Asthma and gastroesophageal reflux

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S. [2]

Overview

The underlying gastro-esophageal reflux disease predisposes the patient to have repetitive episodes of acid aspiration, which subsequently causes repeated airway inflammation and results in irritant-induced asthma.[1][2] The incidence of GERD in patients with asthma is approximately 38%. Asthmatics resistant to therapy are commonly associated with GERD, but identification and treatment of GERD has not shown to relate to the improvement in asthmatic control.[3]

Pathophysiology

There are three mechanisms proposed to explain the pathophysiology of development of asthma in patients with GERD:

  1. Vagal reflex: Both the esophagus and the bronchial tree, as they share a common embryonic origin, are innervated by the vagus nerve. Therefore, when there is reflux of acid contents from the stomach into the esophagus, the receptors in the esophagus are stimulated causing the vagus nerve to fire, which results in a bronchospasm. This phenomenon was demonstrated by Mansfield and Stein by the intraesophageal acid provocation test, which resulted in an increased resistance to airflow.[4] It was further strengthened by another series involving 136 subjects.[5] However, many studies failed to demonstrate a significant relationship between acid reflux and pulmonary function.[6][7]
  2. Heightened Bronchial Reactivity: Acid reflux into the esophagus increases the bronchial response to other stimuli. This was demonstrated by increased bronchial response to methacholine challenge test.[8]
  3. Microaspiration: Microaspiration of acidic contents from stomach into the upper airways and bronchial tree was shown to stimulate bronchial receptors resulting in broncho-constriction in asthmatic patients.[9] A murine study demonstrated that microaspiration of gastric contents caused an immune response similar to that observed in asthma.[10] However, a prospective single blinded study failed to demonstrate any significant bronchoconstriction with acid reflux into the airways.[11]

Epidemiology and Demographics

GERD is commonly seen among patients with asthma. The prevalence ranges between 34%-89%.[12][13][14][15][16]

Diagnosis

History and Symptoms

Patients may present with the following symptoms after eating a high fat meal or foods that lower the lower esophageal sphincter pressure:

Chest X Ray

The chest x-ray in asthmatics is often normal. It is done to exclude other causes of wheeze and aid in the diagnosis of complications such as atelectasis and pneumonia.

Other Diagnostic Studies

  • Esophageal pH testing: Presence of symptoms of GERD, which is refractory to proton pump inhibitors, should undergo esophageal pH testing. This helps in correlating the symptoms of asthma with gastro-esophageal reflux.[17]
  • Upper GI endoscopy: Endoscopy, though not indicated in diagnosis of asthma in GERD, may be done to exclude the presence of Barrett's esophagus.

Treatment

Treatment of asthma in GERD mainly pertains to treatment of GERD. Therefore, patients with poorly controlled asthma should be evaluated for GERD even in the absence of gastric reflux symptoms.

Primary Prevention

  • Patients should be advised to avoid heavy meals, fried foods, caffeine and alcohol.[18]
  • Patients should be advised to avoid meals or drinks at least for 3 hours before sleep.[18]
  • Elevating the head end of the bed is also shown to improve the symptoms.[18]

Secondary Prevention

Lansoprazole has shown to decrease the number of episodes of asthma exacerbations though it does not improve the asthmatic symptoms.[21] Esomeprazole improves peak expiratory flow in subjects with asthma who presents with both GERD and nocturnal symptoms.[22]

Future or Investigational Therapies

The role of fundoplication in patients with asthma and GERD has not yet been established. A meta-analysis of 24 studies concluded that the surgery improved asthma symptoms by 79% but had little effect on expiratory flow rate.[23] Surgical therapy has been found superior to the H2 antagonist. However, the benefit from surgery was not found to be different from those treated with proton pump inhibitors.[24]

