All Title Author
Keywords Abstract

Induced Sputum Substance P in Children with Difficult-to-Treat Bronchial Asthma and Gastroesophageal Reflux: Effect of Esomeprazole Therapy

DOI: 10.1155/2011/967460

Full-Text   Cite this paper   Add to My Lib


Objectives. To assess the induced sputum substance P (ISSP) levels in children having difficult-to-treat asthma (DA) with and without gastroesophageal reflux (GER). We aimed also to evaluate the association of GER with childhood DA, relationship of GER severity with childhood asthma control test (C-ACT), FEV1, peak expiratory flow (PEF) variability, and ISSP. Finally, we tried to evaluate esomeprazole treatment effect on C-ACT and FEV1 in children with DA. Methods. Spirometry, C-ACT, upper gastrointestinal endoscopy, and ISSP measurement were done for children with DA compared to healthy controls. Results. ISSP was high in DA with higher levels in the group having associated GER. In the latter group, ISSP and C-ACT improved significantly after esomeprazole treatment while FEV1 and PEF variability did not improve. Reflux severity was positively correlated with ISSP and negatively correlated with FEV1. Conclusions. GER was found in 49% of our patients with childhood DA. Very high ISSP levels in children with DA may be used as a marker for presence of GERD. Esomeprazole therapy improved asthma symptoms but did not improve lung function. 1. Introduction Asthma is a common chronic complex inflammatory airway disorder characterized by variable degrees of recurring symptoms of airflow obstruction and bronchial hyperresponsiveness [1]. Although the majority of asthma patients can obtain the targeted level of control, some patients will not achieve control even with the best therapy [2]. Patients who do not reach an acceptable level of control with the use of reliever medication plus two or more controllers can be considered to have difficult-to-treat asthma [3]. The association between asthma and gastrooesophageal reflux (GER) has been debated for decades when Sir William Osler first observed the association between worsening asthma and distended stomach in 1892 [4]. The prevalence of symptoms of GER among individuals with asthma is substantially higher than in normal population and similarly the prevalence of asthma in individuals with GER is also higher than in controls [5]. Gastroesophageal reflux (GER) may cause chronic respiratory disease by vagal response and tracheal aspiration of gastric contents [6]. Aspiration of gastric contents changes pulmonary resistance and causes reactive airway obstruction [7]. Gastrooesophageal reflux may contribute to airway inflammatory events, possibly by sensory nerve stimulation and the subsequent release of tachykinins into the airway [8]. The tachykinins as substance P (SP) and neurokinin A are the neuropeptides most


