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2011 The Relationship Between GERD and …

Authors and Disclosures

Kristi M. Issac, BS, PharmD, AE-C
Clinical Assistant Professor of Pharmacy Practice
Xavier University of Louisiana
College of Pharmacy,
New Orleans, Louisiana

From U.S. Pharmacist > Departments > Consult

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The Relationship Between GERD and Asthma
Kristi M. Issac, BS, PharmD, AE-C
Posted: 08/26/2009; US Pharmacist. 2009;34(7):30-35. © 2009 Jobson Publishing


Asthma is a chronic airway disease characterized by airflow obstruction, bronchial hyperresponsiveness, and
inflammation. [1] There are many triggers and comorbid conditions that have been shown to increase asthma
symptoms and/or precipitate asthma exacerbations. The Expert Panel Report 3: Guidelines for the Diagnosis and
Management of Asthma recognizes gastroesophageal reflux disease (GERD) as a comorbid condition of asthma and
recommends medical management of GERD in appropriate patients. [1]

The relationship between asthma and GERD has been discussed for many years. In 1892, Sir William Osler
described an association: "severe paroxysms of asthma may be induced by overloading the stomach, or by taking
certain articles of food."[2] Although these two disorders often occur together, the relationship between GERD and
asthma remains unclear. This article will review the prevalence, proposed pathophysiology, and treatment
recommendations for persons with both asthma and GERD.


In the United States, an estimated 20 million people have asthma, and almost 20% of the U.S. population suffers
from the classic symptoms of GERD, such as heartburn and regurgitation, at least once a week.[3,4] The prevalence
of GERD in patients with asthma is estimated to be 34% to 89%. [5]

Although it remains unclear whether or not a true causal relationships exists, several studies show that GERD
symptoms tend to be increased in patients with asthma. Field et al investigated the prevalence of symptomatic
gastroesophageal reflux using a questionnaire-based survey. [6] Among the 109 patients with asthma who participated
in the study, 77% experienced heartburn and 55% experienced regurgitation; symptoms were higher than in the
control groups. O’Connell et al also utilized a symptom survey to examine prevalence of GERD in 189 patients with
asthma in a Veterans Administration (VA) hospital.[7] Seventy-two percent of the patients reported heartburn. Perrin-
Fayolle et al found reflux symptoms in 65% of 150 surveyed patients with asthma.[8] These results suggest that the
prevalence of GERD symptoms in patients with asthma is increased; however, it does not establish causality.

Pathophysiology of GERD-induced Asthma

Several proposed mechanisms about the pathophysiology of GERD-induced asthma exist, although these
mechanisms are not completely understood. Proposed mechanisms of GERD-induced asthma include a vagally
mediated reflex, heightened bronchial reactivity, microaspiration, and immune system modification.…/707500_print 1/8
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Vagal Reflex

The esophagus and bronchial tree share embryonic origins and innervation through the vagus nerve; therefore, acid in
the esophagus could stimulate esophageal receptors, initiating a vagally mediated reflex. [9] Many studies show that
the vagally mediated reflex mechanism is important to GERD-induced bronchoconstriction, while others report
conflicting data. Mansfield and Stein showed that patients with reflux had a 10% increase in airway flow
resistance.[10] Wright et al measured airflow and arterial oxygen saturation before and after esophageal acid infusions
in 136 individuals.[11] Results indicated that there was a significant decrease in both airflow and arterial oxygen
saturation after infusion of the acid.

Other studies have failed to show significant pulmonary response to esophageal acid. Field analyzed 18 studies that
reviewed the effects of GERD on pulmonary function in adults with asthma.[12] He concluded that the effects of
esophageal acid on pulmonary function are minimal and only affect a minority of subjects. In patients with nocturnal
asthma, Tan et al found no significant changes in airflow resistance when esophageal acid was present. [13]

Heightened Bronchial Reactivity

Another proposed mechanism of GERD-induced asthma is heightened bronchial reactivity. Some data suggest that
exposure to esophageal acid may increase bronchial activity to other stimuli. Herve et al reported on the effects of
esophageal acid on expiratory flow with methacholine challenge testing.[14] When esophageal acid was infused
versus normal saline, the total dose of methacholine needed to reduce the forced expiratory volume in one second
(FEV1) by 20% was significantly lower.


