Gastroesophageal Reflux and Asthma

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Abstract

The medical literature has been deluged with articles on the relation between gastro-esophageal reflux (GER) and asthma. In an effort to piece together the complex puzzle, investigators from all disciplines have gathered their patients with wheezing and heartburn and studied the epidemiology, the possible cause or effect mechanisms and the therapeutic response to GER treatment. Indeed, since humans first began to hunker down and work together to discuss interesting observations, the world has begun to breathe easier. Epidemiological evidence for a GER/asthma association suggests that about three-fourths of asthmatics, independent of the use of bronchodilators, have acid GER, increased frequency of reflux episodes, or heartburn; and 40% have reflux esophagitis. Physiological studies suggest that 2 separate mechanisms are involved in the GER/asthma relationship: (1) a vagally mediated pathway and (2) microaspiration. In any given patient, however, there is no acceptable diagnostic method available to confirm the presence or absence of GER-induced asthma. Clinical trials, using antireflux medical therapy and antireflux surgery have begun to provide some clues about GER-related pulmonary symptoms. The trials of medical therapy using acid suppressing drugs (e.g. histamine-2 receptor antagonists) have ranged from no benefit to modest improvement of only nocturnal asthma symptoms. Studies with proton-pump inhibitors are underway. In uncontrolled surgical studies, antireflux surgery has resulted in partial or complete remission of asthma symptoms in a large proportion of patients. Despite the uncontrolled nature of these studies, many patients have had dramatic subjective improvement in pulmonary symptoms. It appears for now that clinical trials are the only available means to assess whether medical or surgical treatment of GER in patients with both GER and asthma improves the symptoms of asthma and decreases the need for pulmonary medications. One conclusion is certain: We no longer can ignore the important co-existent nature of these 2 afflictions.

Section snippets

Coexistence of GER and Asthma

In a review on pulmonary complications of esophageal disease, Belsey[8]reported that patients with GER were liable to severe, progressive, and disabling pulmonary damage. Of 636 patients referred for surgical correction of severely symptomatic GER, more than 60% had symptoms of pulmonary disease coexisting with the GER.[9]Table 1 shows the published reports of asthma coexisting with GER in both children and adults.

Prevalence of GER in Patients With Asthma

The prevalence of GER in patients with asthma has been described in studies of both children and adults.3, 12, 15, 18, 22, 24, 29, 35

The true prevalence, however, is difficult to determine from these published studies. Most of the studies comprise highly selected referred populations that may not reflect the overall population with pulmonary disease. Despite these limitations, the studies that did attempt to determine prevalence rates reported remarkably similar results. The prevalence of GER

Mechanisms

The mechanisms by which GER might induce asthma have been a subject of debate. Two different mechanisms for GER-induced symptoms have been postulated: (1) activation of a GER-induced vagal reflex arc (vagal mediation) from the esophagus to the lung, resulting in bronchoconstriction,[29]and (2) microaspiration of gastric contents into the lung resulting in an exudative mucosal reaction.[8]

Reflux Abnormalities in Pulmonary Patients

Two retrospective radiographic studies reported on the prevalence of hiatal hernia and barium reflux in patients with pulmonary disease.14, 28Friedland and associates,[28]in a retrospective radiographic review of 54 children with unremitting asthma reported a 48% prevalence rate of hiatal hernia. Using barium x-ray studies and a control group, Mays[14]reported on 28 patients with severe asthma, 64% of whom had hiatus hernia and 46% of whom had barium reflux. These studies were criticized by

Prospective Epidemiologic Data

Recently, investigators have prospectively assessed the epidemiology and the prevalence of GER factors in consecutively studied asthmatic patients. Such epidemiological and cross-sectional studies clearly demonstrated that GER is highly prevalent in asthmatic patients. Recent studies show that about 75% of patients with asthma, independent of the use of bronchodilators,16, 20, 45, 53have heartburn,[16]pathologic acid GER,[20]and increased frequency of reflux episodes.[20]In addition, almost 60%

Effect of Medical Antireflux Treatment on Asthma

The effects on asthma of medical therapy of GER are shown in Table 2. Although improvement in pulmonary symptoms was reported in these studies, there are major problems with data interpretation. The duration of antireflux treatment (up to 8 weeks) is far too short to judge efficacy, and the prescribed dosage of H2-receptor antagonist is much too low to adequately prevent reflux. In addition, the definition of abnormal acid reflux (pH <4 for more than 1% of the time) may be too lenient, and a

Uncontrolled Studies

Early reports of an association between GER and asthma described a reduction or even a disappearance of the asthmatic state after antireflux surgery9, 12, 17, 22, 24, 61, 63, 64, 65, 66, 67, 68In most of these studies, however, pulmonary function tests were not performed before or after surgical repair. Despite the lack of objective data, the dramatic subjective improvement reported in some of the studies (e.g., complete elimination of asthma after 20 years) cannot be ignored. Fig. 1 shows the

Conclusions

The evidence is strong that GER plays an important role in some patients with asthma. Despite sophisticated study methods and technologically advanced diagnostic tests, the results of published studies on mechanisms failed to provide a diagnostic test with a degree of certainty great enough to identify which patients have GER-induced or GER-exacerbated asthma and which patients will respond to antireflux therapy. The difficulties involved in establishing a definite cause-and-effect relationship

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