Gastroesophageal Reflux Disease Newsletter __________ Series 1, Issue 3, 2007

GASTROESOPHAGEAL REFLUX DISEASE AND ASTHMA

P Marco Fisichella, MD
University of California, San Francisco

Marco G Patti, MD
University of California, San Francisco

Gastroesophageal reflux disease (GERD) may be a trigger for symptoms in patients with asthma. An aggressive approach to treatment of reflux symptoms may lead to a reduction in the severity and frequency of asthma symptoms in these patients along with an improvement in the results of pulmonary function tests. Asthma affects almost 20 million Americans and is associated with significant morbidity and limitation in quality of life. Despite recent pharmacologic advances in the treatment of asthma, the condition continues to be poorly controlled in many patients. This newsletter presents the relationship of asthma and GERD and discusses diagnosis as well as medical and surgical approaches to treatment.

Several studies have demonstrated a significant overlap in the comorbidity of patients with these 2 conditions, with up to 77% of people with asthma also experiencing symptoms of heartburn and 55% experiencing regurgitation. Furthermore, up to 78% of episodes of respiratory symptoms such as coughing or wheezing in patients with both asthma and GERD are temporally associated with episodes of reflux. Objective evidence of GERD has further established an association between the 2 conditions; abnormal pH level monitoring results have been demonstrated in 72% of people with asthma, and clinical evidence of esophagitis and/or Barrett esophagus has been found in 39% of patients with asthma. Even in those patients with asthma who do not report symptoms of reflux (approximately 29% of patients), direct pH level monitoring can demonstrate reflux in up to two thirds of cases.

Although GERD is generally considered to be a trigger of asthma, and treatment of the condition has been shown to considerably improve both symptoms and quality of life for patients, a direct cause and effect relationship between the 2 conditions has yet to be definitively established. Several mechanisms have been proposed whereby esophageal acid may lead to the symptoms of asthma; the mechanisms include increased vagal tone, bronchial hyperreactivity, and microaspiration of gastric contents. All of these pathophysiologic processes have been postulated to induce inflammation and bronchoconstriction that ultimately lead to an increased frequency and severity of respiratory symptoms as well as deterioration and abnormalities in the pulmonary function test results observed in patients with asthma. Additional factors may include a relatively higher prevalence of hiatal hernia in patients with asthma and the use of inhaled beta-agonists and oral corticosteroids, which may exacerbate reflux of esophageal acid.

Establishing that a patient’s asthma symptoms are being exacerbated by GERD may not always be straightforward. Although the presence of active symptoms consistent with GERD may be useful in the diagnosis and treatment of a patient with refractory or worsening asthma, as previously mentioned, up to two thirds of the 29% of patients with asthma may be clinically asymptomatic for GERD even though objective testing such as esophageal pH testing would reveal abnormalities. These patients may not experience the typical symptoms of reflux while still experiencing respiratory exacerbations as a result of acid reflux. As studied by the authors’ research group at the University of California in San Francisco, a 24-hour pH level monitoring study may be useful, in such cases, to establish an association between reflux and the reflux-induced respiratory symptoms in the patient with asthma. Specifically, episodes of reflux are considered to be the cause of the patient’s respiratory symptoms when they occur during or within the 3 minutes that precede an episode of respiratory difficulty. Close temporal correlation between respiratory symptoms and episodes of reflux and evidence of proximal reflux (ie, reflux to the upper esophageal sphincter) are associated with better prognosis with medical therapy, while atypical symptoms, poor temporal symptom correlation, and reflux limited to the distal esophagus are typically more difficult to manage. A new investigational technique, esophageal multichannel intraluminal impedance (MII) monitoring, when combined with esophageal pH level monitoring (MII-pH), allows for the detection of both acidic and nonacidic episodes of reflux. MII-pH monitoring may be useful in the evaluation of patients with chronic unexplained cough and typical reflux symptoms resistant to medical therapy.