Microaspiration of gastric acid into the larynx and upper airway could cause stimulation of the upper airway and
increase airway resistance. Jack et al showed that microaspiration of gastric fluid into the upper airway may trigger
asthma symptoms in patients with asthma. [15] When the esophageal and endotracheal pH was decreased, the mean
peak expiratory flow fell 84 L/min. When acid was introduced in the esophagus without microaspiration of gastric fluid
into the trachea, the peak expiratory flow fell only 8 L/min. In an animal study, Tuchman et al found a significant
increase in response when acid was introduced directly into the trachea versus the esophagus.[16] Although
microaspiration may be an inducer of bronchial reactivity, other studies suggest that microaspiration does not play a
significant role in GERD-induced asthma. [17]

Immune System Modification

A recent study conducted at Duke University showed that GERD may alter the immune system’s response to
allergens, further strengthening the link between GERD and asthma.[18] Researchers compared the immune
system’s response to allergens in mice with gastric fluid in the lungs to its response in normal mice. Results showed
that the mice with GERD developed a response similar to that found in patients with asthma by releasing a type 2
helper T cell. The comparison group’s response was more balanced, releasing both type 1 and type 2 helper T cells.
This study shows that microaspiration may lead the immune system to generate an asthmatic response.

Other Factors

Many factors may lead to GERD development in patients with asthma. Potential predisposing elements include an
increased pressure gradient, airway obstruction, and asthma medications. During an asthma exacerbation, there may
be an increase in negative pleural pressure, which increases pressure on the diaphragm. This may override lower
esophageal pressure, thereby promoting reflux. [19]

Airway obstruction may also predispose asthma patients to GERD by relaxing the lower esophageal sphincter (LES).
Zerbib et al showed that airflow obstruction significantly increased the number of LES relaxations and the number of
reflux episodes.[20] The number of LES relaxations decreased when airflow obstruction was reversed.…/707500_print 2/8
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Bronchodilator medications may decrease lower esophageal pressure, which favors gastroenterologic reflux. One
study found a 24% increase in reflux time and a threefold increase in symptoms over baseline with theophylline
therapy. Patients with subtherapeutic levels of theophylline did not have a significant increase in reflux symptoms. [21]
Another study examined the effects of nebulized albuterol versus placebo on lower esophageal relaxation and
reported that albuterol therapy reduced lower esophageal tone and may increase the likelihood of acid reflux in a
subset of patients.[22] Furthermore, oral corticosteroids have been shown to increase esophageal acid contact time
significantly. [23] However, Field et al reported that no asthma medications were associated with an increased
likelihood of having GERD symptoms. [6]

Diagnosing GERD in Patients With Asthma

Every patient with asthma should be asked about GERD as well. Questions should include whether frequent cough
and hoarseness are present and whether asthma symptoms occur after meals or when lying down. In addition,
inhaler use when experiencing GERD symptoms should be assessed. [5] The signs and symptoms of GERD are
listed in TABLE 1.

Table 1. Signs and Symptoms of GERD

Signs and Symptoms of GERD


Chest pain

Sore throat


Frequent throat clearing

Globus hystericus ("lump in the throat" sensation)

Water Brash (regurgitation of excessive saliva)

Regurgitation of foods/liquids


Loss of dental enamel

Source: Reference 31

If typical GERD symptoms are present, a trial of pharmacologic therapy is warranted. Empiric therapy is considered
successful if asthma outcomes are improved. [24] Further testing is recommended in patients in whom empiric therapy
is unsuccessful or who have symptoms suggesting complicated GERD.[5] Of note, many asthma patients with GERD
do not experience reflux symptoms; this subset of patients may be difficult to diagnose.