[1]  U. S. Department of Health and Human Services, National Institute of Health, National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program, “Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma,” Full Report 2007,
[2]  R. A. Nathan, C. A. Sorkness, M. Kosinski et al., “Development of the asthma control test: a survey for assessing asthma control,” Journal of Allergy and Clinical Immunology, vol. 113, no. 1, pp. 59–65, 2004.
[3]  S. Wenzel, “Severe asthma in adults,” American Journal of Respiratory and Critical Care Medicine, vol. 172, no. 2, pp. 149–160, 2005.
[4]  N. Kalach, L. Gumpert, P. Contencin, and C. Dupont, “Dual-probe pH monitoring for the assessment of gastroesophageal reflux in the course of chronic hoarseness in children,” Turkish Journal of Pediatrics, vol. 42, no. 3, pp. 186–191, 2000.
[5]  B. D. Havemann, C. A. Henderson, and H. B. El-Serag, “The association between gastro-oesophageal reflux disease and asthma: a systematic review,” Gut, vol. 56, no. 12, pp. 1654–1664, 2007.
[6]  C. Astarita, D. Gargano, M. Cutajar, A. Napolitano, F. Manguso, and G. F. Abbate, “Gastroesophageal reflux disease and asthma: an intriguing dilemma,” Allergy, vol. 55, no. 61, pp. 52–55, 2000.
[7]  O. Sacco, B. Fregonese, M. Silvestri, F. Sabatini, G. Mattioli, and G. A. Rossi, “Bronchoalveolar lavage and esophageal pH monitoring data in children with “difficult to treat” respiratory symptoms,” Pediatric Pulmonology, vol. 30, no. 4, pp. 313–319, 2000.
[8]  R. N. Patterson, B. T. Johnston, J. E. S. Ardill, L. G. Heaney, and L. P. A. McGarvey, “Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux,” Thorax, vol. 62, no. 6, pp. 491–495, 2007.
[9]  P. J. Barnes, “Neurogenic inflammation in the airways,” Respiration Physiology, vol. 125, no. 1-2, pp. 145–154, 2001.
[10]  S. M. Harding, M. R. Guzzo, and J. E. Richter, “The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms,” American Journal of Respiratory and Critical Care Medicine, vol. 162, no. 1, pp. 34–39, 2000.
[11]  M. D. Crowell, E. N. Zayat, B. E. Lacy, A. Schettler-Duncan, and M. C. Liu, “The effects of an inhaled β2-adrenergic agonist on lower esophageal function: a dose-response study,” Chest, vol. 120, no. 4, pp. 1184–1189, 2001.
[12]  K. Thakkar, R. O. Boatright, M. A. Gilger, and H. B. El-Serag, “Gastroesophageal reflux and asthma in children: a systematic review,” Pediatrics, vol. 125, no. 4, pp. e925–e930, 2010.
[13]  M. Ay, E. Sivasli, Z. Bayraktaroglu, H. Ceylan, and Y. Coskun, “Association of asthma with gastroesophageal reflux disease in children,” Journal of the Chinese Medical Association, vol. 67, no. 2, pp. 63–66, 2004.
[14]  “British Thoracic Society/Scottish Intercollegiate Guidelines Network, British guidelines on the management of asthma,” Thorax, vol. 58, supplement 1, pp. i1–i94, 2003.
[15]  J. J. Leggett, B. T. Johnston, M. Mills, J. Gamble, and L. G. Heaney, “Prevalence of gastroesophageal reflux in difficult asthma: relationship to asthma outcome,” Chest, vol. 127, no. 4, pp. 1227–1231, 2005.
[16]  A. H. Liu, R. Zeiger, C. Sorkness et al., “Development and cross-sectional validation of the childhood asthma control test,” Journal of Allergy and Clinical Immunology, vol. 119, no. 4, pp. 817–825, 2007.
[17]  K. W. Bundy, J. F. Gent, W. Beckett et al., “Household airborne Penicillium associated with peak expiratory flow variability in asthmatic children,” Annals of Allergy, Asthma and Immunology, vol. 103, no. 1, pp. 26–30, 2009.
[18]  M. A. Biltagi, A. A. Baset, M. Bassiouny, M. A. Kasrawi, and M. Attia, “Omega-3 fatty acids, vitamin C and Zn supplementation in asthmatic children: a randomized self-controlled study,” Acta Paediatrica, International Journal of Paediatrics, vol. 98, no. 4, pp. 737–742, 2009.
[19]  V. Khoshoo, R. Haydel, and E. Saturno, “Gastroesophageal reflux disease and asthma in children,” Current Gastroenterology Reports, vol. 8, no. 3, pp. 237–243, 2006.
[20]  J. Kwiecien, E. MacHura, F. Halkiewicz, and J. Karpe, “Clinical features of asthma in children differ with regard to the intensity of distal gastroesophageal acid reflux,” Journal of Asthma, vol. 48, no. 4, pp. 366–373, 2011.