A reasonable approach to patients with asthma who have either symptoms or diagnostic testing consistent with GERD or certain other characteristics (ie, moderate to severe GERD symptoms, long-acting beta-agonist therapy, maintenance corticosteroid therapy) is to begin an empiric trial of acid suppression therapy. The initial trial is usually for a period of 3 months and is with either a histamine 2 (H2) – blocker or a proton pump inhibitor (PPI). Several placebo-controlled studies have reported improvement of respiratory symptoms and pulmonary function tests in patients who have asthma and GERD with both classes of medications. Additional studies have demonstrated the superiority of PPI medications such as pantoprazole, lansoprazole, and esomeprazole in terms of both degree of effect and duration when compared with H2-blockers in inhibiting acid secretion. High-dose (twice a day) PPI therapy is recommended because relatively poor results in suppressing esophageal acid have been noted with once daily dosing of PPI (ie, 20 mg/d of omeprazole). Chronic, long-term acid suppression therapy should be considered for patients who are noted to have an improvement in asthma symptoms or a reduced requirement for asthma medications such as bronchodilator therapy or maintenance corticosteroid therapy.

A few points of caution in interpreting current recommendations may be warranted. In a review of the literature, Harding showed that early studies of H2-blocker therapy included patients who were usually treated with low-dose therapy for periods of time too short to assess true efficacy. Additionally, some studies assessing the efficacy of PPI therapy on GERD in patients with asthma may have been underpowered to see a real effect on respiratory symptoms. In 2003, a Cochrane review examined 12 trials of treatment for GERD in adults and children with a diagnosis of both asthma and GERD. The review concluded that, while no benefit was observed overall in terms of improving lung function, asthma symptoms, nocturnal asthma, or the use of asthma medications, a subgroup of patients might have benefited from medical therapy.

In addition to empiric therapy with acid suppression medication, lifestyle modifications may also be considered. These modifications may help improve symptoms and reduce the duration of esophageal acid reflux. The patient may avoid certain foods known to relax the lower esophageal sphincter, such as peppermint, chocolate, caffeine, and alcohol. Raising the height of the patient’s pillow to 6 inches off the bed may prevent nocturnal acid reflux, as may sleeping in the left lateral decubitus position and not eating a large meal within 2-3 hours of sleep. Weight reduction may be the most effective lifestyle modification for reducing asthma symptoms and esophageal acid reflux.

A select cohort of patients with asthma and GERD may benefit from endoscopic procedures and anti-reflux surgery, though consensus regarding the role of surgery in these patients has not been reached. In 2003, Sontag et al prospectively observed 62 people with asthma and GERD for a minimum of 2 years. These patients were randomized to receive medical therapy with ranitidine 150 mg 3 times a day, surgical therapy with Nissen fundoplication, or antacids (control group). At the end of the study, the mean asthma symptom score of the surgical group improved 43% compared with less than 10% in the medical and control groups; the results of surgery were realized immediately following the procedure. However, in this study and others, no difference was observed between the groups in terms of improving pulmonary function, overall survival rates, and medication requirements.

A significant percentage of patients with asthma also have GERD. The increased esophageal acid may act as a trigger for the respiratory symptoms of asthma. The timely diagnosis and identification of patients with asthma who are eligible for empiric therapy with acid suppression medications for the treatment of established or suspected GERD may significantly reduce the frequency and intensity of their respiratory symptoms and lead to an improvement in their quality of life.

Barnes PJ. The size of the problem of managing asthma. Respir Med. 2004;98 Suppl B:S4-8.

Bytzer P, Havelund T, Hansen JM. Interobserver variation in the endoscopic diagnosis of reflux esophagitis. Scand J Gastroenterol. 1993;28:119-25.

Bredenoord AJ, Tutuian R, Smout AJ, Castell DO. Technology review: Esophageal impedance monitoring. Am J Gastroenterol. 2007;102(1):187-94.

Ciovica R, Gadenstatter M, Klingler A, et al. Quality of life in GERD patients: medical treatment versus antireflux surgery. J Gastrointest Surg. 2006;10(7):934-9.

Costantini M, Crookes PF, Bremner RM, et al. Value of physiologic assessment of foregut symptoms in a surgical practice. Surgery. 1993;114:780-7.