The current asthma guidelines recommend that medical management of GERD be instituted for patients who have
asthma and complain of frequent heartburn (pyrosis), particularly those who have frequent episodes of nocturnal
asthma.[1] Three categories of medications are widely available for the treatment of reflux disease: proton pump
inhibitors (PPIs), H2 antagonists, and antacids.

Proton Pump Inhibitors…/707500_print 3/8
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The PPIs are the most potent inhibitors of gastric secretion available and the recommended therapy when treating
GERD-induced asthma. These medications suppress gastric acid secretion by inhibition of the hydrogen-potassium
adenosine triphosphatase (H+, K+–ATPase) enzyme system found on the surface of parietal cells. PPIs should be
administered 30 to 60 minutes before meals. Dexlansoprazole (the newest PPI), pantoprazole, and rabeprazole may
be taken without regard to timing of meals. A minimum of 3 months of therapy is recommended. Common adverse
effects include abdominal pain, nausea, diarrhea, and headache. [25] The available PPIs, their standard adult dosing,
and their proposed dosing in GERD-related asthma are displayed in TABLE 2 .

Table 2. Proton Pump Inhibitors

Generic (Brand) Standard Adult Dosing Proposed Dosing for GERD-induced Asthma

Dexlansoprazole (Kapidex) 30 mg daily NA

Esomeprazole (Nexium) 20 mg daily 20 mg twice daily

Lansoprazole (Prevacid) 15 mg daily 30 mg twice dice daily

Omeprazole (Prilosec) 20 mg daily 20 mg twice dice daily

Pantoprazole (Protonix) 40 mg daily 40 mg twice dice daily

Rabeprazole (Aciphex) 20 mg daily 20 mg twice dice daily

NA: not applicable. Source: Reference 31,38

Studies evaluating the efficacy of PPIs on asthma outcomes have been conducted. In a trial evaluating the dose of
omeprazole required for adequate acid suppression in 30 nonsmoking adults with asthma and GERD, 73% of
subjects had improved asthma symptoms and/or peak expiratory flow rates after 3 months.[26] Many of the subjects
required more than the standard dose (20 mg/day) to suppress the acid; therefore, a high-dose PPI (i.e., double-
standard or twice-daily dosing) is recommended in the treatment of coexisting asthma and GERD. In a double-blind,
placebo-controlled, crossover study, 107 patients with asthma were randomized to either omeprazole 40 mg/day or
placebo for 8 weeks.[27] A significant reduction in nighttime asthma symptoms was found in the omeprazole group,
although daytime symptoms did not improve. Ford et al noted no improvements in daytime or nocturnal symptoms
using omeprazole 20 mg/day for 4 weeks. [28]

Littner et al reported the effects of lansoprazole on asthma symptoms in patients with severe asthma and reflux. [29]
Lansoprazole did not improve daily asthma symptoms; however, therapy did significantly decrease the number of
asthma exacerbations and improved quality of life. In a study evaluating the effects of esomeprazole on asthma
outcomes in patients with asthma, esomeprazole improved the peak expiratory flow in subjects with both nocturnal
symptoms and GERD. No significant improvement in peak expiratory flow was detected in other subjects. [30]


H2-receptor antagonists inhibit acid secretion by blocking histamine receptors on the parietal cell. Four H2
antagonists are currently available in the U.S.: cimetidine (Tagamet), famotidine (Pepcid), nizat idine (Axid), and
ranitidine (Zantac). Depending on the severity of the disease, H2 antagonists can be given in low (OTC), standard, and
high doses. For example, standard doses of H2 antagonists include cimetidine 400 mg four times daily or 800 mg
twice daily, famotidine 20 mg twice daily, nizatidine 150 mg twice daily, and ranitidine 150 mg twice daily. The
dosage of these medications should be reduced by 50% in patients with moderate-to-severe renal failure. Common
side effects include headache, fatigue, dizziness, and gastrointestinal (GI) disturbances. [31]

