 99(3):613-20. DOI: 10.1016/0016-5085(90)90945-w. View

12.

Johnston B, McFarland R, Collins J, Love A . Symptom index as a marker of gastro-oesophageal reflux disease. Br J Surg. 1992; 79(10):1054-5. DOI: 10.1002/bjs.1800791022. View

13.

Fahy J, Liu J, Wong H, Boushey H . Cellular and biochemical analysis of induced sputum from asthmatic and from healthy subjects. Am Rev Respir Dis. 1993; 147(5):1126-31. DOI: 10.1164/ajrccm/147.5.1126. View

14.

DeRose V, Robbins R, Snider R, Spurzem J, Thiele G, Rennard S . Substance P increases neutrophil adhesion to bronchial epithelial cells. J Immunol. 1994; 152(3):1339-46. View

15.

Ing A, Ngu M, Breslin A . Pathogenesis of chronic persistent cough associated with gastroesophageal reflux. Am J Respir Crit Care Med. 1994; 149(1):160-7. DOI: 10.1164/ajrccm.149.1.8111576. View

16.

Jack C, Calverley P, Donnelly R, Tran J, Russell G, Hind C . Simultaneous tracheal and oesophageal pH measurements in asthmatic patients with gastro-oesophageal reflux. Thorax. 1995; 50(2):201-4. PMC: 473925. DOI: 10.1136/thx.50.2.201. View

17.

Heaney L, Cross L, Stanford C, Ennis M . Substance P induces histamine release from human pulmonary mast cells. Clin Exp Allergy. 1995; 25(2):179-86. DOI: 10.1111/j.1365-2222.1995.tb01024.x. View

18.

Field S, Underwood M, Brant R, Cowie R . Prevalence of gastroesophageal reflux symptoms in asthma. Chest. 1996; 109(2):316-22. DOI: 10.1378/chest.109.2.316. View

19.

Dati F, Schumann G, Thomas L, Aguzzi F, Baudner S, Bienvenu J . Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP Reference Material (CRM 470). International Federation.... Eur J Clin Chem Clin Biochem. 1996; 34(6):517-20. View

20.

Hamamoto J, Kohrogi H, Kawano O, Iwagoe H, Fujii K, Hirata N . Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs. J Appl Physiol (1985). 1997; 82(3):738-45. DOI: 10.1152/jappl.1997.82.3.738. View