[21]  J. P. Lazenby, M. R. Guzzo, S. M. Harding, P. E. Patterson, L. F. Johnson, and L. A. Bradley, “Oral corticosteroids increase esophageal acid contact times in patients with stable asthma,” Chest, vol. 121, no. 2, pp. 625–634, 2002.
[22]  S. M. Harding, “Gastroesophageal reflux and asthma: insight into the association,” Journal of Allergy and Clinical Immunology, vol. 104, no. 2 I, pp. 251–259, 1999.
[23]  C. L. Liu, K. F. Lai, R. C. Chen et al., “The role of airway neurogenic inflammation in gastro-esophageal reflux induced cough,” Zhonghua Jie He He Hu Xi Za Zhi, vol. 28, no. 8, pp. 520–524, 2005.
[24]  G. F. Joos, P. R. Germonpré, and R. A. Pauwels, “Role of tachykinins in asthma,” Allergy, vol. 55, no. 4, pp. 321–337, 2000.
[25]  V. Khoshoo and R. Haydel, “Effect of antireflux treatment on asthma exacerbations in nonatopic children,” Journal of Pediatric Gastroenterology and Nutrition, vol. 44, no. 3, pp. 331–335, 2007.
[26]  V. Khoshoo, S. Mohnot, R. Haydel, E. Saturno, D. Edell, and A. Kobernick, “Bronchial hyperreactivity in non-atopic children with asthma and reflux: effect of anti-reflux treatment,” Pediatric Pulmonology, vol. 44, no. 11, pp. 1070–1074, 2009.
[27]  H. Yüksel, O. Yilmaz, C. Kirmaz, S. Aydogdu, and E. Kasirga, “Frequency of gastroesophageal reflux disease in nonatopic children with asthma-like airway disease,” Respiratory Medicine, vol. 100, no. 3, pp. 393–398, 2006.
[28]  Y. Yoshida, M. Kameda, T. Nishikido, I. Takamatu, and S. Doi, “Gastroesophageal reflux disease in preschool children with asthma,” Arerugi, vol. 57, no. 5, pp. 529–535, 2008.
[29]  S. M. Harding, J. E. Richter, M. R. Guzzo, C. A. Schan, R. W. Alexander, and L. A. Bradley, “Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome,” American Journal of Medicine, vol. 100, no. 4, pp. 395–405, 1996.
[30]  C. Calabrese, A. Fabbri, A. Areni, C. Scialpi, D. Zahlane, and G. Di Febo, “Asthma and gastroesophageal reflux disease: effect of long-term pantoprazole therapy,” World Journal of Gastroenterology, vol. 11, no. 48, pp. 7657–7660, 2005.
[31]  K. St?rdal, G. B. Johannesdottir, B. S. Bentsen et al., “Acid suppression does not change respiratory symptoms in children with asthma and gastro-oesophageal reflux disease,” Archives of Disease in Childhood, vol. 90, no. 9, pp. 956–960, 2005.
[32]  I. V. Maev, E. S. Viuchnova, N. N. Balashova, and M. I. Shchekina, “Use of omeprazole and esomeprazole in patients suffering from bronchial asthma with associated gastroesophageal reflux disease,” Experimental & Clinical Gastroenterology, no. 3, pp. 26–116, 2003.
[33]  H. Teichtahl, I. J. Kronborg T, N. D. Yeomans, and P. Robinson, “Adult asthma and gastro-oesophageal reflux: the effects of omeprazole therapy on asthma,” Australian and New Zealand Journal of Medicine, vol. 26, no. 5, pp. 671–676, 1996.
[34]  M. J. Boeree, F. T. M. Peters, D. S. Postma, and J. H. Kleibeuker, “No effects of high-dose omeprazole in patients with severe airway hyperresponsiveness and (a)symptomatic gastro-oesophageal reflux,” European Respiratory Journal, vol. 11, no. 5, pp. 1070–1074, 1998.
[35]  T. R. Levin, R. M. Sperling, and K. R. McQuaid, “Omeprazole improves peak expiratory flow rate and quality of life in asthmatics with gastroesophageal reflux,” American Journal of Gastroenterology, vol. 93, no. 7, pp. 1060–1063, 1998.
[36]  T. O. Kiljander, E. R. M. Salomaa, E. K. Hietanen, and E. O. Terho, “Gastroesophageal reflux in asthmatics: a double-blind, placebo-controlled crossover study with omeprazole,” Chest, vol. 116, no. 5, pp. 1257–1264, 1999.
[37]  D. Sifrim, L. Dupont, K. Blondeau, X. Zhang, J. Tack, and J. Janssens, “Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring,” Gut, vol. 54, no. 4, pp. 449–454, 2005.
[38]  R. Shaker and W. J. Hogan, “Reflex-mediated enhancement of airway protective mechanisms,” American Journal of Medicine, vol. 108, no. 4, pp. 8–14, 2000.


comments powered by Disqus