Cimetidine, and to a much lesser extent ranitidine, can inhibit the CYP450 system. Drugs metabolized via the…/707500_print 4/8
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CYP450 system, such as theophylline and warfarin, may be affected. Famotidine and nizatidine do not inhibit this
pathway; therefore, drug interactions mediated by hepatic metabolism are not expected. Drug interactions, especially
with cimetidine, should be monitored. [31]

In a study evaluating 18 patients with both asthma and GERD, 14 patients felt that their chest symptoms had
improved significantly after cimetidine therapy.[32] Another trial reported the effects of ranitidine 150 mg twice daily for
4 weeks on reflux and asthma control. Only a modest improvement in nocturnal asthma occurred, with no change in
lung function and peak flow values.[33]


Antacids relieve heartburn and dyspepsia by neutralizing gastric acid. In addition to increasing the intragastric pH,
they may also increase LES pressure. Several nonprescription antacid products are available, including Alka-Seltzer,
Gaviscon, and Maalox (i.e., aluminum and magnesium salts). Most of these products are inexpensive, making them
a desirable option for patients seeking temporary relief of symptoms.[34] Generally, antacids have a short duration of
action, requiring frequent daily administration. Dosing intervals range from hourly to as needed. These products may
cause GI side effects and acid-base disturbances. Significant interactions with drugs, including iron and tetracycline,
may occur.[31] In a trial evaluating the effectiveness of Gaviscon and lifestyle changes in patients with GERD and
asthma, there was a 44% improvement in symptoms only. Lung function tests did not differ between the treatment
and control groups.[35]

Surgical Intervention

Surgical therapy, such as laparoscopic Nissen fundoplication, is an option for patients who have failed to respond to
medications, experience complications of GERD, or have elected to have surgery despite successful medication
therapy. Several studies suggest that surgical intervention improves asthma symptom control. Sontag et al reported
complete resolution of asthma symptoms after surgery in 6 of 13 patients.[36] After reviewing 24 reports of surgical
antireflux therapy in patients with asthma, Field et al reported that GERD and asthma symptoms were improved in
90% and 79% percent of the subjects, respectively.[37] Surgical antireflux therapy has been found superior to an H2
antagonist; comparisons with PPIs were found to be similar.[31]

Lifestyle Modifications

Asthma symptoms associated with GERD can be aggravated by high-fat meals that delay gastric emptying and
foods that lower LES pressure. Eating or drinking acidic foods may also trigger symptoms.[31] Foods and
medications that may worsen GERD symptoms are shown in TABLE 3 .

Table 3. Foods and Medications That May Worsen GERD Symptoms

Foods Medications

Alcoholic beverages Anticholinergics

Carbonated beverages Barbiturates

Citrus fruit drinks Caffeine

Chocolate Calcium channel blockers

Coffee (e.g., dihydropyridine)

Fatty foods Nicotine

Peppermint Nitrates

Spicy foods NSAIDs…/707500_print 5/8
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Tomato products Theophylline

NSAIDs: nonsteroidal anti-inflammatory drugs. Source: Reference 31

Lifestyle changes should be initiated in patients with both asthma and GERD. These modifications include elevating
the head of the bed on 6- to 8-inch blocks, avoiding food and drink at least three hours before retiring, and not lying
down within 2 hours after a meal. Other lifestyle modifications include weight reduction, smoking cessation, and
alcohol avoidance. These patients should also avoid foods and drinks that may worsen symptoms of GERD.


Health care providers should be aware that GERD is a potential trigger of asthma, although not all asthma patients
with GERD experience reflux symptoms. All patients with asthma should be questioned about reflux symptoms, and
antireflux therapy, in particular high-dose PPI therapy, should be initiated if appropriate. If symptoms are not improved
after 3 months of empiric therapy, then either reflux is inadequately controlled or GERD-induced asthma is not
present. Referral to a gastroenterologist may be warranted.


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