Field SK, Gelfand GA, McFadden SD. The effects of antireflux surgery on asthmatics with gastroesophageal reflux. Chest. 1999;116(3):766-74.

Field SK, Underwood M, Brant R, Cowie RL. Prevalence of gastroesophageal reflux symptoms in asthma. Chest. 1996;109(2):316-22.

Gibson PG, Henry RL, Coughlan JL. Gastro-oesophageal reflux treatment for asthma in adults and children. Cochrane Database Syst Rev. 2003;(2):CD001496.

Harding SM. Recent clinical investigations examining the association of asthma and gastroesophageal reflux. Am J Med. 2003;115 Suppl 3A:39S-44S.

Harding SM, Guzzo MR, Richter JE. The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. Am J Respir Crit Care Med. 2000;162(1):34-9.

Harding SM, Guzzo MR, Richter JE. 24-h esophageal pH testing in asthmatics: respiratory symptom correlation with esophageal acid events. Chest. 1999;115(3):654-9.

Harding SM, Richter JE, Guzzo MR, et al. Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome. Am J Med. 1996;100(4):395-405.

Harding SM. Gastroesophageal reflux: a potential asthma trigger. Immunol Allergy Clin North Am. 2005;25(1):131-48.

Kiljander TO. The role of proton pump inhibitors in the management of gastroesophageal reflux disease-related asthma and chronic cough. Am J Med. 2003;115 Suppl 3A:65S-71S.

Kiljander TO, Harding SM, Field SK, et al. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2006;173(10):1091-7.

Kiljander TO, Salomaa ER, Hietanen EK, Terho EO. Gastroesophageal reflux in asthmatics: A double-blind, placebo-controlled crossover study with omeprazole. Chest. 1999;116(5):1257-64.

Lazenby JP, Guzzo MR, Harding SM, et al. Oral corticosteroids increase esophageal acid contact times in patients with stable asthma. Chest. 2002;121(2):625-34.

Leeder PC, Watson DI, Jamieson GG. Laparoscopic fundoplication for patients with symptoms but no objective evidence of gastroesophageal reflux. Dis Esophagus. 2002;15(4):309-14.

Maton PN. Omeprazole. N Engl J Med. 1991;324(14):965-75.

Mays EE. Intrinsic asthma in adults. Association with gastroesophageal reflux. JAMA. 1976;236(23):2626-8.

National Center for Health Statistics, National Health Interview Survey (NHIS), 1982-1996, 2001-2004.

National Heart, Lung, and Blood Institute. Morbidity and Mortality: 2004 Chart Book on Cardiovascular, Lung, and Blood Diseases. Bethesda, MD: National Institute of Health; 2004. Available at: http://www.nhlbi.nih.gov/resources/docs/cht-book.htm. Accessed on April 23, 2007.

Patti MG, Arcerito M, Tamburini A, et al. Effect of laparoscopic fundoplication on gastroesophageal reflux disease-induced respiratory symptoms. J Gastrointest Surg. 2000;4(2):143-9.

Schulman, Ronca and Bucuvalas, Inc. and Glaxo-SmithKline. Asthma in America. 1998. Available at: http://www.asthmainamerica.com/.

Sontag SJ. The spectrum of pulmonary symptoms due to gastroesophageal reflux. Thorac Surg Clin. 2005;15(3):353-68.

Sontag SJ, Schnell TG, Miller TQ, et al. Prevalence of oesophagitis in asthmatics. Gut. 1992;33(7):872-6.

Sontag SJ, O'Connell S, Khandelwal S, et al. Asthmatics with gastroesophageal reflux: long term results of a randomized trial of medical and surgical antireflux therapies. Am J Gastroenterol. 2003;98(5):987-99.

Spivak H, Smith CD, Phichith A, et al. Asthma and gastroesophageal reflux: fundoplication decreases need for systemic corticosteroids. J Gastrointest Surg. 1999;3(5):477-82.

Teichtahl H, Kronborg IJ, Yeomans ND, Robinson P. Adult asthma and gastro-oesophageal reflux: the effects of omeprazole therapy on asthma. Aust N Z J Med. 1996;26(5):671-6.