References

  1. Cuevas Hernández MM, Arias Hernández RM (2008) [Pulmonary gammagraphy study in asthmatic children with gastroesophageal reflux.] Rev Alerg Mex 55 (6):229-33. PMID: 19157219
  2. Shapiro GG, Christie DL (1983) Gastroesophageal reflux and asthma. Clin Rev Allergy 1 (1):39-56. PMID: 6142759
  3. Leggett JJ, Johnston BT, Mills M, Gamble J, Heaney LG (2005) Prevalence of gastroesophageal reflux in difficult asthma: relationship to asthma outcome. Chest 127 (4):1227-31. DOI:10.1378/chest.127.4.1227 PMID: 15821199
  4. Mansfield LE, Stein MR (1978). "Gastroesophageal reflux and asthma: a possible reflex mechanism". Ann Allergy. 41 (4): 224–6. PMID 707849.
  5. Wright RA, Miller SA, Corsello BF (1990). "Acid-induced esophagobronchial-cardiac reflexes in humans". Gastroenterology. 99 (1): 71–3. PMID 2344943.
  6. Field SK (1999). "A critical review of the studies of the effects of simulated or real gastroesophageal reflux on pulmonary function in asthmatic adults". Chest. 115 (3): 848–56. PMID 10084501.
  7. Tan WC, Martin RJ, Pandey R, Ballard RD (1990). "Effects of spontaneous and simulated gastroesophageal reflux on sleeping asthmatics". Am Rev Respir Dis. 141 (6): 1394–9. PMID 2350084.
  8. Herve P, Denjean A, Jian R, Simonneau G, Duroux P (1986). "Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects". Am Rev Respir Dis. 134 (5): 986–9. PMID 3096180.
  9. Jack CI, Calverley PM, Donnelly RJ, Tran J, Russell G, Hind CR; et al. (1995). "Simultaneous tracheal and oesophageal pH measurements in asthmatic patients with gastro-oesophageal reflux". Thorax. 50 (2): 201–4. PMC 473925. PMID 7701464.
  10. Barbas AS, Downing TE, Balsara KR, Tan HE, Rubinstein GJ, Holzknecht ZE; et al. (2008). "Chronic aspiration shifts the immune response from Th1 to Th2 in a murine model of asthma". Eur J Clin Invest. 38 (8): 596–602. doi:10.1111/j.1365-2362.2008.01976.x. PMID 18717828.
  11. Harding SM, Schan CA, Guzzo MR, Alexander RW, Bradley LA, Richter JE (1995). "Gastroesophageal reflux-induced bronchoconstriction. Is microaspiration a factor?". Chest. 108 (5): 1220–7. PMID 7587420.
  12. Harding SM, Richter JE (1997). "The role of gastroesophageal reflux in chronic cough and asthma". Chest. 111 (5): 1389–402. PMID 9149599.
  13. Harding SM (2005). "Gastroesophageal reflux: a potential asthma trigger". Immunol Allergy Clin North Am. 25 (1): 131–48. doi:10.1016/j.iac.2004.09.006. PMID 15579368.
  14. Kiljander TO, Laitinen JO (2004). "The prevalence of gastroesophageal reflux disease in adult asthmatics". Chest. 126 (5): 1490–4. doi:10.1378/chest.126.5.1490. PMID 15539717.
  15. Field SK, Underwood M, Brant R, Cowie RL (1996). "Prevalence of gastroesophageal reflux symptoms in asthma". Chest. 109 (2): 316–22. PMID 8620699.
  16. Harding SM (1999). "Nocturnal asthma: role of nocturnal gastroesophageal reflux". Chronobiol Int. 16 (5): 641–62. PMID 10513887.
  17. DeVault KR, Castell DO, American College of Gastroenterology (2005). "Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease". Am J Gastroenterol. 100 (1): 190–200. doi:10.1111/j.1572-0241.2005.41217.x. PMID 15654800.
  18. 18.0 18.1 18.2 National Asthma Education and Prevention Program (2007). "Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007". J Allergy Clin Immunol. 120 (5 Suppl): S94–138. doi:10.1016/j.jaci.2007.09.043. PMID 17983880.
  19. Harding SM, Richter JE, Guzzo MR, Schan CA, Alexander RW, Bradley LA (1996). "Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome". Am J Med. 100 (4): 395–405. doi:10.1016/S0002-9343(97)89514-9. PMID 8610725.
  20. Kiljander TO, Salomaa ER, Hietanen EK, Terho EO (1999). "Gastroesophageal reflux in asthmatics: A double-blind, placebo-controlled crossover study with omeprazole". Chest. 116 (5): 1257–64. PMID 10559084.
  21. Littner MR, Leung FW, Ballard ED, Huang B, Samra NK, Lansoprazole Asthma Study Group (2005). "Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms". Chest. 128 (3): 1128–35. doi:10.1378/chest.128.3.1128. PMID 16162697.
  22. Kiljander TO, Harding SM, Field SK, Stein MR, Nelson HS, Ekelund J; et al. (2006). "Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial". Am J Respir Crit Care Med. 173 (10): 1091–7. doi:10.1164/rccm.200507-1167OC. PMID 16357331. Review in: Evid Based Med. 2006 Dec;11(6):175
  23. Field SK, Gelfand GA, McFadden SD (1999). "The effects of antireflux surgery on asthmatics with gastroesophageal reflux". Chest. 116 (3): 766–74. PMID 10492285.
  24. Williams DB, Schade RR. Gastroesophageal reflux disease. In: DiPiro JT, Talbert RL, Yee GC, et al.Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY: McGraw-Hill; 2005:613-628.



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